Uterine Factors, Not Just Embryo Quality, Key to Fertility Success

Research by Rutgers Health and Michigan State University indicates that uterine factors, rather than solely embryo quality, contribute to the varying success rates of embryo transfers in fertility treatments. Even with chromosomally normal embryos, live birth rates are about 50%, with 30-35% of embryos failing to implant.

Uterine factors, not solely embryo quality, contribute to varying success rates of embryo transfers, with significant implantation failures even for chromosomally normal embryos.

Study Uncovers GERM Genes in Uterine Lining

The study, published in JCI Insight, identified 556 genes, collectively named the Glandular Epithelium Receptivity Module (GERM). These genes are significantly more active in the gland cells of the uterine lining (endometrium) of fertile women during the uterus's receptive window. Importantly, these genes were not similarly increased in women experiencing infertility.

Nataki Douglas, an associate professor at Rutgers New Jersey Medical School and senior author, emphasized that the research aimed to understand the fundamental changes in the endometrium during its brief receptive phase.

"The research aimed to understand the fundamental changes in the endometrium during its brief receptive phase."

Methodology: Examining Endometrial Receptivity

To avoid disrupting potential pregnancies, researchers enrolled 30 fertile patients from University Hospital in Newark with regular menstrual cycles. Endometrial biopsies were precisely timed with different menstrual cycle phases, confirmed by blood hormone levels and microscopic examination.

Two sequencing approaches, one measuring gene activity across tissue and another cell-by-cell, were utilized. Both methods revealed the largest molecular transition during the mid-secretory phase, which is typically the period for embryo implantation. Significant changes were observed in specialized uterine gland cells, which produce molecules crucial for embryo nourishment and implantation.

Broad Implications Across Diverse Patient Groups

This research provides the first human evidence for the central role of the glandular epithelium in uterine receptivity, building on previous findings in mice and sheep. The study also noted that correlations of findings from diverse patient groups (mostly Black and Hispanic at University Hospital, and mostly white in past research) suggest similar factors influence infertility across different racial groups.

When a GERM score was applied to existing datasets, it consistently showed lower levels in women with recurrent implantation failure or pregnancy loss compared to fertile controls.

Future Directions for Clinical Application

The work is not yet ready for clinical application. Future steps include narrowing down the 556-gene list to a more practical set and conducting prospective studies with patients experiencing implantation failure to test if the gene signature can predict outcomes. The broader objective is to enable clinicians to identify and potentially correct endometrial malfunctions, leading to therapeutic approaches for infertility.