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

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.

Luteal Phase Support Using Subcutaneous Progesterone: A Systematic Review

“…However, more evidence is necessary to better understand the application of subcutaneous Pg in ART. To the best of our knowledge, no RCT compared a subcutaneous Pg vs. oral dydrogesterone which could be a valuable approach for LPS in women undergoing ART (16,39). In addition, so far no studies have been developed in women with a low prognosis to ART (40)(41)(42)(43)(44)(45)(46) or in women at risk of a hyper-response, such as those affected by PCOS (47)(48)(49).…”

Early-Pregnancy Dydrogesterone Supplementation Mimicking Luteal-Phase Support in ART Patients Did Not Provoke Major Reproductive Disorders in Pregnant Mice and Their Progeny

“…DG as an oral application form shows a lower frequency of adverse effects, and thus has a higher level of patient compliance [10]. Moreover, DG has proven itself as a drug with good bioavailability, and exhibits comparable efficacy to other progestogens in terms of clinical pregnancy rates and live birth rates [4,5]. However, data regarding the safety and tolerability of DG are still limited, and there is a knowledge gap regarding potential long-term consequences for the progeny after DG exposure in utero.…”

“…DG, as a synthetic progestogen, has to be supplemented until the 12th week of pregnancy, resembling the complete first trimester of pregnancy. Two recent meta-analyses provided evidence that DG administration as luteal-phase support in ART patients shows at least similar or even higher efficacy compared to vaginal progestogens with regard to clinical pregnancy rates and ongoing pregnancy/live birth rates [4,5]. Moreover, there seem to be no relevant differences in miscarriage rates and other maternal and fetal/newborn adverse effects between both application forms [5].…”

“…Two recent meta-analyses provided evidence that DG administration as luteal-phase support in ART patients shows at least similar or even higher efficacy compared to vaginal progestogens with regard to clinical pregnancy rates and ongoing pregnancy/live birth rates [4,5]. Moreover, there seem to be no relevant differences in miscarriage rates and other maternal and fetal/newborn adverse effects between both application forms [5]. Nevertheless, it has to be admitted that due to the requirement for a continuous supplementation of DG until the luteal-placental shift [6], there are concerns about the safety of DG during the sensible first-trimester pregnancy phase that may not only affect fetal organogenesis, but may also interfere with later health issues in the newborn, growing child, or adult, and may even generate intergenerational effects [3].…”

Novel nucleic acid aptamer gold (Au)-nanoparticles (AuNPs-AptHLA-G5-1 and AuNPs-AptHLA-G5-2) to detect the soluble human leukocyte antigen G5 subtype (HLA-G5) in liquid samples

“…However, the challenge plaguing researchers and first-line clinicians has always been selecting embryos that can better implant and survive throughout the pregnancy. At present, a widely used strategy in clinical diagnosis and treatment is to select embryos for transfer based on embryo morphology scores (36,37). The outstanding problem of this strategy is that it is impossible to establish a complete standard and quantitatively study embryo morphology, which may not be wholly consistent with its developmental potential.…”