Progestogens in women with threatened miscarriage or recurrent miscarriage: A meta‐analysis

• Published in: Acta obstetricia et gynecologica Scandinavica Vol. 103; no. 9; pp. 1689 - 1701
• Main Authors: Zhao, Yunli, D'Souza, Rohan, Gao, Ya, Hao, Qiukui, Kallas‐Silva, Lucas, Steen, Jeremy P., Guyatt, Gordon
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.09.2024; John Wiley and Sons Inc; Wiley
• Subjects: Abortion, Habitual - prevention & control; Abortion, Threatened; Clinical outcomes; Female; Humans; live birth; meta‐analysis; Miscarriage; Patient safety; Pregnancy; Pregnancy complications; Progesterone; Progesterone - administration & dosage; Progesterone - therapeutic use; Progestins - administration & dosage; Progestins - therapeutic use; progestogens; Randomized Controlled Trials as Topic; recurrent miscarriage; Systematic Review; threatened miscarriage; recurrent miscarriage; meta‐analysis; progestogens; live birth; threatened miscarriage
• ISSN: 0001-6349; 1600-0412; 1600-0412
• DOI: 10.1111/aogs.14829

Introduction Clinical practice guidelines provide inconsistent recommendations regarding progestogen supplementation for threatened and recurrent miscarriage. We conducted a systematic review and meta‐analysis to assess the effectiveness and safety of progestogens for these patients. Material and methods We searched Medline, Embase, and Cochrane Central Registry of Controlled Trials up to October 6, 2023 for randomized control trials (RCTs) comparing progestogen supplementation to placebo or no treatment for pregnant women with threatened or recurrent miscarriage. We assessed the risk of bias using a modified version of the Cochrane risk‐of‐bias tool and the certainty of evidence using the GRADE approach. Results Of 15 RCTs (6616 pregnancies) reporting on threatened or recurrent miscarriage, 12 (5610 pregnancies) reported on threatened miscarriage with or without a prior history of miscarriage. Results indicated that progesterone probably increases live births (relative risk (RR) 1.04, 95% confidence interval (CI) 0.99–1.10, absolute increase 3.1%, moderate certainty). Of these RCTs, three (1973 pregnancies) reporting on threatened miscarriage with a prior history of miscarriage indicated that progesterone possibly increases live births (RR 1.06, 95% CI: 0.97–1.16, absolute increase 4.4%; low certainty), while four (2540 pregnancies) reporting on threatened miscarriage and no prior miscarriage left the effect very uncertain (RR 1.02, 95% CI: 0.96–1.10, absolute increase 1.7%; very low certainty). Three trials reporting on 1006 patients with a history of two or more prior miscarriages indicated progesterone probably increases live births (RR 1.08, 95% CI: 0.98–1.19, absolute increase 5.7%, moderate certainty). Six RCTs that reported on 2979 patients with at least one prior miscarriage indicated that progesterone probably increases live births (RR 1.07, 95% CI: 1.01–1.13, absolute increase 5.0%; moderate certainty). Progesterone probably has little or no effect on congenital anomalies (RR 1.06, 95% CI: 0.76–1.48, absolute increase 0.1%; moderate certainty), and other serious adverse pregnancy events (RR 1.07, 95% CI: 0.83–1.40, absolute increase 0.2%, moderate certainty). Conclusions In women at increased risk of pregnancy loss, progestogens probably increase live births without increasing adverse maternal and neonatal events. It remains possible that the benefit is restricted to those with prior miscarriages. Previous meta‐analyses have generated inconsistent summary estimates for progestogen supplementation effects on live birth for women with threatened or recurrent miscarriage. To assess this, we conducted a meta‐analysis and found an increase in the likelihood of a live birth with progestogen supplementation, most convincing in those with prior miscarriage