Restoration of long term ovarian function after heterotopic autotransplantation of cryobanked human ovarian tissue: six year clinical experience

Abstract

Although ovarian cryobanking followed by transplantation appears to be a valuable strategy to preserve fertility, there are many unknowns including long term ovarian function. To assess the long term ovarian function after ovarian transplantation, we analyzed 4 cases of heterotopic autotransplantation of frozen-thawed ovarian tissue during the 6 year period. Prospective clinical study. The study was approved by the institutional review board. Four study patients (three with cervical cancer, one with breast cancer) were identified, and one ovary from each patient was removed and cryopreserved. After cancer treatment, thawed ovarian tissue was transplanted to the space between the rectus muscle and fascia in the abdomen in all 4 patients. A follow-up was lost in one patient because of relapsed disease. Two patients have been followed for 4 years since ovarian transplantation in 2002. The third patient underwent ovarian transplantation in 2005. The restoration and maintenance of ovarian function was monitored by serial blood tests (FSH, LH, E2, Progesterone, Testosterone) and ultrasound. To investigate fertility restoration, three patients underwent IVF cycles. Between 12–20 weeks after transplantation, the return of the ovarian function was evidenced by the elevation of serum estradiol levels and by the decrease of FSH levels (below 15 mIU/ml). However, restored ovarian function lasted only 3–5 months, and 3 patients (except the one with relapsed disease) agreed to undergo second transplantation. The return of ovarian function after the second transplantation was faster in all three patients (between 1–3 months). In contrast to the first transplantation, long term ovarian function (lasting for 9–26 months) was established after the second transplantation. In addition, spontaneous ovulation were evidenced by a sequential hormonal profile and ultrasound. We were able to retrieve 6 oocytes from ovarian grafts in 2 patients between 2003 and 2005. Four MII oocytes were fertilized, developed in vitro for 3 days, and cryopreserved. 1) Long term ovarian function for more than 2 years was established after heterotopic autotransplantation of human ovarian tissue. 2) Follicles developed in the grafts were fertilized and developed up to 6 cell embryos in vitro. 3) When repeated ovarian transplantation is anticipated, transplantation to the hetertopic site can be advantageous, as it is technically easy, non-invasive, and less expensive.