Over the years a number of couples who struggled to conceive a child (or carry it to term) have emailed me and invariably, upon testing, the females had low progesterone levels while the males had high estrogen/prolactin. The high estrogen/prolactin was also often present in females, which is not surprising in light of their low progesterone. Most of these couples managed to conceive after supplementing with progesterone+DHEA, and in some cases by taking just an aromatase inhibitor (AI) or aspirin (also a decent AI). The study below now reveals a possible mechanism behind all such cases – i.e. low progesterone (or high estrogen) signalling results in a state of chronic inflammation, which results in non-viable embryos, which either could not properly implant or were spontaneously aborted. Treatment with P4 at a human-equivalent dose of 3.5mg/kg daily for just a day reversed the inflammatory state, as did treatment with the COX inhibitor carprofen. Carprofen is a drug that is fully exchangeable with aspirin, though with ~2-fold conversion factor, so taking that conversion factor into account and the carprofen dosage used in the study, the human-equivalent daily dose of aspirin would be about 6.5mg/kg, or literally just 2 tablets ( 2 x 325mg) each for a person weighing 100kg. Since most females weigh way less than that, taking 2 tablets of aspirin daily should be more than enough to replicate the design of the study.
https://dx.doi.org/10.1126/sciadv.adt6113
https://medicalxpress.com/news/2025-05-inflammation-reproductive-tract-linked-infertility.html
“…Inflammation in the female reproductive tract may make it difficult to conceive a child, but replenishing a key hormone could keep inflammation in check, according to researchers from the University of Missouri School of Medicine. Progesterone, nicknamed the “pregnancy hormone,” is crucial for embryo growth, the first stage of fetal development. Using a mouse model, researchers found that if the body does not have enough proteins to respond to progesterone, there is also increased inflammation. It’s still unclear if these low protein levels cause inflammation to occur. “What we do know is that inflammation is bad for embryo development,” study author Joy Winuthayanon said. “Embryos are highly sensitive to any stressors in their environment. When we treated the inflammation, more embryos survived long enough to implant themselves in the uterus.” These findings could help improve women’s chances of becoming pregnant. More than 60% of pregnancy losses occur in the first 4–6 weeks, which is often before most patients are aware they are pregnant. Understanding the early stages of the embryo’s development could help save more pregnancies, especially for women with certain conditions like pelvic inflammatory disease. “Women with low progesterone or inflammation in the reproductive system typically have more difficulty conceiving and becoming pregnant,” co-author Dr. Mark Hunter said. “This research presents a potential explanation and opens the door to possible treatments.” Winuthayanon says future research will focus on developing effective, convenient and noninvasive anti-inflammatory treatments, which could include a new medication or an injection.”
