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?