RCT of Low-dose Clomiphene vs. High Dose Gonadotropin Protocol for IVF Poor Responders (CLOVANT)

Randomized Prospective Controlled Non-inferiority Trial of Low-dose Clomiphene Based Antagonist Protocol vs. High Dose Gonadotropin/Antagonist Protocol for IVF Poor Responders

The purpose of this study is compare two commonly-used medication protocols ( low-dose clomiphene citrate and high dose gonadotropin protocols) for the treatment of patients with diminished ovarian reserve (decreased number of eggs remaining in the ovary) undergoing IVF. This research is being done because we do not know if these two medication protocols are equally likely to help a woman become pregnant.

The objective of this protocol is to prospectively evaluate whether a clomid-based, low dose gonadotropin protocol (225 IU) would be non-inferior in terms of mature oocyte yield (eggs that are ready to be fertilized) as compared to a high-dose protocol. Patients meeting the criteria for poor ovarian response will be consented and randomized to either a stimulation protocol involving pretreatment with a 0.1mg estradiol patch in the luteal phase starting 10 days after the LH surge (the hormone released by the brain to cause ovulation to occur, which is detectable in urine) followed by oral clomiphene citrate 100mg on days 2-6 of the menstrual cycle and 225 international units of gonadotropins starting on day 5, or to the control group involving the same pretreatment with 0.1mg luteal estradiol patches starting 10 days after the LH surge, with high dose gonadotropins (600IU) alone, starting on day 2 of the cycle. After randomization, patients will undergo routine IVF procedures, monitoring, blood draws, cancellation criteria, oocyte retrieval, and embryo transfer as non-study participants.

Pretreatment with a 0.1mg estradiol patch in the luteal phase starting 10 days after the LH surge followed by clomiphene citrate 100mgon days 2-6 of the menstrual cycle with 225 international units of gonadotropins (eg Follistim , Menopur) starting on day 5

Pretreatment with a 0.1mg estradiol patch in the luteal phase starting 10 days after the LH surge followed high dose gonadotropins (eg. Follistim. Menopur) 600IU starting on day 2 of the cycle

To evaluate the number of mature oocytes retrieved in two different IVF protocols for poor responders

Inclusion Criteria: Patients age 18-42 undergoing IVF AFC <7 (see definition above) and AMH (see definition above) <0.5 and/or prior poor IVF response Exclusion Criteria: BMI (body mass index) >30 PGD (preimplantation genetic diagnosis, in which embryos are biopsied to rule out chromosomal abnormalities) Age >42 Fragile X carriers (a condition associated with premature ovarian aging) TESE (Testicular sperm extraction) Asherman's syndrome (uterine scarring which can affect implantation and pregnancy) Untreated hydrosalpinx (accumulated fluid in the fallopian tube which may be toxic to embryos) >6 prior attempted cycles