Dydrogesterone as an oral alternative to vaginal progesterone for IVF luteal phase support: A systematic review and individual participant data meta-analysis

PLoS One. 2020 Nov 4;15(11):e0241044. doi: 10.1371/journal.pone.0241044. eCollection 2020.

Abstract

The aim of this systematic review and meta-analysis was to conduct a comprehensive assessment of the evidence on the efficacy and safety of oral dydrogesterone versus micronized vaginal progesterone (MVP) for luteal phase support. Embase and MEDLINE were searched for studies that evaluated the effect of luteal phase support with daily administration of oral dydrogesterone (20 to 40 mg) versus MVP capsules (600 to 800 mg) or gel (90 mg) on pregnancy or live birth rates in women undergoing fresh-cycle IVF (protocol registered at PROSPERO [CRD42018105949]). Individual participant data (IPD) were extracted for the primary analysis where available and aggregate data were extracted for the secondary analysis. Nine studies were eligible for inclusion; two studies had suitable IPD (full analysis sample: n = 1957). In the meta-analysis of IPD, oral dydrogesterone was associated with a significantly higher chance of ongoing pregnancy at 12 weeks of gestation (odds ratio [OR], 1.32; 95% confidence interval [CI], 1.08 to 1.61; P = 0.0075) and live birth (OR, 1.28; 95% CI, 1.04 to 1.57; P = 0.0214) compared to MVP. A meta-analysis combining IPD and aggregate data for all nine studies also demonstrated a statistically significant difference between oral dydrogesterone and MVP (pregnancy: OR, 1.16; 95% CI, 1.01 to 1.34; P = 0.04; live birth: OR, 1.19; 95% CI, 1.03 to 1.38; P = 0.02). Safety parameters were similar between the two groups. Collectively, this study indicates that a higher pregnancy rate and live birth rate may be obtained in women receiving oral dydrogesterone versus MVP for luteal phase support.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Administration, Intravaginal
  • Administration, Oral
  • Dydrogesterone / administration & dosage*
  • Dydrogesterone / adverse effects
  • Female
  • Fertilization in Vitro / adverse effects
  • Fertilization in Vitro / methods*
  • Humans
  • Live Birth
  • Luteal Phase / drug effects
  • Ovulation Induction / adverse effects
  • Ovulation Induction / methods*
  • Pregnancy
  • Pregnancy Rate
  • Progesterone / administration & dosage*
  • Progesterone / adverse effects
  • Progestins / administration & dosage*
  • Treatment Outcome

Substances

  • Progestins
  • Progesterone
  • Dydrogesterone

Grants and funding

The authors declare that the study was supported by Abbott and that one or more of the authors have an affiliation to the company. G.G., H.T. and C.B.’s institution has received investigator fees from Abbott during the conduct of the Lotus I and Lotus II studies. Editorial assistance was provided by Josh Lilly of Alpharmaxim Healthcare Communications, funded by Abbott Established Pharmaceuticals. The funder provided support in the form of salaries for several authors (E.K., C.P.-F., J.I.O., S.D.) but did not have any additional role in the study design, data collection and analysis, decision to publish or preparation of the manuscript. The specific roles of the authors are articulated in the ‘author contributions’ section.