IVF Disasters: No Fertilization
June 30, 2010Carole 43 Comments »Hopefully, this never happens to you, but sometimes after adding sperm to egg or injecting sperm into egg, the next morning, we have nothing good to report. Sometimes, we see the sperm swimming around the egg, with no signs of attachment to the egg. Sometimes, sperm attach all over the egg, but the egg looks unchanged. See my earlier post “Happy Zygote Day!” for pictures of eggs before and after fertilization.
Rescue ICSI. If eggs and several thousand sperm are put together in a drop- the co-culture method- then we have the option of performing “Rescue” ICSI if it looks as though sperm did not enter the egg. It’s a tricky call to make because sometimes the sperm will be inside the egg but we can’t see it. If we inject yet another sperm into the egg, we have injected additional chromosomes and produced an abnormality.
Intracytoplasmic sperm injection or "ICSI"
Criteria for using rescue ICSI. Usually we would do rescue ICSI if zero eggs fertilized. If some were successfully fertilized, we can’t assume that sperm entry was the problem and so we may already have a sperm in those eggs that don’t “look” fertilized. Secondly, we like to see that the egg has only a single polar body, suggesting that it is mature but unfertilized. These two criteria give us some confidence that no sperm are already in the eggs we plan to inject. Rescue ICSI does produce pregnancies but typically is less successful compared to ICSI performed on a fresh egg. Research studies have demonstrated that the earlier the rescue ICSI is performed, the better the outcome, because the egg is “fresher”.
Fertilization Failure Post-ICSI. If none of the eggs fertilized after ICSI, there are few options. You can’t inject another sperm because sperm entry wasn’t the problem if you did the ICSI correctly. Assuming there are not technical issues, a number of problems can explain fertilization failure after ICSI.
- The egg didn’t survive the injection process. Eggs may not survive if the eggs are relatively immature or post-mature due to membrane changes that happen with maturity. Stimulation was sub-optimal.
- The sperm head did not decondense after entering the egg, so the DNA remained locked in the sperm head.
- The egg was not activated and didn’t participate in the intracellular steps of fertilization. Failure of egg activation may the main reason according to a study that performed a microscopic evaluation of the sperm head and cellular structures after injection.
- A small number of eggs were available for injection. For example, the stimulation was poor and only three eggs were retrieved or patients limit the number of eggs injected to three or less for religious reasons. Statistically speaking, you were simply unlucky that the three (or fewer) eggs that were injected did not fertilize.
Experiencing complete fertilization failure after ICSI, while emotionally devastating, does not mean that a future IVF cycle won’t succeed. In a study of 21 patients who had complete ICSI failure, half of them went on to try another cycle and had a 45 percent clinical pregnancy rate per transfer. The point is that often times a poor stimulation can be corrected in a subsequent cycle and make a difference. If sperm were barely motile or immotile at the time of injection, a better sample or donor sample may result in fertilization in a future cycle.
Split ICSI cases. If there are concerns in advance that ICSI may be necessary, but it’s a borderline case, it is possible to use ICSI on half the eggs and conventional co-culture on the other half, to ensure that sperm entry won’t be an issue in half the eggs.
Chemical Activation. It is possible to activate the egg artificially by introducing a calcium ionophore or other chemical agent into the egg with or after injecting the sperm into the egg. This is currently a research application and there are relatively few clinical case studies reported in the literature. This study described chemical activation for a couple with repeated total fertilization failures after ICSI. There is no safety data or longterm outcome data to show that chemical activation is safe. Chemical activation may be validated for clinical use in the future, but currently, it is not considered part of routine clinical care.
Restricting the number of eggs that are fertilized. We have honored patients requests to only inject or inseminate three eggs to avoid the problem of having excess embryos in the freezer. I understand that this is a valid ethical/religious concern for many patients, but it effectively hobbles the full power of the in vitro fertilization technique. We can try to guess which three eggs look most likely to fertilize but we are only guessing. By allowing us to inject only three eggs and throwing away the rest, you have effectively reduced your odds of success with this technique. In the not too distant future, egg freezing may be a highly successful technique in every IVF lab so it won’t be a big deal to only inject three because we can freeze the rest for later. In the future, your previously thawed eggs may be just as fertilizable as the fresh eggs. We are getting close to that dream and some labs report that they are already freezing eggs with great success. But we aren’t there yet in every lab. So technically speaking, it is best to let the lab attempt to fertilize every mature egg to optimize your chances of pregnancy in the fresh cycle. Of course, it is your choice but you should understand the technical risks of this choice.
© 2010, Carole. All rights reserved.
July 18th, 2010 at 5:54 pm
My daughter just had a failed ivf and they performed a rescue ICSI today. They apparently have healthy eggs and active (motile?) sperm and the Dr. did not forsee this. My daughter reported that the Dr. told her the sperm “did not even try” to fertilize the egg, which I am assuming to mean that something is wrong chemically or something. Any advice on what kinds of questions/issues to consider?
July 25th, 2010 at 6:24 pm
Great site. A lot of useful information here. I’m sending it to some friends!
August 1st, 2010 at 1:25 am
We just completed an ivf cycle and had no fertilization..It is very devastating..and the most annoying part is that nobody is able to give a clear answer why. We had 4 mature eggs..I am now looking into finding a really good ivf center with an excellent lab. We have male factor infertility..I would appreciate any suggestions, links, insights..
August 1st, 2010 at 8:21 am
I am so very sorry that you are having such a difficult time! No fertilization is a very devastating and frustrating outcome. I would agree with you that it is important to find a doctor who reports both good pregnancy rates to the CDC and also can explain to your satisfaction the clinical plan he/she is proposing. Two archived posts explain how to use the SART and CDC sites to review ART practice pregnancy rates: Finding a good doctor part one (http://fertilitylabinsider.com/2010/05/finding-a-good-fertility-doctor-part-one/) and part two (http://fertilitylabinsider.com/2010/05/using-cdc-reports-to-find-a-good-fertility-doctor-part-two/). I am not a physician and so can not give you medical advice on your case, just background information so you can have a better discussion with your physician. Questions that you might ask your doctor include: Do you think a different stimulation protocol could give me more mature eggs to work with? In your experience, would you recommend ICSI in our case?(ICSI is often the best tool if the primary issue is male factor and you have had no fertilization with “traditional” IVF.) What fertilization rate could we expect with ICSI for patients like us? What percentage of your patients get ICSI?( Many programs do a lot of ICSI these days, 50% or more of cases is not unusual. If techs are just starting to use ICSI, there is a steep learning curve and some tech training programs are more patient friendly than others.) You might also ask: What is your pregnancy rate for women of my age? The under-35 age rate is most often quoted by practices so sometimes you need to ask specifically about your age group if you are older. Advanced maternal age is a major cause of infertility. We become less fertile with age regardless of how healthy we are otherwise, and unfortunately, ART can’t reverse these effects. If you are over 40, donor eggs may be needed. I hope this helps and I wish you the very best and shortest path to parenthood.
August 1st, 2010 at 3:06 pm
Thanks much Carole! This is very helpful. This last IVF was done based on ICSI. I am 34 years old. The egg number is low for my age. There is no genetic defects both on my end and my husband..We have severe male factor infertility but this time we had pretty good sperm counts as my husband had a varicocele surgery 4 months ago..Doctor says that this is very unusual.., but nothing else..I would expect a doctor say more than just that…Thanks much for all your help! Your website is very useful.
February 7th, 2011 at 12:38 am
*“ that seems to be a great topic, i really love it :`*
April 15th, 2011 at 7:44 am
I’m unfortunately going through the same experience and yes it’s really devastating emotionally and physically speaking.
I’m 38, we are one of these couples with unexplained infertility.
We had one IVF which resulted in no fertilised eggs (10 supposedly good eggs), they were never able to detect the cause. The second time we tried with ICSI again no fertilisation!
I’m not sure they have checked for genetic issues, but I wonder if I should move to another centre.
Any tips would help. Thanks!
Cat
April 29th, 2011 at 11:39 am
Hi,
Just to follow up on my previous post…I met met gyn last week and I unfortunately it was a rather unsatisfactory meeting.
She was not able to tell me the reason for the lack of fertilisation of the eggs during the ICSI; she suspects the eggs not to be good enough as apparently they could only do the ICSI on 4 of the 7 eggs.
However she was not able to tell me what tests the lab did and where the problem was. She said she would call to tell me more, but nothing has happened so far. I’m inclined at this point to consult another clinic. I know doctors do not have a crystal ball, but they should be able to establish a trust link and I don’t feel this is the case for me. Good luck to the others!
Cat
June 25th, 2011 at 6:51 am
Cool!!! I do agree with you
March 29th, 2012 at 6:08 pm
I have a question regarding egg membranes. On some of our lab reports we have seen than the eggs had very thick membranes only to see (with a next cycle) that we had very thin membranes.
What is the reason for this? Does it make a difference and does it indicate anything regarding egg quality?
Can it be changed?
March 29th, 2012 at 6:26 pm
Dear Miela,
I have no idea on this. By membranes, could they be referring to the zona pellucida? That can be thicker or thinner depending on the maturation process of the egg. If the zona is abnormally thick, assisted hatching may be beneficial to open/weaken an area in the zona to make it easier for the embryo to escape the zona or “hatch” which is necessary before implantation. Carole
May 9th, 2012 at 5:12 am
We are about to undergo chemical activation and the information is limited due to the rarity of the situation but if it applies to the couple then it’s use increases fertilisation rates to 75% and pregnancy rates 33%.
They verify if it is required by attempting fertilisation with mouse eggs (MOAT) so donor eggs are not required. This is inexpensive and I’d suggest anyone to have it done before wasting money on another ICSI cycle.
My clinic have had 37 pregnancies and all the children fall within the normal parameters for growth and development.
There is a clinic in AUS, a clinic in US and a clinic in EU that offer it that I know of, so it is available to anyone who needs it.
May 10th, 2012 at 8:22 am
I appreciate your enthusiasm for chemical activation as a treatment for failure of the normal calcium signalling pathways that are activated at fertilization. As you say there are only a handful of clinics that offer this EXPERIMENTAL clinical option. If you have this done, you are participating in human research and should be enrolled in a IRB approved human subjects research clinical trial. if your program offers this without having a clinical trial, that means they did not try to get their medical plan approved by an institutional review board (IRB) that protects patients OR they tried and could not get it approved. Both of these possibilities should give you pause. Here’s a link to a list of recognized clinical trials for IVF http://clinicaltrials.gov/ct2/results?term=ivf There is no trial on chemical activation- although many other trials exist for much more benign interventions. One of the many reasons I feel cautious about this approach is because chemical activation is taking a sledgehammer to activate pathways in the egg-not the highly specific sperm initiated pathway that occurs naturally– and we don’t have any idea what other pathways are being activated in the egg. And since long term studies are not being done for long term effects on kids, these kids arising from these early births are guinea pigs. It may be proven as a safe clinical technique in the future, but right now all we have is anecdotal successes claimed by clinics who haven’t created IRB approved clinical trials to test their theories. Be careful about “new” techniques that only a few programs offer. There is a reason not everyone in the field is jumping on this particular band wagon at this time.
May 16th, 2012 at 9:45 am
They have been using the procedure for several years where i am going and they have had no abnormal children produced. It is all properly regulated.
Your opinion on the technique is very sensational and contradicts what i have been told by the researchers and consultants that have actually been personally been involved in it’s development.
I don’t believe you know anything about it.
The reason it isn’t widely available is because the condition is so rare and donor sperm is often insisted upon by this point.
They can confirm if it is the sperm causing the lack of fertilisation, which protein is missing, which chemical is missing and be very deliberate in what they contribute to the fertilisation process. They do not add anything that would not be there, if for the sperm having the required protein.
May 16th, 2012 at 11:22 am
Dear Anonymous,
I understand your need to believe in this procedure, but belief alone will not keep you or your children safe. If this technique has been scientifically established to be effective and safe, you should be able to provide the references for at least one peer-reviewed published paper in a reputable scientific journal that backs up the clinical validity and claims of safety using this approach in human IVF patients. You should also be able to provide the name of the study, the sponsors of the study, and the IRB protocol number of the human research clinical trial which demonstrated the effectiveness of this approach and it’s safety for patients. Finally, at the very least, the clinical scientists should not be so shy about revealing their names and both their academic and commercial affiliations. Patients enrolled in approved clinical trials are provided with all this information. If they can do none of these things and you must remain anonymous as well, I would be very cautious in proceeding. In the absence of any of this information, you would appear to be the guinea pig for their research. Good Luck!!
November 10th, 2012 at 11:16 am
The worst thing that happened to me was that despite 15 eggs not being fertilised the clinic did not try a rescue ICSI!
They even told me they had a look at the sample 48 hours after and there was still no signs of fertilisation!
I believe they missed the call in my case…
November 10th, 2012 at 3:48 pm
Hi Hpe4bb,
I am sorry that you are having such a hard time. Not all clinics offer rescue ICSI. There are several reasons why it might not have been offered to you. One reason can be that it is difficult to have do an unplanned ICSI in the beginning of the day if they don’t have enough technical staff. Most programs staff for the minimum, not the maximum work load, for scheduled procedures, not unscheduled surprise ICSI failures. The other reason not every program offers this is because they might have tried it and been disappointed at the relatively poor success rate — which is much lower than what one can see with fresh eggs and fresh sperm. The third reason it might not have been offered is that it is difficult to apply rescue ICSI in every case if we have uncertainty regarding sperm penetration. We often see signs that sperm have entered at least some of the eggs. The best candidates for rescue ICSI are those eggs in which sperm attachment failed completely and free sperm are just swimming around, with no signs of attachment. We can be pretty sure no sperm entered the egg. On the other hand, if we see attachment and some eggs did have fertilization, it is hard to tell which eggs might already have sperm inside –you don’t want to inject yet another sperm and cause an abnormality–so rescue ICSI is not done. It does not help you now but if you do have the option of another cycle–you will know that the clinic should probably plan to do ICSI on the fresh eggs and not even try regular IVF. Hopefully, you can discuss these issues with your doctor at the follow-up appointment. Good Luck!!
November 19th, 2012 at 1:44 pm
My wife and I are using donor egg due to a chromosomal issue. In our first cycle only 1 out of 6 fertilized using ICSI. Dr. said he assumed its a sperm issue, since with donor egg you assume the eggs are good. We have done every type of sperm test as well and they are all normal. Also, we had gotten pregnant naturally several times (non successful) prior to learning of my wife’s chromosomal issue. So we are not sure how it could be a sperm issue?
November 19th, 2012 at 4:36 pm
Dear Anonymous,
I a sorry you are having such a difficult time. There are many reasons for fertilization failure. You should ask additional questions of your physician since he has a hypothesis that it is a sperm issue- are there other tests that he can recommend? Why has he ruled out the egg donor? The other thing to remember is that there are molecular issues with sperm or eggs (missing receptors for example) or internal signalling molecule problems that can interfere with normal fertilization. These molecular problems would not be revealed through a semen analysis or any routine testing of egg donors. I would go back to your doctor for more analysis/exploration of why this may have happened and see if he would recommend other sperm tests (eg, sperm integrity testing) if he thinks the sperm is the issue. If you have produced a pregnancy before–recently within the last year– I understand why it seems that the sperm should be okay. It is hard to rule out the egg donor unless the donor has a recent record of offspring from donated eggs. Sometimes an egg donor looks like she should have good eggs based on her youth and medical history, but then the actual first cycle is poor and she is dropped from the donor lists. The only real “test” of eggs and sperm is whether they can create healthy embryos that implant. Unfortunately, we haven’t yet come up with good diagnostic tests that can really test sperm or eggs in advance of use. Good Luck! Carole
March 6th, 2013 at 8:06 am
This is a fabulous site. Thank you Carole. We had a rescue ICSI performed during our first IVF cycle in January after 18 eggs failed to fertilize. 4 eggs did successfully fertilize after the rescue, but all were slow to grow. All 4 were transferred, but I did not get pregnant. We were given 10% odds of getting pregnant after the lab discovered the need to do rescue ICSI. I share this for the poster who didn’t even have the chance at rescue ICSI. We are preparing for cycle #2 and ICSI will be performed much earlier. The previous post about poor diagnostic tools tells me not to spend much time on the “why” but to focus on overcoming the problem. Is there anything besides IVF with ICSI that couples can do when their eggs & sperm don’t react?
March 6th, 2013 at 9:43 am
Hi Rae,
I am sorry you are having a hard time. I am optimistic that ICSI on the same day as retrieval will be likely to improve your outcomes. Rescue ICSI is an uphill battle for good outcomes because the eggs have a relatively short “shelf-life” after ovulation. ICSI within a couple of hours of retrieval is best. There are some studies that suggest that adding chemical agents ( eg. calcium ionophores) to force egg activation at the time of ICSI may be useful for some patients, particularly if they are using immature testicular or epididymal sperm but even then, eggs from younger women do better (link to abstract here http://www.ncbi.nlm.nih.gov/pubmed/19146768). Personally, I’d rather not introduce any chemical agents which can act to turn on multiple signaling pathways. What the sperm does to an egg to activate it is like picking a lock. In contrast, what a calcium ionophore does is like breaking down the door. I am concerned about unintended side effects with the use of activation agents. So the plan you are on seems like a promising one to me. Good Luck!! Carole
March 11th, 2013 at 7:43 pm
We have had 5 unsuccessful IVFs with no or very low fertilization rates. We both seem to be healthy, they even checked our chromosomes and did not find any problem. First, we had 10 mature eggs with no ICSI which resulted no fertilization. 2nd IVF, we had 10 mature eggs 2 fertilized with ICSI and resulted clinical pregnancy, 3rd IVF 6 mature eggs and 2 fertilized with ICSI but resulted no pregnancy, 4th IVF 9 mature eggs and no fertilization. We than changed clinic and we had 3 mature eggs, ICSI and calcium ionophore but had no fertilization again. We are devasted and hopeless. They really can’t find any answer for our infertility. Any hope???
March 12th, 2013 at 8:30 am
Hi Monique,
I am sorry that you are having such a hard time. There is always hope. It may be time to redefine how you think of family building, however. Given that you tried ICSI and even a calcium ionophore activation treatment and two different labs without success, I think that it is probably unlikely that IVF using your own gametes will be successful. It is not obvious whether the egg or the sperm or both are causing the problem. If it is the egg, the only thing still possible to do with your egg are experimental clinical trials that inject mitochondria from your egg stem cells with the sperm during ICSI.http://www.ovascience.com/technology/ I think these experimental treatments are also a long shot. Talk to your doctor about all your options but you may have exhausted the standard protocols. It may be time to let go of the genetic link for your family building. With either donor sperm, donor egg or both, you are much more likely to achieve pregnancy. This is a very personal decision and there is no right or wrong answer regarding whether third party reproduction is acceptable to you, but your situation is not hopeless. It may just be time to pause and reflect on your family building path and consider whether you are open to other options. Good Luck!!! Carole
March 26th, 2013 at 4:58 pm
Hi,
My wife and I have today been told that out of the 8 eggs collected yesterday, only 5 were suitable for ICSI and that 3 had abnormal cell division and the other 2 did not fertilize.
Our first cycle last year we got 2 eggs of which one fertilized to a Grade 1 Embryo. This suggests that we do not have a compatability issue.Unfortunately after inplant the embryo did not take.
2nd Cycle yesterday used frozen sperm as i have an obstruction.I think the clinic slipped up in only thawing sperm after egg collection.If they had thawed out earlier they would have seen that the sperm was not of great quality.The sperm was taken last year and my lifestyle is much healthier now.When the embriologyst called my wife today she said that they struggled to find sperm that was good enough.Should they not have defrosted prior to collection and then they could have retrieved fresh sperm once they realised that is was poor quality?
Absolutely Gutted.
March 26th, 2013 at 5:16 pm
Hi Ryan,
I am so sorry that you are having such a hard time. I expect that policies between IVF labs vary regarding when to thaw the sperm. It would depend in part if it was even possible for the man to produce a fresh ejaculate. Regarding my own lab experience, if fresh collection was possible, that was our #1 option, and we didn’t even bother with the frozen sample. If we had to rely on frozen sperm because a fresh ejaculate was not possible, we would wait until we had at least one egg retrieved so that we wouldn’t thaw and then waste the precious sperm sample if we had no eggs. Completely obstructed patients can’t produce an ejaculate containing sperm so surgical recovery (MESA or TESE) is needed. Surgical recovery is planned for well in advance of the egg retrieval because it requires scheduling of two doctors, two surgical suites etc. so usually can’t get fresh sperm surgically on the day of retrieval unless this is set up in advance. Most, if not all clinics, ask you to make a follow-up appointment if there was no pregnancy result to discuss next steps. if this isn’t offered to you, I would ask for an appointment anyway or at least a phone call so that you can ask the physician or lab director what the policy was and why no one asked you to produce a fresh ejaculate when it was clear that the frozen sample was problematic. I would be diplomatic but you owe it to yourself to have this discussion with your doctor. If you stay with this clinic or move on to another, you should make it clear that you are perfectly willing to provide a fresh sample if needed on the day of collection. Wishing you much Good Luck going forward. Carole
March 27th, 2013 at 3:32 am
Thanks for your reply Carol.
On our first cycle last year the clinic advised me not to eat or drink anything incase they needed to operate for fresh sperm as the only way is via SSR. The obstruction is complete (looking into having this repaired). They defrosted the sperm which was ok i believe as they had one of two fertilize. This time round they didn’t ask me not to eat or drink but i went off my own initiative and made sure that if they required to do an SSR they could. The first nurse seemed to be unsure whether I was producing a sample or not (impossible) or using a frozen straw. If they had allowed for SSR last year on cycle 1 then they should have also allowed for it on cycle 2. I am really disapointed with this. I suppose i will have to take it up with the doctor (diplomaticly).
Thanks.
April 3rd, 2013 at 10:15 pm
Hi Carole,
This is a great site. Thanks for sharing your knowledge. I have done 5 IUIs and just had an unsuccessful IVF. They retrieved 9 mature eggs, none of which fertilized.. Less than 24 hours later we did a rescue ICSI. 7 of the 9 fertilized! We had one 7 and two 6 grade be decided to implant all 7.. Given my age (41) we knew that only 3 had the best chances, and because the others weren’t good enough to freeze we went for broke (and this was the only time I will do IVF).
Unfortunately it didn’t result in a pregnancy, but this has given us a bit more insight on the problem. My husband has very strong sperm so ICSI really wasn’t a consideration from the beginning, but this has given a better indication of the issue.. Maybe the egg was too hard or lacked receptors? We really don’t know.
I also understand that rescue doesn’t generally have high pregnancy rate?
Your thoughts are appreciated.
Rachel
April 3rd, 2013 at 11:40 pm
Hi Rachel,
I am so sorry that your IVF was unsuccessful. Rescue ICSI typically has a lower success rate than early post-retrieval ICSI because the egg has a “short shelf life” and then becomes less able to be fertilized. Fertilization rates are lower with rescue ICSI and so fewer embryos are produced and so the pregnancy rate is lower. Unfortunately, we often discover that the egg or sperm have a fertilization problem (possibly receptors, possibly genetic issues -aneuploidy erc) when there is an actual fertilization failure- which is of little consolation. The CDC reported pregnancy rates for women aged 41 are quite low so deciding to do only one IVF is quite reasonable. Other options such as donor egg, embryo “adoption”or even child adoption may offer other pathways to parenthood. I wish you Much Good Luck in whatever path you choose!!! Carole
April 7th, 2013 at 3:07 pm
Hi,
devestated does not even cut how we both feel. They said not only was there no fertilisation, but the sperm did not even go anywhere near the eggs, and they said that it is doubtful that icsi will even work.
Myself and my husband just got news yesterday that there was no fertilisation with our eggs
Is there no reason at all for why both do not have any interaction? I’ve been left with the opinion that we are simply not compatible. I’m only 26 and my husband is 30, and we are both healthy And my eggs are healthy and his sperm is great! I’m so confused and need answers
April 7th, 2013 at 3:29 pm
Dear Michelle,
I am sorry you are having such a difficult time. When sperm can’t attach is exactly why ICSI is useful so I would double check with your doctor or get a second opinion. Something doesn’t make sense here. Good Luck!!! Carole
April 21st, 2013 at 1:24 pm
Hello Carole.
My husband and I are devastated! We were just informed this morning that none of our 6 ICSI eggs fertilized.
I was in a Follistim 300u/ Menopur 150u for 12 days. My response was slow at the begining we thing due to over suppresion with birth control pills (2 months). The highest my estradiol got was 1516 on day 12. We triggered with HCG and the were able to retrieve 10 eggs of which 3 appeared matured. 4 “almost ready” and the rest immature! They choose the 3 matured plus 3 of the almost matured for a total of 6 that were fertilized with ICSI but only 2 showed signs of dividing cells 16 hours later. Today we were told that none of the eggs, none even the 2 that were showing signs fertilized!
We are trying to figure out if I was under stimulated? Can you offer any help?
Our History= me= fibroids and polyps and corresponding surgeries to correct them. Husband=excellent quantity, poor morphology. Was on male fertilization supplements.
Thanks.
April 22nd, 2013 at 9:16 am
Hi Alexa,
I am so sorry that you are having such a difficult time. Although I can’t really speak to the issue of ovarian stimulation protocols because I am not a doctor, you definitely should ask your doctor what they might do differently next time. There are many possible reasons for a poor stimulation and many alternative stimulation protocols they can try. The support group Resolve has an explanation of some of these options here http://www.resolve.org/diagnosis-management/infertility-diagnosis/poor-responder.html
Here is another paper which describes various approaches in more detail. You might print this out and take this with you to your doctor’s office for your follow-up appointment http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3455002/ Don’t be afraid to keep asking questions until you understand the options you have going forward. If you are not satisfied, you can always seek another opinion. Also, look up your doctor’s IVF outcome stats through SART.org –here’s the link http://www.sart.org/find_frm.html to see how they compare with national stats for women in your age group . Here’s the link for the National Summary through SART. https://www.sartcorsonline.com/rptCSR_PublicMultYear.aspx?ClinicPKID=0 Unless you are in the middle of nowhere with few options, choose a clinic which has stats at least as good as, if not better than, the national average.
Good Luck!!! Carole
May 6th, 2013 at 1:48 pm
Hey all.
Me and my wife had done 2 IVF treatment, first the short method and then long method. The second time the egg had very high quality but the egg did not fertilized. the doctor took out 11 big fine eggs, The doc says that he don’t know what they will do, they will have some extra ordinary meeting to speak about the problem.
we are using donator sperm because I have problem with my sperm.
what is the next step? does anybody know why the egg does not fertilize? we feel that we are on the bottom of the bottle and we don’t know what to do next.
May 7th, 2013 at 6:25 pm
Hi
May 7th, 2013 at 10:28 pm
Hi carol-
Question for you. I read one of your articles about the “window” that needs to be looked through time wise in order to see signs of fertilization, like the two pronuclei. I believe you said this window was 4 hours long or so. How many hours past fertilization does this window come to life?So if for some reason the embryologist does not look during this special window the egg may look as if it has no signs of fertilization because the pronuclei disappear? I had 7 eggs with 5 mature (pretty normal for me, actually identical to 2 past cycles). 5 ICSIed. Today at day one my report was (2) 2PN so good and confirmed, one 3 PN so abnormal and will be discarded and then 2 “NEFs” she called them, which she explained they just could not tell if they were fertilized yet. IE no pronuclei were seen and there was no other signs of fertilization. In your opinion what usually happens to these NEFs after day 1 check? I have no idea if this lab has their stuff together and checked at the exact right time or maybe these 2 are just on their own timeline and were late or early changing the “window”. So if fertilization did actually occur and they just missed the signs, how long after fertilization should you see actually cell division. I want to press them to look again once we would see something happening if it was actually fertilized and they missed it. I mean its half my crop so I just need to know before day 3!! Thanks in advance!
May 8th, 2013 at 8:20 am
Hi Shawna,
To take your questions one at a time.
How many hours past fertilization does this window come to life? 16 to 20 hours after fertilization occurs is when we expect to see signs of fertilization- specifically the presence of two pronuclei structures within the egg.
So if for some reason the embryologist does not look during this special window the egg may look as if it has no signs of fertilization because the pronuclei disappear? Yes, the PN stay visible for only a few hours, then the membranes dissolve and the genomes fuse to make one unique individual. If we miss this window, we can’t tell if the egg is fertilized normally. It may continue to divide for a short period of time even if abnormally fertilized with 0PN or 3PN or multi-PN but eventually it fails. If the 3PN arrises because more than one sperm gets in (polyspermy), the embryo actually can be the origin of a placental cancer if transferred so in a few cases, these abnormal embryos can persist long enough to cause serious trouble. Without seeing the 2PN stage, we would have to do genetic testing on the embryos cells to determine if it was normally fertilized.
If no pronuclei were seen and there was no other signs of fertilization. In your opinion what usually happens to these NEFs after day 1 check? As described above, they may die off without dividing at all, they could divide a few rounds before dying or more rounds and give rise to a cancer.
So if fertilization did actually occur and they just missed the signs, how long after fertilization should you see actually cell division? we always see cell division, at least once, maybe twice by the next morning (another 24 hours).
Different programs handle the NEF (no evidence of fertilization) problem differently. The most conservative approach is to never transfer anything that couldn’t be confirmed as normal by visualization of the 2PN stage. But some programs allow transfers in some cases- for example if they reach blastocysts stage, but since normal looking embryos get transferred and can then fail or more rarely turn into cancer, reaching blastocysts stage is not proof of normality. In my program, we would separate the 3PNs from the normal embryos, grow them out to blast stage (they made lovely blasts) and then freeze for technical practice (eg. freezing technique, biopsy etc) – with patient consent. So the point is that just because they continue to develop for a while doesn’t mean they are normal.
You’ll should discuss these issues in more depth with your doctor before the transfer. Good Luck!! Carole
May 8th, 2013 at 12:55 pm
Carole- Thank you so kindly for your thorough reply. It was very helpful and you are doing a wonderful service here. I have kindly requested that these NEFs be reviewed today after 40 to 48 hrs post insemination to see if they have undergone any cell division at all. I don’t know if they will as your likely aware that most labs don’t look into things day 2.
But just one point of clarification so I can hang onto hope. The question and response below were copied from your reply…just wanted to add, there is a possibility that these NEFs did actually have 2 pronuclei that just disappeared before the “window check” and that they could become viable blastocycsts. Right? In your reply that option was not actually highlighted. It may be more unlikely but I have gotten feedback from a few IVF sisters that this exact thing happen to them and that CGH array showed their NEFs to be normal blasts at the end of the day. I will likely not invest in CGH this go around w/ so few embryos but a blast from a NEF seems to be an OK sign. It might simply be a timing thing with this lab as they seem very understaffed! Thanks again!
“If no pronuclei were seen and there was no other signs of fertilization. In your opinion what usually happens to these NEFs after day 1 check?
As described above, they may die off without dividing at all, they could divide a few rounds before dying or more rounds and give rise to a cancer.”
May 8th, 2013 at 1:11 pm
Carole- Thank you so kindly for your thorough reply. You are doing such a wonderful service here, calming the nerves of complete strangers and giving us hope. Its very helpful.
I have kindly asked that my NEFs be reviewed today 40 to 48 hours post insemination to see if there was any cell division. If not, that is that and Ill forget about those guys. As your likely well aware most labs don’t look at anything day 2 so I don’t know if they will accommodate my curiousity.
Just one point of clarification on the above reply. I copied a quote from your above reply and pasted it below. As far as a future for an NEF, it is possible (although maybe not likely) that an NEF in fact did have 2 nice pronuclei that were simply dissolved before “window check” and that these embryos will go on to make viable blastocycsts. Right? Also, yes, I realize that even abnormal embies can go to blast. You answer just did not highlight this possibility and Id like to hang onto some hope (and future reference). I have had some replies from other IVFers that this exact thing happen to them and CGH array went on to show their NEFs to be normal blasts. It could just be a timing thing with this lab as they seem very understaffed at this clinic. Good, sound and popular but understaffed. Thanks again!
“If no pronuclei were seen and there was no other signs of fertilization. In your opinion what usually happens to these NEFs after day 1 check?
As described above, they may die off without dividing at all, they could divide a few rounds before dying or more rounds and give rise to a cancer.”
May 8th, 2013 at 1:20 pm
Dear Shawna,
I am sorry that I did not make my answer clear. Yes, it is quite possible that normally fertilized eggs could be missed (NEF) and you would expect these to divide and continue normally. The problem is that there is no way to tell, short of genetic analysis, if they are normal or not if there is no evidence of 2PN fertilization. Hope this helps! Good Luck! Carole
May 14th, 2013 at 5:47 am
Sorry for the duplicate posts there….I just wanted to update you on these NEFs…. just for a data point. So my 2 NEFs did fertilize! I just read my lab notes and it was noted on my NEFs that they in fact did have 2 polar bodies at fert check…I only had 5 mature eggs so these 2 meant ALOT to me. In the end I had 4 of 5 fertilize which was my best effort yet. Im DOR.
So the NEFs became a 4 cell grade 2 and also a 9 cell grade 2 on day three. I was very pleased, at lease these were in the game. I also had a 6 cell grade 1 and another 9 cell grade 2. In the end I had some over all slow growers but it was my (2) 9 cells that went the distance. They were both at compacted morula stage early day 5 and early day 6 they hit 2bb which we transferred.
Can I ask you, is there evidence that a slower growing blast (like hitting blast on day 6 vs day 5) has less of a chance at pregnancy? I asked if my day 6 2bbs looked good and were still progressing and they said, yes as far as they could tell but there was no reason to continue culturing to find out. They needed to be transferred ASAP. Which I was great with.
We have severe male factor with 0% Morph AND really high DFI fragmentation like 90% or more. SCSA did not know what to make of it. We were told donor sperm all the way but wanted to give Hubby some goes. This was our first success at making a blast (albeit slow)…which is HUGE for fragmented sperm thus why we were not stopping at 3 day not matter what. I’m cautious but hopeful my egg could repair any DNA damage in the sperm. If only we could have had CGH but with so few embies and slow growing we could get there to have it done. Your thoughts are appreciated on the slow growing blasts question. Thanks in advance!
May 14th, 2013 at 7:58 am
Hi Shawna,
Re: Can I ask you, is there evidence that a slower growing blast (like hitting blast on day 6 vs day 5) has less of a chance at pregnancy?. I think it is fair to say that pregnancies are achieved from blastocysts that get there on both day 5 and day 6. I was trying to find a good research article that looks specifically at that question and didn’t find too much. I recall a paper published a few years ago that showed that day 7 blasts were less likely to implant, but not too many look at day 7 blasts because most programs report that blasts are typically achieved on either day 5 or day 6- only the rare straggler on day 7. I wouldn’t lose any sleep over day 5 vs. day 6 progression.
Re: two polarbodies, to clarify: The fact that two polar bodies were observed is encouraging, assuming that they are two distinct polarbodies and not a first polar body that split into halves or fragments. Sometimes it is hard to tell the difference. At egg maturation to the Metaphase II stage, a first polar body is pushed out of the egg- this polar body contains excess egg chromosomes. We wait for sign of the first PB– Metaphase II stage eggs- to perform ICSI. After fertilization, a second sac is pushed out – the second polar body. The fact of two pronuclei , (the sacs containing the maternal and paternal DNA that stay in the egg) that is the gold standard for detection of normal fertilization.
Yes, I think you should feel encouraged by the good progression of the blasts. Wishing you all the best for a BFP!!! Carole
May 16th, 2013 at 7:37 pm
Hi Carole,
I’m on my 4th round of IVF, and although a lot of egss were collected and most inject, about 80% don’t fertilise. We are using frozen sperm rather than fresh, my husband has trouble producing due to medication for depression. Would this be the cause of the eggs not fertilising, or could it be my egg quality? I’m 41 and my ovarian reserve looks good for my age? FYI we did get pregnant from our first round of IVF but this resulted in a miscarriage at 10 weeks. Each round we’ve only had one egg to transfer and the last 2 rounds were morula transfers not blastocysts. My last egg collection was on Wednesday… we collected 13 eggs, 10 injected and 2 fertilised so far. The other 8 will be re-assessed on Saturday, I hoping that at least a couple more have fertilised.
Any advise you could give would be appreciated.
Thanks
May 17th, 2013 at 7:54 am
Hi Tanya,
The problems you describe, low fertilization, poor embryo development and early miscarriage can all be due to egg issues as well as sperm. The early miscarriage can be a result of aneuploidy (abnormal chromosome number in the eggs). As we age, more and more of the eggs we produce have aneuploidy so we are more prone to problems with embryo development and pregnancy loss. I assume that ICSI (sperm injection) was used with your husband;’s sample to increase the odds of fertilization by bypassing any problems with sperm attachment or sperm entry. If ICSI wasn’t used, I would ask your doctor about using ICSI if you want to try again. But even if more of your eggs were to fertilize, the ability of the embryos to progress is less than optimal. After 4 IVFs, I would have to say that IVF is not working efficiently for you at all. At this juncture, it might be time to consider other options, donor egg would be something to try, but it is very expensive. If you are comfortable with the idea, accepting an embryo donated by another couple who had excess is another option that is much less expensive- just the cost of a frozen embryo transfer usually. Embryo donation usually offers embryos that are of good or excellent quality–precisely because they are embryos remaining after a familiy’s reproductive treatments were successful- so the quality of these embryos is very good. Sometimes these embryos are produced from donor eggs. The reason embryo donation is an attractive option if you are older is that your uterus is usually perfectly capable of carrying a pregnancy long after your ovaries have closed shop. You can still experience pregnancy and birth. Like adoption, embryo donation has implications for the child and the family so counseling before going down this route is recommended by most programs who have identified counselors for patients. Talk to your doctor about other options. If your doctor’s only suggestion is to keep on doing what you have been doing, I would be inclined to get a second opinion. Wishing you Much Good Luck!!!