The Impact of Assisted Reproductive Technology (ART) on the Microbiome

Version For Professionals

Assisted Reproductive Technology (ART) encompasses a range of medical procedures used to address infertility, including in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), and other related techniques. While ART has provided hope and solutions to many couples facing infertility, it also introduces a myriad of physiological changes and stressors that can affect patients’ microbiomes. The microbiome, particularly in the reproductive tract, plays a critical role in reproductive health and pregnancy outcomes. 

The Human Microbiome and Reproductive Health

The human microbiome consists of trillions of microorganisms, including bacteria, viruses, fungi, and other microbes, residing in various body parts, including the gut, oral cavity, skin, and reproductive tract. The reproductive tract microbiome, encompassing the vaginal, uterine, and seminal microbiomes, is integral to maintaining reproductive health. A healthy reproductive microbiome supports normal reproductive functions, protects against infections, and influences pregnancy outcomes.

  1. Vaginal Microbiome: Dominated by Lactobacillus species, the vaginal microbiome plays a crucial role in protecting against pathogens, maintaining an acidic pH, and promoting overall reproductive health. 
  2. Endometrial Microbiome: Though less studied, emerging research indicates that the uterine microbiome also influences implantation and pregnancy success. 
  3. Seminal Microbiome: The seminal microbiome, composed of various bacterial species, affects sperm quality and reproductive outcomes. 

ART Procedures and Microbiome Alterations

ART involves several procedures that can disrupt the natural microbiome balance. Key stages include ovarian stimulation, egg retrieval, embryo culture, and embryo transfer, each with potential impacts on the microbiome.

Ovarian Stimulation: Ovarian Stimulation and Its Effects on the Microbiome

Ovarian stimulation is a critical component of many ART procedures, designed to promote the development of multiple follicles to increase the number of retrievable eggs. This process typically involves the administration of exogenous hormones such as follicle-stimulating hormone (FSH) and luteinizing hormone (LH), along with supplemental oestrogen and progesterone. While these hormonal treatments are essential for the success of ART, they can significantly impact the vaginal and endometrial microbiomes.

  • Hormonal Influence on Microbial Composition:

Oestrogen: Elevated levels of oestrogen during ovarian stimulation can lead to increased glycogen deposition in the vaginal epithelium. Glycogen serves as a substrate for Lactobacillus species, promoting their growth and the production of lactic acid, which maintains the acidic pH of the vaginal environment. However, the dynamic hormonal fluctuations during ART can disrupt this balance, potentially reducing Lactobacillus dominance.

Progesterone: Progesterone supplementation, often used to support the luteal phase in ART cycles, can also influence the vaginal microbiome. While progesterone helps maintain pregnancy and supports endometrial receptivity, it may alter the vaginal pH and microbial environment. This hormone can reduce the relative abundance of Lactobacillus, making the vaginal environment more susceptible to pathogenic bacteria.

  • Risk of Bacterial Vaginosis (BV):

Microbial Dysbiosis: The shift in microbial composition due to hormonal changes can lead to microbial dysbiosis, characterized by a decrease in Lactobacillus species and an increase in anaerobic bacteria such as Gardnerella vaginalis and Atopobium vaginae. These changes can predispose individuals to bacterial vaginosis (BV), a condition marked by an imbalance of the vaginal microbiota.

Clinical Implications: BV is associated with various adverse reproductive outcomes, including lower implantation rates, increased risk of early pregnancy loss, and preterm labour. The presence of BV-related bacteria can induce inflammatory responses and disrupt the endometrial environment, negatively affecting embryo implantation and pregnancy success.

  • Endometrial Microbiome:

Hormonal Effects on the Uterine Environment: Similar to the vaginal microbiome, the endometrial microbiome is influenced by hormonal treatments during ART. Oestrogen and progesterone can alter the microbial communities within the uterus, potentially impacting endometrial receptivity and embryo implantation.

  • Egg Retrieval: The invasive nature of transvaginal oocyte retrieval can introduce external microbes into the reproductive tract. Antibiotic prophylaxis commonly used during this procedure can also disrupt the microbiome, reducing beneficial bacteria and allowing opportunistic pathogens to proliferate​​.
  • Embryo Culture: In vitro embryo culture involves the manipulation of gametes and embryos in a controlled laboratory environment. While the culture medium is designed to support embryo development, it lacks the natural microbiome present in the reproductive tract, potentially influencing embryo quality and implantation success.
  • Embryo Transfer: The transfer of embryos back into the uterus can introduce exogenous microbes and disrupt the endometrial microbiome. The catheter used in the transfer process can act as a conduit for microorganisms, potentially leading to infections or altered microbial communities.

Consequences of Microbiome Alterations

The disruption of the reproductive microbiome during ART can have several consequences:

  1. Implantation Failure and Pregnancy Loss: An imbalanced microbiome, particularly a reduction in Lactobacillus species, is associated with lower implantation rates and increased risk of early pregnancy loss. Studies have shown that certain pathogenic bacteria can trigger inflammatory responses detrimental to embryo implantation​​​​.
  2. Infections: The introduction of pathogens during ART procedures can lead to infections such as endometritis and pelvic inflammatory disease, which negatively impact reproductive outcomes and overall health.
  3. Immune Response and Inflammation: An altered microbiome can influence local immune responses and inflammation, crucial factors in successful implantation and pregnancy maintenance. Dysbiosis can lead to chronic inflammation, adversely affecting endometrial receptivity and embryo development.

Mitigation Strategies

To minimize the impact of ART on the microbiome, several strategies can be employed:

  1. Probiotic Supplementation: Administering probiotics to restore Lactobacillus dominance in the vaginal and endometrial microbiome has shown promise in improving ART outcomes. Probiotics can help maintain a healthy microbial balance, reducing the risk of infections and supporting implantation.
  2. Antibiotic Stewardship: Judicious use of antibiotics during ART procedures is essential to avoid unnecessary disruption of the microbiome. Tailoring antibiotic use based on individual patient needs and microbial profiles can help preserve beneficial bacteria.
  3. Microbiome Screening and Personalization: Pre-treatment screening of the reproductive microbiome can identify dysbiosis and guide personalized interventions. Tailoring ART protocols based on microbiome profiles may enhance treatment success rates.
  4. Non-Invasive Procedures: Developing and adopting less invasive ART techniques can reduce the risk of microbial introduction and disturbance. Innovations in embryo transfer methods, for example, aim to minimize microbial contamination and improve outcomes.

The interplay between ART and the reproductive microbiome is complex and significant. Understanding how ART procedures affect the microbiome is important for optimizing treatment outcomes and minimizing risks. By integrating microbiome-friendly practices and personalized approaches, reproductive specialists can enhance the success of ART while safeguarding patients’ microbial health.