PD09-01: Low birth weight is associated with sperm DNA fragmentation and assisted reproductive technology outcomes in primary infertile men – results of a cross-sectional study

Luca Boeri*, Federico Belladelli, Edoardo Pozzi, Giuseppe Fallara, Massimiliano Raffo, Christian Corsini, Luigi Candela, Antonio Costa, Daniele Cignoli, Nicolò Schifano, Alessia d'Arma, Milan, Italy, Paolo Capogrosso, Varese, Italy, Eugenio Ventimiglia, Luca Pagliardini, Enrico Papaleo, Milan, Italy, Vincenzo Mirone, Naples, Italy, Federico Dehò, Varese, Italy, Francesco Montorsi, Andrea Salonia, Milan, Italy

Introduction: Population based studies have shown that men born with low birth weight (LBW) had higher risk of being diagnosed with or treated for infertility than men born with normal birth weight (NBW). The association between BW and sperm DNA fragmentation (SDF) and assisted reproductive technology (ART) outcomes has never been investigated. We assessed the relationship between clinical, seminal characteristics and ART outcomes with different categories of BW in a cohort of non-Finnish white-European men presenting for primary couple’s infertility

Methods: Complete demographic, clinical and laboratory data from 1361 consecutive infertile men were analyzed. Patients with BW =2500, 2500–4200, and =4200 gr were categorized into LBW, NBW and high birth weight (HBW), respectively. Health-significant comorbidities were scored with the Charlson Comorbidity Index (CCI; categorized 0 vs. =1). Testicular volume (TV) was assessed with a Prader orchidometer. Serum hormones were measured in all cases. Semen analysis parameters were categorized based on 2021 World Health Organization (WHO21) reference criteria. SDF (according to SCSA) was tested in every patient and considered pathological for SDF>30%. ART outcomes were available for 282 (20.7%) patients. Descriptive statistics and logistic regression analyses detailed the association between semen parameters and clinical characteristics and the defined birth weight categories

Results: Of all, LBW, NBW and HBW categories were found in 104 (7.6%), 1078 (79.2%) and 179 (13.2%) men, respectively. HBW men had higher BMI compared to those in the other groups (all p<0.01). A higher rate of CCI=1 was found in LBW men compared to NBW and HBW (17.1% vs. 9% vs. 11%, p<0.001). LBW men had smaller TV than those in NBW and HBW groups, respectively (all p<0.02). Likewise, LBW patients presented higher FSH (p=0.03) but lower total testosterone levels (p=0.02) as compared with the other groups. Sperm progressive motility (p=0.01) and normal morphology (p < 0.01) were lower but SDF values were higher (all p<0.01) in LBW compared to the other groups. SDF>30% was more frequently found in LBW men (69.8%) than NBW (51%) and HBW (44%) (all p=0.02). ART pregnancy outcomes was lower in LBW compared to both NBW and HBW categories (25.1% vs. 35% vs. 35%, p=0.03). At multivariable logistic regression analysis, LBW was associated with SDF>30% (OR 3.7; p<0.001), after accounting for age, CCI, FSH and TV. Similarly, LBW was associated with negative ART outcomes (OR 2.3; p<0.001), after accounting for the same predictors

Conclusions: Results from this study showed that LBW was associated with impaired clinical and semen characteristics in infertile men compared to both NBW and HBW. SDF and ART outcomes were significantly worse in the LBW group. These data confirmed that disrupted embryonic programming and gonadal development during fetal life in men might impaired future reproductive health

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