An integrated approach to endometrial examination in case of repeated failures in ART cycles: a pilot study

Abstract

Background. Female infertility is still an actual issue in gynecology, despite the numerous advances in reproductive medicine. According to the World Health Organization, 17.5% of couples suffer from infertility. At the same time, there is no tendency for this indicator to decrease. A special place in the solution of this problem is occupied by the methods of the assisted reproductive technologies (ART). However, the reasons for repeated unsuccessful attempts of in vitro fertilization have not yet been sufficiently studied. A number of studies have shown that the uterine microbiome of infertile and fertile women differs significantly [1, 2]. In this connection, the study of the influence of the endometrial biotope on embryo implantation ability in order to increase the pregnancy rate in ART cycles remains an urgent issue. Aim. To assess the influence of the endometrial microbiome on the outcome of in vitro fertilization (IVF) programs in patients with infertility and previous failed attempts of assisted reproductive technologies. Patients and methods. A pilot prospective pilot prospective single-center non-randomized study including 22 patients of reproductive age (18 to 45 years) with infertility and repeated failed IVF attempts in history was conducted. All patients were fully examined in accordance with Order No. 803n of 31.07.20 «On the procedure for the use of assisted reproductive technologies, contraindications and limitations to their use». Additionally, from the 15th to the 25th day of the menstrual cycle was performed an endometrial biopsy in order to assess the endometrial microbiome by metagenomic analysis (MEMA). The distribution of patients into groups was carried out on the basis of test results: the first group consisted of patients with a predominance of Lactobacillus>90% of total microorganisms, and the second group consisted of patients with a predominance of pathogenic flora who were treated with etiotropic therapy. The final point of our pilot study was to evaluate the results of in vitro fertilization. Results. According to the results of the metagenomic analysis of the endometrial microbiome of 22 women, only 7 (31.8%) were dominated by Lactobacilli strains, 15 (68.1%) women were dominated by opportunistic microorganisms such as Gardnerella, Streptococcus, Apotobium, Prevotella, Enterococcus, Corynebacterium and others. This group of patients, underwent etiological therapy with antibacterial drugs followed by probiotics was carried out. As a result, the following data were obtained: in group 1, 6 (85.7%) out of 7 women became pregnant after frozen-thawed embryo transfer, in group 2, only 5 (33.3%) out of 15 women became pregnant after the recommended treatment. Conclusions. Women with infertility and repeated failed IVF attempts more often have a «non-lactobacillus» uterine microbiome. In the group with a predominance of Lactobacillus bacteria in the endometrial microflora, more favourable IVF outcomes are observed. Etiotropic antibiotic therapy and probiotic supplementation also increase pregnancy rates. However, given the small number of patients, large-scale studies are needed in this area.