There is a scientist in every physician. But unlike other laboratory scientists striving to understand the workings of the world around us, physicians can apply science to individual patients to make an immediate use of new-found knowledge.
The science of infertility has been helping to make amazing things happen, growing quickly in a relatively short period of time. Even as we learn more though, the limit of our knowledge comes into sharper focus. As scientists, we firmly believe that if we understand how things work, we can solve a problem, but as physicians, the inability to treat something that we don’t understand is very frustrating. “I don’t know” is not a phrase in our vocabulary—at least that is what we are told as medical students. Please bear with me as I work my way through the limitations of what we know to get to the aspects of the uterus and implantation that we do understand.
Understanding IVF & Implantation
The science of how embryos interact with the uterus is an example of what lies at the current limits of what we know. Even during in vitro fertilization (IVF), our most advanced treatment, an embryo is placed in the uterus and then? We wait to see if pregnancy occurs. Anyone who has been through fertility treatments understands how difficult that wait can be. While we know that during that wait time, many important things are happening inside the uterus; our understanding of those processes is very incomplete. The embryo has to interact with the surface of the inside of the uterus and firmly attach to the lining. It then needs to invade the lining and supporting blood vessels to begin the formation of the placenta. Sounds fairly straightforward, still, understanding the implantation process has been difficult.
How Human Embryos Interact With the Uterus After IVF
We are unable to directly study how human embryos interact with the uterus, and so much of what we do know about implantation comes from the study of mice and baboons. This does not often translate to knowledge about human implantation. There are many proteins, genes, and biological processes that appear to be important, but if we don’t know what actions actually occur, then we can’t identify situations where implantation is ineffective. For couples with unexplained infertility, there very well may be an “implantation defect”, though despite much research on the subject, no specific implantation disorder has yet to be identified. And there are no good tests to assess implantation or uterine lining function—which is frustrating for both couples and for physicians. Implantation defects are considered when a woman fails to become pregnant despite multiple opportunities to conceive with good quality embryos placed in the uterus. If there is a concern about an implantation defect, the only treatment we have that can improve implantation is to use another woman’s uterus—a surrogate, or more properly, a gestational carrier.
So, to summarize our limits of knowledge of implantation: we don’t know exactly what happens, it is theoretical that problems might exist, we have no good tests, and we have no good treatments. When patients ask me more specific questions about a potential problem they might have with implantation, this summary is not what they want to hear—especially from an expert in the field. The more reassuring news is that there is much research ongoing. Often tests are introduced that can look at one single step that might be important in the process. At this point with such little global understanding of the entire process, most currently available uterine implantation tests are clinically useless.
Uterine Polyps, Fibroids & Scar Tissue Can Affect Implantation
Here are a few things that we do know can be problems and can interfere with the implantation process. Anatomical changes such as uterine polyps, fibroids, and scar tissue can affect how embryos interact with the uterus. Most of these can be easily identified with current imaging exams, which most women complete during an evaluation. The growth and appearance of the endometrial lining is evaluated during each treatment month, with medication changes made or hormonal support provided if we think the lining is not ideal. And we are now more aware of some of the hormonal changes that can affect how the lining functions during many of our treatments.
The growth and function of the lining of the uterus--the endometrium--is regulated by the normal reproductive hormones that change as eggs grow. During IVF, hormone levels are often 10-20 times higher than in a normal menstrual month, and we have known for a long time that the endometrium during IVF is very different compared to a normal menstrual cycle. There is a very short period of time after ovulation that embryos can attach and invade the lining, and this is called the “window of implantation”. This window is much shorter during IVF, closing sooner than in natural cycles. We have found that some women with slowly developing embryos have a lower likelihood of success because of this accelerated closure—something we call endometrial dyssyncharony.
Frozen Embryo Transfer
If embryos grow more slowly, women have a higher likelihood of pregnancy if these embryos are cryopreserved during this fresh month, and then placed into the uterus during a more normal menstrual cycle (FET- frozen embryo transfer) the very next month. RMA of Connecticut is one of the first clinics in the country to recognize the benefit of this delayed embryo transfer process. Even though the science may be incompletely understood at the level of the endometrium, we are continually trying to apply what has been learned to patient care, and in this instance, with very good results.
More good news is that the use of a surrogate has become medically more common and is an effective method of overcoming most uterine problems that cannot be overcome using other treatments. And if the advances in our knowledge going forward can match what we have learned to get where we are today, then moving beyond the limits of today’s knowledge may be right around the corner.