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Fertility-Sparing Treatment for Atypical Endometrial Hyperplasia and Endometrial Cancer: A Cochrane Systematic Review Protocol

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Abstract

Introduction

Endometrial cancer is the fifth most common cancer in women and atypical endometrial hyperplasia is a precancerous lesion. Obesity is an important risk factor for endometrioid endometrial adenocarcinoma and endometrial hyperplasia. Progesterone is recommended as first-line treatment in endometrial cancer or atypical endometrial hyperplasia in women who wish to preserve fertility, but optimal treatment schedules have not been defined. Metformin or bariatric surgery may also be useful in these women. The effectiveness and safety of fertility-preserving treatments being used for women with atypical endometrial hyperplasia and stage IA grade 1 endometrial cancer is unclear. Therefore, the systematic review aims to determine this point.

Methods

We will search the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, trial registers, conference proceedings, abstracts, cooperative trial groups and reference lists. We will include randomised controlled trials (RCTs) that compare fertility-preserving therapy including orally administered progesterone versus a levonorgestrel-releasing intrauterine system (IUS), metformin, other pharmacological interventions or bariatric surgery, and any of these interventions with womb-removing surgery. Quasi-randomised trials, non-randomised trials and cohort studies will be included. Two review authors will independently assess study eligibility and risk of bias and extract data. The primary outcomes are complete pathologic response and live birth rate. Secondary outcomes include overall survival, progression-free survival, pregnancy rate, need for hysterectomy, adverse events, psychological symptoms and quality of life.

Planned Outcomes

This review aims to clarify the effectiveness and risks of fertility-preserving treatments, including complete pathologic response rate, live birth rates, need for surgical treatment, adverse events, psychological symptoms and quality of life. The broad scope of the review includes the use of progesterone, metformin to reverse insulin resistance, and bariatric surgery or operative hysteroscopy.

Results

The results may help to determine the optimal fertility-sparing treatment in endometrial cancer and atypical endometrial hyperplasia.

Systematic Review Registration

Prospero 2019 number CRD42019145991.

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References

  1. Bray F, Ren JS, Masuyer E, et al. Global estimates of cancer prevalence for 27 sites in the adult population in 2008. Int J Cancer. 2013;132:1133–45.

    CAS  PubMed  Google Scholar 

  2. Cancer Research UK. Uterine cancer incidence statistics. 2015. https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/uterine-cancer#heading-Zero. Accessed 28 July 2018.

  3. National Cancer Institute: Surveillance, Epidemiology, and End Results Program. Stat fact sheets: endometrial cancer. 2015. http://seer.cancer.gov/statfacts/html/corp.html. Accessed 13 Aug 2015.

  4. Reed SD, Newton KM, Clinton WL, et al. Incidence of endometrial hyperplasia. Am J Obstet Gynecol. 2009;200(678):e1-6.

    Google Scholar 

  5. Zaino R, Carinelli SG, Ellenson LH. Tumours of the uterine corpus: epithelial tumours and precursors. In: WHO classification of tumours of female reproductive organs. Geneva: WHO Press; 2014. p. 125–6.

    Google Scholar 

  6. Travaglino A, Raffone A, Saccone G, et al. Endometrial hyperplasia and the risk of coexistent cancer: WHO versus EIN criteria. Histopathology. 2019;74:676–87.

    PubMed  Google Scholar 

  7. Travaglino A, Raffone A, Saccone G, et al. Congruence between 1994 WHO classification of endometrial hyperplasia and endometrial intraepithelial neoplasia system. Am J Clin Pathol. 2020;153:40–8.

    PubMed  Google Scholar 

  8. Kurman RJ, Kaminski PF, Norris HJ. The behavior of endometrial hyperplasia. A long term study of “untreated” hyperplasia in 170 patients. Cancer. 1985;56:403–12.

    CAS  PubMed  Google Scholar 

  9. Lacey JV, Sherman ME, Rush BB, et al. Absolute risk of endometrial carcinoma during 20-year follow-up among women with endometrial hyperplasia. J Clin Oncol. 2010;28:788–92.

    PubMed  PubMed Central  Google Scholar 

  10. Antonsen SL, Ulrich L, Høgdall C. Patients with atypical hyperplasia of the endometrium should be treated in oncological centers. Gynecol Oncol. 2012;125:124–8.

    PubMed  Google Scholar 

  11. Rakha E, Wong SC, Soomro I, et al. Clinical outcome of atypical endometrial hyperplasia diagnosed on an endometrial biopsy: institutional experience and review of literature. Am J Surg Pathol. 2012;36:1683–90.

    PubMed  Google Scholar 

  12. Raffone A, Travaglino A, Saccone G, et al. Endometrial hyperplasia and progression to cancer: which classification system stratifies the risk better? A systematic review and meta-analysis. Arch Gynecol Obstet. 2019;299:1233–42.

    PubMed  Google Scholar 

  13. Barakat RR, Bundy BN, Spirtos NM, et al. Randomized double-blind trial of estrogen replacement therapy versus placebo in stage I or II endometrial cancer: a Gynecologic Oncology Group Study. J Clin Oncol. 2006;24:587–92.

    CAS  PubMed  Google Scholar 

  14. Creasman WT, Odicino F, Maisonneuve P, et al. Carcinoma of the corpus uteri. J Epidemiol Biostat. 2001;6:47–86.

    CAS  PubMed  Google Scholar 

  15. Lee NK, Cheung MK, Shin SY, et al. Prognostic factors for uterine cancer in reproductive-aged women. Obstet Gynecol. 2007;109:655–62.

    PubMed  Google Scholar 

  16. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65:5–29.

    PubMed  Google Scholar 

  17. Navarria I, Usel M, Rapiti E, et al. Young patients with endometrial cancer: how many could be eligible for fertility-sparing treatment? Gynecol Oncol. 2009;114:448–51.

    PubMed  Google Scholar 

  18. American Cancer Society. Survival by stage of endometrial cancer. 2018. https://www.cancer.org/cancer/endometrial-cancer/detection-diagnosis-staging/survival-rates.html. Accessed 28 July 2018.

  19. Crissman JD, Azoury RS, Barnes AE, et al. Endometrial carcinoma in women 40 years of age or younger. Obstet Gynecol. 1981;57:699–704.

    CAS  PubMed  Google Scholar 

  20. Lajer H, Elnegaard S, Christensen RD, et al. Survival after stage IA endometrial cancer; can follow-up be altered? A prospective nationwide Danish survey. Acta Obstet Gynecol Scand. 2012;91:976–82.

    PubMed  Google Scholar 

  21. Chen LM, Berek JS. Endometrial carcinoma. Epidemiology and risk factors. 2017. www.uptodate.com. Accessed 13 Mar 2018.

  22. Corzo C, Barrientos Santillan N, et al. Updates on conservative management of endometrial cancer. J Minim Invasive Gynecol. 2018;25:308–13.

    PubMed  Google Scholar 

  23. Gottschau M, Kjaer SK, Jensen A, et al. Risk of cancer among women with polycystic ovary syndrome: a Danish cohort study. Gynecol Oncol. 2015;136:99–103.

    PubMed  Google Scholar 

  24. Wu QJ, Li YY, Tu C, et al. Parity and endometrial cancer risk: a meta-analysis of epidemiological studies. Sci Rep. 2015;5:14243.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Yang HP, Cook LS, Weiderpass E, et al. Infertility and incident endometrial cancer risk: a pooled analysis from the Epidemiology of Endometrial Cancer Consortium (E2C2). Br J Cancer. 2015;112:925–33.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Jin P, Xie Y. Treatment strategies for women with polycystic ovary syndrome. Gynecol Endocrinol. 2018;34:272–7.

    PubMed  Google Scholar 

  27. Skalkidou A, Sergentanis TN, Gialamas SP, et al. Risk of endometrial cancer in women treated with ovary-stimulating drugs for subfertility. Cochrane Database Syst Rev. 2017. https://doi.org/10.1002/14651858.CD010931.pub2.

    Article  PubMed  PubMed Central  Google Scholar 

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

    PubMed  Google Scholar 

  29. Savelli L, Testa AC, Mabrouk M, et al. A prospective blinded comparison of the accuracy of transvaginal sonography and frozen section in the assessment of myometrial invasion in endometrial cancer. Gynecol Oncol. 2012;124:549–52.

    PubMed  Google Scholar 

  30. Koh WJ, Abu-Rustum NR, Bean S, et al. Uterine neoplasms, Version 1.2018. NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2018;16:170–99.

    PubMed  Google Scholar 

  31. Burke WM, Orr J, Leitao M, et al. Endometrial cancer: a review and current management strategies: part II. Gynecol Oncol. 2014;134:393–402.

    PubMed  Google Scholar 

  32. Rodolakis A, Biliatis I, Morice P, et al. European Society of Gynecological Oncology Task Force for Fertility Preservation: clinical recommendations for fertility-sparing management in young endometrial cancer patients. Int J Gynecol Cancer. 2015;25:1258–65.

    PubMed  Google Scholar 

  33. Stewart K, Campbell S, Frumowitz M, et al. Fertility considerations prior to conservative management of gynecologic cancers. Int J Gynecol Cancer. 2020. https://doi.org/10.1136/ijgc-2020-001783.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Pecorelli S. Revised FIGO staging for carcinoma of the vulva, cervix, and endometrium. Int J Gynecol Obstet. 2009;105:103–4.

    Google Scholar 

  35. Beddy P, Moyle P, Kataoka M, et al. Evaluation of depth of myometrial invasion and overall staging in endometrial cancer: comparison of diffusion-weighted and dynamic contrast-enhanced MR imaging. Radiology. 2012;262:530–7.

    PubMed  Google Scholar 

  36. Kitajima K, Murakami K, Yamasaki E, et al. Accuracy of integrated FDG-PET/contrast-enhanced CT in detecting pelvic and paraaortic lymph node metastasis in patients with uterine cancer. Eur Radiol. 2009;19:1529–36.

    PubMed  Google Scholar 

  37. Selman TJ, Mann CH, Zamora J, et al. A systematic review of tests for lymph node status in primary endometrial cancer. BMC Womens Health. 2008;8:8. https://doi.org/10.1186/1472-6874-8-8.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Leitao MM Jr, Kehoe S, Barakat RR, 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.

    PubMed  Google Scholar 

  39. Eltabbakh GH, Shamonki J, Mount SL. Surgical stage, final grade, and survival of women with endometrial carcinoma whose preoperative endometrial biopsy shows well-differentiated tumors. Gynecol Oncol. 2005;99:309–12.

    PubMed  Google Scholar 

  40. Gallos ID, Yap J, Rajkhowa M, Luesley DM, et al. Regression, relapse, and live birth rates with fertility-sparing therapy for endometrial cancer and atypical complex endometrial hyperplasia: a systematic review and meta-analysis. Am J Obstet Gynecol. 2012;207(266):e1-12.

    Google Scholar 

  41. Gallos ID, Alazzam M, Clark TJ, et al. Management of endometrial hyperplasia. Royal College of Obstetricians and Gynaecologists/British Society for Gynaecologic Endoscopy (RCOG/BSGE). Green top guideline No.67. 2018. www.rcog.org.uk/en/guidelines-research-services/guidelines/gtg67/. Accessed 13 Mar 2018.

  42. Di Spiezio SA, De Angelis MC, Della Corte L, 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.

    Google Scholar 

  43. Ferrari F, Forte S, Arrigoni G, et al. Impact of endometrial sampling technique and biopsy volume on the diagnostic accuracy of endometrial cancer. Transl Cancer Res. 2020;9(12):7697–705.

    Google Scholar 

  44. Niwa K, Morishita S, Hashimoto M, et al. Conservative therapy for endometrial carcinoma in young women treated with repeated curettage and progestogen. Int J Clin Oncol. 1997;2:165.

    Google Scholar 

  45. Plaxe SC, Mundt AJ. Treatment of low-risk endometrial cancer. 2016. www.uptodate.com. Accessed 13 Aug 2017.

  46. Sundar S, Balega J, Crosbie E, et al. BGCS uterine cancer guidelines: recommendations for practice. Eur J Obstet Gynecol Reprod Biol. 2017;213:71–97.

    PubMed  Google Scholar 

  47. Tabrizi AD, Melli MS, Foroughi M, et al. Antiproliferative effect of metformin on the endometrium: a clinical trial. Asian Pac J Cancer Prev. 2015;15:10067–70.

    Google Scholar 

  48. Session DR, Kalli KR, Tummon IS, Damario MA, Dumesic DA. Treatment of atypical endometrial hyperplasia with an insulin-sensitizing agent. Gynecol Endocrinol. 2003;17:405–7.

    CAS  PubMed  Google Scholar 

  49. Kitson S, Ryan N, MacKintosh ML, et al. Interventions for weight reduction in obesity to improve survival in women with endometrial cancer. Cochrane Database Syst Rev. 2018. https://doi.org/10.1002/14651858.CD012513.pub2.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Khwaja HA, Bonanomi G. Bariatric surgery: techniques, outcomes and complications. Curr Anaesth Crit Care. 2010;21:31–8.

    Google Scholar 

  51. Upala S, Anawin S. Bariatric surgery and risk of postoperative endometrial cancer: a systematic review and meta-analysis. Surg Obes Relat Dis. 2015;11:949–55.

    PubMed  Google Scholar 

  52. Adams TD, Stroup AM, Gress RE, et al. Cancer incidence and mortality after gastric bypass surgery. Obesity. 2009;17:796–802.

    PubMed  Google Scholar 

  53. Jenabi E, Poorolajal J. The effect of body mass index on endometrial cancer: a meta-analysis. Public Health. 2015;129:872–80.

    CAS  PubMed  Google Scholar 

  54. Mackintosh ML, Crosbie EJ. Obesity-driven endometrial cancer: is weight loss the answer? Brit J Obstet Gynaecol. 2013;120:791–4.

    CAS  Google Scholar 

  55. Kim ML, Seong SJ. Clinical applications of levonorgestrel-releasing intrauterine system to gynecologic diseases. Obstet Gynecol Sci. 2013;56:67–75.

    PubMed  PubMed Central  Google Scholar 

  56. Miyamoto T, Watanabe J, Hata H, et al. Significance of progesterone receptor-A and -B expressions in endometrial adenocarcinoma. J Steroid Biochem Mol Biol. 2004;92:111–8.

    CAS  PubMed  Google Scholar 

  57. Darvishian F, Hummer AJ, Thaler HT, et al. Serous endometrial cancers that mimic endometrioid adenocarcinomas: a clinicopathologic and immunohistochemical study of a group of problematic cases. Am J Surg Pathol. 2004;28:1568–78.

    PubMed  Google Scholar 

  58. Demopoulos RI, Mesia AF, Mittal K, et al. Immunohistochemical comparison of uterine papillary serous and papillary endometrioid carcinoma: clues to pathogenesis. Int J Gynecol Pathol. 1999;18:233–7.

    CAS  PubMed  Google Scholar 

  59. Raffone A, Travaglino A, Saccone G, et al. Should progesterone and estrogen receptors be assessed for predicting the response to conservative treatment of endometrial hyperplasia and cancer? A systematic review and meta-analysis. Acta Obstet Gynecol Scand. 2019;98:976–87.

    CAS  PubMed  Google Scholar 

  60. Raffone A, Travaglino A, Zullo FM, et al. Predictive accuracy of progesterone receptor B in young women with atypical endometrial hyperplasia and early endometrial cancer treated with hysteroscopic resection plus LNG-IUD insertion. J Minim Invasive Gynecol. 2020. https://doi.org/10.1016/j.jmig.2020.10.009.

    Article  PubMed  Google Scholar 

  61. Raffone A, Travaglino A, Mascolo M, et al. Predictive accuracy of hormone receptors in conservatively treated endometrial hyperplasia and early endometrioid carcinoma. Acta Obstet Gynecol Scand. 2020;99:140.

    PubMed  Google Scholar 

  62. Travaglino A, Raffone A, Saccone G, et al. Immunohistochemical predictive markers of response to conservative treatment of endometrial hyperplasia and early endometrial cancer: a systematic review. Acta Obstet Gynecol Scand. 2019;98:1086–99.

    CAS  PubMed  Google Scholar 

  63. Gunderson CC, Fader AN, Carson KA, et al. 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.

    CAS  PubMed  Google Scholar 

  64. Ushijima K, Yahata H, Yoshikawa H, 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;25:2798–803.

    CAS  PubMed  Google Scholar 

  65. 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.

    Google Scholar 

  66. Shan W, Ning C, Luo X, et al. Hyperinsulinemia is associated with endometrial hyperplasia and disordered proliferative endometrium: a prospective cross-sectional study. Gynecol Oncol. 2014;132:606–10.

    CAS  PubMed  Google Scholar 

  67. Ferguson RD, Gallagher EJ, Cohen D, et al. Hyperinsulinemia promotes metastasis to the lung in a mouse model of Her2-mediated breast cancer. Endocr Relat Cancer. 2013;20:391–401.

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Wang Y, Zhu Y, Zhang L, et al. Insulin promotes proliferation, survival, and invasion in endometrial carcinoma by activating the MEK/ERK pathway. Cancer Lett. 2012;322:223–31.

    CAS  PubMed  Google Scholar 

  69. Xie Y, Wang YL, Yu L, et al. Metformin promotes progesterone receptor expression via inhibition of mammalian target of rapamycin (mTOR) in endometrial cancer cells. J Steroid Biochem Mol Biol. 2011;126:113–20.

    CAS  PubMed  Google Scholar 

  70. Meireles CG, Pereira SA, Valadares LP, et al. Effects of metformin on endometrial cancer: systematic review and meta-analysis. Gynecol Oncol. 2017;147:167–80.

    CAS  PubMed  Google Scholar 

  71. Yates MS, Basen-Engquist K, Zhang Q, et al. Prospective randomized biomarker study of metformin and lifestyle intervention for prevention in obese postmenopausal women at increased risk for endometrial cancer. J Clin Oncol. 2017;35(15 Suppl):1551.

    Google Scholar 

  72. Rock CL, Pande C, Flatt SW, et al. Favorable changes in serum estrogens and other biologic factors after weight loss in breast cancer survivors who are overweight or obese. Clin Breast Cancer. 2013;13:188–95.

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Patterson RE, Marinac CR, Sears DD, et al. The effects of metformin and weight loss on biomarkers associated with breast cancer outcomes. J Natl Cancer Inst. 2018;110:1239–47.

    PubMed  PubMed Central  Google Scholar 

  74. Secord AA, Hasselblad V, Von Gruenigen VE, et al. Body mass index and mortality in endometrial cancer: a systematic review and meta-analysis. Gynecol Oncol. 2016;140:184–90.

    PubMed  Google Scholar 

  75. Luo J, Chlebowski RT, Hendryx M, et al. Intentional weight loss and endometrial cancer risk. J Clin Oncol. 2017;35:1189–93.

    PubMed  PubMed Central  Google Scholar 

  76. Anveden Å, Taube M, Peltonen M, et al. Long-term incidence of female-specific cancer after bariatric surgery or usual care in the Swedish Obese Subjects Study. Gynecol Oncol. 2017;145:224–9.

    PubMed  PubMed Central  Google Scholar 

  77. Winder AA, Kularatna M, MacCormick AD. Does bariatric surgery affect the incidence of endometrial cancer development? A systematic review. Obes Surg. 2018;28:1433–40.

    PubMed  Google Scholar 

  78. Linkov F, Goughnour SL, Ma T, et al. Changes in inflammatory endometrial cancer risk biomarkers in individuals undergoing surgical weight loss. Gynecol Oncol. 2017;147:133–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Modesitt SC, Hallowell PT, Slack-Davis JK, et al. Women at extreme risk for obesity-related carcinogenesis: baseline endometrial pathology and impact of bariatric surgery on weight, metabolic profiles and quality of life. Gynecol Oncol. 2015;138:238–45.

    PubMed  Google Scholar 

  80. Argenta PA, Kassing M, Truskinovsky AM, et al. Bariatric surgery and endometrial pathology in asymptomatic morbidly obese women: a prospective, pilot study. Brit J Obstet Gynaecol. 2013;120:795–800.

    CAS  Google Scholar 

  81. Benito V, López-Tomassetti E, Esparza M, et al. Bariatric surgery: does it play a role in fertility-preserving treatment among obese young women with endometrial cancer? J Minim Invasive Gynecol. 2015;22:906–9.

    PubMed  Google Scholar 

  82. Moher D, Liberati A, Tetzlaff J, PRISMA Group, et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6:1000097. https://doi.org/10.1371/journal.pmed.1000097.

    Article  Google Scholar 

  83. Parmar MK, Torri V, Stewart L. Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Stat Med. 1998;17:2815–34.

    CAS  PubMed  Google Scholar 

  84. Higgins JPT, Altman DG, Gøtzsche PC, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928.

    PubMed  PubMed Central  Google Scholar 

  85. Sterne JA, Hernan MA, Reeves BC, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016;355:i4919. https://doi.org/10.1136/bmj.i4919.

    Article  PubMed  PubMed Central  Google Scholar 

  86. Review Manager 5 (RevMan 5) (Computer program). Version 5.3. Copenhagen: Nordic Cochrane Centre, The Cochrane Collaboration, 2014.

  87. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–88.

    CAS  PubMed  Google Scholar 

  88. Langendam MW, Akl EA, Dahm P, et al. Assessing and presenting summaries of evidence in Cochrane reviews. Syst Rev. 2013;2:81.

    PubMed  PubMed Central  Google Scholar 

  89. Higgins JPT, Thompson SG, Deeks JJ, et al. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–60.

    PubMed  PubMed Central  Google Scholar 

  90. GRADEpro GDT [Computer program]. Version accessed 13 March 2018. Hamilton (ON): McMaster University (developed by Evidence Prime). 2015. www.gradepro.org. Accessed 13 Aug 2017.

  91. Meader N, King K, Llewellyn A, et al. A checklist designed to aid consistency and reproducibility of GRADE assessments: development and pilot validation. Syst Rev. 2014;3:82. https://doi.org/10.1186/2046-4053-3-82.

    Article  PubMed  PubMed Central  Google Scholar 

  92. Baker J, Obermair A, Gebski V, et al. 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;125:263–70.

    CAS  PubMed  Google Scholar 

  93. Koskas M, Uzan J, Luton D, et al. 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;101:785–94.

    PubMed  Google Scholar 

  94. Wei J, Zhang W, Feng L, et al. 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.

    Google Scholar 

  95. Guillon S, Popescu N, Phelippeau J, et al. A systematic review and meta-analysis of prognostic factors for remission in fertility-sparing management of endometrial atypical hyperplasia and adenocarcinoma. Int J Gynecol Obstet. 2019;146:277–88.

    Google Scholar 

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Acknowledgements

The authors would like to thank Jo Morrison for clinical and editorial advice; Jo Platt for designing the search strategy; Gail Quinn, Clare Jess, and Tracey Harrison for their contributions to the editorial process; Marta Roqué for their methodological and technical advice; and José Manuel Martínez-Garcia for data collection. We thank the CERCA programme/Generalitat de Catalunya and IDIBELL for institutional support.

Funding

This project was supported by the National Institute for Health Research (NIHR), via Cochrane Infrastructure funding to the Cochrane Gynaecological, Neuro-oncology and Orphan Cancers Group. The views and opinions expressed herein are those of the review authors and do not necessarily reflect those of the Systematic Reviews Programme, the NIHR, the National Health Service (NHS) or the Department of Health. The journal’s Rapid Service Fee is funded by IDIBELL.

Editorial Assistance

The authors would like to thank Michael Maudsley of the language services of the University of Barcelona for editing the manuscript. Michael Maudsley’s English editing assistance was funded by University of Barcelona.

Authorship

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Authorship Contributions

All authors contributed equally to the development of the protocol.

Disclosures

Maria-Eulalia Fernández-Montolí, Jordi Sabadell and Nayanar Contreras declare that they have no conflicts of interests.

Compliance with Ethics Guidelines

Ethics approval and consent to participate or for publication were not required. The Helsinki Declaration of 1964 and its later amendments were not applicable. This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.

Data Availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Department of Gynaecology, Hospital Universitari de Bellvitge, Universitat de Barcelona-IDIBELL, Barcelona, Spain

    Maria-Eulalia Fernandez-Montoli

  2. Department of Gynaecology, Hospital Universitari Vall d’Hebron, Vall d’Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain

    Jordi Sabadell

  3. Gynecology Department, Hospital El Pilar, Barcelona, Spain

    Nayanar-Adela Contreras-Perez

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  1. Maria-Eulalia Fernandez-Montoli
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  3. Nayanar-Adela Contreras-Perez
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Corresponding authors

Correspondence to Maria-Eulalia Fernandez-Montoli or Jordi Sabadell.

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Fernandez-Montoli, ME., Sabadell, J. & Contreras-Perez, NA. Fertility-Sparing Treatment for Atypical Endometrial Hyperplasia and Endometrial Cancer: A Cochrane Systematic Review Protocol. Adv Ther 38, 2717–2731 (2021). https://doi.org/10.1007/s12325-021-01693-y

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