Dienogest/Estradiol Valerate

This pooled analysis compared the risk of venous thromboembolism (VTE) associated with combined oral contraceptives (COCs) containing estradiol (E2) valerate–dienogest with those containing ethinyl E2–levonorgestrel. Data were retrieved from two large, prospective, observational cohort studies. Propensity score subclassification was applied to balance baseline parameters between the COC user cohorts. Crude and adjusted hazard ratios (HRs) were calculated based on the extended Cox model. The pooled data set included 11,616 E2 valerate–dienogest users and 18,681 ethinyl E2–levonorgestrel users, contributing 17,932 and 29,140 women-years of observation, respectively. A significantly decreased VTE risk in E2 valerate–dienogest COCs compared with ethinyl E2–levonorgestrel COCs was observed (propensity score–stratified HR 0.46, 95% CI, 0.22–0.98). This pooled analysis expands data from a previous postauthorization safety study and provides valuable real-world safety information on the relative safety of current COCs.

During the transitional phase of premature ovarian insufficiency (POI), sporadic resumption of ovulation is possible because of fluctuation of hormonal levels but the chance of spontaneous pregnancy is low, and the main perspective of childbearing in these women is egg donation or adoption. The purpose of the study was to verify whether treatment with estrogens in POI patients in transitional phase could reduce FSH levels and to evaluate if this pre-treatment could improve reproductive outcomes of in vitro fertilization (IVF).

Study patients (26) were administered with valerate estradiol 2 mg daily adding dihydrogesterone 10 mg daily during luteal phase for 3 months before IVF. Control group (26 patients) did not receive any pre-treatment. Ovarian stimulation was conducted in both groups with the same short GnRH-antagonist protocol. Clinical and laboratory data of patients were retrospectively analyzed.

In the study group, 4/26 POI patients became spontaneously pregnant during pre-treatment. In the remaining patients, the mean level of FSH after the pre-treatment was significantly reduced compared with baseline. Levels of circulating estradiol on the day of hCG administration were significantly higher in the study group. The total number of MII oocytes retrieved and fertilized oocytes was significantly higher in the study group, as well as the number of embryos transferred for pickup and clinical pregnancy rate.

Treatment with estrogens in infertile POI patients in transitional phase reduces circulating FSH levels, hence causing potential spontaneous conception. Moreover, in these patients, estrogen pre-treatment seems to improve IVF outcomes in a GnRH-antagonist short protocol compared to no pre-treatment.