P-809: What does one do when there is no response to various attempts at ovulation induction (OI)? The clomiphene citrate (CC) rescue protocol

Abstract

Risk factors to poor ovarian response (POR) after OI are well known, ranging from impeding reproductive menopause to unknown causes. Several strategies, including multiple protocols of OI, have been used with little or no success. Yet costs with gonadotropins due to drug dosage increase, extended pharmacological requirements, and empirical addition of a variety of drugs tagged with high expenses have increased overall patient burden. Traditionally, when a patient has either poor follicle cohort recruitment (≤ 3) or follicles otherwise fail to grow, treatment is cancelled. Due to several reasons including a last attempt at treatment, we proceed with the cancellation of gonadotropins and initiate the administration of CC. Encouraged by the results of follicle maturation, successful retrievals and pregnancies, we now wish to report a series of cases where a CC protocol was used. Prospective pilot study Nine women aged 39.6 ± 4.6 years suffering from infertility for 35.4 ± 9.2 months were treated between 11/04 and 01/06. Average basal FSH was 11.72 ± 5.9 IU/L. Main infertility factor was: endometriosis (2 patients), male (2 patients) and ovarian (5 patients). On menstrual day 2 all women underwent a transvaginal ultrasound (TVUS) to evaluate follicle reserve and had blood drawn (serum E2 and FSH) before receiving recombinant FSH (rFSH); the initial daily dose ranged from 375 to 450 IU. A follow-up TVUS was performed on cycle day 6 and 2 days thereafter if needed. A POR was defined by the presence of ≤ 2 follicles measuring < 8 mm on D8 or by the lack of development on D10. Once POR was confirmed, OI with rFSH was stopped and CC in a dose of 100 mg/day was initiated for a period of 5 days. In case of follicle recruitment and development to 13-14 mm, the administration of daily 150-225 IU rFSH was resumed and GnRH antagonist (Cetrorelix) was began. Administration of αhCG (250 ug) was initiated with follicle diameters ≥ 18 mm. Ovum pick-ups were performed 35 hours later. Mature oocytes were fertilized and embryo transfer was carried out 72 hours later. Estradiol valerate and micronized progesterone were used for luteal phase support. The interval of follicle growth after CC administration lasted 6.0 ± 2.2 days. Eight patients (88.8%) produced at least 1 mature follicle. One patient did not respond to CC (11.1%). Endometrial thickness on D-α hCG administration was 9.1 ± 2.9mm. Two patients became pregnant (25%) and 1 gave birth to a healthy male infant at term. Tabled 1 These findings suggest that CC can be administered to women with POR when they otherwise fail to recruit or develop follicles. This cheap pharmacologic strategy might rescue some “r-FSH-primed follicles” by the early follicular phase administration of r-FSH. Further, these follicles could lead to egg retrieval, normal fertilization, ET, and generate genetically-related healthy infants in a group of women who would have been forced to try egg donation.