Dydrogesterone 10mg tablets

ObjectiveTo compare reproductive outcome between luteal-phase support (LPS) protocols for frozen embryo transfer (FET) cycles with hormone replacement therapy (HRT).MethodsA search was conducted in MEDLINE, Scopus, LILACS, EMBASE, Scielo.br, PROSPERO, CINAHL, PsycINFO, AMED, ClinicalTrials.gov, ICTRP, the Cochrane Library and conference proceedings, with no restrictions on date, geography or language. We included all randomized controlled trials (RCTs) that allocated infertile women to at least two different hormone-based LPS protocols for HRT-FET, with similar baseline characteristics between groups. The Preferred Reporting Items for Systematic reviews and Meta-Analyses extension statement for network meta-analyses (PRISMA-NMA) was followed. A random-effects network meta-analysis was performed for direct and indirect pairwise comparisons to rank available LPS protocols by the surface under the cumulative ranking curve area (SUCRA). Risk of bias was assessed using the Cochrane risk-of-bias tool version 1. Certainty of evidence was evaluated using the Confidence in Network Meta-Analysis (CINeMA) criteria. The primary outcomes were the live birth rate and the combined rate of ongoing pregnancy and live birth; the secondary outcomes were the clinical pregnancy rate and the pregnancy loss rate.ResultsTen RCTs assigned a total of 4216 patients to nine different LPS approaches. Regarding the combined outcome of ongoing pregnancy and live birth, oral dydrogesterone (DYD) combined with gonadotropin-releasing hormone agonist (GnRHa) was significantly more efficacious compared with all other LPS protocols (very low to low certainty of evidence), with SUCRA analysis ranking it as the treatment of choice (SUCRA = 97.3%). When the analysis was restricted to live birth only, vaginal suppository progesterone showed a higher likelihood of being the treatment of choice (SUCRA = 89.7%), but only exhibited a significant difference on pairwise analysis when compared with intramuscular progesterone (odds ratio (OR), 0.53 (95% CI, 0.33-0.84); low certainty of evidence) and intramuscular progesterone + vaginal suppository progesterone (OR, 0.47 (95% CI, 0.32-0.69); low certainty of evidence). For the clinical pregnancy rate, no significant differences between treatments were found (very low to low certainty of evidence), with vaginal suppository progesterone + human chorionic gonadotropin being the highest-ranked treatment (SUCRA = 33.7%). For pregnancy loss rate, intramuscular progesterone + vaginal suppository progesterone was significantly more efficacious compared with either treatment alone (low certainty of evidence), and had the highest chance of being the top-ranked treatment (SUCRA = 51.4%).ConclusionsThere is very-low-to-low-certainty evidence that oral DYD + GnRHa and vaginal suppository progesterone alone could be the most promising LPS approaches to increase the rates of live birth and ongoing pregnancy in women undergoing HRT-FET. However, the low certainty of evidence and the lack of a clear first-ranked treatment, due to inconsistencies in the analysis for some outcomes, stress the need for further RCTs on this subject. © 2025 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

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Background/Objectives: Until recently, oral dydrogesterone has only been established in fresh in vitro fertilization (IVF) cycles, whereas its role in luteal phase support (LPS) for frozen embryo transfer (FET) cycles remains unclear. The aim of this study is to determine whether oral dydrogesterone as LPS in FET cycles results in pregnancy rates comparable to vaginal progesterone, focusing primarily on ongoing pregnancy rates, but also on clinical pregnancy, miscarriage, and live birth rates. Methods: The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Five databases (Embase, MEDLINE®, APA PsycInfo, Global Health, and HMIC) and two additional sources were searched from inception to November 28, 2024. Only randomized controlled trials (RCTs) were included. A common effects model combined risk estimates, and heterogeneity was assessed using I2. Study quality was evaluated with Risk of Bias 2 (RoB2), and evidence certainty was graded using GRADE. Results: Overall, five RCTs with a total of 636 women were included in the meta-analysis. The comparison between oral dydrogesterone and vaginal progesterone for LPS did not yield significant differences for any of the outcomes studied. For ongoing pregnancies, the pooled odds ratio (OR) was 0.90 (95% CI: 0.59-1.35), with no heterogeneity (I2 = 8.7%). For miscarriage events, the OR was 1.41 (95% CI: 0.63-3.13, I2 = 0). For clinical pregnancies, the OR was 0.94 (95% CI: 0.62-1.42, I2 = 49.2%), with heterogeneity attributed to dosage. For live births, the pooled OR was 1.08 (95% CI: 0.67-1.75, I2 = 0%). Two studies were assessed as high risk of bias, two as low risk, and one as moderate. The GRADE assessment indicated low to moderate certainty of evidence. Conclusions: Oral dydrogesterone and vaginal progesterone yield comparable reproductive outcomes for LPS in FET cycles. Given its ease of administration, dydrogesterone may serve as a viable alternative in future FET protocols. However, further RCTs are needed to assess its efficacy against other progesterone administration routes.

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The route of administration significantly influences the pharmacokinetics of progestogens. For luteal phase support (LPS) after fresh embryo transfer in IVF, ESHRE recommends vaginal, intramuscular, subcutaneous progesterone or oral dydrogesterone. This network meta-analysis evaluated the relative effectiveness of progestogen administration routes on clinical pregnancy rate (CPR) and live birth rate (LBR) in fresh IVF cycles. A systematic review identified peer-reviewed, published randomized controlled trials (RCTs) comparing individual progestogens (versus placebo or other progestogens) and reporting CPR. Studies involving frozen-thawed transfers, non-progestogenic LPS or non-available formulations were excluded. Of the 24 RCTs included, oral administration was the only route reaching statistical significance for increased CPR, although overlapping confidence intervals across comparisons indicate uncertainty in clinically relevant superiority. For LBR, only oral and intramuscular routes demonstrated statistically significant improvement versus placebo; vaginal and subcutaneous did not. These findings, supported by sensitivity analyses excluding low-quality and older studies, suggest that oral and intramuscular progestogens may be more effective in improving IVF outcomes, but outcome differences require further studies. This study substantially advances the evidence base by integrating recent data, applying rigorous quality assessment standards and using state-of-the-art network meta-analytic methodology, contributing to refining recommendations for optimal progestogenic LPS in fresh IVF cycles.

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BACKGROUND: Preterm birth remains a major contributor to neonatal morbidity and mortality worldwide. Oral dydrogesterone is used in some clinical settings for preterm birth prevention, despite uncertainty regarding its effectiveness. This systematic review aimed to evaluate the efficacy and safety of oral dydrogesterone compared with placebo in women at risk of preterm birth. METHODS: We conducted a systematic review and meta-analysis in accordance with PRISMA guidelines. Randomized controlled trials comparing oral dydrogesterone with placebo in pregnant women at risk of preterm birth were included; non-randomized, observational, and animal studies were excluded. We searched PubMed, Cochrane Library, Web of Science, and Scopus from inception to December 2024. Risk of bias was assessed using the Cochrane Risk of Bias tool. Random-effects meta-analyses were performed where appropriate. We evaluated Certainty of evidence using the GRADE approach, and trial sequential analysis (TSA) was conducted to assess the conclusiveness of the evidence. The review was registered in PROSPERO (CRD42025639288). RESULTS: Five randomized controlled trials involving 436 participants were included. Compared with the placebo, dydrogesterone showed a non-significant trend toward increased gestational age at delivery (mean difference, 0.42 weeks; 95% CI -0.70 to 1.55) and a reduced risk of neonatal intensive care unit admission (risk ratio, 0.74; 95% CI 0.47 to 1.18). No statistically significant differences were observed for other maternal or neonatal outcomes. The certainty of evidence was rated as low or very low for most outcomes using GRADE. TSA demonstrated that the accumulated evidence remains underpowered and insufficient to draw firm conclusions. CONCLUSION: Current randomized evidence does not demonstrate a statistically or clinically meaningful benefit of oral dydrogesterone over placebo in preventing preterm birth or improving maternal or neonatal outcomes. The low to very low certainty of evidence and inconclusive TSA findings indicate that the existing evidence base is insufficient to support clinical recommendations. Larger, high-quality randomized trials are required before oral dydrogesterone can be considered for routine clinical use.

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