Does microbiota play a role in infertility?

To start, a frequently asked question: what is infertility?

Prof. Ina Schuppe-Koistinen: According to the WHO, infertility is a disease of the male or female reproductive system defined by the failure to achieve a pregnancy after 12 months or more of regular unprotected sexual intercourse ¹. The methods used to estimate its frequency varies across research studies, and this variation makes it difficult to understand and estimate the magnitude of the problem. However, the World Health Organization (WHO) estimates that the Infertility affects approximately 15% of all couples of reproductive age worldwide, this having an impact on their families and communities ^1,2 but this figure masks considerable variation within and between countries. Infertility can be primary or secondary. Primary infertility is when a pregnancy has never been achieved and secondary infertility is when at least one prior pregnancy has been achieved.

Is a treatment currently available to help couples?

I.S.-K.: Infertility is treated with assisted reproduction technologies (sidenote: Assisted Reproduction Technologies (ART) ART includes all fertility treatments in which either eggs or embryos are handled. In general, ART procedures involve surgically removing eggs from a woman’s ovaries, combining them with sperm in the laboratory, and returning them to the woman’s body or donating them to another woman. They do NOT include treatments in which only sperm are handled (i.e., intrauterine—or artificial—insemination) or procedures in which a woman takes medicine only to stimulate egg production without the intention of having eggs retrieved. ) (ART), such as in vitro fertilization (IVF) that have been available for more than three decades, with more than 5 million children born worldwide. However, these technologies are still largely unavailable, inaccessible and unaffordable in many parts of the world, particularly in low and middle-income countries.

Which role plays the vaginal microbiota in infertility?

I.S.-K.: In addition to healthy reproductive organs, a successful pregnancy relies on a functional crosstalk between the immune system and expression of hormones enabling fertilization and implantation of the semi-foreign embryo, while at the same time preventing entry and colonization of pathogens (sidenote: Pathogens A pathogen is a microorganism that causes, or may cause, disease. Pirofski LA, Casadevall A. Q and A: What is a pathogen? A question that begs the point. BMC Biol. 2012 Jan 31;10:6. ) . A healthy vaginal microbiota is dominated by Lactobacillus (sidenote: Lactobacilli Rod-shaped bacteria whose main characteristic is the production of lactic acid, from where they get the name “lactic acid bacteria”.  Lactobacilli are present in the oral, vaginal and gut microbiota of humans, but also in plants and animals. They are found in fermented foods, such as dairy products (e.g. certain cheeses and yoghurts), pickles, sauerkraut, etc. Lactobacilli are also found in probiotics, with certain species recognized for their beneficial properties.   W. H. Holzapfel et B. J. Wood, The Genera of Lactic Acid Bacteria, 2, Springer-Verlag, 1st ed. 1995 (2012), 411 p. « The genus Lactobacillus par W. P. Hammes, R. F. Vogel Tannock GW. A special fondness for lactobacilli. Appl Environ Microbiol. 2004 Jun;70(6):3189-94. Smith TJ, Rigassio-Radler D, Denmark R, et al. Effect of Lactobacillus rhamnosus LGG® and Bifidobacterium animalis ssp. lactis BB-12® on health-related quality of life in college students affected by upper respiratory infections. Br J Nutr. 2013 Jun;109(11):1999-2007. ) species that helps protect against pathogens by producing lactic acid and other molecules that kill pathogens. By that, a vaginal microbiota dominated by Lactobacillus species is important for fertility.

There are a number of studies that associate high levels of inflammatory cells and raised inflammation markers in the vagina and uterus of women with unexplained infertility. Several studies link the vaginal microbiota as driver of local inflammation executed by both compounds produced by the vaginal microbes and inflammatory host response factors ^3,4. With other words, a dysbiotic vaginal microbiota contributes to an inflammatory state that has a negative impact on fertility. 
Finally, several studies have demonstrated an association between the microbiota and diseases and infections influencing fertility, such as bacterial vaginosis, cervical cancer, polycystic ovary syndrome and endometriosis. More research on how the microbiota influences fertility is vital ⁵.

What about bacterial vaginosis?

I.S.-K.: Bacterial vaginosis is a common cause of vaginal inflammation and discomfort in women of reproductive age. In bacterial vaginosis the healthy vaginal microbiota is overtaken by less favorable bacteria. Although the composition of the bacteria in bacterial vaginosis varies between individuals, there are some species such as Gardnerella, Atopobium, Snethia, Megasphera, Dialister and others, that are found most frequently ⁶. The microbial composition of bacterial vaginosis has been linked to various pregnancy outcomes including pre-term birth, and can also affect the semen microbiota after intercourse, which in term could affect sperm quality or motility. The link to infertility is not fully established but data suggests that bacterial vaginosis is leading to reduced fertility ⁷.

Does a perturbation of the vaginal flora have an impact on the outcome of assisted reproductive technology procedures?

I.S.-K.: Studies have shown that a healthy vaginal microbiota with certain Lactobacillus species during assisted reproductive technology procedures may have a positive impact on success while women with bacterial vaginosis have poorer results.

May gut health through intestinal microbiota affect the fertility?

I.S.-K.: The microbiota of the female reproductive tract accounts for approximately 10% of the body’s total microbial population. The vast majority of human microbes are found in the gut. They are highly connected to our health and do not only influence the intestinal milieu but also other organs in the body. Vaginal microbes are mainly derived from the gut, although those mechanisms are not well understood yet. As gut microbes metabolize the female sex hormone estrogen, they are directly affecting female physiology and reproductive health. Therefore, a healthy gut microbiome is not only important for good health but also fertility.

What about men: could the men genital microbiota play a role in fertility?

I.S.-K.: Again, there are few studies that have looked at the microbiome in the male reproductive system ⁹. The male genital mucosa contains a bacterial composition that is similar to adjacent anatomical sites with bacterial species as Prevotella, Staphylococcus, Corynebacterium, and Anaerococcus and is affected by sexual intercourse. Male circumcision seems to influence the penile microbiome. More studies and research are needed to understand the role of the male genital microbiome for fertility.

Any advices to improve fertility considering microbiota plays a role?

I.S.-K.: Most important is to live a healthy life when trying to get pregnant. Environmental and lifestyle factors such as smoking, excessive alcohol intake and stress can affect fertility as well as under- or overweight. A healthy lifestyle also includes a diet that makes your microbiota thrive in the gut and vagina. My advice is to eat a diet rich in vegetables and fruits to feed your microbiota with fibres. Fermented foods like yoghurt, kefir, kimchi or sauerkraut will provide you with the important lactobacilli species that support your fertility.

Women should avoid hygiene habits that influence the sensitive skin in the vulva. Don’t use soap and products that contain perfumes, you don’t have to wash your vagina as it cleanses itself with a natural discharge. Washing would only destroy the vaginal microbiota in the vagina.

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