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In this review we systematically summarize the effects of progesterone and synthetic progestins on neurogenesis, synaptogenesis, myelination and six neurotransmitter systems. Several parallels between progesterone and older generation progestin actions emerged, suggesting actions via progesterone receptors. However, existing results suggest a general lack of knowledge regarding the effects of currently used progestins in hormonal contraception regarding these cellular and molecular brain parameters. Human neuroimaging studies were reviewed with a focus on randomized placebo-controlled trials and cross-sectional studies controlling for progestin type. The prefrontal cortex, amygdala, salience network and hippocampus were identified as regions of interest for future preclinical studies. This review proposes a series of experiments to elucidate the cellular and molecular actions of contraceptive progestins in these areas and link these actions to behavioral markers of emotional and cognitive functioning. Emotional effects of contraceptive progestins appear to be related to 1) alterations in the serotonergic system, 2) direct/indirect modulations of inhibitory GABA-ergic signalling via effects on the allopregnanolone content of the brain, which differ between androgenic and anti-androgenic progestins. Cognitive effects of combined oral contraceptives appear to depend on the ethinylestradiol dose., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Fertility preservation in the cancer setting, known as oncofertility, is a field that requires cross-disciplinary interaction between physicians, basic scientists, clinical researchers, ethicists, lawyers, educators, and religious leaders. Funded by the National Institutes of Health, the Oncofertility Consortium (OC) was formed to be a scientifically grounded, transparent, and altruistic resource, both intellectual and monetary, for building this new field of practice capable of addressing the unique needs of young patients with cancer. The OC has expanded its attention to include other nonmalignant conditions that can threaten fertility, and the work of the OC now extends around the globe, involving partners who together have created a community of shared effort, resources, and practices. The OC creates materials that are translated, disseminated, and amended by all participants in the field, and local programs of excellence have developed worldwide to accelerate the pace and improve the quality of oncofertility research and practice. Here we review the global oncofertility programs and the capacity building activities that strengthen these research and clinical programs, ultimately improving patient care.

Purpose: Oncofertility focuses on providing fertility and endocrine-sparing options to patients who undergo life-preserving but gonadotoxic cancer treatment. The resources needed to meet patient demand often are fragmented along disciplinary lines. We quantify assets and gaps in oncofertility care on a global scale., Methods: Survey-based questionnaires were provided to 191 members of the Oncofertility Consortium Global Partners Network, a National Institutes of Health-funded organization. Responses were analyzed to measure trends and regional subtleties about patient oncofertility experiences and to analyze barriers to care at sites that provide oncofertility services., Results: Sixty-three responses were received (response rate, 25%), and 40 were analyzed from oncofertility centers in 28 countries. Thirty of 40 survey results (75%) showed that formal referral processes and psychological care are provided to patients at the majority of sites. Fourteen of 23 respondents (61%) stated that some fertility preservation services are not offered because of cultural and legal barriers. The growth of oncofertility and its capacity to improve the lives of cancer survivors around the globe relies on concentrated efforts to increase awareness, promote collaboration, share best practices, and advocate for research funding., Conclusion: This survey reveals global and regional successes and challenges and provides insight into what is needed to advance the field and make the discussion of fertility preservation and endocrine health a standard component of the cancer treatment plan. As the field of oncofertility continues to develop around the globe, regular assessment of both international and regional barriers to quality care must continue to guide process improvements., Competing Interests: The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/site/ifc. Alexandra S. RashediEmployment: Cigna (I) Stock or Other Ownership: Cigna (I)Antoinette AnazodoResearch Funding: Merck SeronoCassio SartorioEmployment: Vida Centro de Fertilidade Leadership: Vida Centro de Fertilidade Stock or Other Ownership: Vida Centro de FertilidadeCatharina C.M. BeerendonkTravel, Accommodations, Expenses: GoodlifeEllen M. GreenblattConsulting or Advisory Role: Ferring Pharmaceuticals, EMD Serono Travel, Accommodations, Expenses: EMD SeronoFernando M. ReisHonoraria: Politec Saúde (I) Consulting or Advisory Role: Politec Saúde (I) Speakers’ Bureau: UCB (I) Travel, Accommodations, Expenses: Abbott Laboratories (I)Johan SmitzSpeakers’ Bureau: Ferring Pharmaceuticals Travel, Accommodations, Expenses: Ferring PharmaceuticalsMaria T. BourlonLeadership: Medivation, Astellas Pharma Honoraria: Medivation, Astellas Pharma Speakers’ Bureau: Asofarma Research Funding: Bristol-Myers Squibb Travel, Accommodations, Expenses: Janssen PharmaceuticalsMichel De VosHonoraria: Cook Medical Research Funding: Cook MedicalRichard A. AndersonConsulting or Advisory Role: Roche, HRA Pharma, NeRe Pharmaceuticals Speakers’ Bureau: Roche, Beckman Coulter, IBSA Institut Biochimque Research Funding: Ferring Pharmaceuticals Travel, Accommodations, Expenses: IBSA Institut BiochimqueRoberto de A. AntunesConsulting or Advisory Role: Merck Serono Speakers’ Bureau: Merck Serono Travel, Accommodations, Expenses: Merck Serono, MSDTeresa Almeida-SantosConsulting or Advisory Role: Merck, MSD Research Funding: MerckTeresa K. WoodruffResearch Funding: Ferring Pharmaceuticals (Inst) No other potential conflicts of interest were reported., (© 2020 by American Society of Clinical Oncology.)

Purpose: In the accompanying article, "Survey of Fertility Preservation Options Available to Patients With Cancer Around the Globe," we showed that specific fertility preservation services may not be offered at various sites around the world because of cultural and legal barriers. We assessed global and regional experiences as well as the legal status of third-party reproduction and adoption to serve as a comprehensive international data set and resource for groups that wish to begin oncofertility interventions., Methods: We provide data on the legalities of third-party assisted reproductive technologies and other family-building options in the 28 oncofertility-practicing countries surveyed., Results: We found regional and country differences that will be important in the development of tailored resources for physicians and for patient brochures that are sensitive to these local restrictions and cultural norms., Conclusion: Because many patients first consult Web-based materials, the formal assessment of the availability of these options provides members of the global oncofertility community with data to which they might otherwise not have ready access to better serve their patients., Competing Interests: The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or jco.ascopubs.org/site/ifc. Alexandra S. RashediEmployment: Cigna (I) Stock or Other Ownership: Cigna (I)Antoinette AnazodoResearch Funding: Merck SeronoCassio SartorioEmployment: Vida Centro de Fertilidade Leadership: Vida Centro de Fertilidade Stock or Other Ownership: Vida Centro de FertilidadeCatharina C.M. BeerendonkTravel, Accommodations, Expenses: GoodlifeEllen M. GreenblattConsulting or Advisory Role: Ferring Pharmaceuticals, EMD Serono Travel, Accommodations, Expenses: EMD SeronoFernando M. ReisHonoraria: Politec Saúde (I) Consulting or Advisory Role: Politec Saúde (I) Speakers’ Bureau: UCB (I) Travel, Accommodations, Expenses: Abbott Laboratories (I)Flor SánchezPatents, Royalties, Other Intellectual Property: patent pendingJohan SmitzSpeakers’ Bureau: Ferring Pharmaceuticals Travel, Accommodations, Expenses: Ferring PharmaceuticalsMaria T. BourlonLeadership: Medivation, Astellas Pharma Honoraria: Medivation, Astellas PharmaRichard A. AndersonConsulting or Advisory Role: Roche, HRA Pharma, NeRe Pharmaceuticals Speakers’ Bureau: Roche, Beckman Coulter, IBSA Institut Biochimque Research Funding: Ferring Pharmaceuticals Travel, Accommodations, Expenses: IBSA Institut BiochimqueRoberto de A. AntunesConsulting or Advisory Role: Merck Serono Travel, Accommodations, Expenses: Merck Serono, MSDSergio RomeroPatents, Royalties, Other Intellectual Property: patent pendingTeresa Almeida-SantosConsulting or Advisory Role: Merck, MSD Research Funding: Merck SeronoTeresa K. WoodruffResearch Funding: Ferring Pharmaceuticals (Inst) No other potential conflicts of interest were reported., (© 2020 by American Society of Clinical Oncology.)

The cryopreservation of ovarian tissue with subsequent transplantation of the tissue represents an established method of fertility protection for female patients who have to undergo gonadotoxic therapy. The procedure can be performed at any point in the cycle and thus generally does not lead to any delay in oncological therapy. With the aid of this procedure, more than 130 births to date worldwide have been able to be recorded. The birth rate is currently approximately 30% and it can be assumed that this will increase through the further optimisation of the cryopreservation and surgical technique. The concept paper presented here is intended to provide guidance for managing cryopreservation and transplantation of ovarian tissue to German-speaking reproductive medicine centres.

Fertility-preserving measures are becoming important for patients receiving oncological treatment. One method involves cryopreservation of ovarian tissue and transplanting it when treatment is completed. We report complications resulting from surgical and fertility medicine, and the results of procedures for the removal and transplantation of ovarian tissue carried out within the FertiProtekt network. A survey using a structured questionnaire was conducted among the FertiProtekt network centres between November 2015 and June 2016. The analysis included surgical techniques used to remove and transplant ovarian tissue, surgical complications and results. Laparoscopic removal and transplantation of ovarian tissue have a low risk of complications. Surgical complications occurred in three of the network's 1373 ovarian tissue removals (n = 1302) and transplantations (n = 71); two complications (0.2%) occurred during removal and one during transplantation. Menstruation resumed in 47 out of 58 women (81%) who underwent ovarian tissue transplantation. Hormonal activity occurred in 63.2% of transplantations with a follow-up of 6 months or over. Sixteen pregnancies occurred in 14 patients, with nine births. The risks and complications of removal and transplantation of ovarian tissue are similar to those of standard laparoscopy. These procedures are becoming standard for fertility protection in cancer patients., (Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

The prevention of fertility loss due to cancer treatment as well as non-malignant causes has been gaining importance over the last few decades. Clinically applied modalities for fertility preservation in cancer patients include cryopreservation of oocytes and embryos, the application of GnRH agonists, ovarian tissue banking, and cryopreservation of ejaculated or surgically extracted sperm. In addition, several new possibilities to restore fertility are currently being investigated, such as the establishment of in-vitro culture systems for gonadal tissue, the development of artificial gonads, and the application of germline stem cells. This review aims to provide an update on the methods currently applied in clinical practice for fertility preservation, as well as to summarize the progress made in the development of novel strategies for fertility preservation.

Purpose: To study the influence of xenotransplantation on follicular recruitment and growth in cryopreserved/thawed human ovarian tissue., Method: Two 3-mm pieces of cryopreserved/thawed human ovarian tissue obtained from female cancer patients (n = 11) were xenotransplanted into a subcutaneous neck pouch of 6-week-old ovarectomized SCID mice (n = 33) for 4 (n = 18) and 12 (n = 15) weeks., Result: Thirty-two out of 33 mice survived the entire observation periods. Graft recovery rate was 95.58 % (65 of 68 grafts). The percentages of primordial follicles after 4 weeks (P < 0.001) and 12 weeks (P = 0.009) of grafting were significantly lower in comparison to pregraft controls. The percentage of secondary follicle was significantly higher after 4 weeks of grafting (P = 0.018) and after 12 weeks (P = 0.001) of grafting in comparison to pregraft controls. Ki67 immunohistochemistry showed that proliferative follicles were significantly higher after 4 and 12 weeks of grafting compared to pregraft controls (P < 0.001). All follicles analyzed by TUNEL staining appeared healthy after xenotransplantation. The expression level of PTEN was reduced by 2.47-fold after 4 weeks of xenotransplantation, and this result was significant when 2 -ΔCt were analyzed (P = 0.042)., Conclusion: The higher proportion of growing follicles compared to resting follicles observed after xenotransplantation is most likely due to downregulation of PTEN gene expression followed by acceleration of follicular recruitment., Competing Interests: Compliance with ethical standards Statement of human rights All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Statement on the welfare of animals All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted. Competing interests The authors declare that they have no conflict of interest. Study funding This study was funded by the Tyrolean Research Foundation. S.A. was supported by a scholarship from the Indonesian Directorate General of Higher Education, Ministry of National Education, Indonesia. K.W.-C. was supported by a DOC-fFORTE scholarship from the Austrian Academy of Sciences and the Austrian Federal Ministry of Science and Research.

Fertility preservation in the cancer setting, known as oncofertility, is a field that requires cross-disciplinary interaction between physicians, basic scientists, clinical researchers, ethicists, lawyers, educators, and religious leaders. Funded by the National Institutes of Health, the Oncofertility Consortium (OC) was formed to be a scientifically grounded, transparent, and altruistic resource, both intellectual and monetary, for building this new field of practice capable of addressing the unique needs of young patients with cancer. The OC has expanded its attention to include other nonmalignant conditions that can threaten fertility, and the work of the OC now extends around the globe, involving partners who together have created a community of shared effort, resources, and practices. The OC creates materials that are translated, disseminated, and amended by all participants in the field, and local programs of excellence have developed worldwide to accelerate the pace and improve the quality of oncofertility research and practice. Here we review the global oncofertility programs and the capacity building activities that strengthen these research and clinical programs, ultimately improving patient care.

Due to the increasing number of long-term cancer survivors, physicians of all specialties are confronted with the need to prevent side effects of the applied oncologic treatments. In the field of reproductive medicine fertility preservation has gained importance as most oncologic treatments have detrimental immediate or long-term impacts on male and female fertility. The American Society of Clinical Oncology and the American Society for Reproductive Medicine, as well as the recently founded International Society for Fertility Preservation propose several established and investigational options for fertility preservation. This review aims to summarize currently available techniques for fertility preservation and future perspectives in this field, as well as to provide recommendations for patient follow-up after cancer and during pregnancy.

Objective: To evaluate the impact of dynamic in vitro culture on initiation of early follicular growth in prepubertal mouse ovaries., Design: Ovaries from 8-day-old BALB/c mice were cultured either in a dynamic system (n=28) or in a static system (n=20) for 4 days. Uncultured 8-day-old (n=9) or 12-day-old (n=17) ovaries served as baseline or in vivo controls, respectively., Setting: Academic research center., Animal(s): Newborn female BALB/c mice (n=37)., Intervention(s): None., Main Outcome Measure(s): Histologic follicle classification and counting and assessment of follicular viability via immunofluorescent staining., Result(s): The percentage of secondary follicles after dynamic culture was identical to the 12-day-old in vivo control. In contrast, after static culture ovaries showed a significantly higher percentage of secondary follicles. For immunofluorescent viability assessment 6.78 follicles per ovary could be isolated after dynamic culture, whereas only 3.8 follicles per ovary could be isolated after static culture., Conclusion(s): Dynamic in vitro culture supports physiologic follicular growth initiation, comparable to that observed in vivo. In contrast, accelerated follicular growth was observed after static culture. These findings add additional evidence to the idea that dynamic culture might be a beneficial first step to initiate follicle growth in vitro within the context of fertility preservation., (Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)