2. Superovulation and IUI
Drugs used for ovarian stimulation included clomiphene citrate (CC) (Clomiphene, Young-Poong, Seoul, Korea), letrozole (Femara, Novartis, Basel, Switzerland), and gonadotropins. Gonadotropins included recombinant FSH (Gonal F, Merck Serono, Geneva, Switzerland), highly purified urinary FSH (Metrodin, Merck Serono), hMG (Menogon, Ferring, Copenhagen, Denmark; Pergonal, Merck Serono; IVF-M, LG life science, Seoul, Korea), or HP-hMG (Menopur, Ferring).
Ovarian stimulation was performed by CC alone (15 cycles), letrozole alone (3 cycles), CC+FSH (55 cycles), CC+hMG (56 cycles), CC+ FSH+hMG (38 cycles), letrozole+FSH (10 cycles), letrozole+hMG (24 cycles), letrozole+FSH+hMG (3 cycles), FSH alone (24 cycles), hMG alone (3 cycles), and FSH+hMG (3 cycles). Among them, pituitary suppression was made by GnRH antagonist in 5 cycles and GnRH agonist in 1 cycle. Distribution of the ovarian stimulation regimen was similar between the two groups.
Ovarian stimulation started on the 3rd day of menstruation, after basal ultrasound examination and hormonal assay. Letrozole (2.5 mg/day) or CC (50 to 100 mg/day) was administered for five consecutive days starting from day 3 to 5. The starting dose of gonadotropin was 75 or 150 IU according to the status of the patients, including age, hormonal status, number of cycles, and response in the previous cycle, and was administered every day or every other day from day 3 to 7. Follicular development was monitored by ultrasound and by serum estradiol levels. A single intramuscular injection of 5,000 to 10,000 IU urinary hCG (Profasi, Merck Serono) or 250 µg recombinant hCG (Ovidrel, Merck Serono) was performed if at least one follicle ≥18 mm. A single IUI was performed 36 to 40 hours later. If an LH surge was assumed by positive urine LH test on the triggering day, IUI was performed the day after hCG injection. Sperm preparation was performed by the density gradient method (Sperm gradient kits, Cook Medical, Brisbane, Australia). Sperm parameters were recorded as prepreparation values.
A serum β-hCG test was performed 15 to 20 days after hCG administration. In pregnancy cycles, transvaginal ultrasound was performed 4 to 5 weeks after hCG administration. Clinical pregnancy was defined as the presence of a gestational sac on ultrasonography. Miscarriage was defined as the loss of a pregnancy before the 12th week of gestation.