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Approaches Vary on Ovarian Transplants


 

Two recent births made possible through maternal ovarian transplant procedures were the result of markedly different techniques and approaches.

U.S. expert Sherman Silber, M.D., of St. Luke's Hospital, St. Louis, performed an ovarian allotransplant between 24-year-old identical twins, one of whom had premature ovarian failure. The procedure restored the patient's fertility and her ability to conceive naturally (N. Engl. J. Med. 2005;353:58–63).

In Israel, the transplant performed by Dror Meirow, M.D., of Chaim Sheba Medical Center in Tel Hashomer, and colleagues was an autotransplant of a 28-year-old cancer patient's previously frozen healthy ovarian tissue. Conception was achieved through in vitro fertilization (N. Engl. J. Med. 2005;353:318–21).

In the U.S. patient, a woman who had experienced premature ovarian failure at age 14, laparoscopic examination and ovarian biopsy showed atrophic, elongated (“streak”) gonads with no follicles and a small uterus with an otherwise normal reproductive tract. Her donor sister had three children who had been conceived naturally, and she had been using oral contraception in the year preceding the procedure.

The donor's ovary was laparoscopically removed, and the cortical tissue was dissected ex vivo. Meanwhile, the recipient underwent a minilaparotomy during which the cortex of each streak ovary was resected, exposing the raw surface of the medulla.

Hemostasis was controlled with pinpoint microbipolar forceps and continuous irrigation with heparin-treated saline to prevent the formation of a hematoma under the graft.

One-third of the donor ovary was sutured onto the raw medulla of each recipient ovary, and the remaining third was frozen. Analysis of spare tissue from the recipient's ovaries confirmed that there was extensive fibrosis and that there were no follicles.

Both sisters returned home 1 day after the procedure.

At 71 days after transplantation, a 14-mm follicle was observed in the recipient, her serum estradiol level was 154 pg/mL, and her uterine lining was 8 mm thick. Her first postoperative menses occurred at 80 days, although it lasted only a single day. Her ovaries remained quiescent until 128 days after the procedure when another 14-mm follicle was observed. At 142 days after the procedure, she had a heavy menstrual period.

On day 26 of her second menstrual cycle, her β-hCG level (828 mIU/mL) indicated that she was pregnant, and 5 weeks after her second menstrual period, a normal intrauterine pregnancy was confirmed by ultrasound. She gave birth vaginally to a healthy infant at 38 weeks' gestation.

“It is extremely unlikely that the restoration of ovarian function in this patient after transplantation was due to residual follicles in the streak ovary of the recipient,” Dr. Silber and his associates wrote. “She had a decade-long history of amenorrhea with elevated gonadotropin levels on all occasions on which they were measured and no detectable follicles on pathologic examination.”

The Israeli transplant patient had experienced ovarian failure after high-dose chemotherapy for non-Hodgkin's lymphoma. Ovarian tissue containing many primordial follicles was harvested and frozen before she underwent high-dose chemotherapy but after she had undergone a second-line conventional chemotherapy regimen.

The patient remained free of disease 24 months after undergoing chemotherapy, at which point she requested autotransplantation of the thawed ovarian tissue. Strips of the tissue were transplanted to the left ovary, and small fragments were injected into the right ovary. Menstruation resumed spontaneously 8 months later, and baseline levels of antimüllerian hormone, which were previously undetectable (consistent with ovarian failure), were high—consistent with the presence of active follicles in an early stage of growth. This was followed by a rise in inhibin B to levels reported in ovulatory women. Ultrasonography revealed a preovulatory follicle in the left ovary.

The next month, another spontaneous menstrual period occurred, after which modified natural-cycle in vitro fertilization was performed. A single egg was retrieved and fertilized, and a four-cell embryo was transferred to the uterus. A healthy infant was delivered by cesarean section at 38 weeks' gestation.

“Although we cannot rule out the possibility that the egg was derived from the native ovary, we consider this possibility very unlikely, given the consistent evidence of ovarian failure after high-dose chemotherapy and the timing of restoration of ovarian function after transplantation,” they reported.

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