Progesterone plays a vital role in the successful implantation of embryos and the maintenance of a healthy pregnancy. Insufficient progesterone levels are often a key factor in IVF treatment failure and early miscarriage. In assisted reproductive treatments, progesterone is typically supplemented through various methods, including oral capsules, vaginal suppositories, or injections, to support luteal function or prepare the endometrium for embryo transfer.
However, there are significant individual variations in absorption, particularly with oral progesterone. Some patients may not reach adequate blood or tissue levels of the hormone despite standard or higher doses, which can increase the risk of implantation failure or miscarriage.
A groundbreaking study published in Gut Microbes has revealed a new factor that could be contributing to infertility in women undergoing IVF: a gut microbe, Clostridium innocuum. This bacterium was identified in the gut microbiota of infertile women, and its presence disrupts progesterone metabolism, leading to decreased bioavailability of the hormone and potentially affecting fertility.
The research team discovered that C. innocuum metabolizes progesterone into epipregnanolone, a neurosteroid with minimal progestogenic activity. This process significantly lowers circulating progesterone levels through enterohepatic circulation, impairing progesterone’s essential function.
In mouse models, the researchers found that targeting and suppressing C. innocuum with antibiotics could help raise progesterone levels. On the other hand, prolonged exposure to this bacterium led to disruptions in the estrous cycle and follicular development, mimicking conditions of follicular arrest and anovulation seen in women.
This study not only suggests novel medical strategies for addressing infertility but also contributes to growing evidence of how gut microbiota impacts reproductive health. The research team is now working toward translating these findings into clinical applications, aiming to develop personalized precision medicine approaches for fertility treatments.
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