Desogestrel Versus GnRH Antagonist (Ganirelix) in IVF/ICSI Patients Undergoing Ovarian Stimulation: a Randomized Controlled Trial

Study design A prospective controlled randomized clinical trial (RCT) will be conducted to assess the non inferiority of Desogestrel (75 mcg) versus a flexible GnRH antagonist protocol with ganirelix (0.25 mg/day) in ovarian stimulation cycles.All partecipants will provide informed consent after counselling for infertility treatments and routine IVF procedures.

This will be a prospective non-inferiority trial. Given the possibility of dropouts, the study will be designed to include a total of 165 patients Patients will be recruited consecutively and allocated to one of the two groups in alternating manner.

Sample size The number of oocytes retrieved will be the primary efficacy endpoint of the study. Sample size calculation was performed with the assumptions that the non-inferiority margin is corresponding to three or less oocytes . With the objective to demonstrate that the difference in average number of oocytes retrieved between the Desogestrel and the ganirelix groups would not exceed three, the power for a comparison between the two groups would be equal to 87% for 75 evaluable patients in each treatment groups (for an allocation of 1:1 and a total sample size of 150). To allocate at least 150 patients, an additional 10% to cover possible dropping out were planned to allocate.

Ovarian stimulation Patients will be screened using transvaginal ultrasound on menstrual cycle day 2 to 3 . Patients will be then assigned to either the study or the control group. The study group will be administered follitropin alfa ( Bemfola 150 - 225 UI/die) from day 2-3 onward. The initiating dose of follitropin alfa will be decided upon the antral follicle count (AFC). After 4-5 days, ultrasound examination will be performed and the dose of FSH will be adjusted according to follicle development. Ovulation inhibition will be performed using Desogestrel (Cerazette, 75 mcg) starting on stimulation day 7 or when the leading follicle will reach 14 mm, whichever comes first. When the dominant follicles will reach 18 mm in diameter, the final stage of oocyte maturation will be triggered with triptorelin (Decapetyl) 0.2 mg s.c and serum FSH, LH, E2 and P concentrations will be measured using patients' blood tests on the same day of oocyte maturation. Transvaginal ultrasound-guided oocyte retrieval will be conducted 34 - 36 hours after trigger. All follicles with diameter of more than 10 mm will be retrieved.

An antagonist protocol will be used for the control group. Patients will be administered follitropin alfa (Bemfola 150 - 225 IU/die) from day 2-3 onward, with the dose of FSH administration based on the same criteria as for the study group. After 4-5 days, ultrasound examination will be performed and the dose of FSH will be adjusted according to follicle development. Ovulation inhibition will be performed using ganirelix (Orgalutran, 0.25 mg/die) starting on stimulation day 7 or when the leading follicle will reach 14 mm, whichever comes first. When dominant follicles reach 14 mm in diameter. When a diameter of 18 mm is reached, the final stage of oocyte maturation will be triggered with triptorelin (Decapeptyl) 0.2 mg s.c and serum FSH, LH, E2 and P concentrations will be measured using patients' blood tests on the same day of oocyte maturation.