Is Routine Pathology Evaluation of Tissue Removed for Fertility Preservation Necessary?

BACKGROUND: For all fertility preservation (FP) cases at our institution, a biopsy is performed for routine pathology from all gonadal tissue removed. This is not standard at all centers. We reviewed our experience with biopsy for pathological evaluation of ovarian and testicular specimens in FP cases to determine clinical utility. METHODS: The medical records of individuals who underwent ovarian tissue cryopreservation (OTC) or testicular tissue cryopreservation (TTC) between 2011 and 2023 were retrospectively reviewed under an IRB-approved study at a free-standing tertiary care children's hospital. Patient demographics, diagnosis, operative characteristics, and pathology results were collected. RESULTS: One-hundred and eighty-three patients underwent OTC, and 134 patients underwent TTC. All patients had their gonadal tissue biopsied for routine pathology. Malignancy was identified in the biopsies of 4 OTC patients (2.2%) and 2 TTC patients (1.5%). Two OTC patients (1.1%) and 2 TTC patients (1.5%) did not have germ cells identified in their biopsy. All OTC and TTC patients and families elected to continue storing tissue for FP after discussion of pathology findings. CONCLUSIONS: Pathology results provide another data point to help inform patients and their families when making decisions on ovarian or testicular tissue storage and on how tissue may be utilized in the future to restore fertility and/or hormones. There is a low rate of identifying malignancy in gonadal tissue biopsies taken from FP specimens even in patients with known malignancy. However, when malignancy was identified, it could be unexpected and alter the diagnosis and treatment plan significantly for patients. LEVEL OF EVIDENCE: IV.

A Cross-Sectional Survey of Healthcare Professionals' Knowledge, Attitude and Current Behaviours towards Female Fertility Preservation Services within the UK.

(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.

Fertility protection during chemotherapy treatment by boosting the NAD(P)+ metabolome.

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.

Knowledge, attitudes, and practices of healthcare providers among women oncofertility in Iran: a cross-sectional study.

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.

Comprehensive fertility preservation can be offered in a timely manner around gonadotoxic therapy in children and adolescents.

BACKGROUND: Treatment for certain childhood cancers and nonmalignant conditions can lead to future infertility and gonadal failure. The risk of treatment delay must be considered when offering fertility preservation (FP) options. We examined the timeline from FP referral to return to treatment (RTT) in pediatric patients who underwent FP due to iatrogenic risk for infertility. METHODS: A retrospective review was performed of patients with FP consultation due to an increased risk of iatrogenic infertility at Ann & Robert H. Lurie Children's Hospital of Chicago from 2018 to 2022. Data on diagnosis, age, treatment characteristics, and procedure were collected. RESULTS: A total of 337 patients (n = 149 with ovaries, n = 188 with testes) had an FP consultation. Of patients with ovaries, 106 (71.1%) underwent ovarian tissue cryopreservation (OTC), 10 (6.7%) completed ovarian stimulation/egg retrieval (OSER), and 33 (22.1%) declined FP. Of the patients with testes, 98 (52.1%) underwent testicular tissue cryopreservation (TTC), 48 (25.5%) completed sperm banking (SB), and 42 (22.3%) declined FP. Median time from referral to FP consultation was short (ovaries: 2 days, range: 0-6; testes: 1 day, range: 0-5). OSER had a significantly longer RTT versus OTC and no FP (52.5 vs.19.5 vs. 12 days, p = .01). SB had a significantly quicker RTT compared to TTC or no FP (9.0 vs. 21.0 vs. 13.5 days; p = .008). For patients who underwent OTC/TTC and those who declined FP, there was no significant difference in time from consultation to treatment. CONCLUSIONS: It is feasible to promptly offer and complete FP with minimal delay to disease-directed treatment.

Fertility preservation in pediatric central nervous system tumors: A report from the Children's Oncology Group.

The Oncofertility Consortium Pediatric Initiative Network has published recommendations about the risks of infertility due to gonadotoxic therapy. We abstracted gonadotoxic therapies from central nervous system (CNS) Children's Oncology Group (COG) protocols between 2000 and 2022. We assigned them as unknown, minimal, significant, or high levels of increased risk for gonadal dysfunction/infertility. Seven of 11 CNS protocols placed patients at a high level of risk in at least one treatment arm. Males (7/11) were most commonly at a high level of risk, followed by pubertal females (6/11) and prepubertal females (5/11), highlighting the importance of pre-treatment counseling regarding fertility preservation interventions in this population.

Oncofertility care for children, adolescents, and young adults at risk for treatment-related fertility loss.

As therapy for childhood malignancies becomes more sophisticated and survival has improved, long-term therapy-related sequelae have emerged. Loss of reproductive potential among childhood cancer survivors is one such concern that has become increasingly recognized among patients, families, and healthcare providers. The risk status for infertility based upon therapy received, state of current reproductive technology and outcomes, and an emphasis on adequate referral and counseling for fertility preservation options are reviewed. Contributing factors to infertility are discussed, and options for female and male preservation based upon age and pubertal status are summarized. This article highlights the current state of fertility opportunities for children and adolescents undergoing therapy for cancer. Providers caring for these young patients should be familiar with such options and should routinely initiate evaluations for eligibility of fertility preservation.

Counseling and cryopreservation: evaluation of patient-reported counseling and choice on method of cancer-related fertility preservation.

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.

The Low Survivability of Transplanted Gonadal Grafts: The Impact of Cryopreservation and Transplantation Conditions on Mitochondrial Function.

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.

A dozen years of ovarian tissue cryopreservation at a pediatric hospital: tracking program and patient metrics while adapting to increasing needs.

Objective: To review the program and patient metrics for ovarian tissue cryopreservation (OTC) within a comprehensive pediatric fertility preservation program in its first 12 years of development. Design: Retrospective review. Setting: A tertiary children's hospital in a large urban center between March 2011 and February 2023. Patients: Pediatric patients who underwent OTC. Interventions: Unilateral oophorectomy for OTC. Main Outcome Measures: Patient demographics and clinical course information were collected for analysis. Results: A total of 184 patients underwent OTC in the first 12 years. One hundred fifteen patients were prepubertal at the time of OTC, and 69 were postpubertal. In total, 128 patients (69.6%) received part of their planned therapy before OTC. Starting in 2018, 104 participants (92.0%) donated tissue to research, 99 participants (87.6%) donated blood, and 102 (90.2%) donated media to research. There was a decrease in the median age of patients who underwent OTC from 16.4-6.6 years and an overall increase in the proportion of patients per year that were prepubertal. Forty-eight (26.0%) patients who underwent OTC were outside referrals and traveled from as far as Seattle, Washington. Conclusion: During the first 12 years of this program, oncofertility research increased, annual tissue cryopreservation cases increased, and the median age of those who underwent OTC decreased. The program was adapted to build a stand-alone gonadal tissue processing suite and specialized in prepubertal ovarian tissue processing. The program will continue to adapt to patient needs in the upcoming decades because restoration technologies advance through research supported by this and collaborating programs.

Cancer and Fertility: Exploring Uncertainty Management Strategies of Young Adult Female Survivors.

This study describes young adult female (YA-F) cancer survivors' uncertainty management strategies related to fertility/family building. Cross-sectional data were analyzed (n = 98). Participants reported higher rates of seeking information to reduce fertility-related uncertainty (M = 5.48, ±1.03), than avoiding information (M = 4.77, ±1.29). Controlling for relevant covariates (i.e., reproductive distress, household income, and health literacy), greater avoidance was related to higher reproductive distress (ß = 0.293, p = 0.011) and lower household income (ß = -0.281, p = 0.047). Evidence suggests that some survivors may avoid fertility-related information to manage uncertainty and distress, which may impact family-building success. Fertility avoidance may be an important target of intervention.

Fertility and Pregnancy-Related Issues in Young BRCA Carriers With Breast Cancer.

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 BRCA1/2 (gBRCA1/2) 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 gBRCA1/2 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 gBRCA1/2 PVs carriers and the safety data on having a pregnancy after breast cancer treatment.

Reproductive outcomes of embryo cryopreservation and transfer at the start-up phase of fertility preservation in Japan.

Purpose: To verify the effectiveness of embryo transfer (ET) using cryopreserved embryo as fertility preservation (FP). Methods: This study was a questionnaire survey. The total number of embryo cryopreservation (EC) was investigated between 2014 and 2020. And for patients who underwent ET among study period, details of EC, outcome of ET, number of live births, and mortality were investigated. Results: Of the 150 facilities, 114 responded (76.0%). A total of 1420 EC were performed during the study period; and ET was performed for 417 patients. Breast cancer was the most common primary disease. A total of 199 live births (including prospective) were obtained by ET; 1.7 EC and 2.2 ET were performed per patient, and live birth rate was 21.4% per ET (28.1% on 35-37-year-old patients). The number of EC and ET increased with age. The final birth rate, including pregnancies other than FP, was 51.8%. Ovarian stimulation with aromatase inhibitors was commonly used, although with no effect on live birth rates. Random start stimulation was also common, experienced by 36.3% of breast cancer patients. Conclusion: Reproductive outcomes of ETs following EC as FP are acceptable. This research project was registered in the University Hospital Medical Information Network (UMIN000043664).

Fertility in young-onset colorectal patients with cancer: a review.

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.

Spermatogonial quantity in prepubertal boys undergoing fertility preservation is comparable between haematological and non-haematological cancers.

Fertility restoration potential of immature testicular tissue (ITT) depends on the number of spermatogonial cells in the retrieved tissue prior to cryopreservation in oncofertility programme. There are limited data on the association between type of malignancy and testicular germ cell population. Hence, this study is aimed to investigate the spermatogonial and Sertoli cell population in ITT retrieved from 14 pre-pubertal boys who opted for fertility preservation. Histopathological and immunochemical analysis of seminiferous tubules from haematological (N = 7) and non-haematological (N = 7) malignant patients revealed 3.43 ± 2.92 and 1.71 ± 1.81 spermatogonia per tubular cross section (S/T), respectively. The Sertoli cell number was comparable between haematological and non-haematological group (18.42 ± 3.78 and 22.03 ± 10.43). Spermatogonial quantity in ITT did not vary significantly between haematological and non-haematological cancers. This observation, though preliminary, would contribute to the limited literature on paediatric male oncofertility.

Navigating Fertility Preservation Options in Gynecological Cancers: A Comprehensive Review.

(1) Background: Currently, an increasing number of women postpone pregnancy beyond the age of 35. Gynecological cancers affect a significant proportion of women of reproductive age, necessitating the development of fertility preservation methods to fulfill family planning. Consequently, providing treatment options that preserve fertility in women diagnosed with gynecological cancers has become a crucial component of care for survivors. (2) Methods: We conducted an extensive search of relevant scientific publications in PubMed and Embase databases and performed a narrative review, including high-quality peer-reviewed research on fertility after being treated for gynecologic cancers, reporting pregnancy rates, birth rates, and pregnancy outcomes in cancer survivors as well as therapeutic options which partially preserve fertility and methods for obtaining a pregnancy in survivors. (3) Discussion: The medicine practiced today is focused on both treating the neoplasm and preserving the quality of life of the patients, with fertility preservation being an important element of this quality. This leads to an improved quality of life, allowing these women to become mothers even in the seemingly adverse circumstances posed by such a pathology. However, although there are guidelines on female fertility preservation in the context of neoplasms, an analysis shows that physicians do not routinely consider it and do not discuss these options with their patients. (4) Conclusions: Advancements in medicine have led to a better understanding and management of gynecological neoplasms, resulting in increased survival rates. Once the battle against these neoplasms is won, the issue of preserving the quality of life for these women arises, with fertility preservation being an important aspect for women who have not yet fulfilled their family planning desires at the time of diagnosis. It is important for patients to be informed about the available options for fertility preservation and to be encouraged to make informed decisions in collaboration with their medical team. Standardized recommendations for onco-fertility into guidelines should be taken into consideration in the future.

Current practices in oncofertility counseling: updated evidence on fertility preservation and post-treatment pregnancies in young women affected by early breast cancer.

INTRODUCTION: 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. AREAS COVERED: 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. EXPERT OPINION: 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.

Fertility preservation before cancer treatment: the dilemma of saying 'no' as the price of glory.

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.

Oncofertility as an Essential Part of Comprehensive Cancer Treatment in Patients of Reproductive Age, Adolescents and Children.

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.

Fertility Preservation in BRCA1/2 Germline Mutation Carriers: An Overview.

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.