FSH and IGF-I synergistically stimulate gonadal steroid production; conversely, silencing the FSH or the IGF-I genes leads to infertility and hypogonadism. To determine the molecular link between these hormones, we examined the signaling cross talk downstream of their receptors. In human and rodent granulosa cells (GCs), IGF-I potentiated the stimulatory effects of FSH and cAMP on the expression of steroidogenic genes. In contrast, inhibition of IGF-I receptor (IGF-IR) activity or expression using pharmacological, genetic, or biochemical approaches prevented the FSH- and cAMP-induced expression of steroidogenic genes and estradiol production. In vivo experiments demonstrated that IGF-IR inactivation reduces the stimulation of steroidogenic genes and follicle growth by gonadotropins. FSH or IGF-I alone stimulated protein kinase B (PKB), which is also known as AKT and in combination synergistically increased AKT phosphorylation. Remarkably, blocking IGF-IR expression or activity decreased AKT basal activity and abolished AKT activation by FSH. In GCs lacking IGF-IR activity, FSH stimulation of Cyp19 expression was rescued by overexpression of constitutively active AKT. Our findings demonstrate, for the first time, that in human, mouse, and rat GCs, the well-known stimulatory effect of FSH on Cyp19 and AKT depends on IGF-I and on the expression and activation of the IGF-IR.

Background Young women with cancer now face the complex decision about whether to undergo fertility preservation. Yet little is known about how these women process information involved in making this decision. Objective The purpose of this paper is to expand theoretical understanding of the decision-making process by examining aspects of information processing among young women diagnosed with cancer. Methods Using a grounded theory approach, 27 women with cancer participated in individual, semi-structured interviews. Data were coded and analyzed using constant-comparison techniques that were guided by five dimensions within the Contemplate phase of the decision-making process framework. Results In the first dimension, young women acquired information primarily from clinicians and Internet sources. Experiential information, often obtained from peers, occurred in the second dimension. Preferences and values were constructed in the third dimension as women acquired factual, moral, and ethical information. Women desired tailored, personalized information that was specific to their situation in the fourth dimension; however, women struggled with communicating these needs to clinicians. In the fifth dimension, women offered detailed descriptions of clinician behaviors that enhance or impede decisional debriefing. Conclusion Better understanding of theoretical underpinnings surrounding women’s information processes can facilitate decision support and improve clinical care.

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Objective To prospectively assess anxiety, depression, coping, and appraisal in female fertility preservation patients compared to infertile patients. Design Prospective pre- and post-treatment survey. Setting Academic medical center. Patients 47 women with cancer (FP) and 91 age-matched infertile patients. Interventions None. Main Outcome Measures Depression, anxiety, coping, infertility–related stress, appraisal of treatment, and medical outcomes. Results FP patients reported more symptoms of anxiety and depression than infertile patients, but infertile patients’ symptoms worsened over time. 44% of FP and 14% of infertile patients’ scores exceeded the clinical cut-off for depression at pre-treatment. The interval between surveys and medical treatment data did not predict changes in mood symptoms. Coping strategies and infertility-related stress did not differ between groups and avoidant coping predicted higher depression and anxiety scores. Conclusion FP patients reported more anxiety and depression than infertile patients at enrollment in treatment, with more than one third of FP patients reporting clinically significant depressive symptoms. However, infertile patients’ anxiety and depressive symptoms increased across treatment. This increase was not related to time between registration for IVF and oocyte retrieval or the medical aspects of treatment. FP and infertile patients should be provided psychological consultation prior to treatment to identify mood and anxiety symptoms and to refer patients for counseling as needed to prevent worsening of symptoms.

Objective To understand young women’s reasons for accepting or declining fertility preservation following cancer diagnosis to aid in the development of theory regarding decision making in this context. Design Qualitative descriptive. Setting Participants’ homes or other private location. Participants Twenty-seven young women (mean age = 29 years) diagnosed with cancer and eligible for fertility preservation. Methods Recruitment was conducted via the Internet and in fertility centers. Participants completed demographic questionnaires and in-depth semi-structured interviews. Tenets of grounded theory guided an inductive and deductive analysis. Results Young women’s reasons for deciding whether to undergo fertility preservation were linked to four theoretical dimensions: Cognitive Appraisals, Emotional Responses, Moral Judgments, and Decision Partners. Women who declined fertility preservation described more reasons in the Cognitive Appraisals dimension, including financial cost and human risks, than women who accepted. In the Emotional Responses dimension, most women who accepted fertility preservation reported a strong desire for biological motherhood, whereas women who declined tended to report a strong desire for surviving cancer. Three participants who declined reported reasons linked to the Moral Judgments dimension, and the majority were influenced by Decision Partners, including husbands, boyfriends, parents, and clinicians. Conclusion The primary reason upon which many but not all participants based decisions related to fertility preservation was whether the immediate emphasis of care should be placed on surviving cancer or securing options for future biological motherhood. Nurses and other clinicians should base education and counseling on the four theoretical dimensions to effectively support young women with cancer.

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Cancer treatments can be detrimental to fertility; recent literature has focused on the efforts of fertility preservation for this patient population. It should be recognized, however, that several nonmalignant medical conditions and therapeutic interventions could be similarly hazardous to fertility. Some of these nonmalignant diseases and their treatments that can adversely impact the reproductive axis are gastrointestinal diseases, rheumatologic disorders, nonmalignant hematologic conditions, neurologic disorders, renal disorders, gynecologic conditions, and metabolic diseases. Their negative effects on reproductive function are only now being appreciated and include impaired ovarian function, endocrine function, or sexual function and inability to carry a pregnancy to term. Complications and comorbidities associated with certain diseases may limit the success of established fertility preservation options. Recent advances in fertility preservation techniques may provide these patients with new options for childbearing. Here, we review several fertility-threatening conditions and treatments, describe current established and experimental fertility preservation options, and present three initiatives that may help minimize the adverse reproductive effects of these medical conditions and treatments by raising awareness of the issues and options: (1) increase awareness among practitioners about the reproductive consequences of specific diseases and treatments, (2) facilitate referral of patients to fertility-sparing or restorative programs, and (3) provide patient education about the risk of infertility at the time of diagnosis before initiation of treatment.

Once unimaginable, fertility management is now a nationally established part of cancer care in institutions, from academic centers to community hospitals to private practices. Over the last two decades, advances in medicine and reproductive science have made it possible for men, women and children to be connected with an oncofertility specialist or offered fertility preservation soon after a cancer diagnosis. The Oncofertility Consortium's National Physicians Cooperative is a large-scale effort to engage physicians across disciplines – oncology, urology, obstetrics and gynecology, reproductive endocrinology, and behavioral health – in clinical and research activities to enable significant progress in providing fertility preservation options to children and adults. Here, we review the structure and function of the National Physicians Cooperative and identify next steps.