Oncological treatments have limited effects on the fertility prognosis in testicular cancer: A systematic review and meta-analysis.

BACKGROUND: Testicular cancer is the most common solid tumour among young men in the reproductive phase. After completing cancer treatment, up to 77% of cancer survivors report an interest in paternity after completing cancer treatment. To preserve fertility, most guidelines recommend that physicians should counsel their patients about sperm cryopreservation before initiating gonadotoxic therapy. However, few studies have assessed fertility parameters after testicular cancer therapies over the last 20 years. OBJECTIVES: To close the gap of data regarding gonadotoxicity of testicular cancer therapies to enable more accurate counselling regarding fertility preservation. MATERIALS AND METHODS: A systematic literature search was conducted in Medline, Embase and Cochrane until December 2022. The systematic review included studies of men who had undergone all types of unilateral testicular cancer treatment, whereas the meta-analysis excluded studies with unspecified treatments, less than 10 patients for outcome evaluation or rare tumours. Infertility (i.e. azoospermia, failure to achieve paternity or the usage of cryosperm) was defined as outcome. RESULTS: The qualitative analysis included 30 studies with a total of 13,718 men after unilateral testicular cancer. Treatment comprised active surveillance after unilateral orchidectomy (32.7%), radiotherapy (23.1%), standard- or low-dose chemotherapy (33.7%) and high-dose chemotherapy (1.4%). Post-treatment spermiograms were analysed in 17 studies. The quantitative synthesis included 23 studies, revealing an overall pooled prevalence of infertility (95% CI) of 14% (9%-21%). Azoospermia occurred in 8% (6%-12%). For good-prognosis patients who received standard therapy, the overall prevalence of infertility was only 4% (2%-10%). CONCLUSION: So far, this very first meta-analysis of overall infertility prevalence provides the best approximation of fertility prognosis for men who have undergone testicular cancer therapy. Despite the low prevalence of infertility, it is still recommended to undergo sperm cryopreservation because of the uncertainty of the subsequent therapy and the lack of large longitudinal data on individual treatment effects.

Systematic Review of the Gonadotoxicity and Risk of Infertility of Soft Tissue Sarcoma Chemotherapies in Pre- and Postpubertal Females and Males.

Increasing awareness of gonadotoxicity in cancer treatments and infertility risk is essential for counseling young cancer patients. While fertility preservation options are available in many countries, limited data on gonadotoxicity hinder recommendations, especially for soft tissue cancers. This review, part of the FertiTOX project (www.fertitox.com), organized by FertiPROTEKT (www.fertiprotekt.com), aims to address this knowledge gap to improve fertility preservation guidance. We performed a systematic literature search on gonadotoxicity in soft tissue sarcoma (STS) cancer treatments. Only patients without metastases or recurrent disease were considered. "Suspected infertility" was defined based on low ovarian reserve parameters, low inhibin B levels, high gonadotropin concentration, gonadal dysfunction, amenorrhea, oligomenorrhea, azoospermia, or oligozoospermia due to limited infertility data. The study quality was assessed using the Newcastle-Ottawa Scale. The search yielded 3309 abstracts, with 138 undergoing full-text analysis. Eight studies on STS were included. Suspected infertility was observed in 20 of 28 females (71.4%, range 0-100%) and 38 of 63 males (60.3%, range 34.8-100%) with STS. Six of the eight studies received high-quality scores on the NOS, while two received a fair score. Our data suggest a high risk of infertility from chemotherapy in pre- and postpubertal STS survivors. This underscores the importance of considering fertility preservation measures when counseling these patients.

A Systematic Review of the Gonadotoxicity of Osteosarcoma and Ewing's Sarcoma Chemotherapies in Postpubertal Females and Males.

Data on gonadotoxicity of chemotherapies are essential to better counsel young females and males about the risk of infertility and to better indicate fertility preservation measures before cancer therapies. However, such data have not recently been reviewed for bone cancer. Therefore, a systematic literature search was conducted considering papers published since 2000. This study is part of the FertiTOX® project, which aims to improve the lack of data regarding gonadotoxicity of cancer therapies to enable more accurate counseling regarding fertility preservation. Only relapse-free women and men were included. Gonadotoxic therapy-induced suspected infertility was defined as very low anti-mullerian hormone, high gonadotropin concentration, amenorrhea, oligomenorrhea, azoospermia, or oligozoospermia. The quality of the individual studies was assessed using the Newcastle-Ottawa Scale (NOS). In total, 11 out of 831 studies were included in the review. Suspected infertility was found in 10/190 (5.1%, range 0%-66%) of female patients with osteosarcoma (six studies), in 24/46 (52.2%, range 46%-100%) of male patients with osteosarcoma (three studies), in 18/138 (13.0%, range 3%-18%) of female patients with Ewing's sarcoma (three studies), and in 34/38 (89.5%) of male patients with Ewing's sarcoma (one study). A risk calculation in relation to specific chemotherapies was not possible. Risk of suspected infertility tends to be higher in Ewing's sarcoma in which all patients received chemotherapies with alkylating agents. Two of the 11 included studies received a high NOS quality score, whereas the remaining nine studies received a low quality score, mainly because of the lack of a comparator group. Published data are too limited for precise estimation of the gonadotoxicity. However, data indicate clinically relevant risk for infertility, supporting counseling patients before chemotherapy about fertility preservation measures.

Unmet clinical needs in women with polycystic ovary syndrome in regard to mental health: a cross-sectional study.

PURPOSE: Polycystic ovary syndrome (PCOS) management has hardly been standardized until recent years. Despite the existence of a detailed, evidence-based guideline published by the European Society of Human Reproduction and Embryology (ESHRE), it remains unclear to what extent healthcare providers adhere to this guideline. Our aim is to evaluate the gynaecological medical care provided in women with PCOS, particularly in terms of mental health, from the patients' perspective. METHODS: For this cross-sectional online cohort study in women with PCOS, we designed a standardized, non-validated questionnaire covering aesthetic aspects, metabolism, menstrual cycle, reproduction, mental health, and prevention of chronic non-communicable diseases. RESULTS: Among 1879 participants, various mental health aspects were reported: body image (n = 1879), eating patterns/habits (n = 1878), and emotional well-being (n = 1874). Although nearly all women (99.7%) reported complaints on at least one session of mental health, consultation rates were low (body image 9.7%, eating patterns/habits 16.6%, emotional well-being 4.4%). Mean satisfaction with counselling on the different domains varied from moderate to fairly satisfying, with scores of 56.0 points (SD 31.7), 53.5 points (SD 32.0), and 63.7 points (SD 30.2), respectively. More complaints were associated with lower satisfaction. The overall satisfaction with the management provided by the healthcare practitioner (HCP) was low, averaging 36.5 points (SD 29.7). Consequently, most women wished for more counselling (58.9%). CONCLUSION: Women affected by PCOS are not properly managed according to ESHRE guideline in regard to mental health issues. Overall consultation rates and corresponding satisfaction with management were poor, highlighting the need for significant improvements in healthcare provision.

Evaluation of the Gonadotoxicity of Cancer Therapies to Improve Counseling of Patients About Fertility and Fertility Preservation Measures: Protocol for a Retrospective Systematic Data Analysis and a Prospective Cohort Study.

BACKGROUND: Cytotoxic treatments such as chemo- and radiotherapy and immune therapies are required in cancer diseases. These therapies have the potential to cure patients but may also have an impact on gonadal function and, therefore, on fertility. Consequently, fertility preservation treatments such as freezing of gametes and gonadal tissue might be required. However, as detailed data about the necessity to perform fertility preservation treatment are very limited, this study was designed to fill this data gap. OBJECTIVE: Primary objective of this study is to analyze the impact of cancer therapies and chemotherapies on the ovarian reserve and sperm quality. Secondary objectives are to analyze the (1) impact of cancer therapies and chemotherapies on other fertility parameters and (2) probability of undergoing fertility preservation treatments in relation to specific cancer diseases and treatment protocols and the probability to use the frozen gametes and gonadal tissue to achieve pregnancies. METHODS: First, previously published studies on the gonadotoxicity of chemo- and radiotherapies among patients with cancer will be systematically analyzed. Second, a prospective cohort study set up by approximately 70 centers in Germany, Switzerland, and Austria will collect the following data: ovarian function by analyzing anti-Müllerian hormone (AMH) concentrations and testicular function by analyzing sperm parameters and total testosterone immediately before and around 1 year after gonadotoxic therapies (short-term fertility). A follow-up of these fertility parameters, including history of conceptions, will be performed 5 and 10 years after gonadotoxic therapies (long-term fertility). Additionally, the proportion of patients undergoing fertility-preserving procedures, their satisfaction with these procedures, and the amount of gametes and gonadal tissue and the children achieved by using the frozen material will be analyzed. Third, the data will be merged to create the internet-based data platform FertiTOX. The platform will be structured in accordance with the ICD (International Classification of Diseases) classification of cancer diseases and will be easily be accessible using a specific App. RESULTS: Several funding bodies have funded this study. Ten systematic reviews are in progress and the first one has been accepted for publication. All Swiss and many German and Austrian ethics committees have provided their approval for the prospective cohort study. The study registry has been set up, and a study website has been created. In total, 50 infertility centers have already been prepared for data collection, which started on December 1, 2023. CONCLUSIONS: The study can be expected to bridge the data gap regarding the gonadotoxicity of cancer therapies to better counsel patients about their infertility risk and their need to undergo fertility preservation procedures. Initial data are expected to be uploaded on the FertiTOX platform in 2026. TRIAL REGISTRATION: ClinicalTrials.gov NCT05885048; https://clinicaltrials.gov/study/NCT05885048. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/51145.

Unmet Clinical Needs in Women with Aesthetic Manifestations of Polycystic Ovary Syndrome: A Cross-Sectional Study.

Background: Polycystic ovary syndrome (PCOS) management has hardly been standardized until recent years. There is an accurate, evidence-based guideline published by the European Society of Human Reproduction and Embryology (ESHRE). However, it remains unclear to which extent, if at all, the guideline is followed by health care providers. The aim was to explore the subjectively perceived quality of gynecological medical care in women with PCOS suffering from aesthetic complaints. Materials and Methods: A nonvalidated questionnaire was constructed in a standardized manner covering the domains: aesthetic aspects, metabolism, menstrual cycle, reproduction, mental health, and prevention of chronic noncommunicable diseases. Results: A total of 1960 participants with aesthetic complaints, such as acne (66.2%), alopecia (43.9%), hirsutism (77.9%), or overweight/obesity (72.3%) were included. The percentage of women being counseled was low (acne 20.3%, alopecia 12.9%, hirsutism 17.5%, overweight/obesity 36.2%). Satisfaction with counseling was moderate (40.4-44.1 points). Many women tried at least one therapeutic method (75.9%), whereas only a few were counseled for therapy (acne 27.0%, alopecia 24.6%, hirsutism 24.0%, overweight/obesity 18.8%) with moderate satisfaction for hyperandrogenism (mean 55.1-59.5 points) and good satisfaction for overweight/obesity (mean 60.8 points). Overall satisfaction was rated with a mean of 30.5 points (standard deviation 27.1) on a scale from 0 to 100 and thus considered "not satisfied." Fewer complaints were significantly correlated with higher satisfaction. Most women wished for more counseling (80.8%), as well as more diagnostic (63.2%) and therapeutic options (70.2%). Conclusions: Women affected by PCOS are not properly managed according to the ESHRE guideline. Indeed, this guideline recommends comprehensive history and physical examination for clinical hyperandrogenism as well as holistic approaches in therapy, including education and counseling of patients. Still, overall consultation rates and satisfaction were poor.

Impact of estrogens on resting energy expenditure: A systematic review.

The fear of weight gain is one of the main reasons for women not to initiate or to early discontinue hormonal contraception or menopausal hormone therapy. Resting energy expenditure is by far the largest component and the most important determinant of total energy expenditure. Given that low resting energy expenditure is a confirmed predictive factor for weight gain and consecutively for the development of obesity, research into the influence of sex steroids on resting energy expenditure is a particularly exciting area. The objective of this systematic review was to evaluate the effects of medication with natural and synthetic estrogens on resting energy expenditure in healthy normal weight and overweight women. Through complex systematic literature searches, a total of 10 studies were identified that investigated the effects of medication with estrogens on resting energy expenditure. Our results demonstrate that estrogen administration increases resting energy expenditure by up to +208 kcal per day in the context of contraception and by up to +222 kcal per day in the context of menopausal hormone therapy, suggesting a preventive effect of circulating estrogen levels and estrogen administration on weight gain and obesity development.

Non-antibiotic treatment of bacterial vaginosis-a systematic review.

PURPOSE: Bacterial vaginosis (BV) is one of the most common vaginal complaints of women of reproductive age, characterized by a shift from a Lactobacillus-dominated vaginal microbiome towards a more diverse flora of facultative and obligately anaerobic bacteria. BV can increase the risk of preterm births, contracting sexually transmitted infections and developing other chronic health issues. Standard treatment for BV are antibiotics, however despite initial efficacy, they do not provide effective long-term treatment and recurrence or persistence prevention. This systematic review focuses on describing the current study situation and summarizing the newest data on the efficacy of alternative non-antibiotic options, namely probiotic products containing lactobacilli, lactic acid, sucrose gel, combination products with estriol, and supplementation of antibiotics. METHODS: We conducted a systematic literature search using the MEDLINE database and evaluated the 33 trials which met our inclusion criteria. CONCLUSION: The diverse study designs produced extremely varied outcomes, but so far the results are promising. Furthermore, these alternatives have shown little to no adverse effects and are consequently generally considered safe to use. In general, the results of this review warrant more thorough trials with larger cohort sizes to provide sufficient evidence for these alternatives to be a part of official treatment recommendations.