Microbiota and Fertility: A Literature Review

Introduction

A crucial aspect of the microbiome's role in human health has been recently observed. The human microbiome consists of trillions of microorganisms that live in and on the body, forming complex communities. These microorganisms, including bacteria, viruses, fungi, and archaea, coexist with the human host in a symbiotic relationship. In a mutualistic symbiotic relationship, both the microorganisms and the host organism benefit.^1,2 The microbiome provides various essential functions that contribute to human health, including digestion and nutrient absorption, immune system regulation, protection against pathogens, metabolism and energy regulation, brain function and mood regulation and reproductive tract function (Lactobacilli is the chief bacteria).^3,4

Maintaining a balanced and diverse microbiome is thus essential for overall health and well-being. Disruptions in the microbiome's composition, known as dysbiosis, have been associated with various health conditions, including inflammatory bowel diseases, allergies, autoimmune disorders, and even mental health disorders. Therefore, understanding the dynamics of the microbiome and promoting its health through diet, lifestyle, and targeted interventions may have profound implications for human health.⁵

The role of the genital tract microbiome in fertility is an emerging area of research that has garnered increasing attention in recent years. While much is still being uncovered, evidence suggests that the microbiome of both the male and female reproductive tracts may influence fertility through various mechanisms.

Dysbiosis in the genital tract microbiome can lead to inflammation and immune dysregulation, which may interfere with normal reproductive processes. Chronic inflammation in the reproductive tract can impair gamete quality, disrupt embryo implantation, and increase the risk of pregnancy complications.⁶

Understanding the role of the genital tract microbiome in fertility could have significant implications for diagnosing and treating infertility. Future research may explore the development of microbiome-based interventions, such as probiotics or targeted antimicrobial therapies, to optimize the reproductive microbiota and improve fertility outcomes.

Materials and methods

A literature review focused on the microbiota of the male and female reproductive systems, particularly in the context of assisted reproductive techniques was conducted. We included major search engines like MEDLINE, PubMed, and EMBASE for comprehensive coverage of relevant literature. This search strategy was well-designed to capture relevant literature on the microbiota of the male and female reproductive systems in the context of assisted reproductive techniques (Table 1). We used a combination of keywords such as "vaginal microbiota," "microbiome," "assisted reproductive techniques," "in vitro fertilization," "endometritis," "implantation failure," "male microbiome," "ART," "semen” and "endometrium.

Inclusion criteria: studies involving microbiome, microbiota, fertility, assisted reproductive techniques (ART), in-vitro fertilization (IVF), implantation failure, semen, endometrium.

Exclusion criteria: studies before 2018, non- English

Outcome measures: Impact on fertility, pregnancy rates, detection rate of specific microbiome

Table 1: Studies showing aim, methodology and outcomes.

Discussion

Success of ARTs in the context of male reproductive tract microbiome

Research into the male reproductive tract microbiome and its influence on the success of ARTs has gained significant attention in recent years. Here are some key points that have emerged from studies in this field:

1. Composition of the male reproductive tract microbiome: The male reproductive tract was traditionally thought to be sterile, but emerging evidence suggests the presence of a diverse microbiome. This microbiome can include bacteria, viruses, fungi, and other microorganisms. The composition of the microbiome can vary across individuals and can be influenced by factors such as age, sexual activity, and overall health.⁷
2. Impact on sperm quality and function: Studies have suggested that the microbiome of the male reproductive tract may influence sperm quality and function. Imbalances in the microbiome, such as dysbiosis or presence of pathogenic bacteria, have been associated with sperm abnormalities, reduced sperm motility, and increased levels of reactive oxygen species (ROS), which can damage sperm deoxyribonucleic acid (DNA).⁸
3. Role in infertility and ART Outcomes: There is growing evidence to suggest that the male reproductive tract microbiome may play a role in male infertility and the success of ART procedures such as IVF and intracytoplasmic sperm injection (ICSI). Dysbiosis or infections in the male reproductive tract have been linked to decreased fertility rates and poorer outcomes in ART cycles, including lower fertilization rates, reduced embryo quality, and lower pregnancy rates.⁹
4. Potential therapeutic interventions: Understanding the role of the male reproductive tract microbiome in ART outcomes may lead to novel therapeutic interventions aimed at improving male fertility and enhancing the success of ART procedures. These interventions could include probiotics, antibiotics, or other microbiome-modulating strategies to restore microbial balance and improve sperm quality.¹⁰
5. Challenges and future directions: Despite significant progress, many questions remain unanswered regarding the precise mechanisms by which the male reproductive tract microbiome influences ART outcomes. Further research is needed to elucidate these mechanisms and to develop targeted interventions that can optimize fertility treatments for couples undergoing ART.

Microbiome and its effect on female fertility undergoing ART cycles

Research exploring the impact of the microbiome on fertility in women undergoing ARTs has uncovered several important insights. Here is an overview of key points:

Figure 1: Microbiota in the female reproductive tract.

1. Vaginal microbiome composition: The vaginal microbiome plays a crucial role in maintaining vaginal health and may influence fertility outcomes. Studies have identified several types of vaginal microbial communities, with Lactobacillus species predominating in a healthy microbiome (Figure 1). However, dysbiosis, characterized by an imbalance in microbial composition, has been associated with various gynaecological conditions, including bacterial vaginosis.¹¹
2. Effect on implantation and pregnancy: The vaginal microbiome may influence the success of ART procedures such as IVF and embryo transfer by affecting implantation and pregnancy rates. Research suggests that dysbiosis in the vaginal microbiome, particularly an overgrowth of pathogenic bacteria, may impair embryo implantation and increase the risk of implantation failure and early pregnancy loss.¹²
3. Endometrial microbiome: Recent studies have also focused on the endometrial microbiome, which refers to the microbial communities present in the uterine cavity and endometrial lining. The endometrial microbiome may play a role in embryo implantation and early pregnancy development. Dysbiosis or alterations in the endometrial microbiome have been associated with infertility, recurrent implantation failure, and adverse pregnancy outcomes.¹³
4. Impact of reproductive tract infections: Infections of the female reproductive tract, including sexually transmitted infections (STIs) and bacterial vaginosis, can disrupt the vaginal and endometrial microbiome, potentially affecting fertility and ART outcomes. Treating these infections prior to ART procedures may improve outcomes by restoring microbial balance.¹⁴
5. Therapeutic interventions and future directions: Modulating the vaginal and endometrial microbiome through probiotics, antibiotics, or other microbiome-targeted interventions is an area of active research. Optimizing the microbial Conclusion environment of the female reproductive tract before and during ART procedures may improve implantation rates, embryo development, and overall pregnancy success.¹⁵
6. Personalized medicine approach: There is growing interest in personalized medicine approaches that consider individual variations in the vaginal and endometrial microbiome. Tailoring fertility treatments based on an individual's microbiome profile may enhance the effectiveness of ARTs and improve outcomes for women undergoing infertility treatment.¹⁶

Assisted Reproductive Technologies (ART): The microbiome may also influence the success of assisted reproductive treatments, such as IVF and IUI. Studies suggest that the composition of the uterine and vaginal microbiota may affect embryo implantation rates and pregnancy outcomes following ART procedures.¹⁷

Conclusion

In conclusion, the microbiome of the female reproductive tract, including the vaginal and endometrial microbiomes, exerts a significant influence on fertility and the success of ART procedures. Understanding the role of the microbiome in reproductive health and developing targeted interventions to optimize microbial balance represents a promising avenue for improving fertility treatments in women undergoing ARTs.

Overall, the male reproductive tract microbiome represents a promising area of research with potential implications for understanding and addressing male infertility and optimizing the success of ART procedures. Assisted Reproductive Technologies have revolutionized the field of reproductive medicine, offering hope to couples struggling with infertility. While much attention has been paid to factors such as egg quality, sperm count, and uterine health in the success of ART procedures, the role of the male reproductive tract microbiome is an emerging area of interest. The male reproductive tract was traditionally considered to be sterile, but recent research has revealed the presence of a diverse microbiome in the semen, epididymis, and other parts of the male reproductive system. This microbiome is thought to play a role in sperm health, fertility, and reproductive outcomes.

Several studies have investigated the relationship between the male reproductive tract microbiome and the success of ART procedures such as IVF and ICSI. Some research suggests that certain bacteria in the male reproductive tract may be associated with sperm quality and fertility potential. For example, imbalances in the microbiome, such as an overgrowth of pathogenic bacteria, have been linked to reduced sperm motility and increased levels of DNA damage in sperm. Furthermore, the presence of specific bacteria in the male reproductive tract has been correlated with outcomes of ART procedures. For instance, some studies have found that men with certain bacterial profiles in their semen may have lower success rates with IVF or ICSI.

Microbiome profiling requires international consensus regarding sampling and investigation analyses that should be performed without culture-dependent methods. In future, larger and longer randomised trials are needed to know the statistical significance of microbiome in fertility treatment and its pregnancy related outcomes.