Genetic 'fingerprint' in womb could predict IVF failure

Reproductive researchers have discovered a specific genetic signature in the endometrium that identifies when in vitro fertilization (IVF) is going to fail. The researchers predict that this discovery will lead to a clinical test to help inform infertile couples of their chances for conceiving, according to an article published online January 22, 2016 in Scientific Reports.

“Many women undergo a number of IVF cycles without success despite having good quality embryos and, up to now, it has been unclear whether or not the lining of the womb may be the cause of that,” said the study’s co-lead author Nick Macklon, MBChB, MD, Chair in Obstetrics and Gynaecology, and Director of the Complete Fertility Centre Southampton, at the University of Southampton, in Southampton, UK.

“We have now shown that an abnormal gene expression in the lining can be identified in many of these women and that a specific gene ‘fingerprint’, when present, is always associated with failure, which is very significant in aiding our understanding of IVF failure,” Dr. Macklon said.

In this study, researchers obtained endometrial biopsies from 43 women with recurrent implantation failure (RIF)—defined as the absence of implantation after 3 or more transfers of high quality embryos or after placement of 10 or more embryos in multiple transfers. For comparison, they also obtained biopsies from 72 control subjects, which were women who had live births after IVF or intra-cytoplasmic sperm injection (ICSI).

After the researchers randomized the samples, they used a signature discovery set that identified a genetic signature of 303 genes in 81% of women with RIF. Women who had live births after IVF treatment did not show this genetic signature.

“What this tells us is that a large proportion of women who suffer recurrent implantation failure may be infertile due to a problem with the receptivity of their uterus,” said co-lead author Frank Holstege, PhD, head of the Genomics Laboratory at the University Medical Center Utrecht, the Netherlands. “Their chances of achieving successful pregnancy are likely to be very small and this information gives clinicians much more clarity in counselling patients as to the wisdom of investing further time, effort, and money in ongoing treatment.”

Currently, up to one third of infertile couples have no cause that can be identified by routine investigation. Also, fertility clinicians have no validated test of endometrial receptivity. Thus, infertile couples would benefit from a signature-based diagnostic test that could predict RIF, the authors wrote.

“At the same time, those patients who have undergone a number of unsuccessful cycles of IVF but do not have the genetic pattern could be advised to persist as they have a much better chance of achieving a pregnancy,” Dr. Holstege added.

“While we believe this finding to be a very significant development in international fertility research, the next stage is to trial it as a clinical test to study its effectiveness on a wider scale,” Dr. Macklon said.