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

Adv Ther. 2021 May;38(5):2717-2731. doi: 10.1007/s12325-021-01693-y. Epub 2021 Apr 8.


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.

Keywords: Atypical endometrial hyperplasia; Cochrane protocol; Endometrial cancer; Fertility-sparing treatment; Meta-analysis; Systematic review.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Endometrial Hyperplasia* / drug therapy
  • Endometrial Hyperplasia* / surgery
  • Endometrial Neoplasms* / drug therapy
  • Endometrial Neoplasms* / surgery
  • Female
  • Humans
  • Hysterectomy
  • Intrauterine Devices, Medicated*
  • Levonorgestrel
  • Review Literature as Topic
  • Systematic Reviews as Topic


  • Levonorgestrel