An unknown cause of persistent impaired ovarian function: Long-term mitotane exposure for adrenal cortical carcinoma: Successful fertility management with in vitro maturation of oocytes and late recovery of ovarian function

Fertility management of woman with persistent specific ovarian dysfunction after long-term Mitotane exposure and long term follow up of ovarian function. Case report. Department of reproductive medicine of CHIC Creteil and endocrinology CHU Bicêtre. A 33-year-old patient operated for adrenocortical carcinoma and treated with mitotane 6 years ago, 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, slightly decreased AMH levels (1.4 and 0.7 ng/mL) and antral follicle counts (13) not matching with the high FSH levels. After failure to obtain follicular growth under ovarian stimulation, we performed in vitro maturation (IVM) of immatures oocytes aspirated from the antral follicles in order to be used for microinjection with the patient's partner's spermatozoa. 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, during which the patient remained amenorrheic with similar hormone evaluation, 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. This first pregnancy was marked by acute adrenal insufficiency because of uncontrollable vomiting, quickly resolute by hydrocortisone injection. 3 months after delivery, and 7 years after cessation of Mitotane the patient recovered spontaneous regular cycles and became pregnant without any help. She delivered 2 healthy babies (1.5 and 2.5 kg respectively) by cesarian at 36 weeks of amenorrhea. We report for the first time persistent specific impaired ovarian function 5 years after removing mitotane and the first live birth after IVM in this situation. The patient finally recovered ovarian function 7 years after the withdraw of mitotane, resulting to an unexpected spontaneous pregnancy. We raise the question of fertility preservation before long-term mitotane treatments as the delayed of ovarian function recovery may be too long to allow spontaneous conception or use of PMA if needed.