Ovulatory failure, fertility preservation and reproductive strategies in the setting of gynecologic and non-gynecologic malignancies

The advances in assisted reproductive technology over time have paralleled the insights gained into the natural history of different gynecologic malignancies. Subgroups of young patients with early stage ovarian cancer, endometrial carcinoma and cervical carcinoma may be considered to be at relatively low risk of recurrence and may be treated conservatively with the aim to preserve fertility when this is of prime concern. Unilateral adnexectomy with preservation of the contralateral ovary and uterus may be appropriate for some patients with epithelial ovarian cancers, and certainly should be the procedure of choice for those young women with borderline tumors and early stage sex cord-stromal and malignant germ cell tumors. Administration of high-dose progestins may obviate the need for immediate hysterectomy in a young patient with a well-differentiated endometrial carcinoma desirous of childbearing. The performance of vaginal radical trachelectomy in conjunction with laparoscopic pelvic lymphadenectomies has emerged as a real breakthrough for a highly select group of young women with early invasive tumors of the cervix. In this review, we also discuss reproductive strategies for women who experience chemotherapy-induced ovulatory failure and also address the potential for ovarian cortex cryopreservation and transplantation, and uterine transplantation, all of which are looming on the horizon.

Fertility preservation; Malignancy; Conservative surgery; Infertility

[1] Murdoch W.J., van Kirk E.A., Alexander B.M.: ·'DNA damages in ovarian surface epithelial cells of ovulatory hens". Exp. Biol. Med (Maywood), 2005, 230, 429.

[2] Cash Study Group: "Oral contraceptive use and the risk of ovarian cancer". The Centers for Disease Control Cancer andSteroid Hormone Study. JAMA, 1983, 249, 1596.

[3] Whittemore A.S., Harris R., Itnyre J.: "Characteristics relating to ovarian cancer risk: Collaborative analysis of 12 US case-control studies. II Invasive epithelial ovarian cancer in white women. Collaborative Ovarian Cancer Group". Am. J. Epidemio/., 1993, 137, 92 .

[4] Harris R., W hittemore A.S., Itnyre J.: "Characteristics relating to ovarian cancer risk: Collaborative analysis of 12 US case-control studies. III Epithelial tumors of low malignant potential in white women. Collaborative Ovarian Cancer Group". Am. J. Epidemiol., 1992, 136, 1204.

[5] Ness R.B., Cramer D.W., Goodman M.T. et al.: "Infertility, fertility drugs, and ovarian cancer: A pooled analysis of case-control studies". Am. J. Epidemiol., 2002, 155, 217.

[6] Tewaii K.. Rose G.S., Balderston K.D. et al.: "Fertility drugs and malignant germ cell tumour of the ovary in pregnancy". Lancet, 1998, 351, 957.

[7] Spitz S.: "The histological effects of nitrogen mustards on human tumors and tissues". Cancer, 1948, 383, 1.

[8] Howell S.J., Shalet S.M.: "Spermatogenesis after cancer treatment: Damage and recovery". J. Natl. Cancer Inst. Monogr., 2005, 34, 12.

[9] Minton S.E., Munster P.N.: "Chemotherapy-induced amenorrhea and fertility in women undergoing adjuvant treatment for breast cancer" Cancer Control., 2002, 9, 466.

[10] Schilsky R.L., Lewis B.J., Sherins R.J., Young R.C.: "Gonadal dysfunction in patients receiving chemotherapy for cancer". Ann. Intern. Med., 1980, 93, 109.

[11] Franchi-Rezgui P., Rousselot P., Espie M. et al.: "Fertility in young women after chemotherapy with alkylating agents for Hodgkin and nonHodgkin lymphomas". Hematol. J., 2003, 4, 116.

[121 Gershenson D.M.: "Menstrual and reproductive function after treatment with combination chemotherapy for malignant ovarian germ cell tumors". J. Clin. Oneal., 1988, 6, 270.

[13］Seymour J.F.: "Ovarian tissue cryopreservation for cancer patients: W ho is appropriate?". Reprod. Fertil. Dev., 2001, 13, 81.

[14] Oktay K., Buyuk E.: "The potential of ovarian tissue transplant to preserve fertility". Expert. Opin. Biol. Ther., 2002, 2, 361.

[15] Le Floch 0., Donaldson S.S., Kaplan H.S.: "Pregnancy following oophoropexy and total nodal irradiation in women with Hodgkin's disease" Cancer, 1976, 38, 2263.

[16] Hunter M.C., Glees J.P., Gazet J.C.: "Oophoropexy and ovarian function in the treatment of Hodgkin's disease". Clin. Radio!., 1980, 31, 21.

[17] Williams R.S., Littell R.D., MendenhaII N.P.: "Laparoscopic oophoropexy and ovarian function in the treatment of Hodgkin's disease". Cancer, 1999, 86, 2138.

[18] Holmes G.E., Holmes F.F.: "Pregnancy outcome of patients treated for Hodgkin's disease: A controlled study". Cancer, 1978, 41, 1317.

[19] Horning S.J., Hoppe R.T., Kaplan H.S., Rosenberg S.A.: "Female reproduction after treatment for Hodgkin's disease". NEJM, 1977, 304, 1377.

[20] Makar A.P., Trope C.: "Fertility preservation in gynecologic cancer". Acta Obstet. Gynecol. Scand., 2001, 80, 794.

[21] Perrin L.C., Low J., Nicklin J.L. et al.: "Fertility and ovarian function after conservative surgery for germ cell tumours of the ovary". Aust NZ J. Obstet. Gynaecol., 1999, 39, 243.

[22] Low J.J., Perrin L.C., Crandon A.J., Hacker N.F.: "Conservative surgery to preserve ovarian function in patients with malignant germ cell tumors. A review of 74 cases". Cancer, 2000, 89, 391.

[23] Zanella G., Bonazzi C., Cantu M. et al.: "Survival and reproductive function after treatment of malignant germ cell ovarian tumors". J. Clin Oneal., 2001, 19, 1015.

[24] Tangir J., Zelterman D., Ma W., Schwartz P.E.: "Reproductive function after conservative surgery and chemotherapy for malignant germ cell tumors of the ovary". Obstet. Gynecol., 2003, 101, 251.

[25] Morice P., Camatte S., El Hassan J., Pautier P., Duvillard P., Castaigne D.: "Clinical outcomes and fertility after conservative treatment of ovarian borderline tumors". Fertil. Steril., 2001, 75, 92.

[26] Camatte S., Morice P., Pautier P. et al.: "Fertility results after conservative treatment of advanced Stage serous borderline tumour of the ovary" Br. J. Obstet. Gynecol., 2002, 109, 376.

[27] Beiner M.E., Gotlieb W.H., Davidson B. et al.: "Infertility treatment after conservative management of borderline ovarian tumors". Cancer, 2001, 92, 320.

[28] Chan J.K., Lin Y.G., Loizzi V. et al.: "Borderline ovarian tumors in reproductive-age women. Fertility-sparing surgery and outcome". J. Re prod Med., 2003, 48, 756.

[29] Donnez J., Munschke A., Berliere M. et al.: "Safety of conservative management and fertility outcome in women with borderline tumors of the ovary". Fertil. Steril., 2003, 79, 1216.

[30] Seracchioli R., Venturoli S., Colombo F.M. et al.: "Fertility and tumor recurrence rate after conservative laparoscopic management of young women with early-Stage borderline ovarian tumors". Fertil. Steril., 2001, 76, 999.

[31] Williams T.J.: "Management of ovarian carcinoma in young women". Clin. Obstet. Gynecol., 1976, 19, 673.

[32] Morice P., Wicart-Poque F., Rey A. et al.: "Results of conservative treatment in epithelial ovarian carcinoma". Cancer, 2001, 92, 2412.

[33] Colombo N., Chiari S., Maggioni A. et al.: "Controversial issues in the management of early epithelial ovarian cancer: Conservative surgery and role of adjuvant therapy". Gynecol. Oneal., 1994, 55, S47.

[34] Morice P., Camatte S., Wicart-Poque F. et al.: "Results of conservative management of epithelial malignant and borderline ovarian tumours" Hum. Reprod. Update, 2003, 9, 185.

[35] Yoshinaka A., Fukasawa I., Sakamoto T. et al.: "T he fertility and pregnancy outcomes of the patients who underwent preservative operation followed by adjuvant chemotherapy for malignant ovarian tumors". Arch. Gynecol. Obstet., 2000, 264, 124.

[36] Seiden M.V., Spitzer T.R., McAfee S., Fuller A.F.: "Successful pregnancy after high-dose cyclophosphamide, carboplatinum, and taxol with peripheral blood stem cell transplant in a young woman with ovarian carcinoma". Gynecol. Oneal., 2001, 83, 412.

[37] Brown C.L., Dharmendra B., Barakat R.: "Preserving fertility in patients with epithelial ovarian cancer: The role of conservative surgery in treatment of early stage disease" (abstract). Gynecol. Oncol., 2000, 76, 240. (Annual meeting of the Society of GynecologicOncologists).

[38] Schilder J.M., Thompson A.M., DePriest P.D. et al.: "Outcome of reproductive age women with Stage IA or IC invasive epithelial ovarian cancer treated with fertility-sparing therapy". Gynecol. Oneal., 2002, 87, 1.

[39] Steinkampf M.P., Dharia S.P., Hammond K.: "Assisted reproduction in patients with early-stage ovarian malignancies". Fertil. Steril., 2003, 80, 1510.

[40] J Fasouliotis S.J., Davis 0., Schattman G.: "Safety and efficacy of infertility treatment after conservative management of borderline tumors: A preliminary report". Fertil. Steril., 2004, 82, 568.

[41] Gallot D., Pouly J.L., Janny L. et al.: "Successful transfer of frozen-thawed embryos obtained immediately before radical surgery for Stage Illa serous borderline ovarian tumour: Case report". Hum. Reprod., 2000, 15, 2347.

[42] Pouly J.L., Janny L., Pouly-Vye P., Canis M., Cure A., Dechelotte P.: "Successful oocyte donation after Stage l C serous ovarian cancer". Hum Reprod., 1997, 12, 1589.

[43] Bernardini L., Asch R.H.: "Spontaneous resolution of ectopic pregnancy in a surrogate after oocyte donation and frozen embryo transfer" Hum. Reprod., 1996, 11, 2785.

[44] Wang C.B., Wang C.J., Huang H.J., Hsueh S., Chou H.H., Soong Y.K., Lai C.H.: "Fertility-preserving treatment in young patients with endometrial adenocarcinoma". Cancer, 2002, 94, 2192.

[45] Gotlieb W.H., Beiner M.E., Shalmon B. et al.: "Outcome of fertility-sparing treatment with progestins in young patients with endometrial cancer". Obstet. Gynecol., 2003, 102, 718.

[46] Kim Y.B., Holschneider C.H., Hosh K. et al.: "Progestin alone as primary treatment of endometrial carcinoma in premenopausal women Report of seven cases and review of the literature". Cancer, 1997, 79, 320.

[47] Kowalczyk C.L., Malone J. Jr., Peterson E.P., Jacques S.M., Leach R.E.: "Well-differentiated endometrial adenocarcinoma in an infertility patient with later conception. A case report". J. Reprod. Med., 1999, 44, 57.

[48] Lowe M.P., Bender D., Sood A.K. et al.: "Two successful pregnancies after conservative treatment of endometrial cancer and assisted reproduction". Fertil. Steril., 2002, 77, 188.

[49] Jadoul P., Donnez J.: "Conservative treatment may be beneficial wfor young women with atypical endometrial hyperplasia or endometrial adenocarcinoma". Fertil. Steril., 2003, 80, 1315.

[50] Bokhman I. V., Chepik O.F., Volkova A.T., Vishnevskii A.S.: "Is a cure possible for primary stage-I endometrial cancer using drug therapy9" Vopr. Onkol., 1982, 28, 34.

[51] Randall T.C., Kurrnan R.J.: "Progestin treatment of atypical hyperplasia and well-differentiated carcinoma of the endornetriurn in women under age 40". Obstet. Gynecol., 1997, 90, 434.

[52] Duska L.R., Garrett A., Rueda B.R. et al.: "Endometrial cancer in women 40 years old or younger". Gynecol. Oneal., 2001, 83, 388.

[53] Lowe M.P., Cooper B.C., Sood A.K. et al.: "Implementation of assisted reproductive technologies following conservative management of FIGO grade I endometrial adenocarcinoma". Gynecol. Oneal., 2003, 91, 569.

[54] Yarall H.,B ozdag G.,A ksu T.,A yhan A.: "A successful pregnancy after intracytoplasinic sperm injectionand embryo transfer in a patient with endometrial cancer who was treated conservatively". Fertil. Steril., 2004, 81, 214.

[55] Pinto A.B., Gopal M., Herzog T.J. et al.: "Successful in vitro fertilization pregnancy after conservative management of endometrial cancer". Fertil. Steril., 2001, 76, 826.

[56] Montz F.J., Bristow R.E., Bovicelli A. et al.: "Intrauterine progesterone treatment of early endometrial cancer". Am. J. Obstet. Gynecol., 2002, 186, 651.

[57] Eraslan S., Hamernik R.J., Hardy J.D.: "Replantation of uterus and ovaries in dogs, with successful pregnancy". Arch. Surg., 1966, 92, 9.

[58] Lee S., Mao L., Wang Y. et al.: "Translplantation of reproductive organs". Microsurgery, 1995, 16, 191.

[59] Fageeh W., Raffa H., Jabbad H., Marzouki A.:'Transplantation of the human uterus". Int. J. Gynaecol. Obstet., 2002, 76, 245.

[60] Stehman F.B., Rose P.G., Greer B.E. et al.: "Innovations in the treatment of invasive cervical cancer". Cancer, 2003, 98 (9 suppl.), 2052.

[61] Diakomanolis E., Haidopoulos D., Rodolakis A. et al.: "Laser CO, conization: A safe mode of treating conservatively microinvasive carcinoma of the uterine cervix". Eur. J. Obstet. Gynecol. Reprod. Biol., 2004, 113, 229.

[62] McHale M.T., Le T.D., Burger R.A. et al.: "Fertility sparing treatment for in situ and early invasive adenocarcinoma of the cervix". Obstet. Gynecol., 2001, 98, 726.

[63] Schorge J.O., Lee K.R., Sheets E.E.: "Prospective management of Stage IA(l) cervical adenocarcinoma by conization alone to preserve fertility:A preliminary report". Gynecol. Oneal., 2000, 78, 217.

[64] Dargent D., Mathevet P.: "Shauta's vaginal hysterectomy combined with laparoscopic lymphadenectomy". Baillieres Clin. Obstet. Gynaecol., 1995, 9, 691.

[65] Renaud M.C., Plante M., Roy M.: "Combined laparoscopic and vaginal radical surgery in cervical cancer". Gynecol. Oneal., 2000, 79, 59.

[66] Roy M., Plante M., Renaud M.C., Tetu B.: "Vaginal radical hysterectomy versus abdominal radical hysterectomy in the treatment of earlystage cervical cancer". Gynecol. Oneal., 1996, 62, 336.

[67] Tanguay C., Plante M., Renaud M.C. et al.: "Vaginal radical trachelectomy in the treatment of cervical cancer: The role of frozen section". Int. J. Gynecol. Pathol., 2004, 23, 170.

[68] Dargent D., Martin X., Sacchetoni A., Mathevet P.: "'Laparoscopic vaginal radical trachelectomy: A treatment to preserve the fertility of cervical carcinoma patients". Cancer. 2000, 88, 1877.

[69] Covens A., Shaw P., Murphy J. et al.: "Is radical tracheletomy a safe alternative to radical hysterectomy for patients with Stage IA-B carcinoma of the cervix?". Cancer, 1999, 86, 2273.

[70] Roy M., Plante M.: "Pregnancies after radical vaginal trachelectomy for early-stage cervical cancer". Am. J. Obstet. Gynecol., 1998, 179, 1491.

[71] Shepherd J.H., Mould T., Oram D.H.: "Radical trachelectomy in early stage carcinoma of the cervix: Outcome as judged by recurrence and fertility rates". Br. J. Obstet. Gynecol., 2001, 108, 882.

[72] Bernardini M., Barrett J., Seaward G., Covens A.: "Pregnancy outcomes in patients after radical trachelectomy". Am. J. Obstet. Gynecol., 2003, 189, 1378.

[73] Plante M., Renaud M.-C.. Francois H., Roy M.: "Vaginal radical trachelectomy: An oncologically safe fertility-preserving surgery. An updated series of 72 cases and review of the literature". Gynecol. Oneal., 2004, 94, 614.

[74] Morice P., Dargent D., Haie-Meder C. et al.: "First case of a centropelvic recurrence after radical trachelectomy: Literature review and imphcations for the preoperative selection of patients". Gynecol. Oneal., 2004, 92, 1002.

[75] Bali A., Weekes A., van Trappen P. et al.: "Central pelvic recurrence 7 years after radical vaginal trachelectomy". Gynecol. Oneal., 2005, 96, 854.

[76] Rodriguez M., Guimares 0., Rose PG.: "Radical abdominal trachelectomy and pelvic lymphadenectomy with uterine conservation and subsequent pregnancy in the treatment of early invasive cervical cancer". Am. J. Obstet. Gynecol., 2001, 185, 370.

[77] Ungar L., Palfalvi L., Hogg R. et al.: "Abdominal radical trachelectomy: A fertility-preserving option for women with early cervical cancer" Br. J. Obstet. Gynecol., 2005, 112, 366

[78] Husseinzadeh N., van Aken M.L., Aron B.: "Ovarian transposition in young patients with invasive cervical cancer receiving radiation therapy" Int. J. Gynecol. Cancer, 1994, 4, 61.