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In the last years, thanks to the improvement in the prognosis of cancer patients, a growing attention has been given to the fertility issues. International guidelines on fertility preservation in cancer patients recommend that physicians discuss, as early as possible, with all patients of reproductive age their risk of infertility from the disease and/or treatment and their interest in having children after cancer, and help with informed fertility preservation decisions. As recommended by the American Society of Clinical Oncology and the European Society for Medical Oncology, sperm cryopreservation and embryo/oocyte cryopreservation are standard strategies for fertility preservations in male and female patients, respectively; other strategies (e.g. pharmacological protection of the gonads and gonadal tissue cryopreservation) are considered experimental techniques. However, since then, new data have become available, and several issues in this field are still controversial and should be addressed by both patients and their treating physicians. In April 2015, physicians with expertise in the field of fertility preservation in cancer patients from several European countries were invited in Genova (Italy) to participate in a workshop on the topic of “cancer and fertility preservation”. A total of ten controversial issues were discussed at the conference. Experts were asked to present an up-to-date review of the literature published on these topics and the presentation of own unpublished data was encouraged. On the basis of the data presented, as well as the expertise of the invited speakers, a total of ten recommendations were discussed and prepared with the aim to help physicians in counseling their young patients interested in fertility preservation. Although there is a great interest in this field, due to the lack of large prospective cohort studies and randomized trials on these topics, the level of evidence is not higher than 3 for most of the recommendations highlighting the need of further research efforts in many areas of this field. The participation to the ongoing registries and prospective studies is crucial to acquire more robust information in order to provide evidence-based recommendations.

The European Society of Gynaecological Oncology, the European Society of Human Reproduction and Embryology, and the European Society for Gynaecological Endoscopy jointly developed clinically relevant and evidence-based guidelines focusing on key aspects of fertility-sparing strategies and follow-up of patients with cervical cancers, ovarian cancers, and borderline ovarian tumours. The developmental process of these guidelines is based on a systematic literature review and critical appraisal involving an international multidisciplinary development group consisting of 25 experts from relevant disciplines (ie, gynaecological oncology, oncofertility, reproductive surgery, endoscopy, imaging, conservative surgery, medical oncology, and histopathology). Before publication, the guidelines were reviewed by 121 independent international practitioners in cancer care delivery and patient representatives. The guidelines comprehensively cover oncological aspects of fertility-sparing strategies during the initial management, optimisation of fertility results and infertility management, and the patient's desire for future pregnancy and beyond.

Background Diagnosis of breast cancer in young women has been shown to affect their decision‐making with regard to fertility and family planning. Limited data are available from populations across the U.S. regarding this issue; thus, we sought to describe fertility concerns and efforts to preserve fertility in a national clinical trial population of young breast cancer patients. Methods The young and strong study was a cluster‐randomized controlled trial testing an intervention program for young women with breast cancer. Patients were surveyed within 3 months after diagnosis and at 3, 6, and 12 months after. Surveys asked about sociodemographics, psychosocial domains, fertility concerns, and fertility preservation strategies. Univariable and multivariable models were used to investigate sociodemographic, clinical, and psychosocial predictors of fertility concerns. Results Of 467 women from 54 clinical sites across the U.S. (14 academic, 40 community), 419 were evaluable regarding fertility concerns. Median age was 40 years (range 22–45), 11% were Black, 6% Hispanic, and 75% had children. Tumor stage was I (35%), II (51%), or III (14%); 82% received chemotherapy. At time of the treatment decision, 133 (32%) participants had fertility concerns, among whom 47% indicated this affected their treatment decisions. Sixty percent of participants reported having discussed fertility with their physician. Twenty percent of those with fertility concerns used fertility preservation strategies. History of difficulty becoming pregnant and younger age were associated with higher odds of fertility concerns in multivariable modeling. Conclusion Many young women with newly diagnosed breast cancer are concerned about fertility in a way that impacts their treatment decisions. Concerns were discussed, but few used fertility preservation strategies. These findings have implications for counseling young patients.

PurposeThe purpose of this study is to review patient experience with social fertility preservation (sFP), as compared to medical fertility preservation (mFP), in a context where sFP is fully reimbursed.MethodsWe conducted a retrospective cohort study involving patients who underwent oocyte cryopreservation for mFP between 2017 and 2023 and sFP between 2022 and 2023 at a large ART single center. Additionally, we surveyed patients undergoing sFP and mFP, regarding their experiences, intentions, awareness, and financial consideration.ResultsA total of 97 oocyte retrievals were performed for sFP in 75 women, and 155 were performed in mFP (127 women). Median ages were 36.4 years for sFP and 28.9 years for mFP. Median oocytes retrieved per session were 10 for sFP and 8 for mFP. Ninety-seven percent of of mFP participants were informed by healthcare professionals, while half of sFP participants learned through personal acquaintances. The primary motivation for sFP was a desire for pregnancy while being single. Most respondents in both groups knew that 15–20 oocytes are typically needed for a successful birth. None were aware of the “DuoStim” option, but interest was expressed by most women. Surprisingly, despite full reimbursement for sFP in France, 78% expressed willingness to pay if necessary.ConclusionMany women choose sFP due to concerns about declining fertility, often informed by non-medical sources. Free access to sFP can help mitigate the global decline in natality by allowing women to anticipate age-related fertility decline. This study should be considered by other countries as they may increasingly cover sFP costs in the future.

Purpose A critical ethical analysis of the initiative of several companies to cover the costs of oocyte cryopreservation for their healthy employees. The main research question is whether such policies promote or confine women’s reproductive autonomy. Results A distinction needs to be made between the ethics of AGE banking in itself and the ethics of employers offering it to their employees. Although the utility of the former is expected to be low, there are few persuasive arguments to deny access to oocyte cryopreservation to women who are well informed about the procedure and the success rates. However, it does not automatically follow that it would be ethically unproblematic for employers to offer egg banking to their employees. Conclusions For these policies to be truly ‘liberating’, a substantial number of conditions need to be fulfilled, which can be reduced to three categories: (1) women should understand the benefits, risks and limitations, (2) women should feel no pressure to take up the offer; (3) the offer should have no negative effect on other family-friendly policies and should in fact be accompanied by such policies. Fulfilling these conditions may turn out to be impossible. Thus, regardless of companies’ possible good intentions, women’s reproductive autonomy is not well served by offering them company-sponsored AGE banking.

To date, fertility preservation has mainly been offered to patients prior to gonadotoxic treatment. Ovarian reserve is assessed by analysing blood levels of anti-müllerian hormone (AMH), and gonadal cells or tissue are cryopreserved if indicated and requested by the patient. If primary fertility preservation (Primary FertiProtekt) before gonadotoxic treatment was not performed or was ineffective, secondary fertility preservation should be considered approximately one year after treatment based on a more extensive ovarian reserve analysis including menstrual cycle pattern, antral follicle count, and serum levels of AMH, estradiol and follicle stimulating hormone. Ovarian reserve analysis is also required to consider endocrine treatment in (pre) menopausal patients. Both approaches require the fertility preservation treatment to be tailored to the ovarian reserve status, type of gonadotoxic therapy. For secondary fertility preservation (Secondary FertiProtekt), oocyte freezing may be considered if ovarian reserve is not too low. Monthly treatment cycles, natural cycle or minimal stimulation protocols and follicle aspiration without anesthesia should be preferred. Menopause care management (MenoProtekt) involves acute menopausal symptom relief and prevention of chronic non-communicable diseases. The management needs to be individualized based on type of disease (hormone-dependent or -independent).

PurposeToday, male and female adult and pediatric cancer patients, individuals transitioning between gender identities, and other individuals facing health extending but fertility limiting treatments can look forward to a fertile future. This is, in part, due to the work of members associated with the Oncofertility Consortium.MethodsThe Oncofertility Consortium is an international, interdisciplinary initiative originally designed to explore the urgent unmet need associated with the reproductive future of cancer survivors. As the strategies for fertility management were invented, developed or applied, the individuals for who the program offered hope, similarly expanded. As a community of practice, Consortium participants share information in an open and rapid manner to addresses the complex health care and quality-of-life issues of cancer, transgender and other patients. To ensure that the organization remains contemporary to the needs of the community, the field designed a fully inclusive mechanism for strategic planning and here present the findings of this process.ResultsThis interprofessional network of medical specialists, scientists, and scholars in the law, medical ethics, religious studies and other disciplines associated with human interventions, explore the relationships between health, disease, survivorship, treatment, gender and reproductive longevity.ConclusionThe goals are to continually integrate the best science in the service of the needs of patients and build a community of care that is ready for the challenges of the field in the future.

Research question To what extent have fertility preservation interventions evolved between 2014 and 2023, and what factors have influenced changes in their utilization and prevalence? Design Based on the Ferti PROTEKT registry, comprising 163 centres across Germany, Austria, and parts of Switzerland, the quantitative development of ovarian stimulation for oocyte cryopreservation and ovarian tissue cryopreservation was evaluated from 2014 to 2023. Analyses were stratified according to the kind of participating centre, patient age, and the spectrum of underlying diseases. In addition, data were statistically compared for the periods 2014/2015 (P1) and 2022/2023 (P2). Results Approximately 14,000 women received counselling across all three countries between 2014 and 2023. Among these, 3,996 females underwent ovarian stimulation for oocyte cryopreservation, and 3,478 underwent ovarian tissue cryopreservation. The number of oocyte cryopreservation cycles increased substantially from P1 to P2, whereas the number of ovarian tissue cryopreservation procedures remained relatively stable. The increase in oocyte cryopreservation was substantially greater in private centres (197% increase: 308 to 916 cycles) compared to public institutions (39% increase: 818 to 1,136 cycles; p < 0.001). The rise in oocyte cryopreservation cycles parallels an increase in breast cancer cases presenting for fertility preservation; this temporal coincidence suggests a potential association but does not establish causation. The predominance of breast cancer patients also influenced the age distribution of oocyte cryopreservation cases. Among oocyte cryopreservation procedures, absolute numbers increased across all age groups up to 40 years, with the largest absolute increase in women aged 31–40 years (212 to 732 cycles, 245% relative increase).The overall age distribution of procedures changed only slightly, although younger patients were more likely to undergo ovarian tissue cryopreservation. Additionally, new indications such as endometriosis and gender dysphoria have become increasingly relevant over the past 5 years. Conclusion The number and distribution of fertility preservation procedures have changed notably during the last decade, driven primarily by shifts in the reimbursement strategies and the type of centres providing care. These developments should be carefully considered in the future design and implementation of fertility preservation programmes. However, decisions regarding specific fertility-preserving interventions must also be guided by scientific evidence.

PurposeExtensive follicle loss has been demonstrated in ovarian grafts post transplantation, reducing their productivity and lifespan. Several mechanisms for this loss have been proposed, and this study aims to clarify when and how the massive follicle loss associated with transplantation of ovarian tissue graft occurs. An understanding of the mechanisms of follicle loss will pinpoint potential new targets for optimization and improvement of this important fertility preservation technique.MethodsFrozen-thawed marmoset (n = 15), bovine (n = 37), and human (n = 46) ovarian cortical tissue strips were transplanted subcutaneously into immunodeficient castrated male mice for 3 or 7 days. Histological (H&E, Masson’s trichrome) analysis and immunostaining (Ki-67, GDF9, cleaved caspase-3) were conducted to assess transplantation-associated follicle dynamics, with untransplanted frozen-thawed tissue serving as a negative control.ResultsEvidence of extensive primordial follicle (PMF) activation and loss was observed already 3 days post transplantation in marmoset, bovine, and human tissue grafts, compared to frozen-thawed untransplanted controls (p < 0.001). No significant additional PMF loss was observed 7 days post transplantation. Recovered grafts of all species showed markedly higher rates of proliferative activity and progression from dormant to growing follicles (Ki-67 and GDF9 staining) as well as higher growing/primordial (GF/PMF) ratio (p < 0.02) and higher collagen levels compared with untransplanted controls.ConclusionsThis multi-species study demonstrates that follicle activation plays an important role in transplantation-induced follicle loss, and that it occurs within a very short time frame after grafting. These results underline the need to prevent this activation at the time of transplantation in order to retain the maximal possible follicle reserve and extend graft lifespan.

Cryopreservation of eggs or ovarian tissue to preserve fertility for patients with cancer has been studied since 1994 with R G Gosden's paper describing restoration of fertility in oophorectomised sheep, and for decades previously by others in smaller mammals. Clinically this approach has shown great success. Many healthy children have been born from eggs cryopreserved with the Kuwayama egg vitrification technique for non-medical (social) indications, but until now very few patients with cancer have achieved pregnancy with cryopreserved eggs. Often, oncologists do not wish to delay cancer treatment while the patient goes through multiple ovarian stimulation cycles to retrieve eggs, and the patient can only start using the oocytes after full recovery from cancer. Ovarian stimulation and egg retrieval is not a barrier for patients without cancer who wish to delay childbearing, which makes oocyte cryopreservation increasingly popular to overcome an age-related decline in fertility. Cryopreservation of ovarian tissue is an option if egg cryopreservation is ruled out. More than 37 babies have been born so far with cryopreserved ovarian tissue in patients with cancer who have had a complete return of hormonal function, and fertility to baseline. Both egg and ovarian tissue cryopreservation might be ready for application to the preservation of fertility not only in patients with cancer but also in countering the increasing incidence of age-related decline in female fertility.