The human microbiome plays a significant role in determining the health status of every human body and in fact, bacterial communities coexist in mutualistic symbiotic relationships with the host. Whipps originally defined the term microbiome as “a characteristic microbial community occupying a reasonably well-defined habitat which has distinct physio-chemical properties” Bacterial cells in the human body account for 1-3% of total body weight and are at least equal in number to human cells.
Today, this definition is enriched by a dynamic consideration of microbial activities that result in ecological niches. Specifically, how the microbiome interacts with the host to maintain a healthy environment. Variations in the microbiome’s composition can lead to dysbiosis (imbalance in the microbiome), particularly in stress conditions, where the rapid decrease of microbial diversity promotes the expansion of specific bacteria or pathogens.
A genital Lactobacillus-dominated flora plays a pivotal role in determining fertility and in particular Lactobacillus crispatus. Lactobacilli dominate the microbial community and are commonly associated with a healthy genital status. Lactobacilli produce lactic acid and protect the vagina by maintaining a low pH that is prohibitive to the growth of most pathogenic bacteria. The presence of pathogens in the genital tract, such as Chlamydia trachomatis, Gardnerella vaginalis (Bacterial Vaginosis), Ureaplasma species, and Gram-negatively stained microorganisms, affect fertility. A non-Lactobacillus-dominated microbiome was shown to be associated with dysbiosis. This imbalance has a negative impact on implantation rates in procedures such as IVF and may also be responsible for habitual abortions. A complex interaction of the Lactobacillus species plays a pivotal role in the equilibrium of the normal vaginal flora and in particular appropriate levels of Lactobacillus crispatus are involved as a protective factor against asymptomatic Bacterial Vaginosis (mostly caused by Ureaplasma and Gardnerella vaginalis) a potential impairing factor in infertility. The presence in the cervical flora of Gram-negative bacteria, such as Chlamydia trachomatis and Gardnerella vaginalis, and the lack of Lactobacillus is closely linked with the inability to conceive.
The importance of Lactobacillus specifically Lactobacillus crispatus is linked to its ability to synthesize lactic acid. Estrogen (Estradiol -E2) controls lactic acid production that contributes to the acidic vaginal environment (pH ≈3.0–4.6), suitable for Lactobacillus bacteria harboring, and enabling them to grow, multiply, and dominate the cervicovaginal niche. In addition, lactic acid is considered a healthy Vaginal Mic Microbiome (VMB) marker, due to its mild-acid pH shift, which makes the cervicovaginal environment unsuitable for pathogenic bacterial colonization. To kill other bacteria and to prevent vaginal colonization by pathogens, Lactobacillus crispatus synthesizes hydrogen peroxide (H2O2) and bacteriocins proteins, with also contribute to maintaining a healthy genitourinary status.
In one study, catheters were used to assess the presence of cervical microorganisms and their impact on IVF outcomes. In 143 (51%) of 279 ETs, cultures were positive for pathogenic bacteria, predominantly Escherichia coli (E. Coli) (64%) and Streptococcus species (8%). Although data on patients, IVF procedure, and embryo quality were similar in both the normal and the group with pathogenic bacteria, clinical and ongoing pregnancy rates, as well as implantation rates, were significantly lower in the positive pathogenic bacteria culture group than in the negative (normal) culture group (clinical pregnancy – 6 weeks 24% versus 37%; Ongoing pregnancy 12 weeks 17% versus 28%; and implantation rates 9% versus 16%, respectively).
In another prospective study when bacterial communities from paired endometrial (lining of the uterus) 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. The women were divided into two groups Lactobacillus-dominated microbiota (>90% Lactobacillus spp.) or a non-Lactobacillus-dominated microbiota (<90% Lactobacillus spp. with >10% of other bacteria). The presence of a non-Lactobacillus-dominated microbiota in a receptive endometrium was associated with significant decreases in implantation [60.7% vs 23.1% (P = .02)], pregnancy [70.6% vs 33.3% (P = .03)], ongoing pregnancy [58.8% vs 13.3% (P = .02)], and live birth [58.8% vs 6.7% (P = .002)] rates.
These results demonstrate the existence of a lactobacillus-dominated endometrial microbiome is highly stable and promotes implantation and pregnancy. However, pathological modification of the microbiome is associated with poor reproductive outcomes.
