Fibroblast Growth Factor 21 Attenuates Diabetes-Induced Renal Fibrosis by Negatively Regulating TGF-β-p53-Smad2/3-Mediated Epithelial-to-Mesenchymal Transition via Activation of AKT.

PURPOSE: To investigate the correlation between male high-normal fasting blood glucose (FBG) and semen quality, embryonic development, and pregnancy outcomes of in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI).

MATERIALS AND METHODS: This retrospective cohort study included 921 couples undergoing their first single blastocyst frozen-thawed embryo transfer cycles. Participants were divided into 4 groups depending on quartiles of male FBG (3.90-6.10 mmol/L): from the lowest Quartile 1 (Q1) to the highest Q4. Firstly, semen quality and reproductive outcomes were compared across groups. Next, based on male FBG quartiles, logistic regression models were performed to explore associations between FBG with semen quality and IVF/ICSI outcomes. Finally, with male FBG considered as continuous variables, generalized additive models (GAMs) were conducted to visualize the non-linear relationship of FBG with the outcomes. Primary outcome: live birth rate (LBR). Secondary outcomes: semen quality, embryonic development parameters, biochemical pregnancy rate (BPR), clinical pregnancy rate, miscarriage rate, and other pregnancy outcomes.

RESULTS: Higher FBG quartiles exhibited significantly reduced sperm total motility, progressive motility, and progressive sperm count, alongside increased asthenozoospermia prevalence (p<0.05). BPRs rose from Q1 (4.4%) to Q4 (11.0%) (p=0.033), while LBR showed a declining trend from Q1 (46.7%) to Q4 (36.0%) (p=0.102). Regression analysis indicated that males in Q4 had a higher biochemical pregnancy risk and lower live birth likelihood (p-trend<0.05). GAMs revealed a dose-dependent increase in both asthenozoospermia and biochemical pregnancy risks with rising FBG levels.

CONCLUSIONS: High-normal male FBG is significantly associated with both impaired semen quality (particularly asthenozoospermia) and adverse IVF/ICSI outcomes, including increased biochemical pregnancy risk and reduced LBRs. These findings highlight the significance of assessing paternal metabolic health and suggest that FBG screening may serve as a valuable tool for optimizing IVF/ICSI strategies and improving reproductive success.