Fertility-Sparing Treatment in Young Women Diagnosed with Endometrial Cancer: Review of Safety, Pregnancy Outcomes, and Current Recommendations

Abstract

With the rising incidence of endometrial cancer, including among young women, and the trend of increasing age among first-time mothers, the need for safe and effective fertility-sparing treatments for endometrial cancer and atypical endometrial hyperplasia has become crucial. Focusing on studies from the past decade, this review synthesizes findings on the safety and outcomes of fertility-sparing treatments for endometrial cancer and atypical endometrial hyperplasia and provides an overview of current treatment recommendations. Fertility-sparing treatment, including hysteroscopic tumor resection followed by hormonal therapy with oral progestins and/or the insertion of a levonorgestrel-releasing intrauterine device, can be offered to a selected group of women of reproductive age who wish to preserve their ability to become pregnant in the future. The safety of conservative treatment for women diagnosed with Stage 1A, Grade 1 endometrial cancer without myometrial invasion is high; however, current evidence on the safety of this treatment for women with Grade 1, Stage 2 endometrial cancer is limited. Even though the success rate in terms of pregnancies and deliveries is high, it is not as high as in the general population, and women should be informed of the potential need for assisted reproductive technology.

Keywords

assisted reproductive technology - atypical endometrial hyperplasia - endometrial cancer - fertility preservation

Publikationsverlauf

Artikel online veröffentlicht:
02. Mai 2025

• References

• 1 Bray F, Laversanne M, Sung H. et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2024; 74 (03) 229-263
• 2 Nordcan 2.0. Accessed October 30, 2024 at: https://nordcan.iarc.fr/en/dataviz/trends?key=total&sexes=2&cancers=200&populations=0&age_end=8
• 3 Peeri NC, Bertrand KA, Na R. et al. Understanding risk factors for endometrial cancer in young women. J Natl Cancer Inst 2025; 117 (01) 76-88
• 4 Haidopoulos D, Simou M, Akrivos N. et al. Risk factors in women 40 years of age and younger with endometrial carcinoma. Acta Obstet Gynecol Scand 2010; 89 (10) 1326-1330
• 5 Soliman PT, Oh JC, Schmeler KM. et al. Risk factors for young premenopausal women with endometrial cancer. Obstet Gynecol 2005; 105 (03) 575-580
• 6 Hardiman P, Pillay OC, Atiomo W. Polycystic ovary syndrome and endometrial carcinoma. Lancet 2003; 361 (9371) 1810-1812
• 7 Ribeiro LM, Sasaki LMP, Silva AA. et al. Overweight, obesity and assisted reproduction: a systematic review and meta-analysis. Eur J Obstet Gynecol Reprod Biol 2022; 271: 117-127
• 8 Zhou J, Zhang Y, Teng Y. et al. Association between preconception body mass index and fertility in adult female: a systematic review and meta-analysis. Obes Rev 2024; 25 (10) e13804
• 9 Einarsson S, Bergh C, Friberg B. et al. Weight reduction intervention for obese infertile women prior to IVF: a randomized controlled trial. Hum Reprod 2017; 32 (08) 1621-1630
• 10 Zhang Y, Li D, Yan Q. et al. Weight loss improves pregnancy and livebirth outcomes in young women with early-stage endometrial cancer and atypical hyperplasia. Cancer Manag Res 2021; 13: 5711-5722
• 11 Gonthier C, Walker F, Luton D, Yazbeck C, Madelenat P, Koskas M. Impact of obesity on the results of fertility-sparing management for atypical hyperplasia and grade 1 endometrial cancer. Gynecol Oncol 2014; 133 (01) 33-37
• 12 Nakamura K, Banno K, Yanokura M. et al. Features of ovarian cancer in Lynch syndrome (review). Mol Clin Oncol 2014; 2 (06) 909-916
• 13 Aarnio M, Sankila R, Pukkala E. et al. Cancer risk in mutation carriers of DNA-mismatch-repair genes. Int J Cancer 1999; 81 (02) 214-218
• 14 Dominguez-Valentin M, Sampson JR, Seppälä TT. et al. Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome Database. . Genet Med
• 15 Dallagiovanna C, Filippi F, Riccaboni A. et al. The neglected role of preimplantation genetic testing for Lynch syndrome. Reprod Biomed Online 2023; 46 (03) 421-423
• 16 Rackow BW, Arici A. Endometrial Cancer and Fertility. Vol 18. 2006
• 17 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 (01) 263-270
• 18 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 (02) 477-482
• 19 Falcone F, Leone Roberti Maggiore U, Di Donato V. et al. Fertility-sparing treatment for intramucous, moderately differentiated, endometrioid endometrial cancer: a Gynecologic Cancer Inter-Group (GCIG) study. J Gynecol Oncol 2020; 31 (05) e74
• 20 Yu M, Wang Y, Yuan Z. et al. Fertility-sparing treatment in young patients with Grade 2 presumed Stage IA endometrioid endometrial adenocarcinoma. Front Oncol 2020; 10: 1437
• 21 Hwang JY, Kim DH, Bae HS. et al. Combined oral medroxyprogesterone/levonorgestrel-intrauterine system treatment for women with grade 2 stage IA endometrial cancer. Int J Gynecol Cancer 2017; 27 (04) 738-742
• 22 Clark TJ, Voit D, Gupta JK, Hyde C, Song F, Khan KS. Accuracy of hysteroscopy in the diagnosis of endometrial cancer and hyperplasia: a systematic quantitative review. JAMA 2002; 288 (13) 1610-1621
• 23 Di Spiezio Sardo A, Saccone G, Carugno J. et al. Endometrial biopsy under direct hysteroscopic visualisation versus blind endometrial sampling for the diagnosis of endometrial hyperplasia and cancer: systematic review and meta-analysis. Facts Views Vis ObGyn 2022; 14 (02) 103-110
• 24 Alcázar JL, Gastón B, Navarro B, Salas R, Aranda J, Guerriero S. Transvaginal ultrasound versus magnetic resonance imaging for preoperative assessment of myometrial infiltration in patients with endometrial cancer: a systematic review and meta-analysis. J Gynecol Oncol 2017; 28 (06) e86
• 25 Tameish S, Florez N, Vidal JRP, Chen H, Vara J, Alcázar JL. Transvaginal ultrasound versus magnetic resonance imaging for preoperative assessment of myometrial infiltration in patients with low-grade endometrioid endometrial cancer: a systematic review and head-to-head meta-analysis. J Clin Ultrasound 2023; 51 (07) 1188-1197
• 26 Morrison J, Balega J, Buckley L. et al. British Gynaecological Cancer Society (BGCS) uterine cancer guidelines: recommendations for practice. Eur J Obstet Gynecol Reprod Biol 2022; 270: 50-89
• 27 Rodolakis A, Scambia G, Planchamp F. et al. ESGO/ESHRE/ESGE Guidelines for the fertility-sparing treatment of patients with endometrial carcinoma. Hum Reprod Open 2023; 2023 (01) hoac057
• 28 Concin N, Matias-Guiu X, Vergote I. et al. ESGO/ESTRO/ESP guidelines for the management of patients with endometrial carcinoma. Int J Gynecol Cancer 2021; 31 (01) 12-39
• 29 Giampaolino P, Di Spiezio Sardo A, Mollo A. et al. Hysteroscopic endometrial focal resection followed by levonorgestrel intrauterine device insertion as a fertility-sparing treatment of atypical endometrial hyperplasia and early endometrial cancer: a retrospective study. J Minim Invasive Gynecol 2019; 26 (04) 648-656
• 30 Gallo A, Catena U, Saccone G, Di Spiezio Sardo A. Conservative surgery in endometrial cancer. J Clin Med 2021; 11 (01) 183
• 31 Lucchini SM, Esteban A, Nigra MA, Palacios AT, Alzate-Granados JP, Borla HF. Updates on conservative management of endometrial cancer in patients younger than 45 years. Gynecol Oncol 2021; 161 (03) 802-809
• 32 Falcone F, Laurelli G, Losito S, Di Napoli M, Granata V, Greggi S. Fertility preserving treatment with hysteroscopic resection followed by progestin therapy in young women with early endometrial cancer. J Gynecol Oncol 2017; 28 (01) e2
• 33 Giampaolino P, Cafasso V, Boccia D. et al. Fertility-sparing approach in patients with endometrioid endometrial cancer Grade 2 Stage IA (FIGO): a qualitative systematic review. BioMed Res Int 2022; 2022: 4070368
• 34 Herrera Cappelletti E, Humann J, Torrejón R, Gambadauro P. Chances of pregnancy and live birth among women undergoing conservative management of early-stage endometrial cancer: a systematic review and meta-analysis. Hum Reprod Update 2022; 28 (02) 282-295
• 35 Zhao S, Zhang J, Yan Y. et al. Oncological and reproductive outcomes of endometrial atypical hyperplasia and endometrial cancer patients undergoing conservative therapy with hysteroscopic resection: a systematic review and meta-analysis. Acta Obstet Gynecol Scand 2024; 103 (08) 1498-1512
• 36 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 (37) e8034
• 37 Zhang Q, Qi G, Kanis MJ. et al. Comparison among fertility-sparing therapies for well differentiated early-stage endometrial carcinoma and complex atypical hyperplasia. Oncotarget 2017; 8 (34) 57642-57653
• 38 Azim AA, Costantini-Ferrando M, Oktay K. Safety of fertility preservation by ovarian stimulation with letrozole and gonadotropins in patients with breast cancer: a prospective controlled study. J Clin Oncol 2008; 26 (16) 2630-2635
• 39 Novikova OV, Nosov VB, Panov VA. et al. Live births and maintenance with levonorgestrel IUD improve disease-free survival after fertility-sparing treatment of atypical hyperplasia and early endometrial cancer. Gynecol Oncol 2021; 161 (01) 152-159
• 40 Almutairi H, Aldhalea MS, Almaaz MA. et al. The effectiveness of bariatric surgery on treating infertility in women - a systematic review and meta-analysis. J Clin Med 2024; 13 (18) 5569
• 41 Kwong W, Tomlinson G, Feig DS. Maternal and neonatal outcomes after bariatric surgery; a systematic review and meta-analysis: do the benefits outweigh the risks?. Am J Obstet Gynecol 2018; 218 (06) 573-580
• 42 Mechanick JI, Apovian C, Brethauer S. et al. Clinical practice guidelines for the perioperative nutrition, metabolic, and nonsurgical support of patients undergoing bariatric procedures - 2019 update: cosponsored by American Association of Clinical Endocrinologists/American College of Endocrinology, the Obesity Society, American Society for Metabolic and Bariatric Surgery, Obesity Medicine Association, and American Society of Anesthesiologists. Obesity (Silver Spring) 2020; 28 (04) O1-O58
• 43 Ga H, Taguchi A, Honjoh H. et al. Prognosis of patients with endometrial cancer or atypical endometrial hyperplasia after complete remission with fertility-sparing therapy. Arch Gynecol Obstet 2023; 308 (05) 1629-1634
• 44 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. Fertil Steril 2014; 101 (03) 785-794
• 45 Qin Y, Yu Z, Yang J. et al. Oral progestin treatment for early-stage endometrial cancer: a systematic review and meta-analysis. Int J Gynecol Cancer 2016; 26 (06) 1081-1091