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

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.

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