The influence of paternal overweight on sperm chromatin integrity, fertilization rate and pregnancy outcome among males attending fertility clinic for IVF/ICSI treatment

Abstract

Background Low and middle-income countries are facing a rapid increase in obesity and overweight burden, particularly in urban settings. Being overweight in men is associated with infertility and a higher risk to have a low sperm count or no sperm in their ejaculate. Despite potential limitations, this is one of few studies conducted to determine the potential risk of paternal overweight on sperm standard parameters, sperm chromatin integrity and assisted conception outcome including fertilization, embryo quality, cleavage rate, reduce blastocyst development, implantation, and cumulative live birth rate (CLBR). Methods A cross-sectional study of 750 infertile couples undergoing assisted reproduction technique at a single reproductive medicine center of Salma Kafeel Medical Centre Islamabad. Sperm from men undergoing ART were analyzed for chromatin integrity using sperm chromatin dispersion assay (SCD), Chromomycin A3 staining (CMA3), and toluidine blue (TB) staining, while other semen parameters were assessed on same day includes; standard semen parameters, reactive oxygen species (ROS), sperm deformity index (SDI), teratozoospermic index (TZI), and hypo-osmatic swelling test (HOST). Paternal body mass index (BMI) < 24.5–20 kg/m2 served as the reference group, while the male patients with BMI > 24.5-30 kg/m2 were considered to be overweight. Results In the analysis of the percentage of spermatozoa with chromatin maturity (CMA3) and chromatin integrity (TB) was reduced significantly in overweight men (p < 0.01) compared with a reference group. Increase in paternal BMI correlate with the increase in sperm chromatin damage (SCD r = 0.282, TB r = 0.144, p < 0.05), immaturity (CMA3, r = 0.79, p < 0.05) and oxidative stress (ROS) (r = 0.282, p < 0.001). Peri-fertilization effects were increased in oocytes fertilization in couples with overweight men (FR = 67%) compared with normal-weight men (FR = 74.8%), similarly, after univariant regression paternal weight remain predictor of sperm chromatin maturity, successful fertilization and CLBR. In the embryo, developmental stage number of the embryo in cleavage was higher in normal weight men, while day 3 (D3) embryos, percent good quality embryo D3, and blastocyst formation rate were compared able between the groups. The paternal overweight group had significant (p < 0.001) increased neonatal birth weight (2952.14 ± 53.64gm; within normal range) when compared with the reference group (2577.24 ± 30.94gm) following assisted reproductive technology (ART). CLBR was higher (p < 0.05) in normal weight men compared to couples with overweight male partners. CLBR per embryo transfer and per 2PN was a statistically significant (p < 0.05) difference between the two groups. An inverse association was observed in the linear regression model between paternal BMI with fertilization rate and CLBR. Conclusion The present study demonstrated the impact of paternal overweight on male reproductive health, as these patients had a higher percentage of immature sperm (CMA3) with impaired chromatin integrity (SCD, TB) in their semen and had decreased fertilization rate, CLBR following assisted reproductive treatments. The present study supports that paternal overweight should be regarded as one of the predictors for fertilization, CLBR and useful for counseling, to consider body mass index not only in women but also for men, in those couples opting for ART treatment, and warrant a poor reproductive outcome in overweight men.

Sperm DNA damage: The possible link between obesity and male infertility, an update of the current literature

“…21 Seven studies (Table 1) have been published in the past 5 years assessing the association between paternal overweight/obesity and assisted reproduction outcomes. [24][25][26][27][28][29][30] In all cases bar one, 24 BMI was the only method of adiposity classification utilised (using race-based norms). The overall outcomes were very mixed, with negative associations of obesity in men with live birth rate identified in three studies, [24][25][26] whilst no differences were identified in the other four studies.…”

“…Seven studies (Table 1) have been published in the past 5 years assessing the association between paternal overweight/obesity and assisted reproduction outcomes 24–30 . In all cases bar one, 24 BMI was the only method of adiposity classification utilised (using race‐based norms).…”

“…[24][25][26][27][28][29][30] In all cases bar one, 24 BMI was the only method of adiposity classification utilised (using race-based norms). The overall outcomes were very mixed, with negative associations of obesity in men with live birth rate identified in three studies, [24][25][26] whilst no differences were identified in the other four studies. [27][28][29][30] Three studies also assessed the effects of obesity in men on fertilisation rates, with two 24,27 of three 29 studies showing negative associations with obesity in men.…”

“…Sperm histone retention (incomplete protamination) is a common feature seen in overweight and obese men 25 . Significantly, the regions that retain histones (H2A, H2B, H3 and H4) in sperm DNA are conserved amongst mammalian species, indicating their significance for successful embryo formation 176 .…”

The bibliometric analysis of studies on intracytoplasmic sperm injection from 2002 to 2021

“…ICSI is usually performed when the sperm is unable to fertilize the egg. Only about 5% of infertile men could be treated without ICSI ( 5 ). Therefore, ICSI restores the fertilization rate to normal in couples with unexpectedly low fertilization rates due to a decline in semen quality.…”