Seminal cell-free DNA and sperm characteristic's: An added biomarker for male infertility investigation.

Cell-free DNA (Cf-DNA) fragments may constitute an easy-to-measure molecular tool for guiding the choice of care provided to infertile couples who benefit assisted reproductive technology (ART) programmes. Data on Cf-DNA levels in the seminal plasma of men with sperm alterations are scarce. The objective of the present study was to quantify the presence of Cf-DNA in semen by using a quantitative real-time PCR. We compared men with abnormal sperm characteristics (n = 21) with normospermic controls (n = 21). The PCR assay evidenced significantly higher mean Cf-DNA levels in patients with sperm abnormalities than in controls (2.09 versus 1.18 µg/ml, respectively; p = .0003). The Cf-DNA levels were notably higher in men with azoospermia (3.65 µg/ml, versus 1.34 µg/ml in matched controls; p = .03) and men with teratozoospermia (1.80 µg/ml, versus 1.29 µg/ml in matched controls; p = .008). Our data report a significant association between elevated Cf-DNA levels and sperm abnormalities. These results may open up new diagnostic and prognostic perspectives in male infertility.

High body mass index has a deleterious effect on semen parameters except morphology: results from a large cohort study.

OBJECTIVE: To evaluate the influence of body mass index (BMI) on semen characteristics. DESIGN: Cohort study. SETTING: Single private andrology laboratory. PATIENT(S): All patients (n=10,665) consulting for a semen analysis from October 9, 2010, to October 8, 2011. When analyses were repeated on the same patient, only the first was included. INTERVENTION(S): Recording of self-reported weight and height and of semen analysis. MAIN OUTCOME MEASURE(S): All parameters of standard semen analysis: pH, volume, sperm concentration per mL, total sperm count per ejaculate, motility (%) within 1 hour after ejaculation (overall and progressive), viability (%), and normal sperm morphology (%). Parametric and nonparametric statistical methods were applied, and results are given either with mean±SD, or 10th, 50th, and 90th percentiles. RESULT(S): Semen volume decreased from 3.3±1.6 to 2.7±1.6 mL when BMI increased from normal (20-25 kg/m2) to extreme obesity (>40 kg/m2). The same was true for semen concentration (56.4±54.9 to 39.4±51.0 million/mL), total sperm count (171±170 to 92±95 million), and progressive motility (36.9±16.8% to 34.7±17.1%). The percentage of cases with azoospermia and cryptozoospermia increased from 1.9% to 9.1% and from 4.7% to 15.2%, respectively. The other semen characteristics were not affected. Multivariate models including age and abstinence duration confirmed these results. CONCLUSION(S): In this study, on a large patient sample size, increased BMI was associated with decreased semen quality, affecting volume, concentration, and motility. The percentage of normal forms was not decreased.

Sperm deoxyribonucleic acid damage in normozoospermic men is related to age and sperm progressive motility.

OBJECTIVE: To evaluate sperm DNA fragmentation in normozoospermic male partners of couples undergoing infertility evaluation. DESIGN: Retrospective cohort study. SETTING: Clinical andrology laboratory. PATIENT(S): A total of 1,974 consecutive normozoospermic men selected from a larger cohort of 4,345 consecutive, nonazoospermic men presenting for infertility evaluation. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Clinical parameters, conventional semen parameters, and sperm DNA fragmentation assessed by flow cytometry-based TUNEL assay and reported as percent sperm DNA fragmentation (%SDF). RESULT(S): The mean (± SD) %SDF and the proportion of men with high %SDF (>30%) were significantly lower in the normozoospermic compared with the entire cohort of 4,345 evaluable infertile men (17.6% ± 10.1% vs. 20.7% ± 12.4% and 11% vs. 20%, respectively). In the group of 1,974 normozoospermic men, %SDF was positively correlated with paternal age (r = 0.17) and inversely correlated with progressive motility (r = -0.26). In the subset of normozoospermic men with sperm parameters above the 50th percentile (≥ 73 × 10(6) sperm/mL, ≥ 55% progressive motility, and ≥ 14% normal forms, World Health Organization 2010 guidelines), 5% (4 of 83) had elevated %SDF (>30%). CONCLUSION(S): In this large cohort of normozoospermic men presenting for infertility evaluation, DNA fragmentation level is related to sperm motility and paternal age, and 11% of these men have high levels of sperm DNA fragmentation. Furthermore, the data indicate that a nonnegligible proportion (5%) of normozoospermic men with high-normal sperm parameters may also have significant sperm DNA fragmentation.

Which isolated sperm abnormality is most related to sperm DNA damage in men presenting for infertility evaluation.

BACKGROUND: Sperm DNA damage is common in infertile men and is associated with poor semen parameters but the impact of an isolated sperm abnormality on sperm DNA damage has not been studied. OBJECTIVE: To evaluate sperm DNA damage in a large cohort of infertile men with isolated sperm defects. DESIGN, SETTING AND PARTICIPANTS: Retrospective study of 1084 consecutive, non-azoospermic infertile men with an isolated sperm defect: isolated oligozoospermia (iOligo), isolated asthenozoospermia (iAstheno) or isolated teratozoospermia (iTerato). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We examined and compared clinical parameters, conventional semen parameters and %sperm DNA fragmentation (%SDF, assessed by flow cytometry-based Terminal deoxynucleotidyl transferase-mediated dUTP Nick End-Labeling assay) in the three groups of men. RESULTS AND LIMITATIONS: The mean (±SD) %SDF was significantly higher in the iAstheno compared to the iOligo and iTerato groups (25.0 ± 14.0 vs. 19.2 ± 11.6 and 20.7 ± 12.1 %, respectively, P < 0.0001). Similarly, the proportion of men with high %SDF (>30 %) was significantly higher in the iAstheno compared to the iOligo and iTerato groups (31 % vs. 18 % and 19 %, respectively, P < 0.0001). In the group of 713 men with iAstheno, %SDF was positively correlated with paternal age (r = 0.20, P < 0.0001) and inversely correlated with %progressive motility (r = -0.18, P < 0.0001). In the subset of 218 men with iTerato, %SDF was also positively correlated with paternal age (r = 0.15, P = 0.018) and inversely correlated with %progressive motility (r = -0.26, P = 0.0001). CONCLUSIONS: In this large cohort of infertile men with isolated sperm abnormalities, we have found that the sperm DNA fragmentation level is highest in the men with sperm motility defects and that 31 % of these men have high levels of sperm DNA fragmentation. The data indicate that poor motility is the sperm parameter abnormality most closely related to sperm DNA damage.

Effect of maternal and paternal age on pregnancy and miscarriage rates after intrauterine insemination.

More than 17,000 intrauterine insemination (lUI) cycles were analysed retrospectively with respect to outcome according to differing aetiologies of infertility. The quantity and motility of spermatozoa in the final preparation used for insemination had a positive effect on the outcome, as classically observed in the past. It was found that advanced maternal age had a negative effect on the pregnancy rate and was associated with increased miscarriage rate. More interestingly, an exactly parallel effect was found for paternal age. The impact of increased age on necrospermia and sperm DNA structure is discussed as a probable direct cause of this paternal effect.