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Oncologic safety and reproductive outcomes of conservative therapy for early-stage endometrial disease
Aisha Jamil, Ghulam Sughra, Ghazala Dawood Abbasi, Soukaina Adane, Monica Punshi, Mobashara Ghulam Muhammad, Marium Nausherwan, Yamina Ishtiaq, Muhammad Dawood Hazoor
Aisha Jamil, Department of Obstetrics and Gynaecology, Type C Hospital Karak, Karak 27200, Khyber Pakhtunkhwa, Pakistan
Ghulam Sughra, Department of Obstetrics and Gynaecology, Asian Institute of Medical Sciences, Hyderabad 71000, Sindh, Pakistan
Ghazala Dawood Abbasi, Department of Obstetrics and Gynaecology, Islamic International Medical College, Sargodha 40100, Punjab, Pakistan
Soukaina Adane, Department of Obstetrics and Gynaecology, Xuzhou Medical University, Xuzhou 221006, Jiangsu Province, China
Monica Punshi, Department of Obstetrics and Gynaecology, Dr. Ruth KM Pfau Civil Hospital, Karachi 74400, Sindh, Pakistan
Mobashara Ghulam Muhammad, Department of Obstetrics and Gynaecology, Mohtarma Benazir Bhutto Shaheed Medical College, Mirpur Khas 10250, Sindh, Pakistan
Marium Nausherwan, Department of Obstetrics and Gynaecology, Dartford and Gravesham NHS Trust, Dartford DA2 8DA, Kent, United Kingdom
Yamina Ishtiaq, Department of Obstetrics and Gynaecology, Shifa International Hospital, Islamabad 44000, Pakistan
Muhammad Dawood Hazoor, Department of Internal Medicine, International University of Kyrgyzstan, ISM IUK Eastern Campus, Bishkek 750065, Kyrgyzstan
Author contributions: Jamil A, Sughra G, Abbasi GD, Adane S, Punshi M, Muhammad MG, Nausherwan M, Ishtiaq Y, and Hazoor MD designed the research study; Jamil A, Sughra G, Abbasi GD, Adane S, Punshi M, Muhammad MG, Nausherwan M, and Ishtiaq Y performed the research; Hazoor MD contributed new analytic tools; Jamil A, Abbasi GD, and Hazoor MD analyzed the data and wrote the manuscript; and all authors have read and approved the final manuscript.
Institutional review board statement: The approval by the Institutional Review Board waiver is granted due to its retrospective design involving de-identified medical records.
Informed consent statement: Informed consent was waived due to the retrospective nature of the study, which involved analysis of de-identified existing medical records.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Data sharing statement: This manuscript is original, has not been published, and is not under consideration elsewhere.
Corresponding author: Muhammad Dawood Hazoor, MD, Department of Internal Medicine, International University of Kyrgyzstan, ISM IUK Eastern Campus, 6 Seven April Street, Bish
kek 750065, Kyrgyzstan.
sidhudawood@gmail.com
Received: November 3, 2025
Revised: November 17, 2025
Accepted: February 24, 2026
Published online: March 24, 2026
Processing time: 142 Days and 11.6 Hours
BACKGROUND
Endometrial cancer (EC) is the most common gynecologic malignancy, with rising incidence in young women desiring fertility preservation. Traditional hysterectomy precludes childbearing, prompting fertility-sparing management (FSM) with progestins for atypical hyperplasia (AH) and early-stage, low-grade EC. However, concerns persist regarding oncologic safety, recurrence, and reproductive success. Biomarkers like Ki-67, human epididymis protein 4, and molecular classifications may enhance prognostic stratification. This study hypothesizes that FSM yields favorable outcomes, with biomarkers independently predicting recurrence risk.
AIM
To assess oncologic and reproductive outcomes of FSM in AH and early-stage EC, evaluating biomarker predictive value.
METHODS
Multicenter retrospective cohort study at tertiary hospitals, including 234 women aged 18-45 years with AH or FIGO stage IA grade 1 endometrioid EC (2015-2023). Participants were selected via medical records review with records with estrogen/progesterone positivity and no invasion on imaging. Interventions included levonorgestrel-intrauterine device, megestrol acetate, or combinations, with 3-6 monthly biopsies. Key analyses: Kaplan-Meier for survival, multivariable Cox models for recurrence predictor.
RESULTS
Among 234 patients [126 AH, 108 grade 1 endometrioid adenocarcinoma (G1 EA)], complete response (CR) was 79.9% (187; AH 84.9% vs G1 EA 74.1%, P = 0.249), with mean time to CR 4.0 ± 1.5 months. Recurrence occurred in 25.1% (47/187; mean time 11.4 ± 4.6 months), higher in G1 EA [35.0% vs AH 17.8%, odds ratio = 2.51, 95% confidence interval (CI): 1.25-5.04]. Multivariable analysis showed body mass index > 30 kg/m2 [hazard ratio (HR) = 2.95, 95%CI: 1.12-7.76, P = 0.029], Ki-67 > 20% (HR = 3.12, 95%CI: 1.25-7.81, P = 0.015), and human epididymis protein 4 > 50 pmol/L (HR = 2.78, 95%CI: 1.10-7.02, P = 0.031) predicted recurrence. Molecular subtypes influenced CR: No specific molecular profile 78.4% vs mismatch repair deficient 48.6%. Among 117 attempting pregnancy, live birth rate was 50.4% (59). Disease-specific survival was 99.1%.
CONCLUSION
FSM achieves high response rates and reproductive success with excellent survival; biomarkers independently predict recurrence, enabling personalized risk stratification.
Core Tip: This multicenter retrospective study of 234 women with atypical hyperplasia or early-stage endometrial cancer demonstrates fertility-sparing management’s efficacy, with 79.9% complete response, 25.1% recurrence, and 50.4% live birth rate. Innovatively, biomarkers (Ki-67 > 20%, human epididymis protein 4 > 50 pmol/L) independently predict recurrence (hazard ratios = 3.12 and 2.78), while molecular classification (e.g., no specific molecular profile favorable) refines patient selection, advocating multidisciplinary approaches for optimized oncologic and reproductive outcomes.
