Dataset Information

A multi-center, randomized, open-label, parallel group study of a natural micronized progesterone vaginal tablet as a luteal support agent in Japanese women undergoing assisted reproductive technology.

ABSTRACT:

Purpose

To verify sufficient progesterone supplementation during the luteal phase and to determine the efficacy and safety of a natural micronized progesterone vaginal tablet (FE 999913) in Japanese women undergoing in vitro fertilization-embryo transfer or intracytoplasmic sperm injection.

Methods

In a multi-center, randomized, open-label, parallel group trial, 108 subjects were randomized to receive FE 999913 vaginally twice daily (n = 54) or three times daily (n = 54) for up to 10 weeks. Primary endpoints were the proportion of subjects with serum progesterone concentration ≥10 ng/ml on day 5 and ongoing pregnancy rate at week 5.

Results

Ninety-four subjects completed the trial and 90 subjects underwent embryo transfer. The proportion of subjects with serum progesterone concentration ≥10 ng/ml on day 5 was 98.9 % and the lower limit of 95 % CI of the difference between the current trial and MEGASET trial was -3.6 %, which was within the non-inferiority criterion. The ongoing pregnancy rate was 22.2 %, which is similar to that in actual clinical settings in Japan. No safety concerns were observed.

Conclusions

FE 999913 was useful in this trial from the aspects of sufficient supplementation of progesterone, comparable pregnancy rate with that in clinical practice in Japan, and safety.

Clinical trial registration

ClinicalTrials.gov identifier: NCT01710514.

SUBMITTER: Fujiwara T

PROVIDER: S-EPMC4592497 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description: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/m(2), 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 the progesterone dosing regimen studied and duration of treatment for the patient population examined in this study.Wider implications of the findingsSubcutaneous 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 i.m. routes of administration.Study funding/competing interestsThe study was funded by Institut Biochimique SA (IBSA). CAJ, BC, ST and CJ are employees of IBSA. FH currently consults for IBSA.Trial registration numberNCT00828191.

Project description:Purpose:The aim of this audit was to assess the overall experience and patient convenience of vaginal progesterone tablets (Lutigest®, marketed as Endometrin® in the USA) used for luteal phase support (LPS) during in vitro fertilization (IVF) treatment. Patients and methods:This questionnaire-based audit included responses from 100 patients undergoing IVF treatment at six IVF clinics in the UK from September 2015 to November 2016. Fourteen days after starting progesterone supplementation for LPS during their IVF treatment, patients rated overall experience and perceived convenience of the prescribed progesterone by completing a questionnaire. Results:Of the 100 patients included, 96 received vaginal progesterone tablets for LPS. Overall, 53.1% (51/96) indicated that the progesterone tablets were "very easy" to use; 42.7% (41/96) and 44.8% (43/96) found it "very convenient" or "neither convenient or inconvenient" to administer the tablet, respectively. Overall experience with using progesterone tablets was rated as "very comfortable" by 34.4% (33/96) and "neither comfortable or uncomfortable" by 56.3% (54/96) of patients. The applicator was used by 93.8% (90/96) of patients to administer the tablet, and 86.5% (83/96) indicated that the applicator was easy to clean for repeated use. A total of 33 patients had a previous IVF cycle during which they were prescribed vaginal progesterone pessaries for LPS. Compared with progesterone pessaries, the majority found treatment with progesterone tablets to be more comfortable (60.6%; 20/33) and more convenient (57.6%; 19/33) and indicated that the progesterone tablet was their preferred progesterone formulation for LPS (60.6%; 20/33). Conclusion:These findings offer insights into real-world patient experiences with the progesterone vaginal tablet formulation. The results suggest overall patient convenience, ease, and comfort with using progesterone vaginal tablets for LPS. The majority of patients found progesterone vaginal tablets more convenient and comfortable to use compared with progesterone pessaries.