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.
Highlights
Ovarian stimulation regimens using exogenous follicle-stimulating hormone (FSH) preparations, in combination with gonadotrophin-releasing hormone analogues, are integral components of in vitro fertilization (IVF) treatment protocols [1]
The two studies included in the meta-analysis of Individual participant data (IPD) were Phase III, randomized, multicenter clinical studies evaluating the efficacy and safety of oral dydrogesterone 30 mg (10 mg three times daily [the dosing frequency of oral dydrogesterone (TID)]) versus those of Micronized vaginal progesterone (MVP) capsules 600 mg (200 mg TID) (Lotus I; NCT01850030) [34] or 8% MVP gel 90 mg once daily (Lotus II; NCT02491437) [33] for luteal phase support in fresh-cycle IVF; both studies involved authors of this meta-analysis as investigators
In order to aggregate the available evidence on the efficacy and safety of oral dydrogesterone and MVP for luteal phase support in fresh-cycle IVF, and to identify prognostic factors of positive clinical outcomes, a one-step meta-analysis of IPD was conducted using a combined dataset from randomized controlled trials (RCTs)
Summary
Ovarian stimulation regimens using exogenous follicle-stimulating hormone (FSH) preparations, in combination with gonadotrophin-releasing hormone analogues, are integral components of in vitro fertilization (IVF) treatment protocols [1]. Progesterone for luteal phase support can be administered via oral, intramuscular, intravaginal [7], subcutaneous [8], or rectal routes [9]. Micronized vaginal progesterone (MVP), administered as capsules or an 8% gel, has been prescribed more frequently than intramuscular progesterone–as shown in a worldwide web survey [7]–as MVP avoids the unpleasant administration-related side effects associated with intramuscular administration (such as injection-site pain and abscess formation) [13, 14]. MVP has been shown in a pilot IVF study to affect the local microbiome [16]. It has been postulated, following endometrial alterations in the uterine microbiome in response to inflammation, that a progesterone-resistant endometrium can develop [17]
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