Study question Investigating estradiol in relation with other sperm parameters might reveal new correlations which would help our understanding of male idiopathic infertility Summary answer Statistical significance was found in a series of correlations of E2 levels and sperm, hormonal and health parameters What is known already Male infertility is a rising major health concern, with sperm counts decreasing by 50-60% in the recent decades. The causes for male infertility are very different (genetic, systemic, neurological, infections, trauma, etc.), but at least 44% of cases are idiopathic. Estradiol (E2) regulates spermatogenesis by binding to classical intracellular estrogen receptors or membrane estrogen receptors to trigger genomic and nongenomic signal transduction pathways. Although E2 doesn’t carry any prognostic value by itself, as its levels don’t vary significantly between infertile and fertile men, its association with other parameters may lead to a better understanding of male infertility Study design, size, duration the design of cross-sectional study comprising 111 subjects- 87 infertile patients (median: 34 years, range 20–55 years) and 24 control (median: 33 years, range 20–45 years). The subjects were included in this study during 3 years (between October 2019- September2022). Inclusion criteria: spermatic parameters according to WHO 2010 Standards Exclusion criteria: Radiotherapy and/or pelvic chemotherapy (over the last 6 months), known genetic aberrations, endocrine diseases, urogenital infections, bilateral orchiectomy, vasectomy and occupational exposure. Participants/materials, setting, methods Infertile men were grouped in azoospermia (AZOO), oligoasthenoteratozoospermia (OATS/OATSS) and oligoasthenozoospermia (OAS/OASS). Blood and semen samples were collected and E2 levels were measured in both seminal and blood samples, along with sperm parameters (sperm count, motility, morphology) and other factors (BMI, hormone and vitamin D levels, BsmI polymorphism in the vitamin D receptor gene) were evaluated. E2 levels were assayed using the electrochemiluminescence method with the RocheCobas E601 autoanalyzer. Main results and the role of chance E2 varies slightly between the different patients’ groups, the highest values being found in the OAT/OATSS group. BMI is higher in the infertile group; significant higher values were found for the OAS/OASS (p = 0.002) and OATS/OATS (p = 0.017) groups. Statistical analysis has revealed a significant difference between serum and seminal E2 levels in each group (AZOO p = 0.0355; OATS/OATSS p = 0.0156; control p = 0.0009), but also between OATS/OATSS seminal group and control seminal group (p = 0.0366). The E2/Inhibin ratio presented higher values in patients with OATS/OATSS (p = 0.0031) and azoospermia (p = 0.0059). The lowest values of E2/Vitamin D ratio were detected in the OAS/OASS and OATS/OATSS groups (p = 0.0254), A significant increase of E2 serum level was observed in patients from the OATS/OATSS group in the case of homozygous for mutant allele of BsmI polymorphism (p = 0.0419). The results bring new evidence regarding the role of E2 in male infertility. The obtained data indicates an interplay between E2 and Inhibin B and vitamin D serum levels, highlighting it’s the role in male infertility. Limitations, reasons for caution The study could be extended to a larger population sample, in order to further validate the obtained results Wider implications of the findings Estradiol activity plays an important role in male fertility and along with the investigated parameters could serve as potential markers in the diagnosis and management of male infertility. Trial registration number PN-III-P2-2.1-PED-2019-4402
In the recent years a special attention has been given to a major health concern namely to male infertility, defined as the inability to conceive after 12 months of regular unprotected sexual intercourse, taken into account the statistics that highlight that sperm counts have dropped by 50–60% in recent decades. According to the WHO, infertility affects approximately 9% of couples globally, and the male factor is believed to be present in roughly 50% of cases, with exclusive responsibility in 30%. The aim of this manuscript is to present an evidence-based approach for diagnosing male infertility that includes finding new solutions for diagnosis and critical outcomes, retrieving up-to-date studies and existing guidelines. The diverse factors that induce male infertility generated in a vast amount of data that needed to be analysed by a clinician before a decision could be made for each individual. Modern medicine faces numerous obstacles as a result of the massive amount of data generated by the molecular biology discipline. To address complex clinical problems, vast data must be collected, analysed, and used, which can be very challenging. The use of artificial intelligence (AI) methods to create a decision support system can help predict the diagnosis and guide treatment for infertile men, based on analysis of different data as environmental and lifestyle, clinical (sperm count, morphology, hormone testing, karyotype, etc.) and “omics” bigdata. Ultimately, the development of AI algorithms will assist clinicians in formulating diagnosis, making treatment decisions, and predicting outcomes for assisted reproduction techniques.
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