Abstract
OBJECTIVE: To report a case of unanticipated hyperresponse during controlled ovarian stimulation (COS) despite profoundly suppressed ovarian reserve markers in a patient with long-term combined hormonal contraceptive (CHC) use and discuss the possible mechanisms contributing to this clinical conundrum. DESIGN: Case report. SUBJECTS: A 33-year-old gravida 0 woman presented to the office to discuss planned oocyte cryopreservation. She had been using a vaginal contraceptive ring containing etonogestrel 0.12 mg/day and ethinyl estradiol 0.015 mg/day for the past 12 years. Her antral follicle count and antimüllerian hormone (AMH) at the initial consultation was 1 and 0.17 ng/mL (1.2 pmol/L), respectively. Discontinuation of CHC was recommended. Her cycle day 2/3 follicle-stimulating hormone, luteinizing hormone, and AMH were 5.9 IU/L, 8.1 IU/L, and 0.66 ng/mL (4.7 pmol/L), respectively, 6 months after discontinuing CHC. EXPOSURE: Oocyte cryopreservation and oocyte retrieval for planned oocyte cryopreservation approximately 4 weeks after her most recent ovarian reserve testing. MAIN OUTCOME MEASURES: Total number of oocytes retrieved and cryopreserved after COS. RESULTS: The patient began estrogen priming in the luteal phase of the prior menstrual cycle. Her antral follicle count at the start of COS was 9. The COS was initiated with 300 IU of recombinant follicle-stimulating hormone and 150 IU of human menopausal gonadotropin with a gonadotropin-releasing hormone antagonist protocol. An unanticipated robust response was observed as highlighted by her estradiol levels of 5,992.4 pg/mL (22,000 pmol/L) on the 9th day of COS. Her gonadotropin doses subsequently were decreased over the next 2 days of COS with peak estradiol levels of 7,817.3 pg/mL (28,700 pmol/L). The cumulative gonadotropin dosage during COS was 4,125 IU. She received a gonadotropin-releasing hormone agonist trigger on day 11 of COS; of 55 oocytes retrieved, 50 mature oocytes were cryopreserved. Repeat AMH testing 11 months after discontinuing CHC was 22.4 ng/mL (160 pmol/L). CONCLUSION: Combined hormonal contraceptive may result in profound suppression of ovarian reserve markers even after 6 months of discontinuation; however, rapid reversal of ovarian suppression and hyperresponse may occur once exogenous gonadotropins are administered.