Characterization of the Vaginal Microbiome in Women with Infertility and Its Potential Correlation with Hormone Stimulation during <i>In Vitro</i> Fertilization Surgery

Abstract

Perturbation of vaginal microbiome of reproductive-age women influences all the phases of a woman's reproductive life. Although studies have shown that dynamic changes in vaginal microbiome can affect pregnancy, its role in secondary infertility (i.e., inability to become pregnant or to carry a pregnancy successfully after previous success in delivering a child) and <i><u>i</u>n <u>v</u>itro</i> <u>f</u>ertilization (IVF) remains to be unraveled. To determine the vaginal microbiome in women undergoing <i><u>i</u>n <u>v</u>itro</i> <u>f</u>ertilization and <u>e</u>mbryo <u>t</u>ransfer (IVF-ET) and investigate its potential correlations with hormone stimulation, we recruited 30 patients with secondary infertility and receiving IVF and 92 matched healthy women and analyzed their vaginal microbiome composition using 16S rRNA gene sequencing. Our results show that women suffering from infertility (infertile women) exhibit a significant decrease in microbiome diversity and richness compared with healthy women during the nonovulation period (follicular phase) (<i>P < </i>0.01), whereas vaginal microbiome of healthy women reveals dramatic fluctuations during ovulation (<i>P < </i>0.05). Interestingly, infertility patients show no change of the vaginal microbiome under conditions of <u>g</u>o<u>n</u>adotropin-<u>r</u>eleasing <u>h</u>ormone (GnRH) agonist and <u>r</u>ecombinant <u>h</u>uman <u>c</u>horionic <u>g</u>onadotropin (r-hCG) induction (<i>P > </i>0.05). Moreover, our results indicate that infertile women show characteristic variations in vaginal microbiome, such as increased abundance <i>of Atopobium, Aerococcus</i>, and <i>Bifidobacterium</i> and decreased abundance of <i>Lactobacillus</i> and <i>Leuconostoc</i> <b>IMPORTANCE</b> The microbiome had been hypothesized to be involved in the physiology and pathophysiology of assisted reproduction before the first success in IVF, while the data supporting or refuting this hypothesis were less than conclusive. Thanks to sequencing data from the 16S rRNA subunit, we characterized the microbiome in the reproductive tract of infertile women, and we found that changes in the vaginal microbiome are related to female infertility. We also found that the characteristic microbiome bacteria are mainly members of several genera and that the vaginal microbiome of infertile women is not sensitive to hormonal changes during IVF. In conclusion, our report provides data that can be used for discovering the role of the vaginal microbiome in patients suffering from secondary infertility.