Why didn't my euploid embryo stick?
If you’ve had a PGT-screened, euploid (chromosomally 'normal') embryo transfer - and it wasn’t successful… first of all, I’m so sorry. It’s a really tough situation to be in. You think you’ve finally got your golden embryo, and it doesn’t stick around. It's heartbreaking, truly. And we all (your care team and your loved ones) wish that you had a different result.
Secondly, I’ll share that you’re not alone. Up to 1/3 of people who have euploid embryos transferred don’t end up with a baby. And that’s really tough to accept, but there is sometimes comfort in numbers.
While we know that the broad categories of embryo quality (there is no definitive test that can be done to say what the true quality of an embryo is), endometrial receptivity (which can be tested for using the ERA test), and transfer technique play a role in whether a euploid embryo will implant, there are also many other factors that may contribute to your success.
A recent review article looking at these factors just came out, and I want to summarize its results for you.
Your fertility doctor is likely aware of this data, but I find that when my patients are well informed, they are empowered to ask the right questions and feel more in control of their situation. When you’re struggling to conceive it can feel like so much is out of your hands. Keeping yourself informed is something you can control, along with what you choose to eat, how you choose to exercise, and how you prioritize rest and sleep. These factors all influence your mindset and your ‘healthset’ in positive ways - and as we say at Acubalance, a healthy body is a fertile body.
Let’s get into the factors that have been studied in relation to whether your euploid embryo will implant.
This review paper looked at the research to date, which means that they can’t possibly have reviewed every single thing that impacts embryo implantation, but they’re telling us what the most up-to-date research is saying. Here’s what research has shown ikely plays a role in the implantation of your euploid embryo:
1. Embryonic factors: the morphology (or, appearance) of the blastocyst likely has an impact on whether it will implant. This studies on morphology are conflicting - some showing that morphology makes no difference to implanation, and others showing there is a significant difference. But research is actively being done to tease out the truth. The stage of expansion (whether your blastocyst has ‘hatched’ or not), and day at which the embryo became a blastocyst also seem to play a role. Mitochondrial DNA count in the embryo may possibly play a role - a very high count has been associated with a negative pregnancy outcome in a couple of studies, but further study is necessary.
2. Uterine factors: there is fair evidence that treating chronic endometritis will increase success rates of euploid embryo transfer. There is evidence that prior C section may negatively impact success, and that having an arcuate uterus (the most common uterine abnormality) does not impact implantation rate. Having a ‘difficult transfer’ may relate to poorer pregnancy outcomes, but this connection and the mechanism needs to be confirmed by more studies. Lastly, having an ‘endometrial scratch’ prior to transfer doesn’t appear to improve live birth rate.
3. Protocol factors: the type of ovarian stimulation protocol, trigger type and protocol for frozen transfer don’t seem to impact implantation success. Progesterone levels on the day of transfer are likely important, but there is yet to be a confirmed optimal level of progesterone that clinicians should be aiming for. It appears that too much, or too little, progesterone on transfer day could both negatively impact implantation. There also seems to be an improvement in implantation rates with frozen vs fresh blastocysts - but there are so many individual variables that could impact your personal success, that you want to talk with your doctor about whether a fresh or frozen transfer is best for you. In the case of screening the chromosomes, at this time at the clinics we refer to, fresh transfer isn’t an option as there isn’t enough time to test the biopsy of a fresh embryo. Interestingly, whether the embryo was a previously frozen egg (ie. from previous oocyte freezing) didn’t seem to impact implantation rate.
4. Patient factors: earlier research let us know that maternal age is a major factor in the ability of a patient to be able to generate a euploid embryo. But implantation rates seemed to be pretty steady among women between ages of 35 and 42 if they are all receiving a euploid embryo. However, extremes of maternal age have recently been shown to negatively impact the implantation rate. When the age advances past 41, the success of even euploid transfers does decline. Advanced paternal age (41-50) impacts fertilization, but not implantation or clinical pregnancy rate of blastocysts. Sperm DNA fragmentation seems to not impact pregnancy outcomes in the research to date, but the caveat here is that the technology isn’t well standardized, so studies are hard to combine. Higher maternal BMI was the most significant patient factor that influenced euploid transfer success - in fact, every increase in 1 unit of BMI decreased the probability of live birth by 20%. Interestingly, MTHFR status of the embryo negatively affected implantation - embryos who were 677T homozygous had a lower chance of implantation (unfortunately, MTHFR typing of an embryo isn’t done in a clinical setting or recommended by the ASRM). There isn’t any evidence that low maternal vitamin D negatively impacts pregnancy outcomes, and as long as TSH is <2.5, there seems to be no more optimal TSH level implicated in implantation. When it comes to thyroid, there doesn't seem to be a difference in pregnancy outcome when patients taking Synthroid are compared to those who are not.
5. Embryology protocols: there is good evidence that taking biopsy at certain times does impact clinical pregnancy rate. Similarly, the size of the biopsy and whether the embryo was biopsied more than once can also affect your success. Other lab factors such as type of culture and temperature of the incubator are important considerations and another reason why you want to work with a reputable clinic/lab in your area.
While many (or, perhaps, most) of these factors are out of your control (your age, MTHFR status of your embryo, the temperature of the lab), a select few are modifiable by diet, lifestyle and mindset approaches. Further, we know that there is a difference between your biological age and your chronological age - and that your biological ovarian age is a more important predictor of the likelihood of IVF success. Biological ovarian age is impacted by all of the lifestyle factors that you can control.
It is very important that you are working with a fertility clinic you trust. You want to be sure their lab is using the latest technology, your team is following the most recent guidelines, and fortunately in Vancouver we have several fantastic fertility clinics to choose from. We work very closely with Olive Fertility, whose team I absolutely know are staying updated on the latest research and recommendations to optimize your euploid embryo transfer outcomes.
When it comes to what is in your hands - your diet, how much and how intensely you exercise, and how you prioritize rest, sleep, and cultivating a positive mindset not only give you back a sense of control in a situation like this, but also may positively influence some of your risk factors (like maternal BMI and your biological ovarian age, for example).
If this has happened to you, I want you to know:
1. I’m so sorry
2. You’re not alone
3. It’s not your fault
4. And I’m here to support you in whatever path you choose to take next. There may be factors that we can investigate together that have yet to be studied but could impact your implantation success moving forward. I work with the microbiome, subtle hormonal imbalances, your nutritional status, and the balance of lifestyle factors to both make this process more manageable, and support your overall health and fertility.
Everyone on your team - your fertility clinic, your Acubalance practitioners, and your friends and loved ones - we’re all rooting for you.
If you’d like to chat about how we can support your health and fertility moving forward, I’m always available for a free 15 minute discovery call - find out if we’d be the right fit to help you on this journey.
Dr Kali MacIsaac ND