[Prevention of infertility : recognizing and targeting numerous risk factors]. / Prévention de l'infertilité : reconnaître et cibler les nombreux facteurs de risque.

Follow-up consultations in gynaecology and general practice offer valuable opportunities to discuss fertility and the importance of a pre-conceptional assessment before attempting pregnancy. During these consultations, it is vital for healthcare professionals to provide patients with essential information about considerations before conceiving a child. Additionally, it is important to educate patients about basic hygiene practices that can impact both male and female fertility. The prevention of fertility disorders requires a holistic approach identifying and targeting numerous risk factors.

Les consultations de suivi en gynécologie et en médecine générale offrent des opportunités précieuses pour discuter de la fertilité et de l'importance d'une évaluation préconceptionnelle avant toute tentative de grossesse. Au cours de ces consultations, il est primordial pour les professionnels de santé de fournir aux patients des informations essentielles concernant les aspects à considérer avant de concevoir un enfant. De plus, il convient de sensibiliser les patients aux pratiques d'hygiène de base qui peuvent avoir un impact sur la fertilité masculine et féminine. La prévention des troubles de la fertilité nécessite une approche holistique identifiant et ciblant de nombreux facteurs de risque.

Fertility preservation before and after cancer treatment in children, adolescents, and young adults.

Fertility is a top concern for many survivors of cancer diagnosed as children, adolescents and young adults (CAYA). Fertility preservation (FP) treatments are effective, evidence-based interventions to support their family building goals. Fertility discussions are a part of quality oncology care throughout the cancer care continuum. For nearly 2 decades, clinical guidelines recommend counseling patients about the possibility of infertility promptly at diagnosis and offering FP options and referrals as indicated. Multiple guidelines now recommend post-treatment counseling. Infertility risks differ by cancer treatments and age, rendering risk stratification a central part of FP care. To support FP decision-making, online tools for female risk estimation are available. At diagnosis, females can engage in mature oocyte/embryo cryopreservation, ovarian tissue cryopreservation, ovarian suppression with GnRH agonists, in vitro oocyte maturation, and/or conservative management for gynecologic cancers. Post-treatment, several populations may consider undergoing oocyte/embryo cryopreservation. Male survivors' standard of care FP treatments center on sperm cryopreservation before cancer treatment and do not have the same post-treatment indication for additional gamete cryopreservation. In practice, FP care requires systemized processes to routinely screen for FP needs, bridge oncology referrals to fertility, offer timely fertility consultations and access to FP treatments, and support financial navigation. Sixteen US states passed laws requiring health insurers to provide insurance benefits for FP treatments, but variation among the laws and downstream implementation are barriers to accessing FP treatments. To preserve the reproductive futures of CAYA survivors, research is needed to improve risk stratification, FP options, and delivery of FP care.

Novel therapeutic strategies for injured endometrium: intrauterine transplantation of menstrual blood­derived cells from infertile patients.

BACKGROUND: Menstrual blood-derived cells show regenerative potential as a mesenchymal stem cell and may therefore be a novel stem cell source of treatment for refractory infertility with injured endometrium. However, there have been few pre-clinical studies using cells from infertile patients, which need to be addressed before establishing an autologous transplantation. Herein, we aimed to investigate the therapeutic capacity of menstrual blood-derived cells from infertile patients on endometrial infertility. METHODS: We collected menstrual blood-derived cells from volunteers and infertile patients and confirmed their mesenchymal stem cell phenotype by flow cytometry and induction of tri-lineage differentiation. We compared the proliferative and paracrine capacities of these cells. Furthermore, we also investigated the regenerative potential and safety concerns of the intrauterine transplantation of infertile patient-derived cells using a mouse model with mechanically injured endometrium. RESULTS: Menstrual blood-derived cells from both infertile patients and volunteers showed phenotypic characteristics of mesenchymal stem cells. In vitro proliferative and paracrine capacities for wound healing and angiogenesis were equal for both samples. Furthermore, the transplantation of infertile patient-derived cells into uterine horns of the mouse model ameliorated endometrial thickness, prevented fibrosis, and improved fertility outcomes without any apparent complications. CONCLUSIONS: In our pre-clinical study, intrauterine transplantation of menstrual blood-derived cells may be a novel and attractive stem cell source for the curative and prophylactic therapy for injured endometrium. Further studies will be warranted for future clinical application.

Human rights approaches to reducing infertility.

In April 2023, the World Health Organization (WHO) issued new estimates affirming that one in six individuals experience infertility globally. Yet, many states are unclear on their responsibility to prevent infertility, ensure access to treatment, and to end the harm suffered by individuals who are considered infertile. Responding to this uncertainty, in June 2023, the United Nations Office of the High Commissioner on Human Rights (OHCHR) issued a new research paper explaining states' legal obligations regarding infertility. Importantly, OHCHR underscores that states must take steps to prevent infertility by addressing its root causes and ensure access to treatment. Further, states must address the negative consequences of infertility, including stigma and violence, as well as the discriminatory stereotypes that lead to certain groups facing disproportionate harm from infertility. This article provides an overview of the OHCHR report and explains what this means for healthcare providers, who have a critical role to play in providing care and advocating for legal and policy reform necessary to prevent, diagnose, and treat infertility.

Fertility preservation in pediatric leukemia and lymphoma: A report from the Children's Oncology Group.

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 Children's 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.

Development, Usability Testing, and Implementation Assessment of Cancer Related Infertility Score Predictor, an Online Cancer Related Infertility Risk Counseling Tool.

Purpose: Oncofertility counseling of female cancer patients lacks efficient access to tailored and valid infertility risk estimates to support shared decision-making on fertility preservation treatments. The objective was to develop, conduct user-centered design, and plan clinic-based implementation of the Cancer Related Infertility Score Predictor (CRISP), a web-based tool to support infertility risk counseling. Methods: Using a mixed methods design, literature review was undertaken to abstract data on infertility, primary ovarian insufficiency, and amenorrhea risks of common cancer treatments. The CRISP website was programmed to take user input about patient ages and cancer treatments and generate a risk summary. Using user experience methodology and semistructured interviews, usability testing and implementation assessment were conducted with 12 providers recruited from 5 medical centers in Southern California. Results: The web-based CRISP tool encompasses infertility risk data for 60 treatment regimens among 10 cancer types. Usability testing demonstrated that the tool is intuitive and informed minor modifications, including adding crowd-sourced submission of additional cancer treatments. Participants rated the tool as credible, advantageous over current provider methods to ascertain infertility risks, and useful for tailoring treatment planning and counseling patients. A key barrier was lack of information on some cancer treatments. Fit within clinical workflow was feasible, particularly with electronic health record integration. Conclusions: The novel, web-based CRISP tool is a feasible, acceptable, and appropriate tool to address provider knowledge gap about cancer related infertility risks and use for patient counseling. CRISP has significant potential to support tailored oncofertility counseling in the heterogeneous young cancer patient population.

Investigation of Fertility Preservation Education Videos for Pediatric Patients Based on International and Historical Survey.

Purpose: Recently, direct communication with children about cancer seems to have shifted, but little is known about communication regarding discussions of future infertility risk due to cancer therapy. This study conducted cross-cultural comparisons between Japan and the United States to clarify communication patterns about cancer notification and develop appropriate information about fertility issues. Methods: An online survey was distributed to members of the Japanese Society of Pediatric Hematology/Oncology in July 2019 and the American Society of Pediatric Hematology/Oncology in July 2020. Based on the results from the survey, we developed three types of educational videos: a prepubertal version A, B, and a pubertal version. Next, we conducted a survey to assess whether these were appropriate for clinical practice. Results: We analyzed 325 physicians in Japan and 46 in the United States. In Japan, 80.5%, 91.7%, and 92.1% of the physicians notified patients aged 7-9, 10-14, and 15-17 years of their cancer diagnosis directly, respectively, compared within the United States, where the rate was 100%, regardless of age. Further, 9% and 45% of physicians in Japan and the United States, respectively, discuss fertility issues directly with patients aged 7-9 years. In the survey to assess the educational videos, 85% of the physicians preferred to use the educational videos in clinical practice. Conclusion: This is the first step in bringing concordance to communication patters for emerging cancer care around the globe and that this study and its intervention arm provide guidance in ways that ensure global equity in care.

Banking on Fertility Preservation: Financial Concern for Adolescent and Young Adult Cancer Patients Considering Oncofertility Services.

Purpose: Financial concern is a major issue for adolescent and young adult (AYA) cancer patients. Furthermore, unaddressed oncofertility challenges (e.g., infertility) are linked to psychological distress and decreased overall quality of life. Little is known about how financial concern in terms of oncofertility (i.e., concern regarding affording fertility preservation [FP] services) impacts AYAs' decision making and experiences. Methods: AYA cancer patients (n = 27) aged 12-25 years whose cancer treatment conferred risk of infertility were recruited through electronic health record query. Participants completed semi-structured interviews, which were recorded, transcribed, and deductively coded for themes related to information needs, knowledge of treatment effects on fertility, and reproductive concerns after cancer. Emergent, inductive themes related to financial concern were identified. The Institutional Review Board at the University of Michigan approved this study (HUM#00157267). Results: Financial concern was a dominant theme across the qualitative data. Emergent themes included (1) varied access to health insurance, (2) presence of parental/guardian support, (3) reliance upon financial aid, (4) negotiating infertility risk, and (5) lack of preparation for long-term costs. AYAs relied heavily upon parents for out-of-pocket and insurance coverage support. Some participants sought financial aid when guided by providers. Several participants indicated that no financial support existed for their circumstance. Conclusions: Financial consequences in terms of oncofertility are a major issue affecting AYA cancer patients. The incidence and gravity of financial concern surrounding affording oncofertility services merits attention in future research (measuring financial resources of AYAs' parental/support networks), clinical practice (strategically addressing short- and long-term costs; tailored psychosocial support), and health care policy (promoting legislation to mandate pre- and post-treatment FP coverage).

An Educational Need Regarding Treatment-Related Infertility and Fertility Preservation: a National Survey Among Members of the Dutch Society for Medical Oncologists.

Cancer diagnosis and treatment may influence reproductive planning and impact fertility in patients of reproductive age. Although guidelines have been established in the past decade, education, practice, and attitudes of medical oncologists regarding fertility preservation remain undecided. A nationwide survey was performed among members of the Dutch Society for Medical Oncology. Demographics, practice, knowledge, and barriers were measured regarding information provision of fertility preservation towards cancer patients of childbearing age. From 392 members, 120 oncologists completed the questionnaire (30.6%). Majority of oncologists was convinced it is their responsibility to discuss impact of cancer treatment to fertility (93.2%), yet 68.3% discussed the subject often or always (n = 82). Oncologists employed in district general hospitals were less likely to discuss fertility (p = 0.033). On average, 44.6% of reproductive men and 28.9% of reproductive women is referred to fertility specialists. Half of the respondents declared to possess sufficient knowledge regarding fertility preservation (n = 57, 47.5%). Poor prognosis (53%), unlikely survival (43.1%), and high chances on fertility recovery (28.7%) were identified as barriers to discussing fertility preservation. Among oncologists, impact of cancer treatment on fertility is a well-accepted responsibility to counsel. Despite, self-reported knowledge regarding fertility preservation is strongly varying. In practice, fertility is discussed to some extent, influenced by several barriers and depending on prognosis and type of hospital. Patients benefit from knowledge improvement among oncology care providers concerning fertility effects of cancer treatment. Education during medical school, residency, and among practicing oncologists may raise awareness, together with enhancement of referral possibilities.

Factors Associated With Fertility Preservation in a Pediatric, Adolescent and Young Adult Population.

OBJECTIVE: To determine the patient characteristics associated with pursuing fertility preservation (FP) before gonadotoxic therapy in a pediatric, adolescent and young adult patient population. METHODS: This is a retrospective cohort study of patient data at Cincinnati Children's Hospital Medical Center. Demographics, clinical diagnoses, and treatment characteristics were compared between participants that selected FP versus those that declined. Variables were analyzed separately for males and females by logistic regression. RESULTS: Patients with a hematologic cancer were less likely to be eligible for preservation: 53.9% of ineligible males, P <0.001, and 51.8% of ineligible females, P <0.0001. Among patients who were candidates for FP, those receiving high-risk therapy were more likely to elect for FP (65.3% males, P <0.0001, and 87.5% of females, P <0.0001). Pubertal males were more likely to undergo preservation than prepubertal males (70.5% vs. 29.5%, P <0.0001; however, this trend was not demonstrated among female patients. In both males and females, race, ethnicity, religion, primary language, and insurance status were not shown to be statistically significant factors in predicting utilization of FP. CONCLUSION: Risk of infertility, type of cancer, and developmental status influenced decisions on pursuing FP in pediatric, adolescent and young adult patients facing iatrogenic infertility.

Update on fertility preservation: new opportunities and challenges in the fight against infertility.

Abstract: Infertility has been characterized as a disease by the World Health Organization (WHO) and reportedly affects about 10-12% of couples worldwide, while the incidence is even higher in Italy, at about 15%. The issue of iatrogenic infertility arising from treatments that can compromise an individual's reproductive capacity, it is necessary to inform patients of the possible damage on their future fertility and on the possibilities to preserve it. The complexities inherent in the various techniques and approaches aimed at preserving fertility should be expounded upon thoroughly to the patients, who should also receive proper psychological assistance and counseling, which ought to take into account the ethical distinctive challenges and the possible misgivings that may be caused in patients. Ovarian Tissue Cryopreservation (OTC) and ovarian tissue transplantation (OTT) can constitute a valuable part of the clinical armamentarium for preserving fertility, although the data are still inconclusive, particularly in over-36 patients. The multidisciplinary nature of the healthcare teams involved in such interventions is of paramount importance to optimize results.

Multidisciplinary consensus on the criteria for fertility preservation in cancer patients.

Infertility is one of the main sequelae of cancer and its treatment in both children and adults of reproductive age. It is, therefore, essential that oncologists and haematologists provide adequate information about the risk of infertility and the possibilities for its preservation before starting treatment. Although many international clinical guidelines address this issue, this document is the first Spanish multidisciplinary guideline in paediatric and adult oncological patients. Experts from the Spanish Society of Medical Oncology, the Spanish Fertility Society, the Spanish Society of Haematology and Haemotherapy, the Spanish Society of Paediatric Haematology and Oncology and the Spanish Society of Radiation Oncology have collaborated to develop a multidisciplinary consensus.

Gonadal Failure and Infertility in Cancer Survivors: Clinical Management and Strategies for Prevention.

Modern advances in oncological treatments determined a significant improvement in survival rates for several malignancies. Nevertheless, survivorship and quality of life of cancer survivors may be negatively impaired by metabolic and endocrine side effects related to anticancer treatments, including alterations of pituitary-gonadal axis function. In fact, both medical (chemo- and radiotherapy) and surgical approaches may negatively impact on gonadal function, leading to transient or permanent hypogonadism and infertility. In view of these considerations, fertility preservation (FP) should be a primary concern in all oncological patients who may potentially achieve parenthood, irrespectively from their sex and pubertal status at treatment, and adequate counselling should be provided before undergoing gonadotoxic therapy or gonadectomy. Cryopreservation of gametes, when feasible, represents the mainstay for FP in postpubertal age, while procedures involving storage of tissue specimens or stem cells should still be considered as experimental. Given the complexity of both hormonal and psychological implications in this clinical setting, a multidisciplinary approach is advisable for optimal FP and for early diagnosis and treatment of hypogonadism.

Small and Large Intestine (I): Malabsorption of Nutrients.

Numerous disorders can alter the physiological mechanisms that guarantee proper digestion and absorption of nutrients (macro- and micronutrients), leading to a wide variety of symptoms and nutritional consequences. Malabsorption can be caused by many diseases of the small intestine, as well as by diseases of the pancreas, liver, biliary tract, and stomach. This article provides an overview of pathophysiologic mechanisms that lead to symptoms or complications of maldigestion (defined as the defective intraluminal hydrolysis of nutrients) or malabsorption (defined as defective mucosal absorption), as well as its clinical consequences, including both gastrointestinal symptoms and extraintestinal manifestations and/or laboratory abnormalities. The normal uptake of nutrients, vitamins, and minerals by the gastrointestinal tract (GI) requires several steps, each of which can be compromised in disease. This article will first describe the mechanisms that lead to poor assimilation of nutrients, and secondly discuss the symptoms and nutritional consequences of each specific disorder. The clinician must be aware that many malabsorptive disorders are manifested by subtle disorders, even without gastrointestinal symptoms (for example, anemia, osteoporosis, or infertility in celiac disease), so the index of suspicion must be high to recognize the underlying diseases in time.

A call to action: unified clinical practice guidelines for oncofertility care.

By 2030, WHO estimates that 1.4 million reproductive-aged women will be diagnosed with cancer annually. Fortunately, cancer is no longer considered an incurable disease in many cases. From 2008-2014, 85% of women under the age of 45 years diagnosed with cancer survived. This increase in survival rate has shifted attention from focusing exclusively on preserving life to focusing on preserving quality of life after treatment. One aspect of this is preserving the ability to have a biological family. Oncofertility, the field that bridges oncology and reproductive endocrinology with the goal of preserving fertility, offers these patients hope. Though it is clear that ASCO and ASRM recognize the importance of fertility preservation as an aspect of comprehensive oncology care, there are not yet unified guidelines for oncologists and fertility specialists for treating oncofertility patients. First, we identify the need for reproductive counseling prior to cancer treatment, as many patients report that their fertility preservation concerns are not addressed adequately. We then delineate multi-modal fertility preservation options that are available and appropriate for different patients with corresponding outcomes using different treatments. We discuss the unique challenges and considerations, including ethical dilemmas, for delivering timely and comprehensive care specifically for oncofertility patients. Finally, we address the multidisciplinary team that includes oncologists, reproductive endocrinologists, surgeons as well as their staff, nurses, genetic counselors, mental health professionals, and more. Since oncofertility patient care requires the coordination of both physician teams, one set of unified guidelines will greatly improve quality of care.

Cancer survivorship: Reproductive health outcomes should be included in standard toxicity assessments.

It is well established that cancer and its treatment, whether by chemotherapy, radiotherapy, hormone therapy, or surgery, can adversely impact reproductive function in both women and men. The effects of cancer treatment on reproductive function in both sexes may lead to loss of fertility, sexual desire and function, and hormone deficiency, which results in additional long-term morbidity in more than a third of patients. Given the importance of reproductive function to most people, and the often devastating effect of cancer treatment on it, we propose that proactive assessment of the functional and endocrinological impact of treatment be made a vital component of the assessment of modern cancer treatment, and should be a routine part of discussions with patients before and after treatment, both in trials and in routine care. Reproductive counselling should be proactive and encouraged, as implementation of such counselling has been shown to be beneficial to patient mental health, quality of life, and adherence to treatment. Similarly, efforts should be made to provide more adequate and accurate information to patients, as well as to offer appropriate fertility preservation approaches, which may potentially influence their treatment decisions.

Development of a Set of Lupus-Specific, Ambulatory Care-Sensitive, Potentially Preventable Adverse Conditions: A Delphi Consensus Study.

OBJECTIVE: Individuals with systemic lupus erythematosus (SLE) are at high risk for infections and SLE- and medication-related complications. The present study was undertaken to define a set of SLE-specific adverse outcomes that could be prevented, or their complications minimized, if timely, effective ambulatory care had been received. METHODS: We used a modified Delphi process beginning with a literature review and key informant interviews to select initial SLE-specific potentially preventable conditions. We assembled a panel of 16 nationally recognized US-based experts from 8 subspecialties. Guided by the RAND-UCLA Appropriateness Method, we held 2 survey rounds with controlled feedback and an interactive webinar to reach consensus regarding preventability and importance on a population level for a set of SLE-specific adverse conditions. In a final round, the panelists endorsed the potentially preventable conditions. RESULTS: Thirty-five potential conditions were initially proposed; 62 conditions were ultimately considered during the Delphi process. The response rate was 100% for both survey rounds, 88% for the webinar, and 94% for final approval. The 25 SLE-specific conditions meeting consensus as potentially preventable and important on a population level fell into 4 categories: vaccine-preventable illnesses (6 conditions), medication-related complications (8 conditions), reproductive health-related complications (6 conditions), and SLE-related complications (5 conditions). CONCLUSION: We reached consensus on a diverse set of adverse outcomes relevant to SLE patients that may be preventable if patients receive high-quality ambulatory care. This set of outcomes may be studied at the health system level to determine how to best allocate resources and improve quality to reduce avoidable outcomes and disparities among those at highest risk.