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

Assisted Reproductive Technology (ART) includes medical procedures like in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) to help with infertility. While ART offers hope to many, it also causes changes in the body’s microbiome, especially in the reproductive tract, which is important for reproductive health and pregnancy success.

The Human Microbiome and Reproductive Health

The human microbiome is made up of trillions of microorganisms such as bacteria, viruses, fungi, and other microbes found in different parts of the body, including the gut, mouth, skin, and reproductive tract. A healthy microbiome in the reproductive tract supports normal reproductive functions, protects against infections, and influences pregnancy outcomes.

  1. Vaginal Microbiome: This microbiome is mostly made up of Lactobacillus bacteria, which help protect against harmful pathogens, maintain an acidic environment, and promote overall reproductive health. 
  2. Endometrial Microbiome: Research shows that the bacteria in the uterus also play a role in implantation and pregnancy success. 
  3. Seminal Microbiome: The bacteria in semen affect sperm quality and reproductive outcomes. 

How ART Procedures Affect the Microbiome

ART procedures can disrupt the natural balance of the microbiome. Key stages include ovarian stimulation, egg retrieval, embryo culture, and embryo transfer, each affecting the microbiome in different ways.

Ovarian Stimulation

Ovarian stimulation is a key part of ART, where hormones are used to develop multiple eggs. This involves giving hormones like follicle-stimulating hormone (FSH) and luteinizing hormone (LH), along with oestrogen and progesterone. These hormones can significantly impact the vaginal and uterine microbiomes.

  • Hormonal Influence on Microbial Composition:
    • Oestrogen: High levels of oestrogen can increase glycogen in the vaginal lining, which supports the growth of Lactobacillus bacteria. However, hormone fluctuations during ART can disrupt this balance, reducing Lactobacillus levels.
    • Progesterone: Progesterone, used to support the luteal phase in ART, can also change the vaginal microbiome. It may reduce Lactobacillus levels, making the vaginal environment more prone to harmful bacteria.
  • Risk of Bacterial Vaginosis (BV):
    • Microbial Imbalance: Hormonal changes can lead to an imbalance in the vaginal microbiome, reducing Lactobacillus and increasing harmful bacteria like Gardnerella vaginalis and Atopobium vaginae. This can cause bacterial vaginosis (BV).
    • Health Implications: BV is linked to lower implantation rates, higher risk of early pregnancy loss, and preterm labour. BV-related bacteria can trigger inflammation and disrupt the uterine environment, affecting embryo implantation and pregnancy success.
  • Endometrial Microbiome:
    • Hormonal Effects: The hormones used during ART also affect the bacteria in the uterus, potentially impacting the success of embryo implantation.

Egg Retrieval

Egg retrieval involves collecting eggs from the ovaries using a needle, which can potentially introduce external microbes into the reproductive tract. Antibiotics used during this procedure can also disrupt the microbiome, reducing beneficial bacteria and allowing harmful bacteria to grow.

Embryo Culture

Embryo culture involves growing embryos in a lab before transferring them to the uterus. While the culture medium supports embryo development, it lacks the natural microbiome, which can affect embryo quality and implantation success.

Embryo Transfer

Embryo transfer involves placing embryos into the uterus using a catheter, which can potentially introduce external microbes and disrupt the uterine microbiome. This can lead to infections or alter the microbial community, impacting pregnancy outcomes.

Consequences of Microbiome Alterations

Disrupting the reproductive microbiome during ART can have several consequences:

  1. Implantation Failure and Pregnancy Loss: An imbalanced microbiome, especially reduced Lactobacillus, is linked to lower implantation rates and higher risk of early pregnancy loss. Harmful bacteria can trigger inflammation that hinders embryo implantation.
  2. Infections: Introducing pathogens during ART can cause infections like endometritis and pelvic inflammatory disease, negatively impacting reproductive outcomes and overall health.
  3. Immune Response and Inflammation: An altered microbiome can affect local immune responses and inflammation, which are crucial for successful implantation and maintaining pregnancy. Dysbiosis can lead to chronic inflammation, affecting endometrial receptivity and embryo development.

Mitigation Strategies

To reduce the impact of ART on the microbiome, several strategies can be used:

  1. Probiotic Supplementation: Taking probiotics to restore Lactobacillus levels in the vaginal and uterine microbiomes can improve ART outcomes, maintain a healthy microbial balance, and reduce infection risks.
  2. Antibiotic Stewardship: Using antibiotics carefully during ART procedures helps avoid unnecessary disruption of the microbiome. Tailoring antibiotic use based on individual needs and microbial profiles can help preserve beneficial bacteria.
  3. Microbiome Screening and Personalization: Screening the reproductive microbiome before treatment can identify imbalances and guide personalized interventions, enhancing treatment success rates.
  4. Non-Invasive Procedures: Developing less invasive ART techniques can reduce the risk of microbial introduction and disturbance. Innovations in embryo transfer methods aim to minimize microbial contamination and improve outcomes.

Understanding how ART procedures affect the microbiome is important for optimizing treatment outcomes and minimizing risks. By using microbiome-friendly practices and personalized approaches, fertility specialists can enhance ART success while ensuring patients’ microbial health.