For couples with difficulty conceiving, in vitro fertilization (IVF) is often their only hope for a biologically related child. But while IVF has helped many couples, as many as one in 10 undergo recurrent implantation failure (RIF) despite repeated transfer of high-quality embryos. It’s an expensive and understandably frustrating experience, and one that, at the moment, clinicians can only combat with empiric therapy. It’s clear that there’s a need to better understand the etiology of RIF, and thanks to a longstanding interest in endometrial factors, fertility experts at the University of Southampton have been exploring the genetics behind the problem.

Nick Macklon and his colleagues hypothesized that a disruption of endometrial gene expression may underlie RIF in some patients. After sequencing biopsies from 43 women with RIF and 72 who had undergone successful IVF, they identified and validated a 303-gene profile that appeared be associated with RIF (1). The majority of the changes in expression were downregulations, and gene ontology studies pointed to defects in cell proliferation, motility and ciliary action. This knowledge gives a better understanding of the genetic basis for RIF, and may one day lead to predictive testing for IVF success. “Endometrial genetic testing is beginning to enter clinical IVF,” says Macklon, “but thus far is limited to helping clinicians to identify the best time to place an embryo into the uterus. If we can develop a clinical test based on our findings, it could become part of the routine clinical investigations for infertility, and also guide couples before embarking on IVF.”

Macklon’s team are currently planning a prospective study in couples just beginning their IVF journey to determine the potential for a screening test based on endometrial genetics. At the same time, they’re seeking to understand the pathways that govern the endometrium’s role in implantation. His recommendations for doctors involved in IVF? “I encourage my colleagues to participate in studies of novel therapies with a sound biological rationale, rather than offering expensive but unproven, and possibly harmful empirical therapies.” MS

Image Credit: C Weimar et al., PLoS One 2012