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Abstract & Commentary
Synopsis: There are increasing numbers of women who have been cured of cancer but have residual endocrine and reproductive ovarian failure. In the current report, a novel approach for reconstituting ovarian function in selected patients is presented. Laparoscopically obtained ovarian tissue was cryopreserved and then thawed. Frozen/thawed samples were comparable to fresh samples in several histological and immunohistochemical analyses. Thus, either orthotopic or heterotopic ovarian transplant may eventually be possible for women cured by radiation, chemotherapy, or the combination thereof.Source: Fabbri R, et al. Gynecol Oncol. 2003;89:259-266.
Currently, there are increasing numbers of young women cancer survivors who have been exposed to chemotherapy and/or radiation therapy. These treatments may have had a deleterious effect on ovarian function, and fertility issues may compromise overall quality of life. In the current report, a new strategy for ovarian tissue cryopreservation is evaluated.
Ovarian tissue was obtained by laparoscopy from 22 patients with different malignant conditions. The specimens were frozen under a strict cryopreservation protocol. For analysis, both fresh and frozen thawed tissues were examined by histological and immunohistochemical analyses. Fabbri and colleagues found good stromal and follicular morphology in both the fresh and frozen thawed tissue. Importantly, there was no significant difference found in follicular density, distribution, and diameters in fresh vs frozen thawed tissue. The follicle immunohistochemical analysis showed a high percentage of negative staining for both estrogen receptor and progesterone receptor. Additionally, Ki67 protein and Bcl2 protein had comparable patterns in fresh and frozen thawed specimens. Fabbri et al concluded that human ovarian tissue morphology, antigenicity, cellular proliferation, and anti-apoptotic index were well preserved by the cryopreservation technique used.
Comment by William B. Ershler, MD
Ovarian damage can occur either from ionizing radiation or from certain types of chemotherapy treatments (most notably alkylating agents, antimetabolites, and vinca alkaloids).1,2 Cryopreservation of ovarian tissue represents an attractive strategy for conserving both steroidogenic and gametogenic functions for women at risk for losing ovarian function from cancer treatment. It is apparent that ovarian tissue collection and storage may have significant advantages over egg or embryo storage. Although oocytes can be collected following gonadotropin stimulation, embryo cryopreservation is only relatively efficient. In contrast, primordial follicles, available in large numbers in ovarian tissue, are better suited for cryopreservation because they are small, lack the zona pellucida, and are metabolically quiescent and undifferentiated.3 Fabbri et al suggest that after thawing of the frozen ovarian tissue it could be grafted into its normal site (orthotopic) or into a site other than its normal position (heterotopic). The advantage of an orthotopic placement would be that the engraftment itself would allow the possibility of pregnancy without further medical assistance, whereas the heterotopic engraftment would require in vitro fertilization to obtain pregnancy.
This is a new and very exciting strategy for the preservation of ovarian function after cancer therapy. The results presented herein suggest that ovarian tissue morphology, antigenicity, cellular proliferation, and antiapoptotic index are preserved by the cryopreservation technique used. There remains a tremendous amount of research to be accomplished before this approach will have widespread clinical application.
Dr. Ershler is UNOVA Fairfax Hospital Cancer Center, Fairfax, VA; Director, Institute for Advanced Studies in Aging, Washington, D.C.
1. Meirow D, Nugent D. Hum Reprod Update. 2001;7:647-653.
2. Grundy R, et al. Arch Dis Child. 2001;84:355-359.
3. Newton H, et al. Hum Reprod. 1996;7:1487-1491.