Impact of in vitro fertilization on malignant transformation of endometriotic cysts: A retrospective cohort analysis of endometriosis-associated ovarian cancers.
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This retrospective cohort analysis examined 593 treatment-naïve ovarian cancer patients to identify associations between in vitro fertilization (IVF) exposure and endometriosis-associated ovarian cancers. The study identified four cases of endometriosis-associated ovarian cancer in women under 40 who had previously undergone IVF, with a majority experiencing repeated transvaginal aspiration or sclerotherapy for endometriomas. Key findings indicated that these interventions correlated with advanced disease stages and elevated CA125 levels, while the absence of live births potentially removed parity-associated protective effects against carcinogenesis. The authors concluded that repeated mechanical and chemical insults from cyst interventions may accelerate malignant transformation within a pro-inflammatory microenvironment. This paper is centrally about endometriosis — specifically the risk of malignant transformation of endometriotic cysts into ovarian cancer following assisted reproductive technology interventions.
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Abstract
e17581 Background: Endometriosis, affecting 10% of reproductive-aged women, carries a 1–3% lifetime risk of malignant transformation, predominantly to clear cell carcinoma (CCC) and endometrioid adenocarcinoma [1] . A recent JAMA study noted that deep infiltrating endometriosis and/or ovarian endometriomas may confer a 19-fold increased ovarian cancer risk but did not clarify whether these high-risk patients had undergone assisted reproductive technology (ART) [2] . With the expansion of ART utilization and increasing liberalization of egg-freezing indications, the number of women undergoing ovulation induction (OI) and cyst interventions is rising. This study raises concerns that interventions like repeated cyst aspiration/sclerotherapy may accelerate malignant transformation and contribute to earlier disease onset. Methods: A retrospective cohort analysis of 593 treatment-naïve ovarian cancer patients (2019–2022, University-affiliated Hospital) identified 4 endometriosis-associated ovarian cancer (EAOC) cases (<40 years, prior IVF). All had histologically confirmed endometriomas before IVF treatment. Data included IVF protocols, cyst interventions, histopathology, genetic profiling. Results: 4 EAOC cases (0.67%) with IVF exposure were identified: median age 37.5 years (33–41), median 4 OI cycles (2–6). 3 patients (75%) underwent repeated transvaginal aspiration/sclerotherapy for endometriomas, correlating with advanced-stage (IIB/IIIC) and elevated CA125 (>200 U/mL in 3/4). Histologic subtypes included CCC (n=3, Stages IA/IIB) and adenosquamous carcinoma (n=1, Stage IIIC). Genetic heterogeneity was observed: one patient harbored a germline/somatic BRCA1 mutation, 2 were BRCA1/2 wild-type (HRD−), and one was BRCA wild-type (HRD+). Notably, none of the patients achieved a live birth, potentially diminishing any parity-associated protective effect against ovarian carcinogenesis. Conclusions: Repeated cyst aspiration/sclerotherapy in endometriomas may accelerate malignant transformation. The absence of live births (and thus parity-associated protection) could worsen progression. As ART utilization expands and egg-freezing indications become more liberal, the rising number of women undergoing ovarian stimulation and cyst interventions underscores the urgent need for evidence-based guidelines. From an oncologic perspective, repeated mechanical and chemical insults may foster a pro-inflammatory microenvironment, promoting genomic instability and carcinogenesis. Multidisciplinary care involving reproductive endocrinologists, gynecologic oncologists, and genetic counselors is essential to optimize outcomes. Future research should focus on longitudinal studies to establish causality and develop risk-stratified protocols for endometrioma patients seeking ART. 1. Pearce CL et al. Lancet Oncol . 2012;13:385-94. 2. Velez Edwards DR et al. JAMA . 2024;331:402-15. Clinical characteristics of EAOC patients with prior IVF and endometrioma interventions. Patient ID Age Ovulation Induction (OI) Cycles Pathology Stage Times of needle aspiration and sclerosis Genetic Status 1 37 3 CCC IA 0 g/s BRCA1 mut 2 39 4 CCC IIB 2 g/s BRCA1/2 wt, HRD− 3 33 6 Adenosquamous IIIC 2 g/s BRCA wt, HRD− 4 41 2 CCC IIB 2 g/s BRCA wt, HRD+
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Abstract
e17581
Background
Endometriosis, affecting 10% of reproductive-aged women, carries a 1–3% lifetime risk of malignant transformation, predominantly to clear cell carcinoma (CCC) and endometrioid adenocarcinoma[1]. A recent JAMA study noted that deep infiltrating endometriosis and/or ovarian endometriomas may confer a 19-fold increased ovarian cancer risk but did not clarify whether these high-risk patients had undergone assisted reproductive technology (ART)[2]. With the expansion of ART utilization and increasing liberalization of egg-freezing indications, the number of women undergoing ovulation induction (OI) and cyst interventions is rising. This study raises concerns that interventions like repeated cyst aspiration/sclerotherapy may accelerate malignant transformation and contribute to earlier disease onset. Methods: A retrospective cohort analysis of 593 treatment-naïve ovarian cancer patients (2019–2022, University-affiliated Hospital) identified 4 endometriosis-associated ovarian cancer (EAOC) cases (<40 years, prior IVF). All had histologically confirmed endometriomas before IVF treatment. Data included IVF protocols, cyst interventions, histopathology, genetic profiling. Results: 4 EAOC cases (0.67%) with IVF exposure were identified: median age 37.5 years (33–41), median 4 OI cycles (2–6). 3 patients (75%) underwent repeated transvaginal aspiration/sclerotherapy for endometriomas, correlating with advanced-stage (IIB/IIIC) and elevated CA125 (>200 U/mL in 3/4). Histologic subtypes included CCC (n=3, Stages IA/IIB) and adenosquamous carcinoma (n=1, Stage IIIC). Genetic heterogeneity was observed: one patient harbored a germline/somatic BRCA1 mutation, 2 were BRCA1/2 wild-type (HRD−), and one was BRCA wild-type (HRD+). Notably, none of the patients achieved a live birth, potentially diminishing any parity-associated protective effect against ovarian carcinogenesis. Conclusions: Repeated cyst aspiration/sclerotherapy in endometriomas may accelerate malignant transformation. The absence of live births (and thus parity-associated protection) could worsen progression. As ART utilization expands and egg-freezing indications become more liberal, the rising number of women undergoing ovarian stimulation and cyst interventions underscores the urgent need for evidence-based guidelines. From an oncologic perspective, repeated mechanical and chemical insults may foster a pro-inflammatory microenvironment, promoting genomic instability and carcinogenesis. Multidisciplinary care involving reproductive endocrinologists, gynecologic oncologists, and genetic counselors is essential to optimize outcomes. Future research should focus on longitudinal studies to establish causality and develop risk-stratified protocols for endometrioma patients seeking ART. 1. Pearce CL et al. Lancet Oncol. 2012;13:385-94. 2. Velez Edwards DR et al. JAMA. 2024;331:402-15.Clinical characteristics of EAOC patients with prior IVF and endometrioma interventions.
| Patient ID | Age | Ovulation Induction (OI) Cycles | Pathology | Stage | Times of needle aspiration and sclerosis | Genetic Status |
|---|---|---|---|---|---|---|
| 1 | 37 | 3 | CCC | IA | 0 | g/s BRCA1 mut |
| 2 | 39 | 4 | CCC | IIB | 2 | g/s BRCA1/2 wt, HRD− |
| 3 | 33 | 6 | Adenosquamous | IIIC | 2 | g/s BRCA wt, HRD− |
| 4 | 41 | 2 | CCC | IIB | 2 | g/s BRCA wt, HRD+ |
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© 2025 by American Society of Clinical Oncology.
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Published online: May 28, 2025
Published in print: June 01, 2025
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Renji Hospital Affiliated to Shanghai Jiao Tong University Medical School: Postdoctoral Funding
Shanghai Committee of Science and Technolog: Shanghai Magnolia Talent Program (Class A of Pujiang Project)
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Impact of in vitro fertilization on malignant transformation of endometriotic cysts: A retrospective cohort analysis of endometriosis-associated ovarian cancers.. J Clin Oncol 43, e17581-e17581(2025).
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Taiyang Ye, Yang Zhou, Mingzhe Li, Jie Zhu, Libing Xiang
Journal of Clinical Oncology 2025 43:16_suppl, e17581-e17581
Taiyang Ye, Yang Zhou, Mingzhe Li, Jie Zhu, Libing Xiang
Journal of Clinical Oncology 2025 43:16_suppl, e17581-e17581
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