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Introduction Material and Methods Results Conclusions Our objective was to assess the feasibility of fertility preservation (FP) in women referred for cervix cancer, the long‐term reproductive outcome, and overall survival.Prospective cohort study of patients referred for FP counseling between 1999 and 2021 to the FP program of Karolinska University Hospital, Stockholm, Sweden. Baseline data included age, parity, disease stage, treatment characteristics, and FP methods applied. Data on reproductive outcomes and overall survival (by October 19, 2023) were retrieved from clinical registries and a population‐based register. Trial registration number: ClinicalTrials.gov NTC04602962.In total, 91 women were referred, 67% with stage I cancers and 25%, 7%, and 1% with stages II, III, and IV, respectively. Cancers were diagnosed during pregnancy or postpartum in six cases. Cancer treatments included fertility‐sparing surgery in 14%, hysterectomy in 30%, and radiochemotherapy in 79% of cases. The treatment modality did not rule out the possibility to undergo FP, and following counseling, 68 patients elected to undergo FP by cryopreservation of embryos or oocytes (N = 11), ovarian tissue (N = 54), or both (N = 3). After a mean follow‐up of 8.1 years, 25 women (37%) returned to the center, five women achieved conception either spontaneously or through assisted reproduction, and 11 women became mothers through adoption or surrogacy. In the group of women receiving radical surgery or chemo/radiotherapy, no live births using cryopreserved specimens have yet been achieved. During follow‐up, 7 women (10%) in the FP group and 5 women (24%) in the group without FP had died of their disease. Cancer recurrence was documented in 19 patients.Our findings underscore the complexity and challenges associated with FP in the context of cervix cancer. Results of this study demonstrate that many women diagnosed with cervix cancer at reproductive age desire to achieve parenthood. While fertility‐sparing surgery can allow pregnancy, those who undergo a hysterectomy are limited to adoption, surrogacy, or the emerging possibility of uterus transplantation. [ABSTRACT FROM AUTHOR]

To report the New England Trophoblastic Disease Center (NETDC) experience with atypical placental site nodules (APSN). The NETDC registry was reviewed from 2005 to 2022 and clinical data abstracted. Expert pathologists in GTD reviewed available slides with concurrent immunohistochemical analysis. Targeted deep sequencing was performed for four cases. Among 35 cases of APSN identified, 29 had clinical and demographic data available. Abnormal uterine bleeding (59.3%) was the most common presenting symptom. Most women (79.3%) had an antecedent live birth. Two cases were incidentally diagnosed after hysterectomy for other indications, and one case lost to follow-up. Among the remaining 26 cases, 11 (42.3%) opted for hysterectomy and 15 for re-sampling (57.7%), among whom 3 later underwent hysterectomy for persistent APSN. Subsequent obstetrical outcomes included 3 spontaneous abortions, 1 therapeutic abortion, 1 ectopic pregnancy, 2 cesarean sections, 1 cesarean hysterectomy, and 1 spontaneous vaginal delivery. Subsequent pathology was available for 26 cases: 4 epithelioid trophoblastic tumors (15.4%), 9 APSN (34.6%), 3 PSN (11.5%), and 10 without abnormalities (38.4%). Histopathologic characteristics of APSN included moderate to severe cytologic atypia, median Ki-67 proliferation index of 8%, and typical immunohistochemical profiles (diffuse or multifocal positivity for p63 and GATA-3 and absent or focal CD146). No histopathologic feature predicted ETT. Among 4 sequenced cases, no recurrent genomic features were identified. APSN is a rare form of gestational trophoblastic proliferation with uncertain malignant potential. While normal obstetric outcomes are possible, the persistence rate is high, and definitive management remains hysterectomy. • The rate of subsequent epithelioid trophoblastic tumor following an atypical placental site nodule was 15.4%. • No single clinical or histologic feature correlated with the development of malignancy. • Among cases desiring fertility preservation, the subsequent live birth rate was 26.7%. [ABSTRACT FROM AUTHOR]

Cryopreservation of testicular tissue holds an important role in the field of fertility preservation, particularly for prepubertal boys diagnosed with cancer. However, prepubertal testicular tissue cryopreservation is still considered to be in the experimental stage necessitating the refinement of cryopreservation protocol. Considering the fact that loss of membrane lipids is the primary cause of freeze–thaw-induced loss of testicular cell functions, in this study, we explored the beneficial properties of exogenous supplementation of membrane lipids in the form of liposomes in enhancing the cryosurvival of prepubertal testicular tissue. The freezing medium supplemented with liposomes (prepared from soy lecithin, phosphatidylethanolamine, phosphatidylserine, and cholesterol) was used for the experiments. Prepubertal testicular tissues from Swiss albino mice were cryopreserved in a liposome-containing freezing medium (LFM) composed of 0.25 mg/mL liposomes, 5% DMSO, and 30% FCS in the DMEM/F12 medium using a slow freezing protocol. The tissues were thawed and assessed for various testicular cell functions. Freezing in LFM mitigated the loss of viability, decreased malondialdehyde level (p < 0.05), and reduced apoptosis (p < 0.05) in the testicular cells compared to the testicular tissue cryopreserved in the control freezing medium (CFM). Further, DMSO (5%) appears to be the ideal penetrating cryoprotectant for prepubertal testicular tissue cryopreservation with liposome-based freezing medium. Similar enhancement in cryosurvival of cells was observed in adult human testicular tissue frozen with LFM. These findings highlight the translational value of liposome-based freezing medium in the cryopreservation of testicular tissue of prepubertal boys undergoing chemotherapy. [ABSTRACT FROM AUTHOR]

Chemotherapy induced ovarian failure and infertility is an important concern in female cancer patients of reproductive age or younger, and non-invasive, pharmacological approaches to maintain ovarian function are urgently needed. Given the role of reduced nicotinamide adenine dinucleotide phosphate (NADPH) as an essential cofactor for drug detoxification, we sought to test whether boosting the NAD(P)+ metabolome could protect ovarian function. We show that pharmacological or transgenic strategies to replenish the NAD+ metabolome ameliorates chemotherapy induced female infertility in mice, as measured by oocyte yield, follicle health, and functional breeding trials. Importantly, treatment of a triple-negative breast cancer mouse model with the NAD+ precursor nicotinamide mononucleotide (NMN) reduced tumour growth and did not impair the efficacy of chemotherapy drugs in vivo or in diverse cancer cell lines. Overall, these findings raise the possibility that NAD+ precursors could be a non-invasive strategy for maintaining ovarian function in cancer patients, with potential benefits in cancer therapy. Synopsis: Female fertility is impaired by chemotherapy in cancer patients. Fertility preservation relies on timely freezing of reproductive material prior to treatment, which is not always feasible. As chemo-induced infertility resembles ovarian ageing, we tested an agent that overcomes reproductive ageing. Boosting the nicotinamide adenine dinucleotide (NAD+) metabolome protected against chemotherapy-induced ovarian toxicity and female infertility. Effects on fertility were long-lasting, indicating long-term protection of the ovarian reserve. The efficacy of chemotherapy against tumour growth in mice was not impaired, indicating that ovarian function protection might not come at the cost of impaired cancer treatment. Female fertility is impaired by chemotherapy in cancer patients. Fertility preservation relies on timely freezing of reproductive material prior to treatment, which is not always feasible. As chemo-induced infertility resembles ovarian ageing, we tested an agent that overcomes reproductive ageing. [ABSTRACT FROM AUTHOR]

While international guidelines on oncofertility practice have been published in developed countries, there is limited information available on oncofertility practice in developing countries, which often face limitations in their cancer health support networks. As survival rates improve in the field of cancer and other diseases, there is a growing need for stronger oncofertility services in developing countries. Given that 50% of cancer patients are under the age of 65, many of these patients are of reproductive age and preserving their fertility health prior to starting treatment is valuable. However, due to resource limitations and the heavy burden of treatment costs imposed on these patients and their families, fertility preservation (FP) may not be a top priority for them. As a result, many healthcare providers and their patients focus on eliminating cancer and its related treatments while overlooking the importance of fertility as a factor that can significantly impact their future quality of life. In this review, we have tried to increase the knowledge of healthcare providers involved in the oncofertility network by reviewing current cancer treatments, FP options in female cancer patients, and their challenges in developing countries. [ABSTRACT FROM AUTHOR]

Purpose: Prior to cancer treatment, patients make decisions on whether to undergo fertility preservation (FP) and the method of FP. We sought to learn more about counseling and decision-making on the method of cancer-related FP. Methods: A cross-sectional 26-item online survey was administered to patients with ovaries who underwent cancer-related FP. Associations between demographics and the FP method were made through estimates of risk difference, with a 95% confidence interval. Open-ended responses were analyzed using the constant comparative method. Results: A total of 240 respondents completed the survey: 52% underwent oocyte cryopreservation (OC), 29% underwent embryo cryopreservation (EC), and 19% underwent both oocyte and embryo cryopreservation (OC/EC). Most respondents agreed that if they were to go through the process again, they would make the same decision about FP (80% EC, 72% OC, 59% OC/EC). Women ≥ 35 years reported being counseled more that embryos were superior compared to younger women (risk difference 46%, CI 32.8, 59.1), however were not more likely to freeze embryos (risk difference 6.2%, CI − 9.8, 22.2). Women in long-term relationships reported they were counseled more that embryos were superior compared to those single/dating (risk difference 27%, CI 18.1, 35.9). All women in long-term relationships reported undergoing EC, while the majority of single/dating women reported undergoing OC (74.6%). Conclusion: Most women who have undergone cancer-related FP reported they would choose the same FP method again. Women in long-term relationships or ≥ 35 years reported they were more likely to be counseled that EC is superior; however, only women in long-term relationships were more likely to freeze embryos. [ABSTRACT FROM AUTHOR]

In the last decade, the evolution of oncofertility has sparked a resurgence of interest in in vitro maturation (IVM) due to its suitability in certain oncological scenarios where controlled ovarian hyperstimulation may not be feasible. The retrieval of immature cumulus–oocyte complexes from small antral follicles, regardless of the menstrual cycle phase, presents a swift opportunity to vitrify mature oocytes or embryos post-IVM in urgent situations or when stimulation is not advisable. Harvesting immature cumulus–oocyte complexes and immature oocytes can be achieved transvaginally or directly in the laboratory from extracorporeal ovarian tissue. Although IVM has transitioned from an experimental status due to safety validations, it relies on the intricate process of oocyte maturation. Despite successful live births resulting from IVM in fertility preservation contexts, the comparatively lower developmental competence of in vitro matured oocytes highlights the necessity to enhance IVM culture systems. Recent advancements in IVM systems hold promise in bolstering oocyte competence post-IVM, thereby narrowing the gap between IVM and outcomes from ovarian stimulation. Additionally, for optimizing the chances of conception in cancer survivors, the combination of IVM and ovarian tissue cryopreservation stands as the favored choice when ovarian stimulation is unfeasible. [ABSTRACT FROM AUTHOR]

Given recent advances in cancer therapeutics, there is a growing population of adolescent and young adult (AYA) cancer survivors navigating the physical and psychological consequences of cancer treatment. Fertility preservation (FP) conversations are of increasing importance for these survivors. Decision regret (DR) is a measure of distress or remorse following a health care decision, and it is a useful tool to evaluate the impact of a treatment on quality of life. The aim of this systematic review is to culminate existing literature focused on determinants of FP DR among AYA cancer survivors and to propose future interventions to reduce DR among AYA cancer survivors. An electronic database search was performed using PubMed, Web of Science, and APA PsycINFO for articles published before December 2023 using the following search criteria: PubMed: "Fertility Preservation"[Mesh] AND decision regret, APA PsycINFO and Web of Science: Fertility Preservation AND decision regret. Articles were organized into five categories that emerged after initial review. Nineteen articles that focused on DR and FP in AYA cancer survivors aged ≤40 and ≥12 years were included. Article results were categorized into five categories pertaining to determinants of FP DR: Unmet Informational and Emotional Needs, Need for Developmentally Appropriate Conversations, Insufficiency of Provider Training, Quality and Timeliness of Fertility Preservation Discussions, and Societal Barriers. These results highlight the need for improved patient and provider education on FP, such as future longitudinal studies focused on standardization of FP-related protocols and the impact of their implementation on DR, especially for AYA cancer survivors. [ABSTRACT FROM AUTHOR]

Although the overall incidence and mortality of colorectal cancer have declined, diagnosed cases of young-onset colorectal cancer have increased significantly. Concerns about future fertility are second only to concerns about survival and may significantly affect the quality of life of young cancer survivors. Fertility preservation is an important issue in young-onset colorectal patients with cancer undergoing oncotherapy. Here, we discussed the effects of different treatments on fertility, common options for fertility preservation, factors affecting fertility preservation and improvement measures, and the relationship between fertility and pregnancy outcomes in young-onset colorectal patients with cancer. [ABSTRACT FROM AUTHOR]

While international guidelines on oncofertility practice have been published in developed countries, there is limitedinformation available on oncofertility practice in developing countries, which often face limitations in their cancerhealth support networks. As survival rates improve in the field of cancer and other diseases, there is a growing needfor stronger oncofertility services in developing countries. Given that 50% of cancer patients are under the age of 65,many of these patients are of reproductive age and preserving their fertility health prior to starting treatment is valuable.However, due to resource limitations and the heavy burden of treatment costs imposed on these patients andtheir families, fertility preservation (FP) may not be a top priority for them. As a result, many healthcare providers andtheir patients focus on eliminating cancer and its related treatments while overlooking the importance of fertility as afactor that can significantly impact their future quality of life. In this review, we have tried to increase the knowledgeof healthcare providers involved in the oncofertility network by reviewing current cancer treatments, FP options infemale cancer patients, and their challenges in developing countries.

Background. Every year, the number of patients who face cancer without having time to realize their reproductive function increases. In view of this, there is a growing need to develop and improve various ways to preserve fertility in this category of patients. The most common techniques are in vitro maturation of oocytes and controlled ovarian stimulation followed by vitrification of oocytes and embryos. At the same time, transvaginal puncture (TVP) has a risk of developing complications such as bleeding or an infectious process. Disorders of the vaginal microflora also increase the likelihood of inflammatory diseases. In this regard, the correction of vaginal dysbiosis is an integral part of the protocols of assisted reproductive technologies before the TVP. Aim. Development of an integrated approach to the preservation of reproductive material in patients with oncological pathology. Materials and methods. A prospective randomized study of 39 women with an identified oncological process and bacterial vaginosis was conducted. The patients were divided into 2 groups: oral probiotic was added to clindamycin therapy in group 1, and vaginal probiotic in group 2. The ovarian reserve was examined for everyone, the qualitative composition of the vaginal microflora was determined, pH-metry was performed and related specialists were consulted if necessary. Results. The patients are comparable in age and ovarian reserve. When using an oral probiotic, an improvement in the qualitative composition of the microflora was noted due to a decrease in opportunistic flora (Gardnerella vaginalis) and an increase in the number of lactobacilli. The vaginal probiotic showed comparable results, but the recurrence rate was 28%, while in group 1 it was 18%. It was noted that when taking Enterolactis Duo, the symptoms associated with chemotherapy treatment decrease. During the study, 396 oocytes were obtained, of which 212 are suitable for vitrification and fertilization. Conclusion. Currently, the development of oncofertility methods and their improvement remain one of the urgent problems. Taking an oral probiotic helps to normalize the vaginal microflora, neutralize the risks of infectious complications in TVP, reduce the likelihood of recurrence of dysbiosis and the development of adverse events associated with chemotherapy. The use of ovulation stimulation demonstrates higher rates compared to in vitro maturation. However, a combination of these procedures can be used to increase the amount of material obtained, which is subsequently used in assisted reproductive technology protocols.

Introduction. An increasing number of patients of reproductive age get cancer and are highly interested in preserving fertility. Survival rates for cancer patients are improving. Methods of reproductive technologies are being improved to preserve the ability to bear children. Rehabilitation aimed to ensure a satisfactory quality of life takes on a new meaning, and with the development of new technologies, the level of possible assistance also changes. Today, rehabilitation measures for cancer patients of reproductive age should undoubtedly include all possible ways to preserve and restore fertility. Aim: preservation of fertility in patients with ovarian tumors. Material and Methods. After ovariectomy, the ovaries were transported to the embryology laboratory, where oocyte-cumulus complexes were extracted and subsequently matured using the OTO-IVM (ovarian tissue oocyte in vitro maturation) method. The resulting mature oocytes (Metaphase II) were cryopreserved by vitrification or, if a partner was available, fertilized by ICSI (intracytoplasmic sperm injection), the embryos were cultured to the blastocyst stage and also cryopreserved by vitrification. Cryopreserved oocytes and embryos can be used by patients after cancer treatment in assisted reproductive technology programs. Results. A total of 218 OCCs were recovered, 29.8 % were degraded oocytes (n=65). The proportion of OCC suitable for ripening was 153 (70.2 %). After 36 or 48 hours, 65 oocytes matured in 13 patients, which amounted to 42.5 % of oocytes without signs of degradation. In 11 patients the OCC was removed from the tumor-affected ovary. 149 oocytes were obtained, of which 50 (33.6 %) were oocytes with signs of degradation. The remaining 99 (66.4 %) of OCCs had satisfactory quality; after maturation, the Metaphase II stage reached in 49 (49.5 %) of oocytes. As a result, biological material was cryopreserved in 13 of 15 patients: 5 embryos and 60 oocytes.

Abstract Chemotherapy induced ovarian failure and infertility is an important concern in female cancer patients of reproductive age or younger, and non-invasive, pharmacological approaches to maintain ovarian function are urgently needed. Given the role of reduced nicotinamide adenine dinucleotide phosphate (NADPH) as an essential cofactor for drug detoxification, we sought to test whether boosting the NAD(P)+ metabolome could protect ovarian function. We show that pharmacological or transgenic strategies to replenish the NAD+ metabolome ameliorates chemotherapy induced female infertility in mice, as measured by oocyte yield, follicle health, and functional breeding trials. Importantly, treatment of a triple-negative breast cancer mouse model with the NAD+ precursor nicotinamide mononucleotide (NMN) reduced tumour growth and did not impair the efficacy of chemotherapy drugs in vivo or in diverse cancer cell lines. Overall, these findings raise the possibility that NAD+ precursors could be a non-invasive strategy for maintaining ovarian function in cancer patients, with potential benefits in cancer therapy.

Abstract Background In recent years, Iran has witnessed a remarkable increase in the incidence of cancer. This has led to an emerging challenge in the field of oncofertility, which seeks to address the impact of cancer treatments on fertility and endeavors to preserve reproduction. The study assessed healthcare providers’ awareness, attitudes, and practices regarding fertility preservation (FP) in Iran. Methods A cross-sectional study was conducted to assess healthcare providers’ knowledge, attitudes, and practices regarding oncofertility. An online self-made oncofertility survey of twenty-four items was administered to randomly selected participants from a list of healthcare providers registered with the Medical Council. The data were collected anonymously via Google Forms. Descriptive statistics, including number (n), prevalence (%), mean, and standard deviation, were calculated using SPSS 26.0. Additionally, chi-square tests were used to examine associations between categorical variables. Participants were categorized into oncology, obstetrics and gynecology (OB/GYN), and other specialties. Results A total of 423 responses were received and analyzed. Approximately 60% of the participants were obstetrics and gynecology subspecialists, while the remaining participants represented various disciplines such as surgery (9.7%), radiotherapy (6.4%), nuclear medicine (5.2%), and pediatrics (1.4%). More than 30% of the participants had not received any specific education about oncofertility, and more than 20% stated that FP strategies are not part of their routine treatment plan for young cancer patients. Oncologists had more education than those in the Obstetrics & Gynecology group. Half the participants were unaware of insurance coverage, and FP options were infrequently recommended. Conclusions These findings highlight the urgent need to enhance healthcare workers’ knowledge and attitudes toward FP in Iran and enable them to provide comprehensive support and guidance to cancer patients.

Anticancer treatments have significantly contributed to increasing cure rates of breast cancer in the last years; however, they can also lead to short- and long-term side effects, including gonadotoxicity, and compromised fertility in young women. Oncofertility is a crucial issue for young patients who have not yet completed their family planning at the time of cancer diagnosis. This review aims to cover all the latest available evidence in the field of oncofertility, including the gonadotoxicity of currently adopted anticancer therapies in the curative breast cancer setting, the available strategies for fertility preservation and the feasibility of achieving a pregnancy following anticancer treatment completion. Over the past years, a significant progress has been made in oncofertility care for young women with breast cancer. In the context of the currently available evidence, every young woman with newly diagnosed breast cancer should receive a proper and complete oncofertility counseling before starting any anticancer treatment to increase her chances of future pregnancies. [ABSTRACT FROM AUTHOR]

Purpose of Review: Many breast cancer treatments are gonadotoxic, which can result in infertility in survivors. Patients should be counseled on the impact of cancer treatment on future fertility and their options regarding fertility preservation. The main purpose of this narrative review is to discuss the implications of breast cancer treatment on future fertility and review various strategies for fertility preservation and their safety in this population. Recent Findings: There is no demonstrated effect of ovarian stimulation, GnRH agonist therapy, or ovarian tissue cryopreservation/transplantation on breast cancer outcomes. In regard to oocyte/embryo cryopreservation, women should be counseled on equivalent fertilization and pregnancy outcomes with frozen and fresh oocytes/embryos. To prevent delaying the start of neoadjuvant chemotherapy, "random start" protocols can be used and are equally effective as conventional protocols. After breast cancer treatment, women should be counseled on equivalent disease outcomes for those who become pregnant vs. those who do not, including those who interrupt adjuvant endocrine therapy to carry pregnancies. Summary: Fertility preservation should be discussed and offered to reproductive-aged patients with breast cancer, which has demonstrated safety in this population. [ABSTRACT FROM AUTHOR]

Background: In recent years, Iran has witnessed a remarkable increase in the incidence of cancer. This has led to an emerging challenge in the field of oncofertility, which seeks to address the impact of cancer treatments on fertility and endeavors to preserve reproduction. The study assessed healthcare providers' awareness, attitudes, and practices regarding fertility preservation (FP) in Iran. Methods: A cross-sectional study was conducted to assess healthcare providers' knowledge, attitudes, and practices regarding oncofertility. An online self-made oncofertility survey of twenty-four items was administered to randomly selected participants from a list of healthcare providers registered with the Medical Council. The data were collected anonymously via Google Forms. Descriptive statistics, including number (n), prevalence (%), mean, and standard deviation, were calculated using SPSS 26.0. Additionally, chi-square tests were used to examine associations between categorical variables. Participants were categorized into oncology, obstetrics and gynecology (OB/GYN), and other specialties. Results: A total of 423 responses were received and analyzed. Approximately 60% of the participants were obstetrics and gynecology subspecialists, while the remaining participants represented various disciplines such as surgery (9.7%), radiotherapy (6.4%), nuclear medicine (5.2%), and pediatrics (1.4%). More than 30% of the participants had not received any specific education about oncofertility, and more than 20% stated that FP strategies are not part of their routine treatment plan for young cancer patients. Oncologists had more education than those in the Obstetrics & Gynecology group. Half the participants were unaware of insurance coverage, and FP options were infrequently recommended. Conclusions: These findings highlight the urgent need to enhance healthcare workers' knowledge and attitudes toward FP in Iran and enable them to provide comprehensive support and guidance to cancer patients. [ABSTRACT FROM AUTHOR]

Background/Objective: Fertility preservation is an important part of oncologic care for newly diagnosed gynecologic cancers for reproductive-age women, as many treatment options negatively impact fertility. The goal of this study is to examine factors that influence access to fertility specialists for women with newly diagnosed gynecologic cancer. Methods: This institutional review board approved a retrospective cohort study investigating the impacting factors on the referral rate from gynecologic oncologists (GO) to reproductive endocrinologists and infertility (REI) specialists at a single academic institution between 2010–2022 for patients age 18–41 at diagnosis. Electronic medical records were used to identify demographics and referral patterns. Mixed logistic models were utilized to control cluster effects of the physicians. Results: Of 816 patients reviewed, 410 met the criteria for inclusion. The referral rate for newly diagnosed gynecologic malignancies was 14.6%. Younger patients were more likely to have an REI referral (p < 0.001). The median time from first GO visit to treatment was 18.5 days, and there was no significant difference in those who had REI referrals (p = 0.44). Only 45.6% of patients had fertility desire documented. A total of 42.7% had fertility-sparing treatment offered by a GO. REI referral did not significantly change the time to treatment (p = 0.44). An REI referral was more likely to be placed if that patient had no living children, no past medical history, or if the referring GO was female (OR = 11.46, 6.69, and 3.8, respectively). Conclusions: Fertility preservation counseling is a critical part of comprehensive cancer care; yet, the referral to fertility services remains underutilized in patients with newly diagnosed gynecologic cancer. By demonstrating these biases in REI referral patterns, we can optimize provider education to enhance fertility care coordination. [ABSTRACT FROM AUTHOR]

Oncofertility is a growing medical and research field that includes two main areas: oncology and reproductive medicine. Nowadays, the percentage of patients surviving cancer has exponentially increased, leading to the need for intervention for fertility preservation in both men and women. Specifically, gynecological malignancies in women pose an additional layer of complexity due to the reproductive organs being affected. In the present review, we report fertility preservation options with a cancer- and stage-specific focus. We explore the drawbacks and the necessity for planning fertility preservation applications during emergency statuses (i.e., the COVID-19 pandemic) and comment on the importance of repro-counseling for multifaceted patients during their oncological and reproductive journey. [ABSTRACT FROM AUTHOR]

Purpose:Although fertility preservation for patients with childhood and adolescent cancer is considered standard of care in the high-resource settings, it is rarely offered in low-resource settings. This study explores the experiences and perspectives of oncology health care professionals in Uganda to identify contextual barriers and facilitators to addressing oncofertility in low-resource settings. Methods: Using ground theory, we conducted in-depth face-to-face interviews of health care professionals managing pediatric patients at the Uganda Cancer Institute (UCI). Using a systematic, semi-structured interview guide, participants were asked open-ended questions about their understanding of fertility preservation and their perspectives on implementing this care at their institution. Although all the eligible health care providers were interviewed, interview transcripts were uploaded into NVivo version 12 and openly coded as per theoretical requirements. Codes were refined into categories and later into structured themes. Results: Twelve health care professionals were interviewed. Most participants identified as female (n = 9). Their role in the medical team varied from nurses (n = 6), medical officers (n = 3), pediatric oncologists (n = 2), and pediatric oncology fellow (n = 1). Six themes were noted as follows: (1) importance of information, (2) importance of future fertility, (3) inadequate consideration to future fertility, (4) communication barriers, (5) inadequate knowledge, and (6) resource barriers. Conclusion: Although health care providers at the UCI face contextual barriers to addressing future fertility among patients with pediatric cancer, they value preserving fertility in this population. Future initiatives that aim to introduce oncofertility care in low-resource settings should prioritize educating providers and building capacity to meet the oncofertility needs in this setting. [ABSTRACT FROM AUTHOR]

Purpose: We sought to evaluate physicians' baseline knowledge of fertility preservation services available to patients with a cancer diagnosis within the military health system (MHS). Methods: Data on current cancer prevalence of over 31,000 unique cancer diagnoses were obtained from a comprehensive nationwide MHS dataset. Additionally, a 22-item survey was distributed to physicians practicing within the MHS assessing knowledge of reproductive health benefits, oncofertility counseling practices, and subspecialist referral patterns. Results: From 2020 to 2022, there were 31,103 individuals of reproductive age with cancer receiving care at a military treatment facility. One hundred fourteen physicians completed our survey, 76 obstetrician gynecologists (OB/GYNs), 18 oncologists, and 20 primary care physicians (PCPs). Ninety-three percent of respondents felt conversations about fertility preservation for reproductive-aged patients with cancer were very important. A total of 66.7% of oncologists, 35.5% of OB/GYNs, and 0% of PCPs felt comfortable counseling patients on coverage. A total of 33.3% of oncologists, 29.3% of OB/GYNs, and 0% of PCPs were familiar with oncofertility Defense Health Agency guidelines. Conclusion: Primary care, OB/GYN, and oncology practitioners are well situated to provide fertility preservation counseling to all individuals with a cancer diagnosis, but differences in counseling and referral patterns and a lack of knowledge of current agency policies may impair a patient's timely access to these resources. We propose implementation of an electronic patient navigator to address gaps in oncofertility care and standardize patient counseling in the MHS. This patient-focused guide would serve as a valuable model in all types of health care settings. [ABSTRACT FROM AUTHOR]

Purpose: Assessing patient and guardian experiences regarding their history of ovarian tissue cryopreservation (OTC) years after initial procedure. Methods: Cross-sectional follow-up telephone survey. A questionnaire developed by The Pediatric Initiative Network of the Oncofertility Consortium, modified to assess intent and attitudes regarding OTC, tissue access knowledge, financial burden of tissue storage, and intent to use tissue, was utilized. Interviews were conducted for those who underwent OTC at a metropolitan children's hospital between 2013 and 2022. Results: Of 60 eligible patients, 39 interviews were completed. Contacted patients were 3–28 years old, with minors accompanied by guardians. Average age at OTC was 8.5 years old, and 5.1% (2/39) were deceased at the time of contact. All interviewees underwent OTC for fertility preservation before gonadotoxic treatment. Seventy percent of patients (7/10) and 48.1% (13/27) of guardians stated they would use frozen tissue for pregnancy, with 50% (5/10) of patients and 59.3% (16/27) of guardians not understanding tissue access. Regret occurred in 10% (1/10) of patients and 3.4% (1/29) of guardians. It was associated with 10.8% (4/37) of tissue discard due to failed storage payments. Financial concerns occurred in 29.7% (11/37) of interviewees. Overall, 92.3% (36/39) would recommend OTC, and 94.9% (37/39) would repeat their choice to undergo OTC. Conclusion: Follow-up after OTC is essential to patient understanding of tissue status, access, and payments. Most do not regret OTC, except in cases of financial burden leading to tissue discard. Follow-up should be sequentially scheduled and include counseling on financial assistance programs. [ABSTRACT FROM AUTHOR]

Female survivors of young adult (YA) cancers are at risk of fertility impacts following cancer treatment. For these women, fertility-related distress is both prevalent and persistent. Yet there is little research regarding survivors' perspectives on alternative family-building options, particularly adoption. This exploratory secondary data analysis analyzed semistructured interviews and explored survivors' views of adoption. Overall, female YA survivors reported openness to adoption as a possible substitute for biological conception and an alternative to fertility preservation. It is imperative that this population receives support in decision-making around and consideration of the unique barriers to adoption for cancer survivors. [ABSTRACT FROM AUTHOR]

Purpose: Oncology clinicians are appropriately positioned to facilitate discussions of assisted reproductive technologies including preimplantation genetic testing for monogenic disease (PGT-M), in the context of cancer treatment or surveillance. Yet, reproductive services, including PGT-M, remain one of the least implemented services in oncology. No studies to date have explored which practice resources the clinicians need to increase knowledge of PGT-M. The objective of this study was to explore the specific needs of oncology clinicians to help maximize the reproductive potential of young adult patients with hereditary cancers. Methods: Participants were recruited through notices circulated on social media platforms and snowball sampling. Participants completed a brief online survey to confirm eligibility. Eligible participants completed a virtual, semi-structured interview. Interviews focused on clinician experiences with PGT-M and initiating referrals to fertility specialists. Thematic analysis was conducted using a constant comparative approach to identify current clinical practices. Results: This study found that PGT-M discussions are not necessarily within the scope of responsibilities for oncology clinicians owing to prioritization of cancer treatment and overall lack of knowledge. Participants need accessible resources and timely support for reproductive planning in the context of cancer treatment. Participants desire a streamlined referral pathway to professionals trained in oncofertility to help address their patient's reproductive needs. Conclusion: Our study identified that educational and referral resources to reproductive specialists are needed to maximize reproductive potential across the cancer continuum. These findings provide a foundation for larger studies that can inform standard-of-care recommendations in the emerging field of oncofertility. [ABSTRACT FROM AUTHOR]

Simple Summary: Healthcare professionals recognise the importance of fertility preservation and their responsibility to initiate discussions. However, despite advanced training within respective fields, discrepancies in knowledge remain regarding techniques of fertility preservation, referral pathways and existing educational resources available to patients, preventing efficient implementation of services. Further education and training regarding the methods of fertility preservation and how to refer patients to specialist services are required. Many of the personal barriers faced by healthcare professionals could be overcome through regular teaching on communication skills used for breaking bad news. (1) Background: This study aims to establish the knowledge, attitudes and current behaviours towards female fertility preservation (FP) services amongst healthcare professionals (HCPs) in the UK. (2) Methods: An online survey was advertised publicly on the social media platform Instagram between 25 February 2021 and 11 March 2021. (3) Results: In total, 415 participants fulfilled the inclusion criteria and completed the survey. The majority of HCPs discussed FP techniques either never 39.5% (n = 164), once a year 20.7% (n = 86) or once a month 17.8% (n = 74). The majority rated their knowledge of each type of FP method as 'very poor' or 'poor' and strongly disagreed 14.2% (n = 59) or disagreed 42.2% (n = 175) with the statement they 'felt confident to counsel a patient on FP'. The majority either agreed 37.8% (n = 157) or strongly agreed 22.2% (n = 92) that it was their responsibility to discuss FP and 38.1% (n = 158) agreed or strongly agreed 19.5% (n = 81) they considered the desire for future fertility when planning treatment. The majority 87.2% (n = 362) had not experienced formal training on FP. (4) Conclusions: Discrepancies in knowledge remain regarding techniques of FP, referral pathways, awareness of facilities offering services and existing educational resources. Many HCPs recognise the importance of FP and their responsibility to initiate discussions. The knowledge that FP may not delay the treatment of cancer has also improved; however, training in FP is scarce. [ABSTRACT FROM AUTHOR]

Introduction: This study aims to explore the opinions of female cancer patients regarding the donation of cancer and reproductive cells for reproductive and research purposes. Material and methods: The study involved 373 female cancer patients from 2 hospitals with oncology departments in Poznan, Poland. They completed a pen-and-paper questionnaire-based survey. Results: While most female cancer patients declared their willingness to donate cancer tissues for fertility research (87.9%), they were reluctant to share their reproductive cells for research purposes (82.3%). Additionally, 88.2% of respondents were unwilling to donate embryos that remain after in vitro treatment for research purposes. Simultaneously, 57.1% of woman supported the preservation of fertility cells, 62.5% believed it should be ethically and legally regulated in Poland, and 74% believed it should be re-imbursed by the National Health Fund. Women's opinions were linked to their age, education, place of residence, family status, and declared religiosity. Conclusions: Because most female cancer patients expressed their willingness to share their reproductive cells for reproductive purposes and believed that the preservation of cells for fertility purposes should be reimbursed by the State, there is a need for doctors and nurses to inform patients about the available ways to preserve fertility. However, because donation of reproductive cells for biomedical research raises many concerns, healthcare professionals should be trained to discuss with patients the ethical and legal issues related to fertility preservation and biomedical research involving reproductive cells. [ABSTRACT FROM AUTHOR]

Simple Summary: Gonadal tissue transplantation as a fertility preservation technique is highly conditioned by our current knowledge of functionality following transplantation, tissue cryodamage, and ischemia–reperfusion injury. This paper presents an updated review of the literature on mitochondrial dysfunction and oxidative stress in the context of gonadal tissue cryopreservation and transplantation. Advances in tissue preservation techniques have allowed reproductive medicine and assisted reproductive technologies (ARTs) to flourish in recent years. Because radio- and chemotherapy procedures are often gonadotoxic, irreversible damage can preclude future gamete production and endocrine support. Accordingly, in recent years, the freezing and storage of gonadal tissue fragments prior to the first oncological treatment appointment and autologous transplantation post-recovery have been considered improved solutions for fertility recovery in cancer survivors. Nevertheless, the cryopreservation and transplantation of thawed tissues is still very limited, and positive outcomes are relatively low. This review aims to discuss the limitations of oncofertility protocols with a focus on the impacts of mitochondrial dysfunction, oxidative stress, and the loss of antioxidant defense in graft integrity. [ABSTRACT FROM AUTHOR]

Few studies have examined the distinct reproductive concerns (RC) of men and women in the adolescent and young adult (AYA) cancer patient population. The purpose of this mixed-methods study was to explore and differentiate the RC of AYAs. Participants completed the Reproductive Concerns After Cancer (RCAC) scale and participated in a semistructured interview. Interviews were deductively coded based on an analytic schema derived from the RCAC. After identifying participants through the electronic health record, 27 younger AYAs, ages 12–25, enrolled in the study. Four inductive themes emerged and differed by gender. These include differential temporality, acceptance, and openness to alternatives, partner influence, and parental/guardian influence. AYA men reported fewer RC (M = 49.4, SD = 9.6) compared to AYA women (M = 56.8, SD = 8.4). Oncofertility care providers are advised to account for short- and long-ranging concerns based on AYAs' gender. Future evaluations of patient-reported outcome measures specific to AYA RC are recommended. [ABSTRACT FROM AUTHOR]

A great deal of work has been carried out by professionals in reproductive medicine in order to raise awareness about fertility preservation (FP) techniques, particularly for women, and to ensure that FP is included in the care of young adults treated for cancer or a pathology requiring gonadotoxic treatment. If the importance of the development of our discipline is obvious, our militancy in favour of FP and our emotional projections must not make us forget that medical thinking must be carried out not only on a case-by-case basis, weighing up the benefit-risk balance, but also without losing sight that conceiving a child with one's own gametes is not a vital issue. The cultural importance given to the genetic link with offspring may bias patients' and physicians' decisions, while other ways of achieving parenthood exist, and are often more effective. Systematic information should be provided on the existence of FP techniques, but this should not lead to their systematic implementation, nor should it obscure that early information will also allow patients to begin projecting themselves in alternative options to become parents. [ABSTRACT FROM AUTHOR]

Certain chemotherapy agents, radiation, and surgery can all negatively impact future fertility. Consults regarding treatment-related risk for infertility and gonadal late effects of these agents should occur at the time of diagnosis as well as during survivorship. Counseling on fertility risk has traditionally varied significantly across providers and institutions. We aim to provide a guide to standardize the assignment of gonadotoxic risk, which can be used in counseling patients both at the time of diagnosis and in survivorship. Gonadotoxic therapies were abstracted from 26 frontline Childrens Oncology Group (COG) phase III protocols for leukemia/lymphoma, in use from 2000-2022. A stratification system based on gonadotoxic therapies, sex, and pubertal status was used to assign treatments into minimal, significant, and high level of increased risk for gonadal dysfunction/infertility. Risk levels were assigned to protocols and different treatment arms to aid oncologists and survivor care providers in counseling patients regarding treatment-related gonadotoxicity. Males were most commonly at high risk, with at least one high-risk arm in 14/26 protocols (54%), followed by pubertal females (23% of protocols) and prepubertal females (15% of protocols). All patients who received direct gonadal radiation or hematopoietic stem cell transplant (HSCT) were considered at high risk. Partnering with patients and their oncology/survivorship team is imperative for effective fertility counseling both prior to and post treatment, and this comprehensive guide can be used as a tool to standardize and improve reproductive health counseling in patients undergoing COG-based leukemia/lymphoma care.

Purpose: Oncofertility care for pediatric, adolescent, and young adult cancer patients remains under-implemented across adult and pediatric oncology settings. We pilot tested an electronic health record (EHR)-enabled multicomponent oncofertility intervention (including screening, referral, and fertility consult) in an adult academic oncology program and systematically assessed intervention fit to pediatric and community oncology programs. Methods: Using surveys (n = 33), audits (n = 143), and interviews (n = 21) guided by implementation science frameworks, we pilot tested the EHR-enabled intervention for oncofertility care in young cancer patients at an adult oncology program and evaluated implementation outcomes. We interviewed health care providers from seven regional oncology and fertility programs about intervention fit to their clinical contexts. Results: We recruited 33 health care providers from an adult oncology setting and 15 health care providers from seven additional oncology and fertility settings. At the adult oncology setting, the intervention was found to be appropriate, acceptable, and feasible and improved the screening of fertility needs (from 30% pre- to 51% post-intervention); yet, some patients did not receive appropriate referrals to fertility consults. Providers across all settings suggested content and context modifications, such as adding options to the intervention or allowing the screening component to pop up at a second visit, to improve and adapt the intervention to better fit their clinical care contexts. Conclusions: We found that the EHR-enabled intervention increased the rate of goal-concordant oncofertility care delivery at an adult oncology program. We also identified facilitators, barriers, and needed adaptations to the intervention required for implementation and scaling-up across diverse oncology settings.

Approximately 10% to 15% of breast cancer cases in young women are diagnosed in patients harbouring germline (g) pathogenic or likely pathogenic variants (PVs) in the BReast CAncer 1 (BRCA1) or BReast CAncer 2 (BRCA2) genes. Preclinical and clinical studies showed a potential negative effect of germline BRCA 1/2 (g BRCA1/2) PVs on ovarian reserve and reproductive potential, even before starting anticancer therapies. The aim of this article is to summarize the current literature on the fertility potential of young g BRCA1/2 PVs carriers with breast cancer and the risk of gonadotoxicity associated with anticancer treatments. Moreover, we describe the available evidence on the efficacy of fertility preservation techniques in young g BRCA1/2 PVs carriers and the safety data on having a pregnancy after breast cancer treatment. [ABSTRACT FROM AUTHOR]

Recommendations from the Children's Oncology Group Long-Term Follow-Up (COG-LTFU) Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancer emphasize the importance of reproductive health care, yet little is known regarding adherence to these recommendations and non-fertility-related sexual and reproductive health (SRH) outcomes. Follow-up of outcomes on the basis of the COG-LTFU guidelines was assessed in female patients who underwent fertility preservation consultation before gonadotoxic therapy between 2016 and 2022 at a single institution and were at least 6 months from treatment completion. We included 140 patients, with a mean time of 2.7 years from treatment completion. Eighty-six patients were 12 years old or older, of whom sexual activity was recorded in 59 (68.7%), and 12 of 31 (38.7%) sexually active patients underwent sexual function assessment. The 57 (66.3%) patients at high risk of premature ovarian insufficiency (POI) at diagnosis were more likely than minimal-risk counterparts (29, 33.7%) to have abnormal uterine bleeding (42.1% vs 17.2%, P =.03), to be diagnosed with POI (29.8% vs 0%, P =.01), and to have sexual activity recorded (77.2% vs 51.7%, P =.03). Of 17 patients with POI, 82.4% were on hormone replacement therapy, and 58.8% had undergone bone mineral density testing. This study adds to the limited literature regarding non-fertility-related SRH outcomes after gonadotoxic therapy and illustrates opportunities to improve adherence to the COG-LTFU guidelines. Increased attention to SRH guidelines may increase detection and treatment of SRH conditions, improving the health and quality of life of female cancer survivors. [ABSTRACT FROM AUTHOR]

Purpose: To examine the impact of financial costs on fertility preservation decisions among female young adults (YAs) with cancer. Methods: Female YAs (N = 18; aged 21–36) with a history of cancer and oncology providers (N = 12) were recruited from an National Cancer Institute-designated comprehensive cancer center in a state without insurance coverage for fertility preservation. YAs and providers completed individual interviews and a brief online assessment. Qualitative description using thematic analysis was used to identify, analyze, and report common themes. Descriptive statistics was used to characterize the sample. Results: Female YAs and oncology providers highlighted the critical role that high out-of-pocket costs play in YAs' fertility preservation decisions along with the value that enhanced insurance coverage for fertility preservation would have for increasing female YAs' access to and utilization of fertility preservation. Although providers were concerned about preservation costs for their patients, they reported that their concerns did not impact whether they referred interested female YAs to reproductive specialists. Oncology providers expressed concern about inequities in utilization of fertility preservation for female and racially/ethnically minoritized YAs that were exacerbated by the high out-of-pocket fertility preservation costs. Conclusion: Cost is a significant barrier to fertility preservation for female YA cancer patients. Female YAs of reproductive age may benefit from decision support tools to assist with balancing the cost of fertility preservation with their values and family building goals. Policy-relevant interventions may mitigate cost barriers and improve access to care. [ABSTRACT FROM AUTHOR]

Purpose: To investigate factors that obstruct and facilitate the use of the foster parent and special adoption systems (i.e., foster systems) by cancer survivors, and examine how to effectively provide information. Methods: This was a cross-sectional study that compared the results of a questionnaire survey of foster parents and adoptive parents (i.e., foster parents) who were and were not cancer survivors belonging to foster parent associations in 33 locations in Japan. This study was supported by a 2022 Ministry of Health, Labor, and Welfare Grant-in-Aid for Scientific Research (Grant No. 20EA1004). Results: "Lack of information," an obstructive factor and "Sympathetic understanding and cooperation from my partner and family," a facilitative factor were the highest score in both groups. Significant differences between the two groups were found in "Support from government agencies and others for foster parents," a facilitative factor, which was lower in the cancer survivors' group. There were no other significant differences between both the groups. Conclusion: This study found that when considering the use of the foster systems, a lack of information was the biggest obstructive factor and family understanding was the most helpful for both cancer survivors and noncancer groups. It was thought that stronger government support for cancer survivors might encourage cancer survivors to consider becoming foster parents. It would be effective for cancer treatment facilities, reproductive medical facilities, the government, and foster parent associations to work together to provide information carefully to cancer survivors. [ABSTRACT FROM AUTHOR]

To report pregnancy and live birth resulting from intracytoplasmic sperm injection of ex vivo-retrieved mature oocytes from a woman with bilateral ovarian carcinoma. Case report. Fertility clinic. A 34-year-old nulliparous woman with bilateral ovarian tumor, with a risk of malignancy of 96.1% according to International Ovarian Tumor Analysis Group recommendations for adnexal tumors, who desired fertility preservation before definitive surgical treatment. Cryopreservation of ex vivo-retrieved mature metaphase II oocytes is followed by fertilization with donor sperm and embryo transfer to a gestational carrier. Fertility preservation. After controlled ovarian stimulation, 12 metaphase II oocytes were retrieved from oophorectomized specimens and vitrified. Intracytoplasmic sperm injection with donor sperm was performed in remission, resulting in 9 cleavage-stage embryos, 2 of which were transferred to a gestational carrier, resulting in a normal, healthy singleton pregnancy, and the live birth of a healthy infant. Ex vivo oocyte retrieval after oophorectomy may be a safe alternative to standard oocyte retrieval for fertility preservation in women with ovarian malignancies. [ABSTRACT FROM AUTHOR]

Purpose of Review: Young patients with breast cancer have unique survivorship needs, including fertility and family planning concerns, complications from iatrogenic menopause, and long-term quality-of-life issues. We aim to summarize the latest data on these side effects of cancer care to guide physicians in providing evidence-based survivorship care for this unique group of patients. Recent Findings: Fertility preservation is safe prior to cancer treatment without any adverse impact on disease-free recurrence or overall survival. Pregnancy after breast cancer can be achieved safely; preliminary data from the POSITIVE trial suggest that endocrine therapy can be safely paused to allow for conception prior to age-related declines in fertility. Summary: Additional research will help us understand controversial topics in survivorship care for young breast cancer patients including safe and effective contraception, use of vaginal estrogen for severe genitourinary syndrome of menopause and pausing anti-estrogen therapy to allow for safe conception, pregnancy, and post-partum care. [ABSTRACT FROM AUTHOR]

The last 20 years have seen substantial improvements in fertility and hormone preservation and restoration technologies for a growing number of cancer survivors. However, further advancements are required to fill the gaps for those who cannot use current technologies or to improve the efficacy and longevity of current fertility and hormone restoration technologies. Ovarian tissue cryopreservation (OTC) followed by ovarian tissue transplantation (OTT) offers those unable to undergo ovarian stimulation for egg retrieval and cryopreservation an option that restores both fertility and hormone function. However, those with metastatic disease in their ovaries are unable to transplant this tissue. Therefore, new technologies to produce good-quality eggs and restore long-term cyclic ovarian function are being investigated and developed to expand options for a variety of patients. This mini-review describes current and near future technologies including in vitro maturation, in vitro follicle growth and maturation, bioprosthetic ovaries, and stem cell applications in fertility restoration research by their proximity to clinical application. [ABSTRACT FROM AUTHOR]

Simple Summary: The number of oncological patients of prepubertal and reproductive age is increasing steeply worldwide. Not only have medical innovations and scientific advances over the last few decades enabled more and more patients to survive, but also, they have revolutionised the processes of preserving and restoring fertility. However, not every fertility preservation method is optimal and appropriate after specific oncological treatment, and some of them remain experimental. Therefore, there is a constant need to develop and improve the field of oncofertility. Additionally, governments should facilitate access to fertility preservation programmes for oncological patients and should look after their psychological needs as well. The number of children, adolescents and young adults diagnosed with cancer has been rising recently. Various oncological treatments have a detrimental effect on female fertility, and childbearing becomes a major issue during surveillance after recovery. This review discusses the impact of oncological treatments on the ovarian reserve with a thorough explanation of oncologic treatments' effects and modes of oncofertility procedures. The aim of this review is to help clinicians in making an informed decision about post-treatment fertility in their patients. Ultimately, it may lead to improved overall long-term outcomes among young populations suffering from cancer. [ABSTRACT FROM AUTHOR]

BRCA1 and BRCA2 mutations are responsible for a higher incidence of breast and ovarian cancer (from 55% up to 70% vs. 12% in the general population). If their functions have been widely investigated in the onset of these malignancies, still little is known about their role in fertility impairment. Cancer patients treated with antineoplastic drugs can be susceptible to their gonadotoxicity and, in women, some of them can induce apoptotic program in premature ovarian follicles, progressive depletion of ovarian reserve and, consequently, cancer treatment-related infertility (CTRI). BRCA variants seem to be associated with early infertility, thus accelerating treatment impairment of ovaries and making women face the concrete possibility of an early pregnancy. In this regard, fertility preservation (FP) procedures should be discussed in oncofertility counseling—from the first line of prevention with risk-reducing salpingo-oophorectomy (RRSO) to the new experimental ovarian stem cells (OSCs) model as a new way to obtain in vitro-differentiated oocytes, several techniques may represent a valid option to BRCA-mutated patients. In this review, we revisit knowledge about BRCA involvement in lower fertility, pregnancy feasibility, and the fertility preservation (FP) options available. [ABSTRACT FROM AUTHOR]

Purpose: Despite the increasing number of childhood cancer survivors, significant advances in ovarian tissue cryopreservation (OTC) technique and medical societies' recommendations, fertility preservation (FP) and FP discussions are not always offered as a standard of care in the pediatric context. The aim of this literature review is to understand what ethical, legal, social, and policy issues may influence the provision of FP by OTC in prepubertal girls with cancer. Methods: A critical interpretive review of peer-reviewed papers published between 2000 and January 2023 was conducted, guided by the McDougall's version of the critical interpretive synthesis (Dixon-Woods), to capture recurring concepts, principles, and arguments regarding FP by OTC for prepubertal girls. Results: Of 931 potentially relevant papers, 162 were included in our analysis. Data were grouped into seven thematic categories: (1) risks of the procedure, (2) unique decision-making issues in pediatric oncofertility, (3) counseling, (4) cultural and cost issues, and (5) disposition of cryopreserved reproductive tissue. Conclusion: This first literature review focusing on ethical, legal, social, and policy issues surrounding OTC in prepubertal girls highlights concerns in the oncofertility debate. Although OTC is no longer experimental as of December 2019, these issues could limit its availability and the child's future reproductive autonomy. This review concludes that specific actions must be provided to enable the offer of FP, such as supporting families' decision-making in this unique and complex context, and providing pediatric patients universal and full access to free or highly subsidized OTC. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to examine the association between fertility issues and demographic characteristics of unmarried adolescent and young adult cancer survivors. Methods: We conducted a survey among cancer survivors who were 15–39 years old and unmarried at the time of cancer diagnosis and 20–45 years old at the time of the survey. Views on fertility issues, originally developed based on the results of a qualitative study conducted with the same inclusion criteria, were used to assess thoughts and feelings regarding fertility issues. Results: Through exploratory factor analysis of the 128 respondents who either had children or desired children, two factors related to fertility issues were identified: "anxiety related to the possibility of not being able to have children" and "pressure from others to have children." Multiple regression analysis was performed to examine the association between these factors and demographic characteristics. The analysis revealed that being male and having a partner were significant predictors for both factors for views on fertility issues. Additionally, younger age at the time of diagnosis was a significant predictor for the first factor. Conclusions: Greater fertility issues among unmarried cancer survivors were associated with younger age at diagnosis, having a partner, and being male. Surprisingly, contrary to previous findings, male cancer survivors experienced more significant fertility problems than women. This result may be attributed to the well-established gender roles in Japan, where men are predominantly considered the heirs and inheritors of the family. [ABSTRACT FROM AUTHOR]

To establish the safety and quality of ovarian cortex surrounding epithelial ovarian tumors in women eligible for fertility-sparing surgery by identifying occult malignant lesions and characterizing the ovarian follicle pool. Multicentric retrospective study of 48 subjects (15–45 years), diagnosed with borderline ovarian tumors (BOTs) or early-stage epithelial ovarian cancers (EOCs) and eligible for fertility-sparing surgery. Histological samples of ovarian cortex surrounding tumors were analyzed to characterize the follicle pool, find any occult malignant lesion using tumor-specific markers (cytokeratin 7 and mucin 1), and quantify tumor-infiltrating lymphocytes (TILs) by CD3 and tumor associated macrophages (TAMs) by CD68. Occult ovarian lesions were observed in 6 out of 45 cases investigated (14.6%), including one mucinous stage-I BOT (1/14), one serous stage-I BOT (1/13), 3 advanced-stage serous BOTs (3/11) and one early-stage serous EOC (1/7). Notably, follicle density was significantly lower in subjects diagnosed with ovarian tumors compared to controls (p < 0.001) and at a younger age. Significantly higher follicle atresia was encountered in the ovarian tumor group then in controls (20.1 ± 8.8% vs 9.2 ± 9.4%, p < 0.001) at all ages. Both TILs and TAMs were found in ovarian tumors irrespective of histotype, but no link was established with the status of the ovarian reserve. Personalized counseling for fertility preservation is required in the event of BOTs and early-stage EOCs. Fertility-sparing surgery and adjuvant gamete preservation should be considered, balancing the oncological risks according to tumor stage and histotype and fertility potential, especially at a younger age. • Epithelial ovarian tumors negatively affect the surrounding ovarian follicle pool by increasing follicle atresia. • The ovarian reserve is significantly impacted by ovarian lesions in the youngest patients. • Stage-I BOTs are at intermediate risk of occult lesions within healthy-looking ovarian cortex. • The oncological risk is as high as 27% in case of serous BOTs displaying pelvic implants. • Endometrioid ovarian tumors show low-risk oncological profile. [ABSTRACT FROM AUTHOR]

To examine whether female cancer survivors are more likely to pursue care for infertility after cancer than women without cancer. Population-based cohort study involving detailed interviews regarding reproductive history. Not applicable. Female cancer survivors aged 22–45 years, who were at least 2 years after a cancer diagnosis between the ages of 20 and 35 years (n = 1,036), and age-matched comparison women with no cancer history (n = 1,026). History of cancer vs. no history of cancer. Each cancer survivor was randomly matched to a comparison woman, who was assigned an artificial age at cancer diagnosis equal to that of her match. Matching was repeated 1,000 times. Outcomes of visiting a doctor for help becoming pregnant or undergoing fertility treatment were modeled using Cox proportional hazards regression, comparing survivors after a cancer diagnosis to age-matched comparison women, adjusted for race, income, residence, education, and parity. Only 25.5% of cancer survivors reported meeting their desired family size before a cancer diagnosis. The median time from diagnosis to interview among survivors was 7 (interquartile range 5–11) years. Cancer survivors were more likely to report having no children (32.6%) at the interview compared with women with no cancer history (19.5%). Survivors were not more likely to visit a doctor for help becoming pregnant compared with women without a cancer history, matched on birth year and followed by the age at which cancer survivors received their diagnosis (hazard ratio [HR] 1.16, 95% simulation interval [SI] 0.78–1.74). Compared with cancer-free women, cancer survivors had similar probabilities of pursuing any treatment (adjusted HR [aHR] 0.88, 95% SI 0.46–1.56), using hormones or medications (aHR 0.86, 95% SI 0.46–1.63), or undergoing intrauterine insemination (aHR 1.26, 95% SI 0.40–5.88) to conceive. Cancer survivors were slightly more likely to pursue surgical interventions to become pregnant (HR 1.55, 95% SI 0.67–3.71). Of those who visited a doctor but declined to pursue fertility treatment, one-quarter of women reported declining treatment due to cost. Cancer survivors did not use fertility treatments at higher rates than the general population. Further counseling and education surrounding fertility options are recommended for young adult female cancer patients after treatment is completed. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Twenty years after the inception of the first fertility preservation programme for pre-pubertal boys, what are the current international practices with regard to cryopreservation of immature testicular tissue? SUMMARY ANSWER Worldwide, testicular tissue has been cryopreserved from over 3000 boys under the age of 18 years for a variety of malignant and non-malignant indications; there is variability in practices related to eligibility, clinical assessment, storage, and funding. WHAT IS KNOWN ALREADY For male patients receiving gonadotoxic treatment prior to puberty, testicular tissue cryopreservation may provide a method of fertility preservation. While this technique remains experimental, an increasing number of centres worldwide are cryopreserving immature testicular tissue and are approaching clinical application of methods to use this stored tissue to restore fertility. As such, standards for quality assurance and clinical care in preserving immature testicular tissue should be established. STUDY DESIGN, SIZE, DURATION A detailed survey was sent to 17 centres within the recently established ORCHID-NET consortium, which offer testicular tissue cryopreservation to patients under the age of 18 years. The study encompassed 60 questions and remained open from 1 July to 1 November 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS Of the 17 invited centres, 16 completed the survey, with representation from Europe, Australia, and the USA. Collectively, these centres have cryopreserved testicular tissue from patients under the age of 18 years. Data are presented using descriptive analysis. MAIN RESULTS AND THE ROLE OF CHANCE Since the establishment of the first formal fertility preservation programme for pre-pubertal males in 2002, these 16 centres have cryopreserved tissue from 3118 patients under the age of 18 years, with both malignant (60.4%) and non-malignant (39.6%) diagnoses. All centres perform unilateral biopsies, while 6/16 sometimes perform bilateral biopsies. When cryopreserving tissue, 9/16 centres preserve fragments sized ≤5 mm3 with the remainder preserving fragments sized 6–20 mm3. Dimethylsulphoxide is commonly used as a cryoprotectant, with medium supplements varying across centres. There are variations in funding source, storage duration, and follow-up practice. Research, with consent, is conducted on stored tissue in 13/16 centres. LIMITATIONS, REASONS FOR CAUTION While this is a multi-national study, it will not encompass every centre worldwide that is cryopreserving testicular tissue from males under 18 years of age. As such, it is likely that the actual number of patients is even higher than we report. Whilst the study is likely to reflect global practice overall, it will not provide a complete picture of practices in every centre. WIDER IMPLICATIONS OF THE FINDINGS Given the research advances, it is reasonable to suggest that cryopreserved immature testicular tissue will in the future be used clinically to restore fertility. The growing number of patients undergoing this procedure necessitates collaboration between centres to better harmonize clinical and research protocols evaluating tissue function and clinical outcomes in these patients. STUDY FUNDING/COMPETING INTEREST(S) K.D. is supported by a CRUK grant (C157/A25193). R.T.M. is supported by an UK Research and Innovation (UKRI) Future Leaders Fellowship (MR/S017151/1). The MRC Centre for Reproductive Health at the University of Edinburgh is supported by MRC (MR/N022556/1). C.L.M. is funded by Kika86 and ZonMW TAS 116003002. A.M.M.v.P. is supported by ZonMW TAS 116003002. E.G. was supported by the Research Program of the Research Foundation—Flanders (G.0109.18N), Kom op tegen Kanker, the Strategic Research Program (VUB_SRP89), and the Scientific Fund Willy Gepts. J.-B.S. is supported by the Swedish Childhood Cancer Foundation (TJ2020-0026). The work of NORDFERTIL is supported by the Swedish Childhood Cancer Foundation (PR2019-0123; PR2022-0115), the Swedish Research Council (2018-03094; 2021-02107), and the Birgitta and Carl-Axel Rydbeck's Research Grant for Paediatric Research (2020-00348; 2021-00073; 2022-00317; 2023-00353). C.E is supported by the Health Department of the Basque Government (Grants 2019111068 and 2022111067) and Inocente Inocente Foundation (FII22/001). M.P.R. is funded by a Medical Research Council Centre for Reproductive Health Grant No: MR/N022556/1. A.F. and N.R. received support from a French national research grant PHRC No. 2008/071/HP obtained by the French Institute of Cancer and the French Healthcare Organization. K.E.O. is funded by the University of Pittsburgh Medical Center and the US National Institutes of Health HD100197. V.B-L is supported by the French National Institute of Cancer (Grant Seq21-026). Y.J. is supported by the Royal Children's Hospital Foundation and a Medical Research Future Fund MRFAR000308. E.G. N.N. S.S. C.L.M. A.M.M.v.P. C.E. R.T.M. K.D. M.P.R. are members of COST Action CA20119 (ANDRONET) supported by COST (European Cooperation in Science and Technology). The Danish Child Cancer Foundation is also thanked for financial support (C.Y.A.). The authors declare no competing interests. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]