Comparison of oral dydrogestrone with progesterone gel and micronized progesterone for luteal support in 1,373 women undergoing in vitro fertilization: a randomized clinical study

Ganesh, Ashalatha; Chakravorty, Nishant; Mukherjee, Rajdeep; Goswami, S.K.; Chaudhury, Koel; Chakravarty, Baidyanath

doi:10.1016/j.fertnstert.2011.01.148

Cited by 62 publications

(73 citation statements)

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“…Dydrogesterone also appears to have no affinity for androgenic, estrogenic, glucocorticoid or mineralocorticoid receptors (Schindler, 2009), demonstrating a favorable safety and tolerability profile in pregnancy, both to the mother and child (Queisser-Luft, 2009; Mirza et al ., 2016). Furthermore, data from prospective trials for luteal phase support in IVF show that oral dydrogesterone is as effective as micronized vaginal progesterone (MVP), is well tolerated overall, and has a higher patient satisfaction rate than MVP (Chakravarty et al ., 2005; Patki and Pawar, 2007; Ganesh et al ., 2011; Salehpour et al ., 2013; Tomic et al ., 2015; van der Linden et al ., 2015; Saharkhiz et al ., 2016). …”

Section: Introductionmentioning

confidence: 99%

A Phase III randomized controlled trial comparing the efficacy, safety and tolerability of oral dydrogesterone versus micronized vaginal progesterone for luteal support in in vitro fertilization

et al. 2017

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STUDY QUESTIONIs oral dydrogesterone 30 mg daily (10 mg three times daily [TID]) non-inferior to micronized vaginal progesterone (MVP) 600 mg daily (200 mg TID) for luteal support in in vitro fertilization (IVF), assessed by the presence of fetal heartbeats determined by transvaginal ultrasound at 12 weeks of gestation?SUMMARY ANSWERNon-inferiority of oral dydrogesterone versus MVP was demonstrated at 12 weeks of gestation, with a difference in pregnancy rate and an associated confidence interval (CI) that were both within the non-inferiority margin.WHAT IS KNOWN ALREADYMVP is routinely used in most clinics for luteal support in IVF, but it is associated with side effects, such as vaginal irritation and discharge, as well as poor patient acceptance. Dydrogesterone may be an alternative treatment due to its patient-friendly oral administration.STUDY DESIGN, SIZE, DURATIONLotus I was an international Phase III randomized controlled trial, performed across 38 sites, from August 2013 to March 2016. Subjects were premenopausal women (>18 to <42 years of age; body mass index (BMI) ≥18 to ≤30 kg/m2) with a documented history of infertility who were planning to undergo IVF. A centralized electronic system was used for randomization, and the study investigators, sponsor's study team, and subjects remained blinded throughout the study.PARTICIPANTS/MATERIALS, SETTING, METHODSIn total, 1031 subjects were randomized to receive either oral dydrogesterone (n = 520) or MVP (n = 511). Luteal support was started on the day of oocyte retrieval and continued until 12 weeks of gestation (Week 10), if a positive pregnancy test was obtained at 2 weeks after embryo transfer.MAIN RESULTS AND THE ROLE OF CHANCEIn the full analysis set (FAS), 497 and 477 subjects in the oral dydrogesterone and MVP groups, respectively, had an embryo transfer. Non-inferiority of oral dydrogesterone was demonstrated, with pregnancy rates at 12 weeks of gestation of 37.6% and 33.1% in the oral dydrogesterone and MVP treatment groups, respectively (difference 4.7%; 95% CI: −1.2–10.6%). Live birth rates of 34.6% (172 mothers with 213 newborns) and 29.8% (142 mothers with 158 newborns) were obtained in the dydrogesterone and MVP groups, respectively (difference 4.9%; 95% CI: −0.8–10.7%). Oral dydrogesterone was well tolerated and had a similar safety profile to MVP.LIMITATIONS, REASONS FOR CAUTIONThe analysis of the results was powered to consider the clinical pregnancy rate, but the live birth rate may be of greater clinical interest. Conclusions relating to the differences between treatments in live birth rate, observed in this study, should therefore be made with caution.WIDER IMPLICATIONS OF THE FINDINGSOral dydrogesterone may replace MVP as the standard of care for luteal phase support in IVF, owing to the oral route being more patient-friendly than intravaginal administration, as well as it being a well tolerated and efficacious treatment.STUDY FUNDING/COMPETING INTEREST(S)Sponsored and supported by Abbott Established Pharmaceuticals Division. H.T....

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Section: Introductionmentioning

confidence: 99%

A Phase III randomized controlled trial comparing the efficacy, safety and tolerability of oral dydrogesterone versus micronized vaginal progesterone for luteal support in in vitro fertilization

et al. 2017

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“…injection or vaginal insertion. With the exception of the synthetic progestin dydrogesterone (Ganesh et al , 2011), the oral route of administration has been demonstrated to be less effective compared with the i.m. or vaginal routes (van der Linden et al , 2011).…”

Section: Introductionmentioning

confidence: 99%

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

Baker

Jones²,

Doody

et al. 2014

Human Reproduction

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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...

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“…(9-11) Chakravarty et al (9) and Ganesh et al (10) reported pregnancy rates of 22.8% and 28.7%, respectively, when dydrogesterone 20 mg per day was used for luteal phase support. Salehpour et al reported a pregnancy rate of 25% when dydrogesterone at 40 mg per day was used for luteal phase support in ARTs.…”

Section: Discussionmentioning

confidence: 99%

“…(4) Dydrogesterone, a synthetic retro isomer of progesterone, is also administered orally; however, it has better bioavailability than oral progesterone due to its enhanced confi guration. Randomised studies by Chakravarty et al, (9) Ganesh et al (10) and Salehpour et al (11) showed that the use of dydrogesterone resulted in pregnancy rates that were similar to those from the use of vaginal progesterone. In the randomised study by Chakravarty et al, (9) live birth rates were also comparable between women who used dydrogesterone and those who used vaginal progesterone.…”

Section: Introductionmentioning

confidence: 99%

Live birth rates and safety profile using dydrogesterone for luteal phase support in assisted reproductive techniques

Nadarajah

Rajesh

Wong

et al. 2017

smedj

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, MMed, FRCOG INTRODUCTION Assisted reproductive techniques (ARTs) result in a defi cient luteal phase, requiring the administration of intramuscular, intravaginal or oral exogenous progesterone. Dydrogesterone, an oral retroprogesterone with good bioavailability, has been used in assisted reproductive cycles with outcomes that are comparable to those of vaginal or intramuscular progesterone. However, there are limited reviews on its use for luteal phase support in ARTs, in terms of pregnancy outcomes and associated fetal anomalies. This study aimed to review the live birth rates and associated fetal anomalies of women who were given dydrogesterone for luteal phase support in assisted reproductive cycles at a tertiary hospital in Singapore. METHODS RESULTSThe pregnancy and live birth rates were 34.7% and 27.7%, respectively. Among those who achieved pregnancy, 17.0% miscarried, 0.8% had ectopic pregnancies and 0.3% had molar pregnancies. Fetal anomalies were detected in 1.9% of pregnancies, all of which were terminated by choice.CONCLUSION Since the outcomes of dydrogesterone are comparable to those of intramuscular and vaginal progesterone, it is a reasonable option to provide luteal phase support for women who are uncomfortable with injections or vaginal insertions. Randomised controlled studies are needed to determine the optimal dosage of dydrogesterone for luteal phase support in ARTs.

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Comparison of oral dydrogestrone with progesterone gel and micronized progesterone for luteal support in 1,373 women undergoing in vitro fertilization: a randomized clinical study

Cited by 62 publications

References 37 publications

A Phase III randomized controlled trial comparing the efficacy, safety and tolerability of oral dydrogesterone versus micronized vaginal progesterone for luteal support in in vitro fertilization

A Phase III randomized controlled trial comparing the efficacy, safety and tolerability of oral dydrogesterone versus micronized vaginal progesterone for luteal support in in vitro fertilization

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

Live birth rates and safety profile using dydrogesterone for luteal phase support in assisted reproductive techniques

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