Puberty, Gonadal Function and Pregnancy in Female Patients Following Hematopoietic Cell Transplantation (HCT).

With increasing success of myeloablative HCT for patients with hematologic disorders, development of pre-pubertal children through puberty, return of gonadal function and the ability to become pregnant are of concern. To determine the impact of the preparative regimen on these issues, long-term follow-up records of more than 2,000 patients have been evaluated. Preparative regimens include cyclophosphamide (CY) 200 mg/kg, busulfan (BU) 16 mg/kg plus 120 or 200 mg/kg CY, or CY 120 mg/kg and 12–15.75 Gy total body irradiation (TBI). Among girls who were pre-pubertal at HCT and are now >12 years of age, 24/26 (92%) CY recipients, 11/23 (52%) BUCY recipients, and 46/96 (51%) CY + TBI recipients have developed normally through puberty. Among 148 post-pubertal women transplanted with CY only, 75 (50%) recovered gonadal function at a median of 6 months after HCT and 45 (30%) have become pregnant. This is in contrast to 2 (1%) of the 207 women who received BUCY who have shown gonadal function recovery and 1 has become pregnant. Among the fractionated TBI recipients, 39 (8%) of 460 women who received CY + 12 Gy TBI recovered ovarian function and 17 (3%) have become pregnant whereas among the 366 women who received 14.0–15.75 Gy TBI, 14 (4%) have recovered ovarian function and 4 (1%) have become pregnant. All women who recovered ovarian function after BUCY or TBI regimens were <25 years of age at HCT. The primary pregnancy complication was preterm labor and delivery, but all babies born were normal. For those women who do not recovery ovarian function, in vitro fertilization may be an option, and 14 women in this category have had successful pregnancies with 21 babies born using donated oocytes or pre-HCT stored gametes. These data demonstrate that pre-pubertal girls have more than 50% rate of developing normally through puberty and among women <25 years of age at HCT, recovery of ovarian function varies between 1%-50% depending on preparative regimen and some have become pregnant. For those who do not recover ovarian function, in vitro fertilization may be an option.