Around 12 to 15 percent of couples worldwide struggle to conceive. Some cause or form of infertility from either of the partners contributes to it. For such couples, In vitro fertilization (IVF) serves as the last hope for having children.
However, the success rate of IVF remains below 50 percent on average, with identification of the ideal time in a women's ovulation cycle for its success remaining a challenge. Now, scientists have discovered that a molecule in the womb impedes the process of embryo implantation.
A new multi-institutional research has found that a Teflon-like protein—podocalyxin—makes the surface of the womb slippery, and prevents the implantation of embryos in women undergoing IVF treatment. It was also found that at some point in the menstrual cycle, the level of PCX decreased and made the womb stickier, thereby, presenting a 'golden window' for pregnancy success.
"We've been looking for something that helps embryos stick when the vital part of the puzzle turned out to be a slippery molecule that has the opposite effect -- it prevents them from sticking," said Dr. Guiying Nie, lead author of the research. The findings were published as two studies in the journals Fertility and Sterility and Human Reproduction.
Factor Affecting Adhesion of Embryo
Implantation of an embryo in the human endometrium (the lining of the uterus) is as complex a process as fertilization. The endometrium has to undergo several cellular and molecular alterations in order to transform itself from a non-receptive to a receptive state to facilitate implantation. Nevertheless, mechanisms underlying receptivity, specifically the luminal surface (lining) where the initial interaction of the embryo takes place, is not completely understood.
A widely held notion is that the upregulation of molecules that promote sticking or adhesion—such as integrin αVβIII, L-selectin ligand, and trophinin, among others—is vital. Again, its details are not well understood. Therefore, the team aimed to learn more about how endometrial epithelial receptivity (of the epithelial lining of the uterus), especially adhesiveness, was modulated at the surface for embryo implantation.
Podocalyxin (PCX), a transmembrane protein, emerged as a key negative regulator of endometrial epithelial receptivity. PCX is widely expressed on the luminal surface of most blood vessels in adult vertebrates, including humans. However, its function on these cells is poorly explained.
The discovery challenged the long-held scientific theories surrounding the implantation of embryos in the uterus. And offered new insights into the timing of a 'golden window'. "Every embryo is precious for families struggling with infertility, so getting the timing right is critical," noted Dr. Nie.
A Molecule Impeding Implantation
In the retrospective clinical study, the authors evaluated the levels of PCX in the endometrium of 81 women who were undergoing IVF treatment. A biopsy of the uterus was also conducted at the mid-luteal phase—around seven days following ovulation when the progesterone levels are elevated—of the participants' menstrual cycle; one full cycle prior to the transfer of a frozen embryo.
The scientists discovered that the levels of the Teflon-like molecule on the surface of the womb decrease at a particular point in the menstrual cycle. They also learnt that there was a notable difference in the success rates of IVF when embryos were transferred in the presence or absence of PCX on the uterine surface.
It was found that the success rate of pregnancy (through IVF) was 53 percent in women with low levels of PCX. However, among those in whom the levels did not reduce, the success rate was only 18 percent. Dr. Luk Rombauts, the co-author of the research, averred that the measurement of PCX levels at the mid-luteal phase can be utilized as a screening test.
He also opined that it may potentially suggest a reason for a concern marring pregnancy in women—infertility; thereby, using the molecule as a likely target for treatment. "These findings offer a promising path for us to both improve IVF success rates and potentially treat an underlying cause of infertility," stated Dr. Rombauts.
Potential to Treat Infertility
Armed with the findings of the research, the team has already commenced research in order to gather an improved understanding of the role of PCX and its regulation within the body; aiming to develop treatments for infertility. According to Dr. Nie, probing of PCX could be carried out in a standard pathology laboratory. This can make a future screening test relatively cost-effective and affordable.
"The only way we can currently test for PCX is through biopsies of tissue, which cannot be taken at the time when embryos are transferred," she said. We need further research to develop non-invasive and real-time approaches for measuring PCX on the day of embryo transfer. Our hope is to deliver a simple test that can help patients and boost the precision and personalization of IVF treatment," commented Dr. Nie.
The authors have filed a patent for the technology and its potential clinical applications are being analyzed further. "We hope with further development our discovery could help clinicians identify precisely when each patient has the greatest chance of achieving pregnancy, delivering fully personalized IVF treatment," expressed Dr. Nie.
