Oocyte vitrification for fertility preservation for both medical and nonmedical reasons.

Growing evidence of successful outcomes achieved with the oocyte vitrification technique has greatly contributed to its application in the field of fertility preservation (FP). The population that can benefit from FP includes women at a risk of losing their ovarian function because of either iatrogenic causes or natural depletion of their ovarian reserve. Therefore, oncological patients and healthy women who wish to delay motherhood for various reasons-elective FP-are currently being offered this option. Satisfactory oocyte survival rates and clinical outcomes, including cumulative live birth rates, have been reported in recent years. These studies show that age at oocyte retrieval strongly affects reproductive prognosis after FP. Therefore, elective FP patients should be encouraged to decide before they reach the age of 35 years to significantly increase their chances of success. The effect of age has also been observed in patients with cancer and women diagnosed with endometriosis. The reproductive outcome after FP is worse in patients with cancer, but a direct association between the disease and reproductive outcome is yet to be proven. Young patients (≤35 years) with endometriosis who have undergone cystectomy before oocyte retrieval for FP have worse outcomes than nonoperated women in age-matched groups. In addition, the number of oocytes used per patient is closely related to success in all populations, with considerable improvement in the result with the addition of a few oocytes, especially in healthy young patients.

Fertility preservation in men: a contemporary overview and a look toward emerging technologies.

Cancer and oncologic therapies can have significant adverse effects on male reproductive potential, leaving many men permanently infertile. Fertility preservation has emerged as a key survivorship issue over the past 20 years, and numerous professional societies have published guidelines calling for fertility preservation to become a routine component of oncologic care. Most males with cancer are able to produce a semen specimen for fertility preservation, but numerous other methods of sperm procurement are available for patients who cannot provide a sufficient sample. Despite these options, fertility preservation will remain a challenge for prepubertal boys and men without sperm production. For these patients, experimental and investigational approaches offer the hope that one day they will translate to the clinical arena, offering additional pathways for successful fertility preservation care.

Fertility preservation in men and women: Where are we in 2021? Are we rising to the challenge?

Demand for fertility preservation in women for oncologic, nononcologic, and personal reasons has increased dramatically. Meeting that demand is a major challenge, and we are rising to the challenge. Mature oocyte cryopreservation after ovarian stimulation and ovarian tissue cryopreservation are both methods endorsed by the American Society for Reproductive Medicine (formerly The American Fertility Society), and numerous papers confirmed their efficacy. In girls and women with leukemia or cancers who are at a high risk of ovarian metastasis and who may not be eligible for ovarian tissue transplantation, restoration of fertility can only be achieved by in vitro methods. Male fertility preservation has also become a pressing issue and is extensively reviewed in the present journal issue.

The Adolescent and Young Adult (AYA) Horizon Study: An AYA Cancer Survivorship Cohort.

BACKGROUND: In the United States, >45,000 adolescent and young adult (AYA) women are diagnosed with cancer annually. Reproductive issues are critically important to AYA cancer survivors, but insufficient information is available to address their concerns. The AYA Horizon Study was initiated to contribute high-quality, contemporary evidence on reproductive outcomes for female cancer survivors in the United States. METHODS: The study cohort includes women diagnosed with lymphoma, breast, melanoma, thyroid, or gynecologic cancer (the five most common cancers among women ages 15-39 years) at three study sites: the state of North Carolina and the Kaiser Permanente health systems in Northern and Southern California. Detailed information on cancer treatment, fertility procedures, and pregnancy (e.g., miscarriage, live birth) and birth (e.g., birth weight, gestational length) outcomes are leveraged from state cancer registries, health system databases and administrative insurance claims, national data on assisted reproductive technology procedures, vital records, and survey data. RESULTS: We identified a cohort of 11,072 female AYA cancer survivors that includes >1,200 African American women, >1,400 Asian women, >1,600 Medicaid enrollees, and >2,500 Hispanic women using existing data sources. Active response to the survey component was low overall (N = 1,679), and notably lower among minority groups compared with non-Hispanic white women. CONCLUSIONS: Passive data collection through linkage reduces participant burden and prevents systematic cohort attrition or potential selection biases that can occur with active participation requirements. IMPACT: The AYA Horizon study will inform survivorship planning as fertility and parenthood gain increasing recognition as key aspects of high-quality cancer care.

THERAPY OF ENDOCRINE DISEASE: Novel protection and treatment strategies for chemotherapy-associated ovarian damage.

Fertility and ovarian protection against chemotherapy-associated ovarian damage has formed a new field called oncofertility, which is driven by the pursuit of fertility protection as well as good life quality for numerous female cancer survivors. However, the choice of fertility and ovarian protection method is a difficult problem during chemotherapy and there is no uniform guideline at present. To alleviate ovarian toxicity caused by anticancer drugs, effective methods combined with an individualized treatment plan that integrates an optimal strategy for preserving and restoring reproductive function should be offered from well-established to experimental stages before, during, and after chemotherapy. Although embryo, oocyte, and ovarian tissue cryopreservation are the major methods that have been proven effective and feasible for fertility protection, they are also subject to many limitations. Therefore, this paper mainly discusses the future potential methods and corresponding mechanisms for fertility protection in chemotherapy-associated ovarian damage.

Fertility preservation for female patients with childhood, adolescent, and young adult cancer: recommendations from the PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group.

Female patients with childhood, adolescent, and young adult cancer are at increased risk for fertility impairment when treatment adversely affects the function of reproductive organs. Patients and their families desire biological children but substantial variations in clinical practice guidelines reduce consistent and timely implementation of effective interventions for fertility preservation across institutions. As part of the PanCareLIFE Consortium, and in collaboration with the International Late Effects of Childhood Cancer Guideline Harmonization Group, we reviewed the current literature and developed a clinical practice guideline for fertility preservation in female patients who were diagnosed with childhood, adolescent, and young adult cancer at age 25 years or younger, including guidance on risk assessment and available methods for fertility preservation. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to grade the available evidence and to form the recommendations. This clinical practice guideline leverages existing evidence and international expertise to develop transparent recommendations that are easy to use to facilitate the care of female patients with childhood, adolescent, and young adult cancer who are at high risk for fertility impairment. A complete review of the existing evidence, including a quality assessment, transparent reporting of the guideline panel's decisions, and achievement of global interdisciplinary consensus, is an important result of this intensive collaboration.

Fertility preservation for male patients with childhood, adolescent, and young adult cancer: recommendations from the PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group.

Male patients with childhood, adolescent, and young adult cancer are at an increased risk for infertility if their treatment adversely affects reproductive organ function. Future fertility is a primary concern of patients and their families. Variations in clinical practice are barriers to the timely implementation of interventions that preserve fertility. As part of the PanCareLIFE Consortium, in collaboration with the International Late Effects of Childhood Cancer Guideline Harmonization Group, we reviewed the current literature and developed a clinical practice guideline for fertility preservation in male patients who are diagnosed with childhood, adolescent, and young adult cancer at age 25 years or younger, including guidance on risk assessment and available methods for fertility preservation. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to grade the available evidence and to form the recommendations. Recognising the need for global consensus, this clinical practice guideline used existing evidence and international expertise to rigorously develop transparent recommendations that are easy to use to facilitate the care of male patients with childhood, adolescent, and young adult cancer who are at high risk of fertility impairment and to enhance their quality of life.

Communication and ethical considerations for fertility preservation for patients with childhood, adolescent, and young adult cancer: recommendations from the PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group.

Patients with childhood, adolescent, and young adult cancer who will be treated with gonadotoxic therapies are at increased risk for infertility. Many patients and their families desire biological children but effective communication about treatment-related infertility risk and procedures for fertility preservation does not always happen. The PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group reviewed the literature and developed a clinical practice guideline that provides recommendations for ongoing communication methods for fertility preservation for patients who were diagnosed with childhood, adolescent, and young adult cancer at age 25 years or younger and their families. Moreover, the guideline panel formulated considerations of the ethical implications that are associated with these procedures. Grading of Recommendations Assessment, Development and Evaluation methodology was used to grade the evidence and recommendations. In this clinical practice guideline, existing evidence and international expertise are combined to develop transparent recommendations that are easy to use to facilitate ongoing communication between health-care providers and patients with childhood, adolescent, and young adult cancer who might be at high risk for fertility impairment and their families.

A View from the past into our collective future: the oncofertility consortium vision statement.

PURPOSE: Today, 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. METHODS: The 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. RESULTS: This 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. CONCLUSION: The 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.

Integration of partners of young women with cancer in oncofertility evidence-based informational resources.

Oncofertility has evolved over the years, with a prodigious amount of research documenting the importance of fertility for young patients with cancer, and the potential impact that fertility impairments due to cancer treatments has on their Quality of Life (QoL). Multiple professional bodies and scientific societies have included fertility as an integral part of clinical management. Clinical guidelines advocate that health professionals have the duty to discuss the risk of infertility and fertility preservation options as early as possible and refer to fertility specialists when appropriate. Collectively, fertility decisions are regarded as difficult for both patients and providers. Since providing fertility-related information is vital for better decision making, researchers and policy makers have concentrated their efforts in developing educational tools to aid decisions and guidelines to optimize the delivery of this information, focusing mainly on patients-providers and largely neglecting the role and influence that partners play in this process. Here, we reflect on the importance of partners in fertility decisions, with a focus on the provision of fertility-related information that is also geared towards partner. We highlight the need to involve partners in fertility discussions, and that their needs should be taken into account in both clinical guidelines and in the development of educational tools, for an optimal decision-making process.

Is ovarian cancer surgery stuck in the dark ages?: a commentary piece reviewing surgical technologies.

Ovarian cancer surgery endeavours to remove all visible tumour deposits, and surgical technologies could potentially facilitate this aim. However, there appear to be barriers around the adoption of new technologies, and we hope this article provokes discussion within the specialty to encourage a forward-thinking approach to new-age surgical gynaecological oncology.

Fertility Preservation for Adolescents Receiving Cancer Therapies.

According to the National Cancer Institute, ∼300,000 children globally are diagnosed with cancer each year. Advancements in chemotherapy and radiotherapy have revolutionized cancer treatment and improved long-term survival. Although many survivors will remain in good health with disease-free prognoses, three fourths will experience short-term and long-term effects from treatment. The cancer care paradigm has now appropriately shifted to include quality of life in survivorship with fertility cited as one of the most important quality of life indicators by survivors. A comprehensive approach to fertility preservation in adolescents receiving cancer therapies is described in this chapter.

Reproductive and oncologic outcomes after fertility-sparing surgery for early stage cervical cancer: a systematic review.

This review sought to evaluate the current literature on reproductive and oncologic outcomes after fertility-sparing surgery for early stage cervical cancer (stage IA1-IB1) including cold-knife conization/simple trachelectomy, vaginal radical trachelectomy, abdominal radical trachelectomy, and laparoscopic radical trachelectomy with or without robotic assistance. A systematic review using the preferred reporting items for systematic reviews and meta-analysis (PRISMA) checklist to evaluate the current literature on fertility-sparing surgery for early stage cervical cancer and its subsequent clinical pregnancy rate, reproductive outcomes, and cancer recurrence was performed. Sixty-five studies were included encompassing 3,044 patients who underwent fertility-sparing surgery, including 1,047 pregnancies with reported reproductive outcomes. The mean clinical pregnancy rate of patients trying to conceive was 55.4%, with the highest clinical pregnancy rate after vaginal radical trachelectomy (67.5%). The mean live-birth rate was 67.9% in our study. Twenty percent of pregnancies after fertility-sparing surgery required assisted reproductive technology. The mean cancer recurrence rate was 3.2%, and the cancer death rate was 0.6% after a median follow-up period of 39.7 months with no statistically significant difference across surgical approaches. Fertility-sparing surgery is a reasonable alternative to traditional radical hysterectomy for early-stage cervical cancer in women desiring fertility preservation. Vaginal radical trachelectomy had the highest clinical pregnancy rate, and minimally invasive approaches to fertility-sparing surgery had equivalent oncologic outcomes compared with an abdominal approach. The results of our study allow for appropriate patient counseling preoperatively and highlight the importance of a multidisciplinary approach to achieve the best outcomes for each patient.

The pediatric patient and future fertility: optimizing long-term male reproductive health outcomes.

Globally, male factor infertility accounts for 20%-70% of couples struggling to conceive. Certain male pediatric developmental conditions, such as cryptorchidism, hypospadias, testicular and other childhood cancers, infections, and pediatric varicocele have been associated with future infertility. Early fertility preservation, especially in those with pending chemotherapy or genetic conditions such as Klinefelter syndrome, should be strongly considered in patients expected to experience testicular loss. Although optimal treatment timing may be unknown owing to a paucity of long-term prospective studies, early diagnosis and targeted treatment may optimize fertility potential in adulthood.

State of the Art in Fertility Preservation for Female Patients Prior to Oncologic Therapies.

Quality of life improvement stands as one of the main goals of the medical sciences. Increasing cancer survival rates associated with better early detection and extended therapeutic options led to the specific modeling of patients' choices, comprising aspects of reproductive life that correlated with the evolution of modern society, and requires better assessment. Of these, fertility preservation and ovarian function conservation for pre-menopause female oncologic patients pose a contemporary challenge due to procreation age advance in evolved societies and to the growing expectations regarding cancer treatment. Progress made in cell and tissue-freezing technologies brought hope and shed new light on the onco-fertility field. Additionally, crossing roads with general fertility and senescence studies proved highly beneficial due to the enlarged scope and better synergies and funding. We here strive to bring attention to this domain of care and to sensitize all medical specialties towards a more cohesive approach and to better communication among caregivers and patients.

Breast cancer: an update on treatment-related infertility.

Breast cancer (BC) is the most common malignancy in women with a significant increasing incidence during the reproductive life. However, based on the newest anti-cancer molecular targeting drugs, successful treatments lead to the disease healing particularly in young patients, thus refreshing their motherhood programs. However, as effect of the BC treatment, a premature depletion of the ovarian follicle reserve occurs in more than one-third of patients resulting in permanent infertility. To prevent the cancer treatment-related infertility (CTRI), several options are today utilized. Besides the ovary suppression by gonadotropin-releasing hormone agonist (GnRHa), other procedures include either oocytes or embryos cryopreservation as well as ovarian cortex cryopreservation that are currently adopted before anti-cancer therapies. These modern techniques appear variably successful in terms of pregnancy rate though their safety concerning the hormonal stimulation to promote the folliculogenesis is still debated in relation to the potential oncogenic risk in patients bearing hormone-sensitive tumors as BC, while the ovarian cortex re-implantation often results in a low number of regenerated follicles including oocytes of unknown quality. Recent studies on ovarian stem cells (OSCs) suggest their use for future application in CTRI. In fact, OSCs from ovarian cortex have been shown to differentiate in vitro into oocyte-like cells (OLCs) and express molecular markers of mature oocytes. Once the OSC technology will be optimized and translated to clinical use, oocytes derived from these cells will be molecularly assessed before fertilization to assure their best embryo quality resulting in a safe procedure to treat CTRI in patients as young women with BC.

The role of microRNAs in ovarian function and the transition toward novel therapeutic strategies in fertility preservation: from bench to future clinical application.

BACKGROUND: New therapeutic approaches in oncology have converted cancer from a certain death sentence to a chronic disease. However, there are still challenges to be overcome regarding the off-target toxicity of many of these treatments. Oncological therapies can lead to future infertility in women. Given this negative impact on long-term quality of life, fertility preservation is highly recommended. While gamete and ovarian tissue cryopreservation are the usual methods offered, new pharmacological-based options aiming to reduce ovarian damage during oncological treatment are very attractive. In this vein, advances in the field of transcriptomics and epigenomics have brought small noncoding RNAs, called microRNAs (miRNAs), into the spotlight in oncology. MicroRNAs also play a key role in follicle development as regulators of follicular growth, atresia and steroidogenesis. They are also involved in DNA damage repair responses and they can themselves be modulated during chemotherapy. For these reasons, miRNAs may be an interesting target to develop new protective therapies during oncological treatment. This review summarizes the physiological role of miRNAs in reproduction. Considering recently developed strategies based on miRNA therapy in oncology, we highlight their potential interest as a target in fertility preservation and propose future strategies to make the transition from bench to clinic. OBJECTIVE AND RATIONALE: How can miRNA therapeutic approaches be used to develop new adjuvant protective therapies to reduce the ovarian damage caused by cytotoxic oncological treatments? SEARCH METHODS: A systematic search of English language literature using PubMed and Google Scholar databases was performed through to 2019 describing the role of miRNAs in the ovary and their use for diagnosis and targeted therapy in oncology. Personal data illustrate miRNA therapeutic strategies to target the gonads and reduce chemotherapy-induced follicular damage. OUTCOMES: This review outlines the importance of miRNAs as gene regulators and emphasizes the fact that insights in oncology can inspire new adjuvant strategies in the field of onco-fertility. Recent improvements in nanotechnology offer the opportunity for drug development using next-generation miRNA-nanocarriers. WIDER IMPLICATIONS: Although there are still some barriers regarding the immunogenicity and toxicity of these treatments and there is still room for improvement concerning the specific delivery of miRNAs into the ovaries, we believe that, in the future, miRNAs can be developed as powerful and non-invasive tools for fertility preservation.

FERTILITY PRESERVATION: Progress and prospects for developing human immature oocytes in vitro.

Ovarian cryopreservation rapidly developed from basic science to clinical application and can now be used to preserve the fertility of girls and young women at high risk of sterility. Primordial follicles can be cryopreserved in ovarian cortex for long-term storage and subsequently autografted back at an orthotopic or heterotopic site to restore fertility. However, autografting carries a risk of re-introducing cancer cells in patients with blood-born leukaemias or cancers with a high risk of ovarian metastasis. For these women fertility restoration could only be safely achieved in the laboratory by the complete in vitro growth (IVG) and maturation (IVM) of cryopreserved primordial follicles to fertile metaphase II (MII) oocytes. Culture systems to support the development of human oocytes have provided greater insight into the process of human oocyte development as well as having potential applications within the field of fertility preservation. The technology required to culture human follicles is extremely challenging, but significant advances have been made using animal models and translation to human. This review will detail the progress that has been made in developing human in vitro growth systems and consider the steps required to progress this technology towards clinical application.

Reproductive surgery: glimpses into the past and thoughts for the future (part 2).

This month's Views and Reviews continues with part two of the series regarding reproductive surgery. The roles of reproductive surgery in müllerian anomalies, tubal and pelvic disease, fertility preservation, and male reproductive surgery are included. Augmenting each contribution, authors have added images and videos to their reflections.