ART and the Vaginal Microbiome

Women's health

ART and the Vaginal Microbiome

The link between the vaginal microbiome and pregnancy outcomes is so strong that someone’s vaginal microbiome can actually be used to predict IVF success

embryo-featus-in-womb-illustration

What is the vaginal microbiome?

Your vaginal microbiome is the community of microbes living in your vagina. A healthy vaginal microbiome typically has low diversity and is dominated by a type of good bacteria called Lactobacillus that can protect you from harmful microbes.

The upper female reproductive tract (including the uterus, fallopian tubes and ovaries) also has a microbiome. The microbiome of the upper reproductive tract has lower biomass (i.e. fewer microbes) and is more stable than the vaginal microbiome, but the two are inextricably linked. A healthy uterus is also dominated by lactobacilli [1] and certain changes in the vaginal microbiome exert an effect on the upper reproductive tract [2].  

When the balance of the microbiome in your reproductive tract is disrupted, known as “dysbiosis”, it can increase your risk of infertility problems and adverse pregnancy outcomes. 

What does the vaginal microbiome have to do with ART?

Assisted Reproductive Technology (ART) describes any type of fertility treatment where eggs or embryos are handled outside of the body [3]. The most common type of ART is in vitro fertilization (IVF).

We know that having lactobacilli dominate in your reproductive tract is good, but often patients undergoing ART do not. Multiple studies have found that most patients receiving ART have an “abnormal” endometrial or vaginal microbiome, but those whose ART is successful are usually the ones who have a healthy, Lactobacillus-dominated microbiome [4].

Fewer lactobacilli leaves room for more unfavorable bacteria, such as Enterococcus, Enterobacteriaceae (E. coli and Klebsiella spp.), Streptococcus, and Staphylococcus species, which are correlated with lower pregnancy and increased miscarriage rates [1].

A well-defined example of dysbiosis and poor pregnancy outcomes is in cases of chronic endometritis (CE). CE is the inflammation of the endometrium as a result of infection and is associated with recurrent implantation failure and miscarriage [5, 6]. It is often not detected because the symptoms are very mild or there are no symptoms at all. However, the vaginal microbiome of people with CE is typically more diverse and has less Lactobacillus than that of healthy people [7]. Successful antibiotic treatment of CE has been shown to improve the rate of implantation, clinical pregnancy, ongoing pregnancy and live births [8].

The link between the vaginal microbiome and pregnancy outcomes is so strong that scientists have shown that someone’s vaginal microbiome can actually be used to predict if their IVF will be successful or not, with an accuracy of 94% [9].

What should I look out for in my vaginal microbiome?

1. Good lactobacillus bacteria

Lactobacillus species such as L. crispatus, L. gasseri or L. jensenii should make up the majority of your vaginal microbiome.

2. Low diversity

Unlike your gut microbiome, where diversity is good, your vagina is happy with fewer types of bacteria. There should only be a small number of other species alongside your dominant Lactobacillus.

3. No disruptive bacteria

You ideally want no disruptive bacteria in your vagina, or a minimal amount. Bacteria such as Ureaplasma, Enterococcus, Enterobacteriaceae, Streptococcus, and Staphylococcus are not typically found in large quantities in a healthy vagina.

How can I improve my vaginal microbiome for ART?

Increasing the proportion of beneficial Lactobacillus and decreasing the number of bacterial pathogens in your reproductive tract could improve the pregnancy outcomes of people with abnormal microbiota who are undergoing ART [1].

The first step is to find out what is in your vaginal microbiome so you know what changes, if any, you need to make. If your vagina is already healthy it is best left alone. You can do more harm than good by trying to treat your microbiome in the wrong way.

If you identify disruptive bacteria in your microbiome, you may need specific antibiotic treatment and you should discuss this with your healthcare provider.

If you do not have any lactobacilli, you may benefit from probiotics containing vaginal strains of live Lactobacillus bacteria like L. crispatus, L. gasseri, L. jensenii

If you already have good lactobacilli, you do not need to take probiotics. However, if you only have a small amount of lactobacilli you may benefit from prebiotics to feed the good bacteria and encourage their growth.

Probiotics and prebiotics should be taken with caution as there is possible to have too much Lactobacillus. That’s why it is important to find out what is in your vagina before trying any treatments and, particularly if you are undergoing fertility treatment, to discuss any treatments with your healthcare provider first.

Vaginal microbiome testing provides an easy, cost-effective screen to rule out vaginal dysbiosis as a potential risk factor for adverse ART outcomes.

References
  1. Moreno, I, Simon, C. Deciphering the effect of reproductive tract microbiota on human reproduction. Reprod Med Biol. 2019; 18: 40–50
  2. Wang, J., Li, Z., Ma, X. et al. Translocation of vaginal microbiota is involved in impairment and protection of uterine health. Nat Commun. 2021; 12:4191.
  3. Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion. Infertility. 2021. Available from: https://www.cdc.gov/reproductivehealth/infertility/index.htm [Accessed 28th Apr 2022]
  4. Schoenmakers, S, Laven, J. The vaginal microbiome as a tool to predict IVF success, Curr Opin Obstet. 2020; 32(3): 169-178
  5. Cicinelli E, Matteo M, Tinelli R, Lepera A, Alfonso R, Indraccolo U, Marrocchella S, Greco P, Resta L. Prevalence of chronic endometritis in repeated unexplained implantation failure and the IVF success rate after antibiotic therapy. Hum Reprod. 2015; 30(2): 323-30
  6. Zolghadri J, Momtahan M, Aminian K, Ghaffarpasand F, Tavana Z. The value of hysteroscopy in diagnosis of chronic endometritis in patients with unexplained recurrent spontaneous abortion. Eur J Obstet Gynecol Reprod Biol. 2011; 155(2): 217-20.
  7. Lozano FM, Bernabeu A, Lledo B, Morales R, Diaz M, Aranda FI, Llacer J, Bernabeu R. Characterization of the vaginal and endometrial microbiome in patients with chronic endometritis. Eur J Obstet Gynecol Reprod Biol. 2021; 263: 25-32.
  8. Cicinelli E, Matteo M, Tinelli R, et al. Chronic endometritis due to common bacteria is prevalent in women with recurrent miscarriage as confirmed by improved pregnancy outcome after antibiotic treatment. Reprod Sci. 2014; 21(5): 640-647.
  9. R Koedooder, M Singer, S Schoenmakers, P H M Savelkoul, S A Morré, J D de Jonge, L Poort, W J S S Cuypers, N G M Beckers, F J M Broekmans, B J Cohlen, J E den Hartog, K Fleischer, C B Lambalk, J M J S Smeenk, A E Budding, J S E Laven, The vaginal microbiome as a predictor for outcome of in vitro fertilization with or without intracytoplasmic sperm injection: a prospective study, Hum Reprod. 2019; 34(6): 1042–1054,
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Attributions
Ruth Richards, MSc
Ruth Richards, MSc

Ruth Richards was a Scientist at Juno Bio where she worked on the development of our metagenomics discovery platform. She holds a MSc in Bioinformatics and Theoretical Systems Biology from Imperial College London.

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Leighton Turner, PhD
Leighton Turner, PhD

Leighton Turner is a PhD in Molecular Genetics and is Juno Bio's Chief Technology Officer.

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