A randomized, controlled trial comparing the efficacy and safety of aqueous subcutaneous progesterone with vaginal progesterone for luteal phase support of in vitro fertilization

Abstract

STUDY QUESTIONIs the ongoing pregnancy rate with a new aqueous formulation of subcutaneous progesterone (Prolutex®) non-inferior to vaginal progesterone (Endometrin®) when used for luteal phase support of in vitro fertilization?SUMMARY ANSWERIn the per-protocol (PP) population, the ongoing pregnancy rates per oocyte retrieval at 12 weeks of gestation were comparable between Prolutex and Endometrin (41.6 versus 44.4%), with a difference between groups of −2.8% (95% confidence interval (CI) −9.7, 4.2), consistent with the non-inferiority of subcutaneous progesterone for luteal phase support.WHAT IS KNOWN ALREADYLuteal phase support has been clearly demonstrated to improve pregnancy rates in women undergoing in vitro fertilization (IVF). Because of the increased risk of ovarian hyperstimulation syndrome associated with the use of hCG, progesterone has become the treatment of choice for luteal phase support.STUDY DESIGN, SIZE, DURATIONThis prospective, open-label, randomized, controlled, parallel-group, multicentre, two-arm, non-inferiority study was performed at eight fertility clinics. A total of 800 women, aged 18–42 years, with a BMI of ≤30 kg/m2, with <3 prior completed assisted reproductive technology (ART) cycles, exhibiting baseline (Days 2–3) FSH of ≤15 IU/L and undergoing IVF at 8 centres (seven private, one academic) in the USA, were enrolled from January 2009 through June 2011.PARTICIPANTS/MATERIALS, SETTING, METHODSIn total, 800 women undergoing IVF were randomized after retrieval of at least three oocytes to an aqueous preparation of progesterone administered subcutaneously (25 mg daily) or vaginal progesterone (100 mg bid daily). Randomization was performed to enrol 100 patients at each site using a randomization list that was generated with Statistical Analysis Software (SAS®). If a viable pregnancy occurred, progesterone treatment was continued up to 12 weeks of gestation.MAIN RESULTS AND THE ROLE OF CHANCEUsing a PP analysis, which included all patients who received an embryo transfer (Prolutex = 392; Endometrin = 390), the ongoing pregnancy rate per retrieval for subcutaneous versus vaginal progesterone was 41.6 versus 44.4%, with a difference between groups of −2.8% (95% CI −9.7, 4.2), consistent with the non-inferiority of subcutaneous progesterone for luteal phase support. In addition, rates of initial positive β-hCG (56.4% subcutaneous versus 59.0% vaginal; 95% CI −9.5, 4.3), clinical intrauterine pregnancy with fetal cardiac activity (42.6 versus 46.4%; 95% CI −10.8, 3.2), implantation defined as number of gestational sacs divided by number of embryos transferred (33.2 versus 35.1%; 95% CI −7.6, 4.0), live birth (41.1 versus 43.1%; 95% CI −8.9, 4.9) and take-home baby (41.1 versus 42.6%; 95% CI −8.4, 5.4) were comparable. Both formulations were well-tolerated, with no difference in serious adverse events. Analysis with the intention-to-treat population also demonstrated no difference for any outcomes between the treatment groups.LIMITATIONS, REASONS FOR CAUTIONThe conclusions are limited to th...

Progesterone vaginal capsule versus vaginal gel for luteal support in normoresponder women undergoing long agonist IVF/ICSI cycles

“…Nevertheless, later studies and meta-analyses suggested that there were no differences between the two [3,20,21]. A recent randomized controlled trial comparing the efficacy of subcutaneous and vaginal progesterone forms reported that positive β-hCG, clinical pregnancy and take-home baby rates were comparable between the groups [22]. In a prospective study by Silverberg et al [23], live birth rates were reported to be higher in the vaginal progesterone group than in intramuscular progesterone arm.…”

Has ART Finally Got a Patient-Friendly Progesterone?

“…A prospective, open-label, randomized, controlled, parallel-group, multicenter, two-arm, non-inferiority study was performed at eight fertility clinics [29]. A total of 800 women, aged 18-42 years, with a BMI of B30 kg/m [2], with \3 prior completed assisted reproductive technology (ART) cycles, exhibiting baseline (Days 2-3) FSH of B15 IU/L, and undergoing IVF at eight centers (seven private, one academic) in the USA, were enrolled from January 2009 through June 2011.…”

“…Analysis with the intention-to-treat population also demonstrated no difference for any outcomes between the treatment groups. Baker et al concluded that subcutaneous progesterone represents a novel option for luteal phase support in women undergoing IVF who for personal reasons prefer not to use a vaginal preparation or who wish to avoid the side effects of vaginal or IM routes of administration [29].…”

Didrogesterona versus progesterona como suporte de fase lútea: revisão sistematizada e meta-análise de ensaios clínicos randomizados

“…Recentemente, um estudo comparou uma preparação de progesterona por via subcutânea com a progesterona vaginal (32). Não houve diferenças nos desfechos reprodutivos entre os dois grupos, porém foram relatados efeitos colaterais associados à injeção, como dor local, edema, inflamação e formação de hematoma (32).…”

“…Não houve diferenças nos desfechos reprodutivos entre os dois grupos, porém foram relatados efeitos colaterais associados à injeção, como dor local, edema, inflamação e formação de hematoma (32).…”