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

Published:October 17, 2021DOI:


      Research question

      How should the fertility of a woman with persistent specific ovarian dysfunction after long-term mitotane exposure be managed?


      Case report. A 33-year-old woman who underwent surgery for adrenocortical carcinoma and treated with mitotane was referred for infertility. She rapidly became amenorrhoeic while taking mitotane, a condition that persisted for 5 years after cessation. Repeated serum hormone evaluation showed collapsed androgen levels, low oestradiol, high gonadotrophins (LH 69 and 63; FSH 23 and 43 IU/l), relatively high inhibin B level and slightly decreased anti-Müllerian hormone levels (1.4 and 0.7 ng/ml). An ultrasound scan revealed an antral follicle count of 13, contrasting with high serum gonadotrophin levels. After failure to obtain follicular growth after ovarian stimulation, in-vitro maturation (IVM) of immature oocytes aspirated from the antral follicles was carried out for microinjection with the spermatozoa of the patient's partner.


      Two cycles of unstimulated egg retrieval were carried out, producing seven IVM oocytes, which were microinjected. A total of three cleavage-stage embryos were vitrified and unsuccessfully transferred after endometrial preparation using hormone replacement therapy (HRT). After a 20-month break, two new attempts were carried out under HRT with the aim of achieving a fresh embryo transfer. The last attempt succeeded after transfer of a single day-2 embryo, and the patient delivered a healthy baby.


      Persistent specific impaired ovarian function 5 years after withdrawal of mitotane, and the first live birth after IVM in this situation, are reported. The question of fertility preservation before long-term mitotane treatment is raised.


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      Hélène Bry-Gauillard is a practitioner at the Centre of Reproductive Medicine, Creteil Hospital, and in the department of Reproductive Endocrinology, Bicêtre Hospital, University Paris-Saclay. Her clinical research focuses on reproductive endocrinology disorders and their fertility management. She has published several studies either in her own name or as co-author.
      Key message
      Persistent specific impaired ovarian function is reported 5 years after withdrawal of mitotane given at adjuvant therapy for 5 years, with the first live birth obtained after IVM in this situation. We raise the question of discussing fertility preservation in patients undergoing long-term mitotane treatments.