The lack of evidence behind over-the-counter antioxidant supplements for male fertility patients: a scoping review.

STUDY QUESTION: What is the evidence for over-the-counter antioxidant supplements for male infertility? SUMMARY ANSWER: Less than half of over-the-counter antioxidant supplements for male fertility patients have been tested in a clinical trial, and the available clinical trials are generally of poor quality. WHAT IS KNOWN ALREADY: The prevalence of male infertility is rising and, with this, the market for supplements claiming to improve male fertility is expanding. Up to now, there is limited data on the evidence for these over-the-counter supplements. STUDY DESIGN SIZE DURATION: Amazon, Google Shopping and other relevant shopping websites were searched on 24 June 2022 with the following terms: 'supplements', 'antioxidants', 'vitamins', AND 'male fertility', 'male infertility', 'male subfertility', 'fertility men', 'fertility man'. All supplements with a description of ingredients in English, Dutch, French, Spanish, or German were included. Subsequently, Pubmed and Google Scholar were searched for studies that included the supplements. PARTICIPANTS/MATERIALS SETTING METHODS: Inclusion criteria were supplements with antioxidant properties, of which the main purpose was to improve male fertility. Included supplements must be available without a doctor's prescription. Supplements containing plant extracts were excluded, as well as supplements of which the content or dosage was not clear. The ingredients, dosage, price and health claims of the supplements were recorded. We assessed whether substances in the supplements exceeded the recommended dietary allowance (RDA) or tolerable upper intake level (UL). All clinical trials and animal studies investigating included supplements were selected for this review. Clinical trials were assessed for risk of bias with a risk of bias tool appropriate for the study design. MAIN RESULTS AND THE ROLE OF CHANCE: There were 34 eligible antioxidant supplements found, containing 48 different active substances. The average price per 30 days was 53.10 US dollars. Most of the supplements (27/34, 79%) contained substances in a dosage exceeding the recommended daily allowance (RDA). All manufacturers of the supplements made health claims related to the improvement of sperm quality or male fertility. For 13 of the 34 supplements (38%), published clinical trials were available, and for one supplement, only an animal study was found. The overall quality of the included studies was poor. Only two supplements were tested in a good quality clinical trial. LIMITATIONS REASONS FOR CAUTION: As a consequence of searching shopping websites, a comprehensive search strategy could not be formulated. Most supplements were excluded because they contained plant extracts or because supplement information was not available (in an appropriate language). WIDER IMPLICATIONS OF THE FINDINGS: This is the first review that gives an insight into the market of male fertility supplements as available to infertility patients and other men seeking to improve their fertility. Earlier reviews have focused only on supplements with published clinical trials. However, we show that more than half of the supplements have not been tested in a clinical trial. To our knowledge, this review is the first to assess the dosage of supplements in relation to the RDA. In agreement with the literature, we found that the evidence on male fertility supplements is generally of poor quality. This review should urge pharmaceutical companies to evaluate their products in randomized controlled trials in order to provide people with substantiated information. STUDY FUNDING/COMPETING INTERESTS: The research position of W.R.d.L. is funded by an unrestricted grant from Goodlife Pharma. W.R.d.L., K.F., and J.P.d.B. are in the research team of a clinical trial on Impryl®, one of the supplements included in this review. REGISTRATION NUMBER: N/A.

Molecular Processes in Stress Urinary Incontinence: A Systematic Review of Human and Animal Studies.

Stress urinary incontinence (SUI) is a common and burdensome condition. Because of the large knowledge gap around the molecular processes involved in its pathophysiology, the aim of this review was to provide a systematic overview of genetic variants, gene and protein expression changes related to SUI in human and animal studies. On 5 January 2021, a systematic search was performed in Pubmed, Embase, Web of Science, and the Cochrane library. The screening process and quality assessment were performed in duplicate, using predefined inclusion criteria and different quality assessment tools for human and animal studies respectively. The extracted data were grouped in themes per outcome measure, according to their functions in cellular processes, and synthesized in a narrative review. Finally, 107 studies were included, of which 35 used animal models (rats and mice). Resulting from the most examined processes, the evidence suggests that SUI is associated with altered extracellular matrix metabolism, estrogen receptors, oxidative stress, apoptosis, inflammation, neurodegenerative processes, and muscle cell differentiation and contractility. Due to heterogeneity in the studies (e.g., in examined tissues), the precise contribution of the associated genes and proteins in relation to SUI pathophysiology remained unclear. Future research should focus on possible contributors to these alterations.

Fertility Workup With Video Consultation During the COVID-19 Pandemic: Pilot Quantitative and Qualitative Study.

BACKGROUND: Due to the COVID-19 pandemic, major parts of elective health care in the Netherlands, such as reproductive medicine, were paused. When health care was resumed, video consultation was used as a new solution to continue consultations with the new governmental rules of social distancing. Prior to this COVID-19 situation, video consultation was not used extensively in the Netherlands; therefore, physicians and patients are not familiar with this way of consultation. OBJECTIVE: The purpose of this study was to measure the level of patient centeredness and shared decision making in infertile couples who have undergone fertility workup through video consultation. METHODS: This is a questionnaire study with an additional qualitative part for a more in depth understanding. Infertile couples (ie, male and female partners with an unfulfilled wish for a child after 1 year of unprotected intercourse) were referred to a fertility center and underwent fertility workup through video consultation. The fertility workup consisted of 2 separate video consultations, with diagnostic tests according to a protocol. After the last video consultation couples received a digital questionnaire, which consisted of a modified version of the Patient-Centered Questionnaire-Infertility (PCQ-I) and CollaboRATE questionnaire. Fifty-three eligible infertile couples were approached, and of these, 22 participated. Four women were approached for a semistructured interview. RESULTS: The median score on the modified PCQ-I (scale of 0 to 3) was 2.64. The highest rating was for the subscale communication and information, and the lowest rating was for the subscale organization of care. The median score on the CollaboRATE questionnaire (scale of 1 to 9) was 8 for all 3 subquestions. Patients mentioned privacy, less travel time, and easy use of the program as possible benefits of video consultation. However, patients preferred the first consultation with their physician to be face-to-face consultation as video consultation was considered less personal. CONCLUSIONS: The high levels of patient centeredness and shared decision making show that video consultation is a promising way of providing care remotely, although attention has to be payed to mitigate the more impersonal setting of video consultation when compared with face-to-face consultation.

Genetic variants and expression changes in urgency urinary incontinence: A systematic review.

AIM: To perform a systematic review summarizing the knowledge of genetic variants, gene, and protein expression changes in humans and animals associated with urgency urinary incontinence (UUI) and to provide an overview of the known molecular mechanisms related to UUI. METHODS: A systematic search was performed on March 2, 2020, in PubMed, Embase, Web of Science, and the Cochrane library. Retrieved studies were screened for eligibility. The risk of bias was assessed using the ROBINS-I (human) and SYRCLE (animal) tool. Data were presented in a structured manner and in the case of greater than five studies on a homogeneous outcome, a meta-analysis was performed. RESULTS: Altogether, a total of 10,785 records were screened of which 37 studies met the inclusion criteria. Notably, 24/37 studies scored medium-high to high on risk of bias, affecting the value of the included studies. The analysis of 70 unique genes and proteins and three genome-wide association studies showed that specific signal transduction pathways and inflammation are associated with UUI. A meta-analysis on the predictive value of urinary nerve growth factor (NGF) levels showed that increased urinary NGF levels correlate with UUI. CONCLUSION: The collective evidence showed the involvement of two molecular mechanisms (signal transduction and inflammation) and NGF in UUI, enhancing our understanding of the pathophysiology of UUI. Unfortunately, the risk of bias was medium-high to high for most studies and the value of many observations remains unclear. Future studies should focus on elucidating how deficits in the two identified molecular mechanisms contribute to UUI and should avoid bias.