Skip to main content
SpringerLink
Log in

Fertility-Sparing Treatment Options in Young Patients with Early-Stage Endometrial Cancer

  • Endometrial Cancer (G. Sel, Section Editor)
  • Published:
Current Obstetrics and Gynecology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

To summarize fertility-sparing treatment options in young patients with early-stage endometrial cancer.

Recent Findings

A levonorgestrel-releasing intrauterine device combined with oral progestins seems more effective for patients with endometrial cancer and desiring fertility. Assisted reproductive techniques seem more effective in achieving pregnancy in these young cancer patients than natural conception.

Summary

Endometrial cancer is the most common gynecologic cancer in developed countries. For younger patients who wish to have children, fertility preservation methods are available, but not always reasonable in an individual patient. Furthermore, fertility-preserving treatment has some risks with regard to surgical effectivity. The main criteria for fertility-sparing treatment are reproductive age of the patient, fertility desire, a grade 1 well-differentiated tumor, diagnosis should be performed through D&C, stage 1A tumor with no evidence of myometrial invasion on MRI, and no suspicious adnexal mass. A levonorgestrel-releasing intrauterine device combined with oral progestins seems more effective than using oral progestins alone. D&C should be performed every 3 months after the start of progestin therapy. Patients with two negative endometrial D&C results are considered to have a complete response and eligible for pregnancy. Hysteroscopic resection can be used in patients with grade 1 stage 1 endometrial carcinoma who did not respond to progestin treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87–108.

    PubMed  Google Scholar 

  2. Lee NK, Cheung MK, Shin JY, Husain A, Teng NN, Berek JS, et al. Prognostic factors for uterine cancer in reproductive-aged women. Obstet Gynecol. 2007;109(3):655–62.

    Article  PubMed  Google Scholar 

  3. Duska LR, Garrett A, Rueda BR, Haas J, Chang Y, Fuller AF. Endometrial cancer in women 40 years old or younger. Gynecol Oncol. 2001;83(2):388–93.

    Article  CAS  PubMed  Google Scholar 

  4. Creasman WT, Morrow CP, Bundy BN, Homesley HD, Graham JE, Heller PB. Surgical pathologic spread patterns of endometrial cancer: a gynecologic oncology group study. Cancer. 1987;60(S8):2035–41.

    Article  CAS  PubMed  Google Scholar 

  5. Walsh C, Holschneider C, Hoang Y, Tieu K, Karlan B, Cass I. Coexisting ovarian malignancy in young women with endometrial cancer. Obstet Gynecol. 2005;106(4):693–9.

    Article  PubMed  Google Scholar 

  6. Li J, Zhu Q, Yang B, Ning C, Liu X, Luo X, et al. Risk factors for ovarian involvement in young and premenopausal endometrioid endometrial cancer patients. European Journal of Obstetrics & Gynecology and Reproductive Biology. 2018;222:151–4.

    Article  Google Scholar 

  7. Gallos ID, Yap J, Rajkhowa M, Luesley DM, Coomarasamy A, Gupta JK. Regression, relapse, and live birth rates with fertility-sparing therapy for endometrial cancer and atypical complex endometrial hyperplasia: a systematic review and metaanalysis. American journal of obstetrics and gynecology. 2012;207(4):266. e1-. e12.

  8. DelMaschio A, Vanzulli A, Sironi S, Spagnolo D, Belloni C, Garancini P, et al. Estimating the depth of myometrial involvement by endometrial carcinoma: efficacy of transvaginal sonography vs MR imaging. AJR Am J Roentgenol. 1993;160(3):533–8.

    Article  CAS  PubMed  Google Scholar 

  9. Yamashita Y, Mizutani H, Torashima M, Takahashi M, Miyazaki K, Okamura H, et al. Assessment of myometrial invasion by endometrial carcinoma: transvaginal sonography vs contrast-enhanced MR imaging. AJR Am J Roentgenol. 1993;161(3):595–9.

    Article  CAS  PubMed  Google Scholar 

  10. Sala E, Rockall AG, Freeman SJ, Mitchell DG, Reinhold C. The added role of MR imaging in treatment stratification of patients with gynecologic malignancies: what the radiologist needs to know. Radiology. 2013;266(3):717–40.

    Article  PubMed  Google Scholar 

  11. McEvoy SH, Nougaret S, Abu-Rustum NR, Vargas HA, Sadowski EA, Menias CO, et al. Fertility-sparing for young patients with gynecologic cancer: how MRI can guide patient selection prior to conservative management. Abdominal Radiology. 2017;42(10):2488–512.

    Article  PubMed  Google Scholar 

  12. 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(1):105–8.

    Article  PubMed  Google Scholar 

  13. Dijkhuizen FPH, Mol BW, Brölmann HA, Heintz APM. The accuracy of endometrial sampling in the diagnosis of patients with endometrial carcinoma and hyperplasia: a meta-analysis. Cancer. 2000;89(8):1765–72.

    Article  CAS  PubMed  Google Scholar 

  14. Feichtinger M, Rodriguez-Wallberg KA. Fertility preservation in women with cervical, endometrial or ovarian cancers. Gynecologic oncology research and practice. 2016;3(1):8.

    Article  PubMed  PubMed Central  Google Scholar 

  15. 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(2):103–10.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Park J-Y, Kim D-Y, Kim T-J, Kim JW, Kim J-H, Kim Y-M, et al. Hormonal therapy for women with stage IA endometrial cancer of all grades. Obstet Gynecol. 2013;122(1):7–14.

    Article  CAS  PubMed  Google Scholar 

  17. Hwang JY, Bae HS, Kim M-L, Jung YW, Yun BS, Seong SJ, et al. Combined oral medroxyprogesterone/levonorgestrel-intrauterine system treatment for women with grade 2 stage IA endometrial cancer. International Journal of Gynecologic Cancer. 2017;27(4):738–42.

    Article  Google Scholar 

  18. Ruiz MP, Huang Y, Hou JY, Tergas AI, Burke WM, Ananth CV et al. All-cause mortality in young women with endometrial cancer receiving progesterone therapy. American journal of obstetrics and gynecology. 2017;217(6):669. e1-. e13.

  19. Tewari K, Di PS. Ovulatory failure, fertility preservation and reproductive strategies in the setting of gynecologic and non-gynecologic malignancies. Eur J Gynaecol Oncol. 2006;27(5):449–61.

    CAS  PubMed  Google Scholar 

  20. Decruze S, Green J. Hormone therapy in advanced and recurrent endometrial cancer: a systematic review. International Journal of Gynecologic Cancer. 2007;17(5):964–78.

    Article  CAS  Google Scholar 

  21. 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(2):477–82.

    Article  CAS  PubMed  Google Scholar 

  22. Ramirez PT, Frumovitz M, Bodurka DC, Sun CC, Levenback C. Hormonal therapy for the management of grade 1 endometrial adenocarcinoma: a literature review. Gynecol Oncol. 2004;95(1):133–8.

    Article  CAS  PubMed  Google Scholar 

  23. Thigpen JT, Brady MF, Alvarez RD, Adelson MD, Homesley HD, Manetta A et al. Oral medroxyprogesterone acetate in the treatment of advanced or recurrent endometrial carcinoma: a dose-response study by the Gynecologic Oncology Group. Journal of Clinical Oncology. 1999;17(6):1736-.

  24. Ushijima K, Yahata H, Yoshikawa H, Konishi I, Yasugi T, Saito T, et al. Multicenter phase II study of fertility-sparing treatment with medroxyprogesterone acetate for endometrial carcinoma and atypical hyperplasia in young women. J Clin Oncol. 2007;25(19):2798–803.

    Article  CAS  PubMed  Google Scholar 

  25. 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(1):39–48.

    Article  CAS  PubMed  Google Scholar 

  26. Qin Y, Yu Z, Yang J, Cao D, Yu M, Wang Y, et al. Oral progestin treatment for early-stage endometrial cancer: a systematic review and meta-analysis. International Journal of Gynecologic Cancer. 2016;26(6):1081–91.

    Article  Google Scholar 

  27. Eftekhar Z, Izadi-Mood N, Yarandi F, Shojaei H, Rezaei Z, Mohagheghi S. Efficacy of megestrol acetate (megace) in the treatment of patients with early endometrial adenocarcinoma: our experiences with 21 patients. International Journal of Gynecologic Cancer. 2009;19(2):249–52.

    Article  Google Scholar 

  28. Koskas M, Uzan J, Luton D, Rouzier R, Daraï E. Prognostic factors of oncologic and reproductive outcomes in fertility-sparing management of endometrial atypical hyperplasia and adenocarcinoma: systematic review and meta-analysis. Fertility and sterility. 2014;101(3):785–94. e3.

  29. Bakkum-Gamez JN, Kalogera E, Keeney GL, Mariani A, Podratz KC, Dowdy SC. Conservative management of atypical hyperplasia and grade I endometrial carcinoma: review of the literature and presentation of a series. J Gynecol Surg. 2012;28(4):262–9.

    Article  Google Scholar 

  30. Simpson AN, Feigenberg T, Clarke BA, Gien LT, Ismiil N, Laframboise S, et al. Fertility sparing treatment of complex atypical hyperplasia and low grade endometrial cancer using oral progestin. Gynecol Oncol. 2014;133(2):229–33.

    Article  CAS  PubMed  Google Scholar 

  31. Park J-Y, Kim D-Y, Kim J-H, Kim Y-M, Kim K-R, Kim Y-T, et al. Long-term oncologic outcomes after fertility-sparing management using oral progestin for young women with endometrial cancer (KGOG 2002). Eur J Cancer. 2013;49(4):868–74.

    Article  CAS  PubMed  Google Scholar 

  32. Montz FJ, Bristow RE, Bovicelli A, Tomacruz R, Kurman RJ. Intrauterine progesterone treatment of early endometrial cancer. Am J Obstet Gynecol. 2002;186(4):651–7.

    Article  CAS  PubMed  Google Scholar 

  33. • Gallos ID, Krishan P, Shehmar M, Ganesan R, Gupta JK. LNG-IUS versus oral progestogen treatment for endometrial hyperplasia: a long-term comparative cohort study. Human Reproduction. 2013;28(11):2966–71.This study shows the superiority of levonorgestrel-releasing intrauterine device than oral progestins.

  34. Baker J, Obermair A, Gebski V, Janda M. Efficacy of oral or intrauterine device-delivered progestin in patients with complex endometrial hyperplasia with atypia or early endometrial adenocarcinoma: a meta-analysis and systematic review of the literature. Gynecol Oncol. 2012;125(1):263–70.

    Article  CAS  PubMed  Google Scholar 

  35. Kim MK, Seong SJ, Kim YS, Song T, Kim M-L, Yoon BS et al. Combined medroxyprogesterone acetate/levonorgestrel–intrauterine system treatment in young women with early-stage endometrial cancer. American journal of obstetrics and gynecology. 2013;209(4):358. e1-. e4.

  36. Pronin SM, Novikova OV, Andreeva JY, Novikova EG. Fertility-sparing treatment of early endometrial cancer and complex atypical hyperplasia in young women of childbearing potential. International Journal of Gynecologic Cancer. 2015;25(6):1010–4.

    Article  Google Scholar 

  37. Kim MK, Seong SJ, Song T, Kim M-L, Yoon BS, Jun HS, et al. Comparison of dilatation & curettage and endometrial aspiration biopsy accuracy in patients treated with high-dose oral progestin plus levonorgestrel intrauterine system for early-stage endometrial cancer. Gynecol Oncol. 2013;130(3):470–3.

    Article  CAS  PubMed  Google Scholar 

  38. Arendas K, Aldossary M, Cipolla A, Leader A, Leyland NA. Hysteroscopic resection in the management of early-stage endometrial cancer: report of 2 cases and review of the literature. J Minim Invasive Gynecol. 2015;22(1):34–9.

    Article  PubMed  Google Scholar 

  39. Laurelli G, Di Vagno G, Scaffa C, Losito S, Del Giudice M, Greggi S. Conservative treatment of early endometrial cancer: preliminary results of a pilot study. Gynecol Oncol. 2011;120(1):43–6.

    Article  PubMed  Google Scholar 

  40. Yang H-C, Liu J-C, Liu F-S. Fertility-preserving treatment of stage IA, well-differentiated endometrial carcinoma in young women with hysteroscopic resection and high-dose progesterone therapy. Taiwanese Journal of Obstetrics and Gynecology. 2019;58(1):90–3.

    Article  PubMed  Google Scholar 

  41. Chang Y-N, Zhang Y, Wang Y-J, Wang L-P, Duan H. Effect of hysteroscopy on the peritoneal dissemination of endometrial cancer cells: a meta-analysis. Fertility and sterility. 2011;96(4):957–61. e2.

  42. Chae SH, Shim S-H, Lee SJ, Lee JY, Kim S-N, Kang S-B. Pregnancy and oncologic outcomes after fertility-sparing management for early stage endometrioid endometrial cancer. International Journal of Gynecologic Cancer. 2019;29(1):77–85.

    Article  Google Scholar 

  43. Cramer DW. The epidemiology of endometrial and ovarian cancer. Hematology/Oncology Clinics. 2012;26(1):1–12.

    Article  Google Scholar 

  44. Azim A, Oktay K. Letrozole for ovulation induction and fertility preservation by embryo cryopreservation in young women with endometrial carcinoma. Fertil Steril. 2007;88(3):657–64.

    Article  CAS  PubMed  Google Scholar 

  45. •• Zapardiel I, Cruz M, Diestro MD, Requena A, Garcia-Velasco JA. Assisted reproductive techniques after fertility-sparing treatments in gynaecological cancers. Human reproduction update. 2016;22(3):281–305. This study evaluates the effectivity of assisted reproductive techniques and compares the treatment options for gynecological cancers including endometrial cancer.

  46. Oktay K, Türkçüoğlu I, Rodriguez-Wallberg KA. GnRH agonist trigger for women with breast cancer undergoing fertility preservation by aromatase inhibitor/FSH stimulation. Reprod BioMed Online. 2010;20(6):783–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Gressel GM, Parkash V, Pal L. Management options and fertility-preserving therapy for premenopausal endometrial hyperplasia and early-stage endometrial cancer. Int J Gynecol Obstet. 2015;131(3):234–9.

    Article  Google Scholar 

  48. Cobo A, Garcia-Velasco JA, Domingo J, Remohí J, Pellicer A. Is vitrification of oocytes useful for fertility preservation for age-related fertility decline and in cancer patients? Fertil Steril. 2013;99(6):1485–95.

    Article  PubMed  Google Scholar 

  49. Garcia-Velasco JA, Domingo J, Cobo A, Martínez M, Carmona L, Pellicer A. Five years' experience using oocyte vitrification to preserve fertility for medical and nonmedical indications. Fertil Steril. 2013;99(7):1994–9.

    Article  PubMed  Google Scholar 

  50. Knopman JM, Noyes N, Talebian S, Krey LC, Grifo JA, Licciardi F. Women with cancer undergoing ART for fertility preservation: a cohort study of their response to exogenous gonadotropins. Fertil Steril. 2009;91(4):1476–8.

    Article  PubMed  CAS  Google Scholar 

  51. Ledda S, Leoni G, Bogliolo L, Naitana S. Oocyte cryopreservation and ovarian tissue banking. Theriogenology. 2001;55(6):1359–71.

    Article  CAS  PubMed  Google Scholar 

  52. Lotz L, Maktabi A, Hoffmann I, Findeklee S, Beckmann MW, Dittrich R. Ovarian tissue cryopreservation and retransplantation–what do patients think about it? Reprod BioMed Online. 2016;32(4):394–400.

    Article  PubMed  Google Scholar 

  53. Salama M, Woodruff TK. New advances in ovarian autotransplantation to restore fertility in cancer patients. Cancer Metastasis Rev. 2015;34(4):807–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Fujimoto A, Ichinose M, Harada M, Hirata T, Osuga Y, Fujii T. The outcome of infertility treatment in patients undergoing assisted reproductive technology after conservative therapy for endometrial cancer. J Assist Reprod Genet. 2014;31(9):1189–94.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Okan University School of Medicine, İstanbul, Turkey

    Eray Çalışkan & Cihan Karadağ

Authors
  1. Eray Çalışkan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Cihan Karadağ
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Cihan Karadağ.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Endometrial Cancer

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Çalışkan, E., Karadağ, C. Fertility-Sparing Treatment Options in Young Patients with Early-Stage Endometrial Cancer. Curr Obstet Gynecol Rep 9, 21–26 (2020). https://doi.org/10.1007/s13669-020-00280-2

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13669-020-00280-2

Keywords

Search

Navigation