臨床婦人科産科61巻12号

2007年12月発行

今月の臨床 不妊診療─現在の課題と将来展望

卵巣組織凍結保存への展望―若年女性がん患者における女性としてのQOL向上を志向して

著者： 鈴木直¹ 石塚文平¹

所属機関： ¹聖マリアンナ医科大学産婦人科

ページ範囲：P.1464 - P.1469

文献概要

はじめに

　近年，乳がんや子宮がんなどの若年女性がんの罹患率が上昇傾向を示している．化学療法や放射線療法はがん細胞のみならず正常細胞にまで影響を及ぼすことから，若年女性がん患者は卵巣機能不全などの副作用により生殖機能が失われることが多い．抗がん剤による卵巣機能不全は，稀発月経や無月経また無排卵症を呈し，化学療法誘発性無月経と称されており，その発生頻度は患者の年齢，抗がん剤の種類，抗がん剤の投与量などに依存すると考えられている．若年女性がん患者における抗がん剤による化学療法後の卵巣機能維持は，妊孕性温存という観点のみならず女性としてのQOL保持に欠かせないものとなり，化学療法施行前に卵子あるいは卵巣組織を体外に摘出し凍結保存する試みが，基礎的に臨床的に世界各国で検討されてきた．近年，欧州で若年女性血液腫瘍患者の卵巣組織を凍結後自家移植し，生児を得たとする報告が続いている．

　本論文では文献的考察を中心として，当院産婦人科学教室の基礎的研究成果の一部も加えて，若年女性がん患者に対する女性としてのQOL向上を志向した，卵巣組織凍結保存に関する知見の一端を述べる．

参考文献

1）Gotta G, Capocaccia R, Coleman RP, et al：Childhood cancer survival in Europe ans the United States. Cancer 95：1767-1772, 2002

2）Meadows AT：Pediatric cancer survivors：past history and future challenges. Curr Probl Cancer 27：112-126, 2003

3）Lutchman Singh L, Davies M, Chatterjee R：Fertility in female cancer survivors：pathophysiology, preservation and the role of ovarian reserve testing. Human Reprod Update 11：69-89, 2005

4）Jemal A, Siegel R, Ward E, et al：Cancer statistics. CA Cancer J Clin 56：106-130, 2006

5）Donnez J, Martinez-Madrid B, Jadoul P, et al：Ovarian tissue cryopreservation and transplantation：a review. Human Reprod Update 12：519-535, 2006

6）Bines J, Oleske DM, Cobleigh MA：Ovarian function in premenopausal women treated with adjuvant chemotherapy for breast cancer. J Clin Oncol 14：1718-1729, 1996

7）Wallace WH, Anderson RA, Irvine DA：Fertility presertvation for young patients with cancer：who is at risk and what ca be offered? Lancet 6：209-218, 2005

8）Blumenfeld Z：Preservation of fertility and ovarian function and minimalization of chemotherapy associated gonadotoxicity and presmature ovarian failure ; the role of inhibin-A and -B as maker. Mol Cell Endocrionol 187：93-105, 2002

9）Behringer K, Breuer K, Reineke T, et al：A report from the German Hodgikin's Lymphoma Study Group. Secondary amenorrhea after Hodgkin's lymphoma is influenced by age at treatment, stage of disease, chemotherapy regimen and the use of oral contraceptives during therapy. J Clin Oncol 23：7555-75564, 2005

10）Morice P, Juncker L, Rey A, et al：Ovarian transposition for patients with cervical carcinoma treated by radiosurgical combination. Fertil Steril 29：199-206, 2000

11）京野廣一，福永憲隆：卵巣組織の凍結，移植と体外培養：悪性腫瘍患者の妊孕力保持について．産科と婦人科115：523-529，2004

12）Donnez J, Dolmans MM, Demylle D, et al：Livebirth after orthotopic transplantation of cryopreserved ovarian tissue. Lancet 364：1405-1410, 2004

13）Demeestere I, Simon P, Emiliani S, et al：Options to preserve fertility before oncological treatment：Cryopreservation of ovarian tissue and its clinical application. Acta Clinica Belbica 61：259-263, 2006

14）Donnez J, Dolmans MM：Livebirth after orthotopic transplantation of cryopreserved ovarian tissue. Letter. Lancet 364：2092-2093, 2004

15）Meirow D, Levron J, Eldar-Geva T：Pregnancy after transplantation of cryopreserved ovarian tissue in a patient with ovarian failure after chemotherapy. N Engl J Med 353：318-321, 2005

16）Meirow D, Levron J, Eldar-Geva T, et al：Monitoring the ovaries after autotransplantation of cryopreserved ovarian tissue：endocrine studies, in vitro fertilization cycles, and live birth. Fertil Steril 87：418. e7-e15, 2007

17）Demeestere I, Simon P, Buxant F, et al：Ovarian function and spontaneous pregnancy after combined heterotopic and orthotopic cryopreserved ovarian tissue transplantation in a patient previously treated bone marrow transplantation：case Report. Human Reprod 21：2020-2014, 2006

18）Demeestrere I, Simon P, Emiliani S, et al：Ongoing pregnancy after a second cryopreserved ovarian tissue transplantation procedure. Abs O-109, i43-44, 23rd Annual Meeting of the ESHURE, Lyon, France, 2007

19）Anderson C, Loft A, Ernst E, et al：Assisted reproductive techniques after autotransplantasion of frozen／thawed ovarian tissue. Abs O-104, i41-42, 23rd Annual Meeting of the ESHURE, Lyon, France, 2007

20）Kagabu S, Umezu M：Transplantation od cryoprederved mouse, Chinese hamster, rabbit, Japanese monkey and rat ovaries into rat recipients. Exp Anim 49：17-21, 2000

21）Yeoman RR, Wolf DP, Lee DM：Coculture of monkey ovarian tissue increase survival after vitrification and slow-rate freezing. Fertil Steril 83：1248-1254, 2004

22）Kagawa N, Kuwayama M, Nakata K, et al：Production of the first offspring from oocytes derived from fresh and cryopreserved pre-antral follicles od adult mice. Reprod BioMed Online 2599, 2007

23）Li YB, Zhou CQ, Yang GF, et al：Modified vitrification method for cryopreservation of human ovarian tissues. Chin Med J 20：110-114, 2007

24）Yin H, Wang X, Kim SS, et al：Transplantation of intact rat gonads using vascular anastomosis：effect of cryopresevation, ischemia and genotype. Human Reprod 18：1165-1172, 2003

25）Bedaiwy A, Jeremias E, Gurunluoglu R, et al：Restortion of ovarian function after autotransplantation of intact frozen-thawed sheep ovaries with microvascular anastomosis. Fertil Steril 79：594-602, 2003

26）Arav A, Revel A, Nathan, et al：Oocyte recovery, embryo development and ovarian function after cryopreservation and transplantation of whole sheep ovary. Human Reprod 20：3354-3359, 2005

27）Martinez-Madrid B, Dolmans MM, Langendonckt AV, et al：Freeze-thawing intact human ovary with its vascular pedicle with a passive cooling device. Fertil Steril 82：1390-1394, 2004

28）Pertoianu A, Vasconcellos LS, Alberti LR, et al：The influence of venous drainage on autologous ovarian transplantation. J Surgi Res 124：175-179, 2005

29）Ino M, Saito J, Ishizuka B, et al：to be submitted

30）Donnez J, Dolmans MM, Demylle D, et al：Restortion of ovarian function after orthotopic（intraovarian and periovarian）translantation of cryopreserved ovarian tissue in a woman treated by bone marrow transplantation for sickle cell anemia：Case report. Human Reprod 21：183-188, 2006

31）Oktay K, et al：Endocrine function and oocyte retrieval after autologous transplantation of ovarian cortical strips to the forearm. JAMA 286：1490-1493, 2001

32）Callejo J, et al：Long-term ovarian function evaluation after autografting by implantation with fresh and frozen-thawed human ovarian tissue. J Clin Endocrinol Metab 86：4489-4494, 2001

33）津田千春，斎藤寿一郎，谷内麻子，他：マウス卵巣の凍結保存に関する基礎的研究．日本産科婦人科学会雑誌53：646（S516），2001

34）井埜まり絵，斎藤寿一郎，鈴木直，他：マウス卵巣における卵巣凍結保存に関する研究．日本産科婦人科学会雑誌59：443（S321），2007

35）Lee DM, Yeoman RR, Battaglia DE, et al：Live birth after ovarian tissue transplant. Nature 428：137-138, 2004

36）Suzuki N, Hashimoto S, Igarashi S, et al：to be submitted

37）Suzuki N, Igarashi S, Ino M, et al：to be submitted

38）Elezovic I, Colovic M, Tomin D, et al：Pregnancy after treatment of secondary acute promyelocytic leukemia following Hodgkin's disease：a case report. Medical Oncology 17：222-224, 2000

39）日本病理剖検輯報，日本病理学会編第46輯，2004

40）Sanchez M, Rosello-Sastre E, Teruel J, et al：Incidence of micrometastasses in women with breast cancer requesting ovarian cryopreservation to preserve fertility. Abs O-108, i43, 23rd Annual Meeting of the ESHURE, Lyon, France, 2007

41）Shimada M, Kigawa J, Nishimura R, et al：Ovarian metastasis in carcinoma of the uterine cervix. Gynecol Oncol 101：234-237, 2006

42）Daniel DF, Moore DH, Look KY, et al：The fate of the ovaries after radical hysterectomy and ovarian transposition. Gynecol Oncol 56：3-7, 1995

43）Kim SS：Fertility preservation in female cancer patients：current development and future directions. Fertil Steril 85：1-11, 2006