Live birth after in-vitro maturation of oocytes in a patient with specific ovarian insufficiency caused by long-term mitotane treatment for adrenocortical carcinoma

ABSTRACT Research Question Fertility management of woman with persistent specific ovarian dysfunction after long-term Mitotane exposure Design Case report A 33-year-old patient operated for adrenocortical carcinoma and treated with Mitotane was referred for infertility. She was rapidly amenorrheic on Mitotane, a condition that persisted 5 years after cessation. Repeated serum hormone evaluation showed collapsed androgen levels, low estradiol, high gonadotropins (LH 69 and 63; FSH 23 and 43 IU/L), normal inhibin B and decreased AMH levels (1.4 and 0.7 ng/mL). Ultrasound scan revealed 13 antral follicle counts contrasting with high serum gonadotropins levels. After failure to obtain follicular growth under ovarian stimulation, we performed in vitro maturation (IVM) of immatures oocytes aspirated from the antral follicles for microinjection with the patient's partner's spermatozoa to get embryo transfer and pregnancy. Results Two cycles of unstimulated egg retrieval were performed, leading to 7 IVM oocytes which were microinjected. A total of three cleavage-stage embryos were frozen, and unsuccessfully transferred after endometrial preparation using hormone replacement therapy (HRT). After a 20-month break, two new attempts were performed under HRT with an objective to achieve fresh embryo transfer. The last attempt succeeded after transfer of a single day-2 embryo, and the patient delivered a healthy baby. Conclusion We report for the first time persistent specific impaired ovarian function 5 years after withdraw of Mitotane and the first live birth after IVM in this situation. We raise the question of fertility preservation before long-term Mitotane treatment.