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Theses & Dissertations: Cancer Research

Theses/dissertations from 2024 2024.

Novel Spirocyclic Dimer (SpiD3) Displays Potent Preclinical Effects in Hematological Malignancies , Alexandria Eiken

Chemotherapy-Induced Modulation of Tumor Antigen Presentation , Alaina C. Larson

Understanding the role of MASTL in colon homeostasis and colitis-associated cancer development , Kristina Pravoverov

Dying Right: Supporting Anti-Cancer Therapy Through Immunogenic Cell Death , Elizabeth Schmitz

Therapeutic Effects of BET Protein Inhibition in B-cell Malignancies and Beyond , Audrey L. Smith

Targeting KSR1 to inhibit stemness and therapy resistance , Heidi M. Vieira

Identifying the Molecular Determinants of Lung Metastatic Adaptation in Prostate Cancer , Grace M. Waldron

Identification of Mitotic Phosphatases and Cyclin K as Novel Molecular Targets in Pancreatic Cancer , Yi Xiao

Theses/Dissertations from 2023 2023

Development of Combination Therapy Strategies to Treat Cancer Using Dihydroorotate Dehydrogenase Inhibitors , Nicholas Mullen

Overcoming Resistance Mechanisms to CDK4/6 Inhibitor Treatment Using CDK6-Selective PROTAC , Sarah Truong

Theses/Dissertations from 2022 2022

Omics Analysis in Cancer and Development , Emalie J. Clement

Investigating the Role of Splenic Macrophages in Pancreatic Cancer , Daisy V. Gonzalez

Polymeric Chloroquine in Metastatic Pancreatic Cancer Therapy , Rubayat Islam Khan

Evaluating Targets and Therapeutics for the Treatment of Pancreatic Cancer , Shelby M. Knoche

Characterization of 1,1-Diarylethylene FOXM1 Inhibitors Against High-Grade Serous Ovarian Carcinoma Cells , Cassie Liu

Novel Mechanisms of Protein Kinase C α Regulation and Function , Xinyue Li

SOX2 Dosage Governs Tumor Cell Identity and Proliferation , Ethan P. Metz

Post-Transcriptional Control of the Epithelial-to-Mesenchymal Transition (EMT) in Ras-Driven Colorectal Cancers , Chaitra Rao

Use of Machine Learning Algorithms and Highly Multiplexed Immunohistochemistry to Perform In-Depth Characterization of Primary Pancreatic Tumors and Metastatic Sites , Krysten Vance

Characterization of Metastatic Cutaneous Squamous Cell Carcinoma in the Immunosuppressed Patient , Megan E. Wackel

Visceral adipose tissue remodeling in pancreatic ductal adenocarcinoma cachexia: the role of activin A signaling , Pauline Xu

Phos-Tag-Based Screens Identify Novel Therapeutic Targets in Ovarian Cancer and Pancreatic Cancer , Renya Zeng

Theses/Dissertations from 2021 2021

Functional Characterization of Cancer-Associated DNA Polymerase ε Variants , Stephanie R. Barbari

Pancreatic Cancer: Novel Therapy, Research Tools, and Educational Outreach , Ayrianne J. Crawford

Apixaban to Prevent Thrombosis in Adult Patients Treated With Asparaginase , Krishna Gundabolu

Molecular Investigation into the Biologic and Prognostic Elements of Peripheral T-cell Lymphoma with Regulators of Tumor Microenvironment Signaling Explored in Model Systems , Tyler Herek

Utilizing Proteolysis-Targeting Chimeras to Target the Transcriptional Cyclin-Dependent Kinases 9 and 12 , Hannah King

Insights into Cutaneous Squamous Cell Carcinoma Pathogenesis and Metastasis Using a Bedside-to-Bench Approach , Marissa Lobl

Development of a MUC16-Targeted Near-Infrared Antibody Probe for Fluorescence-Guided Surgery of Pancreatic Cancer , Madeline T. Olson

FGFR4 glycosylation and processing in cholangiocarcinoma promote cancer signaling , Andrew J. Phillips

Theses/Dissertations from 2020 2020

Cooperativity of CCNE1 and FOXM1 in High-Grade Serous Ovarian Cancer , Lucy Elge

Characterizing the critical role of metabolic and redox homeostasis in colorectal cancer , Danielle Frodyma

Genomic and Transcriptomic Alterations in Metabolic Regulators and Implications for Anti-tumoral Immune Response , Ryan J. King

Dimers of Isatin Derived Spirocyclic NF-κB Inhibitor Exhibit Potent Anticancer Activity by Inducing UPR Mediated Apoptosis , Smit Kour

From Development to Therapy: A Panoramic Approach to Further Our Understanding of Cancer , Brittany Poelaert

The Cellular Origin and Molecular Drivers of Claudin-Low Mammary Cancer , Patrick D. Raedler

Mitochondrial Metabolism as a Therapeutic Target for Pancreatic Cancer , Simon Shin

Development of Fluorescent Hyaluronic Acid Nanoparticles for Intraoperative Tumor Detection , Nicholas E. Wojtynek

Theses/Dissertations from 2019 2019

The role of E3 ubiquitin ligase FBXO9 in normal and malignant hematopoiesis , R. Willow Hynes-Smith

BRCA1 & CTDP1 BRCT Domainomics in the DNA Damage Response , Kimiko L. Krieger

Targeted Inhibition of Histone Deacetyltransferases for Pancreatic Cancer Therapy , Richard Laschanzky

Human Leukocyte Antigen (HLA) Class I Molecule Components and Amyloid Precursor-Like Protein 2 (APLP2): Roles in Pancreatic Cancer Cell Migration , Bailee Sliker

Theses/Dissertations from 2018 2018

FOXM1 Expression and Contribution to Genomic Instability and Chemoresistance in High-Grade Serous Ovarian Cancer , Carter J. Barger

Overcoming TCF4-Driven BCR Signaling in Diffuse Large B-Cell Lymphoma , Keenan Hartert

Functional Role of Protein Kinase C Alpha in Endometrial Carcinogenesis , Alice Hsu

Functional Signature Ontology-Based Identification and Validation of Novel Therapeutic Targets and Natural Products for the Treatment of Cancer , Beth Neilsen

Elucidating the Roles of Lunatic Fringe in Pancreatic Ductal Adenocarcinoma , Prathamesh Patil

Theses/Dissertations from 2017 2017

Metabolic Reprogramming of Pancreatic Ductal Adenocarcinoma Cells in Response to Chronic Low pH Stress , Jaime Abrego

Understanding the Relationship between TGF-Beta and IGF-1R Signaling in Colorectal Cancer , Katie L. Bailey

The Role of EHD2 in Triple-Negative Breast Cancer Tumorigenesis and Progression , Timothy A. Bielecki

Perturbing anti-apoptotic proteins to develop novel cancer therapies , Jacob Contreras

Role of Ezrin in Colorectal Cancer Cell Survival Regulation , Premila Leiphrakpam

Evaluation of Aminopyrazole Analogs as Cyclin-Dependent Kinase Inhibitors for Colorectal Cancer Therapy , Caroline Robb

Identifying the Role of Janus Kinase 1 in Mammary Gland Development and Breast Cancer , Barbara Swenson

DNMT3A Haploinsufficiency Provokes Hematologic Malignancy of B-Lymphoid, T-Lymphoid, and Myeloid Lineage in Mice , Garland Michael Upchurch

Theses/Dissertations from 2016 2016

EHD1 As a Positive Regulator of Macrophage Colony-Stimulating Factor-1 Receptor , Luke R. Cypher

Inflammation- and Cancer-Associated Neurolymphatic Remodeling and Cachexia in Pancreatic Ductal Adenocarcinoma , Darci M. Fink

Role of CBL-family Ubiquitin Ligases as Critical Negative Regulators of T Cell Activation and Functions , Benjamin Goetz

Exploration into the Functional Impact of MUC1 on the Formation and Regulation of Transcriptional Complexes Containing AP-1 and p53 , Ryan L. Hanson

DNA Polymerase Zeta-Dependent Mutagenesis: Molecular Specificity, Extent of Error-Prone Synthesis, and the Role of dNTP Pools , Olga V. Kochenova

Defining the Role of Phosphorylation and Dephosphorylation in the Regulation of Gap Junction Proteins , Hanjun Li

Molecular Mechanisms Regulating MYC and PGC1β Expression in Colon Cancer , Jamie L. McCall

Pancreatic Cancer Invasion of the Lymphatic Vasculature and Contributions of the Tumor Microenvironment: Roles for E-selectin and CXCR4 , Maria M. Steele

Altered Levels of SOX2, and Its Associated Protein Musashi2, Disrupt Critical Cell Functions in Cancer and Embryonic Stem Cells , Erin L. Wuebben

Theses/Dissertations from 2015 2015

Characterization and target identification of non-toxic IKKβ inhibitors for anticancer therapy , Elizabeth Blowers

Effectors of Ras and KSR1 dependent colon tumorigenesis , Binita Das

Characterization of cancer-associated DNA polymerase delta variants , Tony M. Mertz

A Role for EHD Family Endocytic Regulators in Endothelial Biology , Alexandra E. J. Moffitt

Biochemical pathways regulating mammary epithelial cell homeostasis and differentiation , Chandrani Mukhopadhyay

EPACs: epigenetic regulators that affect cell survival in cancer. , Catherine Murari

Role of the C-terminus of the Catalytic Subunit of Translesion Synthesis Polymerase ζ (Zeta) in UV-induced Mutagensis , Hollie M. Siebler

LGR5 Activates TGFbeta Signaling and Suppresses Metastasis in Colon Cancer , Xiaolin Zhou

LGR5 Activates TGFβ Signaling and Suppresses Metastasis in Colon Cancer , Xiaolin Zhou

Theses/Dissertations from 2014 2014

Genetic dissection of the role of CBL-family ubiquitin ligases and their associated adapters in epidermal growth factor receptor endocytosis , Gulzar Ahmad

Strategies for the identification of chemical probes to study signaling pathways , Jamie Leigh Arnst

Defining the mechanism of signaling through the C-terminus of MUC1 , Roger B. Brown

Targeting telomerase in human pancreatic cancer cells , Katrina Burchett

The identification of KSR1-like molecules in ras-addicted colorectal cancer cells , Drew Gehring

Mechanisms of regulation of AID APOBEC deaminases activity and protection of the genome from promiscuous deamination , Artem Georgievich Lada

Characterization of the DNA-biding properties of human telomeric proteins , Amanda Lakamp-Hawley

Studies on MUC1, p120-catenin, Kaiso: coordinate role of mucins, cell adhesion molecules and cell cycle players in pancreatic cancer , Xiang Liu

Epac interaction with the TGFbeta PKA pathway to regulate cell survival in colon cancer , Meghan Lynn Mendick

Theses/Dissertations from 2013 2013

Deconvolution of the phosphorylation patterns of replication protein A by the DNA damage response to breaks , Kerry D. Brader

Modeling malignant breast cancer occurrence and survival in black and white women , Michael Gleason

The role of dna methyltransferases in myc-induced lymphomagenesis , Ryan A. Hlady

Design and development of inhibitors of CBL (TKB)-protein interactions , Eric A. Kumar

Pancreatic cancer-associated miRNAs : expression, regulation and function , Ashley M. Mohr

Mechanistic studies of mitochondrial outer membrane permeabilization (MOMP) , Xiaming Pang

Novel roles for JAK2/STAT5 signaling in mammary gland development, cancer, and immune dysregulation , Jeffrey Wayne Schmidt

Optimization of therapeutics against lethal pancreatic cancer , Joshua J. Souchek

Theses/Dissertations from 2012 2012

Immune-based novel diagnostic mechanisms for pancreatic cancer , Michael J. Baine

Sox2 associated proteins are essential for cell fate , Jesse Lee Cox

KSR2 regulates cellular proliferation, transformation, and metabolism , Mario R. Fernandez

Discovery of a novel signaling cross-talk between TPX2 and the aurora kinases during mitosis , Jyoti Iyer

Regulation of metabolism by KSR proteins , Paula Jean Klutho

The role of ERK 1/2 signaling in the dna damage-induced G2 , Ryan Kolb

Regulation of the Bcl-2 family network during apoptosis induced by different stimuli , Hernando Lopez

Studies on the role of cullin3 in mitosis , Saili Moghe

Characteristics of amyloid precursor-like protein 2 (APLP2) in pancreatic cancer and Ewing's sarcoma , Haley Louise Capek Peters

Structural and biophysical analysis of a human inosine triphosphate pyrophosphatase polymorphism , Peter David Simone

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Ovarian Cancer Treatment Decisions: Accessing Gynecologic Oncology Care

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• March 20, 2019
• Affiliation: Gillings School of Global Public Health, Department of Health Policy and Management
• Ovarian cancer is the most fatal gynecologic malignancy and the fifth leading cause of cancer-related deaths among women in the U.S (USCS 2015). The majority (>80%) of women is diagnosed at late stages (III or IV), often when the prognosis is poor and the 5-year survival rate is 37-45% (Howlader et al. 2015; USCS 2015). Poor prognosis has been attributed to a lack of an early detection strategy, lack of access of specialist care, variations in surgical and chemotherapeutic treatment and patient variability in uptake, as well as healthcare systems characteristics that may contribute to variable quality of care and delays (Bristow et al. 2014b; Carney et al. 2002; Cliby et al. 2015; Thrall et al. 2011). While earlier research efforts have shown treatment from a gynecologic oncologist (GO) to be associated with improved survival, studies have suggested that a substantial number of women with ovarian cancer still do not receive care from a GO at any point during their care (Vernooij et al. 2007). Less is known about when women are accessing the care from a GO (i.e. preoperative/consult only, intraoperatively, postoperatively, or continuous involvement at all phases) and how accessing a GO at different phases of care (i.e. timing) impacts survival. Furthermore, gaps still exist in the literature on the role of a patient’s psychosocial experience and voice in ovarian cancer care (Erwin 2010; Herzog et al. 2014). The overall objective of this research was to understand the effect of timing of GO involvement on mortality (Aim 1 and 2) and explore the patient-level preferences and roles around decision-making and decisional self-efficacy among women with ovarian cancer (Aim 3). Through use of cancer registries supplemented with medical record abstraction (n=2,162) and survey data (n=170), this research examined different aspects around when and where ovarian cancer patients accessed a GO and among those largely seen by a GO, we explored patient-centered factors associated with having greater decisional efficacy and/or decisional support needs. Based on our findings, differences in GO involvement were evident by patient age, race, and place of care. The patient’s perception of a GO as the most important physician in treatment decisions about care did not affect decisional efficacy, but other psychosocial domains did. Though our results likely reflects the confluence of clinical management processes, patient- and provider treatment preferences, and the complexities of the patient-provider clinical interaction that determine the extent of care, it underscores the importance of further examining equitable care delivery to all subgroups of women, particularly those whom may be vulnerable to decisional support needs. We expect that our research findings will help future efforts to identify, understand, and implement interventions to improve receipt of continuous, quality care associated with increased survival and consistent with patient needs.
• decision-making
• Public health
• ovarian cancer
• https://doi.org/10.17615/65y5-z206
• Dissertation
• In Copyright
• Wheeler, Stephanie
• Reeve, Bryce
• Hall, Ingrid
• Brewster, Wendy
• Bennett, Antonia
• Doctor of Philosophy
• University of North Carolina at Chapel Hill Graduate School

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Advances in Ovarian Cancer Research

An ovarian tumor grown in a mouse using human cells. Special techniques were used to create the high-resolution, 3-D view of the cancer’s cell structure and inner workings.

The most common ovarian cancers are those that begin in the epithelial cells that line the fallopian tubes or  ovaries . These, along with cancers that form in the peritoneum , are called epithelial ovarian cancers . Other types of ovarian cancer arise in other cells, including germ cell tumors , which start in the cells that make eggs, and stromal cell tumors , which start in supporting tissues. 

NCI-funded researchers are working to advance our understanding of how to prevent, detect early, and treat ovarian cancer.

This page highlights some of what’s new in the latest research in ovarian cancer, including clinical advances that may soon translate into improved care, NCI-supported programs that are fueling progress, and research findings from recent studies.

Prevention of Ovarian Cancer

Women who carry harmful or potentially harmful mutations in the BRCA1 or BRCA2 genes are at increased risk of developing ovarian cancer.  Surgery to remove the ovaries and fallopian tubes in these women is the recommended treatment method and can reduce their lifetime risk of getting ovarian cancer by 95%. However, having this surgery causes immediate menopause. This may cause health problems if it is much earlier than naturally occurring menopause.

Research has shown that the most common type of ovarian cancer begins in the fallopian tubes , not in the ovaries. This discovery has led doctors to reconsider ways of preventing ovarian cancer.

• Removing fallopian tubes only. An ongoing NCI-sponsored clinical trial is testing whether removing the fallopian tubes but delaying removal of the ovaries will be as safe and effective to reduce the risk of ovarian cancer in women with BRCA1 mutations as removing both the ovaries and fallopian tubes at the same time. This would allow women to maintain premenopausal levels of hormones produced by the ovaries and delay many of the complications associated with menopause.
• Removal of fallopian tubes in people seeking to prevent pregnancy. The discovery that epithelial ovarian cancers most often start in the fallopian tubes has also led to changes in the way some gynecologists approach surgery to prevent pregnancy. Women seeking tubal ligation to prevent pregnancy (often called having your tubes tied) may be offered the option of having their tubes removed instead. Doing so might reduce the possibility of ovarian cancer in the future. 
• Removal of fallopian tubes in people undergoing a hysterectomy. Similarly, some gynecologists recommend that their patients who are undergoing a hysterectomy also have their fallopian tubes removed.
• Testing relatives for gene mutations. NCI is funding efforts to test the relatives of women who have been diagnosed with ovarian cancer in the past.  Researchers are locating women diagnosed with ovarian cancer with the hope to test them and/or their family members for ovarian cancer-related gene mutations. As a result, family members who learn they carry a mutation can take steps to reduce their risk. The overall goal is not only to prevent ovarian cancer, but also to find the best ways to communicate sensitive genetic information to ovarian cancer patients and their family members.

Ovarian Cancer Treatment

Surgery and chemotherapy are the main treatments for ovarian cancer. The location and type of cells where the cancer begins, and whether the cancer is high-grade or low-grade , influences how the cancer is treated. Surgery can cure most people with early-stage ovarian cancer that has not spread beyond the ovaries. For advanced ovarian cancer, the goal of surgery is to remove as much of the cancer as possible, called surgical debulking . 

Platinum-based chemotherapy drugs, such as cisplatin or carboplatin , given in combination with other drugs, such as the targeted therapy bevacizumab (Avastin) , are usually effective in treating epithelial ovarian cancer at any stage. However, in most people with advanced ovarian cancer, the cancer comes back. Treating the cancer again with platinum drugs may work, but eventually the tumors become resistant to these drugs.

Targeted Therapy

Targeted therapy uses drugs or other agents to attack specific types of cancer cells. PARP inhibitors are a type of targeted therapy that can stop a cancer cell from repairing its damaged DNA , causing the cell to die. Cancers in people who have certain mutations in the BRCA genes are considered particularly susceptible to PARP inhibitors. That’s because BRCA genes are involved in the repair of some types of DNA damage, so cancers with alterations in these genes already have defects in DNA repair.

The use of PARP inhibitors has transformed treatment for people with advanced epithelial ovarian cancer who have harmful mutations in a BRCA gene. Since the 2014 approval of olaparib (Lynparza) , the first PARP inhibitor to be approved, the number of PARP inhibitors has grown and their uses for people with ovarian cancer have expanded. Now researchers are studying the benefits of combining PARP inhibitors with other drugs.

Clinical trials have shown that using PARP inhibitors as long-term therapy in women with advanced epithelial ovarian cancer delayed progression of the cancer. 

A different targeted therapy, mirvetuximab soravtansine (Elahere) , is now available to treat women with ovarian cancer that is no longer responding to platinum drugs. FDA recently approved the drug to treat people with platinum-resistant ovarian tumors that produce an excess of a protein called FR-α. Results from a large clinical trial showed that people with this type of ovarian cancer treated with mirvetuximab lived longer overall than people treated with standard chemotherapy .

Treatment after Cancer Progression

Typically, chemotherapy and targeted therapies are stopped once ovarian cancer begins to come back. Clinical trials have shown that where there was more than a 6 month delay between stopping treatment and cancer being found again, resuming the drug bevacizumab (Avastin)  in combination with platinum-based chemotherapy for patients previously treated with bevacizumab  slowed the growth of platinum-sensitive disease . And in women who no longer benefited from platinum-based chemotherapy, non–platinum-based chemotherapy combined with bevacizumab kept the cancer in check longer than chemotherapy alone.

Targeted therapies may also be helpful for people with low-grade ovarian cancer. A trial of the drug trametinib in women with low-grade serous ovarian cancer that had come back showed that it delayed the cancer’s growth compared with treating the cancer with chemotherapy again.

Secondary Surgery

For women with advanced epithelial ovarian cancer that has come back after being in remission, clinical trials have studied the use of secondary surgery or surgery to remove more tumor after the initial surgery with varying results. 

• An NCI-funded phase 3 clinical trial, in patients whose doctor felt that a second surgery could be helpful for treating the cancer, found that secondary surgery followed by chemotherapy did not increase overall survival compared with chemotherapy alone. Of the studies listed, this one reflected the most likely scenario in real-world practice.
• A trial done in China studied a group of patients more likely to benefit from the intervention. The trial tested secondary surgery followed by chemotherapy and did show improvements in how long women with recurrent epithelial ovarian cancer lived without their cancer growing .
• In a third trial, conducted in Europe, researchers identified people with recurrent ovarian cancer who were most likely to benefit from surgery. They found that women who had secondary surgery followed by chemotherapy lived an average of nearly 8 months longer than women who only received chemotherapy.

In the Chinese and European trials, and in an analysis of 64 clinical trials and other studies , the benefits of secondary surgery were observed only in women who had all of their visible cancer removed.

NCI-Supported Research Programs

Many NCI-funded researchers at the National Institutes of Health campus, and across the United States and the world, are seeking ways to address ovarian cancer more effectively. Some research is basic, exploring questions as diverse as the biological underpinnings of ovarian cancer and the social factors that affect cancer risk. And some is more clinical, seeking to translate this basic information into improving patient outcomes.

The Women’s Malignancies Branch in NCI’s Center for Cancer Research conducts basic and clinical research in breast and gynecologic cancers, including early-phase clinical trials at the NIH Clinical Center in Bethesda, Maryland. 

The Ovarian Specialized Programs of Research Excellence (SPOREs) promote collaborative translational cancer research. This group works to improve prevention and treatment approaches, along with molecular diagnostics , in the clinical setting to help people with ovarian cancer.

The Ovarian Cancer Cohort Consortium , part of the NCI Cohort Consortium, is an international consortium of more than 20 cohort studies that follow people with ovarian cancer to improve understanding of ovarian cancer risk, early detection, tumor differences, and prognosis. 

NCI’s clinical trials programs, the National Clinical Trials Network , Experimental Therapeutics Clinical Trials Network , and NCI Community Oncology Research Program , all conduct or sponsor clinical studies of ovarian cancer.

Clinical Trials for Ovarian Cancer

NCI funds and oversees both early- and late-phase clinical trials to develop new treatments and improve patient care. Trials are available for the treatment of ovarian cancer.

Ovarian Cancer Research Results

The following are some of our latest news articles on ovarian cancer research:

Approval of Elahere Expands Treatment Options for Some Advanced Ovarian Cancers

Implanted “Drug Factories” Deliver Cancer Treatment Directly to Tumors

Trametinib Is a New Treatment Option for Rare Form of Ovarian Cancer

When Ovarian Cancer Returns, Surgery May Be a Good Choice for Selected Patients

How Does Ovarian Cancer Form? A New Study Points to MicroRNA

Ovarian Cancer Studies Aim to Reduce Racial Disparities, Improve Outcomes

View the full list of Ovarian Cancer Research Results and Study Updates .

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Ovarian Cancer: An Integrated Review

Affiliations.

• 1 Carolina's Medical Center, Charlotte, NC. Electronic address: [email protected].
• 2 Assistant Vice President Patient Care Services, Carolina's Medical Center, Rock Hill, SC.
• 3 Interim Dean, Harris College of Nursing & Health Sciences, Associate Dean for Nursing & Professor, Texas Christian University, Ft Worth, TX.
• PMID: 30867104
• DOI: 10.1016/j.soncn.2019.02.001

Objective: To provide an overview of the risk factors, modifiable and non-modifiable, for ovarian cancer as well as prevention, diagnostic, treatment, and long-term survivorship concerns. This article will also examine current and future clinical trials surrounding ovarian cancer.

Data sources: A review of articles dated 2006-2018 from CINAHL, UpToDate, and National Comprehensive Cancer Network guidelines.

Conclusion: There is no screening test for ovarian cancer and with diagnosis often in the late stages, recurrence is high in this population. Early identification can range from knowing the vague symptoms associated with the cancer to prophylactic surgical removal of at-risk tissue. Standard treatment for ovarian cancer is surgery followed by combination chemotherapy. Although advances are being made, ovarian cancer remains the most fatal female gynecologic cancer.

Implications for nursing practice: Becoming familiar with and educating women about risk factors and the elusive symptoms of ovarian cancer can increase patient autonomy and advocacy, as well as potentially improve patient outcomes for those affected by ovarian cancer.

Keywords: BRCA; gynecologic; oncology; ovarian cancer; prevention; risk factors.

Copyright © 2019 Elsevier Inc. All rights reserved.

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Ovarian cancer articles from across Nature Portfolio

Ovarian cancer is an abnormal cell growth (tumour) arising in the ovary. The majority of ovarian cancers are epithelial and develop in women over 50. Screening is highly recommended in women with a family history of ovarian cancer.

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Indirect reference interval estimation using a convolutional neural network with application to cancer antigen 125

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Single-cell long-read targeted sequencing reveals transcriptional variation in ovarian cancer

Long-read sequencing allows the detection of RNA isoforms, but is hampered by low throughput and potential artefacts. Here, the authors develop the scTaILoR-seq hybridisation capture method for long-read RNA sequencing to improve transcript detection, and use this method to detect isoforms at the single-cell level in ovarian cancer.

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53BP1 loss elicits cGAS-STING-dependent antitumor immunity in ovarian and pancreatic cancer

p53-binding protein 1 (53BP1) is a component of the DNA double-strand break signaling and repair. Here the authors show that that loss of 53BP1 in cancer cells leads to cGAS/STING pathway activation and anti-tumor immune responses in ovarian and pancreatic cancer models.

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• Dipanjan Chowdhury

Proteomic landscape of epithelial ovarian cancer

It remains essential to find clinically relevant biomarkers in epithelial ovarian cancer (EOC). Here, the authors perform a comprehensive proteomic profiling of tissue and plasma samples from EOC and control patients; they find potential biomarkers for EOC early detection and develop methods for tumour recurrence prediction.

• Liujia Qian
• Jianqing Zhu
• Tiannan Guo

Gynecologic Cancer InterGroup CA125 response has a high negative predictive value for CHK1 inhibitor RECIST response in recurrent ovarian cancer

• Kristen R. Ibanez
• Duncan Donohue
• Jung-Min Lee

Large-scale proteomics reveals precise biomarkers for detection of ovarian cancer in symptomatic women

• Emma Ivansson
• Julia Hedlund Lindberg
• Stefan Enroth

News and Comment

Mirvetuximab soravtansine has activity in platinum-sensitive epithelial ovarian cancer.

• Diana Romero

Mirvetuximab soravtansine superior to chemotherapy in platinum-resistant epithelial ovarian cancer

• Peter Sidaway

A medley of resistance in ovarian cancers

Multi-omic profiling of lesions at autopsy reveals a plethora of resistance mechanisms present within individual patients with ovarian cancer. This highlights the extreme challenge faced in treating end-stage disease and underscores the need for new methods of early detection and intervention.

• Barbara Hernando
• Geoff Macintyre

A biomarker-driven therapy for ovarian cancer

An antibody–drug conjugate showed impressive anti-cancer activity in selected patients with platinum-resistant ovarian cancer, and could become a new standard of care.

• Karen O’Leary

Beating the odds: molecular characteristics of long-term survivors of ovarian cancer

High-grade serous ovarian cancer, the most common form of the disease, is often fatal. This study investigated the genomic and immune characteristics of tumors from women who survived more than 10 years after their initial diagnosis, and compared them with short-term and moderate-term survivors.

Cytoreductive surgery effective after relapse

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Page 1 of 34

The diagnostic performance of CA-125 for the detection of ovarian cancer in women from different ethnic groups: a cohort study of English primary care data

CA-125 testing is a recommended first line investigation for women presenting with possible symptoms of ovarian cancer in English primary care, to help determine whether further investigation for ovarian cance...

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Ovarian cancer derived extracellular vesicles promote the cancer progression and angiogenesis by mediating M2 macrophages polarization

Extracellular vesicles (EVs) are mediators between cancer cells and other types of cells, such as tumor-associated macrophages (TAMs), in the tumor microenvironment. EVs can remodel the tumor microenvironment ...

Stem cell-based therapeutic potential in female ovarian aging and infertility

Premature ovarian insufficiency (POI) is defined as onset of menopause characterized by amenorrhea, hypergonadotropism, and hypoestrogenism, before the age of 40 years. The POI is increasing, which seriously a...

Prognostic analysis of peritoneal washing cytology during interval debulking surgery in advanced ovarian cancer

Interval debulking surgery (IDS) following neoadjuvant chemotherapy is a treatment option for advanced ovarian cancer. Optimal surgery is required for better survival; however, while peritoneal washing cytolog...

Preovulatory progesterone levels are the top indicator for ovulation prediction based on machine learning model evaluation: a retrospective study

Accurately predicting ovulation timing is critical for women undergoing natural cycle-frozen embryo transfer. However, the precise predicting of the ovulation timing remains challenging due to the lack of cons...

Correction: Amniotic fluid-derived exosomes attenuated fibrotic changes in POI rats through modulation of the TGF-β/Smads signaling pathway

The original article was published in Journal of Ovarian Research 2023 16 :118

Granulosa cell insight: unraveling the potential of menstrual blood-derived stem cells and their exosomes on mitochondrial mechanisms in polycystic ovary syndrome (PCOS)

Polycystic ovary syndrome (PCOS) presents a significant challenge in women’s reproductive health, characterized by disrupted folliculogenesis and ovulatory dysfunction. Central to PCOS pathogenesis are granulo...

A metabolome-wide Mendelian randomization study prioritizes causal circulating metabolites for reproductive disorders including primary ovarian insufficiency, polycystic ovary syndrome, and abnormal spermatozoa

Accumulating studies have highlighted the significant role of circulating metabolomics in the etiology of reproductive system disorders. However, the causal effects between genetically determined metabolites (...

Evaluation of ovarian reserve and the assisted reproductive technology (ART) cycles’ outcome as well as the relapse rate within one year after ART in women with multiple sclerosis: a case-control study

To compare the ovarian reserve and the results of infertility treatment, as well as to investigate the relapse rate in the first year after the assisted reproductive technology (ART) cycle in patients with mul...

CA-125:CA72-4 ratio − towards a promising cost-effective tool in ovarian cancer diagnosis and monitoring of post-menopausal women under hormone treatment

Ovarian cancer (OC) is the most lethal gynecological cancer in the developed world. Most cases are diagnosed at late stage III-IV with a very low 5-year overall survival rate. Several studies revealed an eleva...

Effect of astaxanthin supplementation on female fertility and reproductive outcomes: a systematic review and meta-analysis of clinical and animal studies

Oxidative stress (OS) plays a harmful role in female reproduction and fertility. Several studies explored various dietary interventions and antioxidant supplements, such as astaxanthin (AST), to mitigate the a...

Dachsous cadherin related 1 (DCHS1) is a novel biomarker for immune infiltration and epithelial-mesenchymal transition in endometrial cancer via pan-cancer analysis

Dachsous cadherin related 1 (DCHS1) is one of calcium-dependent adhesion membrane proteins and is mainly involved in the development of mammalian tissues. There is a lack of more detailed research on the biolo...

Emerging role of mucins in antibody drug conjugates for ovarian cancer therapy

Ovarian cancer stands as the deadliest gynecologic malignancy, responsible for nearly 65% of all gynecologic cancer-related deaths. The challenges in early detection and diagnosis, coupled with the widespread ...

Extracellular vesicles and their content in the context of polycystic ovarian syndrome and endometriosis: a review

Extracellular vesicles (EVs), particles enriched in bioactive molecules like proteins, nucleic acids, and lipids, are crucial mediators of intercellular communication and play key roles in various physiologica...

The molecular prognostic score, a classifier for risk stratification of high-grade serous ovarian cancer

The clinicopathological parameters such as residual tumor, grade, the International Federation of Gynecology and Obstetrics (FIGO) score are often used to predict the survival of ovarian cancer patients, but t...

Drug-free in vitro activation combined with ADSCs-derived exosomes restores ovarian function of rats with premature ovarian insufficiency

Drug-free in vitro activation (IVA) is a new protocol to activate residual dormant follicles for fertility restoration in patients with premature ovarian insufficiency (POI). However, several deficiencies have...

Effects of licorice extract in combination with a low-calorie diet on obesity indices, glycemic indices, and lipid profiles in overweight/obese women with polycystic ovary syndrome (PCOS): a randomized, double-blind, placebo-controlled trial

Polycystic ovary syndrome (PCOS) is the most common ovarian dysfunction. Recent studies showed the effectiveness of licorice on metabolic profiles with inconsistent findings. So, we investigated the effect of ...

Unveiling G-protein coupled receptors as potential targets for ovarian cancer nanomedicines: from RNA sequencing data analysis to in vitro validation

Genetic heterogeneity in ovarian cancer indicates the need for personalised treatment approaches. Currently, very few G-protein coupled receptors (GPCRs) have been investigated for active targeting with nanome...

Correction: Metformin modifies plasma microbial-derived extracellular vesicles in polycystic ovary syndrome with insulin resistance

The original article was published in Journal of Ovarian Research 2024 17 :136

Effects of mind-body interventions on polycystic ovary syndrome: a comprehensive meta-analysis

Mind-body interventions (MBI) have emerged as a potential therapeutic approach, but their effectiveness in the treatment of Polycystic Ovary Syndrome (PCOS) remains inconclusive. This study systematically eval...

The natural menstrual cycle revisited – can natural cycle be trusted

The serum progesterone (P4) level during the luteal phase (LP) plays a crucial role in the initiation and maintenance of pregnancy. However, it is unclear whether the natural cycle consistently provides the be...

External validation of Standardized KELIM and platinum-resistant recurrence scores in patients with advanced epithelial ovarian cancer

Neoadjuvant chemotherapy followed by interval debulking surgery is currently a common treatment option for advanced epithelial ovarian cancer (EOC). The Standardized CA-125 ELIMination rate constant K (Std KEL...

Hsa_circ_0043532 contributes to PCOS through upregulation of CYP19A1 by acting as a ceRNA for hsa-miR-1270

Polycystic ovarian syndrome (PCOS) accounts for about 75% of anovulatory infertility. The cause of PCOS is not clear. CircRNAs acting as miRNA sponges mediate the post-transcriptional regulation of multiple ge...

Acetylation model predicts prognosis of patients and affects immune microenvironment infiltration in epithelial ovarian carcinoma

Epithelial ovarian carcinoma (EOC) is a prevalent gynaecological malignancy. The prognosis of patients with EOC is related to acetylation modifications and immune responses in the tumour microenvironment (TME)...

Targeted proteomics of plasma extracellular vesicles uncovers MUC1 as combinatorial biomarker for the early detection of high-grade serous ovarian cancer

The five-year prognosis for patients with late-stage high-grade serous carcinoma (HGSC) remains dismal, underscoring the critical need for identifying early-stage biomarkers. This study explores the potential ...

The role of vitamin D3 in follicle development

Vitamin D3 plays a crucial role in female reproduction. As research progresses, the mechanisms of action of vitamin D3 on follicular development have been widely discussed. Firstly, key enzymes involved in the...

Effects of vitamin D supplementation on metabolic parameters in women with polycystic ovary syndrome: a randomized controlled trial

The aim of this study was to explore the effects of vitamin D supplementation on metabolic parameters in women with polycystic ovary syndrome (PCOS).

Causal association between telomere length and female reproductive endocrine diseases: a univariable and multivariable Mendelian randomization analysis

The relationship between leukocyte telomere length (LTL) and female reproductive endocrine diseases has gained significant attention and research interest in recent years. However, there is still limited under...

The impact of Paclitaxel-based hyperthermic intraperitoneal chemotherapy in advanced high-grade serous ovarian cancer patients - interim analysis of safety and immediate efficacy of a randomized control trial (C-HOC trial)

This study evaluates the potential superiority of combining paclitaxel-based hyperthermic intraperitoneal chemotherapy (HIPEC) with sequential intravenous neoadjuvant chemotherapy over intravenous neoadjuvant ...

The possible short-term of Nigella sativa – L in the management of adolescent polycystic ovarian syndrome: results of a randomized controlled trial

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive age and the most common cause of infertility due to anovulation. PCOS in adolescents is concerning. Nigella sativa is effe...

Resveratrol ameliorates mitochondrial biogenesis and reproductive outcomes in women with polycystic ovary syndrome undergoing assisted reproduction: a randomized, triple-blind, placebo-controlled clinical trial

This study was designed to examine the effect of resveratrol on mitochondrial biogenesis, oxidative stress (OS), and assisted reproductive technology (ART) outcomes in individuals with polycystic ovary syndrom...

Comprehensive analysis of hub genes associated with cisplatin-resistance in ovarian cancer and screening of therapeutic drugs through bioinformatics and experimental validation

To identify key genes associated with cisplatin resistance in ovarian cancer, a comprehensive analysis was conducted on three datasets from the GEO database and through experimental validation.

Depletion of placental brain-derived neurotrophic factor (BDNF) is attributed to premature ovarian insufficiency (POI) in mice offspring

Premature ovarian insufficiency (POI) is one of the causes of female infertility. Unexplained POI is increasingly affecting women in their reproductive years. However, the etiology of POI is diverse and remain...

The intratumoral microbiota biomarkers for predicting survival and efficacy of immunotherapy in patients with ovarian serous cystadenocarcinoma

Ovarian serous cystadenocarcinoma, accounting for about 90% of ovarian cancers, is frequently diagnosed at advanced stages, leading to suboptimal treatment outcomes. Given the malignant nature of the disease, ...

Ovarian fibrosis: molecular mechanisms and potential therapeutic targets

Ovarian fibrosis, characterized by the excessive proliferation of ovarian fibroblasts and the accumulation of extracellular matrix (ECM), serves as one of the primary causes of ovarian dysfunction. Despite the...

Effect of melatonin supplementation on cardiometabolic risk factors, oxidative stress and hormonal profile in PCOS patients: a systematic review and meta-analysis of randomized clinical trials

To investigate whether melatonin supplementation can enhance cardiometabolic risk factors, reduce oxidative stress, and improve hormonal and pregnancy-related factors in patients with PCOS.

Co-administration of GnRH-agonist and hCG (double trigger) for final oocyte maturation increases the number of top-quality embryos in patients undergoing IVF/ICSI cycles

The utilization of a double trigger, involving the co-administration of gonadotropin-releasing hormone agonist (GnRH-a) and human chorionic gonadotropin (hCG) for final oocyte maturation, is emerging as a nove...

Metformin modifies plasma microbial-derived extracellular vesicles in polycystic ovary syndrome with insulin resistance

This study investigated changes in plasma microbial-derived extracellular vesicles (EVs) in patients with polycystic ovary syndrome and insulin resistance (PCOS-IR) before and after metformin treatment, and ai...

The Correction to this article has been published in Journal of Ovarian Research 2024 17 :155

Ultrasonographic and histopathological investigation of the effect of N-acetylcysteine on doxorubicin-induced ovarian and uterine toxicity in rats

This study aimed to investigate the mitigating effect of N-acetylcysteine (NAC) on doxorubicin (DOX)-induced ovarian and uterine toxicity in rats using laboratory tests, ultrasonographic (US) imaging, and hist...

Folliculogenesis and steroidogenesis alterations after chronic exposure to a human-relevant mixture of environmental toxicants spare the ovarian reserve in the rabbit model

Industrial progress has led to the omnipresence of chemicals in the environment of the general population, including reproductive-aged and pregnant women. The reproductive function of females is a well-known t...

Genomic alteration discordance in the paired primary-recurrent ovarian cancers: based on the comprehensive genomic profiling (CGP) analysis

Ovarian cancer (OC) is characterized by a high recurrence rate, and homologous recombination deficiency (HRD) is an important biomarker in the clinical management of OC. We investigated the differences in clin...

Single-cell RNA sequencing of human oocytes reveals a differential transcriptomic profile associated with agar-like zona pellucida

Agar-like zona pellucida (ZP) is the most common type of abnormal ZP, and is one of the causes of low fertility or infertility. However, the molecular mechanism of agar-like ZP is unclear. Single-cell RNA-sequ...

Predicting CD27 expression and clinical prognosis in serous ovarian cancer using CT-based radiomics

This study aimed to develop and evaluate radiomics models to predict CD27 expression and clinical prognosis before surgery in patients with serous ovarian cancer (SOC).

Pretreatment with or without GnRH-agonist before frozen–thawed embryo transfer in patients with PCOS: a systematic review and meta-analysis

This study was aimed to systematically evaluate the efficacy of artificial cycle-prepared frozen–thawed embryo transfer (FET) with or without gonadotrophin-releasing hormone agonist (GnRH-a) pretreatment for w...

Amplifications of EVX2 and HOXD9-HOXD13 on 2q31 in mature cystic teratomas of the ovary identified by array comparative genomic hybridization may explain teratoma characteristics in chondrogenesis and osteogenesis

Teratomas are a common type of germ cell tumor. However, only a few reports on their genomic constitution have been published. The study of teratomas may provide a better understanding of their stepwise differ...

Combined analysis of estradiol and β-hCG to predict the early pregnancy outcome of FET: a retrospective study

The accurate prediction of pregnancy outcomes in in vitro fertilization (IVF) cycles is crucial. While several studies have been conducted on the predictive power of serum estradiol (E 2 ) and β-hCG concentrations ...

The experıance of tertıary center for adult granulosa cell tumor: whıch factors predıct survival?

This retrospective study aims to evaluate the clinical course and long-term outcomes of patients diagnosed with adult granulosa cell tumors (AGCT).

High expression levels of centromere protein O participates in cell proliferation of human ovarian cancer

Ovarian cancer is a common malignant tumor in women, with a high mortality rate ranking first among gynecological tumors. Currently, there is insufficient understanding of the causes, pathogenesis, recurrence ...

Autoimmune thyroid disease and ovarian hypofunction: a review of literature

Thyroid hormones(THs) are essential for the proper functioning of the ovaries, and multiple studies have shown that thyroid abnormalities, especially during adolescence and reproductive age, can lead to lifelo...

Correction: Alteration of the N 6 ‑methyladenosine methylation landscape in a mouse model of polycystic ovary syndrome

The original article was published in Journal of Ovarian Research 2023 16 :157

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A new FDA approved phase I/II clinical trial on recurrent ovarian cancer is now open for enrollment.

Currently recruiting patients at the Brown Cancer Center, University of Louisville, Louisville, KY. UofL. IRB# 22.0392. NCT# 05610735. Please contact: Dr. Whitney Goldsberry or Dr. Sham S. Kakar .

Read more here .

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Ovarian Cancer Research Highlights

Ovarian cancer causes more deaths in women living in the United States than any other cancer of the female reproductive system. The American Cancer Society’s (ACS) research programs help find answers to critical questions:

• How can ovarian cancer be diagnosed early?
• How can the risk of developing ovarian cancer be lowered?
• Are there more effective treatments?
• What could help survivors have a better quality of life?

We continue to fund research to help save more lives in the future.  

Ovarian Cancer Still Causes the Most Deaths from Gynecological Cancer

About 90% of cases are epithelial ovarian cancer, and most of those cases are high-grade serous tumors, which have the fewest established risk factors and the worst prognosis.

Risk & Prevention Studies

We've learned more about the risk of developing ovarian cancer.

Thanks to CPS-II and CPS-3 participants!   

The ACS’s CPS-II Nutrition Cohort is part of the Collaborative Group on Epidemiological Studies of Ovarian Cancer. This group helped establish the increased risk for ovarian cancer in women with excess body weight and the decreased risk of ovarian cancer for women who use oral contraceptives.”

Alpa Patel, PhD

Senior Vice President Population Science

American Cancer Society

Ovarian Cancer Statistics on Age

It's rare for women younger than 40 to have ovarian cancer.

Half of all ovarian cancers are found in women age 63 or older.

Featured Term: Biomarker

A measurable molecular, genetic, chemical, or physical characteristic in the blood or other bodily fluids, such as sweat and tears, that is a sign of a normal or abnormal process or of a health condition or disease. A biomarker may be used to see how well the body responds to a treatment for a disease. 

Featured Term: Susceptibility Biomarkers

A biomarker that signals the potential, or risk, a person has to develop a disease before they have symptoms. For instance, low-density lipoprotein (LDL) cholesterol is a susceptibility biomarker for heart disease.

Early Detection Studies

Glowing “fingerprint” from a blood test may find ovarian cancer early.

Machine learning and tiny glowing nanosensors enable the detection of ovarian cancer from a blood test.  

Ovarian Cancer May Start in Fallopian Tube Cells

By studying fallopian tube cells from cancer-free women, researchers learned more about the origin of the most deadly type of ovarian cancer.

A New Gene Is Linked with the Deadliest Type of Ovarian Cancer

Researchers develop a new genetically engineered mouse ovarian cancer model to explore potential new drug targets to treat epithelial ovarian cancer.

Ovarian Cancer Statistics on Racial Disparities

the rank Black people have on a 1-to-5 scale (with 5 as the lowest) for the incidence rate of ovarian cancer based on race and ethnicity

the rank Black people have on a 1-to-5 scale (with 5 as the lowest) for the death rate of ovarian cancer based on race and ethnicity

the rank American Indian and Alaska Native people have on a 1-to-5 scale (with 5 as the lowest) for incidence rate AND death rate for ovarian cancer based on race and ethnicity

Treatment Studies

New gene-testing tools may personalize ovarian cancer care.

Researchers say using next-generation sequencing technology as a diagnostic tool may increase precision treatment plans for people with ovarian cancer.

Chromosome-Hoarding Ovarian Cancer Cells May Help Treatment

Using new CRISPR tools, researchers learn extra chromosomes promote tumor growth and paradoxically may help activate some treatments.

Testing Nanoparticles to Deliver Drugs to Mice with Ovarian Cancer

Researchers find that drugs successfully attack metastasized ovarian tumors when they're given via teeny nanoparticles injected directly into the abdomen.

Ovarian Cancer Advocacy

Listen to Vanessa's story: She's an ovarian cancer survivor and now advocates to help other survivors have access to care.

ACS Ovarian Cancer Research News

Sitting Too Much Increases Cancer Risk in Women

Statistics (Downloadable PDFs)

Cancer Facts & Figures 2024

Special Section Ovarian Cancer

Useful Links

Ovarian Cancer - ACS Cancer Statistics Center

Glossary for Nonscientists

We Fund Ovarian Cancer Researchers Across the US

The ACS funds scientists who conduct research about ovarian cancer at medical schools, universities, research institutes, and hospitals throughout the United States. We use a rigorous and independent  peer review process  to select the most innovative research projects proposals to fund. 

These grant statistics are as of July 15, 2024.

ovarian cancer research grants

funding for ovarian cancer research

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Ovarian cancer: New treatments and research

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By Nicole Brudos Ferrara

Three cancers — ovarian epithelial cancer, fallopian tube cancer and primary peritoneal cancer — are commonly called ovarian cancer. They arise from the same kind of tissue and are treated similarly.

"The ovaries and fallopian tubes are so anatomically close to each other that we sometimes can't tell if the cancer is coming from the ovary or the fallopian tube," says S. John Weroha, M.D., Ph.D. , a Mayo Clinic oncologist and chair of Mayo Clinic Comprehensive Cancer Center's Gynecologic Cancer Disease Group. "When we diagnose patients with primary peritoneal cancer, I explain that under the microscope, and in the pattern of spread through the body, it looks like ovarian cancer even though the ovaries are not involved."

Primary peritoneal cancer forms in the peritoneum, the tissue that lines the abdominal cavity and the organs within it. Fallopian tube cancer forms in the tissue lining the inside of the tubes that eggs travel through to move from the ovaries to the uterus.

About 85% to 90% of ovarian cancers are ovarian epithelial cancers, also known as epithelial ovarian carcinomas, which form in the tissue lining the outside of the ovaries.

Dr. Weroha says new treatments are helping more people survive ovarian cancer of all types, and researchers are studying new treatments and screening methods in clinical trials. If you've been diagnosed with ovarian cancer, he wants you to know there is hope. Here's why:

New targeted therapies are improving survival.

Surgery and chemotherapy are no longer the only options for ovarian cancer treatment . Targeted therapies use drugs to target and attack cancer cells. These include monoclonal antibodies and poly (ADP-ribose) polymerase, or PARP, inhibitors.

Monoclonal antibodies

Monoclonal antibodies are molecules engineered in the laboratory to find and attach to specific proteins associated with cancer cells. Bevacizumab is a monoclonal antibody used with chemotherapy to treat ovarian cancer recurrence by preventing the growth of new blood vessels that tumors need to grow.

Researchers are combining bevacizumab with new drugs to improve outcomes. One example is a monoclonal antibody recently approved by the Food and Drug Administration (FDA) called mirvetuximab soravtansine for people with ovarian cancer recurrence. This drug is used when a person's cancer was previously treated with at least one systemic therapy to target a protein called folate receptor alpha.

"Ovarian cancers have many folate receptors. Most normal cells don't," says Dr. Weroha. "This drug is an antibody that has chemotherapy stuck onto it. Think of it as a guided missile traveling the body and sticking to cells with folate receptors. In patients whose ovarian cancer has recurred and whose tumors have many folate receptors, mirvetuximab soravtansine can shrink tumors far better than any other therapy. The response rate is about double what you see with any other treatment."

PARP inhibitors

PARP inhibitors are drugs that block DNA repair, which may cause cancer cells to die. Olaparib is an example of a PARP inhibitor used to prevent recurrence in people with ovarian cancer whose tumors have BRCA1 or BRCA2 gene mutations. Research has shown that olaparib can significantly improve survival without recurrence in people with this diagnosis. "This is a front-line treatment, which means this is part of the first treatment regimen patients receive when they are newly diagnosed," says Dr. Weroha.

A vaccine may one day be used to fight ovarian cancer.

Matthew Block, M.D., Ph.D. , a Mayo Clinic medical oncologist, and Keith Knutson, Ph.D. , a Mayo Clinic researcher, are developing a vaccine to prevent ovarian cancer tumors from returning in people with advanced ovarian cancer whose tumors have recurred after surgery and chemotherapy.

White blood cells are extracted from a blood draw and manufactured to become dendritic cells — immune cells that boost immune responses. These cells are returned to the patient in vaccine form to trigger the immune system to recognize and fight the cancer.

The vaccine will be given in combination with an immunotherapy drug called pembrolizumab to identify and kill any tumors that don't respond to the dendritic cells.

"Pembrolizumab is in a category of drugs called immune checkpoint inhibitors ," says Dr. Weroha. "This drug is designed to release the brakes on the immune system to allow it to do what it naturally wants: kill things it doesn't like. The hope is that the vaccine combined with the immunotherapy drug will kill a lot of ovarian cancer. It's exciting research."

A screening test may be on the horizon.

There is no screening test for ovarian cancer, but Jamie Bakkum-Gamez, M.D. , a Mayo Clinic gynecologic oncologist, is hoping to change that. She and her research team discovered that methylated DNA markers could be used to identify endometrial cancer through vaginal fluid collected with a tampon. Eventually, this same science could extend to ovarian cancer.

Methylation is a mechanism cells use to control gene expression — the process by which a gene is switched on in a cell to make RNA and proteins. When a certain area of a gene's DNA is methylated, the gene is turned off or silenced, indicating that a gene is a tumor suppressor. The silencing of tumor suppressor genes is often an early step in cancer development and can suggest cancer.

Dr. Bakkum-Gamez and her colleagues developed a panel of methylated DNA markers that could distinguish between endometrial cancer and noncancerous tissue in vaginal fluid. Based on this research, she hopes to develop an affordable tampon-based home screening test for endometrial, ovarian and cervical cancers, as well as high-risk HPV .

"This is exciting because this type of screening test can be used by people living in rural areas,” says Dr. Weroha. “If it's successful, it could help healthcare professionals identify ovarian and other gynecologic cancers sooner, when they're more treatable, in people living in all the communities we serve.”

A gynecologic oncologist and clinical trials can help you get the best possible treatment.

If you've been diagnosed with ovarian cancer, Dr. Weroha recommends making an appointment with a gynecologic oncologist . "A gynecologic oncologist will be up to date on the current treatment recommendations and the management of side effects. That's important," he says. "Once the plan is set, however, any medical oncologist could implement it.”

Dr. Weroha also recommends newly diagnosed patients ask their care teams if they are candidates for PARP inhibitors, mirvetuximab or clinical trials. "PARP inhibitors and mirvetuximab are newer treatments that could influence the outcome of your overall treatment. Always ask about clinical trials because when ovarian cancer recurs, there is no treatment so good that we can stop looking for something better," he says. "There is a very realistic hope that if your cancer were to come back, we would have something better that we don't have today."

Learn more about ovarian cancer and find a clinical trial at Mayo Clinic.

Join the Gynecologic Cancers Support Group on Mayo Clinic Connect , an online community moderated by Mayo Clinic for patients and caregivers.

Join the next virtual Gynecologic Cancer Support Meeting: Women of S-Teal . Monthly meetings are held every second Monday from 5:30 to 6:30 p.m. ET.

Also, read these articles:

• A step toward detecting endometrial cancer earlier
• Harnessing the immune system to fight ovarian cancer
• Life after ovarian cancer: Coping with side effects, fear of recurrence, and finding support
• New surgical method for ovarian cancer lights up lesions
• Is a cancer clinical trial right for me?
• New chemotherapy approach for late-stage cancers

Related Posts

Dr. Brad Nitzsche explains why there isn't a universal screening program for ovarian cancer and the symptoms to watch for.

Dr. Maria Linnaus discusses the link between obesity and cancer risk and how bariatric surgery may reduce that risk.

Dr. Kristina Butler discusses health disparities in cancers of the ovaries, uterus, cervix, vulva and vagina and makes recommendations for prevention.

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Article Contents

Ovarian cancer risk prediction – a clinical epidemiology perspective.

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Nicolas Wentzensen, Kari Ring, Britt K Erickson, Brett Reid, Thomas O’Donnell, David Check, Shelley S Tworoger, Parichoy Pal Choudhury, Ovarian Cancer Risk Prediction – a Clinical Epidemiology Perspective, American Journal of Epidemiology , 2024;, kwae293, https://doi.org/10.1093/aje/kwae293

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Ovarian cancer is a rare and highly heterogeneous disease usually detected at late stages when outcomes are poor. Population-based screening approaches have not been successful at reducing ovarian cancer mortality, but preventive bilateral salpingo-oophorectomy is highly effective at preventing ovarian cancer in high-risk populations. Ovarian cancer risk prediction models may allow identification of populations at increased risk of ovarian cancer for preventive interventions or targeted early detection. We propose a life-course approach to ovarian cancer risk prediction based on the time at which a risk model should be applied and the risk factors that are available. The discriminative ability of ovarian cancer risk prediction models published so far is limited, with areas under the curve ranging from 0.58-0.65 for different combinations of risk factors and genetic susceptibility markers. Currently proposed absolute risk thresholds for preventive surgery are around 4% lifetime risk. The absolute risk predicted by ovarian cancer risk models ranges from 0.6-2.5% lifetime risk in the general population, highlighting the need to improve ovarian cancer risk prediction models and evaluating new preventive approaches that can be offered to individuals at lower risk.

• epidemiology
• ovarian cancer

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Synergistic cytotoxicity of histone deacetylase and poly-adp ribose polymerase inhibitors and decitabine in breast and ovarian cancer cells: implications for novel therapeutic combinations.

1. Introduction

2.1. sensitivity of breast and ovarian cancer cell lines to hdacis, parpis, and decitabine, 2.2. synergistic cytotoxicity of hdacis, parpis, and decitabine in breast and ovarian cancer cell lines, 2.3. drug-mediated inhibition of cell proliferation and parylation, and effects on survival and apoptosis protein markers, 2.4. the three-drug combinations inhibit parylation and enhance cleavage of caspase 3 and parp1, 2.5. hdaci, parpi, and decitabine combinations affect the levels of proteins involved in dna damage response and repair, 3. discussion, 4. materials and methods, 4.1. cell lines and drugs, 4.2. determination of ic 50 and drug synergism, 4.3. colony formation/clonogenic assay, 4.4. mtt assay and western blot analysis, 4.5. drug concentrations for colony formation/clonogenic assay, mtt assay, and western blot analysis, 4.6. statistical analysis, supplementary materials, author contributions, institutional review board statement, informed consent statement, data availability statement, conflicts of interest, abbreviations.

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Valdez, B.C.; Tsimberidou, A.M.; Yuan, B.; Baysal, M.A.; Chakraborty, A.; Andersen, C.R.; Andersson, B.S. Synergistic Cytotoxicity of Histone Deacetylase and Poly-ADP Ribose Polymerase Inhibitors and Decitabine in Breast and Ovarian Cancer Cells: Implications for Novel Therapeutic Combinations. Int. J. Mol. Sci. 2024 , 25 , 9241. https://doi.org/10.3390/ijms25179241

Valdez BC, Tsimberidou AM, Yuan B, Baysal MA, Chakraborty A, Andersen CR, Andersson BS. Synergistic Cytotoxicity of Histone Deacetylase and Poly-ADP Ribose Polymerase Inhibitors and Decitabine in Breast and Ovarian Cancer Cells: Implications for Novel Therapeutic Combinations. International Journal of Molecular Sciences . 2024; 25(17):9241. https://doi.org/10.3390/ijms25179241

Valdez, Benigno C., Apostolia M. Tsimberidou, Bin Yuan, Mehmet A. Baysal, Abhijit Chakraborty, Clark R. Andersen, and Borje S. Andersson. 2024. "Synergistic Cytotoxicity of Histone Deacetylase and Poly-ADP Ribose Polymerase Inhibitors and Decitabine in Breast and Ovarian Cancer Cells: Implications for Novel Therapeutic Combinations" International Journal of Molecular Sciences 25, no. 17: 9241. https://doi.org/10.3390/ijms25179241

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• Ovarian Cancer Essays

Ovarian Cancer Essays (Examples)

Filter by keywords:(add comma between each), example essays.

Ovarian Cancer What Exactly Is

A mutation of the gene causing colorectal cancer or epithelial ovarian cancer are major risk factors for ovarian cancer, and genetic testing within the laboratory can identify most of these. However, the women who possess these inherited genes are at less risk than those women who do not have any family history of ovarian cancer, and while the former group can be treated with advanced planning and genetic counseling, the latter group cannot be prepared in this manner. (What are the risk factors of ovarian cancer?) Some women who have already suffered from breast cancer at an earlier stage in their lives may be at increased risk for ovarian cancer because the reproductive organs are somehow connected with each other, and the inherited breast cancer gene, that is the BCA1 or the BCA2, drastically increases the risk factor for ovarian cancer. Some studies have indicated that those women, who use…...

mla References Define Cancer. Retrieved at   on 27 January, 2005 http://www.google.co.in/search?hl=en&lr=&oi=defmore&q=define:cancerAccessed  Dolson, Laura. The whisperings of ovarian cancer. Retrieved at Accessed on 27 January, 2005 http://www.baymoon.com/~gyncancer/library/weekly/aa011001a.htm. Oncology Channel, Ovarian Cancer. August 24, 2004. Retrieved at Accessed on 27 January, 2005 http://www.oncologychannel.com/ovariancancer/. Ovarian Cancer: National Cancer Institute. Retrieved at   on 27 January, 2005 http://www.nci.nih.gov/cancertopics/types/ovarianAccessed 

Women's Health Issue Ovarian Cancer

These include bloating, abdominal or pelvic pain, frequent and/or urgent urination, and difficulty eating because one feels very full very quickly (MedicineNet, 2009). However, these were only agreed upon in 2007 and not all doctors feel that these are the best markers of ovarian cancer (MedicineNet, 2009). A lot of women experience at least the first two of these symptoms quite often during their menstrual cycle, and the others are not that uncommon, either. Women cannot be running to the doctor every time they have one small symptom, but a group of symptoms that appears and is persistent is certainly worth checking out, if only to provide peace of mind for a woman who may be worried about whether she has cancer or something much more benign (MedicineNet, 2009). Like many other cancers, ovarian cancer does seem to have some genetic link. In other words, if a lot of people…...

mla References MedicineNet (2009). Ovarian Cancer. Retrieved from:   cancer/article.htm http://www.medicinenet.com/ovarian_  MedlinePlus (2009). Ovarian Cancer. U.S. National Library of Medicine. Retrieved from:   http://www.nlm.nih.gov/medlineplus/ovariancancer.html  National Cancer Institute (2009). Ovarian Cancer. U.S. National Institutes of Health. Retrieved from:   http://www.cancer.gov/cancertopics/types/ovarian/

Plight of Ovarian Cancer Sufferers

usiness Research Terms and Concepts KNOWING THE DIFFERENCES Understanding Research Terms and Concepts Quantitative Research Methods and Instruments Quantitative research tests hypotheses from theories or approximates the magnitude of a particular phenomenon (Eau Claire, 2014). Participants or volunteers are assigned at random to different aspects or derive data from them to control their influence on a dependent variable. Probability sampling may be used if the intent is to generalize (Eau Claire). Quantitative data collection methods utilize and depend on random sampling and structured data collection instruments (Euau Claire, 2014). These methods and their instruments are suited to different anticipated types of responses. Their findings are easy to determine, summarize, analyze, compare and generalize. The most typical methods are experiments or clinical trials, observation and recording of a specific event, securing data from an entity's management information systems, and surveys with closed-ended questions. Surveys are conducted through interviews or questionnaires as instruments (Eau Claire). Interviews may be…...

mla BIBLIOGRAPHY Al-Benna, et al. (2010). Descriptive and inferential statistical methods used in Bruno research. Vol. 36 Issue 3, Burns: Elsevier. Retrieved on January 16. 2014 from   http://www.sciencedirect.com/science/article/pii/S030541790001405  Brown, B.L. (2010). Descriptive statistics. Encyclopedia of Research Design: Sage Journals. Retrieved on January 17, 2015 from http://www.srmo.sagepub.com/view/encyc-of-research-design/n111.xml Eau Claire (2014). Quantitative and qualitative data collection methods. Wisconsin University Eau Claire. Retrieved on January 17, 2015 from   http://people.uwec.edu/piercech/ResearchMethods/Data%20collection%20methods/DATA%20COLLECTION%20METHODS.htm

Ovarian Cancer and Cancer

Phenoxodiol, a Medication for Cancer Clinical studies have predominantly focused on a couple of standard benzopyrans, namely flavopiridol and phenoxodiol (by Novogen, via MEI Pharma, the company's subsidiary at the time). Although a benzopyran, the former's method of action apparently differs from phenoxodiol's action neither of the two aforementioned benzopyrans has gained FDA (Food and Drug Administration) or EMA (European Medicines Agency) approval. The height of research on phenoxodiol was one 'Phase III' research on resistant cancer cells in the ovaries. Although slow recruitment led the trial at this phase to formally close down, results clearly displayed that oral consumption of phenoxodiol would most probably not have benefited patients, if the trial phase had been completed. Phenoxodiol results (in combination with others) led to the following hypothesis by Novogen: the problem with phenoxodiol pertained to bioavailability (in other words, the ingested drug wasn't reaching the site of cancer in adequate quantities);…...

mla References Marc Sinatra. (2015). Novogen Limited. Lodge Partners Research. Marshall Edwards Inc.2003Investigational New Drug Status Cleared By FDA for Phenoxodiol in Oral Formpr Newswire Paul Howard. (2015, November 1). Why The FDA Rejected A Drug That Helps Cure Lung Cancer -- And What We Can Do To Fix It. Forbes. U.S. Department of Health and Human Services1998Guidance for Industryrockvillefood and Drug Administration

Care of Cancer Diagnosis in Many Cases

Care of Cancer Cancer diagnosis In many cases the sooner cancer is diagnosed and treatment begins the better the chances of a person recovering fully. If one develops cancer they can improve the chance of early detection if they have regular medical checkups and do some self-exams. Doctors often find early cancer during a physical exam or when carrying out routine tests even when there were no symptoms presented. There are several methods that are used to diagnose cancer .with technological advancement these methods are now better as they help in a better understanding of cancer .there are now many diagnostic tools that can be used in cancer detection. Once cancer I suspected a diagnosis is made by pathologists and oncopathologists and imaging radiologists. The common diagnostic methods are; Biopsy This test involves a small tissue sample being taken from the area where cancer is suspected using a fine tipped needle, surgical excision or…...

mla References Mandal, A.(2010). Cancer Diagnosis.Retrieved September 24,2013 from   http://www.news-medical.net/health/Cancer-Diagnosis.aspx  American Society of Clinical Oncolog.(2013). Stages of Cancer. Retrieved September 24,2013 from   http://www.cancer.net/all-about-cancer/treating-cancer/stages-cancer  Armstrong, B.(2012).What are the different stages of cancer and what do they mean? Retrieved September 24,2013 from http://www.cancerinstitute.org.au/patient-support/what-i-need-to-know/about-cancer/what-are-the-different-stages-of-cancer Info.com.(2013).Cancer complications. Retrieved September 24,2013 from http://topics.info.com/Cancer-Complications_3416

Maturing From My Mom's Cancer

Maturing From My Mom's Cancer High School is a very difficult stage in any teenager's life. The experiences that one has to go through and the hurdles that need to be overcome can sometimes prove to be overwhelming. This is truly a challenging phase in any individual's life as they are growing up to face situations both on a social as well as a personal level. My story of acquiring a more mature outlook on life is no different. My transition into High School was not an easy one. From the beginning I had to face the fact that academics was not one of my strong sides. The grades which I achieved were near to average, something one should not be proud of. However, at the same time while I suffered on the academic front, my social life was doing well. In fact flourishing would be a more appropriate word to describe…...

How to Cope With Cancer

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mla Telch, C.F. & Telch, M.J. "Group skills instruction and supportive group therapy for cancer patients: A comparison of strategies." Journal of Consulting and Clinical Psychology. 1966, 54, 802-808. Kyngas, H.; Mikkonen, R. et al. Coping with the onset of cancer: coping strategies and resources of young people with cancer. European Journal of Cancer Care, Mar2001, Vol. 10 Issue 1, p6. Coping with Cancer

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This then leads to the activation of a number of genes whose products trigger cell-cycle arrest, apoptosis, or DNA repair" (Lakin 1999, p. 7644). In research led by Hussain, he investigated the targets of free radicals, which are DNA, proteins, NA, and lipids. He noted that, "mutations in cancer-related genes or post-translational modifications of proteins by nitration, nitrosation, phosphorylation, acetylation or polyADP-ribosylation-by free radiacals or lipid peroxidation byproducts…are some of the key events that can increase the cancer risk" (Hussain 2003, p. 276). Furthermore, changes in DNA occur when the person has been exposed to high levels of nitric oxide or NO. p53 plays a role in that it acts as a mediator to stress but NO "causes p53 accumulation and post-translational modifications that inhibit cellular growth" (Hussain 2003, p. 278). His research has revealed that when exposed to NO during chronic inflammation sans wild-type p53, there might be increased…...

mla References American Cancer Society (n.d.) Cancer Facts & Figures 2010, [online] Available at:   [Accessed: April 19, 2011]. http://www.cancer.org/research/cancerfactsfigures/cancerfactsfigures/cancer-facts-and-figures-2010  American Cancer Society (n.d.) What Causes Cancer?, [online] Available at:   [Accessed: April 19, 2011]. http://www.cancer.org/Cancer/CancerCauses/index  Croce, C. (2008) Oncogenes and Cancer, N Engl J. Med, 358, p. 502-511. Hasty, P. (2005) the impact of DNA damage, genetic mutation and cellular responses on cancer prevention, longevity and aging: observations in humans and mice, Mech Ageing Dev, 126(1), p.71-77.

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mla Works Cited Kean, S. (2014). The 'Other' Breast Cancer Genes. Science, Vol. 343. Retrieved April 7, 2014, from   http://www.sciencemag.org .

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mla References Cancer Gap Between Whites, Blacks May Be Biological in Part. (2009). Retrieved August 11, 2009, from   http://healthday.com/Article.asp?AID=628785  Carcinogen Found in KFC's New Grilled Chicken. (2009). Retrieved August 13, 2009, from News and Media Center Web site:   http://www.pcrm.org/news/release090521.html  National Breast Cancer Awareness Month. (2008). Retrieved August 11, 2009, from American

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infer an answer to a particular section, then you must so state and JUSTIFY your statement. DO NOT LEAVE ANY SECTION BLANK. Caution: Do not provide a "Yes" or "no" answer without an EXPLANATION. YOU MUST JUSTIFY ALL YOUR RESPONSES ALL responses must be written in YOUR OWN WORDS. Do NOT use quotes. Morike Adekemi Full and Complete Reference for the Article: Hagan, Teresa L, BSN, RN., B.A., & Donovan, Heidi M, Phd., R.N. (2013). Ovarian cancer survivor's experiences of self-advocacy: A focus group study. Oncology Nursing Forum, 40(2), 140-7. Retrieved from http://searchproquest.com/docview/1325739253?accountid-35812 You must submit the full article in PDF form. Critiques submitted without the PDF will not be accepted. Problem What is the problem the study was conducted to address? (1) Response: The problem this study was conducted to address was self-advocacy in clinical research as well as practice. Despite self-advocacy being cited as a trait desirable among patients, not much explanation or description of this concept is…...

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mla References Cell Reproduction. (n.d.). Retrieved February 23, 2011, from   http://www.mhhe.com/biosci/genbio/virtual_labs/BL_23/BL_23.html  Hardman, A.E., & Stensel, D.J. (2009). Physical activity and health the evidence explained. London: Routledge. Hong, W.K., & Bast, R.C. (2009). Holland Frei Cancer Medicine Volume 8. (2nd ed., Vol. 8). Hartford, Conn.: PHPM-U.S.. Kolata, G.B. (1975). A Major Difference Between Normal Cells and Cancer Cells. The Science Journal, 188(4190), 819-822. Retrieved February 15, 2011.

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mla ReferencesAhmad, A., Kumar, M., Bhoi, N. R., Badruddeen, Akhtar, J., Khan, M. I., ... & Ahmad, M. (2023). Diagnosis and management of uterine fibroids: current trends and future strategies. Journal of Basic and Clinical Physiology and Pharmacology, 34(3), 291-310.Dubbewar, A., Srivastava, A., Hiremath, R. N., Ghodke, S., Chourey, N., & Sreenivas, A. (2022). A rare case of spontaneous heterotopic pregnancy with intrauterine gestational trophoblastic neoplasia and tubal ectopic pregnancy at a remote secondary care hospital. Journal of Family Medicine and Primary Care, 11(7), 3996-3998.Martin, M. L., Halling, K., Eek, D., & Reaney, M. (2020). “Lower abdominal pains, as if I was being squeezed… in a clamp”: A Qualitative Analysis of Symptoms, Patient-Perceived Side Effects and Impacts of Ovarian Cancer. The Patient-Patient-Centered Outcomes Research, 13, 189-200.Vitale, A. M., & Lockwood, G. M. (2020). Urine Microscopy: The Burning Truth–White Blood Cells in the Urine. Urine Tests: A Case-Based Guide to Clinical Evaluation and Application, 143-166.

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Ovulation induction drug and ovarian cancer: an updated systematic review and meta-analysis

1 The First Affiliated Hospital of Nanjing Medical University, The First Clinical Medical College of Nanjing Medical University, Nanjing, 210029 China

2 Department of Gynecology, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University，The first clinical medical college of Nanjing Medical University, Nanjing, 210029 China

3 Department of Gynecology, Jiangsu Province Hospital, the First Affiliated Hospital of Nanjing Medical University, Nanjing, 210036 China

Associated Data

This meta-analysis was based on the data from the published articles and independent of any patient involvement. All the data will be made available to the editors of the journal for review or query upon.

To explore the association between ovulation induction drugs and ovarian cancer.

Systematic review and meta-analysis.

Not applicable.

Women without ovarian cancer who ever or never underwent ovarian induction.

Intervention(s)

An extensive electronic search of the following databases was performed: PubMed, EMBASE, MEDLINE, Google Scholar, Cochrane Library and CNKI, from inception until January 2022. A total of 34 studies fulfilled our inclusion criteria and were included in the final meta-analysis. The odds ratio (OR) and random-effects model were used to estimate the pooled effects. The Newcastle-Ottawa Scale was used to assess the quality of included studies. Funnel plots and Egger tests were used to assess publication bias.

Main outcomes

New diagnosed borderline ovarian tumor (BOT) and invasive ovarian cancer (IOC) between ovulation induction (OI) group and control (CT) group considering fertility outcome, OI cycles and specific OI drugs.

Primarily, there was no significant difference in the incidence of IOC and BOT between the OI and CT groups. Secondly, OI treatment did not increase the risk of IOC and BOT in the multiparous women, nor did it increase the risk of IOC in the nulliparous women. However, the risk of BOT appeared to be higher in nulliparous women treated with OI treatment. Thirdly, among women exposed to OI, the risk of IOC and BOT was higher in nulliparous women than in multiparous women. Fourthly, the risk of IOC did not increase with increasing OI cycles. Lastly, exposure to specific OI drugs also did not contribute to the risk of IOC and BOT.

Overall, OI treatment did not increase the risk of IOC and BOT in most women, regardless of OI drug type and OI cycle. However, nulliparous women treated with OI showed a higher risk of ovarian cancer, necessitating their rigorous monitoring and ongoing follow-up.

Supplementary Information

The online version contains supplementary material available at 10.1186/s13048-022-01084-z.

Introduction

Infertility affects more than 48.5 million couples worldwide [ 1 – 3 ]. It is emerging as a public health problem, driving the demand for assisted reproductive treatment [ 4 ]. Ovulation induction (OI) is a process in which the ovaries are drugged to stimulate the production of many follicles containing eggs, which usually begins early in the menstrual cycle. OI treatment is highly desirable, especially for isolated anovulatory infertility [ 5 ]. OI treatment is associated with ovarian hyper-stimulation and multiple follicular ovulations. As we know, ovulation is a common injurious process associated with an inflammatory response and destruction of ovarian epithelial cells [ 6 , 7 ]. According to the incessant ovulation and gonadotropin hypothesis, high levels of gonadotropin and excessive ovulation may engage patients into repeated cycles of injury, inducing inflammation and regeneration, which could potentially increase the risk of ovarian cancer by inducing somatic cell mutations [ 8 – 10 ]. Previous studies have debated whether OI could increase the risk of invasive ovarian cancer (IOC) and borderline ovarian tumors (BOT) [ 11 , 12 ]. Although most studies have concluded that OI does not contribute to the risk of IOC and BOT, some scholars still proposed that OI may be associated with them. Therefore, we performed this updated systematic review and meta-analysis to find out whether exposure to OI treatment significantly increases the risk of IOC and BOT.

Materials and methods

Search strategy.

The PRISMA guidelines were used for this study. A systematic literature search was then conducted in PubMed, EMBASE, MEDLINE, Google Scholar, Cochrane Library and CNKI, which included records up to January 2022. The main keywords included the following domains of Medical Subject Heading terms: “ ovulation induction “ and “ ovarian cancer “. The retrieval strategy adopted the combination of subject terms and free words. These terms were then combined with “AND” or “OR”. Also, to broaden the search, review articles were used to ensure that all relevant citations were identified and imported.

Study screening

Two independent researchers (YL and WQQ) simultaneously screened the titles, abstracts and full text of the literature according to the inclusion and exclusion criteria. Any disagreements were discussed and solved by consensus or third-party arbitration (ZS). The inclusion criteria were as follows: (1) Cohort studies and case-control studies with adequate samples; (2) Exposure to ovulation induction drugs such as clomiphene citrate (CC), gonadotrophin (GDT) and gonadotropin-releasing hormone analogs (GnRH-a); (3) Follow-up in the cohort study was sufficiently long to demonstrate treatment differences; (4) The study had a clear description of the exposure to OI drugs and essential information about enrolled patients;(5) The type of cancer included borderline ovarian tumor (BOT) or invasive ovarian cancer (IOC). The exclusion criteria were as follows: (1) Non-English or Non-Chinese literature; (2) Non-human studies; (3) Literature with incomplete data; (4) Duplicate and inaccessible literature.

Data extraction

Two independent researchers (YL and SJF) performed the data extraction after viewing the complete manuscripts of the eligible literature. Relevant data was input into separate spreadsheets and then cross-checked by each researcher to maintain the quality of the data. The data of bibliography (year and author), study design (sample size, study type, study duration and study location), outcome measures (cancer type and incidence of individual ovarian cancers in group) and other endpoint evaluation (fertility outcome, OI drug type and OI cycles) were extracted from each study. If necessary, discussions with the third-party arbitration (XW) would solve all disputes.

Quality evaluation

Two researchers (YL and YWN) independently assessed the quality of the literature by using the NOS scale (Newcastle-Ottawa Scale). The main components of the NOS scale included: patient selection, intergroup comparability and outcome measurement [ 13 ]. Disagreements were solved by consensus or third-party arbitration (WXL) when they appeared. A total score of more than 6 was considered to be of satisfactory quality [ 14 ].

Statistical analysis

Data aggregation and basic meta-analysis.

The meta-analysis was performed by using STATA 12.0. Binary variables were evaluated by odds ratio (OR) and its 95% confidence interval (95% CI). P  < 0.05 was regarded as statistically significant.

Depending on heterogeneity, the appropriate model (random or fixed) was then selected to merge the outcome indicators [ 15 ]. The I 2 value less than 50% were deemed to be low heterogeneity, 51–75% were deemed to be moderate heterogeneity, and greater than 75% were deemed to be high heterogeneity [ 16 ]. If the I 2 value exceeded 50%, the random-effect model was chosen. Otherwise, if the I 2 value was less than 50%, both the random effects and fixed effects models were acceptable [ 17 ].

Assessment of publication bias

In principle, funnel plot analyses were performed to accompany meta-analyses involving more 10 studies and to judge the publication bias [ 18 ]. If there was no significant publication bias, the funnel plot was supposed to be symmetrical. A complementary approach for funnel plots was to perform Egger’s test to objectively measure bias [ 19 ].

Details of ethical approval

This meta-analysis was based on the data from published articles and independent of any patient participation. As such, institutional review board (IRB) approval was not required.

Study characteristics and quality evaluation

A flowchart detailing the process of identification and inclusion for the target literature was shown in Supplemental Material Fig.  1 . Three hundred seven articles were included in the initial screening phase. Of these articles, 42 articles met the criteria for full-text review. Finally, a total of 34 articles were included in the meta-analysis, 14 of which were case-control studies and 20 of which were cohort studies. The final meta-analysis included a total of 3,643,303 participants. All the included literature was of adequate quality. The quality evaluation of the included literature was presented in Supplemental Material Table S1 .

Part I: the risk of ovarian cancer between OI and CT group

Of the 34 studies, 12 reported BOT [ 12 , 20 – 30 ] and 30 reported IOC [ 11 , 12 , 20 , 21 , 23 – 26 , 29 , 31 – 51 ]. Basic information of the included studies was given in Supplemental Material Table S2 . For further study, we conducted subgroup analyses to assess the risk of IOC and BOT between groups according to study type.

The cancer risk between groups in case-control study

In the subgroup analysis of case-control studies, 12 studies reported IOC [ 11 , 23 , 29 , 32 , 36 – 43 ] and 5 studies reported BOT [ 23 , 27 – 30 ]. Among these studies, only 1 study showed a significantly higher risk of IOC in the OI group than in the CT group [ 11 ] and 3 studies showed a higher risk of BOT in the OI group than in the CT group [ 28 – 30 ]. Pooled result indicated that the risk of IOC (OR = 1.09, 95%CI: 0.88–1.35, I 2  = 54.9%, Table ​ Table1, 1 , Fig. ​ Fig.1A) 1 A) and BOT (OR = 1.90, 95%CI: 0.89–4.09, I 2  = 73.4%, Table ​ Table1, 1 , Fig. ​ Fig.1B) 1 B) did not show significant difference between groups.

Odd ratios (with confidence intervals) and heterogeneity for each of the cancer risks analysed

CC Clomiphene citrate, GDT Gonadotrophin, GnRH-a Gonadotropin-releasing hormone analogues, HCG human menopausal gonadotropin, HMG human chorionic gonadotropin, IOC invasive ovarian cancer, BOT borderline ovarian tumor, OI ovulation induction group, CT control group, OR odds ratio, 95%CI 95% confidence interval

A Forest plot of IOC risk between OI group and CT group based on case-control studies; B Forest plot of IOC risk between OI group and CT group based on cohort studies; C Forest plot of BOT risk between OI group and CT group based on case-control studies; D Forest plot of BOT risk between OI group and CT group based on cohort studies

The cancer risk between groups in cohort study

In the subgroup analysis of cohort studies, 18 studies reported IOC [ 12 , 20 , 21 , 24 – 26 , 31 , 33 – 35 , 44 – 51 ] and 7 studies reported BOT [ 12 , 20 – 22 , 24 – 26 ]. Of these studies, 3 studies showed a higher risk of IOC [ 12 , 21 , 31 ] in the OI group than in the CT group and 3 studied showed a higher risk of BOT in the OI group than in the CT group [ 21 , 24 , 25 ]. Again, the results showed no significant difference between groups in the incidence of IOC (OR = 1.11, 95%CI: 0.91–1.35, I 2  = 21.8%, Table ​ Table1, 1 , Fig. ​ Fig.1C) 1 C) and BOT (OR = 1.34, 95%CI: 0.97–1.83, I 2  = 50.5%, Table ​ Table1, 1 , Fig. ​ Fig.1 1 D).

Part II: the incidence of ovarian cancer between OI and CT group according to fertility outcome

In this section, we sought to find out whether the multiparous and nulliparous women treated with OI presented an increased risk of ovarian tumors when compared to those who had not been treated with OI. Relevant data were presented in Supplemental Material Table S3 .

The cancer risk between groups in multiparous women

Firstly, 10 studies of IOC [ 11 , 12 , 34 , 36 – 38 , 40 – 42 , 50 ] and 3 studies of BOT [ 12 , 22 , 28 ] analyzed the risk of ovarian cancer in multiparous women with or without OI treatment. None of these studies demonstrated a higher risk for IOC and BOT in the OI group. Pooled result remained consistent, indicating that OI treatment did not increase the risk of IOC (OR = 0.83, 95%CI: 0.65–1.05, I 2  = 21.3%, Table ​ Table1, 1 , Fig.  2 A) and BOT (OR = 1.17, 95%CI: 0.55–2.48, I 2  = 73.5%, Table ​ Table1, 1 , Fig. ​ Fig.2B) 2 B) in multiparous women.

A Forest plot of IOC risk between OI group and CT group in multiparous women; B Forest plot of BOT risk between OI group and CT group in multiparous women; C Forest plot of IOC risk between OI group and CT group in nulliparous women; D Forest plot of BOT risk between OI group and CT group in nulliparous women

The cancer risk between groups in nulliparous women

In the second part, 8 studies of IOC [ 11 , 12 , 34 , 36 , 38 , 40 – 42 ] and 3 studies of BOT [ 12 , 22 , 28 ] reported the risk of ovarian cancer in nulliparous women with or without OI treatment. Of these studies, only 1 study showed a significantly higher risk of IOC in the OI group than in the CT group [ 11 ]. The summarized result for IOC showed no difference in cancer risk between groups (OR = 1.55, 95%CI: 0.94–2.57, I 2  = 69.5%, Table ​ Table1, 1 , Fig. ​ Fig.2C). 2 C). Additionally, none of these studies reported a higher risk of BOT in the OI group. However, after pooled analysis, the risk of BOT appeared to be higher in nulliparous women treated with OI than in those nulliparous women who had not been treated with OI (OR = 1.49, 95%CI: 1.03–2.15, I 2  = 0%, Table ​ Table1, 1 , Fig. ​ Fig.2 2 D).

Part III: the risk of ovarian cancer between the multiparous and nulliparous women in OI group

In this chapter, we attempted to figure out the differences in cancer risk between the multiparous and nulliparous woman in the OI group. Relevant data were presented in Supplemental Material Table S4 . In total, 8 studies of IOC [ 11 , 12 , 34 , 36 , 38 , 40 – 42 ] and 3 studies of BOT [ 12 , 22 , 28 ] reported on the risk of ovarian cancer in the nulliparous and multiparous women treated with OI. The summarized results showed a significantly higher risk of IOC (OR = 3.35, 95%CI: 2.10–5.34, I 2  = 52.2%, Table ​ Table1, 1 , Fig.  3 A) and BOT (OR = 2.58, 95%CI: 1.76–3.79, I 2  = 0%, Table ​ Table1, 1 , Fig. ​ Fig.3B) 3 B) in the nulliparous women treated with OI than in those multiparous women treated with OI.

A Forest plot of IOC risk between nulliparous and multiparous women with OI treatment; B Forest plot of BOT risk between nulliparous and multiparous women with OI treatment

Part IV: the relationship between number of OI cycles and cancer risk

Then, we tried to find out whether cancer risk increased with more OI cycles. Totally, 8 studies provided relevant data for IOC [ 20 , 24 , 25 , 36 , 39 , 41 , 42 , 46 , 47 ]. Regrettably, data for BOT were not available for meta-analysis. Relevant data were presented in Supplemental Material Table S5 .

Using a cut-off of 3 cycles, we did not find a higher cancer risk in those women who received less than 3 cycles when compared to the CT group (OR = 1.05, 95%CI: 0.72–1.52, I 2  = 42.9%, Table ​ Table1, 1 , Fig.  4 A). Meanwhile, we found a similar result in those women who received more than 3 cycles (OR = 0.98, 95%CI: 0.79–1.22, I 2  = 0%, Table ​ Table1, 1 , Fig. ​ Fig.4A). 4 A). Using 6 cycles as a cut-off, those women who received less than 6 cycles did not present an increased cancer risk when compared to the CT group (OR = 0.85, 95%CI: 0.64–1.12, I 2  = 0%, Table ​ Table1, 1 , Fig. ​ Fig.4B) 4 B) and a similar result was found in those women who received more than 6 OI cycles (OR = 0.88, 95%CI: 0.59–1.31, I 2  = 0%, Table ​ Table1, 1 , Fig. ​ Fig.4B). 4 B). Lastly, using 12 cycles as a cut-off, we did not find a significantly increased cancer risk in those women who received less than 12 cycles when compared to the CT group (OR = 0.87, 95%CI: 0.69–1.10, I 2  = 0%, Table ​ Table1, 1 , Fig. ​ Fig.4C). 4 C). Also, a similar result was found in those women who received more than 12 OI cycles (OR = 0.78, 95%CI: 0.49–1.22, I 2  = 0%, Table ​ Table1, 1 , Fig. ​ Fig.4 4 C).

A Forest plot of IOC risk between OI group and CT group based on a cut-off value of 3 cycles; B Forest plot of IOC risk between OI group and CT group based on a cut-off value of 6 cycles; A Forest plot of IOC risk between OI group and CT group based on a cut-off value of 12 cycles

Part V: the relationship between specific OI treatment and cancer risk

At last, we wished to find out whether specific OI drugs were associated with an increased cancer risk. For further study, we divided the subjects into three groups according to the type of OI drug. These were the clomiphene citrate group (CC), the gonadotrophin group (GDT) and the gonadotropin-releasing hormone analog group (GnRH-a). Relevant data were provided in Supplemental Material Table S6 .

The relationship between CC and cancer risk

We firstly analyzed the relationship between CC and cancer risk. This part of analysis included 17 studies of IOC [ 25 , 29 , 35 , 36 , 38 , 41 – 43 , 45 – 47 , 50 , 51 ] and 7 studies of BOT [ 12 , 20 , 22 , 25 , 27 – 29 ]. Only 1 study reported a higher cancer risk in the CC group than in the CT group [ 12 ]. However, pooled results showed that the risk of IOC (OR  =  1.01, 95%CI: 0.88–1.17, I 2  = 0%, Table ​ Table1, 1 , Fig.  5 A) and BOT (OR = 1.32, 95%CI: 0.79–2.21, I 2  = 72.6%, Table ​ Table1, 1 , Fig. ​ Fig.5A) 5 A) were not significantly higher in the CC group when compared to the CT group.

A Forest plot of IOC and BOT risk between CC group and CT group; B Forest plot of IOC and BOT risk between HMG group and CT group; C Forest plot of IOC and BOT risk between HCG group and CT group; D Forest plot of IOC and BOT risk between GDT group and CT group; E Forest plot of IOC risk between GnRH group and CT group

The relationship between GDT and cancer risk

Secondarily, we focused our attention on GDT and performed a subgroup analysis in this section. GDTs mainly consisted of human menopausal gonadotropin (HMG) and human chorionic gonadotropin (HCG). However, some studies did not further categorized GDT. For IOC, there were 5 studies of HMG [ 29 , 35 , 38 , 41 , 47 ], 2 studies of HCG [ 38 , 43 ] and 6 studies of unclassified GDT [ 25 , 33 , 36 , 43 , 49 , 51 ]. Only 1 study reported a higher cancer risk in HMG group than in the CT group [ 29 ]. Nevertheless, pooled results indicated that HMG (OR = 1.07, 95%CI: 0.44–2.57, I 2  = 71.6%, Table ​ Table1, 1 , Fig. ​ Fig.5B), 5 B), HCG (OR = 1.10, 95%CI: 0.71–1.71, I 2  = 34.7%, Table ​ Table1, 1 , Fig. ​ Fig.5C) 5 C) and unclassified GDT (OR = 1.08, 95%CI: 0.80–1.44, I 2  = 0%, Table ​ Table1, 1 , Fig. ​ Fig.5D) 5 D) did not increase the cancer risk.

While for BOT, 2 studies of HMG [ 28 , 29 ], 2 studies of HCG [ 22 ] and 3 studies of GDT [ 22 , 25 , 27 ] were included in this part of analysis. Consistently, we found similar results that HMG (OR = 5.31, 95%CI: 0.73–38.72, I 2  = 83.3%, Table ​ Table1, 1 , Fig. ​ Fig.5B), 5 B), HCG (OR = 1.28, 95%CI: 0.71–2.31, I 2  = 56%, Table ​ Table1, 1 , Fig. ​ Fig.5C) 5 C) and unclassified GDT (OR = 1.73, 95%CI: 0.88–1.93, I 2  = 54.1%, Table ​ Table1, 1 , Fig. ​ Fig.5D) 5 D) did not increase tumor risk.

The relationship between GnRH-a and cancer risk

Thirdly, we only found 2 studies which provided analyzable data on the relationship between the risk of IOC and GnRH-a [ 43 , 47 ]. Along the same lines, we did not find an increased risk of IOC (OR = 0.49, 95%CI: 0.07–3.66, I 2  = 71.9%, Table ​ Table1, 1 , Fig. ​ Fig.5E) 5 E) in the GnRH-a group when compared to the CT group. However, it was regrettable that another meta-analysis focusing on the relationship between the risk of BOT and GnRH-a could not be performed due to lack of data.

Publication bias

In our analysis, funnel plot analysis and Egger regression analysis were performed to judge the publication bias of the included studies. Neither the funnel plot (Supplemental Material Fig.  2 A) nor the Egger test showed evidence of publication bias in our analysis (Supplemental Material Fig.  2 B).

The following points are currently discussed regarding the possible induction of ovarian cancer with the use of OI drugs: (1) the incessant ovulation hypothesis stated that ovarian epithelium could be destroyed and repaired during uninterrupted ovulation. When a sufficient amount of damage is caused, malignant transformation of ovarian epithelial cells will be triggered [ 8 ]. Furthermore, cancer risk had been found to decrease with increasing numbers of pregnancies and live births, longer duration of breastfeeding and use of oral contraceptives [ 52 – 57 ]. The effects of these anovulation factors confirmed the above observations. Thus, it is thought that the number of ovulatory cycles during the lifetime was associated with ovarian cancer risk, this finding has been observed in several animal models and epidemiological studies [ 58 – 62 ]. (2) The gonadotropin hypothesis suggested that excess gonadotropins could hyper-stimulate the ovaries and induce estrogen production. The amount of estrogen secreted in one gonadotropin-stimulated cycle was equivalent to the total production of natural cycles over a two-year period [ 63 ]. Meanwhile, there appeared to be growing evidence that estrogen conferred increased ovarian cancer risk [ 64 – 66 ]. Thus, gonadotropin-induced elevated estrogen levels might promote the malignant transformation of normal ovarian epithelium [ 63 , 67 ]. The above hypotheses had been tested in hen models but not in humans [ 68 , 69 ]. Therefore, speculation regarding the relationship between the use of ovulation induction drug use and ovarian cancer development continues.

Research in this area was based on cohort studies, case series and case-control studies. And, there were still no randomized controlled trials regarding the relationship between ovulation inducing drugs and ovarian cancer due to ethical issues, the relatively low incidence of ovarian cancer and recall bias after ovulation induction [ 70 ]. This updated systematic review and meta-analysis was based on cohort studies and case-control studies. Some of included studies provided supportive evidence that OI treatment might increase the risk of IOC. However, according to subgroup analysis based on study type, we found no convincing evidence that OI treatment could induce an increased risk of IOC. Compared with previous systematic reviews [ 71 , 72 ], we expanded our search to include more recent studies in our analysis and obtained consistent results.

BOTs are morphologically similar to IOCs and follow a similar pathogenesis [ 73 , 74 ]. As the etiology of BOT was still unknown, it was difficult to explain the possible causal relationship between infertility and OI drugs. In our analysis, no significant increased risk of BOT was found following OI treatment, which appeared to contradict the increasing risk of BOT reported by Barcroft et.al (OR = 1.69, 95%CI: 1.27–2.25). With more studies included in our pooled analysis, we used further subgroup analyses based on study type to circumvent the heterogeneity issues caused by retrospective studies. Ultimately, the results of subgroup analysis were highly consistent in that OI treatment did not increase the risk of BOT.

In addition, during the review of the literature, we found several studies supporting that OI treatment could induce an increased risk of ovarian cancer in the nulliparous women [ 11 , 12 ]. A cumulative analysis conducted by Whittemore et.al indicated an increased risk of ovarian cancer (OR = 27.0, 95%CI: 2.3–315.6) in the nulliparous women who ever received OI treatment. Reigstad et.al also noted a greater increased risk of ovarian cancer (HR 2.49, 95% CI 1.30 to 4.78) in the nulliparous women treated with OI. As we know, parity was known as an established protective factor for ovarian cancer [ 75 ]. Previous studies have shown that the greatest reduction in ovarian cancer risk was associated with the first pregnancy and each subsequent pregnancy could also reduce the risk of ovarian cancer [ 11 , 75 , 76 ]. This protective mechanism has been attributed to anovulation, reduced gonadotropin production and increased progesterone levels [ 77 ]. Hence, whether OI treatment would increase the ovarian cancer risk in nulliparous and multiparous women remained controversial. Therefore, we conducted supplementary analyses based on fertility outcomes in light of the above questions. Among the multiparous women, we did not find a higher risk of IOC and BOT in the OI group than in the CT group. Similarly, among the nulliparous women, OI treatment also did not increase the risk of IOC. However, an increased risk of BOT was found in the nulliparous women treated with OI when compared to those nulliparous women who had not been treated with OI. Nonetheless, none of these included studies initially reported a higher risk of BOT in nulliparous women treated with OI. Based on a review of the included studies, this finding might be due to a lack of ovulatory pause caused by pregnancy and exposure to ovarian hyper-stimulation [ 8 – 10 , 12 ]. Notably, the BOTs were generally seen in younger women [ 78 – 81 ]. Hence, the above association might also be due to a diagnostic bias occurring in young nulliparous women who might pursue medical attention and undergo intensive monitoring [ 41 ].

Rodriguez et.al previously found that infertility itself might increase ovarian cancer risk without concomitant exposure to OI drugs [ 82 ]. A current meta-analysis based on nine prospective cohort studies also suggested that infertility in women was associated with an increased risk of ovarian cancer [ 83 ]. Moreover, a number of diseases that cause infertility, including polycystic ovary syndrome (PCOS) and endometriosis, had been found to be associated with ovarian cancer development. Previous studies had indicated that the genetic and epigenetic profile of patients with PCOS was similar to that of ovarian cancer [ 84 ]. Further, the risk of ovarian cancer, particularly serous borderline ovarian tumor, was shown to be increased in patients with PCOS [ 85 – 87 ]. We also found that ovarian clear cell carcinoma and endometrioid carcinoma were most often associated with ovarian endometriosis in previous studies [ 88 , 89 ]. Thus, infertility itself might be an independent risk factor for ovarian cancer [ 90 ]. In parallel, whether there existed a difference in cancer risk between nulliparous and multiparous women treated with OI was under discussion, as it was difficult to separate OI treatment from infertility as a risk factor for ovarian cancer. In our analysis, we used OI exposure as a control variable to evaluate the relationship between infertility and ovarian cancer and found that the nulliparous women treated with OI showed a higher risk of IOC and BOT than those multiparous women treated with OI. Nieto et.al performed a retrospective study of ovarian cancer in first-degree relatives of infertile patients and showed an increased risk of ovarian cancer in infertile patients who failed to conceive despite receiving OI treatment, which supported our findings [ 91 ]. Rizzuto et.al also noted that the risk of BOT was slightly higher in nulliparous women treated with OI than in multiparous women [ 72 ]. In summary, we believed that there was a necessity to conduct a rigorous medical follow-up in those nulliparous patients treated with OI. Consistent with previous studies, the vast majority of patients were found within 5 years after ovulation induction [ 92 – 98 ]. In our analysis, the included cohort studies had a follow-up period of more than 5 years, which in our opinion is sufficient to detect ovarian cancer. Therefore, follow-up periods longer than 5 years should be considered.

Indeed, it would be arbitrary to diagnose the relationship between OI and ovarian cancer solely based on the history of OI exposure. According to incessant ovulation hypothesis, more ovulatory cycles appeared to be associated with a higher risk of developing ovarian cancer [ 75 , 99 , 100 ]. Whether such a cumulative effect exists remained controversial. After reviewing previous studies, we found no meta-analysis reported an association between OI cycles and the risk of ovarian cancer. Thereby, we performed a further subgroup analysis based on OI cycles, which was the focal point of our analysis. In our analysis, we used 3, 6 and 12 OI cycles as cut-off points, respectively. Compared to the control population, we found no correlation between increasing OI cycles and increased cancer risk. Unfortunately, the data for BOT in this aspect were not available for meta-analysis.

In accession, several studies had reported the risk of individual ovarian cancers due to specific OI drug exposure [ 12 , 29 , 101 ]. Consequently, for further study, we performed subgroup analyses according to the type of OI drug to assess whether specific OI drugs would increase the risk of ovarian cancer. CC was the most common drug to induce ovulation, especially in patients with ovulatory disturbances [ 102 ]. Reigstad et.al reported an increased risk of cancer in nulliparous women exposed to CC (HR = 2.5, 95%CI: 1.3–4.8). Rossing et.al also reported an increased ovarian tumor risk in women exposed to CC (SIR = 2.5, 95%CI: 1.3–4.5). A current meta-analysis conducted by Barcroft et.al supported the view mentioned above, which concluded that the exposure to CC was associated with a significant increased cancer risk (OR = 1.40, 95%CI: 1.10–1.77). However, in our meta- analysis, we included additional studies but did not find an increased cancer risk in those women exposed to CC. GDTs were also commonly used in women with proven hypopituitarism and in women who were not sensitive to CC [ 103 , 104 ]. Shan et.al reported a slight increased ovarian cancer risk in women exposed to HMG (OR = 3.95, 95%CI: 1.3–12.2). While in our study, we found that GDTs were not associated with an increased risk of IOC and BOT. GnRH-a was introduced in anovulatory women, which could reproduce spontaneous menstrual cycle and induce ovulation [ 105 , 106 ]. Our findings indicated that GnRH-a did not increase the risk of IOC. Due to the lack of the data on BOT risk in women exposed to GnRH-a, further meta-analysis could not be performed. In summary, CC, GDT and GnRH-a were proven to be safe for OI treatment without increasing ovarian tumor risk.

Most of our findings were generally consistent with previous studies on this topic [ 71 , 72 , 107 , 108 ]. A new study was included in this latest update of the systematic review and meta-analysis compared to previous studies in this area. This study provides new data on the risk of BOT and IOC to CC exposure. To assess the impact of the latest studies on the outcome of this update, an additional sensitivity analysis was conducted. The sensitivity analysis without the latest study did not change the results that exposure to CC did not increase the risk of IOC (OR = 1.05, 95%CI: 0.89–1.21) and BOT (OR = 1.73, 95%CI: 0.96–2.50). And this latest study made the results more reliable. The results of the sensitivity analysis were shown in Supplemental Material Table S7 . To summarize, OI treatment was relatively safe and cancer risk was not increased more cycles of OI and specific OI drugs. However, for those nulliparous women treated with OI, they appeared to have a higher tumor risk. Therefore, rigorous monitoring and sufficiently long follow-up were necessary for these women.

Strengths and limitations of the study

This study included 34 studies from around the world and provided an up-to-date meta-analysis to explore the potential impact of OI treatment on ovarian cancer risk. The inclusion and exclusion criteria for this systematic review and meta-analysis had been made more rigorous. In addition, the included studies were updated and the process of meta-analysis was made more rigorous. In our analysis, lessons learned from previous studies were incorporated and further subgroup analyses were conducted based on study type, tumor type, parity, OI cycle and specific OI drugs. Of note, this meta-analysis was the first study to evaluate the relationship between the OI cycles and ovarian cancer.

However, our study still had some objective shortcomings. Firstly, further work should focus more attention on patient demographics and specific data including drug combinations, cycles of use, use dosage and administration methods. Secondly, loss of follow-up existed in included studies in our analysis and retrospective studies were always considered to be lower quality evidence due to the presence of recall bias. We needed more large and long-term prospective cohort studies with careful follow-up. Thus, follow-up process needed to be improved. Last but not least, the formation of symbiotic relationships between cancer registries and fertility services should be encouraged to link fertility data with cancer information. Communication and collaboration between fertility services should also be encouraged in order to collect adequate data. We believe that further exploration in this area will facilitate the further development of reproductive science.

Conclusions

OI treatment did not increase risk of ovarian cancer, regardless of treatment regimen and treatment cycle. However, nulliparous women treated with OI might have an increased risk of BOT compared to the nulliparous women not treated with OI. Meanwhile, nulliparous women treated with OI appeared to have a higher risk of IOC and BOT than multiparous women treated with OI. In view of the above, OI treatment was relatively safe but those nulliparous women treated with OI must be followed up rigorously.

Abbreviations

Authors’ contributions

YL & SJF performed the database search. YL & WQQ collected the data. YL performed the analysis and wrote the manuscript. ZS & XW supplemented the database search, polished the language of the article and provided third party arbitration. WXL provided guidance on research directions. All the authors participated in this analysis and approved the final version of the manuscript.

This work was supported by Jiangsu Provincial Commission of Health and Family Planning scientific research project (H2018017), Jiangsu Provincial Women’s and Children’s Health key talent project (RC201709).

Availability of data and materials

Declarations.

All authors agreed publication of the manuscript.

The authors declare no financial, personal, intellectual and professional conflicts of interest.

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Liang Yu, Jiafan Sun, Qiqin Wang and Wennian Yu contributed equally to this work.