Correction of uterine microbiome and implantation window as a personalized approach to overcome recurrent implantation failure
Authors:   Russian Medical Academy of Continuous Professional Education, Moscow, Russian Federation, Podzolkova N.М. ,   Botkin Moscow Multidisciplinary Scientific and Clinical Center, Moscow, Russian Federation, Shamugia N.L. ,   Russian Medical Academy of Continuous Professional Education, Moscow, Russian Federation,   “GMS IVF ” LLC, Moscow, Russian Federation, Varlakova P.М. ,   Russian Medical Academy of Continuous Professional Education, Moscow, Russian Federation,   “GMS IVF ” LLC, Moscow, Russian Federation
Published: February 2025

The success in assisted reproductive technology (ART) programs mainly depends on the quality of embryos and endometrium. The problem of recurrent implantation failure (RIF) has increased attention to endometrial assessment and preparation. This is because, in contrast to current diagnostic methods for embryo quality, endometrial factors remain less well understood. The use of modern molecular genetic technologies in ART provides new opportunities to study endometrial factors, such as endometrial functional state and uterine microbiome composition. Investigation of the effect of endometrial factors on the development of RIF will help to improve the efficacy of ART programs in patients with RIF.
Objective. To study the effect of endometrial factors on the development of RIF and to improve the efficacy of frozen embryo transfer (FET) in patients with RIF by endometrial assessment using modern molecular genetic technologies.
Patients and methods. The study included 98 patients who underwent FET in a cycle of hormone replacement therapy (HRT). All patients were divided into the study group (n = 47) and the comparison group (n = 51). In the study group, patients underwent a personalized FET after establishing the implantation window according to the recommended time determined by the ERA test. In the comparison group, a standard FET was performed (120 hours after micronized progesterone injection). The study group additionally underwent metagenomic analysis of endometrial functional state and uterine microbiome, with subsequent
correction of uterine microbiome composition and implantation window. In each group, patients with embryos that underwent preimplantation genetic testing (PGT) were separately identified. After FET in a cycle of HRT, implantation rate (IR), clinical pregnancy rate (CPR) and live birth rate (LBR) were comparatively evaluated in both groups.
Results. Among patients without embryo PGT, there were significantly higher IR, CPR and LBR in the study group – 77.78%, 72.22% and 72.22% in relation to the comparison group – 47.83%, 39.13% and 39.13%, respectively. Among patients with PGT, there was also a higher IR, CPR and LBR in the study group – 79.31%, 79.31% and 72.41% in relation to the comparison group – 53.57%, 46.42% and 46.42%, respectively (in all cases, p < 0.05). The rate of implantation window shift in the study group of patients with RIF was 51.07%. The rate of Lactobacillus spp. reduction in the study group of patients with RIF was 74.47%. The rate of uterine microbiome dysbiosis in the study group of patients with RIF amounted to 14.89%.
Conclusion. The study of uterine microbiome and endometrial functional state with identification of the implantation window and subsequent treatment allows to achieve higher IR, CPR and LBR in patients with RIF.
Key words: implantation failure, uterine microbiome, endometrial receptivity, implantation window, IVF failure, metagenomic analysis of endometrial microbiome