Impact of thyroid autoimmunity in euthyroid women on live birth rate after IUI.

Study question: Does thyroid autoimmunity (TAI) predict live birth rate in euthyroid women after one treatment cycle in IUI patients?

Summary answer: TAI as such does not influence pregnancy outcome after IUI treatment.

What is known already: The role of TAI on pregnancy outcome in the case of IVF/ICSI is largely debated in the literature. This is the first study to address this issue in the case of IUI.

Study design, size, duration: This was a retrospective cohort study. A two-armed study design was performed: patients anti-thyroid peroxidase (TPO)+ and patients anti-TPO-. All patients who started their first IUI cycle in our fertility center between 1 January 2010 and 31 December 2014 were included. After exclusion of those patients with or being treated for thyroid dysfunction, 3143 patients were finally included in the study.

Participants/materials, setting, methods: After approval by the institutional review board we retrospectively included all patients who started their first IUI cycle in our center between 1 January 2010 and 31 December 2014 with follow-up of outcome until 31 December 2015. Patients with clinical thyroid dysfunction were excluded (thyroid-stimulating hormone (TSH) <0.01 mIU/l; TSH >5 mIU/l) as were patients under treatment with levothyroxine or anti-thyroid drugs. These patients were then divided into two main groups: patients anti-TPO+ and patients anti-TPO- (= control group). Live birth delivery after 25 weeks of gestation was taken as the primary endpoint of our study. As a secondary endpoint, we evaluated differences in live birth delivery after IUI according to different upper limits of preconception TSH thresholds (<2.5 and <5.0 mIU/l). Furthermore, the influence of thyroid function (TSH, free thyroxine (fT4)), anti-TPO status, age, smoking, BMI, parity, ovarian reserve (anti-mullerian hormone (AMH) and FSH), IUI indication and IUI stimulation on live birth rate was analyzed.

Main results and the role of chance: Between-group comparison did not show any significant difference between the anti-TPO+ and anti-TPO- group with respect to live birth delivery-, pregnancy- or miscarriage rate with odds ratio at 1.04 (95% CI: 0.63; 1.69), 0.98 (95% CI: 0.62; 1.55) and 0.74 (95% CI: 0.23; 2.39), respectively. In addition, there were no significant differences in live birth delivery-, pregnancy- or miscarriage rate when comparing subgroups according to TSH level (TSH ≥2.5 mIU/l vs. TSH <2.5 mIU/l) with an odds ratio at 1.05 (95% CI: 0.76; 1.47), 1.04 (95% CI: 0.77; 1.41) and  0.95 (95% CI: 0.47; 1.94), respectively.

Limitations, reasons for caution: This study was powered for the primary aim, live birth rate. The limitations of this study are the absence of region-specific reference ranges for thyroid hormones and the absence of follow-up of TSH values during ART and subsequent pregnancy. Moreover, there was a time difference of 5 months between thyroid assessment and the start of stimulation. The area where the study was conducted corresponds to a mild iodine deficient area and data should be translated with caution to areas with different iodine backgrounds.

Wider implications of the findings: Our findings indicate comparable pregnancy-, abortion- and delivery rates in women with and without TAI undergoing IUI. Moreover, we were unable to confirm a negative effect of TSH level above 2.5 mIU/l on live birth delivery rate. We therefore believe that advocating Levothyroxine treatment at TSH levels between 2.5 and 4 mIU/l needs to be considered with caution and requires further analysis in a prospective cohort study.

Study funding/competing interest(s): No external funding was used for this study. No conflicts of interest are declared.