Q from U: if I transfer this embryo, will I get pregnant?

June 6, 2015Carole 6 Comments »

One question that comes up again and again from IVF patients is: If I transfer this embryo, will I get pregnant?  Patients send me their pictures of embryos and ask me to evaluate them and predict whether this embryo is “the one” that will become their longed for child.

I deeply understand this need to see into the future and gain the knowledge to make the right decision in the present, but it is impossible to predict with certainty an outcome from IVF- especially from a photo. It might help to understand why this is still impossible to do.

Embryologists are tasked to recommend embryos for transfer based on information they can collect while they have the embryos growing in the lab. The 3 main indicators used by embryologists to determine the best embryos are:

1. Does the embryo look “good”? This was the first tool embryologists used but it has been eclipsed by two other tools I’ll talk about in a little bit. Even with only a weak correlation between appearance and implantation/pregnancy success, embryologists were desperate to identify some measures to predict which embryos were most likely to implant and go to term. Some traits –such as an even number of same sized cells at each cleavage stage –seemed advantageous for implantation. Likewise, very little fragmentation of cells also seemed like a good trait for an embryo to have. So regular, even embryos with no or few fragmented cells received higher scores than embryos that had irregular shaped cells and/or lots of fragments. It might have spoken more to our bias regarding beauty- we like symmetrical things and even numbers- and was not based on compelling science that these traits always correlated with pregnancy success. This lesson was brought home to me with two IVF cases very early in my career. One patient was 40 years old with perfect-scoring textbook-looking 8 cells on day 3. The other patient was in her twenties, had a large number of embryos, with each one scoring worse than the next due to large amounts of fragmentation. In fact, it was hard to tell for some embryos if a cell was actually a cell or a large fragment. Based on scoring, we had higher expectations for the 40 year old, but it was the younger patient who got pregnant and this lovely baby was the first IVF baby I was privileged to hold when the patient brought her into the office when she was a couple of months old. This taught me that embryo scores alone could be misleading.

2.  Did the embryo hit certain developmental stages on time or did it stall or lag? This is a functional question which is more directly tied to whether an embryo is likely to keep growing, than an embryo score. Our first real chance to evaluate embryo function was with the advent of sequential culture systems which allowed embryologists to grow embryos for 5-6 days, allowing them to determine if the embryo was able to reach blastocyst stage- the stage just before implantation. We now know that for some patients, a significant number of embryos get stalled at cleavage stages. When embryos were routinely cultured to day 3 to transfer embryos at cleavage stage – and the cycle failed- there was no way to know if this particular embryo would have also stalled out in culture. Now, this embryo has a chance to fail in culture and not be selected for transfer. With the advent of time-lapse continual video monitoring of embryos, and mathematical analysis of these videos- embryologists are able to determine the average times to reaching developmental stages for embryos that go on to implant.  This analysis of an embryo’s functional capacity to grow– has been taken to another level.

3. Does the embryo have a normal number of chromosomes? Chromosomes are twisted strands of DNA that contain all the genetic information passed on from the parents. With only a few exceptions, having an abnormal number of chromosomes is incompatible with continued embryo growth, implantation, pregnancy and live birth. For instance,  Trisomy 21 (an extra Chromosome 21) is compatible with life and these kids are born with Downs Syndrome. With pre-implantation genetic screening (PGS) of embryos, we can tell if an embryo has a normal number of chromosomes. This is a big deal. While aneuploidy testing does not rule out the possibility that an embryo could be harboring smaller stretches of DNA sequences that could doom it along the way- it does rule out really big problems like the absence or addition of entire chromosomes. It is also possible to use pre-implantation genetic diagnosis (PGD)  testing to look for abnormal gene sequences that are harbingers of severe medical conditions later on- but these usually don’t impact implantation potential- in the way that most kinds of aneuploidy do.

The good news is that embryologists have more and better tools at their disposal to evaluate embryos for their potential to implant- and these are certainly evolving and existing tools will improve and new tools will be added as time goes on- but even if your embryologist can find your “best chance” embryo, it still does not guarantee your pregnancy.

IVF is a team effort, not just in the clinic, but also between the patient and the clinic. The physician has to be aware and counsel the patient of other issues that may also be reducing the patient’s chances of conception and a healthy pregnancy.

  • Endocrine problems (eg. thyroid conditions)  that effect reproductive function. If a patient is hypothryoid or hyperthyroid, these conditions must be brought under control first.
  • Insufficient (thin) uterine linings that are inhospitable to embryo implantation. In some cases, a frozen embryo transfer may be more optimal because it separates the IVF case into a ’embryo production” phase in which egg quality and selection can be optimized hormonally and an “embryo implantation” phase in which the uterine lining can be optimally hormonally primed for implantation. The best hormonal protocol for each are often not the same and the lining gets short changed to get more eggs at retrieval.
  • General health of the patient. Patients that are at the extremes of weight (over or under) may have more difficulty conceiving. Patients who smoke also reduce their fertility- this applies to both males and females. There are lots of factors that go into good reproductive health- these are just a few. It is important to share all your medical information with your doctor so they can try to help you optimize your reproductive health before you spend a lot of emotional and financial resources on IVF.

Bottom line, getting pregnant should be easy, but it often isn’t. Even high tech procedures can’t guarantee pregnancy. You can, however,  position yourself for the best possible outcome by finding a highly effective IVF team (look at www.sart.org for  best pregnancy rates in your area)  that will work with you to diagnose the problem (look for good two-way communication between the patient and clinic), grow and find the best embryos to transfer (look for a good lab that uses modern tools) and helps you optimize your fertility before you even get started (good physician practice).

I have a lot of faith in patients to make the right decisions if they have all the information they need along the way. I choose patient education over a crystal ball any day to get a happy answer to the question: Will I get pregnant if I transfer this embryo?


Making your case for IVF coverage

April 20, 2015Carole No Comments »

The dance between doctors and insurance companies  to get medical procedures covered is a common part of medical treatment. Doctors will often write letters to the insurance company to confirm that the patient 1) needs the procedure and 2) the procedure is likely to work or provide benefit to the patient.

You can enlist your doctor’s help and provide him with ammunition to use in his letter on your behalf by visiting the Fertility Within Reach website  at http://www.fertilitywithinreach.org/infertility-resources/ and checking out all their free resources.

Tip of the Day. If you provide your first name and your email to sign up for their newsletter, you will get a free copy of Policymaker’s Guide to Infertility Health Benefits. This booklet contains lots of easily digestible facts to share with your insurance company and/or your employer that demonstrate that fertility benefits for everyone- and specifically you!!- are a win-win for all concerned.

Fertility Within Reach also offers patient coaching for a fee if you want it but there is a lot of free information that is very accessible on the web site and there is no pressure to buy the coaching sessions. But if you want to have a patient navigator, there is no one better than Fertility Within Reach founder Davina to coach you. She has been an infertility patient herself and knows what having infertility coverage means for a patient. The website and Policymaker’s guide are a compilation of all the wisdom she has accumulated over the years helping patients get access to IVF coverage.

Other resources for advocating for insurance benefits:

Via Fertility Within Reach:

Infertility Insurance Resource Information by State: http://www.fertilitywithinreach.org/infertility-insurance-information/lobbying-101/state-resource-information/

Free Policy Makers Guide: http://www.fertilitywithinreach.org/policymakers-guide/

Communicating with your Insurance Provider: http://www.fertilitywithinreach.org/communicating-with-your-insurance-provider/

Communicating with your Employer: http://www.fertilitywithinreach.org/communicating-with-your-employer-about-fertility-benefits/

Via Patient Advocacy Foundation (General medical- not infertility specific)

How to Write an Appeal Letter if you are denied: http://www.patientadvocate.org/resources.php?p=36

Remember that just because you don’t have coverage or your coverage is incomplete today- that doesn’t mean that it needs to stay that way. There are effective methods to get the coverage you need and organizations to guide you on your way.

UPDATE: If you are in Massachusetts, Fertility Within Reach is having a special seminar on empowering patients to get health insurance coverage. The event is happening on May 16, 2015 This workshop is called, Funding Fertility Treatment: Empowering Yourself to Access Insurance Benefits & Financial Resources and is being held in Natick, MA.  For more information and to register, go  to Davina’s blog post.

FWR Funding Fertility Tx Workshop


Can supplements really improve sperm quality?

January 25, 2015Carole No Comments »

One of the questions I often get is from patients who want to know if there is a supplement they can take to restore their fertility. Some of the supplements are little more than a tweaked daily vitamin with a “fertility optimized” mix of vitamins. They probably won’t hurt you but hard scientific evidence is weak at best to enthusiastically recommend that everyone get on the supplement bus.

All of us would like if science could issue a unequivocable result for every question we are struggling with. How can we find the best health care practices when there are so many studies with conflicting results? Which studies should we believe? How can we better understand what the science is telling us? One method is through the Cochrane Collaboration which is an organization and a methodology to look at multiple studies that are asking the same question and identifying studies that were well done (appropriate controls used, good statistics, reproducibility of results) and looking for a common, evidence-based message.  The purpose of doing an Cochran review is to find the truths in studies so that patients can benefit from evidence based health care instead of anecdotal stories and a physician’s own limited experience.  The methodology that is used for a Cochrane review is explained here.  Briefly, a Cochran systemic review “is a high-level overview of primary research on a particular research question that tries to identify, select, synthesize and appraise all high quality research evidence relevant to that question in order to answer it.

Key Points:

  1. Systematic reviews seek to collate all evidence that fits pre-specified eligibility criteria in order to address a specific research question
  2. Systematic reviews aim to minimise bias by using explicit, systematic methods
  3. The Cochrane Collaboration prepares, maintains and promotes systematic reviews to inform healthcare decisions: Cochrane Reviews

A patient wanted to know which supplements are best to treat DNA fragmentation in the sperm head, which degrades fertility.

In a published Cochran review in 2013, Dr. Marian G. Showell and colleagues published “Antioxidants for Male Subfertility”. The abstract of their study can be found here and the full article with a “plain language summary” here, and copied below:

Review question: do supplementary oral antioxidants improve fertility outcomes for subfertile men when compared with placebo, no treatment or another antioxidant?

Background: many subfertile men who are part of a couple undergoing fertility treatment are also taking dietary supplements in the hope of improving their fertility. It is important that these men have access to high quality evidence that informs them on the benefits and risks of taking an antioxidant. This review aimed to assess whether oral antioxidants would increase the chances of a couple with a subfertile male partner achieving a clinical pregnancy and ultimately a live birth. This review did not examine the use of antioxidants in men with normal sperm.

Study characteristics: the Cochrane review authors included in this updated review 48 randomised controlled trials that compared single and combined antioxidants with placebo, no treatment or another antioxidant in a population of 4179 subfertile men. The duration of the trials ranged from 3 to 26 weeks with follow up ranging from 3 weeks to 2 years. The men were aged from 20 to 52 years. Most of the men enrolled in these trials had low total sperm motility and sperm concentration. One study enrolled men after varicocelectomy (surgical removal of an engorged vein in the scrotum), one enrolled men with a varicocoele (an engorged vein in the scrotum) and one recruited men with chronic prostatitis (infection of the prostate gland). Three trials enrolled men who, as a couple, were undergoing in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) and one trial enrolled men who were part of a couple undergoing intrauterine insemination (IUI). The data were current to 31 January 2014.

Funding sources were stated by 15 trials. Four of these trials stated that funding was from a commercial source and the remaining 11 obtained funding through non-commercial sources or university grants. Thirty-three trials did not report any funding sources.

Key results: antioxidants may have been effective in treating subfertile men but the reporting of studies was too inconsistent to be confident in these findings. The live birth results suggest that we would expect a live birth of a baby for 5 out of 100 subfertile men who did not take any antioxidants, compared to between 10 and 31 out of 100 men who were taking antioxidants. The results for the clinical pregnancy rate showed an expected clinical pregnancy for 6 out of 100 subfertile men who did not take any antioxidants, compared to between 11 and 28 out of 100 men who were taking antioxidants. Adverse events were poorly reported and we could not make conclusions on any harmful effects. More high quality, larger placebo-controlled trials reporting on these outcomes and adverse events are needed to draw definite conclusions.

Quality of the evidence: the quality of the evidence for live birth and clinical pregnancy was deemed ‘low’ while adverse events was assessed as ‘very low’. These ‘low’ and ‘very low’ assessments were due to the lack of a clear description of trial methods and inconsistent, inadequate reporting of live births and clinical pregnancies. Not enough trials compared the same interventions to make any conclusions about whether one intervention worked better than the other.

Bottom line: We need better studies to determine whether oxidants are beneficial.  In the absence of these studies, it is prudent to have a discussion with your doctor about the risks/benefits of any supplement you may be considering.

Fireworks at Fertilization

December 26, 2014Carole 1 Comment »

A new study shows that the genesis of a new human being is accompanied by fireworks. The amazing fireworks display that the egg puts on using zinc atoms when the egg is fertilized is shown in the video below.

In an article published in Nature Chemistry, Dr. Theresa Woodruff and her team discovered that the newly fertilized egg releases tiny packages of one million zinc atoms each that creates waves of light, called zinc sparks. These waves of lights happen four to five times in the first hours after fertilization and are necessary steps for the egg to begin its development to an embryo.

This discovery could be the beginnings of an analytical method to distinguish the healthiest fertilized eggs among a group of in vitro fertilized eggs. Being able to better select the healthiest fertilized eggs would increase the likelihood that only one embryo can be selected for  transfer and that the selected single embryo will be able to go the distance, implant and produce a healthy pregnancy and child.

Here is another article about this discovery with quotes from the team.

INVOcell- Analysis of Risk vs Benefit

November 11, 2014Carole 2 Comments »

Just the other day, I stumbled across an article published on Oct 24, 2014 that discussed a oral presentation presented at the recent ASRM meeting about a low cost IVF alternative called INVOcell. To my surprise, I found comments I made more than two years ago appearing in the current article although no one actually contacted me before they wrote the latest piece. So I thought I would revisit the issue, look at the new data and see whether I can learn to love INVOcell.

What is INVOcell?

INVOcell is IVF without the in-lab culture part. Like IVF, the INVOcell procedure has an ovarian stimulation cycle part to recruit eggs (check). An egg retrieval is performed  to get eggs (check). Eggs and sperm are put together (check), – in a plastic container which is placed in the vagina so the patient can vaginally incubate her gametes. (Whaat?= that’s the INVOCell part).  After 3-5 days, embryos are removed from the container and transferred back to the patient’s uterus.

So, back in 2011 I had two main concerns with this low cost alternative to IVF which I expressed in this post:

Invocell- not nearly IVF

Concern One. If eggs in cumulus and sperm are added to a small culture volume, these other cells will degrade the quality of the culture  medium as they incubate. That is why we remove these excess cells at fertilization check the next morning and place in fresh media. The newest version of the INVOCell technique uses either a very short co-incubation period for sperm and eggs with removal of excess cells before the egg goes into the container or ICSI to minimize the cellular material from the beginning to one egg with a sperm inside. Both of these are good solutions to the media degradation issue and so I am not worried about this any longer.

Concern Two: The fertilization check step is skipped. The window during which normal fertilization can be seen in the form of two pronuclear structures (2PN) inside the egg visible using a microscope happens during the time the egg is incubated in the INVOcell device inside the vagina- so obviously it doesn’t happen. The physician has the option to remove the vaginal device and open it, remove the embryos and check for fertilization but this is not routinely done. After all, the low cost part of INVOcell is due in part to the fact that you don’t do a lot of monitoring and checking during culture (reduced staff) , and don’t need to buy a lot of incubators (reduced equipment overhead since the patient brings her own vagina or that of a good friends to the case). I think INVOcell can be offered at half the price of regular IVF. The stim cycle drugs and physician/nurse time are still expensive but the lab expense can be minimal.

So what’s the big deal with skipping the fertilization check step? 

The reason we don’t skip this step in the IVF lab is because even abnormally fertilized eggs pretty routinely grow into very nice looking blastocysts which can’t make a normal baby but can make trouble if transferred- namely resulting in a molar pregnancy which is one of the complications under the category of gestational trophoblastic disease (GTD) .  Very rarely, a cancer (choriocarcinoma) can arise from GTD.

What causes the most common form of GTD ( hydatiform moles- aka.  molar pregnancies)  which can (rarely) result in choriocarcinomas?

Two types of fertilization errors cause GTD. First, an extra sperm enters the egg, resulting in a 3PN state, DNA from three gametes  (egg, sperm, sperm) instead of two (egg, sperm). Alternatively, the egg can fail to toss out its extra set of chromosomes before a single sperm gets inside- again you have DNA from three gamete sources (2 from the egg plus one sperm) causing a 3PN state instead of the normal 2PN state.

Can we tell if we have a normally fertilized egg or not and remove it from the pool of embryos eligible for transfer?

Yes, traditional IVF procedures require a “fertilization check” step to visually examine the fertilized egg under the microscope during a specific time period (16-20 hrs after sperm are added to the egg) to verify whether 2 pronuclei are visible (normal 2PN state) or more than two are visible (abnormal 3PN) state.

The INVOCell procedure does not include a check for 2PN status.

How often does gestational trophoblastic disease happen? From the American Cancer Society link:

Gestational trophoblastic disease (GTD) occurs in about 1 pregnancy out of 1,000 in the United States. Most of these are hydatidiform moles.

How often does GTD convert into a cancer? From the National Cancer Institute link:

The reported incidence of choriocarcinoma, the most aggressive form of GTD, in the United States is about 2 to 7 per 100,000 pregnancies. The U.S. age-standardized (1960 World Population Standard) incidence rate of choriocarcinoma is about 0.18 per 100,000 women between the ages of 15 years and 49 years.[2]

So the incidence of this across all pregnancies (natural and presumably some from IVF in this sample)  is relatively rare.

So why worry about GTD at all?

One reason I am not 100% relieved at this low incidence rate is that we don’t actually know what the rate of molar pregnancy is in IVF patients. I do know that in my experience, we could expect to have a least one molar pregnancy a year in our program.

What was the clinical outcome for IVF patients with a molar pregnancy? These patients had a D&C and then they were counseled not to attempt pregnancy for another 12 months just in case some of the cellular material was retained and could result in an undiagnosed choriocarcinoma. Molar pregnancy was a relatively infrequent event, but something that was treated very seriously when it happened.

There are various anecdotal reports of molar pregnancies in the published literature but I couldn’t find any  national statistics in the incidence of molar pregnancies arising from IVF. Yet, almost every program will, if asked, tell you that yes, they  have had IVF patients with molar pregnancies – and this is under regular IVF protocols in which  3PN embryos are routinely detected and removed from the groups of normal embryos for transfer.

So what can we expect if we skip this step? Will increased use of INVOcell unwittingly lead to the transfer of more abnormal 3PNs – some of which may implant and cause GTD?

Although we may not know the incidence of molar pregnancies in US IVF programs, I know that 3PNs are commonly present among the normally fertilized eggs of many of our patients. How do I know this? I know this because my lab would freeze these non-clinical embryos on a weekly basis (with patient permission) to use these as embryos for technical training. Techs could practice moving embryos from dish to dish or practice freezing or thawing them. We had 3PNs every week to freeze. We pulled them out of the clinical transfer pool but they were routinely arising in our culture system. They made great practice cells because they looked so normal.

So if we don’t look for them in the INVOcell system, does that mean they don’t happen?

My first post back in 2011- caused a big reaction on the part of a reader “Boris”. I took the bait and responded to him in a second, snarky post.INVOcell post strikes a nerve. It’s hard to tell who was suffering from more nerve pain- me or Boris.

In any case, more than two years after my last INVOcell post, earlier this month at the ASRM meeting in Honolulu, data from a small US study was presented that showed encouraging results with INVOcell compared side by side with regular IVF. You can decide if the new data warrants the exuberant headline from the  ASRM press release “Intravaginal incubation of embryos is safe and could save patients money.”

This new INVOcell study was presented by Dr. Kevin Doody from Bedford, Texas as an oral presentation at the meeting. The ASRM abstract data is presented below and  the entire abstract can be found at this link.  There’s not a lot there about how the INVOcell procedure was done except for this: “After a 2-4 hour co-incubation with sperm, up to 10 eggs were placed into the INVOcell device or into traditional incubators. After 5 days, one or two embryos were transferred into the uterus.” Since the window for fertilization check is after 16-20 hours, it’s probably correct to say that fertilization check step is still not part of the INVOcell procedure.

Incubator INVOcell
Number of cycles (patients) 16 17
Mean age 32.3 (26-38) 32.8 (26-38)
Mean body weight (pounds) 162.0 (121-207) 151.5 (109-184)
Mean number of oocytes inseminated 7.6 (1-10) 6.7 (3-10)
Mean number of embryos transferred 1.8 1.65
Mean blastocyst quality score (BQS) 27.24 26.14
Ongoing pregnancy rate /cycle 62.5% 58.8%

The patients in the study are fairly young (on average less than 35) and there were 16 patients in the Incubator method and 17 in the INVOcell method. Statistically speaking, 17 test patients is probably insufficient to detect the risk of GTD.

According to the Medscape article, another clinician, Dr. Lucena, in Bogota, Columbia says that she has seen no adverse outcomes in approximately 500 cycles, which while encouraging is probably still not enough cycles to detect an increased risk of GTD. It is also possible that other factors like advanced maternal age, may make a patient more prone to producing 3PN embryos. We just don’t know enough yet.

These early results are promising in that these patients had very comparable pregnancy rates between regular IVF and INVOcell. The FDA has not approved INVOcell yet for routine use in the US, but one INVOcell clinical trial(2011) is listed on the US government list of clinical trials.

I would be happier if we had more data and I would be ecstatic if we had some test to tell that these embryos are normal when they are removed from INVOcell culture and before they are used clinically. In theory,  genetic testing could be performed on INVOcell embryos but that would make INVOCell more expensive.

Is INVOcell safe? I don’t know. Most of the time when you drive around in a car without seat belts, no harm done. But sometimes, if you are unlucky, you can have preventable injuries if the car does crash. I would rather see more patients have access to insurance policies that pay for traditional IVF that has all the safety features, rather than encourage patients to use a cheaper procedure which may be riskier. Most patients will have no trouble but a few may have very bad trouble. In the end, it boils down to an analysis of risk vs. benefit. If you are enrolled in a clinical trial with INVOcell, hopefully the risk of GTD –as much as can be known- will be disclosed to you before you take part in a trial and you can decide:  Do you feel lucky?


Disclosure: As an ex- embryologist,  I have no financial interest in the performance of  EITHER regular IVF or INVOcell. As a patient advocate, I am always hoping for better infertility treatments and better access to these treatments for patients.

Egg freezing is no guarantee for future fertility

October 19, 2014Carole No Comments »

In 2013, the American Society for Reproductive Medicine (ASRM) declared that egg freezing was no longer experimental. Here is a link to the professional guidelines, which say in part: “There is good evidence that fertilization and pregnancy rates are similar to IVF/ICSI with fresh oocytes when vitrified/warmed oocytes are used as part of IVF/ICSI for young women. Although data are limited, no increase in chromosomal abnormalities, birth defects, and developmental deficits has been reported in the offspring born from cryopreserved oocytes when compared to pregnancies from conventional IVF/ICSI and the general population. Evidence indicates that oocyte vitrification and warming should no longer be considered experimental.”

I have highlighted some important caveats to this declaration.

  • The method of freezing makes a difference. Old-style slow freezing is not included because most US labs never demonstrated that slow egg freezing could repeatedly be performed with good results- although some Italian labs were successful with slow egg freezing. Vitrification is not considered experimental- when done expertly.
  • To get the best fertilization results, thawed eggs must be fertilized using ICSI (aka. egg injection) because the egg membranes harden and sperm in culture have a very difficult time pushing their way in to fertilize the egg; the sperm must be injected using a microscopic needle.
  • Outcome data are limited regarding whether the resulting offspring are normal but early results are encouraging.

If you read the entire document- which I strongly encourage you to do if you are thinking about egg freezing- you will notice that the authors raise the issue of generalizability of these results to all labs everywhere. The pregnancy data that was referenced was all from the frontier labs who took this method up as a major initiative in their lab and really worked hard to get those positive results. Even with vitrification, egg freezing is not an easy technique. It does not take long to do but in that short time between immersing an egg into toxic cryopreservation fluids, and plunging the container with the egg into liquid nitrogen, there are about twenty different ways to make a mistake and little or no time to fix it so you better be both fast and good at the hand work. That takes both excellent training and practice. This is made more complicated because there are about 10 different containers to freeze eggs in and various kinds of vitrification medium being produced by different companies all vying to tell labs that their method/media/container is the best. So it is not like there is one obvious best method that all labs can just get busy and learn to do well. There is no obvious best standard of care.

In one of my labs, we had great difficulty in reproducibly getting good results with vitrification even though our pregnancy rates with IVF and FET cycles were the best in the state. This is evidence that just because you have mastered one skill set, doesn’t mean that a new technique won’t require significant time and effort to master.  So when the “experimental” label was removed from egg freezing, my first reaction was dismay because I knew that a lot of clinics would recognize an opportunity to offer a new service –and make a lot of money–without necessarily making the investment in staff and training to do it expertly. A lot of first patients at these rush-to-offer egg freezing clinics would be guinea pigs who would happily pay their money and not know whether they had gotten any value for years.

So how are clinics doing? Nobody really knows- it’s not currently part of the data set that must be reported to the CDC- but that will change in the future.  Sure, good clinics are tracking their data internally now but until you thaw (warm) an egg and try to fertilize it and grow it to a blastocyst stage embryo for transfer, you have no idea whether the vitrification and warming worked and your egg is still alive and functional.  Women who are freezing for the future aren’t going to even try to use those eggs for years, so actually getting pregnancy data from vitrified eggs will be slow in coming– making it hard  today for patients to distinguish good egg freezing programs from bad egg freezing programs.

Now Apple and Facebook are covering egg freezing as a benefit for the employees. On the one hand, it is a great thing to remove barriers from reproduction for people who want to have kids. But the potential harm here is that women will think egg freezing is a slam dunk- and that by freezing eggs now, they have a guarantee that they will have functional eggs for producing a pregnancy in the future. I wouldn’t make that bet right now unless your program can prove to you that it has pregnancy outcome data from many, many patients who successfully used their vitrified eggs and are now happily raising these kids.

I know of at least one program that crowed about their success with achieving a single pregnancy from a vitrified egg but then failed to reproduce that event for another patient for months! Actually, I don’t know if they ever did have a second birth. They didn’t believe in writing down their methods so they couldn’t reproduce their success.  That didn’t stop them from aggressively marketing that first pregnancy using every social and media outlet they could find. I am sorry for all the women who went to that clinic based on one case. Yes, eggs were put in storage for the patients the marketing brought in, but there is no guarantee that they can rely on those eggs when they need them. And by the time those thaws happen in any real numbers and patients are unhappy, the greedy bastards who froze their eggs will have retired.

My advice to young women is that they should really push for pregnancy data from any clinic that wants to sell them egg freezing. Unless the clinic can document in writing that their birth rate for women of your age using frozen eggs are are no different than same-aged women using fresh eggs – AND- they have hundreds of successful pregnancies, not just one – don’t use their clinic. And don’t be fooled by their pregnancy data with embryo freezing. Embryo freezing is about 100 times easier than egg freezing so the success rates for one doesn’t necessarily translate into success rates for the other.

If your employer is paying for egg freezing, it’s a good idea to make sure your employer is also paying for annual storage fees and the IVF cycle(s) you’ll need in the future to actually use your frozen eggs.




Persistent Ebola virus detected in semen

October 11, 2014Carole No Comments »

The CDC has updated its recommendation regarding steps to prevent Ebola infection via contaminated semen through intercourse. They recommend that male survivors consistently use condoms during sex to avoid the spread of Ebola because persistent virus has been detected in semen for a much longer than expected time period post infection.  Ebola virus was detected in an Ebola survivor’s semen more than 199 days after he had sex with a woman who then became infected with Ebola. There were no other known exposures for the woman except sex with the Ebola survivor. The CDC does not believe that this condom use recommendation will be life-long for Ebola survivors (unlike HIV)  but until more research can establish the longest possible persistence of the virus in semen, protected sex is the official recommendation. NPR covered this story here.

The original blog post is below:

We hear disturbing news about the Ebola outbreak in the media.  Ebola is a virus that is “difficult to spread” in the sense that we can’t just breathe the virus from the air, but actually need to touch someone who is sick and pick up the virus from contact with their bodily fluids (saliva, mucus, vomit, feces, sweat, tears, breast milk, urine, and semen). Surprisingly, the better known measles virus is one of the most contagious viruses around because on average, each measles patient infects 18 other people, compared to the average Ebola patient who infects two people. While meant to be reassuring, this type of statistic gives me little joy because we shake hands (and even hug) relative strangers every day- and have much more intimate physical contact with the people closest to us.

Well-run Andrology and Embryology (IVF) labs already have effective procedures in place to protect both patients and health care workers from viruses that are spread through contact with bodily fluids. The viruses we have long been concerned with include HIV and hepatitis C, among others. Recently, Ebola has been added to the list of viruses that IVF lab technicians should be aware of. Currently, the odds of being hit by lightning are a thousand (million?) times greater than contracting Ebola in the United States, but it does no harm to be informed and may cause great harm to be ignorant.

The CDC and the World Health Organization (WHO) have published the following information on their respective websites:

CDC information on Ebola in semen  http://www.cdc.gov/vhf/ebola/transmission/)
WHO information on Ebola in semen (http://www.who.int/mediacentre/factsheets/fs103/en/) and (http://www.who.int/mediacentre/news/ebola/06-october-2014/en/)

Perhaps the most troubling piece of information is not that Ebola has been found in semen – that is to be expected since semen is a bodily fluid, but that it has been detected in semen as much as 91 days after the infection has been diagnosed. This surprising observation suggests that perhaps the virus may embed with a round of sperm cells that are in production at the time of the infection– and until they are flushed from the system when mature- the virus persists in this niche. The CDC recommends: Once someone recovers from Ebola, they can no longer spread the virus. However, Ebola virus has been found in semen for up to 3 months. People who recover from Ebola are advised to abstain from sex or use condoms for 3 months.

This underlines the fact that in a lab setting, technicians must develop consistent adherence to universal precautions for their own safety and the safety of their patients to avoid infection with both old and new viruses. Universal precautions includes the consistent use of personal protective equipment (such as gloves) and frequent hand washing.

Everyone should know that there is some risk of exposure to the virus through sex for up to 3 months after an Ebola patient recovers from the life threatening acute infection.



Q from U: How many embryos should I transfer?

September 26, 2014Carole 4 Comments »

The question of how many embryos to transfer in a fresh IVF transfer comes up fairly often in one form or another. The question below is derived from one recently asked.
Q:. I’m starting my first IVF cycle, just before I turn 41. At age 37/38, I had done two cycles to freeze eggs, and so have about 30 eggs on ice. I am scheduled to do a fresh cycle because that a fresh cycle is covered by my insurance and a frozen embryo transfer cycle is not. The clinic is pushing me to agree to a single embryo transfer, even before I know if I get any eggs, let alone embryos.  I know that in most cases, a singleton pregnancy is safer than a multiple pregnancy but on the other hand I know my age makes it very unlikely any given embryo will implant. Do you have any information that would be helpful to be in making this decision?

A: Yes!!, there is a resource to help doctors (and patients) make these decisions. The American Society for Reproductive Medicine (ASRM) publishes guidelines for how many embryos to transfer. This document is free for download to anyone from this link:  I have recreated the table from the article below.

Stage-Prognosis Under 35 35-37 38-40 41-42
Cleavage -Favorable 1-2 2 3 5
Cleavage-Other 2 3 4 5
Blastocysts- Favorable 1 2 2 3
Blastocysts – Other 2 2 3 3

These professional guidelines are written by a committee of physicians and represent a consensus view of what is a reasonable number of embryos to transfer for most patients depending on three factors- maternal age, stage of the embryo (day 3 cleavage or day 5 blastocyst) and whether the prognosis for pregnancy is favorable or “other”.

The patient’s maternal age is the largest contributing factor to infertility, followed by every other infertility factor. If a patient has no or few other factors that could decrease their chances of getting pregnant, they have a ‘favorable” expectation of pregnancy from the transfer. Alternatively, if they have other variables that make it less likely that they will achieve pregnancy, then they have an unfavorable prognosis or as termed in the guidelines– “other” than favorable prognosis.

The transfer number recommendation is an attempt to balance the need to increase the patient’s chance of getting pregnant at all (transfer more embryos) while decreasing the chance of a multiple pregnancy occurring  which could end badly for the patient (transfer fewer embryos).

As we age, our chance of pregnancy plummets because more of our eggs, (and therefore our embryos), will have an abnormal number of chromosomes which makes the embryo unable to progress in pregnancy even if it initially implants. To compensate for this, it is suggested that more embryos be transferred per attempt in older patients.

The older patient who asked the question about how many to transfer was being encouraged to transfer only a single embryo – which falls outside of these recommendations. It is possible that her doctor has made a judgement that ANY chance of multiples is too hazardous for this particular patient- perhaps because of some  known uterine issues specific to this patient.

More and more embryo transfers are made with blastocyst stage embryos. Why transfer fewer blastocyst embryos than cleavage stage embryos? The reason is that embryos that reach blastocyst stage have proven that they are healthier than another embryo that stalls out on day 3 or 4 and never makes it to blastocyst stage. If you are transferring on day 3, you have less information about the embryos and so have to assume some will stall out, so more are typically transferred on day 3. Of course, if your embryos are all good on day 3, you have just really increased your chances of a multiple pregnancy- !- which is a problem and  is why day 3 transfers are falling out of fashion.

Patients should understand that they have a right to ask the doctor to explain why they are recommending one course of clinical action over another. Most doctors don’t mind doing this at all. If you encounter a lot of resistance to questions or the answers don’t make a lot of sense, it might be time to find another doctor who is more accepting of their role as educator and health care partner.

Any professional recommendation may change for a particular patient based on additional or new  information that may be available. For instance,  pre-implantation genetic testing (PGD)  to identify embryos that are genetically abnormal from those that are normal can result in a recommendation that only one embryo be transferred. If only normal embryos are transferred, it is  more likely that the normal embryo will implant –and stay!!- than an abnormal one.  The table above assumes that we have no genetic information- and some of the embryos available will be normal and more likely to result in a good pregnancy and others will be abnormal and have little or  no chance of creating a viable pregnancy. So if a doctor has a known group of normal embryos to choose from, typically, they are inclined transfer fewer or just one in a single transfer attempt.

When cryopreservation of embryos was less successful than it is today, the thawed embryos would be partially damaged and not look so good at thaw. Because they were considered lower quality in terms of their odds of implanting, more thawed embryos would be transferred to a patient in a thaw cycle than a fresh cycle. Today, vitrified embryos look as good as fresh, so there is no need to transfer more previously-vitrified embryos.

In a case where the embryos are derived from donor eggs, the recommendation to transfer disregards the age of the recipient (intended mother) all together. Most donors are well below 35 years of age, so the recommended number to transfer will be based on this age group, not the age of the intended mother.

Medicine is still more an art than a science, and although we are always on the lookout for more tests to give us more information to make better decisions and recommendations, there is still lots of gray area where the physician leans on his/her experience in addition to the data.  I think it is useful for patients to understand the professional guidelines that exist, especially when their doctor recommends a course of action outside of the professional guidelines. Hopefully, this will lead to better conversations between doctors and patients.

Q from U: When should you consider donor eggs?

August 13, 2014Carole 4 Comments »

I received this question from a reader today:

When a woman (very close to 40 ) has her first IVF cycle and responds great to medication, they retrieve 13 eggs – and only 1 fertilizes (with great sperm) and some of the eggs appear to have abnormalities, does she chalk it up to bad eggs or bad luck with that cycle? Even If she conceived naturally 3 years ago, with 2 miscarriages in between. How common is this in the ivf world and is it realistic that changes to protocol DHEA etc. make a difference, Or does this often signal a time that doctors recommend Donor Eggs.

This patient’s situation is not unusual. Having an average number of eggs retrieved and having successful fertilization, while an encouraging and necessary step in treatment does not  guarantee that the embryos produced have a normal number of chromosomes- especially in a patient approaching or past 40. The past history of recurrent miscarriages can be explained if the embryos in those pregnancies had an abnormal number of chromosomes.

As we age, we produce more eggs that didn’t segregate their chromosomes properly in the last stages of egg production and the resulting mature egg has more or less chromosomes than what is normal. You can read more about the link between chromosomal number abnormalities  (aneuploidy) and miscarriage here.

DHEA which is a male hormone or androgen, has been  used with IVF stimulation  in an attempt to improve parameters of the IVF success (eggs retrieved, eggs fertilized, embryos available for transfer, and pregnancy rate).  Some studies support the use of DHEA but it is still controversial, with many opposed to its routine use for all patients, due to its effect on increasing androgen levels. DHEA is used in menopausal women to relieve some menopausal symptoms– bone loss and sexual function issues. DHEA is also used for lupus patients to reduce the effective dose of steroids they need to take. DHEA may be helpful for certain patients but side effects are not understood and DHEA should only be used under doctor’s supervision.

Doctors vary in when they decide it is time to suggest donor eggs. If they believe in DHEA, they may offer that first. If they have good results with aneuploidy testing of embryos, they might suggest another round of IVF in which every embryo is tested for chromosomal number and abnormals are not transferred. This approach also has its detractors because to have anything left after testing, you need a goodly number of eggs (and embryos) to start with–a situation which is precisely lacking in the older patient. Donor eggs is usually suggested sooner rather than later at most clinics because this is the fastest, most reliable method, to get older patients pregnant and on their way as a pregnancy success.

Hopefully the doctor who suggests donor egg as a treatment also takes same time to explain why donor eggs are not just a technical fix and require a little more consideration than most other interventions. If you use donor eggs, you will be able to experience pregnancy first hand (in most cases) but your child will not be genetically related to you. We live in a society composed of individuals with wide religious and cultural attitudes toward the use of donor eggs (or sperm or embryos) . But almost every culture has a great reverence for genetic relatedness and genetic family – whether it is overt or subtle. We relish finding evidence of that genetic link- “You have your father’s eyes, etc”.

You need to ask yourself:

  • Will I ever regret that this child is genetically unrelated to me?
  • Will the people that are closest to me accept this child?
  • Will I have to keep the origin of the child a secret from my closest friends and family or from the child?
  • What will I do if my child wants to know who the egg donor is at some future date? Does the clinic offer a means to connect with this donor in the future? (Often, donor eggs are 100% anonymous and the child has no way to access their egg donor information- ever. Records are not required to be kept past 10 years – at the longest- so the records are often long gone when the child is 18. That is why some groups have formed to find donor siblings if they know the donor code and the ART clinic but this is a hit or miss method to find donors).

These social and emotional issues are difficult for many patients. Egg donor is an easy technical fix- you are much more likely to get pregnant if you use a donor’s eggs- but make sure that you are comfortable with the  long term implications for you and your family.  Most good programs can refer patients to therapists who specialize in this third party reproduction issues so that patients have a chance to think about and speak with their partner about as many implications of the procedure as they can before they agree to use donor eggs.

You need IVF but can’t afford it. What next?

July 16, 2014Carole No Comments »

So you just received the devastating news that you and your beloved won’t be having children the old fashioned way because one or both of you have some reproductive medical issues that are getting in your way. IVF could help you but you can’t afford the $20,000 average price of an IVF cycle. You looked into adoption but that can cost twice as much, especially if you are adopting a child overseas or you may already be too old to adopt because of some adoption rules. So what can you do?

You might want to look at some strategies for finding insurance that covers IVF treatment or determine whether your employer’s insurance plan may already actually provide some of the benefits you need. Or if you can make a compelling business sense to do so (and you can), you might be surprised to find your employer may well add IVF benefits to the company plan.

Fertility within Reach is a non-profit organization that can be your guide in understanding the facts behind insurance coverage for infertility to:

1) determine what your existing insurance plan will cover.

2) talk to your fertility  doctor about your options.

3) explain to your HR department why adding IVF insurance may well benefit the company with minimal cost.

4) talk to your legislator about why the current state laws need to be changed to add infertility coverage to basic insurance plans.

Money Magazine recently interviewed Davina Fankhauser, Co-founder of Fertility Within Reach about how FWR can help people suffering from infertility negotiate the insurance maze.  Davina is an amazing advocate for infertility patients. I met her in person at last year’s ASRM meeting in Boston -although we’d spoken by phone and emailed for more than a year before. I was and continue to be impressed by her passion to help others help themselves. She’s a small person, but an energetic dynamo when it comes to making a difference for fertility patients.

She will tell you that you are not alone and you do have options to explore.  You can read the Money Magazine article  online or buy the print copy at new stands now. You can also see a list of other resources for conception help here.

Don’t assume that you can’t afford IVF. You may have options you don’t know you have. Check out Fertility Within Reach’s website  and see what you can do for yourself. You might even surprise yourself by just how powerful you can be!