Abstract
In vitro fertilization-embryo transfer (IVF-ET) is now widely applied in treating infertility. As the number of IVF cycles continues to increase, recurrent implantation failure (RIF) has become a big challenge. The cause of RIF is very complex and remains largely unrevealed, especially for those without any pathological features. It has been proved that vaginal microbiota is associated with many female reproductive diseases, such as pregnancy-related diseases, sexually transmitted diseases, tubal factor infertility, and first trimester miscarriage after in vitro fertilization (IVF) and so on. Hence, vaginal microbiota and its metabolome may also relate to RIF. In this study, we characterized the vaginal microbiota and metabolome of patients with unexplained RIF, while patients who achieved clinical pregnancy in the first IVF cycle were used as controls. Results Based on 16S rDNA sequencing of the vaginal microbiota, the RIF group presented higher microbial α-diversity than the control group (0.80±0.50 vs 0.50±0.39, P-value=0.016) and harbored more non-Lactobacillus microorganisms, including 25 significantly increased genera of both aerobic and anaerobic bacteria. The metabolomic profile showed that the relative abundances of 37 metabolites among 2,507 metabolites were significantly different between the two groups. Among them, 2',3-cyclic UMP and phosphoinositide were the top two metabolites significantly upregulated in the RIF group, while glycerophospholipids and benzopyran were important metabolites that were significantly downregulated. Lysobisphosphatidic acid (LPA) and prostaglandin (PG) metabolized from glycerophospholipids are key factors affecting implantation and decidualization. Benzopyran, as a selective estrogen receptor modulator (SERM), may affect the outcome of pregnancy. All of the metabolome outcomes may result in or from the differential microbiota composition in the RIF patients. Conclusions In conclusion, significant differences were presented in the vaginal microbiota and metabolome between RIF patients and women who became pregnant in the first IVF cycle, which are related to embryo implantation. This study not only deeply investigates the relationship between RIF and the vaginal microbial community and its metabolites but also provides a profound understanding of the pathogenesis of RIF.
Association of progesterone receptor polymorphisms with recurrent implantation failure after in vitro fertilization and embryo transfer
