Association between bacterial vaginosis and fecundability in Kenyan women planning pregnancies: a prospective preconception cohort study

Abstract

STUDY QUESTION Is bacterial vaginosis (BV) associated with fecundability? SUMMARY ANSWER Women with BV may be at increased risk for sub-fecundity. WHAT IS KNOWN ALREADY While BV has been associated with poor IVF outcomes, the association between vaginal microbiota disruption and non-medically assisted conception has not been thoroughly explored. STUDY DESIGN, SIZE, DURATION Kenyan women with fertility intent were enrolled in prospective cohort that included monthly preconception visits with vaginal fluid specimen collection and pregnancy testing. Four hundred fifty-eight women attempting pregnancy for ≤3 menstrual cycles at enrollment were eligible for this fecundability analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS At monthly preconception visits, participants reported the first day of last menstrual period and sexual behavior, underwent pregnancy testing and provided vaginal specimens. Discrete time proportional probabilities models were used to estimate fecundability ratios (FRs) and 95% CI in menstrual cycles with and without BV (Nugent score ≥ 7) at the visit prior to each pregnancy test. We also assessed the association between persistent BV (BV at two consecutive visits) and fecundability. MAIN RESULTS AND THE ROLE OF CHANCE Participants contributed 1376 menstrual cycles; 18.5% (n = 255) resulted in pregnancy. After adjusting for age, frequency of condomless sex and study site, BV at the visit prior to pregnancy testing was associated with a 17% lower fecundability (adjusted FR (aFR) 0.83, 95% CI 0.6–1.1). Persistent BV was associated with a 43% reduction in fecundability compared to cycles characterized by optimal vaginal health (aFR 0.57, 95% CI 0.4–0.8). LIMITATIONS, REASONS FOR CAUTION Detection of vaginal microbiota disruption using Gram stain and a point-of-care test for elevated sialidase identified a non-optimal vaginal environment, but these non-specific methods may miss important relationships that could be identified by characterizing individual vaginal bacteria and bacterial communities using molecular methods. In addition, results may be subject to residual confounding by condomless sex as this was reported for the prior month rather than for the fertile window during each cycle. WIDER IMPLICATIONS OF THE FINDINGS Given the high global prevalence of BV and infertility, an association between BV and reduced fecundability could have important implications for a large number of women who wish to conceive. Multi-omics approaches to studying the vaginal microbiota may provide key insights into this association and identify potential targets for intervention. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by a National Institutes of Health grant (NICHD R01 HD087346-R.S.M.). R.S.M. received additional support for mentoring (NICHD K24 HD88229). E.M.L. was supported by pre- and post-doctoral fellowships (NIAID T32 AI07140, NICHD F32 HD100202). Data collection and management were made possible using REDCap electronic data capture tools hosted at the University of Washington’s Institute of Translational Health Science supported by grants from NCATS/NIH (UL1 TR002319). The content of this paper is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. R.S.M. receives research funding, paid to the University of Washington, from Hologic Corporation, and has received honoraria for consulting from Lupin Pharmaceuticals. L.E.M. receives research funding, paid to the University of Washington, from Hologic Corporation, and has received honoraria for service on scientific advisory boards from Hologic and Nabriva Therapeutics. TRIAL REGISTRATION NUMBER N/A.

Vaginal washing behaviour and fecundability among Kenyan women in a prospective preconception cohort

“…9,23,24 We previously reported associations between recent and persistent BV and lower fecundability in this cohort. 13 Our current analysis assessing vaginal washing had similar results in adjusted models with or without BV. Due to the timing of sample collection visits and monthly assessment of vaginal washing behaviour, we are unable to employ marginal structural models to assess mediation of the association between vaginal washing and lower fecundability by BV.…”

“…Whether associations between vaginal washing and adverse reproductive outcomes are causal versus due to a BV episode that precipitated the vaginal washing is debated 9,23,24 . We previously reported associations between recent and persistent BV and lower fecundability in this cohort 13 . Our current analysis assessing vaginal washing had similar results in adjusted models with or without BV.…”

“…In July 2018, a question was added to the monthly interview for report of additional first days of LMPs (‘interim menstrual cycles’) for women who missed preconception visits ( n = 82 cycles reported). One‐hundred and thirty participants had visits prior to July 2018, and in these cases, ‘interim menstrual cycles’ were derived ( n = 41 cycles), as previously described 13 …”

“…For each participant, number of menstrual cycles to first incident pregnancy was calculated using reported first days of LMPs and monthly urine pregnancy test results. 13 In July 2018, a question was added to the monthly interview for report of additional first days of LMPs ('interim menstrual cycles') for women who missed preconception visits (n = 82 cycles reported). One-hundred and thirty participants had visits prior to July 2018, and in these cases, 'interim menstrual cycles' were derived (n = 41 cycles), as previously described.…”

The associations between low abundance of Mycoplasma hominis and female fecundability: a pregnancy-planning cohort study

“…A meta-analysis showed that the female infertility was associated with vaginal microbiota, [ 3 ] but most evidence was derived from case–control studies, which limited the causal inference. Recently, two prospective cohort studies illustrated that the female time-to-pregnancy (TTP) index was associated with the vaginal microenvironment or bacterial vaginitis (BV) status [ 4 , 5 ]. TTP is a typical indicators reflecting couples’ fecundability, which is defined as a couple’s probability of conception in one menstrual cycle, given regular intercourse and no method of contraception [ 6 ].…”