Sperm morphology and testosterone shifted for years after COVID-19 in infertile men

A large retrospective study of infertile men in China has found that some measures of sperm quality and reproductive hormones changed markedly during and after the COVID-19 pandemic, and that several of these changes had not returned to pre-pandemic levels even two years after pandemic restrictions ended. The analysis, published in Basic and Clinical Andrology, drew on 90,125 patient records collected between January 2017 and December 2024 at a single reproductive medicine center in Chongqing, and it is among the first to track male reproductive parameters across a pre-pandemic baseline, the pandemic itself, and two distinct post-pandemic phases.

The most striking finding concerned sperm morphology, the percentage of sperm cells with a normal shape. The proportion of men whose samples met the World Health Organization clinical threshold of at least 4 percent normally shaped sperm fell from 88.9 percent before the pandemic to 72.7 percent during it, 62.4 percent in the first post-pandemic phase, and 55.1 percent in the second post-pandemic phase, with all pairwise comparisons reaching statistical significance at p < 0.001. By the end of 2024, nearly half of the men in the study had normal morphology values below the WHO diagnostic threshold, a proportion that had almost quadrupled from the 11.1 percent recorded before the pandemic. The median morphology rate itself stayed at 4 percent across all periods, but the interquartile range narrowed from 4 to 6 percent before the pandemic to 3 to 4 percent in the pandemic and both post-pandemic phases, signaling a downward shift in the entire distribution rather than a collapse in the typical value.

Hormonal measurements told a quieter but still consistent story. Median serum testosterone declined from 4.46 nanograms per milliliter before the pandemic to 4.19 nanograms per milliliter in the second post-pandemic phase, an absolute drop of 0.27 nanograms per milliliter and a relative reduction of 6.1 percent, with the pre-pandemic versus post-phase 2 comparison yielding p = 0.006. Levels in the first post-pandemic phase, with a median of 4.31 nanograms per milliliter, were also significantly lower than pre-pandemic values at p = 0.011, while no significant difference separated the pre-pandemic and pandemic periods, where the comparison produced p = 0.591. Luteinizing hormone declined progressively from the pre-pandemic period through the first post-pandemic phase, follicle-stimulating hormone remained stable, and estradiol showed only minor fluctuations. The authors note that the combination of falling testosterone and luteinizing hormone with preserved follicle-stimulating hormone resembles the profile often associated with secondary hypogonadism, although they caution that the clinical meaning of this pattern remains uncertain and that it could reflect an adaptive response to systemic stress rather than a true endocrine disorder.

Importantly, the testosterone decline stayed modest in absolute terms. The median value in the final study period remained well above the conventional clinical threshold for biochemical hypogonadism, typically set at less than 3.0 nanograms per milliliter, meaning most men in the cohort did not cross into a hypogonadal range. The researchers suggest that even moderate reductions might have subtle effects on libido, energy, or body composition at the individual level, but they emphasize that the observed shift is unlikely to represent a widespread, clinically overt endocrine disorder at the population level.

The study’s design grouped records into four consecutive calendar periods aligned with the pandemic timeline in China: a pre-pandemic period from January 2017 through December 2019, the pandemic period from January 2020 through December 7, 2022 under stringent control policies, a first post-pandemic phase from December 8, 2022 through December 2023 following the major policy adjustment, and a second post-pandemic phase covering all of 2024. Participants were further stratified into four age groups: 30 years or younger, 31 to 35 years, 36 to 40 years, and older than 40 years. All patients were attending the clinic for infertility evaluation, and those with sexual dysfunction preventing sample collection, congenital or developmental abnormalities of the reproductive organs, histories of hormone or antioxidant supplement use, or previous testicular surgery were excluded.

A methodological transition shaped what the researchers could and could not compare. Routine semen parameters, including sperm concentration, total count, and motility, were measured by manual counting before the pandemic but by computer-assisted semen analysis, or CASA, from the pandemic period onward. Because this switch could introduce artificial differences, the team restricted all formal statistical comparisons for these parameters to the three CASA-consistent periods, treating pre-pandemic data as descriptive only. In contrast, sperm morphology, acrosomal function, seminal plasma biochemistry, reproductive hormones, and immunological testing were performed with the same laboratory methods throughout all eight years, allowing uninterrupted comparisons for those outcomes. Within the CASA-consistent window, the researchers observed that semen volume dipped transiently in the first post-pandemic phase before recovering, sperm concentration stayed stable and then rose significantly in the second phase, total sperm count dipped slightly before a substantial increase, and progressive motility improved in the first post-pandemic phase before partially declining while remaining above pandemic-period levels.

Age emerged as a clear modifier of these trajectories. Using generalized estimating equations that included a time-by-age interaction term, the researchers found significant interaction effects for semen volume, total sperm count, progressive motility, and non-progressive motility. In men aged 40 or younger, semen volume dipped transiently in the first post-pandemic phase and then recovered, total sperm count rose steadily across phases, and progressive motility peaked in the first post-pandemic phase and stayed above pandemic levels in the second. In men older than 40, semen volume remained stable, total sperm count was consistently lower than in younger men although it increased in the second post-pandemic phase, and progressive motility rose in the first post-pandemic phase but returned to pandemic-period levels by the second. Trends for concentration and immotility mirrored those of younger groups, but absolute values were poorer in the older men.

Seminal plasma biochemistry shifted in parallel with the morphology findings. Zinc and neutral alpha-glucosidase levels decreased during the pandemic, with alpha-glucosidase, an epididymal marker, returning to pre-pandemic levels by the second post-pandemic phase while zinc remained depressed. Fructose levels increased in the late post-pandemic phase. The authors interpret the persistent zinc depletion and morphology deficit as possibly reflecting more enduring alterations in the spermatogenic epithelium and prostate gland function, though they stress this remains a hypothesis requiring histological or cellular validation. Anti-sperm antibody positivity, by contrast, showed a transient pattern: it surged during the pandemic, stayed elevated in the first post-pandemic phase, and fell significantly by the second phase, approaching pre-pandemic levels.

The authors are careful about what their design can and cannot establish. Because the analysis compared population-level temporal trends rather than individual infection status, the observed changes may reflect a combination of viral infection, pandemic-associated stressors such as psychological distress, lifestyle changes, and healthcare disruptions, and other temporal factors. The cohort consisted of men presenting for infertility evaluation at a single regional center in China, limiting generalizability to fertile populations or other geographic and ethnic groups. Sperm morphology assessment carries inherent inter-observer variability, and although the same two experienced technicians performed these assessments throughout and the laboratory joined a national external quality assessment program from 2021 onward, no external quality data exist for the 2017 to 2020 period. The absence of data on sperm DNA fragmentation and other functional assays further limits the picture, and the observational associations identified by the statistical models cannot establish causality.

Nevertheless, the clinical implications the authors draw are measured. Citing previous longitudinal research indicating that each one-percentage-point decrease in normal morphology is associated with a 5 to 10 percent reduction in natural conception rates, they argue that the population-level shift toward poorer morphology may carry non-negligible fertility consequences, particularly for couples already at the margin of subfertility. The persistent depletion of seminal zinc, a cofactor for sperm chromatin stability and antioxidant defense, remains of uncertain clinical significance because well-defined fertility thresholds for seminal zinc are lacking. The team concludes that major global health crises can be associated with prolonged and heterogeneous shifts in population-level male reproductive health markers, and they call for age-stratified reproductive health surveillance following major population-level stressors, along with future research integrating genetic, immunological, and multi-omics data to clarify the specific roles of viral infection, systemic stress, and host factors in shaping post-pandemic reproductive trajectories.

Subject of Research: Long-term changes in semen quality and reproductive hormones among infertile men across the COVID-19 pandemic and post-pandemic periods

Article Title: Divergent long-term trends in semen quality and reproductive hormones across the COVID-19 pandemic era in infertile men: an age-stratified retrospective study

Article References: Li, P., Liu, S., Chen, K., & Gao, Y. (2026). Divergent long-term trends in semen quality and reproductive hormones across the COVID-19 pandemic era in infertile men: an age-stratified retrospective study. Basic and Clinical Andrology, 36(1), Article 10. https://doi.org/10.1186/s12610-026-00309-1

Image Credits: AI Generated

DOI: 10.1186/s12610-026-00309-1

Keywords: COVID-19, sperm morphology, testosterone, male infertility, semen quality, reproductive hormones, luteinizing hormone, seminal plasma biochemistry, age-stratified analysis, retrospective study, hypogonadism, male reproductive health