menopur in gonadotrophin-releasing hormone (gnrh) antagonist cycles with single embryo transfer

Conditions: Infertility

Summary: the main purpose of this clinical research trial was to compare the ongoing pregnancy rate between two gonadotrophins for controlled ovarian stimulation (menopur and recombinant follicle-stimulating hormone (fsh)), in cycles where a gonadotrophin-releasing hormone (gnrh) antagonist was used for prevention of premature luteinizing hormone (lh) surge and where a single embryo was transferred at the blastocyst stage.

this was a randomized, open-label, assessor-blind, parallel groups, multicentre trial comparing the efficacy of highly purified menotrophin (menopur; ferring) and recombinant fsh (puregon/follistim; msd/merck) in women undergoing controlled ovarian stimulation following a gnrh antagonist protocol. the use of oral contraceptives for programming of the trial cycle was prohibited. on day 2-3 of the menstrual cycle, participants were randomized in a 1:1 fashion to treatment with either highly purified menotrophin (menopur) or recombinant fsh, and stimulation was initiated. the gonadotrophin starting dose was 150 international units (iu) daily for the first 5 days. hereafter, the participants were seen on stimulation day 6 and subsequently at least every 2 days when a transvaginal ultrasound was made to monitor response to stimulation. from stimulation day 6 and onwards, dosing could be adjusted according to individual patient response with the purpose of achieving 8-10 oocytes at the time of oocyte retrieval. the dose adjustment could be by 75 iu per adjustment and could not be done more frequently than every 4 days. the maximum allowed gonadotrophin dose was 375 iu daily and participants could be treated with gonadotrophin for a maximum of 20 days. coasting was prohibited. the gnrh antagonist (orgalutran/ganirelix acetate injection; msd/merck) was initiated on stimulation day 6 at a daily dose of 0.25 mg and continued throughout the gonadotrophin treatment period. a single injection of recombinant human chorionic gonadotrophin (hcg) 250 µg (ovitrelle/ovidrel; merck serono/emd serono) was administered to induce final follicular maturation as soon as 3 follicles of ≥ 17 mm were observed; i.e., the day of reaching the hcg criterion or the next day. oocyte retrieval took place 36h (± 2h) after hcg administration. oocytes were inseminated using partner sperm by intracytoplasmic sperm injection (icsi) 4h (± 1h) after retrieval. oocyte, embryo and blastocyst quality was assessed daily from oocyte retrieval till 5 days after. on day 5 after oocyte retrieval, a single blastocyst of the best quality available was transferred and all remaining blastocysts were frozen. vaginal progesterone capsules (utrogestan; seid) 600 mg/day were provided for luteal phase support from the day after oocyte retrieval till the day of the beta human chorionic gonadotrophin (βhcg) test (13-15 days after embryo transfer); prolonged luteal phase support beyond this time point was not allowed. clinical pregnancy was confirmed by transvaginal ultrasound 5-6 weeks after embryo transfer and ongoing pregnancy was confirmed by transvaginal ultrasound 10-11 weeks after embryo transfer. post-trial follow-up included pregnancy outcome (e.g. live birth) and neonatal health from the fresh trial cycle. additional post-trial activities included follow-up of frozen embryo replacement cycles initiated within 1 year after the participant's randomization date.

Eligibility criteria:
inclusion criteria: * informed consent documents signed prior to screening evaluations * in good physical and mental health * pre-menopausal females 21-34 years of age * body mass index (bmi)18-25 kg/m2 * eligible for intracytoplasmic sperm injection (icsi) * unexplained infertility or partner with mild male factor infertility * infertility for at least 12 months before randomization * regular menstrual cycles of 24-35 days, presumed to be ovulatory * hysterosalpingography, hysteroscopy, or transvaginal ultrasound documenting a uterus consistent with expected normal function * transvaginal ultrasound documenting expected normal function of the ovaries * early follicular phase serum levels of fsh between 1 and 12 iu/l * early follicular phase total antral follicle (diameter 2-10 mm) count ≥ 10 for both ovaries combined * willing to accept transfer of one blastocyst in the fresh cycle * willing to undergo frozen embryo replacement cycles with transfer of one blastocyst per cycle within the first year after randomisation exclusion criteria: * known polycystic ovarian syndrome or known endometriosis stage i-iv * diagnosed as "poor responder" in a previous controlled ovarian stimulation (cos) cycle * severe ovarian hyperstimulation syndrome (ohss)in a previous cos cycle * history of recurrent miscarriage * current or past (12 months prior to randomization) abuse of alcohol or drugs, and/or current (last month) intake of more than 14 units of alcohol per week * current or past smoking habit of more than 10 cigarettes per day * hypersensitivity to any active ingredient or excipients in the medicinal products used in the trial * hypersensitivity to gonadotrophin-releasing hormone (gnrh) or any other gnrh analogue * previous participation in the trial * use of any non registered investigational drugs during 3 months before randomization