Safety of ovarian cryopreservation and transplantation in patients with acute leukemia: a case series

• Published in: American journal of obstetrics and gynecology 2024-01, Vol.230 (1), p.79.e1-79.e10
• Main Authors: Sönmezer, Murat, Şükür, Yavuz Emre, Saçıntı, Koray Görkem, Özkavukçu, Sinan, Kankaya, Duygu, Atabekoğlu, Cem Somer, Cengiz Seval, Güldane, Oktay, Kutluk H.
• Format: Article
• Language: English
• Subjects: acute lymphoblastic leukemia; acute myeloid leukemia; Adult; Anti-Mullerian Hormone; Cryopreservation; Female; fertility preservation; Fertility Preservation - methods; Humans; Leukemia, Myeloid, Acute - pathology; Leukemia, Myeloid, Acute - therapy; ovarian cryopreservation; ovarian transplantation; Ovary - transplantation; Pregnancy; Young Adult
• ISSN: 0002-9378; 1097-6868; 1097-6868
• DOI: 10.1016/j.ajog.2023.08.032

With increased success, ovarian tissue cryopreservation has recently become a standard technique for fertility preservation. However, malignant cell introduction through ovarian tissue transplantation remains a major concern for patients with acute leukemias. This study aimed to investigate the safety of performing autologous ovarian tissue transplantation in survivors of acute leukemia. Clinical, histopathological, and molecular data of 4 women with acute myeloid leukemia and 2 women with acute lymphoblastic leukemia who underwent ovarian tissue cryopreservation and transplantation were analyzed in this case series. Following cryopreservation of 66% to 100% of an ovarian cortex with a slow freezing method, all women received high-dose multiagent alkylating preconditioning chemotherapy for allogeneic hematopoietic stem cell transplantation. Before the ovarian tissue transplantation, (1) antral follicle counts, serum antimüllerian hormone and follicle-stimulating hormone levels were assessed to confirm primary ovarian insufficiency; (2) all recipients were cleared by their hematologist-oncologists; (3) representative cortical strips were screened for leukemia infiltration by histologic (hematoxylin and eosin staining), immunohistochemical (CD3, CD20, CD34, CD68, CD117, CD163, PAX-5, Tdt, lysozyme, and MPO), and molecular marker evaluation (BCR/ABL p190 and AML1/ETO) where appropriate. The median age was 20 years (interquartile range, 15–32) at ovarian tissue cryopreservation. Before undergoing hematopoietic stem cell transplantation, all patients received induction or consolidation chemotherapy that included cytarabine + daunorubicin or Berlin-Frankfurt-Munich-95 protocol and were in remission. The mean serum antimüllerian hormone was 1.9±1.7 ng/mL before ovarian tissue cryopreservation. In all cases, ovarian tissue screening for leukemic cells was negative. Ovarian transplantation was performed laparoscopically with or without robotic assistance, after a median of 74.5 months (interquartile range, 41–120) after ovarian tissue cryopreservation. Ovarian function resumed in all patients after a median of 3.0 months (range, 2.5–4.0), and 2 women had 1 live birth each. The median graft longevity was 35.5 months (interquartile range, 18–57) after ovarian tissue transplantation. After a median follow-up of 51 months (interquartile range, 20–74), all patients remained relapse-free. In 1 patient, the graft was removed during cesarean delivery and was negative for i