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New relation between dysbiosis of the vaginal and endometrial microbiota and RIF found

2019; Elsevier BV; Volume: 112; Issue: 3 Linguagem: Inglês

10.1016/j.fertnstert.2019.07.962

1556-5653

Takuhiko Ichiyama, Yoko Nagai, Daichi Urushiyama, Motoharu Ohno, Takashi Yamaguchi, Motoi Nagayoshi, Yoshiyuki Sakuraba, Fumio Yamasaki, Keiji Kuroda, Kenichiro Hata, Shingo Miyamoto, Atsushi Tanaka, Atsuo Itakura, Satoru Takeda,

Reproductive Health and Contraception

Repeated implantation failure (RIF) is estimated to occur in 15%–20% of infertile women undergoing in vitro fertilization-embryo transfer (IVF-ET). Molecular identification recently confirmed that the uterine microbiota may have implications for reproductive and obstetrical outcomes. We evaluated dysbiosis of the vaginal and endometrial microbiota in patients with RIF to comprehensively analyze their microbiota using 16S rRNA gene sequencing and compared the microbiota profiles in the RIF patients and healthy women. This study was conducted from October 2017 to June 2018. It was performed retrospectively for 166 women who consented to participate. It was approved by the Saint Mother Clinic's ethical committee. 145 women who had been diagnosed with RIF were enrolled in the study. 21 healthy women were also enrolled as controls. We investigated their vaginal and endometrial microbiotas using 16S rRNA gene sequencing and compared the microbiota profiles in the RIF patients and controls. The endometrial microbiotas had a higher alpha diversity than did the vaginal microbiotas (controls p=2.41e-07; RIF patients p<2.2e-16). To compare the compositional dissimilarity between the endometrial and vaginal microbiotas, the beta diversity was analyzed. By the principal coordinates analyses (PCoA) based on weighted UniFrac distance, significant associations were observed between microbiotas (p=0.001). Assessing the alpha diversity revealed no significant differences between the control and RIF groups in either the uterus or vagina. Beta diversity of the endometrial microbiota showed no significant associations between the controls and RIF patients (p=0.301). Beta diversity of the vaginal microbiota did not differ significantly between the controls and RIF patients (p=0.052), but a weak difference in bacterial composition was noted. In the endometrial microbiotas, 20 bacterial genera (Delftia, Schlegelella, Burkholderia, Gardnerella, Sphingobacterium, Prevotella, Megasphaera, Cloacibacterium, Dietzia, Rothia, Enterococcus, Atopobium, Micrococcus, Staphylococcus, Ralstonia, Exiguobacterium, Hydrogenophaga, Sediminibacterium, Limnohabitans, and Vagococcus)exhibited significantly different levels between the controls and RIF patients (all p<0.05). In the vaginal microbiota, 7 bacterial genera (Corynebacterium, Atopobium, Megasphaera, Varibaculum, Gardnerella, Peptoniphilus, and Prevotella) Showed significantly higher levels in the RIF patients (p<0.05). In contrast to previous reports, we discovered no significant differences in the endometrial Lactobacillus, with average levels of 51.6 ± 38.33% in the controls and 51.15 ± 37.48% in the RIF patients (p=0.961). However, the average vaginal Lactobacillus levels differed significantly at 91.8 ± 22.73% in the controls and 76.38 ± 38.85% in the RIF group (p=0.015). Analysis of the vaginal and endometrial microbiota using 16S rRNA gene sequencing may be a new biomarker of RIF and may help treat RIF and consequentially help raise the implantation success rate for RIF patients.