Ovarian tissue cryopreservation - new opportunity to preserve fertility in female cancer patients

Introduction: Malignant disease and the therapy are major factors that may result in complete loss of fertility. There are several strategies for fertility preservation in fertile women faced with cancer. A modern and potentially effective method of reproductive function protection is ovarian tissue cryopreservation.

Materials and methods: This paper summarizes the medical and scientific knowledge in this interesting multidisciplinary medical field. Furthermore, the authors' own experience with this novel and interesting method of ovarian tissue protection is presented. Ovarian tissue was obtained during laparoscopic surgery in five nuliparous women (aged 19-33) with a diagnosis of lymphoma before chemotherapy from 2004 to 2006. After laboratory preparation, tissue was frozen by a slow cooling technique and stored in liquid nitrogen.

Results: In total 75 women with malignant lymphoma before chemotherapy were referred to our center for consultation--68 chose ovarian inactivation by GnRH analogues during chemotherapy, two IVF cycles with embryo or oocyte cryopreservation and five ovarian tissue cryopreservation. In these five women one to two slices of ovarian cortex from both ovaries were recovered. Totally 20 cryotubes with three pieces of tissue in each were cryopreserved. In no case was metastasis of cancer cells found by histological evaluation.

Conclusions: Cryopreservation of ovarian tissue represents an effective alternative or addition to the cryopreservation of embryos or oocytes for women at risk of premature ovarian failure due to chemotherapy. Reproductive function protection requires close cooperation between oncology departments and assisted reproduction centers.

Cancer, lnfertilty, Chemotherapy, Ovary, Cryopreservation

[1] Ries L.G., Pollack E.S., Young J.L. Jr.: "Cancer patient survival: Surveillance, epidemiology, and end results program, 1973-79". J. Natl. Cancer Inst., 1983, 70, 693.

[2] The Institute of Health Information and Statistics of the Czech Republic: "Cancer Incidence in Czech Republic 2003". NOR, 2006, 44, 1.

[3] Blatt J.: "Pregnancy outcome in long-term survivors of childhood cancer". Med. Pediatr. Oncol., 1999, 33, 29.

[4] Lutchman Singh K., Davies M., Chatterjee R.: "Fertility in female cancer survivors: pathophysiology, preservation and the role of ovarian reserve testing". Hum. Reprod. Update, 2005, 11, 69.

[5] Ataya K., Rao L.V., Lawrence E., Kimmel R.: "Luteinizing hormone-releasing hormone agonist inhibits cyclophosphamide-induced ovanan follicular depletion in rhesus monkeys". Biol. Reprod., 1995, 52, 365.

[6] Goswami D., Conway G.S.: "Premature ovarian failure". Hum. Reprod. Update, 2005, 11, 391.

[7] Crha I., Ventruba P., Petrenko M. et al.: "Cryopreservation of sperm before neoplasm therapy-7 years'experience". Ceska Gynekol., 2002, 67, 324.

[8] Tucker M., Morton P.. Liebermann J.: "Human oocyte cryopreservation: a valid alternative to embryo cryopreservation7". Eur. J. Obstet. Gynecol. Reprod. Biol., 2004, 113 (suppl. I), S24.

[9] Borini A., Bonu M.A., Coticchio G., Bianchi V., Cattoli M., Flamigni C.: "Pregnancies and births after oocyte cryopreservation". Fertil. Steril., 2004, 82, 601.

[10] Marrs R.P., Greene J., Stone B.A.: "Potential factors affecting embryo survival and clinical outcome with cryopreserved pronuclear human embryos". Am. J. Obstet. Gynecol., 2004, 190, 1766.

[11] Blumenfeld Z., Eckman A.: "Preservation of fertility and ovarian function and minimization of chemotherapy-induced gonadotoxicity in young women by GnRH-a". J. Natl. Cancer Inst. Monogr., 2005, 40.

[12] Donnez J., Dolmans M.M., Demylle D. et al.: "Livebirth after orthotopic transplantation of cryopreserved ovarian tissue". Lancet, 2004, 364, 1405.

[13] Donnez J., Godin P.A., Qu J., Nisolle M.: "Gonadal cryopreservation in the young patient with gynaecological malignancy". Curr. Opin. Obstet Gynecol., 2000, 12, 1.

[14] Meirow D., Fasouliotis SJ., Nugent D., Schenker J.G., Gosden R.G., Rutherford A.J.: "A laparoscopic technique for obtaining ovarian cortical biopsy specimens for fertility conservation in patients with cancer". Fertil. Steril., 1999, 71, 948.

[15] Donnez J., Bassil S.: "Indications for cryopre、ervation of ovarian tissue". Hum. Reprod Update, 1998, 4, 248.

[16] Gosden R.G., Bairdt D.T., Wade J.C., Webb R.: "Restoration of fertility to oophorectomized sheep by ovarian autogrnfts stored at -196 degrees C". Hum. Reprod., 1994, 9, 597.

[17] Hovatta O.: "Methods for cryopreservation of human ovarian tissue". Reprod. Biomed. Online, 2005, 10, 729.

[18] Newton H., Aubard Y., Rutherford A., Sharma V., Gosden R.: "Low temperature storage and grafting of human ovarian tissue". Hum. Re prod., 1996, 11, 1487.

[19] Newton H., Fisher J., Arnold J.R., Pegg D.E., Faddy MJ., Gosden R.G.: "Permeation of human ovarian tissue with cryoprotective agents in preparation for cryopreservation". Hum. Rep rod., 1998, I 3, 376.

[20] Gook D.A., Edgar D.H., Borg J., Archer J., Lutjen PJ., mcbain J.C.: "Oocyte maturation, follicle rupture and luteinization in human cryopreserved ovarian tissue following xenografting". Hum. Rep rod., 2003, I 8, 1772.

[21] Candy CJ., Wood MJ., Whittingham D.G.: "Restoration of a normal reproductive lifespan after grafting of cryopreserved mouse ovaries" Hum. Reprod., 2000, 15, 1300.

[22] Almodin C.G., Minguetti-Camara V.C., Meister H. et al.: "Recovery of fertility after grafting of cryopreserved germinative tissue in female rabbits following radiotherapy". Hum. Reprod., 2004, 19, 1287.

[23] Candy CJ., Wood MJ., Whittingham D.G.: "Follicular development in cryopreserved marmoset ovarian tissue af,ter transplantation". Hum Reprod., 1995, 10, 2334.

[24] Kim S.S., Yang H.W., Kang H.G. et al.: "Quantitative assessment of ischemic tissue damage in ovarian cortical tissue with or without anttoxidant (ascorbic acid) treatment". Ferti/. Steril., 2004, 82, 679.

[25] Oktay K., Tilly J.: "Livebirth after cryopreserved ovarian tissue autotransplantation". Lancet, 2004, 364, 2091, author reply 2092.

[26] Meirow D., Levron J., Eldar-Geva T. et al.: "Pregnancy after transplantation of cryopreserved ovarian tissue in a patient with ovarian failure after chemotherapy". N. Engl. J. Med., 2005, 353, 318.

[27] Bedaiwy M.A., Falcone T.: "Ovarian tissue banking for cancer patients: reduction of post-transplantation ischaemic injury: intact ovary freezing and transplantation". Hum. Reprod., 2004, 19, 1242.

[28] Torrents E., Boiso I., Barri P.N., Veiga A.: "Applications of ovarian tissue transplantation in experimental biology and medicine". Hum. Reprod Update, 2003, 9, 471.

[29] Oktay K., Bu yuk E., Veeck L. et al.: "Embryo developm􀅅nt after heterotopic transplantation of cryopreserved ovarian tissue". Lancet, 2004, 363, 837.

[30] Practice Committee of the American Society for Reproductive Medicine: Ovarian tissue and oocyte cryopreservation. Fertil. Steril., 2004, 82, 993.

[31] Martinez-Madrid B., Dolmans M.M., Van Langendonckt A., Defrere S., Donnez J.: "Freeze-thawing intact human ovary with its vascular pedicle with a passive cooling device". Fertil. Steril., 2004, 82, 1390.

[32] Schrader M., Heicappell R 呵Muller M., Straub B., Millier K.: "Impact of chemotherapy on male fertility". Onkologie，2001, 24, 326

[33] Gook D.A., Edgar D.H., Stern C.: "Cryopreservation of human ovarian tissue". Eur. J. Obstet. Gynecol. Reprod. Biol., 2004, 113 (suppl. I), S41.