Future prospects for the advancement of treatment of men with NOA: focus on gene editing, artificial sperm, stem cells, and use of imaging.

Akeem Babatunde Sikiru, Manh Nguyen Truong, Wael Zohdy
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Abstract

Nonobstructive azoospermia (NOA) affects about 60% of men with azoospermia, representing a severe form of male infertility. The current approach to manage NOA primarily involves testicular sperm retrieval methods such as conventional testicular sperm extraction (c-TESE) and microdissection testicular sperm extraction (micro-TESE). While combining testicular sperm retrieval with intracytoplasmic sperm injection (ICSI) offers hope for patients, the overall sperm retrieval rate (SRR) stands at around 50%. In cases where micro-TESE fails to retrieve sperm, limited options, like donor sperm or adoption, can be problematic in certain cultural contexts. This paper delves into prospective treatments for NOA management. Gene editing technologies, particularly clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) protein 9 (CRISPR/Cas9), hold potential for correcting genetic mutations underlying testicular dysfunction. However, these technologies face challenges due to their complexity, potential off-target effects, ethical concerns, and affordability. This calls for research to address key challenges associated with NOA management within the clinical settings. This also necessitate ongoing research essential for developing more sensitive diagnostic tests, validating novel treatments, and customizing current treatment strategies for individual patients. This review concluded that the future of NOA management may entail a combination of these treatment options, tailored to each patient's unique circumstances, providing a comprehensive approach to address NOA challenges.

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治疗男性无精子症的未来前景:关注基因编辑、人工精子、干细胞和成像技术的使用。
非梗阻性无精子症(NOA)影响着约 60% 的男性无精子症患者,是一种严重的男性不育症。目前治疗无精子症的方法主要包括传统睾丸取精术(c-TESE)和显微解剖睾丸取精术(micro-TESE)。虽然将睾丸取精与卵胞浆内单精子显微注射(ICSI)相结合为患者带来了希望,但总体取精率(SRR)约为 50%。如果显微睾丸取精术(micro-TESE)未能取回精子,在某些文化背景下,捐精或收养等有限的选择可能会造成问题。本文将深入探讨无精子症的前瞻性治疗方法。基因编辑技术,尤其是成簇的规则间隔短回文重复序列(CRISPR)/CRISPR相关(Cas)蛋白9(CRISPR/Cas9),具有纠正睾丸功能障碍的基因突变的潜力。然而,这些技术因其复杂性、潜在的脱靶效应、伦理问题和经济承受能力而面临挑战。这就要求开展研究,以解决与临床环境中 NOA 管理相关的关键挑战。这也要求进行持续的研究,这对开发更灵敏的诊断测试、验证新型治疗方法以及为个体患者定制当前的治疗策略至关重要。本综述认为,NOA 管理的未来可能需要结合这些治疗方案,并根据每位患者的独特情况量身定制,从而提供一种全面的方法来应对 NOA 挑战。
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