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The infertility of many couples rests on an enigmatic dysfunction of the man's sperm. To gain insight into the underlying pathomechanisms, we assessed the function of the sperm-specific multisubunit CatSper-channel complex in the sperm of almost 2,300 men undergoing a fertility workup, using a simple motility-based test. We identified a group of men with normal semen parameters but defective CatSper function. These men or couples failed to conceive naturally and upon medically assisted reproduction via intrauterine insemination and in vitro fertilization. Intracytoplasmic sperm injection (ICSI) was, ultimately, required to conceive a child. We revealed that the defective CatSper function was caused by variations in CATSPER genes. Moreover, we unveiled that CatSper-deficient human sperm were unable to undergo hyperactive motility and, therefore, failed to penetrate the egg coat. Thus, our study provides the experimental evidence that sperm hyperactivation is required for human fertilization, explaining the infertility of CatSper-deficient men and the need of ICSI for medically assisted reproduction. Finally, our study also revealed that defective CatSper function and ensuing failure to hyperactivate represents the most common cause of unexplained male infertility known thus far and that this sperm channelopathy can readily be diagnosed, enabling future evidence-based treatment of Affected couples., Introduction Infertility is on the rise, but the underlying causes still remain mostly unknown. In fact, for about a third of infertile men, semen parameters are within reference limits (normozoospermia) [...]

The European Academy of Andrology (EAA) merged with the International Network of Young Researchers in Andrology (NYRA) in 2023, benefiting both organizations. The EAA held various educational events, including Schools in Ultrasound, Microsurgery, and Semen Analysis. The EAA also accredited a new Andrology Training Center in Doha, Qatar, and re-accredited several existing centers. Andrology, the official journal of EAA and ASA, celebrated its second decade with a high impact factor and published important guidelines and thematic issues. [Extracted from the article]

Introduction: Male contraception with exogenously administered hormones suppresses both luteinizing hormone and follicle stimulating hormone leading to low intratesticular testosterone concentration. This results in reversible suppression of spermatogenesis and marked decrease in sperm output in the ejaculate and preventing pregnancy in the female partner. Prior Studies: Studies of testosterone administered alone or in combination of another gonadotropin suppressive agent such as a progestin or gonadotropin releasing hormone (GnRH) analog showed decisively that the exogenous hormone administrations are effective in suppressing sperm output with few adverse events that are not anticipated. In contraceptive efficacy studies, testosterone alone or combined with a progestin are as effective in preventing pregnancies as female contraceptive methods. Conclusion: Hormone combinations for male contraception are in late‐phase clinical trials and hold the promise of being the new, reversible contraception method for men in over half a century. Lessons learned from the male hormonal contraceptive development pave the way for new targeted approached to regulate male fertility. [ABSTRACT FROM AUTHOR]

Backgrounds: Despite a wide spectrum of contraceptive methods for women, the unintended pregnancy rate remains high (45% in the US), with 50% resulting in abortion. Currently, 20% of global contraceptive use is male‐directed, with a wide variation among countries due to limited availability and lack of efficacy. Worldwide studies indicate that >50% of men would opt to use a reversible method, and 90% of women would rely on their partner to use a contraceptive. Additional reasons for novel male contraceptive methods to be available include the increased life expectancy, sharing the reproductive risks among partners, social issues, the lack of pharma industry involvement and the lack of opinion makers advocating for male contraception. Aim: The present guidelines aim to review the status regarding male contraception, the current state of the art to support the clinical practice, recommend minimal requirements for new male contraceptive development and provide and grade updated, evidence‐based recommendations from the European Society of Andrology (EAA) and the American Society of Andrology (ASA). Methods: An expert panel of academicians appointed by the EAA and the ASA generated a consensus guideline according to the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) system. Results: Sixty evidence‐based and graded recommendations were produced on couple‐centered communication, behaviors, barrier methods, semen analysis and contraceptive efficacy, physical agents, surgical methods, actions before initiating male contraception, hormonal methods, non‐hormonal methods, vaccines, and social and ethical considerations. Conclusion: As gender roles transform and gender equity is established in relationships, the male contribution to family planning must be facilitated. Efficient and safe male‐directed methods must be evaluated and introduced into clinical practice, preferably reversible, either hormonal or non‐hormonal. From a future perspective, identifying new hormonal combinations, suitable testicular targets, and emerging vas occlusion methods will produce novel molecules and products for male contraception. [ABSTRACT FROM AUTHOR]

To locate and fertilize the egg, sperm probe the varying microenvironment prevailing at different stages during their journey across the female genital tract. To this end, they are equipped with a unique repertoire of mostly sperm-specific proteins. In particular, the flagellar Ca2+ channel CatSper has come into focus as a polymodal sensor used by human sperm to register ligands released into the female genital tract. Here, we provide the first comprehensive study on the pharmacology of the sperm-specific human Slo3 channel, shedding light on its modulation by reproductive fluids and their constituents. Weshow that seminal fluid and contained prostaglandins and Zn2+ do not affect the channel, whereas human Slo3 is inhibited in a non-genomic fashion by diverse steroids as well as by albumin, which are released into the oviduct along with the egg. This indicates that not only CatSper but also Slo3 harbours promiscuous ligandbinding sites that can accommodate structurally diverse molecules, suggesting that Slo3 is involved in chemosensory signalling in human sperm. [ABSTRACT FROM AUTHOR]