Abstract

Low serum testosterone is found in approximately 15% of subfertile men. Although testosterone is essential in spermatogenesis, it is unclear whether low testosterone levels may have a negative impact on the semen parameters of men belonging to infertile couples with a total sperm count greater than 5 million. Furthermore, it is debatable whether the initial evaluation of the subfertile male should include an endocrine assessment. This was a retrospective, single-center cohort study conducted at a tertiary fertility clinic. Male partners of infertile couples undergoing in vitro fertilization (IVF), with a total sperm count greater than 5 million, were included. All men provided morning blood samples, and none had been on exogenous testosterone or other relevant medications. Low total testosterone (TT) was defined as <264 ng/dL. Free T was calculated using TT and sex hormone-binding globulin (SHBG) levels (nmol/L) by a constant albumin concentration of 43 g/L. In total, 853 patients were included: 116 had low TT (<264 ng/dL) and 737 had normal TT (≥264 ng/dL). Semen volume, sperm cell count, progressive (A + B) motility and morphology (≥4% strict Kruger) were lower in the low TT group but not significantly different between low and normal TT groups (3.2 ± 1.79 vs. 3.23 ± 1.64, p = 0.87; 76.82 ± 83.18 vs. 67.55 ± 57.70, p = 0.7; 54.89 ± 19.45 vs. 56.25 ± 19.03, p = 0.6; 5.77 ± 3.23 vs. 6.89 ± 3.94, p = 0.23). The percentage of patients with below-reference sperm volume (<1.5 mL), cell count (<15 × 106/mL), motility (A + B) (<32%) and morphology (<4%) was higher in the low TT group but not statistically different compared to the normal TT group. Multivariable regression analysis revealed that low TT and free T levels had no significant effect on the aforementioned semen parameters (coefficient: 3.94, 0.88, 1.37, 0.39; p = 0.53, 0.8, 0.3, 0.2; coefficient: 0.001, 0.06, 0.007, 0.0002; p = 0.73, 0.52, 0.85, 0.98). Despite our robust methodological approach, the presence of biases related to retrospective design cannot be excluded. Our findings highlighted the lack of association between low TT levels and semen parameter alterations in male partners of infertile couples undergoing IVF, with a total sperm count greater than 5 million. However, it is important to emphasize that more patients in the low TT group had subnormal semen parameters, albeit the difference was not statistically significant. Larger, prospective studies are warranted in order to validate these findings, as well as to investigate the existence of a TT threshold below which semen parameters might be negatively affected.

Highlights

  • Male factor infertility accounts for approximately 40–50% of all infertility cases [1], with studies reporting a significant overall decline in semen parameters over the last decade [2]

  • The results of our large retrospective study demonstrated that low TT (

  • Our results were partly in line with a recent post hoc analysis of a large randomized controlled trial (RCT) evaluating couples with unexplained infertility undergoing intrauterine insemination (IUI), which revealed that low TT levels (

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Summary

Introduction

Male factor infertility accounts for approximately 40–50% of all infertility cases [1], with studies reporting a significant overall decline in semen parameters over the last decade [2]. Semen analysis remains the cornerstone of investigation of male factor infertility [3], its predictive value remains limited [4]. Low blood serum testosterone (T) has been observed in approximately 15% of infertile men [5]. T is the major androgen regulating spermatogenesis in the testis. It is produced by Leydig cells in response to the luteinizing hormone (LH) signal and acts as a paracrine factor by diffusion into the seminiferous tubules where the Sertoli cells are located [6]. Sertoli cells represent the primary target for T signalling, whose effects are mediated via the androgen receptor (AR) present in both nucleus and cytoplasm [7]

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