Live Birth After Allografting of Ovarian Cortex Between Genetically Nonidentical Sisters

Abstract

Options available to preserve fertility in women who need to undergo aggressive chemotherapy include embryo, oocyte, and ovarian tissue cryopreservation. When none of these options are available or appropriate at the time of treatment, allografting should be considered for a patient who has not undergone previous oocyte, embryo, or ovarian tissue cryopreservation. Allografting has the potential to restore ovarian activity and natural fertility. In a recent report, allografting of ovarian cortex between genetically nonidentical sisters restored ovarian function in 3 cases. The present report describes the first pregnancy and live birth in one of these cases. The patient was a 32-year-old woman who had presented with homozygous sickle cell anemia in 1992 at 15 years of age and at that time received chemotherapy (busulfan, cyclophosphamide) and total body irradiation before bone marrow transplantation; the donor was her human leukocyte antigen (HLA) genetic-compatible sister. Subsequent HLA group analysis showed complete chimerism (HLA compatibility) between the sisters. To restore ovarian function in this patient who was planning to be married, an allograft was performed using ovarian tissue from the same sister who had donated bone marrow 17 years earlier. Immunosuppressive treatment was not required, and there was no sign of rejection. Three and a half months after reimplantation, restoration of ovarian function was demonstrated by increased vaginal estradiol levels and follicular development (detected with ultrasound). The patient showed regular ovulatory cycles for 9 months but failed to become pregnant because of proximal tubal occlusion (unknown at the time of the procedure); this made microsurgical anastomosis impossible. Therefore, in vitro fertilization was mandatory. Sixteen months after grafting, stimulation was initiated. Subsequently, 3 oocytes were retrieved and 2 embryos obtained; one was frozen and the other transferred, resulting in an ongoing intrauterine pregnancy. The patient was followed up every 3 weeks and delivered a healthy baby girl weighing 3.150 g at 37 2/7 weeks of gestation. These findings describe the first pregnancy to occur after ovarian cortex allografting between sisters who are genetically different but fully HLA compatible due to previous bone marrow transplantation.