Autotransplantation of Thawed Ovarian Tissue Temporarily Restores Ovulatory Function

Emma Hitt, PhD

October 16, 2003

Oct. 16, 2003 -- Thawed ovarian tissue autotransplanted into a human subject caused temporary restoration of endocrine function and spontaneous ovulatory function, indicating a promising strategy for fertility conservation in women with cancer, new research suggests.

S. Samuel Kim, MD, from the Eulji University School of Medicine, in Seoul, Korea, and colleagues presented their findings in an oral presentation Wednesday at the 59th annual meeting of the American Society of Reproductive Medicine in San Antonio, Texas.

According to the researchers, previous reports have suggested that fresh ovarian tissue can regain its ovulatory function after heterotopic autotransplantation, but this has not been demonstrated with cryopreserved ovarian tissue.

The study was conducted in only one patient, but Dr. Kim told Medscape in a phone interview that he would expect this procedure to work in other patients. Furthermore, although the report states that the initial transplant ceased working after 31 weeks, a subsequent transplant of frozen tissue into the same patient continues to function one year after transplant, he said.

In their report, Dr. Kim and colleagues describe the case of a 37-year-old regularly menstruating woman diagnosed with stage Ib squamous cell carcinoma of the cervix. The woman was scheduled for radical hysterectomy, lymph node dissection, and radiotherapy. Before treatment, the patient consented to bilateral salpingo-oophorectomy to preserve her ovarian tissue.

The ovaries, sliced into thin cortical sections (1 x 1 x 5 mm), were frozen and stored in liquid nitrogen. For autotransplantation, 40 cortical sections of stored ovarian tissue were thawed and separated into two groups. The researchers transplanted one group into the space between the pectoralis muscle and breast tissue and the other group into the space between the rectus sheath and the rectus muscle.

Dr. Kim and colleagues measured serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, and progesterone. For 10 weeks after transplantation, blood hormone levels "...were consistent with a postmenopausal state," the researchers report.

However, after 14 weeks, hormone levels indicated the reestablishment of ovarian function. Serum estradiol was 57.5 pg/mL and FSH was 39 IU/L. In addition, a dominant follicle was detected (8.5 x 11 mm).

Starting 24 weeks after transplantation, hormone levels were measured every two days for five weeks. During this stage, spontaneous ovulation was indicated by a surge of LH (69.8 IU/L) followed by increased levels of progesterone (9.6 ng/mL). Before the LH surge, estradiol level was 305 pg/mL.

Ultrasound revealed a dominant follicle (10 x 10 mm) in the abdominal site but no sign of follicular development in the breast site.

"A problem of ovarian transplantation is ischemic damage -- we are not connecting blood vessels in this procedure," Dr. Kim said. "Therefore, we selected the rectus muscle as a location because it is highly vascular," he said. Breast tissue was selected because of its estrogen dependence, similar to ovarian tissue. "But transplant to this location did not work well, probably because the circulation is not as good as it is to the rectus muscle," Dr. Kim explained.

Ovarian function ceased around 31 weeks after transplantation, as measured by decreased FSH and undetectable estradiol levels.

"The present study demonstrated not only restoration of endocrine function but also spontaneous ovulation after heterotopic autotransplantation of frozen-thawed human ovarian tissue," the researchers conclude in their abstract.

The study was independently funded. The authors reported no pertinent financial disclosures.

ASRM 2003 Annual Meeting: Abstract O-248. Presented Oct. 15, 2003.

Reviewed by Gary D. Vogin, MD

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