Background: Maternal subclinical hypothyroidism (SCH) is a risk factor for adverse pregnancy outcomes. However, it is still unclear whether SCH affects male fertility. The aim of this study was to determine the association between paternal SCH and clinical outcomes after in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). Methods: This retrospective study included 2511 couples with paternal euthyroidism (n = 2282) or SCH (n = 229) who visited our clinic for infertility treatment between April 1, 2017, and September 30, 2019. The primary outcomes were the fertilization rate and clinical pregnancy rate; the secondary outcomes were the good-quality embryo rate, blastocyst formation rate, implantation rate, and early miscarriage rate. These outcomes were compared between the euthyroid and the SCH groups after adjusting for various potential confounders. Results: The mean paternal ages in the euthyroid and SCH groups were 34.5 and 36.0 years, respectively (p = 0.002). Semen parameters and sperm DNA fragmentation index were similar between the two groups (all p > 0.05). The adjusted fertilization (0.69 vs. 0.71, p = 0.30), good-quality embryo (0.49 vs. 0.52, p = 0.31), blastocyst formation (0.51 vs. 0.53, p = 0.57), and early miscarriage (0.11 vs. 0.10, p = 0.81) rates were also similar between the two groups. There was a significantly decreased adjusted clinical pregnancy rate [confidence interval, CI] and implantation rate [CI] in the paternal SCH group compared with the euthyroid group (0.32 [0.26-0.40] vs. 0.42 [0.40-0.45], p = 0.009 for the clinical pregnancy rate; 0.24 [0.19-0.29] vs. 0.29 [0.27-0.31], p = 0.037 for the implantation rate). Stratified analysis indicated that these differences were only significant in men aged ≥35 years (p = 0.009 and 0.022, respectively) and not in men <35 years (p = 0.39 and 0.45, respectively). Conclusions: Paternal SCH was associated with worse clinical outcomes after IVF/ICSI, whereas this detrimental impact was only present in males ≥35 years old. Prospective studies and basic research are warranted to confirm these results and to clarify the mechanisms underlying these associations, respectively.
Keywords: IVF/ICSI; clinical outcomes; subclinical hypothyroidism; thyroid function.