Embryo stages, progression and pregnancy outcomes
November 10, 2010Carole 255 Comments »Did I mention I love getting blog topic suggestions from my readers? I get in a rut too. So I was happy to find this request in my inbox. “Carole, please could you discuss the various stages and the required number of cells the fertilized egg goes through up until it is vitrified on day 6? Also please could you explain the terms “cleaved”, “compacted”, “non-expanded” blastocysts and possibly give some percentages as to the chance of pregnancy when, e.g. a compacted 6 day blast is transferred.”
This post also gives me the opportunity to thank Dr. Liz Sanders from the Mississippi Fertility Institute and Dr. Robert Shabanowitz from Geisinger Medical Center for their generous permission to use their embryo images in this blog.
First things first. The first embryonic stage is the fertilized egg or zygote stage. Eggs usually show signs of fertilization between 16-18 hours after insemination. What embryologists look for are two well-defined transient structures called pronuclei in the center of the fertilized egg. In the picture below, the PN look like two chocolate chip cookies inside the egg. These “cookies” contain the male and female DNA and for normal fertilization, there should be exactly two pronuclei or as embryologists like to shorthand, “2PN”.
Normally fertilized egg with a paternal and maternal pronucleus (2PN) visible. Photo courtesy of Dr. Liz Sanders, Mississippi Fertility Center, Jackson, MS.
What is significant about the 2PN stage? This stage is brief, lasting only a few hours and occurring approximately 16-18 hours after insemination. Seeing more than 2PN (say 3, 4, 6PN or more) are all abnormal numbers of pronuclei which can not be corrected and result in an abnormal embryo which may fail to develop further. 3PN zygotes can cleave and continue to develop but will not produce a healthy pregnancy. Embryologists need to identify these abnormally fertilized eggs and remove them from the viable embryo pool.
Some clinics use a zygote scoring system or Z-score based on the appearance of the PNs to try to identify the fertilized eggs that will cleave and progress from this early stage. If the 2PN stage zygote looks like the egg swallowed two chocolate chip cookies, then the tiny spots within each cookie that look like chocolate chips are the nucleoli. Nucleoli are small, typically round granular bodies composed of protein and RNA that are usually associated with a specific chromosomal site, These nucleoli are involved in ribosomal RNA synthesis and the formation of ribosomes. Characteristics including the number of nucleoli within each pronucleus, the similarity in size of these nucleoli and whether they are lined up along the edges where the “cookies” touch are all factored into the Z-score. The usefulness of the Z-score is in dispute and is not used by many clinical labs.
Cleavage stages. When the fertilized egg divides for the first time and forms two cells, it has entered the cleavage stage of development. The term “cleaved” simply means that the cell has divided from one cell to two. Divided =cleaved. The cells in the the two-cell embryo continue to divide, creating a four-cell embryo. Each cell in the four cell embryo divides or cleaves again, forming an eight cell embryo. You can watch a great video of development from the fertilized egg to the blastocyst stage on the NIH stem cell website. A note about “days of culture” related to embryo stages: When I refer to day 3 of culture, day zero of culture is egg retrieval day. Signs of fertilization are visible on day 1 of culture. Cleavage to two-cell stage is typically expected on day 2 of culture and cleavage of the embryo to an eight-cell is expected on day 3 of culture.
What is significant at cleavage stage? Embryologists have long looked for characteristics at this stage which will identify which embryos will go the distance. 
Characteristics that are favored by embryologists include same sized cells with little or no fragmentation. The four cleavage stage embryos in the picture at the right are a good example of nice cleavage stage embryos on day 3, when the embryo is expected to have cleaved into at least 8 cells. There is some variability in the cell number that we see on day 3. We expect the best prognosis from embryos that have reached 7-12 cells. If the embryo is only two cells on day 3, this is not a good sign and likely indicates the embryo has ceased to grow. Normal embryos have a fairly strict rate of progression which starts at the time of fertilization. If the time of fertilization is delayed (for example, if rescue ICSI is used), the start time of the embryo’s progression program is delayed and the embryo may reach the eight cell on day 4, not day 3 of culture since fertilization occurred a day later than expected. But except for delays in fertilization, progression should follow an expected predictable rate. Embryos don’t usually speed up to catch up if they are lagging.
Morula stages of development. The morula stage is characterized by a transformation from a loosely associated group of cells to tightly connected cells that are acting more like a tissue. The process by which cells change from loose association to tight association is called compaction. A compacted morula is a group of cells (usually around 30) which have squeezed together inside the zona. This stage is usually seen on day 4 of culture. 
The photo to the right shows two typical morula stage embryos that have compacted. The name morula comes from mulberry (Latin: morum), perhaps because the morula looks somewhat like a mulberry.
What is significant at this stage? Sometimes embryos get stuck at cleavage stage and never compact. This is a bad sign and the embryo is no longer viable unless it makes this transition. Embryologists like to see that most of the cells are incorporated into the morula. Cells or large fragments that are left outside of the compacted morula are non-viable. In the picture on the right, you can see a little fragmentation between the morula and zona pellucida (the shell) but not too much. These morula look pretty good. Notice that in each picture from fertilized egg to zona, the zona is still about the same size, but the dividing cells within it are getting smaller and smaller with each division.
The blastocyst stage. Reaching the blastocyst stage of development is considered a very favorable sign for implantation and pregnancy. In a typical IVF cycle, some embryos fail to go on at each stage. It is unusual for 100% of a patient’s fertilized eggs to get to blastocyst stage but it can happen. Embryologists talk about expanded blastocysts, non-expanded blastocysts and hatching blastocysts- all stages in the continuum of blastocyst development. By the blastocyst stage, the embryo has reached 50-150 cells and is starting to strain at the confines of the zona pellucida. 
This straining is not simply due to cell division but also active pumping of fluid by embryo cells into the inner space of the blastocyst, forming a cavity or blastocoel. The filling of this space with fluid expands the blastocyst and we call this embryo an expanded blastocyst. Before creation of this fluid space, the embryo is called non-expanded. You can see a group of blastocysts that have expanded in the photo to the right. The expansion of the blastocyst helps thin the zona and eventually helps to rupture the zona and let the blastocysts escape or hatch from the zona pellucida. In the expanded blastocyst, the embryologist can see the inner cell mass (ICM) within the blastocyst. I have labeled the ball of cells that make up the ICM in the photo. The ICM contains the cells that will give rise to the actual cells of the fetus. The other cells that surround and protect the ICM and line the inner side of the zona pellucida are the trophectoderm cells. The cells of the trophectoderm give rise to the fetal part of the placenta. The mother also provides cells to the placenta.
What is significant at this stage? The embryo must have a inner cell mass. The absence of an ICM means game over for the embryo since these cells have died off within the blastocyst. These blastocysts are not transferred. The other troublesome sign is when the blastocysts seems to have a low number of cells, suggesting that the transformation program began before cell division was completed, leaving the embryo with an inadequate cell base for development. The blastocyst stage typically occurs on day 5 of culture and we would see hatching early on day five, especially if the zona was hatched earlier for embryo biopsy. Sometimes the blastocyst will not become expanded until day 6. Differences in culture medium or other features between programs may explain why some programs see full expansion and hatching on day 5 and others see this more on day 6. In our program, we expected to see most if not all the embryos in a patients group of embryos reach this stage on day 5.
There’s another interesting feature of blastocysts and that is their ability to expand- and contract. Expanded blastocysts may “collapse” in culture and look unexpanded. With time, the blastocyst will re-pump the fluid and “re-expand”. A “compacted” blastocyst is likely a transient condition in which the fully pumped up blastocyst has “deflated’. As long as the blastocyst is capable of expansion, this temporary deflation is not a problem. In fact, prior to vitrification, many programs routinely deflate their blastocysts to optimize the vitrification procedure. After freezing and thawing, a sign of recovery is re-inflation or re-expansion of the blastocyst, showing that the embryo is alive and pumping- literally.
In vitro artifact or source of identical twins? Interestingly, one study using time lapse photography of collapsing and re-expanding blastocysts found a connection between the frequency of collapse and the size of collapsing blastocysts and an increasing frequency of monozygotic or identical twins from IVF. Researcher Dianna Payne described her theory that the frequent collapse was a sign of local areas of cell death. The frequent collapses allowed embryonic cells to move and relocate to a second site within the blastocyst, setting up two ICMs that could lead to identical twins. Excessive cycles of collapse and reexpansion could kill the blastocyst if it becomes unable to expand. In another study, the ability of a blastocyst to reexpand after thawing was used as a predictor of better pregnancy outcomes.
Hatching Blastocysts. The photo to the right shows an empty zona and four fully expanded blastocysts in various stages of hatching. 
You can see a bubble of cells sticking out (hatching) out of the left side of the top left embryo. Directly below this embryo, you can see an embryo that is completely free of its shell and its empty shell or zona pellucida has floated to the top of the photo. If you look closely, you will notice that the edges of this hatched embryo is irregular and not shiny like those of the blastocysts that are still enclosed by the zona. The two smaller blastocysts to the right of the hatched blastocysts are still expanding, note their relatively smaller size.
In the picture below, you can see another photograph of a blastocyst in the middle of hatching, half in and half out of its shell. 
You can see an area in the middle of the embryo that appears more open. This is the blastocoel. Notice how thin and small the zona looks relative to the first photo of the fertilized egg. Some of the newer culture mediums are better designed to allow the natural thinning of the zona in preparation for hatching, making assisted hatching procedures to artificially open a hole in the zona largely unnecessary except for cases in which embryo biopsy is required. Embryo biopsy (removal of one or more cells) from the embryo for genetic analysis requires that a hole is made in the zona at either the eight cell or blastocyst stage embryo.
What does all this embryo progression, embryo scoring and achieving blastocyst stage mean for a person’s chance of pregnancy? Determining which embryo will implant and make a baby is the holy grail of embryology. Evaluation or scoring based on appearance of the fertilized egg, cleavage stage or blastocyst stage embryos have all been proposed by embryologists to determine which embryos have pregnancy potential and which don’t. Some clinics have done retrospective studies of embryo progression- a functional test. The embryo progression of sibling embryos was compared from patients who got pregnant to patients who did not get pregnant after day 3 transfer. Did these sibling embryos stall out or progress to blastocyst stage? Generally speaking, patients whose excess embryos went to blastocyst stage were more likely to get pregnant than those patients whose remaining embryos did not progress to blastocyst stage. So progression is a good functional test of viability and selection of embryos at day 5 of culture is a good tool to identify the embryos that can make it at least that far. Genetic testing for embryonic abnormalities that prevent pregnancy may be the key to identifying the embryos that make babies but those tests are still under development. Testing of embryo metabolism or metabolomics is another promising arena for developing new predictive tools to determine embryo viability.
The bottom line is that even with all embryo characteristics that have been proposed as predictors of implantation and pregnancy, there is not yet one test which accurately predicts which embryos will develop into babies. I am hopeful that a combination of existing evaluation methods and future analytical tests will one day identify those embryos that will produce a healthy pregnancy and child.
© 2010, Carole. All rights reserved.
November 11th, 2010 at 11:10 pm
Many thanks to the in-depth reply above.
I was wondering if there is any truth to the following thinking regarding the two different types of CGH, namely 3 day and 5 day.
Up to day 3, the embryo is reliant on the energy in the maternal DNA, (which in my case is 42 years old) to reach the 8 cell stage. Assuming 3 day CGH is performed, 1 cell is removed and once again it’s the old, maternal energy that has to be used to bring the embryo back to the 8 cell stage.
However, with day 5 CGH, a few blastomeres are removed at the 5/6 day stage when the blastocyst is growing using the energy of the blastocyst, which is young and fresh and thus in my eyes can easily regenerate and is the less invasive procedure.
Please tell me if my thinking is fallacial. I have had day 3 CGH of 9 embryos where none made it being good enough to freeze. I have done a day 6 (my embryos are old and slow!) CGH after which 5 were and still are frozen. I have one more retrieval coming up before a FET and would like your opinion on my thoughts.
November 12th, 2010 at 8:02 am
Hi C,
Let me try to sort this out for you. You are talking about the switch-genomic activation- that happens in the early embryo on day 3. Before day 3 the embryo is relying on stored materials in the egg like RNA and protein (not DNA) that the developing egg transcribed from the maternal DNA prior to fertilization. The DNA of the the embryo is already a mixture of male and female DNA which commingle at fertilization. Unfortunately, there is not a rejuvenation of DNA with embryo development after genome activation. At genome activation, the embryo relies on its genome (a mixture of male and female DNA) which may have abnormal chromosomes in it. Aneuploidy or an abnormal number of whole chromosomes (can also be the presence of abnormal regions within chromosomes) are present in the egg (or the sperm) and probably persist indefinitely through all stages. It is possible, if the aneuploidy arose after fertilization in only one cell- a condition called genetic mosaicism- this cell might be weeded out as the embryo continues to develop. This concept is controversial and not universally accepted so I wouldn’t expect the embryo to “cure” itself of aneuploidy-especially if it arose from the egg. If the aneuploidy is present in the egg, it will likely persist and be equally detectable on either day 3 or day 5(or 6)- so CGH should work reliably well on either day. To diminish the risk of false results from sampling a non-representative cell (due to genetic mosaicism), trophectoderm biopsy on day 5 is useful because a greater number of cells can be sampled from the embryo. Unfortunately, your age is working very much against you. If you are like most women in your age group, aneuploidy is likely to be a problem in the majority of your embryos. The good news is that CGH should be able to detect this problem at either day of culture. I wish you the very best in a difficult situation. Please keep in mind all the other options you have for motherhood if this cycle and FETs do not work. Good Luck!!!
December 12th, 2010 at 6:26 pm
If an embryo was grade 3 (grade 4 being the best) on day 3 but a morula on day 5 when it was transferred, and there are no other embryos to compare progression with, what chances of implantation can be expected for <35 age group?
December 12th, 2010 at 7:19 pm
It is really impossible to say. A late morula is just a few hours away from an early blastocyst, so I wouldn’t rule out implantation. We use cell stages and progression as a rough indicator of viability but embryos can and do surprise us.
December 30th, 2010 at 10:48 pm
Hi Carole
Thanks very much for hosting such an informative blog!
My question is regarding PGD. Due to my husband and I being a cariers of a thalassemia we have to undergo PGD. We are also looking for an HLA match with our baby who has thalassemia and want to start the process asap. We met 2 IVF experts (both highly regarded in our area) for consultation and both recommend very different approaches
Option 1 – PGD for Thalassemia + HLA match + Aneuploidy (I am 36 yr old) on day 3 embyo with a fresh tansfer on day 5
Option 2 – PGD for Thalassemia + HLA match + 24 chromosome testing on day 5 blastocyst with a FET in the subsequent cycle/month. The FET is needed becasue the PGD and chromosome tesitng will not be done in time to enable fresh transfer.
My husband and I are very confused –
While upside of option 2 is that the cells for genetic testing will come out of the blastocyst rather than embyo so it will be removing cell(s) from a larger vs. smaller embyo and thereby lesser potential damage. Is this correct?
The potential downside of this option is that it will need freezing and thawing of the blastocyst so there will be extra stress to the blastocyst.
So we dont know if the upside of option 2 outweighs the downside. Can you help us with some more insights regarding benefits/drawback of each option? Please help!
Thanks
Melrose
December 31st, 2010 at 10:02 am
The short answer to your question is that either option CAN work very well. The key is determining which program has the best track record with their favored approach. Ask for statistics on their outcomes- not just the number of successful pregnancies but also the number of PGD cycles they have done using their methods and how long they have been using their preferred technical approach. You are correct in that option 2 has both advantages (more cells sampled), but also more potential for problems, since the team must be excellent at not only PGD but also cryopreservation. I would avoid a program that does NOT use vitrification for the freezing step. Older methods are more stressful to the embryo. If vitrification is the freezing method used and if it is performed competently, stress to the embryo is minimal. You’ll need to get some more data from the lab and physician about the number of cycles they have done (for PGD with or without freezing) and their pregnancy outcomes for patients in your age group. If the program can’t or won’t give you this information, that suggests to me that either 1) they are not tracking this data and so are doing no real quality control or 2) their results are preliminary because the procedure is new for the team or done infrequently or 3) they are not seeing very good results. Good Luck. Best wishes for a healthy baby (and sibling) in the new year!!
January 2nd, 2011 at 7:04 pm
Hi Carole
A very happy new year to you!
Thanks so much for your clear response. It is really helping us think clearly. A few other things -
1. How many PGD cycles of an institute can be considered as a good sample size to estimate success rate? As PGDs are still quite limited what should we consider good enough.
2. Can you suggest a few labs in the NY-NJ area which are the cutting edge labs for vitrification cryopreservation or the ones you have heard good reviews about?
Thanks so much once again!
Melrose
January 2nd, 2011 at 8:39 pm
These are both tough questions because the national pregnancy success rates reported to the CDC don’t break out cycles that use PGD or vitrification, so there is no PGD- specific or vitrification-specific reports to allow you to evaluate programs. You can get a general idea about how good a program is at everything they do if you look at their overall CDC or SART reported pregnancy rates for your age group. I have two earlier posts that explain how to find a good clinic using these sites:
http://fertilitylabinsider.com/2010/05/finding-a-good-fertility-doctor-part-one/
http://fertilitylabinsider.com/2010/05/using-cdc-reports-to-find-a-good-fertility-doctor-part-two/
The CDC and SART sites are state-specific databases so you can investigate NY-NJ clinics specifically). I’m sorry but I can’t recommend specific clinics–even though physicians have asked me to!–in my blog. My blog is more useful and credible if it remains independent.
Generally speaking, If you are using a clinic that has a 50% pregnancy rate in its under 35 year age group and does at least 200-300 cycles a year including 10% PGD, that’s probably a decent program, Their PGD pregnancy rate should not be much lower than their overall pregnancy rate for each age group. f you want to know specifically about a program’s success rates only with PGD cycles and vitrification, you will have to ask the program to provide you with accurate up-to-date statistics on their success rates with both vitrification and PGD.
Regarding your first question– It is hard to define a minimum number of PGD cycles necessary for proficiency. The clinic should be doing more than anecdotal PGD cases. It should be a routine offering. Our program was relatively small (only 200 cycles a year) but we had on average 1-2 PGD cases a month. If we didn’t have a scheduled case, we did biopsy practice just to stay “in shape” for our biopsy cases.
The PGD lab may also be a good referral source to find a good IVF program. You can call the PGD lab which probably serves multiple IVF programs and ask them which IVF program they prefer to work with. If they know you are already aligned with program A, you may not get an unbiased opinion but if you are still looking for an IVF program- the PGD lab may give a useful recommendation. An IVF lab that is not very good at preparing slides or otherwise causes problems for the PGD lab may not be the one you want to handle your precious samples.
Regarding vitrification, I would use a clinic that ONLY uses vitrification for cryopreservation of their current cases. They might have used slow freeze in the past and still utilize slow thaw on those stored embryos, but I would want them to use vitrification on all fresh embryos and would like to see that they been using this method for several years. You might find my earlier post about finding a good egg freezing clinic helpful. The same principles apply. http://fertilitylabinsider.com/2010/08/finding-a-good-egg-freezing-clinic/
I hope this helps. Best Wishes.
July 4th, 2011 at 10:29 am
Hi there,
Am pretty new to the ivf world and haven’t been given good explanation nor didn’t know what to look for and ask about regarding my embryos grade.
I got 2 embryos on day 5, one with 10 cells and the other had 9 cells.
Doc told me they were rather slow and not to put my hopes up.
What are the chances of implantation with these findings.?
Thnak you and kind regards,
Sara
July 4th, 2011 at 6:16 pm
Hi Sara,
Usually, we would expect to see 50-100 embryo cells on day 5. Also on day 5, the embryo would have reached blastocyst stage with recognizable structures such as an inner cell mass (future baby) and trophectoderm cells (future fetal part of placenta) and a space between (the blastocoel). Although I never say never, the expectation for implantation of 10 and 9 cell embryos on day 5 would be very low, as your doc indicated. I am sorry I can’t be more optimistic. Best wishes, Carole
August 29th, 2011 at 5:43 am
Hi I am 40 years and recently had an IVF done in India. The doc said that embryo was 4 cell and they implanted it on the 2 day only. I had only 2 matured oocyte (female eggs),but the quality of embryo was A. and the linning of the uterus was 8mm which is below normal. The outcome was that I didnot conceive. What would you suggest shall i go for the second trial and if yes on which day is it best to implant an embryo( how many celll division should it have)for the best result. And if i had only 2 oocyte and an 8mm inner linning of the Uterus what are the chances of the IVF sucess. Thanks
Rita
November 25th, 2011 at 9:53 pm
[...] is implantation-ready).One of my most popular posts is about the progression of embryo development, “Embryo stages, progression and pregnancy outcomes”, with lots of embryo photos- courtesy of some very generous colleagues and friends in IVF-, so I [...]
December 6th, 2011 at 7:19 pm
Hi Carol,
Very useful blog.
I am 38. I got a transfer of 3, 8 embryos cells on day 3. What stage is ideal for transfer? Or what is the criteria to go ahead with an embryo transfer either at cleavage, morula or blastocysts stage?
Thank you,
Adela
December 12th, 2011 at 10:27 am
Generally speaking, at any stage, we look for the “best” embryo or embryos to put back fresh. What constitutes the criteria for determining what is best? Until we develop methods to look at what is happening inside the embryo, we are limited to evaluation of what the embryo looks like and whether it hit certain embryonic milestones on time- just like a baby is expected to reach specific developmental milestones on time, For instance, for cleavage stage embryos that are being evaluated for transfer, we like to see about 8cells plus or minus 2 cells, nice even cells with minimal fragmentation. If they have fewer than 6 cells, they are clearly lagging and may have stopped dividing so these would be a poor choice to return to the uterus. At the blastocyst stage on day 5, we like to be able to see all three distinctive structures- a well developed trophectoderm layer, well developed inner cell mass and a fluid-filled cavity between them. If the embryo lacks an inner cell mass – the cells devoted to producing the future baby, it should not be returned to the uterus. If the trophectoderm has very few cells, it might be a poor candidate embryo to make a healthy placenta and would be a lower-ranked embryo to choose for transfer. Hope this helps.
Carole.
December 17th, 2011 at 4:40 pm
What a great informative blog. I just had two expanded blastocysts transferred on day 5. Both were graded CC. With my last IVF we did a SET with expanded blastocyst, grade BB that resulted in a chemical pregnancy. In your mind is it more important that they are expanding blastocyst or the grade? (would an early blastocyst grade AA be better)….should we consider implanting on Day 3 (when we had 8 embryos still around)? Lots of research but no definitive answers.
December 18th, 2011 at 8:45 pm
Hi Sydney,
Best wishes,
An “AA” graded blastocyst just means that at the time of assessment, the embryo has a lot of cells in both it’s inner cell mass and the trophectoderm. It is an easy choice to transfer because it has reached an advanced stage. A “CC” graded blastocyst means fewer cells in both cellular compartments at the time of assessment but it does not mean that the embryo can’t implant. Transfer of cleavage stage embryos on day 3 and transfer of blast stage embryos on day 5 both result in pregnancies. Growing to day 5 is useful if we want to identify the most advanced embryos in a group of embryos. But even slower progressing embryos implant so grade is less important if they reach the blastocyst stage on day 5 (or even day 6). Your question is a good one so I wrote a new post http://fertilitylabinsider.com/2011/12/understanding-the-gardner-blastocyst-grading-scale/ based on your question that has much more details in it and a link to graded embryos which may be useful to you. So please don’t despair, it’s way too early to give up on this embryo and this chance at pregnancy.
Carole
December 19th, 2011 at 7:52 am
Thank you! You have made my morning and the rest of the week. It is so helpful to have some one like you on the web!
December 19th, 2011 at 11:13 pm
jUST WONDERING IM ABOUT TO GO IN FOR A DAY 5 TRANSFER TOMORROW AND THE CLINIC RANG ME THIS MORNING TO TELL ME THAT OUT OF MY 6 EGGS ONLY 4 ARE PROGRESSING AND ONLY 2 ARE DOING OK.
I HAVE ONE THIS MORNING AT 10 CELLS AND THEN THEY RANG TO MAKE MY TRANFER APPOINTMENT 3 HOURS LATER AND IT HAD MOVED FROM 10 CELLS TO 12 CELLS. THE OTHER ONE WAS 6 CELLS AND HAD MOVED TO 8 CELLS. SHOULD I BE WORRIED THAT THESE ARE JUST TOO SLOW AND I WONT GET A PREGNANCY OUT OF THESE?????
December 20th, 2011 at 5:29 pm
The best thing to do is ask your doctor what is the pregnancy rate you can expect from embryos that look like yours for patients who are as old as you in THEIR program. That’s what you really want to know. In our lab, we would be concerned that they are somewhat slow UNLESS they are compacted and are actually forming a morula- the pre-blastocyst stage on day 4. I can’t really answer your question specifically because every lab is a little different. Best Wishes for a BFP. Carole
December 20th, 2011 at 9:43 pm
Thanks for that i went in for my transfer today and i had a compacting blasto and a morula that was compacting and growing to the early blasto stage. Im hoping that they are right on track for day 5 now the dr seemed happy with their progress should they be at this stage?
December 21st, 2011 at 8:51 am
I would feel optimistic at this point. They haven’t stopped dividing! Best wishes!!
December 22nd, 2011 at 6:23 am
If implantation was to occur when does that happen now I have had a transfer. Yesterday was a day 5 transfer.. Thanks for all your help
December 22nd, 2011 at 6:27 am
If implantation was to occur when does that happen now I have had a transfer. Yesterday was a day 5 transfer.. Thanks for all your help I wish this was around for my other cycles.
December 22nd, 2011 at 7:06 pm
Hi Kristie,
About 2 days after the day 5 transfer, the blastocyst should be hatched and starting to burrow into the uterine lining. The implantation process continues for several days and the embryo start to secrete hCG which is the pregnancy hormone detected in the blood or urine. Here a link with a nice chart of what happens after either day 3 or day 5 of pregnancy. Best wishes and Good Luck!! Carole
January 6th, 2012 at 12:08 pm
Hi! I would love to hear your independent thoughts on the quality of my blasts based on your experience. I am 43 and I’ve had 7 natural IVF cycles resulting in 6 blastocysts. The 7th embryo arrested on Day 4. They have been frozen via vitrification. Here are the blast ratings my dr.’s office shared with me and they said they never rate a blast as an “A”:
1st number: stage of blast
1 – early blast
2 – regular blast
3 – expanded blast
2nd number: ICM
The lower the number, the better
3rd number: Placenta
The lower the number, the better
Here are my blasts:
1. 5-day, “4-2-3″, “B”
2. 5-day, “2-2-3″, “B”
3. 6-day, “2-3-3″, “B-C”
4. 5-day, “2-2-3″, “B”
5. 7-day, “3-2-2″, “B”
6. 5-day, “3-2-3″, “B-C”
Your initial thoughts?
Is it common for a 43-year old to obtain 6 blasts out of 7 natural cycles?
Might I have better than normal pregnancy odds than an average woman might my age?
Would the 7-day, expanded blast be considered to be higher quality than the 5-day regular blast? Or would a 5-day always be considered stronger than a 7-day?
Are there specific questions I should ask my embryologist?
We may pursue 2 more blasts before starting SET’s.
January 6th, 2012 at 7:54 pm
Val,
Unfortunately, even with the very precise description you provided of the embryo scoring of your embryos, I can’t answer the question likely most important to you- the implantation potential of your embryos. The reason is that what any embryo looks like is less important than what is going on inside the embryo.
The embryo’s viability depends in part on its chromosomal normality. The biggest hurdle women over 35 years of age have in getting pregnant is that as they age, they start producing eggs with either too few or too many chromosomes (aneuploidy). Most forms of aneuploidy are not compatible with a viable pregnancy. The condition of Down’s syndrome is one exception to this rule because a third chromosome 21 does allow implantation. pregnancy and life- although a shortened life span with significant health and developmental challenges. As you probably know, the risk of having a child with Down’s syndrome increases with the age of the mother- this correlation is due to increased aneuploidy in embryos with age. Generally speaking, an embryo that reaches the blastocyst stage on day 5 is progressing at the expected pace whereas an embryo that requires two additional days to reach the same stage is abnormally slow and would be less likely to implant, in my opinion. Embryo development has milestones similar to childhood developmental ilestones. Babies may reach them at different times but there is a range of normal. In both embryos and babies reaching these milestones later can suggest underlying issues delaying development.
Good Luck!! Carole
January 12th, 2012 at 8:27 pm
Hi Adele,
Either stage (cleavage or blast) can result in implantation or pregnancy. If a patient has many fertilized eggs in excess of the number desired for transfer, giving the embryos a chance to progress in culture can reveal the best growing embryos and so the best two can be transferred. If the patient only has two cleavage stage embryos on day 3, there is not any advantage (in so far as selecting the best two) by allowing the two to keep growing in culture for two days. At cleavage stage, embryos that have around 8 cells (6-10) with little fragmentation and evenly shaped cells would be preferred for transfer. At blastocyst stage, we would select embryos with a well-defined inner cell mass and trophectoderm. The inner cell mass has the cells that give rise to the future child and the trophectoderm cells give rise to the fetal placental structures. Both structures are equally important to the future success of the pregnancy so we like to see that these structures consist of well-organized groups of cells. The morula stage is a sort of in between stage when the embryo is reorganizing itself from a uniform collection of loose cells to a more tissue like organism. Morulas are the ugly duckling transitional stage between cleavage and blast. Morulas can be transferred and they do result in pregnancies (assuming they continue to develop after transfer). Transferring 3 8 cell embryos in your age group sounds promising. Best wishes for a positive pregnancy test! Hope this info helps, Carole
January 26th, 2012 at 2:41 am
Hi Carole, the information on your site is fascinating. I had PGD done so knew the gender of my day 5 embryos transferred. 1 good looking blastocyst (about 100 cells) = boy. 1 morula somewhat fragmented, only about 10 cells = girl. Both implanted and at 7 wks there were 2 heartbeats, but one of them – baby B – was much smaller and lagging behind, slower heartrate and doc didn’t expect it to catch up. By 10 wks it was clear that baby B had stopped growing and was disappearing. We assumed I’d be having a boy since that was the healthier looking embryo at transfer. I’m now 16 wks and at today’s ultrasound, my doc is 95% sure that I’m having a girl! I am so surprised that the little girl morula that the doc didn’t think would be good enough to freeze would beat out the boy blastocyst that was developing right on track. Have you any comment or insight into how this comes about?
January 27th, 2012 at 2:13 pm
Can you please give me some help? I just did a 3 day transfer. We transferred 3 embryos (11 cell, 6 cell, 4 cell). At first I was excited about the 11 cell but with more reading it seems on day 3 there should be 6-10 cell and the 11 cell may have grown too fast indicating it is abnormal. Is that correct? Thanks SO much for your time! Melissa
January 27th, 2012 at 2:33 pm
I would not be overly concerned about the 11 cell, that’s not far removed from the 8-10 cell “ideal”. I would be more concerned if it had even more cells- say, 13 or more cells and no sign of compaction. No need to worry at this point. Be hopeful. Good Luck! Carole
February 1st, 2012 at 11:08 am
Carole,
I have gone through 3 failed IVFs (2 fresh, 1 frozen). I have transferred 5 blasts to date (all which were rated as “perfect”.) Unfortunately, I have also suffered from thin linings during FETs and recurring fluid in my uterus. My doctor feels that I have a uterine issue and is treating me accordingly.
However, a second opinion with another RE stated that it may not be my uterus, and than even with “perfect” blasts, they could all be abnormal.
I currenlty have 6 frozen 2PNs, 1 frozen 5 day blast and 4 frozen 6 day blasts. I am 32 years old and my only diagnoses have been blocked tubes which I had removed and hypothyroid which I am treating.
What are the odds that All of my blasts are abnormal????????? I always assumed a surrogate was my last resort but now I am afraid I might not have that option.
Also, my Dr. suggested biopsying my blasts after thawing them and then performing the FET. He said we could perform CGH restrospectively if things failed. Is this highly risky to do to the embryos?????
February 1st, 2012 at 1:10 pm
Dear Em,
I am sorry that you are having such a hard time. I don’t know what the odds are that all your blasts are abnormal. You are only 32 years old so having 100% abnormal blasts is more UN-likely in a young woman (under 35) such as yourself compared to a woman over 40. I think what your doctor is talking about is thawing the 2PNS, growing them out to either cleavage stage and biopsy (test results back in 2 days for a day 5 fresh ET) or biopsy at blast stage. Biopsy at blast stage usually means refreezing the blasts and storing them pending results and a future FET. However, some testing labs are offering overnight testing so results are back in time for a day 6 fresh transfer, so the embryos don’t have to be frozen (or refrozen in your case). You could thaw the blasts, biopsy them and depending on when the test results get back, either refreeze or transfer fresh a day late, if overnight results are available in time. In theory, if you get aneuploidy results on each embryo, you can choose to just transfer the embryos that have a normal chromosome number. Doing that could remove one reason that you are having trouble getting pregnant but as you mention, there might be other factors as well. CGH testing costs several thousand dollars and probably is not covered by most insurance plans (but you should always check in advance just to be sure). Biopsy and CGH testing is still considered research, not routine clinical care because the biopsy can go wrong, providing an inadequate sample for testing, resulting in NO RESULTS or even damaging the embryo. Shipping to the testing lab can go wrong and again you might have no results you can use. Refreezing also has risks. “Perfect” embryo scores are not terribly meaningful as usually it is only based on appearance of the embryo – how even the cells are and how much fragmentation is present. I’d bet on an “ugly” embryo from a young woman before I’d bet on a “beautiful” embryo from an older women, because what’s inside (what we can’t see) is more crucial to whether the embryo will implant or not, and we know pregnancy rates decline with age due to maternal factors. Another option is to go ahead and transfer some of your stored embryos in more FET cycles. Just because it didn’t work before does not mean it’s guaranteed to fail in the future. I wish I had an easy answer for you. Good Luck, Carole
February 2nd, 2012 at 11:23 am
Carole,
Thank you for your response. I am really enjoying reading your blog.
To clarify, my RE is suggesting that we thaw my embryos do a biopsy, and then transfer them before acutally performing CGH. He then suggested that I only spend the $ on CGH if my FET fails (since he will already have done the biopsy.) I plan to transfer 3, so this would only allow him to biopsy 3 of my 5 blasts.
The thought is that if I fail another cycle, this might give a more definitive answer as to whether my uterus or my embryos are the problem. (Maybe neither and next time is my time). But, I am not sure if only testing 3 would give the whole story?
Also, I can’t find anything on-line about biopsying blasts after a thaw. Usually it is done before. I’m not sure how high the risk is that the embryos will become damaged in their fragile state.
Thoughts?
Thank you!
February 2nd, 2012 at 11:32 am
Em, I don’t know of anyone who does the biopsy, then transfers the embryos without the benefit of the test result. The whole point of testing is to start the pregnancy with a healthy embryo to prevent you the heartache of a miscarriage. Also, testing detects chromosomal abnormalities like Trisomy 21 which are completely compatible with pregnancy but you’ll have a child affected by Downs Syndrome. You can’t assume that abnormal embryos won’t implant, they do, but cause issues down the road. This does not seem like a great option for you as I understand it. You are also correct that testing 3 only gives you information about those 3 and tells you nothing about the other embryos you have. You might be best served with a second (or third) medical opinion from a physician. Good Luck, Carole
February 3rd, 2012 at 3:19 am
Hi Carole
Just wanted to tell you thanks SO much for answering my question. You made me feel much better!
Melissa
February 3rd, 2012 at 3:26 am
[...] 15 Just a little info for anyone interested. I found a good website where an embryologist blogs about IVF stuff. Very informative but the best part is at the very bottom of the page you can submit questions and she will actually answer them for you. I asked about my 11 cell embryo and she responded 20 min later to answer my question! Hope this helps. Embryo stages, progression and pregnancy outcomes | Fertility Lab Insider [...]
February 3rd, 2012 at 7:09 am
You are very welcome! Good Luck!! Carole
February 4th, 2012 at 11:21 pm
Hi Carole,
I just had an FET from a blast frozen from my second IVF–the cycle that gave us twins! We had two frozen blasts left and one made it through the thaw–it was grade 2 out of 3 at the time of freezing (it was from 2004 before the clinic changed it grading). They said it looked good and the embriologist gave me a picture after the thaw picture to show me it was “expanding”….I feel like this is good, but what else should I have asked? What else should I look for? Does it help that it was from a previous successful cycle or does the freezing change that?
February 5th, 2012 at 8:53 am
Hi Kim,
It is good that these embryos came from a previously successful cycle and expansion suggests that your embryo survived the thaw and is going about it’s business of continuing to grow. All good signs. There’s nothing else to do or ask but to get through the time until your pregnancy test. “Don’t worry, be happy” may be trite but it is actually a good plan-if you can manage it- until you know how things have turned out. Good Luck!! Carole
February 5th, 2012 at 9:58 am
on day 3 i did embryo transfer with 18cells it is good or not scared can anybody help me with this please
thanks
February 5th, 2012 at 10:22 am
Rosy,
Don’t be scared. Embryo scoring is subjective. Large fragments can be scored as cells, inflating the cell number. Your IVF team would have selected embryos to transfer based on what they have seen create pregnancies in the past. If you had nothing they felt was viable, you wouldn’t have had a transfer. Try not to worry. Good Luck!! Carole
February 5th, 2012 at 2:07 pm
thank you so much Carole! Its so nice to have this forum!
February 9th, 2012 at 10:47 am
Hi i m 27 yr old i m undrgng ivf tretment his is my 8 day after ET.this os my first ivf cycle got 25 follicle,11 are fertilised nd 3 are transfer in that one is compacted,one is compacting,nd one is 8 cell on 4 day transfer how much is the chance of geting pregnant?
February 9th, 2012 at 11:13 am
Generally speaking, your age (under 35) is definitely in your favor. I really can’t predict whether you will get pregnant or not. Your doctor, however, should be able to look at his (or her) previous clinical cases and tell you what percentage of patients at your age with your history and embryology stats became pregnant. This is the best predictor of your success. Good Luck!! Carole
February 9th, 2012 at 8:18 pm
thankss a lot..bt i am askng from my embryo ststaus is that good? nd my ingertlty r due to tubal factor prebsly i had ectopic.from last 2 year m unable to concive,just repy abt my embryo is that gd in 4 day transfer to becme pregnant plz reply…
February 11th, 2012 at 9:07 pm
Jan 2002 I transfered 2 gradeC 8cell and was successful…both implanted but lost one at four weeks. I froze the remaining two which are 8 cell graded B…. Weird that they took the one that were graded C first..
My age was 29 at retrieval time….
What are the chances of my embryos making it through the thaw (slow freeze)
What about implanting.now that I am 38? my lining on cd14 was 10mm triple line…
February 12th, 2012 at 7:32 pm
Hi Meagan,
Although most programs typically transfer the best scoring embryos and freeze any others meeting freezing criteria, some programs freeze the best. Wny? In the past, it was not unusual to lose 50% of the cells after thawing from a slow -freeze protocol. Vitrification, done correctly, preserves the cells better so you don’t have to factor in a loss of cells when deciding which embryos to freeze. Some programs may want to be sure that most of their patients have something to freeze and freezing the best and transferring the rest helps to accomplish that goal. You’ll need to ask your clinic what their results are-for instance, ask “typically, what is your pregnancy rate using embryos frozen and thawed using the same protocols used for my embryos? Protocols change at clinics over time, so their success rate during the time period your embryos were frozen is most pertinent to your success. The ovaries suffer most from aging. Wtih hormonal priming, your uterus can carry a pregnancy even after menopause. You may have read the news accounts of a grandmother serving as a gestational carrier for her own daughter, in effect giving birth to her own grandchildren. This is possible because the uterus retains function longer than the ovaries, so if your lining develops appropriately in response to the hormones you’ll receive, your age should not be an issue.
Good Luck,
Carole
February 12th, 2012 at 10:43 pm
Hii.
my ET was done at 02/02/2012 this is my first ivf.
with 3 embryo(8cell)fr last night since12/02/2012 i had small amnt bleeding …morng also bleedng…(blood colour r pinkish brownish) is that i lost everythng .i m cring pkz plese help.why this bleedng oon 12 day post tramsger?
February 13th, 2012 at 7:15 am
Dear Varsha,
Please call your doctor to answer this question. There are many causes for bleeding and it doesn’t always mean that you have lost the pregnancy. There is implantation bleeding which can occur at the time of implantation. Some women have bleeding episodes at various times in pregnancy and have the pregnancy survive. Please see your doctor for help. Good Luck!!
Best Wishes, Carole
February 13th, 2012 at 10:19 am
Hi,
I’m 45 years old and have gone through several ivf trials with no success. The last was a donor who was 33 at the time of retrieval and I had a transfer with day 3 embryos which were a 4 cell and an 8 cell. I got pregnant there was a yolk sack but no fetus. It has now been 8 months since this transfer and I haven’t gotten a period. I went to my doctor and they told me I have gone into menopause. I have to frozen embryos left both at the 3 day stage. One is 5 cells and the other is 10 cells. My husband and I are very ambivilant about whether to attempt another transfer with these embryos. Do we have any chance at pregnancy with this history.
February 13th, 2012 at 11:10 am
Jessie,
I don’t know is the honest answer. There is always a chance but whether there is a good chance–what you really want to know– is more difficult to answer. On day 3, embryos should be at least 6 cells, 8 cells is the ideal and some embryologists feel that much past 8 cell (10 or more without signs of compaction) could also be problematic. You should ask your doctor what his/her experience has been transferring embryos like yours. This is probably the time to sit down with your husband and really decide what you want at the end of the day. Certainty that you have exhausted all options? Or is it time to move on and try some other avenues to parenthood? I can’t answer that for you but I truly wish you the very best going forward. Good Luck!! Carole
March 4th, 2012 at 1:41 pm
Hi, I was just wondering what would cause my embryos to arrest at the day 1 – 2 stage?
I have done 3 cycles. First one at age 30 resulted in 6 mature eggs, 4 fertilized with ICSI (we went to ivf because of severe male factor). By day 2 – one was 4 cells, one was 2 cells and one was dying and the fourth was not dividing properly. We transferred the 4 and 2 cell, I got pregnant with a singleton, but m/c just before 9 weeks.
2nd cycle at 31 years old I again got 6 eggs and 4 fertilized. By day 2 only 2 were still alive. We did a day 3 transfer of a 6 & 7 cell embryo and I got pregnant with twins, but twin B died at 21 weeks. I gave birth at 31 weeks because of pre-eclampsia.
Now 2 years later we decided to cycle again for another child. Everything was going good when I triggered on day 13 (had 11 mature follicles), but at ER they were only able to retrieve 4 eggs. Yesterday which was day 2 past ER they called with the fertilization report to say out of the 4 eggs collected, only 2 fertilized and they both arrested (like my 2nd cycle they must have arrested at the zygote stage before even cleaving once).
Just wondering why so many of my embryos are not even getting past the one cell stage. Is it just bad eggs or is it the lab? 2nd and 3rd cycle were done at the same place (first one was done at a different clinic). Also how can this be possible. I am not even 34 yet and before we started ivf all my tests were fine (I ovulate every month etc), it was just my husbands low sperm count that lead us to ivf. Both me and my husband have also had our karyotyping done and we are both normal.
March 4th, 2012 at 4:36 pm
Dear cp,
The short answer is I don’t know. There are many reasons that an egg might become fertilized but then not divide at all or only divide once. We don’t even understand all the molecular pathways in the embryo that make it “go” and do the stuff it does. Genetic problems like having an abnormal number of chromosomes in the gametes is one possibility for failed cleavage- even if your karotype is okay, there are problems with aging (increased incidence of aneuploidy) that affect us all. Then there are cytoplasmic factors- proteins, enzymes, growth factors etc –again many largely unknown- that have to function correctly for cell division. It is probably less likely that the lab screwed this up since you had success with this lab before- especially if their success rates are greater than 50% overall. And you shouldn’t even consider going to a program with less than a 50% success rate in the youngest age group. Whatever the reason, IVF is not working very efficiently for you. The question becomes- how much more emotional and financial reserves will you want to use here? You have gotten pregnant with IVF but if IVF works only once per every 3-4 tries, it may not be the best option for you for enlarging your family. Your physician should be able to give you more specific advice going forward. I am sorry I don’t have a better answer but I wish you all the best going forward. Good Luck!! Carole
March 9th, 2012 at 11:38 am
Hi,
I was wondering if you could help me? I’ve had a day 5 embryo transferred 2 days ago. When the clinic phones me they said my blastocyst was collapsed but this is normal and I had it transferred later that day. I had 3 day 3 frozen embryos, 2 survived the thaw, the clinic decided to grow to day 5, only 1 was viable ( the collapsed blasto) I’m in a but of a panic as what are the chances of this embryo implanting? I had an fet 3 years ago, that was a day 3 and resulted in a successful pregnancy. Please can you put some clarification on this collapsed blastocyst?
Thanks x
March 9th, 2012 at 12:08 pm
Hi Michelle,
I would feel pretty good about an embryo that was thawed and continued to grow for two more days until blastocyst stage. Blastocysts expand by two means- producing more cells and pumping themselves full of fluid-literally. The space between the inner cell mass and the trophectoderm fills with fluid and the embryo grows bigger. Sometimes, the embryo collapses, meaning it releases this fluid and has to pump itself up again. Sometimes we do this on purpose.To get better results with vitrification, embryologists will deliberately deflate or collapse the blastocyst by lasering a gap between two of the trophectoderm cells, causing it to collapse. The embryo recovers from this rather well and reinflates itself post-thaw. So don’t worry about the fact that it collapsed before transfer- that’s likely just a temporary stage in it’s development. So please don’t worry. i know it’s a long two week wait but this is not something to worry about. Also, you got pregnant before so be hopeful.
Good Luck!! Carole
March 10th, 2012 at 4:26 am
Thank you so much for putting my mind at rest! So good to be able to talk to someone like you on the net! Excellent blog by the way
x
March 12th, 2012 at 4:55 pm
Your blog and responses to comments are such a tremendous resource! I am home after a FET this afternoon. I transfered a single 4AA blast in July, which resulted in a pregnancy that we sadly had to terminate in the second trimester due to a severe heart defect. We had three other 5day blasts frozen: 4AA, 3AB, 4AC.
Today we trasferred the pre-freeze 4AA 5 day blast. What has me concerned is that the photo of the blast they gave me today looked so sketchy post thaw. I’ve read here about the concept that blasts are supposed to rexpand after thaw. I don’t know how many hours after thaw my blast was transferred. My RE said there weren’t black areas indicating cell death. He said post thaw they rate them as good/fair/poor, and that mine is still a 4AA blast but has a fair rating post-thaw.
How bad of a sign is this post-thaw rating? I’ll be really grateful for any information you can provide – I haven’t found much information about blast ratings post-thaw. Thanks!
March 13th, 2012 at 8:11 am
Hi Jflower,
I think the post-thaw rating system your doctor describes is an in-house thing. Most embryologists have an idea what they want to see post-thaw but there is not a standard rating “system” that most labs use for post-thaw assessment. He is correct that we look for dark areas as a sign of cell death and if your embryos didn’t have any post–thaw that is a good thing. I wouldn’t worry about the fact that the embryo did not look expanded in your photo. That can take some hours so if they thawed and transferred pretty quickly, the embryo might not have had a chance to re-expand before being transferred. We often collapse the embryo before we freeze it for vitrification because it freezes better so don’t worry about it still being collapsed at thaw. That would be expected. If it is healthy post-thaw, it can re-expand inside you just fine so don’t worry about that. Good Luck!!! Carole
March 13th, 2012 at 11:46 am
Thank you for your quick and helpful reply. I talked to the embryologist today, and she said that at our clinic there is a 57% success rate with “good” post-thaw blasts and a 52% success rate with “fair” post-thaw blasts. That also set my mind at ease a bit – yesterday I was imagining a more significant difference between the two in-house ratings. Thank you for being willing to share information with so many people – it’s such a comfort and a tremendous service.
March 16th, 2012 at 12:01 pm
Hiii..i m 29 yr old recently i had ivf in feb 2012but after 2month miscarriage.total my 11eggs fertilize nw 8 embryo in hosp. frreze.nw i m planing to go for my frozen embryo is that good nd how much is chance nnd sucess rate with frozen cycle.8 cell embryo frozen
March 16th, 2012 at 1:35 pm
Hi Mayu,
You’re best answer to that question would come from your doctor at your IVF lab because they are keeping data on pregnancy outcomes for their patients. Post-thaw success rates can vary a lot between clinics so I don’t want to even attempt to guess, but nothing you said should rule out a good outcome in the future. Best Wishes, Carole
March 17th, 2012 at 3:20 pm
Hi! I was supposed to have a 5-day transfer today but was told my embryos are not where they should be yet. They are having me come back tomorrow for a 6-day transfer. Is that common? Is implantation less likely with 6-day embryos? Thank you!
March 17th, 2012 at 8:54 pm
Hi Anonymous,
Pregnancies happen with blastocysts that reached blast stage on either day 5 or day 6. There is some evidence that the pregnancy rate is higher when the embryos reach blast stage on day 5 http://www.ncbi.nlm.nih.gov/pubmed/11384637. In my experience in several labs, our day 6 pregnancy rate is less than day 5. But remember that reaching blastocyst stage is a milestone, whether it happens on day 5 or day 6 and pregnancies occur from embryos that reach this milestone on either day, so don’t give up. Wishing you much Good Luck!!! Carole
March 17th, 2012 at 9:23 pm
Thank you so much for taking the time to write!
March 21st, 2012 at 6:08 am
Hi! i must congratulate you for this very informative blog. my wife and I are TTC for the last 3 years now with no luck. she is youg (29 yrs) but has had high FSH (21) in the last 2 yrs and recently high LH (15) too. we have had one IUI without success and moved to an IVF cycle recently. since my wife’s LH was high, our doctor told us that he could not give stim meds as he would not be able to control the balance between fsh and lh and moved us on with a natural cycle. we were betting on the single egg that was to come and the doctor followed up with many u/s and finally a mature egg was retrieved which was then injected thru ICSI. the egg got fertilized and got us all excited – but on the the day of the transfer (day 3) we were called and told that the fertilized egg did not divide further. that really left us heartbroken and with emotions which are impossible to describe. could you please throw some light on why this happened? if the egg was mature and the sperm sample was OK – we thougth ICSI would give the doctors maximum control over the situation but that was not the case.
would really appreciate your inputs.
thanks,
hb
March 21st, 2012 at 5:27 pm
Hi hb,
I am so sorry to hear of the difficult time you are having. First, I would seek a second opinion from another RE. I am not an expert in stimulation protocols but i have worked with many REs who have gotten good results with various protocols for patients with various hormonal issues so I don’t think that a natural cycle is your only option. if there are any REs reading this, please weigh in with your expertise. A natural cycle for IVF is a long shot proposition because at every stage in IVF, there is a loss on viable eggs or embryos. My previous post discusses this in detail http://fertilitylabinsider.com/2011/02/egg-count-mathematics-why-the-numbers-change-between-retrieval-and-transfer/ The next thing you should know is that even with ICSI, you can have failed fertilization or failed embryo development because the only thing that ICSI ensures (when done properly) is that one sperm entered the egg. But getting into the egg is only the first step of many to call the egg fertilized. See this post for more information on fertilization http://fertilitylabinsider.com/2010/06/ivf-disasters-no-fertilization/ Fertilized eggs sometimes fail to divide for any number of reasons, both known and unknown. Another reason to start IVF with 10-12 eggs, not 1. I think the first step is getting a second medical opinion if you are planning on doing another IVF cycle. Good Luck!!! Carole
March 22nd, 2012 at 2:04 pm
Hi Carol,
I am a bit confused! We had transfer of two embryos on day five on Monday. Our 5 embryos were very slow developing apparently and on day four we had an arrested 2 cell, two 5 cells, a 6 cell and a 7 cell. We were told that we may not get to transfer any. On Monday we were told that the 6 cell was showing signs of compaction as was one of the 5 cells! We were also told that there was still a chance of pregnancy in this situation but it was reduced as the embryos should have reached blastocysts by day five. I was just wondering how realistic a pregnancy from these embryos is. From what i can make out they are particularly slow and i cant seem to find anything about 5 or 6 cells starting to compact or what this might mean. Many thanks in advance
March 26th, 2012 at 10:01 pm
Hi Carol,
I had a 5 day tranfer of 2 embro’s yesterday and was told I had 1 early blastocysts stage and 1 Morula stage. I am 42 years of age and the is my 5th IVF cycle. What are the chance of these progessing or are they 2 slow.
Regards
Leanne
March 27th, 2012 at 7:32 am
Hi Leanne,
The embryo progression is fine, blast on day 5 is as expected. A morula on day 5 can still become a blastocyst on day 6 and blasts on day 6 do create pregnancies but at a somewhat lower rate than day 5 blasts. Your embryo progression is fine. Your main obstacle to becoming pregnant is most likely the increased risk of producing embryos with aneuploidy (an abnormal number of chromosomes). This increased risk is unfortunately a normal feature of aging that is unaffected by good health practices. Aneuploid embryos will go along fine for some time and look normal but then most will fail. Exceptions include trisomy 18 embryos (an extra chromosome 18 causing Downs Syndrome). At 42, the CDC reported pregnancy rate for women age 42 using their own eggs is “Pregnancy rate = 18.1%, Live birth rate=10.0%, Singleton live birth= 8.6%” http://www.cdc.gov/art/ART2009/sect2_fig6-15.htm#15 You didn’t mention using donor egg, but if you used donor egg from a younger women, your chance of pregnancy can more than double- essentially your predicted pregnancy rate is now the same as the age of the donor. Anyway, I sincerely hope this works for you but if it doesn’t, it may be time to reconsider other options for parenthood after 6 failed IVF cycles. Good Luck!!! Carole
March 29th, 2012 at 5:14 pm
Hi Caroline
I am 36 years old. We have done 8 IVF’s. 5 Fresh ICSI/IMSI cycles and 3 FET’s. We have had beautiful blastocysts in the past, in one cycle even 6 extra to freeze.
BUT, the last 3 cycles we have seen that on day 3 our embryos look great. They are 8-10 cells with little fragmentation. But then on day 5 they are still just morulas and only on day 6 some of them move to the blastocyst stage. So after day 3 something goes wrong.
We have sperm morphology problems and with IMSI we had almost no fertilization while regular ICSI give us anything between 65-99% fertilization.
We are using a really good lab. Do you have any ideas? Can it really just be bad sperm or might it be an egg problem. Or maybe a combination? What is the most likely reason for this pattern?
Any ideas why we have such bad fertilization with IMSI? (We always have at least 15+ eggs)
Thank you so much for your time.
March 29th, 2012 at 5:16 pm
Sorry, me again…I forgot to mention that we have had 3 pregnancies, but all ended in miscarriages. With the first 2 pregnancies we transferred 3AA blastocysts and with the last pregnancy we transferred a Morula on day 5.
March 29th, 2012 at 6:07 pm
Hi Miela,
First, I wouldn’t do IMSI again if fertilization rate is so poor and regular ICSI gives you between 65-99% fertilization which is what we would expect. IMSI is a newer method based on the idea that by selecting sperm whose nucleus look normally shaped at high power (using a special microscpe at higher power than normal) results in better pregnancy rate. Because you had good fertilization with regular ICSI and no or very little fertilization with IMSI, it might be a technical issue with IMSI. If this is a brand new offering at the program, the techs might not all be proficient. Pregnancies also occur from embryos that get to blastocyst stage on day 6 instead of day 5, although usually the pregnancy rate is somewhat less for d6 blasts. Failure to progress is difficult to diagnose, could be sperm, could be egg, could be both. Could be the lab can’t grow embryos to day 5 consistently but that’s not the case if it’s a good lab. Heading over to you next question now. TBC, Carole
March 29th, 2012 at 6:15 pm
Dear Miela,
Miscarriages suggest something is wrong with the embryos, perhaps aneupoloidy. Aneuploidy means that the embryo has the wrong number of chromosomes and this can arise in either the egg or the sperm before fertilization or arise spontaneously in the daughter cells of the developing embryo. It is expensive but it is possible to biopsy and test sample cells from the embryo at either day 3 or day5 to see if the cell is normal, which suggests the embryo is normal-at least in terms of total chromosome number. I don’t know if this option was discussed with you but you might ask your RE about this. If you are producing mostly aneuploid embryos, that could be one explanation for the miscarriages. You are a little young to be at the highest risk of aneuploidy, but risk increases with increased age after age 35.It’s a normal process of aging. You should discuss these concerns with your doctor. They are better able to provide you advice based on their understanding of your special circumstances. good Luck!! Carole
April 11th, 2012 at 10:38 am
Hi Carole,
Thank you for such an informative blog. I’d be interested to hear your thoughts on my situation. I am 30 yrs. old and my husband is 31. My husband has a separated vas deferens and had TESE to remove sperm. Other than that, we did not realize we had fertility issues until starting IVF.
Our first cycle, we had 11 of 14 eggs fertilize. Things looked great until day 3. By day 5, only 1 embryo made it to the blast stage. We transferred the blast and 1 morula, but it didn’t result in pregnancy.
Our doctor explained that sperm quality can vary between vials and suggested we try the same protocol, but do a 3 day transfer for IVF 2.
For our second IVF, we had 11 of 12 eggs fertilize. Had 3 8-cell embryos on day 3, 2 10-cell, a 7-cell, a 6-cell, and a few lesser quality. We were optimistic. Again, none of these made it to blast.
I’m not sure if we should continue trying. It seems like our embryos just will not develop past day 3.
April 11th, 2012 at 1:03 pm
Hi CM,
I am sorry you are having such a hard time. I guess the first thing to rule out is lab issues with day 5 culture so I would find out whether your clinic routinely cultures embryos out to day 5 and that this is successful for the vast majority of their patients. Having said that, there is a correlation with having very low sperm count due to congenital absence of the vas deference or obstructed vas deferens (more similar to your husband;s situation) with increased chromosomal abnormalities in sperm. Sperm chromosomal abnormalities in the embryo is one possible explanation for arrested embryos before they get to day 5. The good news is that some of your embryos made it to blast or nearly (morula) in IVF 1 so it’s not a case of 100% arrest. In IVF 2, the normally progressing were likely transferred so if only lesser quality embryos were left in culture, failure to reach blast is not too surprising. The bottom line is I really don’t know what to tell you. If you went to a program that offered microarray aneuploidy screening to look for chromosomal abnormalities (avoid FISH screening- it is not very accurate) you could do another cycle but test the embryos on day 5, then transfer back in a frozen embryo transfer cycle. However this plan does not guarantee that you will get pregnant (or even a transfer) and adds several thousands of dollars to the cost of IVF so this is not without considerable risk. It may be time to look at all your options and see if you have the stomach to continue down this IVF path which has not been very kind to you or try something else- donor sperm, embryo adoption, child adoption??? It’s a hard place to be but you are asking good questions. Good Luck!!!
April 11th, 2012 at 2:07 pm
Thanks so much for your response! I really appreciate it. I should have mentioned that my husband’s separated vas deferens is actually due to Cystic Fibrosis. We’ve been told that the disease should not affect the sperm quality.
The IVF facility we’ve gone to typically does 5 day transfers with blasts so I don’t think the lab is to blame (unfortunately).
I was thinking it might be worthwhile to have the sperm tested so we know what we’re dealing with.
April 12th, 2012 at 5:33 am
I had a five day transfer with hatching blastocyst grade 1. I had pain on left side of ovary for two days then woke up and found very small amount of blood one wipe and pink tmi! Now have no symptoms at all on day four after transfer. I had icsi and four of my eight eggs fertilised all four made to blast three expanded (grade 2 and one grade 1) and one hatching. I am 37 with pcos and endimetriosis. Should I be having more symptoms than this? Thanx
April 12th, 2012 at 7:44 am
HI CM,
You could always have more tests done. Aneuploidy testing http://www.tdlpathology.com/services-divisions/tdl-andrology/sperm-aneuploidy
http://www.andrologyjournal.org/cgi/content/full/29/2/124 Professional Guidelines for The clinical utility of sperm DNA integrity testing can be downloaded from ASRM here http://www.asrm.org/Guidelines/ The problem with all these sperm tests is that if your husband has a poor test result, it will suggest that you might do better with ICSI, which you are already doing, so I am not sure it is worth it to you to get a confirmation of that. Furthermore, these tests tell you that a percentage of all the sperm in a sample are bad but don’t give the tech a method to pick out “good” sperm for ICSI. They will still be mixed in with all the sperm. There are some pre-ICSI sperm selection methods (PICSI dishes, hyaluronate coated dishes commercial site info here http://art.biocoat.com/products.htm) that some labs are using. We used it in one of my labs and it seemed to be beneficial for some of our patients. If you are looking for more information in making a decision about using donor sperm, a really bad test result might lean you more in that direction. Anyway, more tests may not help you get pregnant unless you can use the info to adjust your treatment path or method.
Best of Luck! Carole
April 12th, 2012 at 7:47 am
Hi Baby Chick,
I really can’t answer those questions because they are outside of my area. Your doctor and/or nursing staff should be able to talk to you about what symptoms their patients experience after transfer. Best of Luck!! Carole
April 14th, 2012 at 7:12 pm
Hi,
Love your blog. It’s great!
For the last 2 years, we’ve had a total of 5 transfers (2 fresh and 3 frozen), only one was successfully implanted but resulted in miscarriage. We currently have 15 day 3 embryos frozen. About to do another FET. Our question is, should we thaw the day 3 embryos and wait to day 5 (blast stage) before transferring or just transfer the day 3 embryos? From all we’ve read on the Internet, day 5 embryos seem to have better chance to implant. Btw, I’m 35 years old and we used donor eggs from a 23 years old. Thank you.
April 16th, 2012 at 7:44 am
Dear Marie,
Because your eggs came from a 23 year old, and assuming the clinic is good at freezing and thawing, you may very well have 3 embryos survive thaw and be availalbe for transfer which would probably be excessive. ASRM has issued guidelines for how many embryos to transfer. In patients under 35 (your category now that you are using eggs from a 23 yr old donor) with a good prognosis for pregnancy (if there are no other major issues affecting implantation), they recommend transferring one blastocyst or 1-2 cleavage stage embryos. You case is complicated by the fact that you have had a miscarriage before which tends to make physicians want to transfer more, assuming 1-2 might have issues. The main reason to grow embryos out in culture is to test them to see if they can continue to grow, assuming that the stronger embryos that are more likely to implant will make it to blastocyst stage. Extended culture is a method to transfer less better embryos rather than more of unknown progression ability. Because you have 15 embryos, you could do more transfers if you transfer 2 at a time, instead of three and also reduce your risk of triplets. If the previous miscarriage was due to egg factors, that is not the case anymore. If the previous miscarriage was due to a problem with the uterus, you probably don’t want to overload the uterus with three fetuses. Having said all this, your doctor has your entire history in hand and should be able to advise you best. Personally, I am happy never to see more than 2 transferred because twins can be managed in most people- triplets are much more problematic. Good Luck!! Carole
April 16th, 2012 at 9:04 pm
Hi,
We retrieved 19 eggs. 16 have fertilized. On Day 2 the embryologist determined we would do a Day 5 transfer. They called me Day 3 with an embryo report. I thought I would get details regarding how many are still surviving, their grade, etc. However the nurse told me the embryologist does not provide grading for the embryos until the day of transfer (Day 5). The nurse mentioned something about it being detrimental to the embryos to have them out any longer than necessary; therefore they take them out long enough to determine whether or not things still look good for a Day 5 transfer, but not long enough to grade each embryo. MY QUESTION: is this a fairly typical practice? I guess I thought I’d be getting daily somewhat detailed reports as opposed to just a vague, “Everything still looks good for a Day 5 transfer.” I suspect I’m just being impatient and I tend to be thirsty for knowledge. It makes me feel like I have a modicum of control over a situation I know I really have no control over at this point.
April 17th, 2012 at 5:14 am
Thank you for your feedback. I am worried about my recent second ICSI cycle. I produced 16 eggs but only 2 became embryos on day 3, 6 and 7 celled. In the first ICSI I produced 8 with 4 getting to 7 and 8 celled embryos by day 3, but did not have a positive result.
My husband has very low sperm count but morphology seems to be ok. I am 33 and he is 45. I am wondering, how likely is it that the reason for the poor response is sperm? The RE just said they cant tell whether its sperm or egg quality issues. But I want to know in your experience is it more likely sperm or egg at that stage? I am worried about about the next cycle, we don’t want to use donor sperm. Was the fertilization rate acceptable in the first cycle?
April 17th, 2012 at 7:53 am
Hi Anne,
I would have to say that scoring embryos on day 3 is typically done very quickly. We have a 2 minute rule such that the embryos can only be out of the incubator for 2 minutes at most (1 minute is better) so the scoring that is done is never leisurely. If we are doing a longer procedure- such as ICSI or stripping cumulus cells, we use a HEPES buffered medium and warming surfaces to control pH and temperature. But HEPES buffer is not good for regular culture. We used to check embryos everyday but over the years, and as we gained confidence with the culture medium, we stopped checking so much. I think your clinic’s approach is very reasonable. You can look at an embryo in a second and see that it has about 8 cells and so good to go for day 5, but it might take a bit longer to count every cell exactly and consider the amount of fragmentation and uneveness that is reviewed to create a score. If that day 3 scoring info has no clinical use- why do it? It just exposes the embryos to less than ideal conditions. If it is not going to be used to make a clinical judgement, the only purpose of the day 3 score is for patient satisfaction- customer service- patients like to hear about their embryos. But in this case, you and the embryos are probably better off to just wait until day 5. With so many fertilized embryos and a “good to go” for day 5 assessment, I think you will likely be pleased with your day 5 report. Good Luck!!!Carole
April 17th, 2012 at 8:11 am
Hi Lola,
Maternal age is the biggest factor normally in determining IVF success so at 33 (under 35ya) this should be working in your favor. I would have expected better fertilization. You husband’s sperm quality may be part of the problem.
Some links to papers/articles on maternal and paternal age and IVF success
http://www.ncbi.nlm.nih.gov/pubmed/22082792
http://www.ivf1.com/male-age-infertility/
http://doctor.ndtv.com/storypage/ndtv/id/4794/type/news/Fathers_age_and_IVF_success.html
The most pertinent paper is this one (http://www.ncbi.nlm.nih.gov/pubmed/22040161 “Poor sperm quality and advancing age are associated with increased sperm DNA damage in infertile men.Varshini J, Srinag BS, Kalthur G, Krishnamurthy H, Kumar P, Rao SB, Adiga SK.Andrologia. 2011 Nov 1. doi: 10.1111/j.1439-0272.2011.01243.x. [Epub ahead of print])
which specifically talks about the effect of paternal age on poor embryo progression and failed or poor fertilization. The study showed that older men (over age 40) with poor sperm quality were more likely to have sperm DNA damage which could easily explain the poor fert and poor embryo progression you are seeing. Ask your doctor about doing a sperm DNA fragmentation test. Anyway- here is the abstract copied from PubMed. If his fragmentation is high, donor sperm should be considered. Good Luck! Carole
“With increasing evidence for faulty paternal contribution to reproduction, there has been a steady increase in studies highlighting an association between sperm DNA damage, failed/delayed fertilisation and aberrant embryo development. Owing to prevailing ambiguity, the aims of the study were to analyse the genetic integrity of the male gamete and then to understand its association with age, standard semen parameters, lifestyle and occupational factors. The study included 504 subjects, attending university infertility clinic for fertility evaluation and treatment. Semen characteristics were analysed by standard criteria; terminal deoxynucelotidyl transferase-mediated nick end-labelling assay was employed for DNA damage assessment. The average incidence of sperm DNA damage in patients with normozoospermic semen parameters was <10%. Patients with oligozoospermia, severe oligozoospermia, oligoasthenoteratospermia, asthenoteratozoospermia and necrozoospermia had significantly higher level of sperm DNA damage (P < 0.001). Patients above 40 years of age had significantly high levels of DNA damage (P < 0.001) compared with their counterparts. Patients with varicocele and a history of alcohol consumption had higher incidence of spermatozoa with DNA damage (P < 0.01). Poor sperm characteristics in the ejaculate are associated with increased sperm DNA damage. Age-related increase in sperm DNA damage and association of the same with varicocele and alcohol consumption are also demonstrated."
April 17th, 2012 at 8:11 am
Hi Carole,
I just wanted to say a quick thank you for your incredibly prompt and informative response. I have great faith in my RE, and I believe his lab to be world class. That being said, your insight is very reassuring and makes me feel better. Again, thank you for your incredible site and dedication to answering our questions.
Appreciatively Yours,
Anne
April 18th, 2012 at 4:20 pm
Hi Carole,
Thank you for such a wonderful and informative post. I found your website today while trying to find out information to help understand what it means that my 2PNs (frozen) haven’t cleaved at ~27 hours post-thawing. I was told that they haven’t died but haven’t progressed and will be checked again tomorrow morning. Not sure if it’s reasonable to harbor at least a little bit of hope or if this is very bad news.
April 19th, 2012 at 7:53 am
Hi CG,
I tried to find some precise data on the expected range for hours post thaw before cleavage typically resumes. I was able to find data for fresh, not frozen zygotes. Generally speaking, it is about 24 hours from time of sperm entry but some researchers have reported a rather wide time range in non-frozen fresh zygotes from the time of sperm entry to first cell division which can be between 22 and over 30 hours. http://humrep.oxfordjournals.org/content/17/2/407.full
http://humrep.oxfordjournals.org/content/13/6/1606.abstract?ijkey=b464981d6da75f4fedb0e0816ec78edb1f1992d0&keytype2=tf_ipsecsha and this paper Payne, D., Flaherty, S.P., Barry, M. and Matthews, C. (1997) Preliminary observations on polar body extrusion and pronuclear formation in human oocytes using time-lapse video cinematography. Hum. Reprod., 12, 532–541. So there is a larger range around 24 that is possible. Recovering from the thaw process may slow things down also. So although they are not on the early side of cleavage, they may still cleave. I think your lab gave you good advice. Wait until 48 hours have passed and then you can be sure. Hang in there. Good Luck! Carole
April 20th, 2012 at 10:39 pm
[...] can also read more about zygote/embryo/blastocyst development at http://fertilitylabinsider.com/2010/11/embryo-stages-progression/ I’ve just given you some of the basics. There is soo much more. I find it so very [...]
May 6th, 2012 at 5:30 pm
Hello Carole,
I am 43 and just did a day 3 six cell ET on May 1. We only have one. Fertalized of three, and the Dr said it was of medium grade with some fragmantaion. I know it is an age factor, all other areas a fine. I am 6 days PT and wanted to know if you have seen any success with just one embryo and that being only a 6 cell on day three?
Thanks for any insight.
May 6th, 2012 at 7:29 pm
Hi Cori,
Yes, I have seen pregnancies with embryos with less than optimal grades. It’s too early to give up. Good Luck!!
May 10th, 2012 at 7:58 pm
[...] Embryo stages, progression and pregnancy outcomes | Fertility Lab Insider [...]
May 13th, 2012 at 6:59 am
Hi Carol
I can’t tell you how interesting I have found your blog – I have been devouring the information over the last 24 hours. I think the medical profession really underestimate how much women are able to understand when it comes to IVF. At consultations I am often asked what I do for a living and when my reply states that it has nothing to do with the medical profession then I feel I am given a frustratingly brief answer to my questions. Your blog provides invaluable support to so many women going through this isolating journey and helps us by providing a clear, knowledgeable, sympathetic yet honest response.
I am 38 years old and on my second cycle of IVF.At egg collection I had 6 eggs, 4 of these fertilised. By day 3 I was told that these were ‘textbook’ embryos of excellent quality and so the decision was made to push them to blastocyst. Yesterday (day 5) , 2 were early blastocysts (2cc) and 2 were still at morula stage. The 2 morulas have been left to grow to see whether they are good enough to freeze – hopefully I will hear more tomorrow. I am currently feeling extremely deflated because what it seems that the embryos haven’t gone on to do as well as expected. The embryologist said that it is extremely difficult to grade the embryos at this stage and was reluctant to tell me the grading as she said that the embryos change extremely quickly at this stage.
I have read both the ‘embryo stages…’ and ‘Understanding the Gardner…’ blogs and found these really useful. What I can’t quite understand is whether a 2cc blastocyst can then become say a 4aa etc? Or is this early low grade indiciative of how the blastocyst will develop? Or is it really just impossible to tell? At the moment I feel as though I’m bracing myself for another failure.
Many thanks
Janie
May 13th, 2012 at 9:11 am
Hi Janie,
Good Luck!! Carole
Don’t give up hope yet. Although you didn’t say it explicitly, it sounds from your comment, that your clinic probably transferred the two blasts (grade 2CC) to you on day 5. The designation 2 means that there was a fluid filled cavity but the cc means the cells were sparse in both the inner cell mass and the trophectoderm, so these are some hours behind what we have come to expect as ideal for day 5. However, that doesn’t mean that they won’t continue to develop inside your uterus. They have several days to catch up and still implant in a receptive uterus so don’t give up on them yet. Prediction of pregnancy success from appearance of the embryos is at best a very inexact science and we are often surprised by embryos who apparently haven’t read our text books!!
May 13th, 2012 at 12:41 pm
Hi Carole – many thanks for your reply. Yes, you’re correct it was the two grade 2cc blasts that were transferred. I just heard that the morulas didn’t make it so I guess that makes me all the more nervous that the blasts that were transferred were also on their ‘way out’. Guess we just have to tough it out now for two weeks.
Thanks again for your reply.
May 17th, 2012 at 11:47 am
Hi Carole,
I am currently undergoing my second IVF attempt…first was one year ago when I was 36. 29 eggs were retrieved with 21 being fertilized. The day of our transfer we received a call from the RE advising us not to come in as only two of the embryos were looking viable for transfer but they wanted to wait one more day. We had a transfer of one on day 6 which resulted in a BFN. The eggs had arrested development and fragmentation which I believe started around day 3. This cycle he did not do lupron, lowered my gonal f dose and added ganirellex and omnitrope to hopefully boost the quality of the egss. 17 were retreived with 15 mature and 11 fertilzed. My RE called today with an update…said things are looking “good”. Some are showing signs of fragmentation and some are not. Once I heard fragmentation I started freaking out and am worried I did not ask the proper questions. First of all should I be concerned? I assume that even under the most normal cirmcumstances embryos will fragment and not make it to the transfer stage. Should I be calling back and asking for more specific information? Any insight would be greatly appreciated!
Dannielle
May 17th, 2012 at 12:39 pm
Hi Dannielle,
Some fragmentation is not that unusual and does not mean that you will not get pregnant this cycle. When fragmentation gets to be 25% or greater, it starts to be more worrisome. Even then, it is not necessarily the kiss of death. I have told this story elsewhere on the blog but one of my first IVF pregnancies was with embryos that were so badly fragmented, I couldn’t with confidence say they were even alive- yet they resulted in the birth of a beautiful baby girl. That same week, we transferred 3 beautiful textbook perfect looking 8 cell embryos —and no pregnancy. The second patient was in her forties. The first patient was younger. So, the bottom line is, don’t freak out. Some fragmentation does not rule out implantation and pregnancy. Hang in there. Sending you some positive thoughts!! Carole
May 18th, 2012 at 2:48 pm
Hi Carol,
I am 39 and we have had 2 fresh icsi cycles and 2 fet. One gorgeous boy and one miscarriage from those cycles. On wednesday we transferred one blastocyst grade 5bc, which had started hatching and a compacting morula. The icm and te were only grade b and c, so I wonder how good the blastocyst actually was. How much do you think that will impact the viability of the blastocyst?
Thanks
Sheen
May 18th, 2012 at 3:03 pm
Hi Sheena,
Grading systems describe a snapshot of development at a specific time. They are somewhat useful but are far from 100% predictive. The fact that the embryos were a compacting morula and a hatching blastocyst means they have already passed several developmental milestones. At this point, with your history of one successful pregnancy, be optimistic. Good Luck!! Carole
May 18th, 2012 at 3:52 pm
Hello carole
I have just completed an egg sharing cycle where 10 eggs were retrieved so 5 for me.
After the most stressful week of my life I amazingly have one precious little two day embryo on board… we had only two eggs mature so we were very lucky the 2 day embryo is a three cell slightly asymmetrical, two cells are slightly bigger than the third, no fragmentation but embryologist said it was good quality I am worrying if my little embie has continued dividing as I know blasts are generally more successful dont get me wrong I am so lucky to have this little miracle and a chance but do I have a good chance? I love this little embie already so much I am trying to stay positive and relaxed. Im worried about the slight assymetry? and the fact its 3 cell? thanks so much, I keep googling sending myself crazy ha ha
May 18th, 2012 at 5:19 pm
Dear Anonymous,
Please don’t drive yourself crazy. There is little difference between a 3 and a 4 cell embryo on day 2- both are okay; the developmental change between 3-4 cells can happen in a few hours. Just take it one day at a time. Your embryo has already met several milestones. Be hopeful and happy for that. Wishing you much good luck!! Carole
May 21st, 2012 at 4:03 pm
Hello again Carole,
You were kind enough to answer my question regarding my day 3 update from my RE last week and that some of the embryos were showing signs of fragmentation. Sadly we receieved a call the day of the transfer that only two had continued to grow. We live 45 minutes from the clinic and were literally pulling into the parking lot when we got the call. We went in to meet with our doctor and it was his recommendation that we wait one more day to determine if there would be a transfer. This answer did not sit well with my husband and I as something in our gut told us to go for the transfer right away. They stressed over and over that these had not made it to the blast stage yet and we were taking a chance that these would end up to not be viable. We were okay with this and decided with the transfer. My last IVF cycle we had a transfer of one that had continued to show signs of growth from day 5 to 6. When I compared the photos they gave us from last cycle vs. this cycle of what was transferred the images were drastically different. The photo from last cycle showed what appeared to be the likeness of a day 3 embryo where the photos of this transfer the embryos (in my very NON medical opinion) showed much more compaction and appear to be more at the morula stage. So…I guess the long and short of my question is are the photos shown explaining the gardner grading system really a good comparison or can things vary so much that I should not be using this as a guide to what my little guys looked like? Also in your opinion do you think we did the right thing by transferring on day 5 rather than waiting until day 6 or rather have you seen cases similar to this?
May 21st, 2012 at 5:41 pm
Hi Anonymous,
I appreciated your question about fragmentation so much that I used it as a basis for my most recent blog post. http://fertilitylabinsider.com/2012/05/q-from-u-embryo-fragmentation/
Regarding the transfer: yes, I think you did the right thing because you said the IVF staff conveyed their concerns and you understood that there was a chance that they could not be viable and you still wanted to proceed. That is the basis of informed consent and while there is always a chance that the embryos may prove not to be viable, if they look like morula’s on day 5, I would still give them the benefit of the doubt. As I have said many times before, using morphology or exact developmental time tables will give you good predictive value much of the time but embryos consistently manage to surprise us. So be happy about the transfer. I am wishing you much good luck!!! Carole
May 23rd, 2012 at 6:15 am
First off, thank you so much for doing thus blog! This is such a new venture, we are minimally informed and rely a lot on Google elp us understand. Ivf is all about hope, so its hard not to remain positive, more information helps make being positive easier.
My question is about day 3 versus day 5 transfer. I am 37 and I had fibroids ( myomectomy , open , to preserve chances of fertility at 35). Started ivf at 36, 1 round fresh (2 transferred day 5), 2 Fet – nothing. Second round, different doctor. Noted some fluid in my uterus from first round scans, so he sucked fluid out before day 5 transfer. Chemical pregnancy. I did another hsp which showed blocked tubes, so I had both tubes removed. Transferred 2 Fet, no dice. This clinic is rated the ‘best’ in the dc metro area, and they boast high success rates.
Third round, no fluid, no tubes, I am all in for ivf. 9 eggs retrieved, 7 mature, 5 fertilized. Day 3, doctor recommended day 5 transfer b/ c j had 2 8 cell, 1 7 cell, 1 5 cell. I tried a day 5 transfer of 4 blastocysts in
2 Seperate occasions, so this time, I decided to ask for day 3 transfer. I was transfered 4 days ago, my 2 number 8s. The number 7 cell made it to blasts but was slow growing so did not make frezing quality. Number 5 cell just died off.
You have stated what most of us understand – day 5 is better selection b?c survival of the fittest, and the best are chosen. You also stated that day 5 has better birth rates than day 6.
My questions are:
1) any idea on births between day 3 and day 5 transfer? You mentioned that the ‘extra’ embies grown in culture serve as good comparisons to what your transferred embies are doing, but the transferred usually are the best of the bunch. Any studies on comparing same stage embies, culture to late blastocysts versus birth rates? Ie. Who REALLY grows it better, a great lab, or my uterus? I tried a great lab twice, I decided to try my uterus this time!
2) we are familiar with the blast stage, we all want that stage to be reached, but what is the furthest stage (and or # of cells) that embryologists have grown embies to that can still be viable for birth? Can someone, somewhere grow to, say for example day 10, and have an even higher success rate?
Your feedback is invaluable to a desperate hopeful Mom to be . Thank you so much for your time.
Julie
May 23rd, 2012 at 7:49 am
Hi Carole
I emailed a week ago because I had concerns about 2x2cc 5 day blasts that were transferred. I just thought I would update you that I had a BFP but sadly I have since had heavy bleeding so I believe this is what is called a chemical pregnancy. I have lots of worries about why this may have happened but I know you can’t answer these questions. I guess from an embryo point of view it’s probably not that surprising and they just ran out of steam. Does this seem a fair comment?
Many thanks – your website is invaluable for women going through a time of very high stress.
Janie
May 23rd, 2012 at 8:43 am
Hi Julie,
I am glad you’ve found the blog useful. Your questions and my answers (in italics) below:
1) any idea on births between day 3 and day 5 transfer? Implantation rate and therefore pregnancy rates tend to be greater when day 5 embryos are transferred. THis is probably due to the “weeding out” of non-progressing embryos You mentioned that the ‘extra’ embies grown in culture serve as good comparisons to what your transferred embies are doing, but the transferred usually are the best of the bunch. Any studies on comparing same stage embies, culture to late blastocysts versus birth rates? Ie. Who REALLY grows it better, a great lab, or my uterus? I tried a great lab twice, I decided to try my uterus this time! There are selection pressures to sort out embryos which may count as a benefit from culture in the lab (see previous) , but there is no evidence that lab culture is superior to growth in your uterus and obviously, without your uterus, there is no pregnancy.
2) we are familiar with the blast stage, we all want that stage to be reached, but what is the furthest stage (and or # of cells) that embryologists have grown embies to that can still be viable for birth? Can someone, somewhere grow to, say for example day 10, and have an even higher success rate? Currently, embryos are not cultured past day 5 or 6 if they are to be transferred to the uterus. I don’t know of any one who will transfer a day 7 embryo. The embryo in culture past day 6 is looking for a place to implant and a tissue culture dish doesn’t offer that kind of environment (not 3D, not proper growth hormones; no interaction with uterine cells etc.) Now if you want to grow embryonic stem cells, then you can grow the cells longer in a tissue culture dish, but it is no longer a implantable embryo and is disaggregated at some point. Hope that answers your question. Wishing you much good luck with this latest round! Carole
May 23rd, 2012 at 8:48 am
Hi Janie,
Unless your clinic has confirmed that the beta has reduced to background levels, I wouldn’t use bleeding alone as a guarantee that the pregnancy is gone. Heavy bleeding is not good but some bleeding can be compatible with pregnancy. Please follow-up with your clinic. Even if the result is negative, most docs like to follow the beta back down to make sure that there is no ectopic pregnancy. It is usually not possible to diagnose why a pregnancy fails. There are unfortunately, many possibilities. If that is indeed what has happened, I am so sorry for your loss. Best Wishes, Carole.
May 24th, 2012 at 10:12 pm
Hi Carole
I know this is a question I should ask my clinic but I saw your blog and it prompted me. I have never tried to get pregnant before but appear to have no issues other than age. I am just 43 and on my 2nd ICSI cycle. The first provided 8 eggs, 7 or which fertilised and divided. I had a 5 day ET of 1 Blasto & 1 Morula which resulted in a BFP but ‘miscarriage’ 1 week after the Positive. Nothing was frozen of the remaining embryos. The 2nd cycle progressed exactly the same but with 10 eggs collected resulting in 9 fertilising and dividing and again 5d trfr of 1 Blasto & 1 Morula but again nothing to freeze. Should I be worried that I haven’t been able to freeze any embryo’s or is it just a reality of my age or possibly something else ? Thanks.
May 25th, 2012 at 8:11 am
Hi Carole,
Thank you so much for providing this information and answering so many questions!
My question is about the timing of a day 5 transfer. You mention above that “Normal embryos have a fairly strict rate of progression which starts at the time of fertilization.” You also mentioned that late morulas are just a few hours away from early blastocysts. If my eggs were retrieved in the morning, but then weren’t ICSI’d until mid afternoon, should we ideally be looking for the embryos to be expanded blasts by that same time of day in the afternoon on day 5, or should they have gotten there by early in the morning on day 5?
I ask because my transfer just got moved from later in the day to 10:00am due to scheduling, and I’m wondering how that would affect what we should ideally hope to see. During my last IVF cycle which unfortunately resulted in a m/c, we were able to transfer a 5AA, a 2BA, and a 1BB, but our transfer wasn’t until 4pm in the afternoon on day 5. When I look at the embryology report, when the embryos were checked in the morning at 9am, the one that became the 5AA had been a 2BA in the morning, and the other two were noted as c/2, which I think is compacting 2 (there was another one on there marked as a c/1that we did not transfer, which I’m guessing is an earlier morula?). The time noted for ICSI on the sheet was 3:20pm on day 0.
So I see how quickly things can change, but this time we’re not going to have the benefit of the extra hours to wait to the afternoon. Ideally should we still hope to see full blasts in the morning or would morulas be considered still reasonably on schedule in the morning?
I am 40 and only have 3 fertilized embryos this cycle, so we are planning on transferring as many of them as possible if any of them are still even growing on day 5, so I don’t think my RE will push us to day 6, since we won’t be trying to choose the best out of many.
Thank you again so much for answering our questions!
Julie
May 25th, 2012 at 8:47 am
Hi Cathy,
Even in younger women, it is common to see an attrition of embryos in culture. See my earlier post http://fertilitylabinsider.com/2011/02/egg-count-mathematics-why-the-numbers-change-between-retrieval-and-transfer/ And yes, unfortunately, as you age past 35, the probability that more of your eggs are aneuploid (chromosomally abnormal in number) increases, so observing that some of these embryos are not be able to progress is not unexpected. I am not surprised that you were unable to freeze any embryos, again due to natural attrition and increased aneuploidy rate with advanced maternal age. Having excess embryos to freeze would be highly unusual at age 43. This blog post on aneuploidy and microarray testing may be of interest http://fertilitylabinsider.com/2011/01/what-is-aneuploidy/ Good Luck! Carole
May 25th, 2012 at 9:01 am
Hi Julie,
If the ICSI occurs later in the day, then the Fertilization “start time” will be later, so any milestones will be later. We see this often when we do a “rescue” ICSI on unfertilized eggs the next AM after fert check. Any eggs that fertilize from the rescue ICSI will naturally be a half day or so behind their companions (if any) that fertilized from the original ICSI. But although the timing of your transfer may affect when your embryologist looks at your embryo report, it is just a snapshot in time and although your embryo report may not be as “advanced” as you like, as long as there are sufficient normally progressing embryos (1-2) to transfer on day 5, your score will not affect whether you get pregnant or not. As you noted, a 2BA in the morning can be a 5AA in the afternoon. If the 2BA had been transferred to you in the morning, you would still have had a 5AA in you in the afternoon, you just would have been blissfully unaware of the score. The score is a useful tool for embryologists to select the most advanced embryos from a cohort but it is not very useful as a pregnancy predictor because unless the embryo dies, it will push through those milestones whether anyone is watching or not. You will get no benefit from “the extra hours in the afternoon” unless your embryos are indistinquishable in stage (need more selective pressure from time in culture) or haven’t met the minimum milestones for that time in culture (suggesting they are non-viable). Otherwise, nature will take care of itself. Please try not to fixate on scores. See my answer to Cathy and links to previous posts regarding aneuploidy. Good Luck!! Carole
May 27th, 2012 at 3:26 pm
Hi I had day5 blasto done last Sunday today 28/5/12 is day 7 for me I did a test and it was a bfn! Is it to early to test or has it just. Not worked?? I am getting allot of cramping in my lower tommy and my period Is 6 days late. Can some one please help me…..
May 27th, 2012 at 5:38 pm
Hello,
Here’s a link that should be reassuring. http://www.nyufertilitycenter.org/ivf/embryo_transfer Based on this calendar, day 9 is the earliest you could expect a blood test to be positive and home pregnancy tests tend to be less sensitive. It is too early to assume that you are not pregnant but you should make the clinic aware of your symptoms. Good Luck!!
May 27th, 2012 at 5:49 pm
Thank you so much I feel allot better xxx Sam
May 30th, 2012 at 1:13 pm
Hi carole,
Today is day 10 after blastocyst I had a 5. Day blasto done again I tested today and it was a bfn tomorrow is my testing day but as it was bfn today what is the chance of that changing over night.
I’ve had period like pains over the last 4days and been taki g paracetamols that’s not helping this is our first icsi and I feel it’s not worked. Can you help???
May 30th, 2012 at 1:19 pm
Dear Sam,
Unfortunately, I don’t know what I can do to help except encourage you to keep in touch with your doctor regarding your symptoms and wish you good luck for your official test. I agree that the signs are not good but the official blood test is the one that will be definitive. Good Luck. Carole
May 30th, 2012 at 1:21 pm
Hi carole,
I had a day 5 blasto done and today is day 10 after egg transfer. I did a test this. Morning and it was a bfn. My test day is tomorrow so can this change I doubt it. I am disappointed and it ws bfn today.but can this change over night.
I am also getting period like pains in my lower belly getting worse dy by day been told to take paracetamols so its helping a little
But main concern is has it worked if its bfn today????
May 30th, 2012 at 1:21 pm
Hi Cathy,
I am 33, and my DH is 37. We just had an IVF cycle in which 14 mature follicles were retrieved, 10 fertilized, and 7 made it to blast stage (day5: three 5AB, two 5BB; day6: two 5BB). We were so happy to hear that, but then the news came in: only 1 day 6 5BB embyos was normal, as well as 2 were no-result (day 5 5AB and 5BB). We are at a clinic that has a high success rate for FET. How likely is it that no result embryo is normal? Should we do FET with our 1 normal blast and 1 unknown or retest our 2 unknown blasts? How typical is it to only have 1 normal out of these number of blasts? If we fail this cycle, can the next IVF produce more nomal embyos or should we look at other options (egg donor, adoption)?
Thank you,
Val
May 30th, 2012 at 3:52 pm
Dear Val,
These are all good questions you should ask your RE and your genetic counselor. Sorry, but I am not qualified to answer these questions. Good Luck! Carole
June 1st, 2012 at 12:49 pm
Hi Carole,
Is it ok to freeze by vitrification at the 2pn stage after performing ICSI? I am 40+ so worry a little that the removal of the zona cells to perfom ICSI will impact survival of the vitrified 2pn?
Thanks, Kim
June 1st, 2012 at 1:08 pm
Hi Kim,
In my experience, if the lab is proficient at vitrification, excellent results can be obtained at any embryonic stage, including 2PN. When ICSI is performed, the granulosa cells (the cloud of follicular cells surrounding the zona shell) are removed. The zona itself, which is a carbohydrate rich shell is NOT removed for ICSI. Removal of granulosa cells should not affect the vitrification procedure and may be helpful, in some cases. Best Wishes, Carole.
June 2nd, 2012 at 7:00 pm
Hi Carole -
I am 32 years old and have high FSH (17 and 20 on the last two tests) / only about 7 visible andral follicles on both ovaries. My husband also has male fertility factor issues (2% morphology on last reading and has had motility issues on past samples too). We just underwent our first IVF cycle which resulted in the retrieval of 4 eggs (we only had 3 visible follicles over 14 cm on the sonogram – 20, 19 and 17 cm on last scan before retrieval). Only 2 eggs were mature, and both fertilized normally via ICSI and made it to day 3 – a 9 cell (no fragmentation) and a 6 cell (5% fragmentation). We were so excited given all the speeches the clinics had given about how bad it was expected my eggs to be… We were advised to wait until a day 5 transfer (not sure 100% why). The doctor said it would give them “more information”. He sounded optimistic and so we took this advise. This AM was supposed to be the 5 day transfer, but the clinic called to tell us that the embryos “aren’t ready” – one is in the morula stage and the other 6 cell only grew to 7 cells. They said they would wait another day to see if the morula forms a blast tomorrow and if it does they will freeze it(though I’m not particularly optimistic since the embryo was slightly “ahead” of schedule at 9 cells on day three). My question is this – when the clinic says this outcome will provide “information” – is arrested development at the Day 3-4 stage a clear indication of poor egg quality due to DOR? We’re so disappointed as we thought the point that both mature eggs proceeded to cleavage stage with minimal / no fragmentation was a good sign that my issue is a quantity, but not necessarily “quality” issue.
Also, our only other attempt using fertility meds was a clomid cycle IUI using a different doctor. That doctor said there were 3 large follicles brought up on the sonogram (he didn’t say the size). So how is it possible that 5 measly clomid pills could have yielded the same result as 375 ml Gonal F / 150 ml Monopur IVF protocol? Would a mini-IVF cycle make more sense for us as perhaps the extra stims didn’t helping much beyond a point? What would you recommend? Thank You in Advance for your help!
June 3rd, 2012 at 9:17 am
Dear Linzie,
I understand your frustration with your current cycle. I would not worry about a 9 cell on day 3 being too fast; that is normal variability for embryo progression. Sometimes a large fragment can be graded as a cell too so, again, don’t fret about the cell number. Regarding arrested development; the two large categories that explain arrested development are problems within the embryo (usually genetic) which don’t support normal cell division or problems in the culture system which don’t support continued growth. If one embryo proceeds and the other doesn’t, the first option is more likely. High FSH does affect egg quality. This link to more information about FSH and poor egg quality in both older and younger women like you may help you have a better conversation with your doctor regarding your questions http://www.drmalpani.com/highFSH.htm
The rest of your questions are outside of my expertise as an embryologist and are better answered by a reproductive endocrinologist. Typically, when a cycle does not result in a pregnancy or in your case, at best a freeze without transfer, you can expect to have a follow-up appointment with your RE to discuss in detail the previous cycle and what can be done differently for further treatment. It is important that you feel that you have had your questions answered in a manner that lets you effectively understand your treatment and enables you to make good decisions going forward. If you aren’t getting that, you might consider another RE for a second opinion.
Good Luck!!
Carole
June 3rd, 2012 at 8:14 pm
Thank you, Carole. Our embryo made it to blast today, but it was only a Grade 1 CC so it could not be frozen and we were told that day 6 is too late to do transfers. The RE said the lining is usually too thin? I know Grade 1/CC isn’t as likely to implant as higher grade blasts, but we are still really kicking ourselves now for not doing a day 3 transfer…In your experience, does poor egg quality typically first present itself this way in the morula phase? This is all so confusing. Thank you!
June 3rd, 2012 at 8:57 pm
Hi Linzie,
I am sorry that this cycle didn’t work out. I think your RE should be better-positioned to answer these questions for you at your follow-up meeting. Yes, poor egg quality can reveal itself by poor progression, but poor culture conditions (or poor sperm quality) can also effect embryo viability and ability to progress. Be sure to ask your doctor all these questions, including what he/she would suggest be done differently in a next cycle. It is never a bad idea to get a second opinion as well. Good Luck!! Carole
June 5th, 2012 at 10:21 am
Hi Carole,
Thank you for a highly informative blog.
We are going through our first IVF cycle (ICSI) and have just had our day 5 blastocyst transfer. I am 31 and have no known fertlity issues. My husband’s sperm count was borderline normal hence ICSI.
I have two questions if that is ok.
Firstly, 17 eggs were retrieved of which 14 fertlised and 12 were still alive by day 5. However, of these, none were suitable for freezing by day 6 and only two were considered ok to transfer. The two that were transferred back into me were ‘below average’ in terms of grading. My first question is, is there a reason that despite the high number of retrieved and fertlised eggs and most of them reaching day 5 we didn’t get any higher grade blastocysts?
If this isn’t successful is there anything we should ask the clinic or be asking in the future?
My second query relates to the likelihood of pregancy from the two transferred blastocysts. Our blastocysts were 3CB and 4CC. I know that blastocysts can improve but are you able to able to give a ‘best guess’ liklihood percentage of pregnancy?
Thank you very much in advance,
Naomi
June 5th, 2012 at 11:29 am
Hi Naomi,
A previous post of mine, “Egg count mathematics:why the numbers change between retrieval and transfer”, should answer your question regarding the very common attrition rate that you observed. Our ability to determine sperm and egg quality is very crude. Both sperm and egg can have intrinsic genetic problems (eg. aneuploidy or an incorrect number of chromosomes) which can cause the embryo to fail to progress. Aneuploidy can also arise spontaneously as the cells divide. So unfortunately, even with no obvious female issues and a borderline normal count, there is still plenty of opportunity for things to go wrong. There are also lab conditions to consider. If the lab is not very good at growing embryos to blast stage, you can also get poor development in vitro. If this does not work, you should ask your doctor to discuss what he/she thinks contributed to the low efficiency and what suggestions they have for a different approach next time. If the answers you receive are not useful to you, you can always get a second opinion.
But here is the important point. You may still become pregnant this cycle, so it is too soon to give up on your embryos. Grading is subjective and can only show you a snapshot of time so I wouldn’t be overly concerned about grade. I can not give you a meaningful guess at your chances of pregnancy. Your youth is on your side and grading as a pregnancy predictor has fooled many an embryologist. Good Luck! Carole
June 5th, 2012 at 12:33 pm
Thank you so much for replying so quickly Carole, it is massively appreciated. We will take your advice! Thank you so much again
June 5th, 2012 at 4:27 pm
Hiya Carole,
Thank you so much for taking the time to answer all our questions.
I’v had 2 cycles of ivf with ICSI, both times 7 eggs collected and 6 injected. The following day all had fertilised but each cycle 6 out of the 7 embryo’s had black spots in so were unusable. Embryologist said this is rare but can happen . So only one embryo transfered each time.. After first cycle it was negative, but second cycle resulted in a pregnancy. After a rough start my daughter is now 6months old.
Have you come accross the black spots/areas in fertilised embryo’s ? Do u know what could be the cause, and what does it mean?
Thanks so much
Janey2011
June 5th, 2012 at 5:11 pm
Hi Janey,
I am not sure exactly what you mean by black spots in embryos. Dark areas in embryos usually mean that the cells are dead. For instance, in the bad old days of slow freezing, we expected to see some cells in the embryo looking dark, having not survived the freeze/thaw process. Since you say “fertilized embryos” , maybe you meant fertilized eggs. Eggs can have dark areas as well. Here is a link to an older paper which found good pregnancy outcomes even in eggs with abnormalities including dark spots humrep.oxfordjournals.org/content/11/3/595.full.pdf . This previous post http://fertilitylabinsider.com/2012/01/egg-vacuoles-in-ivf/, may be helpful. Although primarily about vacuoles, it does mention other types of egg abnormalities that can reduce the fertilization rate or viability of eggs and there is a link to a paper which talks about these kinds of egg abnormalities. But I am just guessing about what they might have seen. Your clinic should be better positioned to answer these questions specific to your case. When have they seen these type of dark spots before? What do they mean? Can the stimulation be adjusted to help prevent their occurrence? Anyway, congratulations on having a six month old! Best Wishes, Carole
June 6th, 2012 at 12:20 am
Thanks for your reply Carole,
I did mean fertilised egg, sorry it was all very confusing at the time. They did say if I was to have another treatment cycle then I would be better off using doner eggs, so possibly the eggs showing abnormalities. Thank you so much for your reply
Xxx
June 6th, 2012 at 12:23 am
Thank you so much for your reply,
I did mean fertilised egg I think, it was all so confusing at the time. They did say if I was to have another treatment cycle then I would be better off using doner eggs, so maybe most of my eggs showing abnormalities.
Thank you again
Janey xxx
June 11th, 2012 at 10:34 pm
Hello Carole,
I found this website and it is the best one I have ever found
!!! you are so thorough in all your answers!!!!! Thank you in advance!!!!
I am 40 and I have done 5 IVF cycles and all failed. I just recently did a donor cycle with a 24 years old donor. She produced 20 eggs and 17 were matured and 6 of them made to blastocyst. I transferred 3 and the fertilized normal just like the picture on your website (2 rings inside the egg). I transferred on Wednesday 06/06/2012 and I have minor crams here and there and I am really worry. Are these symptoms sign of impending period???? my lining was above 9 even a week before transferred ( I assumed the lining was greater than 10 on the day of transfer)….I did not have the 3 line in my uterus. PLEASE help ease my mind. My blood pregnancy test will on Monday 06/18 and the wait is killing me
….Thank you a bunch Carole!!!!!!!
June 12th, 2012 at 7:44 am
Dear Juliana Grace,
Don’t panic. Some women report experiencing cramping at the time of implantation so your symptoms are not necessarily cause for worry. But, as always, you should ask these questions of your clinic staff because they know your entire history and can best advise you regarding your medical concerns. Good Luck!! Carole
June 13th, 2012 at 9:54 pm
Thank you so very much Carole!!!! I couldn’t help myself..so I did a HPT last night 6.5 days after 5 days transfer and it was a big NEGATIVE
I have a friend and she did the same 6 days after 5 days transfer and got a positive. She has twins girl. Does this mean it’s over for me? I am so sorry to bug you!!!! Thank your bunch for your expertise!!! God bless you!!!! For all that you do!!!!
June 14th, 2012 at 10:34 am
Hi Juliana Grace,
You can have a false positive or a false negative result if you test too soon. I know it is hard to wait but the timing of the test is to get you past the window of false results. I don’t know how it will turn out for you but I am wishing you lots of good vibes and good luck. Hang in there. Carole
June 18th, 2012 at 10:07 am
Thank you so much for your blog. Very informative. I am 37 years old with no know fertility issues (other than age) using donor sperm. My first IVF a few months ago, I responded very well to low dose stim producing 13 mature eggs. However, 7 of the 13 fertilized as 3PN – we did iCIS on all of them. We transfered 3 day 3 embroyos. There was nothing to freeze and I miscarried at 8 weeks. The lab is very reputable. I just completed my second IVF (using a different donor). I was on the same protocol but lower doses. This time I produced 14 eggs (I fracture and one abnormal). Out of the 12, 6 fertlized (we tried to do IVF on 4 and only 1 fertlized and arrested very soon). We had 5 good quality embryos by day 3 and pushed to day 5. On day 5, I only had 3 morulas, a grade 1, 2 and 3. We transfered the 1 and 2 and am in my 2ww. The third morula turned into a high quality blast (5AB) by day 6 and was frozen (wish it was frozen!). My question is any reason for the abnormally high number of 3PN during my first cycle? The dr only explanation is that maybe my eggs were overmature or my E2 was too high. Also, give that none of my embroys made it to blast by day 5, my dr thinks I may have an egg quality issue (we used a very proven donor). Is this any egg quality issue? Thank you so much.
June 18th, 2012 at 2:31 pm
Thank you for this VERY informative website. We just finished our first cycle of IVF (now enduring the long wait to see if it was successful). I am 27 and our infertility was unexplained. We had seven eggs retrieved and all looked great up to day 3. When we arrived at the office for a day 5 transfer we only had one that had matured to a blastocyst. He mentioned that this was a much lower number than expected and was probably due to genetic abnormalities. From your experience, would this be more of an egg or sperm issue (all of our previous tests came back normal), or something else? What follow up questions would your recommend we ask our doctor? Thanks!
June 18th, 2012 at 2:51 pm
Dear Cherry,
Regarding the abnormally high number of 3PNs after ICSI: The condition of having 3PN (3 pronuclei) at fertilization is abnormal. There should be 2, one from mom and one from dad. The extra nuclear body can arise from an extra sperm or the failure of the egg to extrude it’s extra nuclei via the second polar body. We can rule out an extra sperm because if ICSI is performed properly, only one sperm is inserted per egg. The other possibility (failure to extrude) does point to an egg problem. Which (my guess) is why for your second cycle, your doc adjusted your stim (to avoid overly high E2 levels) as well a suggested a different donor. A less than optimal stim does affect egg quality and failure to fertilize or failure to extrude a second polar body may be seen with poor egg quality. Unfortunately, the first IVF can often be suboptimal because it is impossible to predict how an individual patient will do with a stim protocol. One size does not fit all. Poor embryo progression can also be due to either (or both) egg or sperm quality. It is encouraging that your morula in culture did turn into a blast, although it was a little slower than optimal. D6 blasts are somewhat less likely to result in pregnancy than day 5 blasts, but both can produce a pregnancy. Good Luck!! Carole
June 18th, 2012 at 3:03 pm
Hi Gina,
First, don’t give up on this cycle yet. You may still be pregnant.
Failure to progress in culture can be due to many factors. Aneuploidy (an incorrect number of chromosomes) in the embryo is one common reason. Since both sperm and egg contribute to the embryo, either can be the source of abnormal chromosome numbers, and aneuploidy can also arise spontaneously in the embryonic cell lines after cell division. Semen analysis does not give you information on the “per sperm” level, just the overall population so diagnostic tests are not usually very useful to figure out if the sperm that “made it” into the egg was normal or not. Diagnostic tests about ovarian reserve also do not tell you anything about specific eggs. SO even though “all tests came back normal” that is more useful for suggesting a treatment plan than for diagnosing failure to progress in a specific embryo.
Poor culture conditions are another reason for failure to progress. Hopefully, your physician will not be offended if you ask about this. If they are good, they will have thought about this too and will be able to tell you that other patients exposed to the same media, incubator etc did as expected. If day 5 culture is new for them, and they are using sequential culture systems which require a media change on day 3, it is possible to do this incorrectly (use wrong media or do not rinse off old media sufficiently) but this mistake is easily avoided with adequate training so that is probably not likely. But as always, if your doc gets overly defensive and doesn’t answer your questions to your satisfaction, you always have the option of getting a second opinion. Hopefully, none of this will be necessary. Good Luck!!
June 18th, 2012 at 5:23 pm
Wow Carole, thank you so much for your quick response. I have one further question if that is ok. Any idea how many day 5 morula turn into blasts?
June 18th, 2012 at 6:16 pm
Hi Cherry,
It really varies. There is no meaningful probability I could give you. It depends on the embryo’s potential. In my experience, most patients had the majority of their blasts by day 5, and very few had embryos left at morula stage to go on at that point. Carole
June 21st, 2012 at 3:47 pm
Hi Carole,
I am 28 & hubby is 33. We had one faile ivf cycle after transferring 2 grade AA blasts on day 5. I still got BFN even after those perfect embryos. We had FET done & transferred 3 day 6 embryos. 1 of them was hatching grade 1 (on a scale of 1-4: 1 being the best), 1 was fully expanded & the 3rd one had started expanding. I wonder if it’s going to work this time. I do not believe in my clinic anymore since nothing worked last time although they said everything was perfect. We do not have any infertility issues but my hubby is HIV positive so we are taking this as a precautionary action. My lining was 12.5 2 days before the transfer.
Thank you in advance.
June 21st, 2012 at 3:57 pm
Dear Hopeful,
Scoring and grades are not 100% predictive. I have seen high scoring embryos fail to implant and low-scoring embryos make beautiful babies. That is why you should take every cycle as a new chance. Don’t give up yet. It is too soon. Good Luck! Carole
June 22nd, 2012 at 1:21 pm
[...] Blog Entries6 Just to make sure that everyone understands, there are 2 ways to evaluate an embryo- the chromosomes and metabolic health. The progression and transfer state is very important. The major difference between a morula and a blastocyst is the presence of an ICM- Inner Cell Mass- if the embryos stalls, no ICM develops and the embryo never makes it to blast stage, then it can never become a baby. Transferring a morula is taking the chance that the embryo will continue to develop and develop an ICM. You have no idea if it does so after transfer obviously. When you transfer a blast or a HB, you know there is an ICM, all the parts are there so it is much more likely that a blast or HB will implant and result in a live birth. Now, obviously morulas can become babies and there is a study that says that girls are slower growers but you just cannot know if it will progress if you transfer before it becomes a blast. A HB however is seeking something to grab onto to implant right away- it is hatching to do just that so much more likely to stick. Just wanted to clarify. This is a great post by Carole, the lab guru on here- Embryo stages, progression and pregnancy outcomes | Fertility Lab Insider [...]
June 22nd, 2012 at 6:02 pm
Hi! My doctor and team are not responsive to questions and now my doc is out of the country anyway. They wouldn’t give me any rate info other than that at 44, I have a 4% success rate. It’s too late to change clinics and I didn’t learn until it was too late they have a poor general success rate compared to other clinics. Anyway I ended up with 4 eggs then 3 embryos. Because of my age and discomfort with waiting for genetic info we decided to do pgd. At day 5 I have 1 early blast and 2 morulas. I found out if the morulas have not progressed by tomorrow they would discard them. They can’t be tested with pgd. I don’t want to do another cycle after this so it’s my last chance and now I feel bad about tossing out the day 6 morulas. Since my clinic won’t give me any info (the nurse said she didn’t know what they did with morulas and would not even tell me what doctor was handling cases while my doctor is abroad) I have no idea what kind of success rate there could be for a day 6 morula that is frozen and then thawed. I also wonder if the chance of genetic issues is elevated since the development is slowed. Maybe my early blast will be strong and grow but I feel bad about the others. I wish I had done my research on the clinic in advance. I think this has been unnecessarily painful and confusing. When the nurse told me that maternal stress and depression has no known impact on miscarriage and also yelled at me for asking the same question more than once I really wished I could change docs mid cycle. Anyway any morula info would be appreciated. I did read some of the stuff you posted (thanks!) but I have read some successes with day 6 morulas and fets with morulas so am confused. Thanks! Mm
June 22nd, 2012 at 6:33 pm
Hi Mm,
I am sorry you are having such a difficult time. Don’t feel bad about the day 6 morulas. It is highly unlikely that they would have made a baby; they are lagging by two days. Freezing and thawing does not improve an embryos chances; at best, freezing and thawing does no harm. So I would not expect a better sucessrate with freezing/thawing day 6 morulas. Yes, the chances of genetic issues (meaning the risk of abnormal chromosome number called aneuploidy) is increased with severely lagging embryos and also is increased, unfortunately, due to your age. Generally speaking, you asked about morulas. Embryos that reach morula stage on day 4 of culture are proceeding at the right pace and have every chance of implanting if transferred, assuming there are no other problems. The problem is if the embryo reaches morula stage a day or more later than day 4; this signals a problem with the embryo and the expectation for implantation is much less. Good Luck with the early blast. I agree that you want to find another physician/clinic and if this does not work, you may want to consider the possibility of using donor eggs. Good Luck!!
June 23rd, 2012 at 3:15 am
Wow. I’m incredibly grateful for your time and energy in answering my question. I didn’t think freezing would help but I thought it might hurt quite a bit. my clinic won’t transfer without freezing at this point because it doesn’t fit their schedule so I’m kind of thinking about whether there is any chance for the morulas if we froze them and used them later (once ive built up a lining again) because the other option is just to discard But since we cant test the morulas and it sounds like their development is problematic, your answer that there is likely an issue puts me more at peace. I hate to let the little things go because I truly can’t stand to do this process again, even with egg donor, but I don’t want to transfer them if they have a strong chance of having issues. I don’t even know what kind of freezing process the lab uses but it’s a moot point now that they’ve told me I just have to go with their protocol. If the embryos had reached morula at day 4 but were still morulas at day 6, this still shows low potential right, even if they were ok at day 4? The lab person actually said they didn’t have good results with freezing morulas. I guess i also dont know what to do if the early blast is still too early a blast at day 6 for pgd tomorrow and if it would make sense if it is stalled at early blast on day 6 do i skip pgd but still freeze and transfer if it survives thaw? My problem if that im uncomfortable with termination post cvs for me personally and also uncomfortable about a child with aneuploidy so i feel very anxious. At any rate, bless your heart for helping me feel a little better in the midst of this traumatic process. I’m truly grateful. Mm
June 23rd, 2012 at 12:53 pm
Hi Mm,
You asked “If the embryos had reached morula at day 4 but were still morulas at day 6, this still shows low potential right, even if they were ok at day 4? “. That is correct. Morula on day 4 is the appropriate stage for the embryo. Morula on day 5 is slow. Morula on day 6 may no longer be alive and certainly has the poorest probability (if any) of continuing. Embryos continue to develop or die, they can’t take a “time out” or rest, so when they stop going forward, it’s not good. Most good programs can biopsy an early blast as well, although it is more difficult because the structures are less-defined. Unfortunately, some techs are trained to biopsy hatching blasts only because that is easier but blasts don’t always progress according to the clinic’s transfer schedule, leaving you with the choice of cancelling the PGD and doing the transfer. If you are uncomfortable with termination, then you should probably not skip the PGD, because the PGD is your only method to deselect abnormal embryos before pregnancy actually occurs. Good Luck! Carole
June 23rd, 2012 at 3:36 pm
Hi I’m 41 and had 2 day five blastocysts seven days ago. I have started to notice soms spots of blood and cramping as though I am going to start my period. Does this mean the ivf hasn’t worked
June 23rd, 2012 at 6:55 pm
Dear Adele,
Some women report experiencing cramping at the time of implantation so your symptoms are not necessarily cause for worry. But, as always, you should ask these questions of your clinic staff because they know your entire history and can best advise you regarding your medical concerns. Good Luck!! Carole
June 24th, 2012 at 1:28 am
If an embryo was grade 3 on day 3 but a compact morula on day 5 when it was transferred, what chances of implantation can be expected for <30 age group?
June 24th, 2012 at 6:30 am
Dear Dinken,
Since grading varies somewhat between clinics and since outcomes vary between clinics even with the same “grade” embryos, the answer to your questions is highly clinic specific. You need to ask your clinic what their statistics are for patients in your age who have embryos like yours. Carole
June 24th, 2012 at 10:01 am
Thanks Carole
June 26th, 2012 at 7:09 am
Hi Carole,
I am presently doing a donor cycle (recipient) and I just got the day 3 results. At retrieval they got 12 eggs, and at day 3, the results are as follows: 2 compacting Morulas, 8x8cell, 1x6cell, and 1x4cell. My question therefore is: is it ok for morulas to be evolving as early as day 3? The lab seem happy, but I just wanted your opinion. Thank You for a fascinating insight into what goes on in the lab!
June 26th, 2012 at 7:18 am
Hi Krissey,
I think your donor’s cycle is going really well. I wouldn’t worry about a compacting morula on day 3. What they look like on day 5 will be the determining factor. A compacting morula may be 10 cells that are starting to show evidence of “compaction”. Morulas are disorganized and kind of ugly looking–sometimes this is the designation for more advanced embryos that aren’t easily categorized so don’t get overly hung up on what could be anything on day 3. The picture will be much clearer by day 5. Good Luck!
June 26th, 2012 at 2:36 pm
[...] That is a great thing! It means they are transforming into a compacted morula. The morula stage is the stage right before they turn into a blast. The morula stage is characterized by a transformation from a loosely associated group of cells to tightly connected cells that are acting more like a tissue. The process by which cells change from loose association to tight association is called compaction. A compacted morula is a group of cells (usually around 30) which have squeezed together inside the zona. This stage is usually seen on day 4 of culture. Embryo stages, progression and pregnancy outcomes | Fertility Lab Insider [...]
July 4th, 2012 at 4:52 pm
Hi Carole
I am 39 and just nearing the end of my first cycle in the 2ww. I am a bit concerned about the progress of our embryos between day 3 to 5. I had 7 eggs collected, 6 fertilised, 5 eight cell @ 3 days and 1 four cell. By day 5 transfer we had 1 blast and 1 compact moroula and 3 still at 8 cells. Is this normal for only 1 blast? By day six the moroula had progressed to early blast unsuitable for freezing. What percentage of embryos usually make it to blast is one from five particularly low?
July 4th, 2012 at 8:00 pm
Hi Sarah,
It is typical to lose eggs and embryos at every step in IVF. In my experience, if we had 10 eggs, on average we could expect 70% to fertilize, meaning sometimes it was 100% but other times it might be 50%, depending on the patient. Of those that fertilize, maybe 70% would go all the way to blast but sometimes only 50%. So 70% of 10 eggs means 7 will fertilize. Of the 7 that fertilize, we would expect 3-5 to get to blast. If you start with 7 eggs, then you might only have 5 fertilized (you had 6), of 6 fertilized, 3-4 may get to blastocyst. You had 1 blast at day 5 and 1 compact morula which might be slightly low if you were under 35, but given that you are 39, it’s not unexpected. At this point, I would feel good about the blastocyst you had transferred and try not to worry too much. The 2WW is nerve wracking but it is too soon to give up. Good Luck! Carole
July 4th, 2012 at 10:54 pm
I am going crazy, I have 3 embryo’s. Yesterday at day 2, I had 1 3 cell and 2 at 4 cells. Does it mean the 3 cell may catch up. they are trying to get me to 5 days for implant.
The embryologist said the 4 cells ones won’t die off overnight, is that true?
I am so confused.
Any help would be great
July 5th, 2012 at 7:22 am
Hi Leah,
Having a 3 cell and two 4 cells on day 2 is fine. Assessments are typically made first thing in the morning. if this is the case at your lab, the 3 cell easily could have divided later in the day to a 4 cell. The 4 cells are fine on day 2. There is no reason to believe that the 4 cells will die overnight. Please don’t go crazy. It simply will not help. Take each day at a time. So far, so good. Good Luck! Carole
July 10th, 2012 at 4:39 am
Hi Carole,
I am 25 years old as is my partner. I had a day 2 transfer 4 days ago using ICSI. 15 eggs were retrieved, 10 eggs were mature and 4 eggs fertilised (I’m guessing this may be why I had a day 2 transfer as the clinic said that they are better off inside me than out). On the day of the transfer I had 3 that were all at 4 cells and 1 was at 7 cells. I had the 7 cell one transferred. I still feel a little bruised from collection, but I also have hot flushes, light headedness at times and an increased appetite. Are these symptoms normal (maybe due to medication), and when will I start to feel anything? Also were my embryos good quality.Thank you
July 10th, 2012 at 12:25 pm
Hi Baby-dust,
On day 2, 4 cells and even a 7 cell are about where we would expect them to be. By day 3, we like to see 8 cells so they are well on their way to that goal. Usually clinics will give you a “grade” for each embryo which depends on their appearance. Round even cells “score” better than irregular uneven cells. No or little fragmentation “scores” better than significant fragmentation. Hopefully, you will freeze the non-transferred embryos at some point. Regarding your physical symptoms, please discuss these with your clinic doctor or nurse. They can best advise you about these symptoms. Good Luck! Carole
July 10th, 2012 at 4:18 pm
Hi Carole,
Thank you so much for your reply. i was not given a grade for my embryos, but i have had my three 4 cell embryos frozen. i can see that you give fantastic advice to everyone on here!
July 12th, 2012 at 7:14 am
Hi Carole. i had a 2day transfer and currently on day 6 post transfer. i have a sore chest and an upset tummy (could be due to progesterone). my question is when is the earliest i can take a hpt, and also my menstraul cycle is irregular (currently day 19) does this mean that even if i dont bleed during 2ww it may not be pos on my test day as it will be day 27 of my usual say 35-42 cycle? Thank you.
July 12th, 2012 at 7:38 am
Hi Faith,
First, you need to ask your doctor/clinic nurse about any symptoms you are concerned about (your sore chest and tummy). Here’s a link with a chart that tells you what typically happens each day after transfer for day 3 transfers. Add a day for your situation. One day after day 3 transfer is 2 days after day 2 transfer, for example. The chart gives guidelines on when hcg (the pregnancy hormone detected by your hpt) starts to be secreted if implantation occurs. I would not change (stop) any of your doctors instructions for medications until you get the official blood test. The reason I say this and the reason your clinic typically tries to discourage hpt tests is because sometimes the home pregnancy tests get it wrong. The test can pick up residual hCG from your trigger shot if you do it too early and give you a false positive result. The later you take it , the more likely it is to be correct but not always. It is better to wait if you can for the official test. Regarding your question about your regular cycle- disregard any expectations from any natural cycle. The hormones you have taken have overridden your usual pattern. Good Luck. Carole
July 12th, 2012 at 11:08 am
Thank you Carole, much appreciated.
July 16th, 2012 at 7:04 am
Hi Carole. I to like Faith above am in the middle of my 2ww and have an irregular cycle. On Friday and Saturday i had abdominal discomfort as if my insides were being stretched. i responded well to stims and had retrieval on day 11. Iam currently on day 21 of my cycle. Is it true that if i have no bleeding up until and beyond my test day which is in 4days time that this means success? If not, will the cycle mimic the 28 day cycle? Thank you.
July 16th, 2012 at 12:14 pm
Hi Leigh,
I think that you shouldn’t necessarily expect this stimulated cycle to act anything like your normal cycle because you have been exposed to a lot more gonadotropins. I think there is little if any correlation between incidental bleeding (spotting) during the 2WW and whether or not you are pregnant. Everyone wants a “sign” before their pregnancy test to let them know what’s going on but there aren’t any that are reliable predictors for everyone. As far as your symptoms, please discuss these concerns with your clinic. They really can give you much better advice (and treatment if necessary) than I can. Good Luck! Carole
July 16th, 2012 at 4:03 pm
Thank you
July 18th, 2012 at 7:11 am
Hi Carole
i feel so sad and disheartened, i tested this morning (2days early) currendly 12dp day 2 transfer and got a bfn! It was an online hpt that is a month or two out of date. I had cramping foyr days ago as if af was here, but apart from that nothing. i had a m/c with a normal preg a while back and now starting to think is it my body.
July 18th, 2012 at 8:39 am
Hi baby-Dust,
I am so sorry that you are going through this now. If at all possible, please get your actual test done in two days and don’t stop your meds until your doctor/nurse advises you to. While I agree, the odds look bad now, you are two days early testing with an out of date home test. Just give it two more days and wait to get the blood test. Sometimes, we have found patients who assumed they were not pregnant based on a hpt and then got a positive result at the official test. That’s why clinics discourage early at home testing. Good Luck! Carole
July 19th, 2012 at 12:10 pm
[...] Embryo stages, progression and pregnancy outcomes 2. Egg Count Mathematics: Why the numbers change between retrieval and transfer. 3. Sperm [...]
July 20th, 2012 at 4:23 pm
So just did a FET today… They were frozen years ago as 8-cell. They were viable yesterday with >50%intact. One wasc4-cell, one was 5-cell. There was no growth overnight…however the RE still wanted to continue with transfer. These were our last 2. It wasn’t quite 24hrs, just about 20…. Is there sometimes a delay before replication with FET? Or am I reaching for pixie dust?
July 20th, 2012 at 4:43 pm
Hi Shell,
When there is significant fragmentation, it is discouraging but it is too soon to give up hope. One of the most beautiful IVF babies I ever saw came from an embryo that we had all but given up hope for. So, you see, it may not be over yet. Good Luck!!! Carole
July 25th, 2012 at 1:34 pm
Hello,
I had a 3 day transfer on 7/21/2012. One 8 cell and one 12 cell.
I think there was some framenting. I am 40 yrs old. This is my 2nd cycle of IVF.
Can you give me your thoughts? If the 12 cell implants will it be abnormal?
What questions can I ask my doctor to make me feel more at ease?
July 30th, 2012 at 10:09 pm
rochii de seara ieftine…
[...]Embryo stages, progression and pregnancy outcomes | Fertility Lab Insider[...]…
August 7th, 2012 at 8:53 am
Hi carole… i ‘m 33 years old. this is my first ivf. i had a day 3 transfer. the embriologist told me that out of 5 only 1 can be transfered which is with 5 cell. and she also told me that i only got 1% chance in getting pregnant.
Can you give me your thoughts?
August 7th, 2012 at 3:11 pm
Hi Fizah,
It’s too early to give up. A five cell embryo does have fewer cells than ideal –we like to see 8 cells after three days of culture–but I have seen pregnancies even with a less than ideal number of cells. Your youth is in your favor. If this doesn’t work, I would check the programs success rate at http://www.sart.org. If they are not reporting AT LEAST a 50% live birth rate in the under 35 years of age patient group (your group) I would consider finding another program. Good Luck!! Carole
August 8th, 2012 at 10:32 pm
thanks carole….
August 16th, 2012 at 12:25 pm
Hello,
I have undergone 2IVFs. The 2nd cycle we did was at one of the best clinic in US (CCRM) hoping to get better results & some answers. I am 36yr old & we are unexplained. No sperm issues. 24 eggs were retrieved, 18 mature & only 7 fertilized using ICSI. Out of the 7 none made to it blasts. There were 4 good embryos on Day 3 – 10 cell, 9 cell & 2 8-cell .We were gonna get our embryos CCS tested, hence had decided to push them to Day 5. My doc thinks it is definitely an egg issue. What are your thoughts on my case? Do u really think it is an egg issue? And lastly, my 1st cycle also did not make any blasts & hence we did Day 3 transfer with nothing to freeze. Your thoughts will be much appreciated.
August 16th, 2012 at 5:49 pm
Hi CM,
I am so sorry you are having such a hard time. It’s really impossible for me to know whether it is an egg or sperm (or embryo) problem. It sounds like your embryos stop growing after about the 8 cell stage. Aneuploidy (defined as an abnormal number of chromosomes) can occur in either the sperm or egg, causing problems with either fertilization or later embryo development. In addition, it is possible for aneuploidy to arise spontaneously in the embryo during the course of multiple divisions, which can also cause the embryo to stop dividing. Deficiencies in the egg cytoplasm (eg. a low number of mitochondria) also can cause the embryos to stop dividing since mitochondria “power” the work of the cell. You are on the young side –aneuploidy-related problems are more common as we age–but even younger women (or men) can have aneuploidy problems. The only (possibly) helpful thing I can say is that although we don’t know why you are having this problem, you are one of those patients who unfortunately are experiencing a very low efficiency with IVF (lower than expected fertilization) and then poor progression, no transfer and no frozen “surplus” embryos. Since there is no obvious sure cure and you have been using a good lab, it might be time to reconsider other routes to parenthood. You are spending a lot of emotional and financial reserves and it is not working well for you. The problem is that since it is hard to know why you are experiencing low fert rates and poor progression, the next often proposed step, (egg donation) may also not work and is even more expensive. Sperm donation, though less expensive, still usually involves IVF and may not fix the problem. I wish we had better diagnostic capabilities to understand the source of the problem to guide you but we aren’t there yet. Other options besides gamete donation (of either egg or sperm) are embryo donation or adoption. Perhaps a break from treatments to reassess would be most helpful to you now. Good Luck!!!
August 23rd, 2012 at 12:53 pm
Carole – Thanks for your reply.
One important thing I forgot to mention is that the embryologist pushed the 3 embryos upto 7 days to study their growth. On his recommendation we biopsied those embryos to have some answers during that cycle. As it turned out all the 3 embryos were aneuploid. He & the RE both are of the same opinion that it is an egg issue, cause all the sperm tests have come back normal. They also informed me that in 95% of the cases it is always the egg issue, when they see this kind of cases.
Any thoughts?
September 13th, 2012 at 8:41 am
Hi carole,i am 31years old with one fersh ivf cycle day 3 transfer failed.3 clomid cycl failed not ovalating.on sep 20 started my fet cycle for day 5 transfer. On day three I got call that I lost two embryos and third one is 60% o.k.(they said that embryo lost four cell out of nine cell ) I did not had hope but monday on day five I got call my embryo reached bioplast stage with 1BB grade. I want know wheter have chance success with this embryo and want know about embryo stops expanding and rexpands. Please mail the reply thank u
September 22nd, 2012 at 1:07 pm
Hi we just had a fresh transfer, they transferred two five day morulas, and I just found out that the other four didn’t make it so none to freeze. I have a picture of the two they put back but no other information. What questions should I be asking the embryologist about my morulas.
September 22nd, 2012 at 1:08 pm
OH and will morulas result in pregnancy?
September 22nd, 2012 at 1:15 pm
Hi Ricarda,
Yes, morulas do result in pregnancy, even if they are morulas on day 5 instead of day 4. It is disappointing that none of the others made freezing criteria but I wouldn’t give up on the two you had transferred. One question you can ask your embryologist is what has been their experience (pregnancy rate, take home baby rate) with transfer of day 5 morula in women in your age group. Good Luck!!
Carole
September 22nd, 2012 at 2:18 pm
Wow thanks for the quick response. I guess I could have shared…
This is my third ivf. however the eggs were from a 31 year old donor.
I am 42, no issues other than mild endometreosis
Ist ivf, three 3 day embies
2nd ivf, four 2 day embits
third ivf with donor cancelled
and this one with same donor, 9 eggs, 8 injected 6 fertilized 2 morulas put back and like I mentioned none to freeze.
i have been given a 60% chance. My final question.. will hatching the two morulas increase the implantation rate? they did hatch them.
and is there anything i need to aviod or do to encourage implantation?
September 22nd, 2012 at 2:49 pm
Hi Ricarda,
Assuming that the lab is proficient at hatching–and if they have a laser, it’s very easy to do well–there should be no downside to hatching. I think you should ask your clinic about what they recommend for you in the 2WW. Typically, most programs suggest that you stick to your normal routine, unless your normal routine is running a marathon, sky jumping or otherwise overly stressing yourself. On the other hand, bed rest is not needed and is not recommended. Take your daily multivitamin but not excessive doses of anything. Be moderate in all things and find ways to keep your mind busy and spirits up so you don’t fret about the pending pregnancy test. It’s a cliche but “Don’t worry. Be happy” is a good goal if you can manage it. Good Luck!!
September 26th, 2012 at 11:32 am
Hi Carole,
Thanks for blogging and taking the time to answer questions. I am 36 y.o. with 1 miscarriage (at 7 wks), 4 failed IUIs, 3 failed IVFs. We are currently on our 4th IVF cycle. Today on Day 5 after fertilization, we were told that we have 5 embryos, no blasts. When the nurse called on Day 3, we had “two good ones” and the lab wanted to delay us to Day 5 to give the others more time to develop. Today they did not say whether we had morulas, just no blasts and that none have arrested development yet. One embryo fertilized late on Day 1, since our fertilization report initially came back with 4. We are wondering if we should be hopeful that this late one and others still have a chance to become blasts on Day 6. Nurse didn’t think the probability was good, but at least the embryologist wanted to give the embryos more time. To have 5 embryos on Day 5 that are still developing, while slow is the best progress we’ve made so far. Cycle #1 we had 2 to transfer on Day 3, Cycle #2 none to transfer, Cycle #3 1 to transfer on Day 3. We are so anxious and nervous! Thank you in advance.
September 26th, 2012 at 12:39 pm
Hi Nik,
Different programs have different policies on when to transfer (d3,5,6) and what stage to transfer (multicellular, morula, early blast, expanded blast, hatching) . The programs I have been with would transfer what was most advanced on day 5–even if those are early blasts or morulas. Some programs will transfer only blastocysts and will wait until day 6 to reach that milestone. Your program appears to take the later route. They place a very high value on what they see in culture and are comfortable with not transferring anything that didn’t hit the milestones exactly on time in vitro. Others might argue that embryos do better in the body and put them back sooner. I don’t know what’s best. The important thing is that you feel good about the plan and if you have concerns or unanswered questions, I would go back to your doctor and have him explain the thinking behind their policy. They may have data to show that they never get pregnancies from transferring morulas–though I would doubt that. The other thing is that although you are young, IVF is not working for you very well and it may be time to get a second opinion from another RE or move on to another family building strategy. As a rule of thumb, if you don’t get pregnant after 3 tries, it’s time to move on. Whatever happens, I wish you the very best and much Good Luck!! Carole
September 30th, 2012 at 8:58 am
Hi …
x
I am 23 years old with mild pcos &’low motility I have just had my embryo transfer it is my 2nd icsi cyle , 18 eggs retreived 15 mature 8 fertilized only 1 made blast on day 6 today what are my chances of a pregnancy my. 1st cyle I had 13 eggs 10 mature & only 4 fertilized had 2 4 cells grade 1 put back on d2 bfn no frosties my embrolasgest is very happy with my 1 blast please help I’m so worried of failure again
September 30th, 2012 at 11:04 am
Hi Jessica,
Carole
I can’t tell you what your probability of being pregnant are this cycle but I can tell you that you have two very important things going for you: You are young and your embryo made it to blastocyst stage before transfer. Don’t worry. Worry will not help and will only make you miserable while you wait. Follow your doctors instructions and try to occupy yourself with other good things going on around you during this 2WW. Good Luck!!!
October 8th, 2012 at 7:44 pm
Hi Carole,
I have a question about interpreting the embryology development for my upcoming IVF day 5 transfer. Specifically, I’m wondering if any of the following results show cleavage that is too advanced for Day 3? My basic stats are that I am 40, 18 eggs were retrieved, 15 were mature, 12 fertilized. As I mentioned, I am scheduled for a day 5 transfer. On day 3, all 12 fertilized embryos were still developing: two were described as “expanding and compacting,” one 11-cell; two 10-cell; four 8-cell; one 7-cell; one 6-cell, one 4-cell. l realize that at least one is cleaving too slowly to indicate normal development, but what is the range of normalcy for day 3 and are any of these embryos so rapidly cleaving as to suggest poor quality? Unfortunately, I do not have additional information about fragmentation, etc. Thanks very much.
October 8th, 2012 at 8:15 pm
Hi Alexandra,
In my program, we would favor the on-target embryos over their slower or faster siblings if we were transferring on day 3, we would be interested in transferring from the four 8-cells you have first. The “range of normalcy” is not clear cut but the textbook expectation is 8 cells on morning of day 3. That may be too rigid a criteria of normality. But since you are going on to day 5 with your embryos, you should have more info about their growth potential by then. Some culture systems support expanded blasts and even hatching blasts on day 5. Other programs report that in their system, they see the majority of blasts on day 6. Your lab can advise you as to what their experience is regarding the best day to transfer and what their best blast for implantation looks like on that day. They will probably want to transfer any expanded blasts you have or even hatching blasts. Good Luck!!
October 9th, 2012 at 2:35 pm
Hi Carole,
What a great site you have for people with infertility questions.
I had a FET transfer last week. 2 of the 3 made the thaw. They were graded 2BC’s day 6 embryos. I am not sure when they thawed the embryos. The paperwork said 0% re expanded done at 830AM. My transfer was at 915AM but the doctor said they were slowly re expanding. He said they like to see them expand more but they for sure survived the thaw. One had >20% cell loss and other >30%.
My question is how crucial is the re expanding of the blasts? I am not sure when they were thawed. He did say that they showed improvement 10 minutes before transfer. Thank you to any insight. This is our last shot with our own DNA before pursuing adopted embryos (I am age 35, he’s 30 with MFI factors).
Also, we had 1 failed IVF resulting in our frozen embies but I believe we had implantation issues as my lining was over 18mm at trigger date.
Thank you for your time- Rachel
October 9th, 2012 at 2:43 pm
Hi Rachel,
I think it is a good sign is the blasts showed signs of re-expansion just before transfer. That means they are alive because expansion is an active process. It can easily take a few hours for re-expansion so I wouldn’t be alarmed that they were not expanded at 8:30AM but by 9:15AM showed signs of expansion. That is fairly typical. If I understand your email, you are in the middle of the 2WW before your pregnancy test and no doubt getting anxious. That’s normal. Just try to distract yourself with some good things happening around you right now. In spite of the male factor issues, your relatively young age is working in your favor. Good Luck! Carole
October 10th, 2012 at 3:36 pm
Thank you Carole for the reply.
I asked the lab today and they said 12 hours thawed before transfer. My test is the 15th. I think the doctor said that to try and make me feel better.
Your help was greatly appreciated.
Rachel
October 13th, 2012 at 10:11 pm
Hi Carole,
I trust my doctor, but I’d like to get your opinion too. I’m 33 with unexplained infertility, my husband is 35 with good sperm. We have been TTC for 3.5 yrs. We are just finishing up our first ivf. I had 11 follicles, 6 eggs, 5 mature, with 4 that fertilized. My doctor wants to do a 3 day transfer, that will happen tomorrow. The clinic here rates the embryos 1-4, with 1 being the best. This morning on Day 2 my 4 embryos were
6 cells Grade 2
4 cells Grade 2
4 cells Grade 1
3 cells Grade 1
I’m not sure what they will look like tomorrow, but which ones would you transfer? Assuming they double tomorrow maybe? Also, why not wait until day 5, isn’t there a better chance of success if we do? Also, can I suggest one on day 3 and one on day 5?
Thank you for your advice!
October 14th, 2012 at 7:53 am
Hi Rachel,
On day 3- I would transfer 8 cell embryos even if they have a slightly lower score. If you wait to day 5, you will know which ones were able to progress to blastocyst (implantation ready) stage. As you are young, most clinics would transfer only 1-2 embryos based on maternal age (if there are no other factors that otherwise would diminish your odds of pregnancy) so longer culture may help show which embryos are most progressive when there are more candidates on day 3 than the 1-2 for transfer. Since 3 of your embryos are at least 4 cells on day 2, some docs would want to see more development to pick 1 or 2 best on day 5. You should discuss this further with your doctor as you still have questions. I would NOT transfer some on day 3 and some on day 5. Every time you put the catheter into the uterus, there is some risk of scratching the endometrium (uterine lining) which would pretty well nix your chances of implantation. Good Luck!!! Carole
October 15th, 2012 at 8:50 pm
Thank you very much for your answer! They ended up putting 2, 8 cell embryos in, and freezing two. Great resource you have. Thanks again!
October 15th, 2012 at 8:58 pm
oh, and all four had progressed overnight to a 1 rating, (the best). I had 3, 8 cell and 1, 10 cell. Some had even starting developing into the next stage, I forgot what she had called it. I was very upset when they had only gotten 6 eggs, but now I’m super happy with the results. I wish we could have waited until day 5, but initially they said because it was a low number they recommend a 3 day transfer. I hope it was the right choice. They seemed optimistic about it. Thanks again for the answer, info, and the blog!
October 16th, 2012 at 6:35 am
Good Luck Rachel!
October 21st, 2012 at 7:37 am
Hello Carole,
Ive had 2 failed ICSI cycles and am now waiting for the results of my third IVF. I was surprised when the embryologist siad they were doing IVF this time.
Last two cycles I produced 11 eggs and which most fertilised but on day three Ive always had 4-5 cell embryos to transfer.
This cycle I only produced 4 eggs of which 3 fertilised. I was on teh short protocol and was on150 menupur and 0.25 cetrotide. We were told on the morning of transfer that there were two 5cells to transfer. When we got there in the early afternoon one had split into a 6 cell and teh other was still a 5 cell.
I am 30 years old and had my first ICSI when I was 28.
What are my chances with slow growing embryos?
Sara
October 21st, 2012 at 8:32 am
Hi Sara,
I am sorry you are having such a hard time. As far as trying to understand why you are having such slow growing embryos at such a young age, it’s impossible for me to know for sure. But there are a few things to consider.
First, I assume you have checked the success rates of your program and that for women in your age group, the pregnancy rate is above 50%. SART has a website (www.sart.org) that has an easy-to-use tool for looking up pregnancy rates on most every center in the US. If you find poor rates in the youngest age group in a program, I would consider finding a program with higher rates.
If you can rule out lab quality issues, the other common cause of embryo slowness or failure to progress is aneuploidy- meaning some chromosomal abnormality exists in the embryo (two few or too many chromosomes) which can arise from either the male or female side. These problems with chromosome number can occur during egg or sperm production or in the early cell divisions of the embryo after the egg is fertilized. it is possible to test the embryos by removing a cell and sending it to a genetic testing lab (embryo biopsy and PGS Screening) to see if that cell is normal. With that test result on each embryo, normal embryos can be chosen for transfer, upping your odds of pregnancy. But aneuploidy testing adds to the cost of IVF- so that is not always possible. And sometimes patients find out that all their embryos in that cycle are abnormal and they have no transfer–which is very disappointing.
I can’t give you a probability of pregnancy with embryos that only have 5-6 cells on day 3 but I agree that if the embryos aren’t ever reaching 8 cells on day 3 of culture or blastocyst by day 5 or early day 6, the probability of pregnancy with IVF is suboptimal and it might be time to consider other paths you have available to you. I wish you the very best. Good Luck! Carole
October 21st, 2012 at 8:46 am
Thankyou very much Carole for the fast reply. I’m hoping that the embryos transfered will stick. Ive had all my cycles in England nearer to where I reside. So I’m looking at going abroad if this cycle does not work.
I would just like to take the opportunity to thank you and reading the other posts and your replies has helped alot!
It means so much you’ve taken your valuable time out to answer my question!
October 22nd, 2012 at 1:19 pm
Hi Carole, First all of thank you so much for this blog and helping several women with their questions like me. You are so kind.
I am 31 year old and dealing with infretility. I am doing my 2nd IVF cycle and had 14 Eggs Retreived, 13 Mature performed ICS1 and 11 fertilized. Today was day 5 for the embryos and I heard that there are 9 left and are not blastocysts yet and may be slow and become Blasts tomorrow. So they will call me tomorrow and we will not have fresh trasnfer. I have some questions for you, if they make to blasts tomorrow(early Day6), is it bad that they become blasts late or what is the impact and then should we transfer more embroys since they are day 6 blasts than we were going to transfer if they were day 5 blasts. We are also doing PGD on them..in case they are PGD normal Day 6 blasts , is it good to transfer.. Even in my last cycle, none egg made to blasts on day 5 either. I am just worried if it is worth transfer day 6 blasts..i mean dont have a choice..i do not have any blasts that grow in 5 days only 6 day if I get good response tomorrow.
Sorry for all the questions..your time and response is highly appreciated.
October 23rd, 2012 at 1:58 am
Hi PA,
If they are PGD normal, I would transfer the blasts, even on day 6. Culture systems vary enough that at some labs, most of their embryos are blasts on day 5. In others, they might see a good number reach blast only by day 6. Your embryologists should have a better idea of what to expect when d6 embryos are transferred in their lab. Don’t be afraid to ask your embryologist or doctor for their specific experience with their system as it applies to your medical situation. With PGD, some programs routinely delay transfer until day 6 to accommodate 24 hr testing between day 5 and day 6 so day 6 transfer does result in pregnancies. Good Luck!! Carole
October 23rd, 2012 at 10:57 am
Thanks Carol for the response. I got an answer today that we got 4 Blasts today Day 6 and have been sent for PGD. We will know results in a week as we cannot do fresh transfer. It is a good idea you said that I should ask my doctor or embroyologust their experience with my situation.
October 23rd, 2012 at 2:11 pm
Hi carole,am 35,on my first ivf,3eggs was retrieved n the 3 fertilized but very slow on day 5 they were still on stage 3,it was transferd on dat day 5 cos doc said they r still alive n I was given a shot to help d growth of the embryo,hope it works n I get pregnant,is it so bad dat on day 5 my embies were still in stage 3.
October 24th, 2012 at 4:12 pm
Hi Viv,
I am not sure what you mean by stage 3. On day 3 in culture, we like to see that the embryo has around 8 cells, has fairly even cells with minimal fragments. By day 5, we like to see a well-defined embryo called a blastocyst that has two parts- one part that will make the baby and the rest is for making a healthy placenta. It is concerning when embryos don’t hit the milestones when they should because it often signals that the embryo might have stopped growing. You should discuss these concerns with your doctor/embryologist to get the specific details of your case. Good Luck!!
October 25th, 2012 at 11:27 am
Hi Carole, geat post. I just completed a 5 day transfer with eSET (grade AA blastocyst) that was beginning to hatch. Of the 4 eggs fertilized in my cycle, ALL made it to blast stage and were either AA or AB. The clinic (the largest clinic in the mid atlantic, based out of MD) seemed rather optimistic about my cycle given the lack of decline my embryos experienced. Is this indicative of pregnancy outcomes? I was actually quite surprised that the embryos did so well given my husbands severe male factor problems, including 0% morphology, so I am hesitant to get my hopes up. I am 31 and my husband is 33. We have 4 iui failures with donor sperm for a bit of history. Thanks!
October 25th, 2012 at 9:46 pm
Hi Anna,
There are no guarantees but it is always a great sign when embryos reach blastocyst stage with high morphology scores. Your and your husband’s youth are also working in your favor. Good Luck!!
October 29th, 2012 at 5:13 am
Hi Carole I am 31 and boyfriend is 29. I have endometriosis and a low AMH of 6.25 for my age but boyfriend has no problems. At collection, last Wednesday, 10 eggs were retrieved, 9 fertilised but only 2 made it to transfer on day 3, both 6 cells and grade 3 with 4 being the top grade. The other 7 embryos stopped dividing at just 2 cells. Please can you shed some light on why so many embryos stopped developing and what are the realistic chances of the 6 cell embryos lasting the distance. I feel very disheartened that I don’t have the magic 8 despite the fact that literature quotes 6 -8 is normal for day 3. Any help is appreciated, thanks.
October 29th, 2012 at 11:50 am
Hi VJH,
I am sorry that you are feeling so low. There can be many reasons for why embryos don’t progress. This can reflect problems in either the embryo or the culture system. The only way you can assure yourself that the culture system is good at your clinic is to choose a clinic that does at least 150 cycles a year (practice does make perfect) and they report a pregnancy rate in the youngest age group of at least 50%. Sometimes embryos are slower if they have an abnormal number of chromosomes (aneuploidy). There is no way to eyeball the embryo and tell if this is the case. Representative cells from each embryo need to be sent to a testing lab and submitted to genetic testing but that adds to the expense of the IVF cycle so that is not always possible. If an embryo is struggling with lots of fragmentation, it may appear to be slower but actually is on target but cells are being lost to fragmentation along the way. The timing of the morphology check also affect the number of cells. So in spite of the fact that your embryo did not hit the “magic 8″, don’t give up yet. Embryos surprise us all the time and your youth is on your side. Good Luck!!
November 1st, 2012 at 1:26 pm
Hi Carole. I’m reading your blog and have a few questions. I recently had my third FET. We had 3 (3 day) embryos transferred. Two of them lost some cells during the thawing process but quickly recovered and went on to be 10 and 11 cells by the time we transferred. The 3rd one was a 9 cell. It did not lose any cells during thawing, but it also had not grown at all in 24 hours. The Dr. placed all 3 back saying “I’m sure that even if we cultured the 9 cell embryo that hasn’t grown in the lab for another 2 days it wouldn’t go anywhere-so I’m OK with putting 3 back”. This was on 10/10. I had my HCG checked at 8 days past transfer (or 11 dpo) and it came back at 100! Progesterone was 42.4. I was tested again 4 days later and HCG was 444 (doubling time 49 hours) and progesterone 38.6. I had another draw 2 days after that. HCG was 1021 (doubling time 36 hours) and progesterone 38.7. I had a blood draw on 10/30 measuring my progesterone at 55.8 and estrogen at 555. I did not get an HCG value. We also had an ultrasound done to measure early uterine activity. Obviously only hoping to see a sac. Instead we saw 3!
The Dr. said the middle sac is “questionable” and we need to wait it out. Each sac is 3mm, but the middle is a “tish” smaller than the others. I have another U/S scheduled for next week.
What are the clinical chances that all 3 sacs turn into viable babies…and if the 9 cell hadn’t grown for 24 hours…isn’t it odd that it implanted?
I have 3 children from previous FET cycles. B/G twins (daughter passed away at 6 hours old) that was 4 embryos transferred. and a Son from 3 embryos transferred.
November 2nd, 2012 at 7:58 am
Dear Carol,
I had egg retrieval 2 days ago ad 10 eggs were collected. 4 were inseminated conventionally but 0 fertilized. 4 were icsed and 2 fertilized. We have poor sperm motility and morphology . So I only have 2 embryos in culture. The clinic wants to perform a 5 day transfer. I am worried that if we wait that long I may have nothing to transfer.
What would you advise in such a situation?
November 2nd, 2012 at 8:33 am
Hi Liz,
The short answer is that I can’t tell you the probability that all three sacs will turn into viable babies. There are many possible scenarios that affect the number of viable babies when embryos are put back. I have seen embryos split after transfer so that we transfer two and see three sacs. In your case, when the questionable third was put in, it is possible that it didn’t make it but one of the other two may have split- resulting in three sacs. Whether that happened is not possible to discern this early in the process. The other explanation is that the embryologists’ scoring of the nine cell may have been off. Sometimes, cells divide but than fragment so the number is unchanged but the embryo is still alive- less likely but possible. I also have seen cases where three sacs are present at the beginning but some of them-hopefully not all!- demise over time. As an embryologist, I tend to want to be conservative and only put one or at most two embryos back per cycle because especially if patients have been pregnant before, embryos have a way of defying our expectations when we assume some will fail. Based on your history , your doctor made an educated guess that the three won’t all make it but we really never know what an embryo is going to do after transfer. I wish our system supported multiple transfers of one embryo at lower cost rather than gambling with more but that probably won’t change any time soon. At this point, wait and see how it goes and consider carefully how you feel about triplets- and what obstetrical issues triplet pregnancies pose-if you have an obgyn, it might be good to discuss these issues with them. Sometimes embryos may demise –especially if you see a smaller sac–and you may well end up with a twin or singleton pregnancy but it is too soon to know. I wish you all the best!! Good Luck!!
November 2nd, 2012 at 8:44 am
Dear Gudz,
I would ask your doctor to tell you–based on his/her statistics in their own lab–what is the probability of your embryos getting to the blastocyst stage? Also, ask them, how allowing the embryos to go to blastocyst stage will affect their choice of which ones to put back? If they are already planning to put two back in if you have them, there seems little advantage to waiting to see if both make it through their culture system–because failure to make it can be a sign of either a poor embryo or a poor culture system. If you are hoping to only transfer one, it would be useful to see if one is more advanced then the other by day 5-assuming the culture system is good. If you are having genetic testing done, it may be necessary to go to day 5 to 1) get the results back after day 3 biopsy or 2) do trophectoderm biopsy. If neither genetic testing or elective single embryo transfer applies to your situation, these reasons can can be ruled out as a reason to culture longer. I think you need to have another conversation with your doctor to understand what he/she hopes to accomplish with this approach. If there is no compelling reason to continue to day 5 or their past success with day 5 culture is low (and if you will be charged more for day 5 culture), it might make sense to ask for a day 3 transfer instead. Good Luck!!
November 2nd, 2012 at 9:25 am
Thank you Carole for your prompt response. I am going to speak to my doctor today to get more information. It seems it is standard for them to culture to day 5 or 6 .
We were planning to transfer 2 anyways and no genetic testing necessary so there really is no reason to wait but I will speak to my doctor today and get his opinion and find out if we can do a day 3 transfer .
November 2nd, 2012 at 3:05 pm
Thanks Carole. My next appt is Monday…so we will see more then. I’m really holding out hope to only have 1 healthy baby in there! I can be OK with two…but 3! After losing our daughter….I’m just in shock that it’s possible that the 9 cell may have “taken off” and implanted. My Dr. told me I need to relax (little freaked out here lol) and just because I see 3 sacs…doesn’t mean 3 babies just yet. He said, in his professional opinion, that my numbers more represent a twin vs a triplet pregnancy. Especially given my progesterone numbers. Thoughts on that?
November 2nd, 2012 at 3:57 pm
Hi Liz,
I can’t weigh in on that- that’s a medical, not lab/embryo question. But if your three sacs resolved to two sacs, you wouldn’t be the first. Good Luck!!
November 5th, 2012 at 6:57 pm
Hello Dr and thank you so much for all your info.
My wife had 2 blastocytes implanted last week and she sent for her blood test Sunday, and later that day they called to say she is pregnant. Im very excited to say the least, but also very nervous. This is not our first attempt although the 1st time with good news so far. My question is, from this first blood test and a positive pregnancy reading, what are the chances going fwd of a complete pregnancy? Is it still to early to celebrate? Or is this a good sign with good chances? She goes back tomorrow for another blood test to ensure her levels are still increasing.
Thanks for your time.
Rob
November 5th, 2012 at 7:36 pm
Dear Rob,
First, let me say Congratulations!! I can’t tell you what your chances are for the pregnancy to go to term. Your doctor would be the better person to ask about your specific situation. I will say this. You just need to take each day one day at a time. If I were you, I would enjoy every bit of good news that you get, just realize that it is early. Some couples wait until the end of the first trimester to share their pregnancy news with their family and friends because the pregnancy is less likely to be lost the longer it goes. But every successful pregnancy has gone through these early days that you are going through now so every pregnant day is a good day and you don’t want to rob yourself of today’s joy because you fear the worst. Frankly, as a parent, you will always fear for your child- this is only the beginning. I wish you and your wife every happiness and Much Good Luck!! Carole
November 9th, 2012 at 9:47 am
Carole,
Thank you, and very sound advice. We are very excited and thus far all good news. Each day that passes and new tests are performed, my wife is doing splendidly.
I did not phrase my question as clear as I intended. What I should have asked was are there any differences between IVF using blasto’s vs. normal pregnancy from the moment a mother knows (or is told) she is pregnant? Meaning, blasto’s are artificially placed so is there a greater chance they may not “take” or once we are told of the status pregnancy is it safe to assume they have attached/taken? More simpler, once pregnancy is established, is there any difference from that point on between a normal conception and an IVF conception? Or from that point on, equal in chance for the most part? My wife must still do Progesterone injections which a normal conception would not be doing so I do see differences in that regard. Is the primary intention of the meds to increase chances?
Thank again for all your time and expertise,
Rob
November 9th, 2012 at 10:22 am
Hi Rob,
Whether pregnancy comes about through intercourse or through transferring a healthy blastocyst to the uterus, in both cases the blastocyst stage embryo burrows into the uterine lining and produces hCG, the hormone produced by the trophoblast/future placenta which is detected by the pregnancy test. So yes, if you find hCG in the blood or urine. the most likely explanation is that you have implantation. (There are exceptions –you can have a false positive result if an IVF patient tests too soon before the hcg from the trigger shot is cleared from the blood; also some tumors can cause hcg production (testicular cancers have been detected this way)) From implantation on, an IVF pregnancy and an intercourse pregnancy should be highly similar, if not identical. The reason your wife needs supplemental progesterone now is to counterbalance the overly high estradiol levels produced by ovaries in response to the stim drugs. The uterus needs to have a progesterone dominant hormonal balance to support the pregnancy and placental development. Later in pregnancy, the placenta is a big enough organ, producing enough progesterone on its own so that the supplemental progesterone is no longer needed. Unfortunately, as you know, pregnancies can fail later in pregnancy for a host of reasons so a good start is no guarantee. Your iVF doctor, who is a reproductive endocrinologist, should be able to give you a very good explanation of all of these questions and what to expect going forward. I would still urge you to discuss these medical questions with your doctor- he/she is the hormonal expert. I hope this helps. Good Luck!! Carole
November 13th, 2012 at 9:23 pm
Hi. Thank you for this blog. Your responses to others have been very helpful. I am 33, husband is 32 and we are currently in the 2ww. I don’t have any issues that I know of, husband has bad morph of 1% and low but not terrible motility, and average count. Had 10 eggs retrieved, 8 mature, 6 fertilized. On day 5 we had only 2 embryos remaining and were not to the blast or morula stage. The embryologist said they were compacting 20 cell embryos that were still growing- just slow. We had them transfered and embryologist said we had a good chance and that they see embryos like mine turn to blasts on day 6 all the time. I am skeptical. I hear about success stories with morulas on day 5 but nothing really earlier than that. Are they only morulas when they reach 30 cells? Mine were deffinitely forming a center mass so perhaps in a couple hours they would have been. In your opinion, what are the chances of embryos like ours turning into blasts post transfer and thus viable pregnancies? If this doesn’t work out should we shop for a new clinic? I read on this site that the success rate should be at least 50% for the lowest age group. Our clinic has 43% for MFI cases (36% for all cases) and they do 500+ cases per year. Or is this type of embryo development to be expected for MFI cases with bad morph? Thank you so much for your time.
November 14th, 2012 at 8:01 am
Hi KIm,
The 2ww is very stressful. It is true that embryos routinely make blasts on day 6 as well as day 5–but generally most blasts become blasts on day 5, not day 6. The pregnancy rate with day 6 blasts is typically lower than with day 5 blasts, but pregnancies do occur. Which day favors the majority of blastocysts will vary among clinics, depending on their culture system and media used as well as on the progression potential of the embryos themselves. Unfortunately, you’ll have to wait and see how this turns out. Why do some embryos progress more slowly than others? MFI could help explain slow progression but that is only one possible factor. Almost every possible factor has been proposed to account for slow embryo development (egg factors, sperm factors, genetic problems, culture problems) but there is no way to look at the embryos and know what’s going on.
Because you are thinking of changing clinics before you even know whether you are pregnant or not, I am guessing that you have been dissatisfied with your program along the way. The pregnancy rate you quote is not terrible and not infrequently observed as patient volume goes up or as new staff/doctors are added. Part of what works well for patients is having an individualized treatment plan–this takes more care, time for patients and attention to detail. Some programs scale up and do this well, others struggle and their rates may drop. If you are pregnant, all these questions will be of no consequence. If you aren’t pregnant, then you can consider whether you can get better treatment elsewhere. A program can’t guarantee that you will get pregnant. But they should be able to guarantee that they will address all your concerns, answer all your questions, provide some well-considered treatment options for your consideration based on a careful review of your situation and help you decide what to do next. If you have options of going to a clinic with higher rates that do at least 200 cycles a year, by all means consider a change if you have other reasons to be dissatisfied with your current program.
In the meantime, please try to distract yourself with other things that you enjoy or are otherwise important to you -that may have gotten ignored lately or might have been on the back burner –to make this 2WW time go by as quickly as possible. Above all, Good Luck!!
November 16th, 2012 at 4:51 pm
Hi! I found lots of information here so thank you for your website. I am a carrier and although this is the 4th time I have done this, only one other time was a 3 day transfer so I forget some things. We had 13 retrieved with 11 fertilizing and all progressing to the 3rd day. On day 3 we had six 8-cell compacting embryos and the rest of various sizes from 6-cell to 4-cell. We transferred (1) the best 8-cell compacting embryo that we had. I know that compacting is a very good sign but is there any more specific data about the success of a compacting day 3 embryo? Donor is 35 and there are no fertility issues.
Thanks for your help!
November 16th, 2012 at 8:16 pm
Hi JennyLou97,
I don’t have any specific data on the success of transferring one day 3 compacting 8 cell from a donor- but you should be in really good shape. (Your clinic may track their patient data to look at their success rates with transferring one embryo so I would pose this question to them. Also, data from their clinic would be most applicable to your embryos. The CDC data isn’t parsed that finely. You have good progressing embryos from a donor. So I would feel optimistic at this point. Good Luck!! Carole
November 18th, 2012 at 2:09 pm
Hi Carole,
Thank you for all of the information you provide on this blog. I just had one 4AA blastocyst transferred on day 5. The blastocyst was actually in the process of collapsing when the embryologist took a picture of it for us. How common is this? From your description it sounds like it happens frequently, but after reading the info on the Payne study I became a little concerned (less about the possibility of twins and more that it could indicate a problem). Have there been other studies to date that expand her findings? Thank you for any information!
November 19th, 2012 at 4:23 pm
Hi Colleen,
Blastocyst collapse (and subsequent re-expansion) is very common and I would not be concerned about it. For vitrfication, the blastocyst is deliberately collapsed for better freezing. I am not sure which article by Payne you are referring too, but embryos collapse and re-expand without any obviosu effect on embryo viability. Good Luck on your transfer! Carole
November 27th, 2012 at 2:36 pm
Hello Carole,
I wrote to you about a month ago asking about athe chance of a slow growing embryo. I would just like to update and confirm I achieved a pregnancy with a slow growing 6 cell and a 5 cell day 3 embryos and yesterdays scan confirmed I was 8 weeks pregnant with a singleton.
The reason for my update is to just give hope to those people that don’t have perfect embryos. I hope my story helps someone.
I would also like to thank you as you provided quick proffesional advice which gave me alot of confort and reassurance when I needed it most!
November 27th, 2012 at 3:42 pm
Hello Sara,
Good Luck and Best Wishes! Carole
Congratulations on your pregnancy! I am very happy for you and glad that I could help in a small way.
March 24th, 2013 at 12:53 am
test
March 26th, 2013 at 9:05 pm
Is this still active?
March 27th, 2013 at 7:25 am
Yes, I have not closed any of the comment boxes. You can ask questions here or email me privately at info. Best Wishes, Carole
March 27th, 2013 at 2:16 pm
I emailed you! Thank you!!
March 27th, 2013 at 2:18 pm
You are very welcome. Good Luck!!
March 29th, 2013 at 4:35 pm
Hi,
I’ve had two failed FETs of 5 day blasts..both rated high quality by my clinic. Both times, the embryo was reported to be “collapsed”. Both times, the RE informed me this was nothing to worry about –that everything was fine and there was no reason to think the embryo wouldn’t stick. Both times it didn’t. Then I met with my RE who said that likley the fact they they were collapsed embryos is implicated in why i didn’t get pregnant. She’s proposing to now thaw 2 and transfer the least collapsed one and discard the other. I don’t like this plan–because if indeed the other two REs were correct and a collapsed embryo has the same chances as non-collapsed embryos–then I’m just tossing good chances away. Am I right? Is there a implantation issue with collapsed embryos? They were collapsed for freezing–and both looked to be partially reexpanded prior to transfer. I have photos of each if this helps your comment..
thanks–just looking for info as I make my next decisions..
March 29th, 2013 at 5:59 pm
Hi Cindy,
I am sorry you are having a hard time. I don’t think that being collapsed at thaw is a problem, especially if you have evidence that the blasts were in the process of re-expansion before transfer. The fact that they were re-expanding is good evidence that they survived the thaw and were alive. If you just want to transfer one, I would thaw one and wait a few hours to see what it does before transfer. If it doesn’t look viable–ie doesn’t begin to expand at all, a second can be thawed. Even if the embryo is alive, it does not guarantee implantation. Both the embryo and the uterus have a lot of collaborative work to do to make a healthy placenta and pregnancy. Also the embryo needs to have a normal chromosome number or it usually doesn’t continue to a term pregnancy, if it is able to implant at all. So it is very hard to determine why the last two transfers didn’t work-could be many reasons. If blasts do not re-expand ever, it is probably because they are no longer alive- and did not survive thaw. If yours were re-expanding, they were alive. Good Luck!
March 29th, 2013 at 8:24 pm
Thank you so much for responding so quickly.
It matters so much to know I wasn’t fed a line by the REs who told me it was fine to proceed with collapsed embryos. It also helps me plan my next steps–particularly if future embryos are just slow expanders.. I don’t want to throw embryos away just because one doc seems to think they have a poorer chance. So thank you!
April 1st, 2013 at 4:27 pm
My wife and i just did a 5 day transfer, on day 3 we had 2 8′s, 3,6s and a 5. they called the morning of day 5 and said the trasfer was on, we were very excited, but when we got there, we found out that the 8′s had only turned into one 10 and one 11, thoses are the ones the implanted.by the pictures they gave me they looked like they where about to turn morula. Our R.E. said we still had a chance of pregnancy of about 30%, whats you option on this, we are very depressed.
April 1st, 2013 at 4:57 pm
Hi Dave,
I am sorry that you are disappointed. Yes, we like to see embryo progress to morula on day 4 and blastocyst on day 5. The embryos you describe are a little behind. Having said that, it is too soon to be without hope. Embryos do surprise us, all the time. I am wishing you much good luck for good news! If this cycle does not work, there will be a follow-up appointment. You will want to find out what your doctor can propose doing differently next time. Best Wishes for a good outcome!!! Carole
April 3rd, 2013 at 9:28 am
I just had a 3 day transfer yesterday of a 5 cell embryo that “looked great” according to the RE and embryologist, but just a “bit behind”. Out of 4 eggs retrieved, 3 mature, this is the only one that fertilized and we did ICSIthis time. This is our 2nd ivf and our first one was same antagonist protocol with slightly lower dose of meds and we got 6 eggs and 4 fertilized properly without icsi. That was in June and 3 made it to day 5 ans they transferred a morula and early blast and it was a bfn. In September we tried a MDL protocol and my body didn’t respond at all so my re had me take dhea for 4-5 months to see if it would be helpful to get more eggs. I am 35 now and have severe endometriosis with an endometrioma so large on 1 ovary that she can’t get any eggs from that side. I’m worried that, a 5 cell on day 3 transfer just won’t work and also I’m confused as to why fertilization seemed better without icsi and why we got less eggs after taking dhea. My amh went from 1.6 a year ago to .33 last month after taking dhea. My fsh stayed basically the same though. I really appreciate your insight!
April 3rd, 2013 at 9:46 am
Hi Nat,
I am so sorry you are having such a hard time. IVF isn’t working very well for you. You have a complex history and several hurdles to overcome. As an embryologist, I can say that the 5 cell on day 5 is significantly lagging, and although nothing is absolute, the chance of pregnancy is low for an embryo that is lagging to such an extent than for one that is on target. The AMH decline is most troubling but I can’t advise about the endocrinology since that is outside of my expertise. The accumulation of hurdles over time (endometriosis, only one available ovary to retrieve eggs from, and rapidly declining AMH.) even in a young woman are significant issues and can well explain the poor outcomes– like lower fertilization the second time even if you did ICSI. I would, of course, follow up with your own doctor to explain what, if anything, might be done differently in another try if this one doesn’t work. If you can find another RE with good SART statistics (greater than 50% take home baby rate in the under 35 age group), you might benefit from a second opinion and another perspective on whether it is worth it to continue down this road or whether it is time to consider other options- donor eggs, surrogacy or embryo “adoption”. I wish I could offer more help!! Wishing you Much Good Luck!!! Carole
April 3rd, 2013 at 10:42 am
Carole,
Thank you for your response! My 5 cell embryo was actually on a 3 day tranfer, does that mean it is not so significantly lagging? Thank you for your response. I really appreciate you taking the time!
Nat
April 3rd, 2013 at 11:27 am
Carole,
Thank you for your response! My 5 cell embryo was actually on a 3 day tranfer, does that mean it is not so significantly lagging? Thank you for your response. I really appreciate you taking the time!
Nat
April 3rd, 2013 at 11:44 am
Nat,
Thanks for your clarification. 5 cell on day 3 is a better picture, still not ideal (8 cell is what we like to see) but better. If it was observed early and on the verge of dividing, it could be a 6 cell by transfer. Good Luck!!! Carole
April 12th, 2013 at 8:30 pm
Hello and thank you in advance,
We started with 11 fertilized eggs, on day 5 we had 4 morulas and we transferred two, we got a call a few days later saying that the other two made it blast on day 7. Is this a cause for concern or does it just mean we have some VERU slow growers?
We are both in our late twenties, here is a photo of the two we put in :
http://m743.photobucket.com/albumview/albums/tysonito/morula.jpg.html?o=0&newest=1
April 13th, 2013 at 9:05 am
Hi Tyson,
Having a morula on day 5 is somewhat slow. We prefer to see blastocysts on day 5. Likewise, seeing a blastocyst stage only on day 7 is quite delayed. There are some studies that show pregnancy rate is best with day 5 blasts, somewhat reduced with day 6 blasts and pretty rare with day 7. In my experience, most labs don’t freeze day 7 blasts. The good news is that you are very young and youth is such a positive factor it overcomes other issues- so you and your partner might well get pregnant. So don’t give up on this cycle!!!
Having said that, I would have expected better embryo progression and better compaction in embryos from most young patients- unless there are other complicating medical issues. Have you checked the live birth rates reported to the CDC for your clinic? You can look these up on the CDC site or on the SART site which is slightly more user-friendly http://www.sart.org/find_frm.html If you don’t get pregnant for this cycle, it might be time to get a second opinion. I always suggest that patients look for clinics that report at least a 50% live birth rate in the under 35 age group patient. Another issue that can contribute to less than ideal embryo progression is if the lab just recently started growing embryos to blast or made other changes in lab personnel or protocol. There may be lab problems but those are impossible to diagnose from the outside. If you discover a really low pregnancy rate or inexperience with blastocyst culture, it might be time to look for a more successful clinic.
In any case, I wish you Much Good Luck for a positive pregnancy test and birth from this transfer!!!
Carole
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