How does the microbiota influence fertility?

By (gynecologist), (embryologist), (embryologist) and (psychologist).
Last Update: 01/17/2022

It has long been known that the bacterial population inhabiting the human body plays an essential role in certain processes, both in healthy people and in certain diseases. For example, the intestinal microbiota is essential for digestion.

Thanks to the advance of new technologies in the field of genomics (study of genetic information), it has been possible to study these microorganisms more exhaustively. Knowing how microflora influences fertility is one of the new challenges in the field of assisted reproduction, as it can help to improve the results of these treatments.

Importance of the microbiota

Before delving into the world of the microbiota, it is important to be clear about what we mean when we talk about microbiota and the microbiome.

What is the microbiota?

The microbiota, also known as microflora, is the group of bacteria and fungi that normally inhabit our body.

Each of us has a particular microflora in each area of our body and it is influenced by our diet, our environment, whether we have taken antibiotics, and even our age or hormonal status.

We have such a close relationship with our microbiota that, until recently, it was said that for every cell we have, we have ten belonging to microorganisms.

It is now known that, although the proportion is not so exaggerated, it is true that in our body we have more microorganism cells than our own. This leads us to believe that its function may be very relevant and invites us to investigate it.

What is the microbiome?

In recent years, the emergence of "omics" has brought about a revolution in the field of biomedicine. This name is given to the set of disciplines that study the totality or the whole of something, such as, for example, the totality of:

  • Genomics: genetic information of an individual.
  • Proteomics: proteins of an organism or system.
  • Interactomics: interactions between molecules.

The application of these new sciences to the analysis of the microbiota facilitates the study of the microbiome, which is the set of microorganisms that inhabit our body and their genomes (i.e., the microbiota and its genetic material).

The Human Microbiome Project is the most important research that has been done on this subject to date and consisted of identifying and characterizing the microbiome present in healthy volunteers and finding out what changes occur in this microbiome when there is a disease.

Thanks to this project and other studies, the analysis of the microbiome present in the female and male reproductive tracts is beginning to deepen. Knowledge of these microorganisms, their relationships, their functions and their implications for fertility may help to improve the outcome of assisted reproduction treatments, even in patients whose cause of sterility or infertility is currently unknown.

Normal vaginal microbiota

The vaginal microbiota has been extensively studied and, although it differs in each woman and is influenced by various factors, bacteria of the genus Lactobacillus are common. These include L. crispatus, L. iners, L. jensenii and L. gasseri.

This microbiota has a protective effect against other pathogenic microorganisms due to the production of lactic acid. This production creates an acidic environment in the vagina (pH 3.5-4.5) that prevents the growth of other pathogenic microorganisms, which would cause infection. In this sense, the administration of probiotics (orally or vaginally) has been shown to change the vaginal flora and increase the proportion of Lactobacillus. Therefore, the study of the microbiota and its possible restoration by means of probiotics is gaining importance, especially before seeking gestation.

Microbiome and fertility

The involvement of microorganisms in human sterility has been known for a long time. For example, some sexually transmitted diseases (STDs), such as chlamydia, are known to cause tubal factor infertility in many women.

Thanks to studies of the human microbiome, we can obtain new information about the relevance that these populations may have in achieving pregnancy.

Gametogenesis

Several investigations have studied the influence of the microbiome on sperm quality, mainly through seminal fluid analysis. Depending on which bacteria are predominant in the sample, semen quality parameters may be altered.

In addition, ovarian follicles have a very active microbiota, although some bacteria may adversely affect follicular development and even inhibit the response to sex hormones.

Thus, we see that the microbiome can affect the development of sex cells or gametes (gametogenesis) in both males and females.

Endometrial receptivity and pregnancy

Another area that has recently been found not to be sterile, as was thought until recently, is the uterine cavity. It is beginning to be seen that the microbiome of the innermost layer of the uterus, the endometrium, may influence its ability to allow an embryo to implant. In other words, the microbiome can affect endometrial receptivity and condition success in achieving gestation.

It has also been shown that the microbiome can influence the later stages of pregnancy. For example, in premature delivery or even miscarriage.

A recent study in IVF treatment patients has found that if Lactobacillus bacteria are not predominant in the endometrial microbiome (i.e. there is more than 10% of other bacteria), the chances of implantation, pregnancy, and birth are lower.

Therefore, the existence of bacteria other than Lactobacillus in the endometrium may be the cause of some implantation failures and miscarriage.

Applications

In-depth knowledge of the microbiome involved in reproduction allows us to explore new therapeutic strategies for infertile and infertile patients.

An example would be through probiotic foods, which are live microorganisms with beneficial effects on our microflora. Transplants of healthy microbiota could also be performed in patients with an altered microbiome.

Another approach would be to rigorously analyze how assisted reproduction treatments alter the microbiome, as they may affect it through hormonal stimulation or the antibiotics used. In the event that they negatively influence the results obtained in these techniques, protocols could be modified to try to minimize the harmful effect they may have.

Considering undergoing a fertility treatment? By getting your individual Fertility Report your will see different clinics especially selected for you out of the pool of clinics that meet our strict quality criteria. Moreover, it will offer you a comparison between the fees and conditions each clinic offers in order for you to make a well informed choice.

It would also be interesting to study how the microbiomes of different systems are related and their influence. That is, not to study the microflora of isolated organs, but to study the microbiome of the human body as a whole, in an integrative manner. In this way, it would be possible to find out whether, for example, the gut microbiome can influence fertility. In this line, some studies relate autism to alterations in the intestinal microbiome.

By analyzing the microorganisms present and personalized treatment, we could increase the chances of success, for example, by improving gamete quality or endometrial receptivity. Therefore, further research is needed in this field to obtain more benefits from modifications in the microbiome.

Traditionally, microorganisms have been seen as enemies of assisted reproduction techniques, and much effort has been devoted to avoiding them. Thanks to research on the microbiome, our perspective will gradually change and we will see that they can also be our allies to improve the results of these treatments.

FAQs from users

Does microbiota affect fertility?

By Jessica García Cataño M.D., M.Sc. (gynecologist).

The microbiota is the set of bacteria or microorganisms found in various organs of human beings. These organisms live in balance, with specific functions and their presence at adequate levels is very important for our health.

The microbiota varies greatly among women and seems to be different according to the phases of a woman's life. In principle, the vagina and the endometrium are mainly populated by lactobacilli.
Various factors such as the use of contraceptives, hormonal levels, antibiotics, etc. can modify this microbiota and alter the balance.

Alterations in the endometrial microbiota and especially the presence of pathogenic bacteria are associated with a higher rate of miscarriage and implantation failure.

There are endometrial tests that can detect alterations in the endometrial microbiota and the presence of pathogenic bacteria that cause infections within the endometrium. The identification of alterations and their treatment with probiotics or antibiotics seem to have a positive effect on the pregnancy rate naturally or during fertility treatment.

More studies are needed to determine the real impact of the microbiota on fertility but current medical information suggests that it is very important.

Can the microbiome affect offspring?

By Rebeca Reus BSc, MSc (embryologist).

Yes, it has been shown that the mother's microbiome affects her offspring. For example, there are studies on how the maternal microbiota influences the obesity of her offspring. Transmission can occur at different times, such as during pregnancy, childbirth, the first days of life or breastfeeding.

If I have a mouth infection, can it affect my fertility?

By Rebeca Reus BSc, MSc (embryologist).

Yes, periodontal disease (of the tissues affecting the tooth) is caused by bacteria and is associated with inflammatory processes that activate the immune system. This leads to a relationship between poor dental hygiene and general health. Several studies have found a relationship between this pathology, sterility and alterations in pregnancy. Therefore, the oral microbiota may have an effect on reproduction.

Can I modify my microbiome?

By Rebeca Reus BSc, MSc (embryologist).

Our microbiome is influenced by many factors, such as stress, food, environment, antibiotic use or even the microbiome of our partners. We can improve it through probiotic foods or a healthier diet, for example, but we cannot control it 100%, as it depends on many elements.

Is there microbiota in the placenta?

By Silvia Azaña Gutiérrez B.Sc., M.Sc. (embryologist).

The results regarding the study of the placental microbiome are controversial. While some studies have succeeded in determining the placental microbiota, others claim that the placenta does not contain a microbiome.

For more information on male reproductive tract infections, please visit the following link: Seminal fluid infections: orchitis, epididymitis, and prostatitis.

If, on the other hand, you are interested in sexually transmitted diseases, you can read this article: Sexually transmitted diseases (STDs) in men and women.

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References

Anahtar MN, Gootenberg DB, Mitchell CM, Kwon DS. Cervicovaginal Microbiota and Reproductive Health: The Virtue of Simplicity. Cell Host Microbe. 2018 Feb 14;23(2):159-168.

Basavaprabhu HN, Sonu KS, Prabha R. Mechanistic insights into the action of probiotics against bacterial vaginosis and its mediated preterm birth: An overview. Microb Pathog. 2020 Apr;141:104029.

Garcia-Grau I, Perez-Villaroya D, Bau D, Gonzalez-Monfort M, Vilella F, Moreno I, Simon C. Taxonomical and Functional Assessment of the Endometrial Microbiota in A Context of Recurrent Reproductive Failure: A Case Report. Pathogens. 2019 Oct 24;8(4):205.

García-Velasco JA, Menabrito M, Catalán IB. What fertility specialists should know about the vaginal microbiome: a review. Reprod Biomed Online. 2017 Jul;35(1):103-112.

Kyono K, Hashimoto T, Kikuchi S, Nagai Y, Sakuraba Y. A pilot study and case reports on endometrial microbiota and pregnancy outcome: An analysis using 16S rRNA gene sequencing among IVF patients, and trial therapeutic intervention for dysbiotic endometrium. Reprod Med Biol. 2018 Oct 25;18(1):72-82.

Martín R, Soberón N, Vázquez F, Suárez JE. La microbiota vaginal: composición, papel protector, patología asociada y perspectivas terapéuticas [Vaginal microbiota: composition, protective role, associated pathologies, and therapeutic perspectives]. Enferm Infecc Microbiol Clin. 2008 Mar;26(3):160-7. Spanish.

Moreno I, Garcia-Grau I, Bau D, Perez-Villaroya D, Gonzalez-Monfort M, Vilella F, Romero R, Simón C. The first glimpse of the endometrial microbiota in early pregnancy. Am J Obstet Gynecol. 2020 Apr;222(4):296-305.

Moreno I, Simon C. Deciphering the effect of reproductive tract microbiota on human reproduction. Reprod Med Biol. 2018 Nov 1;18(1):40-50.

Moreno I, Simon C. Relevance of assessing the uterine microbiota in infertility. Fertil Steril. 2018 Aug;110(3):337-343.

Reid G, Beuerman D, Heinemann C, Bruce AW. Probiotic Lactobacillus dose required to restore and maintain a normal vaginal flora. FEMS Immunol Med Microbiol. 2001 Dec;32(1):37-41.

Reid G, Charbonneau D, Erb J, Kochanowski B, Beuerman D, Poehner R, Bruce AW. Oral use of Lactobacillus rhamnosus GR-1 and L. fermentum RC-14 significantly alters vaginal flora: randomized, placebo-controlled trial in 64 healthy women. FEMS Immunol Med Microbiol. 2003 Mar 20;35(2):131-4.

Tomusiak A, Strus M, Heczko PB, Adamski P, Stefański G, Mikołajczyk-Cichońska A, Suda-Szczurek M. Efficacy and safety of a vaginal medicinal product containing three strains of probiotic bacteria: a multicenter, randomized, double-blind, and placebo-controlled trial. Drug Des Devel Ther. 2015 Sep 25;9:5345-54.

Vazquez F, Fernández-Blázquez A, García B. Vaginosis. Vaginal microbiota. Enferm Infecc Microbiol Clin. 2019 Nov;37(9):592-601. English, Spanish.

FAQs from users: 'Does microbiota affect fertility?', 'Can the microbiome affect offspring?', 'If I have a mouth infection, can it affect my fertility?', 'Can I modify my microbiome?' and 'Is there microbiota in the placenta?'.

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Authors and contributors

 Jessica García Cataño
Jessica García Cataño
M.D., M.Sc.
Gynecologist
Degree in Medicine from the University of Guadalajara in Mexico, specializing in Gynecology and Obstetrics at the Fray Antonio Alcalde Civil Hospital. After completing a Master's in Human Reproduction at the Complutense University of Madrid, she became part of the Clinica Ginefiv Madrid gynecology team. More information about Jessica García Cataño
 Rebeca Reus
Rebeca Reus
BSc, MSc
Embryologist
Degree in Human Biology (Biochemistry) from the Pompeu Fabra University (UPF). Official Master's Degree in Clinical Analysis Laboratory from the UPF and Master’s Degree about the Theoretical Basis and Laboratory Procedures in Assisted Reproduction from the University of Valencia (UV). More information about Rebeca Reus
 Silvia Azaña Gutiérrez
Silvia Azaña Gutiérrez
B.Sc., M.Sc.
Embryologist
Graduate in Health Biology from the University of Alcalá and specialized in Clinical Genetics from the same university. Master in Assisted Reproduction by the University of Valencia in collaboration with IVI clinics. More information about Silvia Azaña Gutiérrez
License: 3435-CV
Adapted into english by:
 Cristina  Algarra Goosman
Cristina Algarra Goosman
B.Sc., M.Sc.
Psychologist
Graduated in Psychology by the University of Valencia (UV) and specialized in Clinical Psychology by the European University Center and specific training in Infertility: Legal, Medical and Psychosocial Aspects by University of Valencia (UV) and ADEIT.
More information about Cristina Algarra Goosman
Member number: CV16874

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