Evidence that the endometrial microbiota has an effect on implantation success or failure

• Published in: American journal of obstetrics and gynecology 2016-12, Vol.215 (6), p.684-703
• Main Authors: Moreno, Inmaculada, PhD, Codoñer, Francisco M., PhD, Vilella, Felipe, PhD, Valbuena, Diana, MD, PhD, Martinez-Blanch, Juan F., PhD, Jimenez-Almazán, Jorge, PhD, Alonso, Roberto, Alamá, Pilar, MD, PhD, Remohí, Jose, MD, PhD, Pellicer, Antonio, MD, PhD, Ramon, Daniel, PhD, Simon, Carlos, MD, PhD
• Format: Article
• Language: English
• Subjects: assisted reproductive techniques; bacterial pathogens; Bacterial Typing Techniques; Case-Control Studies; Embryo Implantation; Embryo Transfer; endometrial microbiota; endometrial receptivity array; Endometrium - microbiology; Female; Fertilization in Vitro; Gardnerella vaginalis - genetics; Genome, Bacterial; Humans; Infertility - therapy; Lactobacillus - genetics; Live Birth - epidemiology; Logistic Models; Luteinizing Hormone; Menstrual Cycle; Microbiota - genetics; Multivariate Analysis; Obstetrics and Gynecology; Pilot Projects; Polymerase Chain Reaction; Pregnancy; Pregnancy Rate; Prevotella - genetics; Principal Component Analysis; Prospective Studies; RNA, Ribosomal, 16S - genetics; Sequence Analysis, RNA; Spain - epidemiology; Treatment Outcome; Vagina - microbiology
• ISSN: 0002-9378; 1097-6868
• DOI: 10.1016/j.ajog.2016.09.075

Background Bacterial cells in the human body account for 1–3% of total body weight and are at least equal in number to human cells. Recent research has focused on understanding how the different bacterial communities in the body (eg, gut, respiratory, skin, and vaginal microbiomes) predispose to health and disease. The microbiota of the reproductive tract has been inferred from the vaginal bacterial communities, and the uterus has been classically considered a sterile cavity. However, while the vaginal microbiota has been investigated in depth, there is a paucity of consistent data regarding the existence of an endometrial microbiota and its possible impact in reproductive function. Objective This study sought to test the existence of an endometrial microbiota that differs from that in the vagina, assess its hormonal regulation, and analyze the impact of the endometrial microbial community on reproductive outcome in infertile patients undergoing in vitro fertilization. Study Design To identify the existence of an endometrial microbiota, paired samples of endometrial fluid and vaginal aspirates were obtained simultaneously from 13 fertile women in prereceptive and receptive phases within the same menstrual cycle (total samples analyzed n = 52). To investigate the hormonal regulation of the endometrial microbiota during the acquisition of endometrial receptivity, endometrial fluid was collected at prereceptive and receptive phases within the same cycle from 22 fertile women (n = 44). Finally, the reproductive impact of an altered endometrial microbiota in endometrial fluid was assessed by implantation, ongoing pregnancy, and live birth rates in 35 infertile patients undergoing in vitro fertilization (total samples n = 41) with a receptive endometrium diagnosed using the endometrial receptivity array. Genomic DNA was obtained either from endometrial fluid or vaginal aspirate and sequenced by 454 pyrosequencing of the V3–V5 region of the 16S ribosomal RNA (rRNA) gene; the resulting sequences were taxonomically assigned using QIIME. Data analysis was performed using R packages. The χ2 test, Student t test, and analysis of variance were used for statistical analyses. Results When bacterial communities from paired endometrial fluid and vaginal aspirate samples within the same subjects were interrogated, different bacterial communities were detected between the uterine cavity and the vagina of some subjects. Based on its composition, the microbiota in the endometr