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Male reproductive aging: can men with oligospermia become azoospermic over time?

International Journal of Impotence Research volume 35, pages 505–508 (2023)Cite this article

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While it is recognized that female fertility progressively decreases with age, the same paradigm is not necessarily true for men. Despite a growing body of literature evaluating advanced paternal age, male fertility is assumed to remain relatively constant over time. We have observed an uncommon phenomenon, however, in which a small proportion of men with oligozoospermia (sperm count < 15 million sperm/mL) progress to severe oligozoospermia (sperm count < 5 million sperm/mL) or nonobstructive azoospermia (NOA) over time. Herein, we discuss possible etiologies for this progression, areas of needed research, and possible management strategies to maximize reproductive potential.

The semen analysis is the current gold standard test in the evaluation of male infertility. However, it only represents a cross-sectional snapshot of an individual, without any bearing on past or future fertility potential. NOA specifically represents a failure of spermatogenesis with a majority of men demonstrating primary testicular failure due to an intrinsic defect in either the initiation or progression of spermatogenesis. While the majority of males are thought to have lifelong NOA, a small number who are initially oligospermic may lose the ability to produce sperm in the ejaculate reliably over time. A study by Song et al. followed thirty-nine patients with severe oligospermia with no medical or surgical intervention [1]. Throughout the follow-up period, 5 (12.8%) patients became NOA over a median duration of 42.0 months (range, 6.0–62.0 months). Furthermore, seven (17.9%) patients experienced severely declining sperm counts only detectable after centrifugation (cryptozoospermia). Ultimately, it remains unclear why some men progressed to overt NOA. It is important to note that the study may suffer from an observational bias where follow-up for these patients was ended prematurely, and that longer follow up may have shown normalization. However, we anecdotally have also observed this phenomenon with men having NOA after previously having sperm in the ejaculate. Multiple factors may have played a role in the process including aging, genetic defects, and environmental/behavioral influences.

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Fig. 1: Approach to the abnormal semen analysis.

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Authors and Affiliations

  1. Desai Sethi Urology Institute, University of Miami Miller School of Medicine, Miami, FL, USA

    Mehul Patel, Akhil Muthigi, Parris Diaz & Ranjith Ramasamy

  2. Institute of Reproductive and Regenerative Biology, Centre of Reproductive Medicine and Andrology, University of Münster, Münster, Germany

    Sandra Laurentino

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  1. Mehul Patel
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  2. Akhil Muthigi
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  3. Sandra Laurentino
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  4. Parris Diaz
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  5. Ranjith Ramasamy
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Contributions

MP, AM, and SL contributed to writing the manuscript. MP, AM, PD, and RR all contributed to study design, editing, and revisions. PD contributed to figure development.

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Correspondence to Mehul Patel.

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Patel, M., Muthigi, A., Laurentino, S. et al. Male reproductive aging: can men with oligospermia become azoospermic over time?. Int J Impot Res 35, 505–508 (2023). https://doi.org/10.1038/s41443-022-00634-9

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