A critical appraisal of safety data of dydrogesterone for the support of early pregnancy: a scoping review and meta-analysis

Alexander Katalinic, Lee P Shulman, Jerome F Strauss, Juan A Garcia-Velasco, John N van den Ankere
Reproductive BioMedicine Online. Available online 10 April 2022. In Press, Journal Pre-proof. 2022 doi:


No data support the suggestion that first-trimester dydrogesterone use increases the risk of foetal abnormalities; however, two low-quality retrospective studies (one retracted by the journal) have suggested such a link. A scoping review and meta-analysis were carried out to address this discrepancy. We reviewed the literature and were unable to identify any evidence of a plausible mechanism for potential causality between dydrogesterone and foetal abnormalities. To investigate whether evidence existed we undertook a preliminary meta-analysis of clinical studies published since 2005 on first-trimester dydrogesterone use with assessment of foetal abnormalities. A fixed effect model was used to determine pooled 2 odds ratios with 95% confidence intervals (CIs). From 83 articles identified, six randomised clinical trials were included. Pooled risk ratios (RR) for maternal dydrogesterone use and foetal abnormalities gave a RR approaching 1 (RR 0.96 [95% CI: 0.57, 1.62]) confirming previous conclusions of no causal association between foetal abnormalities and first trimester dydrogesterone use. Physicians, scientists, and journal reviewers should exercise due diligence to prevent promulgation of retracted data. We are confident in using dydrogesterone, if indicated, in the treatment of threatened or recurrent miscarriage, and believe that its favourable safety profile should extend to its appropriate use in assisted reproductive technologies.