Assessing endometrial receptivity after recurrent implantation failure (RIF) – a prospective controlled cohort study

Abstract Research Question What is the prevalence of disrupted markers of endometrial function among women experiencing recurrent implantation failure (RIF), and does the prevalence differ from a control cohort? Design Prospective controlled cohort study. In total 86 women with a history of RIF and 37 women starting their first fertility treatment were recruited for this study. Endometrial and blood profiling were carried out in a hormone-substituted cycle using estradiol and progesterone. Endometrial biopsies were analysed by histology, immune cell profiling, and the ERA® test (Igenomix, Spain). The vaginal microbiome was analysed using a NGS-based technology (ArtPRED®, The Netherlands). Blood tests included estradiol, progesterone, prolactin, TSH, vitamin D and anti-phospholipid antibody levels. Results Patients with RIF demonstrated a range of test abnormalities. Compared with controls, women with RIF had a higher prevalence of chronic endometritis (23.5% vs. 5.6%), a lower vitamin D level, and a borderline lower progesterone level. Women with RIF had a more favourable vaginal microbiome compared with controls. While the RIF cohort was older than the controls (mean age 33.8 years vs. 30.2 years) no differences between the groups were observed with regards to immune cell profiling and the ERA test. Conclusion These data demonstrate that a single test/treatment for the endometrial factor in RIF is unlikely to be clinically effective. Diagnosing the endometrium in women with RIF permits targeted rather than blind interventions. Relative Vitamin D deficiency, lower mid-luteal progesterone, and chronic endometritis are ready targets for treatment. Understanding the role and treatment of an unfavourable vaginal microbiome in RIF needs further investigation.