Potential Influence of the Microbiome on Infertility and Assisted Reproductive Technology

Ido Sirota; Shvetha M. Zarek; James H. Segars

Disclosures

Semin Reprod Med. 2014;32(1):35-42. 

In This Article

Abstract and Introduction

Abstract

Although an altered vaginal microbiota has been demonstrated to affect parturition, its role in assisted reproductive technologies is uncertain. Nevertheless, the effect of known pathogens such as Mycoplasma tuberculosis, Chlamydia trachomatis, and Neisseria gonorrhoeae is clear, causing subclinical changes thought to be risk factors in subfertility. The Human Microbiome Project (HMP) has allowed for metagenomic studies to aid in characterizing normal vaginal flora. Recent findings from the HMP demonstrate that many different species of Lactobacillus are present in the vaginal tract, with a few that predominate. Studies that characterize the vaginal microbiome in assisted reproductive technology support the hypothesis that colonizing the transfer-catheter tip with Lactobacillus crispatus at the time of embryo transfer may increase the rates of implantation and live birth rate while decreasing the rate of infection. In addition, there is some evidence that a progesterone-resistant endometrium might increase the risk of an abnormal vaginal microbiome.

Introduction

The publication of the human genome sequence was heralded in 2001 as a notable achievement in the field of biology.[1] However, many noted that without the knowledge of the "second genome," namely, the genome of the microorganisms that inhabit the human body, our understanding would be woefully incomplete.[2 3] Thus, by 2007, there was a global effort to sequence the microbiome, which is the ecological community of commensal, symbiotic, and pathogenic microorganisms. Worldwide efforts by China, Canada, Singapore, France, Australia, Japan, the European Union, and the United States sought to understand the microbial community in states of good health and disease.[4]

In the United States, the project was named the "Human Microbiome Project" (HMP) and was launched in 2007 by the National Institutes of Health (NIH) as an initiative of the NIH Roadmap for Biomedical Research.[5] Although some countries like the Sino-French project sought to understand the microbiome in states of disease like obesity, the HMP desired to characterize the human microbiome from at least four body sites from normal volunteers, including the vagina as a major site of study in healthy women. In reproductive age women, the vaginal microbiota is affected by factors including age, sexual activity, pregnancy, and exogenous hormones.[5 6]

Many studies have implicated the vaginal microbiota in parturition. Neonates generally acquire intestinal microbial communities within the first week of life with relative equilibrium reached within the first year. Infants delivered via cesarean birth have higher rates of colonization by environmentally acquired microbes such as Clostridium difficile and Klebsiella and Enterobacter species, and have enhanced colonization of the neonatal oral cavity and intestine by components of the skin microbiome. In addition, the Ureaplasma species as well as Mycoplasma hominis are associated with preterm birth (PTB).[7,8,9,10,11,12,13]

The role of the vaginal microbiome in fertility and assisted reproductive technology (ART) is not as clear. Although known pathogens such as Mycoplasma tuberculosis, Chlamydia trachomatis, and Neisseria gonorrhoeae can cause infertility, subclinical changes in the microbiota in states like bacterial vaginosis (BV) are also thought to be risk factors in subfertility. Infertility affects a substantial proportion of reproductive-aged women and men in the United States. Data from CDC's 2002 National Survey of Family Growth show that among surveyed married U.S. women 15 to 44 years of age, an estimated 7.4% were affected by infertility (defined as failing to become pregnant after 1 year of trying with the same partner), while 12% of all women 15 to 44 years of age had impaired fecundity (defined as difficulty in getting pregnant or carrying a child to term).[14,15,16,17,18,19]

In this article, we review the potential role of the reproductive-tract microbiome in ART outcomes. We discuss the current status of knowledge, the direction of research now under way, and a research agenda to answer the questions most likely to allow optimization of outcomes.

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