Factors responsible for multiple pregnancies after ovarian stimulation and intrauterine insemination with gonadotropins

Purpose: The present study was undertaken in order to analyze possible factors that could be responsible for multiple pregnancies in normoovulatory women undergoing superovulation with gonadotropins and intrauterine artificial insemination. Methods: We retrospectively analyzed several clinical parameters in patients that achieved gestation with this treatment. Patients were divided into two groups depending on sperm origin (husband and donor sperm). Furthermore, they were subclassified as follows: (a) cycles resulting in single pregnancies (n=366), (b) cycles ending in multiple pregnancies (n=126), and (c) a control group composed of unsuccessful cycles (n=366). Results: In cycles employing husband's sperm, the age, number of cycles necessary to reach pregnancy, serum estradiol (E₂) levels, and number of follicles were significantly (P<0.05) different in multiple pregnancies compared to single or nonpregnant cycles. In donor insemination, women with multiple pregnancies were significantly younger than nonpregnant patients. There was a significant increase in the number of follicles developed (P<0.00001) and serum E₂ levels on the day of hCG (P<0.05) in multiple compared to single pregnancies and unsuccessful cycles. The number of motile sperm in the insemination specimen was not different among the established groups. When both types of treatments were grouped, pregnant patients were significantly (P<0.00001) younger than women with failed cycles. In addition, multifetal pregnancies were significantly (P<0.05) more frequent in women <30 years old. E₂ production was significantly (P<0.00008) higher in twin and multifetal pregnancies than in single or nonpregnant cycles. Follicular development was also significantly (P<0.00001) higher in twin and multifetal pregnancies compared to failed cycles. Conclusions: The results suggest that young women (<30 years) who develop more than six follicles with E₂ >1000 pg/ml when stimulated with gonadotropins are at higher risk of multiple gestation. These data may be helpful in preventing this undesired complication of assisted reproduction techniques.