Fertility Preservation Strategies in Gynecologic Cancers

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Sikarn Satitniramai
Chuenkamon Charakorn
Lukkana Promwattanaphan


The incidence of most gynecologic malignancies significantly reaches their peaks after the age of 50, a substantial number of women encounter the diagnosis of gynecologic cancer during their reproductive year. Seeing that, fertility preservation has an important role in good quality of life in adolescents and young adults, the gynecologic oncologists should thoroughly discuss the potentiate infertility with all patients and refer them to reproductive specialists as earliest as possible to broaden the fertility preservation options and reduce decisional regret. There are roles of fertility preservation treatment in appropriately selected patients such as early stage cervical cancer (IA1-IB1), early stage of endometrial carcinoma with well-differentiated endometrioid subtype, and some subtypes of ovarian cancer (epithelium ovarian cancer stage IA, unilateral IC, malignant ovarian germ cell tumor, sex-cord stromal tumor, borderline ovarian tumor) which the fertility-preserving procedure yields the optimal oncologic outcomes and acceptable obstetrics result. Patients should be insistently informed that the fertility-sparing treatment is not the standard of care and accepted possibilities of impaired survival. The doctors should emphasize comprehensive surveillance and a complete surgical staging following family completion must be achieved.


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Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin 2020;70:7-30.

Moser EC, Meunier F. Cancer survivorship: A positive side-effect of more successful cancer treatment. EJC Suppl 2014;12:1-4.

Duffy C, Allen S. Medical and psychosocial aspects of fertility after cancer. Cancer J 2009;15:27-33.

Oktay K, Harvey BE, Partridge AH, Quinn GP, Reinecke J, Taylor HS, et al. Fertility preservation in patients with cancer: ASCO Clinical Practice Guideline Update. J Clin Oncol 2018;36:1994-2001.

Fertility preservation in patients undergoing gonadotoxic therapy or gonadectomy: a committee opinion. Fertil Steril 2019;112:1022-33.

Quinn GP, Vadaparampil ST, Lee JH, Jacobsen PB, Bepler G, Lancaster J, et al. Physician referral for fertility preservation in oncology patients: a national study of practice behaviors. J Clin Oncol 2009;27:5952-7.

Chan JL, Letourneau J, Salem W, Cil AP, Chan SW, Chen LM, et al. Regret around fertility choices is decreased with pre-treatment counseling in gynecologic cancer patients. J Cancer Surviv 2017;11:58-63.

Thomson AB, Critchley HO, Kelnar CJ, Wallace WH. Late reproductive sequelae following treatment of childhood cancer and options for fertility preservation. Best Pract Res Clin Endocrinol Metab 2002;16:311-34.

Critchley HO, Bath LE, Wallace WH. Radiation damage to the uterus -- review of the effects of treatment of childhood cancer. Hum Fertil (Camb) 2002;5:61-6.

Infertility workup for the women’s health specialist: ACOG Committee Opinion, Number 781. Obstet Gynecol 2019;133:e377-e84.

Cobo A, García-Velasco JA, Coello A, Domingo J, Pellicer A, Remohí J. Oocyte vitrification as an efficient option for elective fertility preservation. Fertil Steril 2016;105:755-64.e8.

Doyle JO, Richter KS, Lim J, Stillman RJ, Graham JR, Tucker MJ. Successful elective and medically indicated oocyte vitrification and warming for autologous in vitro fertilization, with predicted birth probabilities for fertility preservation according to number of cryopreserved oocytes and age at retrieval. Fertil Steril 2016;105:459-66.e2.

Fertility preservation and reproduction in patients facing gonadotoxic therapies: an Ethics Committee opinion. Fertil Steril 2018;110:380-6.

Oktay K, Harvey BE, Loren AW. Fertility preservation in patients with cancer: ASCO Clinical Practice Guideline Update Summary. J Oncol Pract 2018;14:381-5.

Pacheco F, Oktay K. Current success and efficiency of autologous ovarian transplantation: a meta-analysis. Reprod Sci 2017;24:1111-20.

Buonomo B, Multinu F, Casarin J, Betella I, Zanagnolo V, Aletti G, et al. Ovarian transposition in patients with cervical cancer prior to pelvic radiotherapy: a systematic review. Int J Gynecol Cancer 2021;31:360-70.

Moore HC, Unger JM, Phillips KA, Boyle F, Hitre E, Porter D, et al. Goserelin for ovarian protection during breast-cancer adjuvant chemotherapy. N Engl J Med 2015;372:923-32.

Demeestere I, Brice P, Peccatori FA, Kentos A, Dupuis J, Zachee P, et al. No Evidence for the benefit of gonadotropin-releasing hormone agonist in preserving ovarian function and fertility in lymphoma survivors treated with chemotherapy: final long-term report of a prospective randomized trial. J Clin Oncol 2016;34:2568-74.

Cancer STAT facts: cervical cancer. National Cancer Institute, Surveillance, Epidemiology, and End Results Program.2020 [Internet]. Jun 30, 2020 [cited 2020 Jun 30]. Available from: https://seer.cancer.gov/statfacts/html/cervix.html.

Abu-Rustum NR, Yashar CM, Bean S, Bradley K, Campos SM, Chon HS, et al. NCCN Guidelines Insights: Cervical cancer, Version 1.2020. J Natl Compr Canc Netw 2020;18:660-6.

Kyrgiou M, Koliopoulos G, Martin-Hirsch P, Arbyn M, Prendiville W, Paraskevaidis E. Obstetric outcomes after conservative treatment for intraepithelial or early invasive cervical lesions: systematic review and meta-analysis. Lancet 2006;367:489-98.

Gwacham NI, McKenzie ND, Fitzgerald ER, Ahmad S, Holloway RW. Neoadjuvant chemotherapy followed by fertility sparing surgery in cervical cancers size 2-4 cm; emerging data and future perspectives. Gynecol Oncol 2021;162:809-15.

Shah JS, Jooya ND, Woodard TL, Ramirez PT, Fleming ND, Frumovitz M. Reproductive counseling and pregnancy outcomes after radical trachelectomy for early stage cervical cancer. J Gynecol Oncol 2019;30:e45.

Stewart K, Campbell S, Frumovitz M, Ramirez PT, McKenzie LJ. Fertility considerations prior to conservative management of gynecologic cancers. Int J Gynecol Cancer 2021;31:339-44.

Nezhat C, Roman RA, Rambhatla A, Nezhat F. Reproductive and oncologic outcomes after fertility-sparing surgery for early stage cervical cancer: a systematic review. Fertil Steril 2020;113:685-703.

Practice Bulletin No. 149: Endometrial cancer. Obstet Gynecol 2015;125:1006-26.

Broughton DE, Moley KH. Obesity and female infertility: potential mediators of obesity’s impact. Fertil Steril 2017;107:840-7.

Nitecki R, Woodard T, Rauh-Hain JA. Fertility-sparing treatment for early-stage cervical, ovarian, and endometrial malignancies. Obstet Gynecol 2020;136:1157-69.

Obermair A, Baxter E, Brennan DJ, McAlpine JN, Muellerer JJ, Amant F, et al. Fertility-sparing treatment in early endometrial cancer: current state and future strategies. Obstet Gynecol Sci 2020;63:417-31.

Soliman PT, Oh JC, Schmeler KM, Sun CC, Slomovitz BM, Gershenson DM, et al. Risk factors for young premenopausal women with endometrial cancer. Obstet Gynecol 2005;105:575-80.

Shih KK, Garg K, Levine DA, Kauff ND, Abu-Rustum NR, Soslow RA, et al. Clinicopathologic significance of DNA mismatch repair protein defects and endometrial cancer in women 40 years of age and younger. Gynecol Oncol 2011;123:88-94.

Cosgrove CM, Cohn DE, Hampel H, Frankel WL, Jones D, McElroy JP, et al. Epigenetic silencing of MLH1 in endometrial cancers is associated with larger tumor volume, increased rate of lymph node positivity and reduced recurrence-free survival. Gynecol Oncol 2017;146:588-95.

Cohn DE, Frankel WL, Resnick KE, Zanagnolo VL, Copeland LJ, Hampel H, et al. Improved survival with an intact DNA mismatch repair system in endometrial cancer. Obstet Gynecol 2006;108:1208-15.

Leitao MM, Jr., Kehoe S, Barakat RR, Alektiar K, Gattoc LP, Rabbitt C, et al. Comparison of D&C and office endometrial biopsy accuracy in patients with FIGO grade 1 endometrial adenocarcinoma. Gynecol Oncol 2009;113:105-8.

Di Spiezio Sardo A, De Angelis MC, Della Corte L, Carugno J, Zizolfi B, Guadagno E, et al. Should endometrial biopsy under direct hysteroscopic visualization using the grasp technique become the new gold standard for the preoperative evaluation of the patient with endometrial cancer? Gynecol Oncol 2020;158:347-53.

Lago V, Martín B, Ballesteros E, Cárdenas-Rebollo JM, Minig L. Tumor grade correlation between preoperative biopsy and final surgical specimen in endometrial cancer: the use of different diagnostic methods and analysis of associated factors. Int J Gynecol Cancer 2018;28:1258-63.

Larish A, Kumar A, Weaver A, Mariani A. Impact of hysteroscopy on course of disease in high-risk endometrial carcinoma. Int J Gynecol Cancer 2020;30:1513-9.

Zarbo G, Caruso G, Caruso S, Mangano U, Zarbo R. Endometrial cancer: preoperative evaluation of myometrial infiltration magnetic resonance imaging versus transvaginal ultrasonography. Eur J Gynaecol Oncol 2000;21:95-7.

Concin N, Creutzberg CL, Vergote I, Cibula D, Mirza MR, Marnitz S, et al. ESGO/ESTRO/ESP Guidelines for the management of patients with endometrial carcinoma. Virchows Arch 2021;478:153-90.

Tewari KS, Di Saia PJ. Ovulatory failure, fertility preservation and reproductive strategies in the setting of gynecologic and non-gynecologic malignancies. Eur J Gynaecol Oncol 2006;27:449-61.

Eskander RN, Randall LM, Berman ML, Tewari KS, Disaia PJ, Bristow RE. Fertility preserving options in patients with gynecologic malignancies. Am J Obstet Gynecol 2011;205:103-10.

Gunderson CC, Fader AN, Carson KA, Bristow RE. Oncologic and reproductive outcomes with progestin therapy in women with endometrial hyperplasia and grade 1 adenocarcinoma: a systematic review. Gynecol Oncol 2012;125:477-82.

Wei J, Zhang W, Feng L, Gao W. Comparison of fertility-sparing treatments in patients with early endometrial cancer and atypical complex hyperplasia: A meta-analysis and systematic review. Medicine (Baltimore) 2017;96:e8034.

Mazzon I, Corrado G, Morricone D, Scambia G. Reproductive preservation for treatment of stage IA endometrial cancer in a young woman: hysteroscopic resection. Int J Gynecol Cancer 2005;15:974-8.

Erkanli S, Ayhan A. Fertility-sparing therapy in young women with endometrial cancer: 2010 update. Int J Gynecol Cancer 2010;20:1170-87.

Carugno J, Wong A. Fertility-sparing approach for endometrial cancer: the role of office hysteroscopy. Minim Invasive Ther Allied Technol 2021:30:296-303.

Viollet B, Guigas B, Sanz Garcia N, Leclerc J, Foretz M, Andreelli F. Cellular and molecular mechanisms of metformin: an overview. Clin Sci (Lond) 2012;122:253-70.

Zhang Q, Celestino J, Schmandt R, McCampbell AS, Urbauer DL, Meyer LA, et al. Chemopreventive effects of metformin on obesity-associated endometrial proliferation. Am J Obstet Gynecol 2013;209:24.e1-24.e12.

Kaku T, Yoshikawa H, Tsuda H, Sakamoto A, Fukunaga M, Kuwabara Y, et al. Conservative therapy for adenocarcinoma and atypical endometrial hyperplasia of the endometrium in young women: central pathologic review and treatment outcome. Cancer Lett 2001;167:39-48.

Matsuo K, Machida H, Shoupe D, Melamed A, Muderspach LI, Roman LD, et al. Ovarian conservation and overall survival in young women with early-stage low-grade endometrial cancer. Obstet Gynecol 2016;128:761-70.

Jia P, Zhang Y. Ovarian preservation improves overall survival in young patients with early-stage endometrial cancer. Oncotarget 2017;8:59940-9.

Cancer STAT facts: ovarian cancer. National Cancer Institute, Surveillance, Epidemiology, and End Results Program 2020. [Internet]. Jun 30, 2020 [cited 2020 Jun 30]. Available from: https://seer.cancer.gov/statfacts/html/ovary.html.

Shah JS, Mackelvie M, Gershenson DM, Ramalingam P, Kott MM, Brown J, et al. Accuracy of intraoperative frozen section diagnosis of borderline ovarian tumors by hospital type. J Minim Invasive Gynecol 2019;26:87-93.

Park JY, Lee SH, Kim KR, Kim YT, Nam JH. Accuracy of frozen section diagnosis and factors associated with final pathological diagnosis upgrade of mucinous ovarian tumors. J Gynecol Oncol 2019;30:e95.

Tomao F, Peccatori F, Del Pup L, Franchi D, Zanagnolo V, Panici PB, et al. Special issues in fertility preservation for gynecologic malignancies. Crit Rev Oncol Hematol 2016;97:206-19.

Melamed A, Rizzo AE, Nitecki R, Gockley AA, Bregar AJ, Schorge JO, et al. All-cause mortality after fertility-sparing surgery for stage I epithelial ovarian cancer. Obstet Gynecol 2017;130:71-9.

Sinno AK, Fader AN, Roche KL, Giuntoli RL, 2nd, Tanner EJ. A comparison of colorimetric versus fluorometric sentinel lymph node mapping during robotic surgery for endometrial cancer. Gynecol Oncol 2014;134:281-6.

Fruscio R, Ceppi L, Corso S, Galli F, Dell’Anna T, Dell’Orto F, et al. Long-term results of fertility-sparing treatment compared with standard radical surgery for early-stage epithelial ovarian cancer. Br J Cancer 2016;115:641-8.

Santos ML, Pais AS, Almeida Santos T. Fertility preservation in ovarian cancer patients. Gynecol Endocrinol 2021;37:483-9.

Skírnisdóttir I, Garmo H, Wilander E, Holmberg L. Borderline ovarian tumors in Sweden 1960-2005: trends in incidence and age at diagnosis compared to ovarian cancer. Int J Cancer 2008;123:1897-901.

Lou T, Yuan F, Feng Y, Wang S, Bai H, Zhang Z. The safety of fertility and ipsilateral ovary procedures for borderline ovarian tumors. Oncotarget 2017;8:115718-29.

Trillsch F, Mahner S, Woelber L, Vettorazzi E, Reuss A, Ewald-Riegler N, et al. Age-dependent differences in borderline ovarian tumours (BOT) regarding clinical characteristics and outcome: results from a sub-analysis of the Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) ROBOT study. Ann Oncol 2014;25:1320-7.

Armstrong DK, Alvarez RD, Bakkum-Gamez JN, Barroilhet L, Behbakht K, Berchuck A, et al. Ovarian cancer, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2021;19:191-226.

Rao GG, Skinner EN, Gehrig PA, Duska LR, Miller DS, Schorge JO. Fertility-sparing surgery for ovarian low malignant potential tumors. Gynecol Oncol 2005;98: 263-6.

Plett H, Harter P, Ataseven B, Heitz F, Prader S, Schneider S, et al. Fertility-sparing surgery and reproductive-outcomes in patients with borderline ovarian tumors. Gynecol Oncol 2020;157:411-7.

Schumer ST, Cannistra SA. Granulosa cell tumor of the ovary. J Clin Oncol 2003;21:1180-9.

Smith HO, Berwick M, Verschraegen CF, Wiggins C, Lansing L, Muller CY, et al. Incidence and survival rates for female malignant germ cell tumors. Obstet Gynecol 2006;107:1075-85.

Gershenson DM. Management of early ovarian cancer: germ cell and sex cord-stromal tumors. Gynecol Oncol 1994;55:S62-72.

Morrison A, Nasioudis D. Reproductive outcomes following fertility-sparing surgery for malignant ovarian germ cell tumors: a systematic review of the literature. Gynecol Oncol 2020;158:476-83.