Successful pregnancy after whole ovary microvascular transplantation

Abstract

OBJECTIVE: Cortical grafting for ovary transplantation has been robustly successful, but results in dramatic decrease in oocyte numbers. Microvascular transplantation of the whole ovary may obviate the problem of ischemic follicle loss.DESIGN: Single case report of initial attempt at intact whole ovary microvascular transplantation in the human.MATERIALS AND METHODS: A 38 year-old pair of monozygotic twins requested ovary transplantation because although one of them had normal ovarian function and two children, the other had undergone premature ovarian failure (POF) at age 15. Her FSH level was 81 m/IU/ml and she had a history of amenorrhea for 22 years. The donor ovary was removed via laparoscopy by dividing the ligament at its base to obtain maximum length, while the recipient infundibulopelvic ligament was transected close to the ovary (after first securing with microvascular clamps) via minilaparotomy. The donor ovarian veins (3.0mm diameter) were anastomosed to the recipient's ovarian veins with 9-0 nylon interrupted sutures, and the ovarian arteries (0.5mm diameter) were anastomosed with 10-0 nylon interrupted sutures.RESULTS: Normal blood flow was immediately observed through the ovarian vessels of the transplanted ovary. The recipient's first menstruation in 22 years occurred on day 101 after transplantation and her day 3 FSH level dropped to 7.4 mIU/ml (the same as her sister) by day 158. Ultrasound revealed normal blood flow to the transplanted ovary and normal follicular development. She had normal, regular menstrual cycles until by day 427 her home pregnancy test was positive, and her beta-HCG was 174. A healthy pregnancy ensued. Her 7, 10, and 12-week scans for prenatal evaluation were completely normal with good interval growth and fetal heartbeat of 170. A healthy pregnancy ensued. Follow-up bone scans one and a half years post-op showed continuing resolution of her osteoporosis.CONCLUSIONS: To our knowledge, this is the first successful human intact whole ovary transplant leading to healthy pregnancy, now approaching term. The low serum FSH suggested minimal effects of the brief ischemia on ovarian reserve. The delay of 101 days (3 months) until the first menstruation precisely supports the theories of Gougeon on the dynamics of follicular growth in humans, i.e., that it requires 85 days for eggs in primordial follicles leaving their resting phase to reach sufficient maturity to enter the menstrual cycle and ovulate. OBJECTIVE: Cortical grafting for ovary transplantation has been robustly successful, but results in dramatic decrease in oocyte numbers. Microvascular transplantation of the whole ovary may obviate the problem of ischemic follicle loss. DESIGN: Single case report of initial attempt at intact whole ovary microvascular transplantation in the human. MATERIALS AND METHODS: A 38 year-old pair of monozygotic twins requested ovary transplantation because although one of them had normal ovarian function and two children, the other had undergone premature ovarian failure (POF) at age 15. Her FSH level was 81 m/IU/ml and she had a history of amenorrhea for 22 years. The donor ovary was removed via laparoscopy by dividing the ligament at its base to obtain maximum length, while the recipient infundibulopelvic ligament was transected close to the ovary (after first securing with microvascular clamps) via minilaparotomy. The donor ovarian veins (3.0mm diameter) were anastomosed to the recipient's ovarian veins with 9-0 nylon interrupted sutures, and the ovarian arteries (0.5mm diameter) were anastomosed with 10-0 nylon interrupted sutures. RESULTS: Normal blood flow was immediately observed through the ovarian vessels of the transplanted ovary. The recipient's first menstruation in 22 years occurred on day 101 after transplantation and her day 3 FSH level dropped to 7.4 mIU/ml (the same as her sister) by day 158. Ultrasound revealed normal blood flow to the transplanted ovary and normal follicular development. She had normal, regular menstrual cycles until by day 427 her home pregnancy test was positive, and her beta-HCG was 174. A healthy pregnancy ensued. Her 7, 10, and 12-week scans for prenatal evaluation were completely normal with good interval growth and fetal heartbeat of 170. A healthy pregnancy ensued. Follow-up bone scans one and a half years post-op showed continuing resolution of her osteoporosis. CONCLUSIONS: To our knowledge, this is the first successful human intact whole ovary transplant leading to healthy pregnancy, now approaching term. The low serum FSH suggested minimal effects of the brief ischemia on ovarian reserve. The delay of 101 days (3 months) until the first menstruation precisely supports the theories of Gougeon on the dynamics of follicular growth in humans, i.e., that it requires 85 days for eggs in primordial follicles leaving their resting phase to reach sufficient maturity to enter the menstrual cycle and ovulate.