O-133 Association between normal-range paternal serum free thyroxine concentrations and outcomes of assisted reproductive technologies
Authors: Rao M , Wang L , Yan G , Chen M , Zhao S , Tang L 
Published: June 2022

Abstract

Study question
Are paternal serum free thyroxine (FT4) concentrations within the reference range associated with outcomes of assisted reproductive technologies (ART)?

Summary answer
Men of older reproductive age (≥ 35 years old) with low FT4 concentrations within the reference range are associated with a decreased live birth rate.

What is known already
The impact of maternal thyroid dysfunction on ART outcomes has been widely elucidated. However, few studies have investigated the impact of paternal thyroid dysfunction on ART outcomes. Our previous study showed a detrimental impact of paternal subclinical hypothyroidism (SCH) on the clinical outcomes of ART. Patients with SCH had relatively lower concentrations of FT4 compared to those with euthyroidism. Therefore, it remains to be determined whether the detrimental impacts of paternal SCH on ART outcomes arise from low concentrations of FT4.

Study design, size, duration
This retrospective cohort study included 4,066 couples who received 4,894 ART treatment cycles in our clinic between 1 April 2016 and 31 August 2021.

Participants/materials, setting, methods
The differences in sperm parameters and ART outcomes across the paternal FT4 tertiles were compared using generalised linear models or generalised estimation equation models. The primary outcomes were the clinical pregnancy rate (CPR) and live birth rate (LBR), and the secondary outcomes were sperm parameters, fertilisation rate, good-quality embryo rate, blastocyst formation rate, and implantation rate.

Main results and the role of chance
The mean ages of the males and their female partners were 33.0 and 31.0 years, respectively. No significant differences are observed in the sperm parameters and ART outcomes across the paternal FT4 tertiles in the overall population. However, stratified analysis of men aged ≥ 35 shows a non-significantly lower CPR in the lower paternal FT4 tertile (adjusted rate: 0.36, 95% CI: 0.27–0.45) relative to the middle (adjusted rate: 0.45, 95% CI: 0.38–0.53) and upper (adjusted rate: 0.43, 95% CI: 0.36–0.51) tertiles. The adjusted LBR is 0.21 (95% CI: 0.15–0.30) for men aged ≥ 35 in the lower FT4 tertile (p = 0.024, with reference to the upper tertile), 0.27 (95% CI: 0.21–0.35) for those in the middle tertile and 0.30 (95% CI: 0.23–0.38) for those in the upper tertile. No differences in these outcomes are seen among men aged &lt; 35. The nonlinear smoothing curve obtained by using FT4 as a continuous variable further supports these findings.

Limitations, reasons for caution
Due to the retrospective design of the study, a causal relationship between paternal FT4 concentrations and ART outcomes could not be established. In addition, the study participants were patients who sought fertility treatment, which may have biased the results when we analysed the associations between FT4 concentrations and sperm parameters.

Wider implications of the findings
These results suggest that in older men, low paternal FT4 concentrations, although within the reference range, are associated with worse ART outcomes, especially LBR. Future prospective studies are warranted to confirm the detrimental effects of low paternal FT4 concentrations on ART outcomes.

Trial registration number
Not applicable