In Vitro Fertilization and Embryo Transfer in Seminatural Cycles for Patients With Ovarian Aging

Abstract

Although controlled ovarian hyperstimulation (COH) has proved more effective than in vitro fertilization (IVF) done on natural cycles, poor responses related to ovarian status defects are not rare and may account for cancellation rates as high as 24% in IVF-embryo transfer (ET) cycles. Both women with low ovarian reserve and those responding poorly to previous ovarian stimulation may be affected. This prospective study was an attempt to determine whether seminatural cycles are a reasonable approach to patients with ovarian aging. A total of 158 cycles were monitored in 75 women. Participants were infertile women less than 38 years of age who had ovulatory cycles every 25 to 35 days and ovarian aging, defined as low ovarian reserve and characterized by high levels of follicle-stimulating hormone by cycle day 3, high estradiol and/or low inhibin B levels, and/or previous cycle cancellations because of a poor ovarian response to COH. Up to 3 cycles were offered. The dominant follicle, selected from cycle day 8 onward, was monitored by ultrasonography and hormone measurements. When it appeared, as evidenced by a serum estradiol exceeding 100 pg/mL and a diameter of more than 12 mm, patients received a gonadotropin-releasing hormone (GnRH) antagonist followed by human menopausal gonadotropin. Oocyte pickup was done 36 hours after administration of human chorionic gonadotropin. Embryo transfers were carried out 2 days after oocyte retrieval. The luteal phase was supported by micronized progesterone. The cancellation rate for 158 cycles was 17.7%. Oocyte pickups were done in 75.3% of cycles, and 91 mature oocytes were retrieved (57.6%). The rate of embryo transfer was 42.4%. Nineteen clinical pregnancies occurred, 5 of which resulted in spontaneous abortion. Seven of the pregnancies occurred in the first treatment cycle. The cumulative rate of pregnancy per patient after 3 treatment cycles was 35.2%. The investigators concluded that IVF with a seminatural cycle protocol is a useful alternative to COH for those who fail to respond well. Candidates include women who require IVF, those with endocrinologic evidence of ovarian aging, and those having a history of one or 2 canceled COH cycles. Better results may be expected as the dose and duration of treatment with a GnRH antagonist are appropriately modified and as the oocyte pickup technique improves.