Abstract
The microorganisms of the reproductive tract have been implicated to affect in vitro fertilization (IVF) outcomes. However, studies on the reproductive tract microbiota of infertile women are limited and the correlation between cervical microbiota and IVF outcome remains elusive. This study aimed to characterize the cervical microbiota of IVF patients undergoing embryo transfer (ET) and assess associations between the cervical microbiota and pregnancy outcomes while exploring the underlying contributing factors. We launched a nested case-control study of 100 patients with two fresh or frozen-thawed cleavage embryos transferred per IVF cycle. Cervical swabs were collected on the day of ET and divided into four groups according to clinical pregnancy outcomes. Variable regions 3 and 4 (V3-V4) of the 16S rRNA gene were amplified and sequenced on the Illumina MiSeq platform. In fresh IVF-ET cycles, the clinical pregnancy group (FP, n = 25) demonstrated higher α diversity (P = 0.0078) than the non-pregnancy group (FN, n = 26). Analysis of similarity (ANOSIM) revealed a significant difference in β diversity between the two groups (R = 0.242, P = 0.001). In frozen-thawed ET cycles, though not significant, similar higher α diversity was found in the clinical pregnancy group (TP, n = 27) compared to the non-pregnancy group (TN, n = 22) and ANOSIM analysis showed a significant difference between the two groups (R = 0.062, P = 0.045). For patients in fresh IVF-ET groups, Lactobacillus, Akkermansia, Desulfovibrio, Atopobium, and Gardnerella showed differentially abundance between pregnant and non-pregnant women and they accounted for the largest share of all taxa investigated. Among them, Lactobacillus was negatively correlated with the other genera and positively correlated with serum estradiol levels. Logistic regression analysis suggested that the composition of the cervical microbiota on the day of ET was associated with the clinical pregnancy in fresh IVF-ET cycles (P = 0.030). Our results indicate that cervical microbiota composition has an impact on the outcome of assisted reproductive therapy.
Highlights
At least a billion microorganisms settle on the female reproductive tract and interact with the host to maintain a series of physiological processes such as immunity and metabolism (Jie et al, 2021)
To the best of our knowledge, this is the first study on the cervical microbiota of in vitro fertilization (IVF) patients with different clinical pregnancy outcomes
Whether in fresh or frozen-thawed embryo transfer (ET) cycles, Lactobacillus is the predominant genus present in the cervical microbiota of IVF patients
Summary
At least a billion microorganisms settle on the female reproductive tract and interact with the host to maintain a series of physiological processes such as immunity and metabolism (Jie et al, 2021). Researchers divided the cervicovaginal microbiota of women at childbearing age into six main community state types (CSTs), of which four were predominated by either Lactobacillus crispatus (CST I), Lactobacillus gasseri (CST II), Lactobacillus iners (CST III) or Lactobacillus jensenii (CST V), and two (CST IV-A and CST IV-B) comprised a wide array of strict and facultative bacterial anaerobes, where CST IV-A was characterized with the higher abundance of BVAB1 (Elovitz et al, 2019). The composition of the vaginal microbiota is affected by various factors including race, personal hygiene, sexual activity, and menstrual cycle (Gajer et al, 2012), with a shift to facultative or strictly anaerobic bacterial dominance causing the clinical syndrome called bacterial vaginosis (BV) (Mendling, 2016). Previous studies have demonstrated the association between BV and adverse obstetric outcomes such as late-term abortion and premature delivery (Nelson et al, 2007; Foxman et al, 2014)
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