Progesterone may raise chances of having a baby for couples with unexplained infertility

Couples with unexplained infertility who are seeking parenthood may benefit from progesterone treatment, which can increase the livebirth rates and decrease miscarriage rates by twofold, according to data from the PiNC* trial.

In a cohort of 143 couples, 15 of the 72 women (15.3 percent) who received luteal-phase progesterone support (treatment group) had a livebirth as opposed to only 10 of 71 of those (7.0 percent) who received no luteal-phase support (control group). Progesterone treatment doubled the likelihood of a successful delivery (odds ratio [OR], 2.38, 95 percent confidence interval [CI], 0.78–7.24). [ESHRE 2023, abstract O-023]

Miscarriage occurred in three women in the treatment group and in four women in the control group (20 percent vs 40 percent). One pregnancy in the treatment group was ectopic, while one pregnancy in the control group was terminated due to foetal anomalies.

Although the livebirth rate was more than doubled and the miscarriage rate was halved with treatment, the small numbers mean that this could have happened by chance, according to lead investigator Dr Claudia Raperport, a researcher at Queen Mary University of London, London, UK.

“We need to do further research to prove these results in a larger group of people, but the PiNC trial suggests a potential treatment for couples with unexplained fertility,” Raperport added.

Elevation in progesterone levels occur in the second half of the menstrual cycle to prepare the womb for pregnancy. However, high progesterone levels do not always guarantee a healthy lining of the womb, said Raperport. Other factors can also affect the chances of pregnancy.

“It could be that treating women with vaginal progesterone is helping the womb to become more receptive to a fertilized egg,” she added.

Cheap, noninvasive alternative

Currently available treatments recommended for treating unexplained infertility are intrauterine insemination and in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). Both methods are costly and require invasive procedures.

In contrast, progesterone treatment is inexpensive, with the estimated cost for 3 months of treatment being around EUR 200 or less, according to Raperport.  “[P]rogesterone … also carries far less clinical risk, and physical and emotional burden for the couples involved.

“The treatment investigated here represents a simple, noninvasive, and inexpensive option that is acceptable to couples with unexplained infertility and may increase their chance of pregnancy and livebirth,” she continued. “Given progesterone’s safety and low price, there is no harm in offering this treatment in the meantime.”

Raperport believes that if vaginal progesterone is proven to yield similar delivery success rates to stimulated intrauterine insemination, the hormone treatment would likely become a first-line option for many couples worldwide.

The study population included couples with normal semen analysis (WHO 2020), regular ovulation, bilateral patent tubes, a female partner who was at least 42 years of age and had a body mass index of not more than 30 kg/m². All couples used ovulation test kits to plan intercourse for three menstrual cycles.

Women in the treatment group received progesterone 400 mg via a twice-daily vaginal suppository for 14 days. Each couple participated for three menstrual cycles, and they were followed up until either the end of a third nonconceptual cycle or up to delivery.

*Progesterone in Natural Cycles with a study showing that luteal-phase progesterone support