Fresh Human Orthotopic Ovarian Cortex Transplantation: Long-term Results

Abstract

An increasing number of young women are being diagnosed with cancer, and most cancer treatments have irreversibly negative effects on reproduction. Ovarian stimulation and preservation of oocytes or embryos is far from an ideal solution, in part because hormonal treatment may adversely affect some cancers. Another possibility is cryopreservation of ovarian tissue for later autotransplantation, but the ischemic damage caused by the procedure can lead to follicle loss. Using the ovarian medulla for orthotopic ovarian cortex transplantation might limit the risk of ischemia because the ovarian artery would assure a good blood supply. In addition, the medulla may have a role in follicular development. This prospective case-control study examined the effects of ischemia on long-term ovarian function in 12 premenopausal women who had abdominal hysterectomy for uterine disease and also bilateral fresh orthotopic transplantation of the entire ovarian cortex. Five control women had only hysterectomy. Serum levels of follicle-stimulating hormone (FSH) and anti-Müllerian hormone (AMH) were monitored over 2 years, and ovulatory cycles were identified by vaginal ultrasonography and estimating serum progesterone. Bilateral cortex resection and transplantation took about 30 minutes and caused no complications. Ovulation returned in 11 of the 12 grafted patients (91.7%). The mean number of ovulations was 9.3, compared to 12.0 in control women. Nine study patients remained ovulatory 2 years after surgery. Five of the 12 women in the study group had the same pattern of FSH secretion as the control women. In six cases the serum FSH increased postoperatively and then declined to less than 20 IU/liter after 5 months. Two patients ultimately had menopausal levels of FSH. In only one grafted patient did ovarian function cease after surgery. AMH levels correlated less closely with normal ovarian function than did FSH levels. Serum AMH tended to decline after surgery, but was higher in women whose FSH patterns suggested normal ovarian function. Although this is a small-scale study, the results indicate that fresh orthotopic ovarian cortex transplantation maintains normal ovarian function for at least 2 years in a majority of women, and also may protect against ovarian ischemia.