Kemal HANSU, Alev ÖZER, İlter BAKKALOĞLU
Anatolian Journal of Obstetrics and Gynecology Research - 2025;2(3):99-110
Threatened miscarriage affects approximately 20% of pregnancies and results in pregnancy loss in around half. Progesterone therapy is the most commonly applied pharmacological approach. The efficacy and safety of dydrogesterone were systematically evaluated and compared with micronized/vaginal progesterone for management of threatened miscarriage using analysis of randomized controlled trials (RCTs). Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, RCTs published between January 1, 1980, and September 1, 2025, were screened. The inclusion criteria comprised patients diagnosed with threatened miscarriage in the first trimester, use of dydrogesterone or micronized/vaginal progesterone as intervention, and placebo or conservative approach as comparator. Twelve RCTs involving around 6000 participants were included. Miscarriage rates across the studies ranged from 10% to 33.3%. Large-scale, placebo-controlled studies did not show a significant improvement in live birth rate with vaginal/micronized progesterone compared to placebo (e.g., 20% vs. 22% miscarriage rate, p>0.05). Similarly , dydrogesterone did not provide significant superiority compared to placebo in large trials (12.8% vs. 14.3%, p=0.772). However, smaller studies reported a significant reduction in miscarriage rates compared to conservative approach (e.g., 12.5% vs. 28.4%, p<0.05). Some studies showed that dydrogesterone was associated with earlier cessation of vaginal bleeding, while vaginal progesterone reduced pain and uterine contractions. Adverse events were uncommon but sedation occurred more frequently with vaginal or micronized progesterone. Although pharmacovigilance data have suggested possible associations of dydrogesterone with hypospadias and congenital heart anomalies, no such relationship was confirmed in RCTs. RCT evidence regarding progesterone support in threatened miscarriage is heterogeneous and does not demonstrate a consistent effect in increasing live birth in the general population. While dydrogesterone has advantages for symptom control and practical ease of use, its effect on live birth is no different from other management strategies. Progesterone therapy should be individualized considering patient risk profile and clinical characteristics. Future biomarker-guided RCTs with robust methodology may help resolvie uncertainties and defining the specific subgroups that would benefit from personalized treatment.
