The association between the pre-pregnancy vaginal microbiome and time-to-pregnancy: a Chinese pregnancy-planning cohort study

Abstract

Background Although sexually transmitted infections are regarded as the main cause of tubal infertility, the association between the common vaginal microbiome and female fecundability has yet to be determined. The objective of this study was to find convincing evidence relating to the impact of the vaginal bacterial structure on the fecundability of women planning pregnancy. Methods We recruited women who took part in the Free Pre-pregnancy Health Examination Project from 13 June 2018 to 31 October 2018 (n = 89, phase I) and from 1 November 2018 to 30 May 2020 (n = 389, phase II). We collected pre-pregnancy vaginal swabs from each subject; then, we followed up each subject to acquire the pregnancy-planning outcome in 1 year. In phase I, 16S rRNA gene sequencing was performed to investigate the vaginal bacterial content between the pregnancy and non-pregnancy groups. These findings were verified in phase II by applying a quantitative real-time polymerase chain reaction for the measurement of the absolute abundance of specific species. Cox models were used to estimate fecundability ratios (FR) for each vaginal microbiome type. Results In phase I, 59.6% (53/89) of women became pregnant within 1 year. The principal coordinate analysis showed that the pre-pregnancy vaginal microbial community structures of the pregnant and non-pregnant groups were significantly different (PERMANOVA test, R2 = 0.025, P = 0.049). The abundance of the genus Lactobacillus in the pregnancy group was higher than that of the non-pregnant group (linear discriminant analysis effect size (LDA) > 4.0). The abundance of the genus Gardnerella in the non-pregnant group was higher than those in the pregnant group (LDA > 4.0). In phase II, female fecundability increased with higher absolute loads of Lactobacillus gasseri (quartile Q4 vs Q1, FR = 1.71, 95%CI 1.02–2.87) but decreased with higher absolute loads of Fannyhessea vaginae (Q4 vs Q1, FR = 0.62, 95%CI 0.38–1.00). Clustering analysis showed that the vaginal microbiome of type D (characterized by a higher abundance of Lactobacillus iners, a lower abundance of Lactobacillus crispatus and Lactobacillus gassri) was associated with a 55% reduction of fecundability (FR = 0.45, 95%CI 0.26–0.76) compared with type A (featuring three Lactobacillus species, low Gardnerella vaginalis and Fannyhessea vaginae abundance). Conclusions This cohort study demonstrated an association between the pre-pregnancy vaginal microbiome and female fecundability. A vaginal microbiome characterized by a higher abundance of L. iners and lower abundances of L. crispatus and L. gasseri appeared to be associated with a lower fecundability. Further research now needs to confirm whether manipulation of the vaginal microenvironment might improve human fecundability.

Association between adverse nutrition status by BMI and increased time-to-pregnancy in planed pregnancy couples: A cohort study in Guangzhou, China

“…In this cohort study, 1,684 couples were included, with 1,127 achieving pregnancy, constituting 67.0% of the total couples included. The observed pregnancy rate surpassed that of other NFPCP-related studies [23,25], potentially attributed to excluding couples discontinuing efforts to conceive after the examination in our inclusion analysis. In three distinct Cox regression models, both overweight and obesity in both males and females were linked to prolonged TTP compared to normal weight.…”

Change of the vaginal microbiome with oral contraceptive therapy in women with polycystic ovary syndrome: a 6-month longitudinal cohort study

“…The frozen swabs were eluted with phosphate-buffered saline, and TIANamp bacterial DNA kits (Tiangen Biochemical Technology, Beijing, China) were used to extract and purify the nucleic acids. DNA was extracted, as previously described [ 17 ]. Using universal primers (338F:5′-ACTCCTACGGGAGGCAGCA-3′, 806R:5′-GGACTACHVGGGTWTCTAAT-3′), the V3–V4 region of the 16S rRNA gene was amplified by polymerase chain reaction and then sequenced on an Illumina HiSeq 2500 platform (Beijing Biomarker Technologies Co. Ltd. Beijing, China).…”

Microbial transmission, colonisation and succession: from pregnancy to infancy

“…Although much attention on the female microbiome has been focused on the perinatal period, the prepregnancy microbiome, which may play a vital role in fecundability and pregnancy outcomes, cannot be ignored. 17 The microbiome composition of healthy nonpregnant women varies depending on genetics, ethnicity, age, lifestyle and daily diet. [18][19][20][21][22][23][24] In general, microbial diversity decreases with increasing industrialisation.…”