Exploring Progesterone Deficiency in First-Trimester Miscarriage and the Impact of Hormone Therapy on Foetal Development: A Scoping Review.

Background and Objectives: Progesterone deficiency during pregnancy may lead to various complications, including first-trimester miscarriage, which is the most common pregnancy complication. However, progesterone therapy may play a role in pregnancy maintenance and foetal development. The aim of this scoping review is to present evidence on the link between progesterone deficiency and first-trimester miscarriage among pregnant women and assess the impact of progesterone therapy on foetal development. Methods: A comprehensive global systematic search of mainly primary research studies was conducted using several databases. Peer-reviewed studies published between 2010 and 2023 were included. The scoping review was conducted using the framework outlined by the Joanna Briggs Institute (JBI) and reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Extension for Scoping Reviews (PRISMA-ScR) statement. Results: Twenty-three articles (which included 35,862 participants) were included in the analysis. Most studies were conducted in mid- to high-income countries. All 23 articles reported a significant positive relationship between progesterone deficiency and first-trimester miscarriage. Furthermore, the majority of studies reported a higher risk of miscarriage when lower levels of progesterone are combined with other declined hormones. While most studies reported that progesterone therapy may reduce the rate of first-trimester miscarriage among pregnant women, no evidence of health-related harm to offspring development was reported. Conclusions: The findings from this systematic-scoping review indicate possible benefits of progesterone replacement therapy in maintaining a healthy pregnancy and foetal development. Rigorous studies that include large sample sizes and systematic reviews are required to confirm these findings further.