Letrozole in Stimulated IVF Cycles

Trial design:

Infertile women undergoing IVF treatment will be randomized into one of the following two groups by an online randomization program:

Letrozole group: letrozole 2.5mg daily will be given at the start of the antagonist during ovarian stimulation i.e. day 5 of stimulation.

Control group: standard care with FSH alone during ovarian stimulation.

Intervention:

Subjects can be put on oral contraceptive pill in the preceding cycle for scheduling stimulation. On day 2-3, a pelvic ultrasound will be performed for antral follicle count.

Letrozole group:

Daily 150-225 IU human menopausal gonadotrophin (HMG) / Follicle stimulating hormone (FSH) from cycle day 2-4 (at least 5 days after stopping the oral contraceptive pill) and co-treatment with letrozole 2.5 mg daily from stimulation day 5 until the day before hCG administration. GnRH antagonist (cetrotide or orgalutran) 0.25 mg daily from stimulation day 5 until the day of hCG administration.

Control group:

Daily 150-225 IU HMG/FSH cycle day 2-4 (at least 5 days after stopping the oral contraceptive pill) until the day before hCG administration. GnRH antagonist 0.25 mg daily from stimulation day 5 until the day of hCG administration.

A blood sample will be taken and analyzed in the local laboratory for serum E2, P and testosterone levels on cycle day 2 or 3 (baseline) and day of hCG (or the day before). The remaining serum will be frozen and stored for later analysis.

A sample of follicular fluid (FF) will be collected from the first blood free follicle. The FF will be frozen and stored for later analysis: Estradiol, testosterone, inhibin B and AMH levels.

All techniques of IVF including harvesting of oocytes, insemination with specially prepared sperm, embryo culture in the laboratory, embryo transfer and luteal phase support will be according to local protocols. One or two embryos or blastocysts will be replaced.

A pregnancy test will be carried out 2 weeks after embryo transfer in both arms. All women who have a positive pregnancy test 2 weeks after embryo transfer will undergo a transvaginal ultrasound scan to identify the presence and number of gestation sac with a fetal heart signifying an ongoing pregnancy. Pelvic scan will be repeated at 8 weeks, 12 weeks, 24 weeks and 36 weeks of gestation for fetal growth.

Inclusion criteria

• women under 42 years of age
• medical indication for IVF treatment
• antral follicle count prior to ovarian stimulation >=3
• informed consent

Exclusion criteria

• women using donor oocytes
• women undergoing preimplantation genetic diagnosis
• women with abnormal uterine cavity shown on hysterosalpingogram or saline infusion sonogram
• women with hydrosalpinges shown on scanning and not corrected
• previous documented poor response (<=3 oocytes) to ovarian stimulation using at least FSH 225 IU daily