Inside the Reproductive Microbiome: A Three-Part Series About Fertility, Testing & Treatment
Part 1: Understanding the Landscape "Tiny Ecosystems, Big Impact: What We Know About the Reproductive Microbiome and Fertility"
A note on gender and language: the word “female” is used to refer to anyone, of any gender identity, who has a uterus and/or a vagina.
A glossary of terms is included at the end of this blog.
Information about the gut microbiome is everywhere these days - even your doctor is probably encouraging you to start eating more sauerkraut and yogurt, and for good reason! However, it’s not just your digestive system that has its own special ecosystem of helpful and harmful bacteria. An emerging area of microbiome research focuses on the bacteria living within the female reproductive tract. If you’ve ever battled a vaginal yeast infection or case of bacterial vaginosis, you have some intimate familiarity with your reproductive microbiome.
The Reproductive Tract Is Not Sterile
From the vagina to the cervix, uterus, and even follicular fluid, we now know that the upper reproductive tract is not a sterile environment by any means. Each of these areas has its own distinct bacterial and microbial compositions. What’s more is that research suggests that changes in each environment can have an impact on female fertility and pregnancy outcomes. A 2020 study by Rowe et al., looked at the microbiota of ovarian follicular fluid in women undergoing IVF treatment and found that bacteria belonging to the genus Lactobacillus spp. were associated with higher rates of successful embryo transfer and improved pregnancy outcomes compared to other genera of bacteria (Rowe et al., 2020).
Similarly, an endometrial microbiome made up of greater than 90% Lactobacillus spp. and less than 10% other bacteria was found to be more conducive to embryo implantation, ongoing pregnancy, and live birth (Rowe, 2020). Lactobacillus spp. also plays an important role in the vaginal microbiome. A reduction in Lactobacillus spp. in the vagina is associated with many adverse outcomes, including but not limited to preterm birth, pelvic inflammatory disease, increased risk and transmission of sexually transmitted infection and infertility (Petrova, et al., 2015 as cited in Younes et al., 2018).
Dysbiosis is an imbalance of bacteria that can occur when there are too few beneficial bacteria or too many potentially harmful bacteria. Vaginal dysbiosis can appear with some common infections like yeast and bacterial vaginosis. In addition to these more common infections, elevated levels of certain types of unhelpful reproductive bacteria along with low levels of friendly ones, has been associated with struggles to get and/or stay pregnant as well as the diagnosis of endometriosis (Koedooder et al., 2019). Such troublesome bacteria include Staphylococcus, Streptococcus, Enterococcus, Ureaplasma Atopobium, and Gardnerella. These types of disrupted vaginal microbiomes have been associated with decreased implantation, conception, and ongoing pregnancy rates as well as increased rates of early pregnancy loss (Koedooder 2019). This type of vaginal dysbiosis has also been associated with an increase in early pregnancy loss rate and lower rates of clinical pregnancies per embryo transfer among women undergoing IVF (Lledo 2022).
Conversely, higher levels of Lactobacillus spp. in the vagina have been associated with positive outcomes from assisted reproductive technologies like embryo transfers, higher implantation rates, pregnancy rates, and ongoing pregnancy rates (Koedooder 2019; Younes et al., 2018).
The Ebb and Flow of the Vaginal Microbiome
Given its accessibility, the vaginal microbiome is certainly the easiest of the reproductive microbiomes to study. We know that the vagina, like many other areas of the reproductive tract, is dominated by Lactobacillus species. Depending on the level of Lactobacillus versus other genera found, vaginal microbiomes are organized into five distinct categories, or Community State Types (CSTs). You can learn more about these five CTSs in the glossary below. In a nutshell, a healthy vaginal microbiome, which seems to be related to increased fertility, is one with low bacterial diversity and high levels of Lactobacillus spp. (Lehtoranta et al., 2022).
What is it about Lactobacillus spp. that makes it such a great vaginal ally? Well, several things. First, a reproductive microbiome colonized by Lactobacillus spp. is much less susceptible to colonization by unfavorable bacteria simply because of resource restriction. There’s not an infinite amount of space in the vagina, so every square micrometer occupied up by happy little bacteria is a micrometer less for a bacterial foe to colonize. Lactobacillus spp. also produces lactic acid which not only has antimicrobial properties but helps to maintain optimal vaginal pH which in turn makes the vagina inhospitable to pathogens (Rowe 2020; Liu et al., 2023).
Lactobacillus spp. isn’t the only guardian of healthy vaginal pH levels. Estrogen, due to its role in lowering vaginal pH and keeping the vagina’s mucosal layer healthy, is helpful in maintaining Lactobacillus spp. dominance. The vaginal microbiome fluctuates in response to estrogen levels. During pregnancy, when estrogen production in the body increases (thanks, placenta!), Lactobacillus spp. dominance is increased, and the composition of vaginal microbiota is much more stable. In times of life when estrogen levels are low, like postpartum (bye, placenta!) and in menopause (bye, ovarian function!), the vaginal microbiome often presents with a more diverse bacterial composition, lower levels of lactobacillus, and potentially an increase in vaginal infections and symptoms (MacIntyre et al., 2015; Auriemma et al., 2021).
Because high levels of Lactobacillus spp. often correlate to lower levels of other bacteria and vice versa, it's hard to say whether the presence of Lactobacillus spp. or of unfriendly bacteria is more important when it comes to fertility. We do know, however, that these less friendly bacteria can cause a variety of things that create unfavorable implantation and pregnancy environments like causing yeast infections or bacterial vaginosis. Some, like a strain of Staphylococcus that can be found in the cervix, has a direct effect on insemination, causing sperm agglutination and death during in vitro experimentation (Rowe et al., 2020).
The Gut-Vagina Axis
Although we’ve been focusing predominantly on the bacteria living within the vagina and upper reproductive tract, we would be remiss not to mention the mother of all microbiomes - the gut. Most people living with a vagina understand this “gut-vagina axis” on an intuitive level. Who hasn't had to deal with an uncomfortable yeast infection after taking a round of antibiotics? And, further illustrating the close connection between the gut and vagina, one of the most effective ways to manage that vaginal yeast infection is an anti-candida diet.
But, it’s always nice when science corroborates what we already know intuitively. According to our current and evolving understanding in this area, there are three main ways the gut microbiome can influence the reproductive microbiome, particularly within the vagina. This can be referred to as the “gut-vagina axis” (Thomas-White, 2025).
First, the gut acts as a kind of “reservoir” for bacteria that are then liable to make their way into other accessible areas of the body, like the vagina. The bacteria of the gut and vagina are particularly linked because of their close proximity to one another. Especially with cases of bacterial vaginosis, antagonistic bacteria are often found to have previously colonized the gut prior to colonizing the vagina (Marrazzo et al., 2012). Secondly, imbalances in the gut can contribute to widespread inflammation which leaves many body systems, including the reproductive tract, vulnerable to infection. The third way that the gut and vagina are connected on a microbiotic level has to do with hormones. As described above, estrogen and other hormones play important roles in creating and maintaining an environment that is hospitable to beneficial bacteria. The gut, interestingly, plays an important role in regulating hormone levels within the body. A healthy gut encourages healthy hormone levels which encourages a healthy vaginal microbiome (Evvy, 2025).
Research around the gut-vagina axis is evolving. Despite the fact that we need more studies about the intricacies and importance of this relationship, it is abundantly clear that there is one.
Stay tuned for Part 2 which is all about testing, and Part 3 on treatment options.
Glossary
Microbiome: The total genomic (DNA) content of the microbiota. The microbiome refers to not only the microbiota, but their genetic material, metabolites, environmental conditions, and other factors.
Microbiota: The bacteria, fungi, yeast and archaea that make up the microbiome.
Microbes: Microscopic organisms, aka microorganisms, that exist all around us. Includes bacteria, viruses, fungi, and more
Holobionts: A holobiont is an assemblage of a host and the many other species living in or around it, which together form a discrete ecological unit through symbiosis.
Dysbiosis: Bacterial imbalance
Levels of taxonomic classification from broadest to most specific: Domain, Kingdom, Phylum, Class, Order, Family, Genus (i.e Lactobacillus), Species (i.e crispatus)
Genera: plural of genus
Implantation failure: As defined by IVF clinics: Failure to achieve clinical pregnancy after transfer of at least four good quality embryos in at least three fresh or frozen cycles in a woman under 40 years of age
Lactobacillus: A genus of bacteria commonly found throughout the vaginal (and gut) microbiome. There are several different relevant species of Lactobacillus that are found in the vaginal microbiome, including crispatus, gasseri, iners, and jensenii.
Community State Types: categories of vaginal microbiome composition indicative of overall vaginal health. CSTs are determined based on the tested microbiome’s dominant bacteria. There are 5 CSTS:
Type 1: Dominated by Lactobacillus crispatus, typically protective
Type 2: Dominated by Lactobacillus gasseri, typically protective
Type 3: Dominated by Lactobacillus iners, typically neutral, may be protective or disruptive
Type 4: Diverse bacteria, no Lactobacillus dominance, typically disruptive
Type 5: Dominated by Lactobacillus jensenii, typically protective
References
Auriemma, Renata S., et al. “The Vaginal Microbiome: A Long Urogenital Colonization throughout Woman Life.” Frontiers, Frontiers, 21 June 2021, www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2021.686167/full.
Banfield-Nwachi, Mabel. “The Vaginal Microbiome: How to Look after It – and What to Avoid.” The Guardian, Guardian News and Media, 11 Sept. 2023, www.theguardian.com/society/2023/sep/11/the-vaginal-microbiome-how-to-look-after-it-and-what-to-avoid.
Cassano, Olivia. “Fact Check: Do Period Products Affect Vaginal Health?” RSS, Evvy, 7 May 2024, www.evvy.com/blog/do-period-period-products-affect-vaginal-health?_kx=0mvZjwCmF979VA6gbQtckrMizCkjDZKPHu50zH8TLUeLPoOWtTSjH37-UrWhL-Tk.VJFqcy.
Koedooder, R et al. “The vaginal microbiome as a predictor for outcome of in vitro fertilization with or without intracytoplasmic sperm injection: a prospective study.” Human reproduction (Oxford, England) vol. 34,6 (2019): 1042-1054. doi:10.1093/humrep/dez065
Kostakioti, M., Hadjifrangiskou, M., & Hultgren, S. J. (2013). Bacterial biofilms: development, dispersal, and therapeutic strategies in the dawn of the postantibiotic era. Cold Spring Harbor perspectives in medicine, 3(4), a010306. https://doi.org/10.1101/cshperspect.a010306
Lehtoranta, Liisa, et al. “Healthy Vaginal Microbiota and Influence of Probiotics across the Female Life Span.” Frontiers, Frontiers, 22 Feb. 2022, www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.819958/full.
Liu, Peng, et al. “Use of Probiotic Lactobacilli in the Treatment of Vaginal Infections: In Vitro and in Vivo Investigations.” Frontiers, Frontiers, 23 Mar. 2023, www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2023.1153894/full.
Lledo, B., et al. “Identification of Vaginal Microbiome Associated with IVF Pregnancy.” Nature News, Nature Publishing Group, 26 Apr. 2022, www.nature.com/articles/s41598-022-10933-2.
MacIntyre, David A., et al. “The Vaginal Microbiome during Pregnancy and the Postpartum Period in a European Population.” Nature News, Nature Publishing Group, 11 Mar. 2015, www.nature.com/articles/srep08988.
Marrazzo, Jeanne M et al. “Extravaginal reservoirs of vaginal bacteria as risk factors for incident bacterial vaginosis.” The Journal of infectious diseases vol. 205,10 (2012): 1580-8. doi:10.1093/infdis/jis242
Petrova, M. I., Lievens, E., Malik, S., Imholz, N., & Lebeer, S. (2015). Lactobacillus species as biomarkers and agents that can promote various aspects of vaginal health. Frontiers in physiology, 6, 81. https://doi.org/10.3389/fphys.2015.00081
Rowe, Melissah et al. “The Reproductive Microbiome: An Emerging Driver of Sexual Selection, Sexual Conflict, Mating Systems, and Reproductive Isolation.” Trends in ecology & evolution vol. 35,3 (2020): 220-234. doi:10.1016/j.tree.2019.11.004
Abbe, Carmen, and Caroline M. Mitchell. “Bacterial Vaginosis: A Review of Approaches to Treatment and Prevention.” Frontiers, Frontiers, 15 May 2023, www.frontiersin.org/journals/reproductive-health/articles/10.3389/frph.2023.1100029/full.
Song SD, Acharya KD, Zhu JE, Deveney CM, Walther-Antonio MRS, Tetel MJ, Chia N, 2020.Daily Vaginal Microbiota Fluctuations Associated with Natural Hormonal Cycle, Contraceptives, Diet, and Exercise. mSphere5:10.1128/msphere.00593-20.https://doi.org/10.1128/msphere.00593-20
Thomas-White, Krystal. “The Gut-Vagina Axis: Evvy.” RSS, Evvy, 2 Jan. 2025, www.evvy.com/blog/gut-vagina-axis.
Younes, Jessica A, et al. “Women and Their Microbes: The Unexpected Friendship.” Trends in Microbiology, U.S. National Library of Medicine, pubmed.ncbi.nlm.nih.gov/28844447/. Accessed 2 Dec. 2024.
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Arrive Reproductive Medicine is an acupuncture and functional medicine practice dedicated to fertility and hormone support. When it comes to fertility, we know how exhausting it can be to not only navigate treatment but also stay informed about the constantly changing research and best practices in the field. We stay up to date on all the latest research in the field of reproductive medicine so that you can dedicate all your energy to growing your family.
Authors:
Anne Chiaramonte, licensed acupuncturist and owner, Arrive Reproductive Medicine
Clara Miller, certified doula and owner, Portal Birthwork
