Letrozole in Stimulated IVF Cycles
Condition: Subfertility
MeSH terms: Infertility
Study type: Interventional
Phase: Phase 3

Summary: 
      In-vitro fertilization (IVF) is the treatment of choice for couples with prolonged
      infertility. The treatment usually involves hormonal stimulation of the ovaries by follicle
      stimulating hormone (FSH), followed by surgical removal of eggs which are then mixed with
      sperm in the laboratory to create embryos. The success rates of IVF treatment remain
      unsatisfactory and are no longer increasing. One of the reasons is an adverse effect of high
      serum estradiol levels following FSH stimulation on the lining of the uterus.

      Letrozole is a drug used in the prevention of recurrence of breast cancer because of its
      action to reduce the intra-ovarian aromatization of androgens to estrogens. It is now
      increasingly used for ovulation induction and is as safe as clomiphene citrate. Use of
      letrozole during standard ovarian stimulation for IVF producing adequate numbers of oocytes
      with physiological levels of estradiol may increase the present success rate of standard IVF
      treatment.

      The aim of this randomized study is to compare the live birth rate of FSH alone versus
      combined FSH and letrozole used for ovarian stimulation in IVF treatment.
    

Detailed description: 
      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.
    

Intervention name(s): Letrozole
Intervention type(s): Drug
Intervention description(s): Daily 150-300 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.
Other intervention name(s): Letrozole-Teva
Intervention MeSH terms: Letrozole
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Subfertility; In-vitro fertilization; Letrozole