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Fertility preservation is an emerging discipline, which is of substantial clinical value in the care of young patients with cancer. Chemotherapy and radiation may induce ovarian damage in prepubertal girls and young women. Although many studies have explored the mechanisms implicated in ovarian toxicity during cancer treatment, its molecular pathophysiology is not fully understood. Chemotherapy may accelerate follicular apoptosis and follicle reservoir utilization and damage the ovarian stroma via multiple molecular reactions. Oxidative stress and the radiosensitivity of oocytes are the main causes of gonadal damage after radiation treatment. Fertility preservation options can be differentiated by patient age, desire for conception, treatment regimen, socioeconomic status, and treatment duration. This review will help highlight the importance of multidisciplinary oncofertility strategies for providing high-quality care to young female cancer patients.

The ovarian reserve represents the stock of quiescent primordial follicles in the ovary which is gradually depleted during a woman’s reproductive lifespan, resulting in menopause. Müllerian inhibiting substance (MIS) (or anti-Müllerian hormone/AMH), which is produced by granulosa cells of growing follicles, has been proposed as a negative regulator of primordial follicle activation. Here we show that long-term parenteral administration of superphysiological doses of MIS, using either an adeno-associated virus serotype 9 (AAV9) gene therapy vector or recombinant protein, resulted in a complete arrest of folliculogenesis in mice. The ovaries of MIS-treated mice were smaller than those in controls and did not contain growing follicles but retained a normal ovarian reserve. When mice treated with AAV9/MIS were paired withmale breeders, they exhibited complete and permanent contraception for their entire reproductive lifespan, disrupted vaginal cycling, and hypergonadotropic hypogonadism. However, when ovaries from AAV9-MIS–treated mice were transplanted orthotopically into normal recipient mice, or when treatment with the protein was discontinued, folliculogenesis resumed, suggesting reversibility. One of the important causes of primary ovarian insufficiency is chemotherapy-induced primordial follicle depletion, which has been proposed to be mediated in part by increased activation. To test the hypothesis that MIS could prevent chemotherapy-induced overactivation, mice were given carboplatin, doxorubicin, or cyclophosphamide andwere cotreated with AAV9-MIS, recombinant MIS protein, or vehicle controls. We found significantly more primordial follicles in MIS-treated animals than in controls. Thus treatment with MIS may provide a method of contraception with the unique characteristic of blocking primordial follicle activation that could be exploited to prevent the primary ovarian insufficiency often associated with chemotherapy.

Abstract STUDY QUESTION How should fertility-sparing treatment of patients with endometrial carcinoma be performed? SUMMARY ANSWER Forty-eight recommendations were formulated on fertility-sparing treatment of patients with endometrial carcinoma. WHAT IS KNOWN ALREADY The standard surgical treatment of endometrial carcinoma consisting of total hysterectomy with bilateral salpingo-oophorectomy drastically affects the quality of life of patients and creates a challenge for clinicians. Recent evidence-based guidelines of the European Society of Gynaecological Oncology (ESGO), the European SocieTy for Radiotherapy & Oncology (ESTRO) and the European Society of Pathology (ESP) provide comprehensive guidelines on all relevant issues of diagnosis and treatment in endometrial carcinoma in a multidisciplinary setting. While addressing also work-up for fertility preservation treatments and the management and follow-up for fertility preservation, it was considered relevant to further extend the guidance on fertility-sparing treatment. STUDY DESIGN, SIZE, DURATION A collaboration was set up between the ESGO, the European Society of Human Reproduction and Embryology (ESHRE) and the European Society for Gynaecological Endoscopy (ESGE), aiming to develop clinically relevant and evidence-based guidelines focusing on key aspects of fertility-sparing treatment in order to improve the quality of care for women with endometrial carcinoma across Europe and worldwide. PARTICIPANTS/MATERIALS, SETTING, METHODS ESGO/ESHRE/ESGE nominated an international multidisciplinary development group consisting of practising clinicians and researchers who have demonstrated leadership and expertise in the care and research of endometrial carcinoma (11 experts across Europe). To ensure that the guidelines are evidence-based, the literature published since 2016, identified from a systematic search was reviewed and critically appraised. In the absence of any clear scientific evidence, judgement was based on the professional experience and consensus of the development group. The guidelines are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines were reviewed by 95 independent international practitioners in cancer care delivery and patient representatives. MAIN RESULTS AND THE ROLE OF CHANCE The multidisciplinary development group formulated 48 recommendations in four sections; patient selection, tumour clinicopathological characteristics, treatment and special issues. LIMITATIONS, REASONS FOR CAUTION Of the 48 recommendations, none could be based on level I evidence and only 16 could be based on level II evidence, implicating that 66% of the recommendations are supported only by observational data, professional experience and consensus of the development group. WIDER IMPLICATIONS OF THE FINDINGS These recommendations provide guidance to professionals caring for women with endometrial carcinoma, including but not limited to professionals in the field of gynaecological oncology, onco-fertility, reproductive surgery, endoscopy, conservative surgery and histopathology, and will help towards a holistic and multidisciplinary approach for this challenging clinical scenario. STUDY FUNDING/COMPETING INTEREST(S) All costs relating to the development process were covered from ESGO, ESHRE and ESGE funds. There was no external funding of the development process or manuscript production. G.S. has reported grants from MSD Italia S.r.l., advisory boards for Storz, Bayer, Astrazeneca, Metronic, TESARO Bio Italy S.r.l and Johnson & Johnson, and honoraria for lectures from Clovis Oncology Italy S.r.l. M.G. has reported advisory boards for Gedeon Richter and Merck. The other authors have reported no conflicts of interest. DISCLAIMER This document represents the views of ESHRE, ESGO and ESGE which are the result of consensus between the relevant stakeholders and where relevant based on the scientific evidence available at the time of preparation. The recommendations should be used for informational and educational purposes. They should not be interpreted as setting a standard of care, or be deemed inclusive of all proper methods of care nor exclusive of other methods of care reasonably directed to obtaining the same results. They do not replace the need for application of clinical judgement to each individual presentation, nor variations based on locality and facility type.

Purpose: To determine the impact of the establishment of a dedicated oncofertility clinic on the frequency of patient referrals for fertility preservation (FP) consultation and the time from patient referral to consultation. Methods: A retrospective chart review of all women aged 21 to 44 years with an active cancer diagnosis who were referred for FP consultation from 2011 to 2015. Results: A total of 6895 female patients eligible for FP were seen at the Massachusetts General Hospital (MGH) Cancer Center. Of those eligible, a total of 209 patients were referred for FP consultation with 150 included in the final analysis. Since the establishment of the oncofertility clinic, the mean time to nonemergent consultation with a reproductive endocrinologist decreased by 27%, from 10.4 to 7.6 days (P = .03). Furthermore, the proportion of reproductive-aged females seen at the MGH Cancer Center referred for FP consultation increased from 1.7% to 3.0% (P < .01). Conclusion: A dedicated oncofertility clinic increases physician referrals for FP and decreases the mean time to consultation, improving access to FP consultation for reproductive-aged women with cancer.

The prodigious rise of cancer survival rates enables many cancer survivors to live long lives. Therefore, the side effects of cancer treatments as well as the long-term quality of life after cancer have become more relevant. Ovarian toxicity is a major off-target effect of anticancer agents for childhood and young adult female cancer patients. Both chemotherapy and irradiation have been demonstrated to damage the ovary and increase the risks of premature ovarian failure (POF), early menopause, ovarian endocrine disorders, and sub- or infertility. Oncofertility is an emerging and multidisciplinary research and medical field that focuses on providing cancer patients with fertility preservation options. Oocyte quality and quantity are one of the most important factors to determine women's fertility success; therefore, preserving oocytes is paramount for maintaining the ability of young female cancer patients' reproduction after their recovery. This review summarizes peer-reviewed literature on current oocyte preservation options in oncofertility. We describe in-depth oocyte and embryo cryopreservation, ovarian suppression, ovarian tissue cryopreservation, in vitro maturation, ovarian transposition, and adjuvant therapy. Further, we discuss current guidelines and practices of female fertility preservation that cover preserving oocytes. Summary sentence Preserving oocytes is fundamental for maintaining the ability of young female cancer patients' reproduction. Graphical Abstract

Background: Primary care physicians not only coordinate referrals to oncology services but can play a crucial role in successful fertility preservation referrals in cancer-diagnosed patients. Hence, it is important to assess their knowledge and attitudes towards fertility preservation. Methods: An eighteen-item oncofertility survey was administered to primary care physicians between May 2019 to September 2020.  Results: A total of forty-six responses were received and analysed. About 60% of primary care physicians did not have adequate knowledge about available fertility preservation options and only 26-32% were aware of international guidelines recommending fertility preservation in cancer patients.  Conclusions: Imparting awareness and knowledge of fertility preservation and its options to primary care physicians could enable an integrated cancer care model while also facilitating successful oncofertility referrals in countries like India.

Germline mutations in genes governing DNA repair, cell cycle regulation, and epigenetic modification are now recognized as common etiological factors for both cancer predisposition and reproductive dysfunction. This reveals a profound intersection between reproductive biology and oncogenesis. A systematic narrative review was conducted. The literature search spanned PubMed/MEDLINE, Scopus, and Web of Science using keywords and MeSH terms related to infertility phenotypes, cancer predisposition syndromes, and shared molecular mechanisms (e.g., DNA repair, epigenetics). The analysis identifies a core set of genes including , and with pleiotropic roles. Mechanistically, defects in pathways like homologous recombination and mismatch repair disrupt meiotic fidelity, causing gametogenesis failure (e.g., -mediated azoospermia), while fostering genomic instability that drives carcinogenesis. Clinically, distinct phenotypes emerge, such as -associated premature ovarian insufficiency and -related germ cell apoptosis. Mouse models validate these links, showing that homozygous loss often causes complete sterility. Translational strategies, including PGT-M for high-risk variants and microsurgical testicular sperm extraction (micro-TESE) with intracytoplasmic sperm injection (ICSI) for azoospermia, offer concrete methods for risk mitigation within integrated oncofertility programs. Infertility and cancer susceptibility are fundamentally linked through shared genetic vulnerabilities and molecular pathways. This necessitates a paradigm shift toward dual-risk management, involving universal genetic screening in idiopathic infertility, the development of polygenic risk models, and close multidisciplinary collaboration. While ethical challenges persist, these advances pave the way for personalized care that simultaneously addresses reproductive and oncologic health.

Abstract Background Sperm cryopreservation offers male cancer patients a critical opportunity to preserve fertility prior to gonadotoxic therapy, yet utilization of banked sperm remains modest, typically under 10%. A structured understanding of barriers across the cancer survivorship continuum is needed to support patients in utilization of cryopreserved sperm in alignment with their reproductive goals. Materials and Methods This expert review synthesizes current evidence and clinical experience to explore the multifaceted barriers to cryopreserved sperm use and propose specific solutions. Key intervention timepoints are examined, including the post-treatment fertility return visit, long-term cryopreservation while remote from family building, readiness for family building, and posthumous considerations. We subsequently outline an optimal Oncofertility Patient Care Pathway. Results Multiple clinical, psychosocial, and financial obstacles limit the transition from sperm banking to use. Approximately one-third of survivors do not attend post-treatment fertility return visits, reducing opportunities for counseling and longitudinal reproductive planning. Psychological factors—including fear of cancer recurrence and delayed readiness for family building—contribute to prolonged storage. Many patients remain underinformed about the efficacy and processes of assisted reproductive techniques, while financial concerns are significant. These intersecting barriers hinder use of cryopreserved sperm. Opportunities exist to intervene at key timepoints, as outlined in the Oncofertillity Patient Care Pathway. Conclusion A multidisciplinary and structured oncofertility pathway, such as detailed in this review, is needed to support cancer survivors in achieving their reproductive goals. Enhanced counseling, technology-enabled follow-up systems, targeted psychological support, and policies promoting broader insurance coverage for assisted reproduction represent key strategies to overcome existing barriers.