Embryo Development After Heterotopic Transplantation of Cryopreserved Ovarian Tissue

Patients with cancer might want to avoid infertility and premature menopause as sequelae of chemotherapy and other treatments. Most patients with cancer do not have time for ovarian stimulation as a prelude to in vitro fertilization (IVF). An alternative approach, which could also be useful for single women who do not want to use donor sperm and for children, is to cryopreserve oocytes, but this also requires several weeks of ovarian stimulation. Ovarian function has been preserved experimentally after orthotopic transplantation of frozen-thawed ovarian tissue and heterotopic grafting of fresh human ovarian cortical pieces. This study intended to restore fertility by subcutaneously transplanting frozen, banked ovarian tissue. One ovary was removed from a woman aged 30 years with breast cancer before starting gonadotoxic chemotherapy. Cortical pieces were cryopreserved using a slow freezing technique and dimethylsulfoxide as a cryoprotectant. The tissue was transplanted beneath the abdominal skin 6 years later, after the patient had entered menopause. There were an estimated 11,000 follicles that could potentially last for 12 months. All 15 ovarian cortical pieces were transplanted in the lower abdominal wall. Tissue was suppressed with a combination of follicle-stimulating hormone and human menopausal gonadotropin before every cycle of ovarian stimulation. Oocyte maturity was induced by recombinant human chorionic gonadotropin. Oocytes were retrieved 36 to 40 hours later and intracytoplasmic sperm injection was carried out. A lump was felt at the transplant site 85 days after transplantation, and ovarian endocrine function resumed (Fig. 1). Eight percutaneous oocyte retrievals were carried out over 8 months, 6 of them after ovarian stimulation. Eight of 20 oocytes taken from transplanted tissue were suitable for IVF. One of them fertilized normally and developed into a high-grade 4-cell-stage embryo 24 hours later that was transferred to the patient’s uterus. This experience indicates that endocrine function and fertility could be restored by long-term cryopreservation of ovarian tissue.Fig. 1: Resumption of ovarian function after ovarian transplantation. Peak estradiol concentration accords with that of a typical cycle and is accompanied by a luteinizing hormone surge, but no follicle-stimulating hormone increase is seen. Reproduced with permission. Lancet 2004;363:837–840.