The impact of thyroid autoimmunity on IVF/ICSI outcome: a systematic review and meta-analysis.

BACKGROUND: Thyroid autoimmunity (TAI) is the most frequent autoimmune condition and the first cause of thyroid dysfunction among women of reproductive age. Notably, it has been associated with adverse obstetric outcomes during all trimesters of pregnancy. Furthermore, since most studies show an increased prevalence of TAI among women attending infertility clinics, a detrimental impact of this condition on natural fertility and on the rate of success of assisted reproductive techniques has been suggested. However, to date, the results have been inconsistent.

OBJECTIVE AND RATIONALE: The objective of this study was to define the relation between TAI per se and the outcome of in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) cycles.

SEARCH METHODS: A systematic literature review and meta-analysis were conducted. A Medline search was performed to identify all the comparative studies published from January 1990 to November 2015 in the English language literature on IVF/ICSI outcome in women with and without TAI, using combinations of the medical subject heading terms 'thyroid autoimmunity', 'thyroid autoantibodies', 'IVF', 'ICSI', 'pregnancy', 'miscarriage' and 'delivery'. The primary outcome was live birth rate (LBR). Our secondary outcomes were number of oocytes retrieved (NOR), fertilisation rate (FR), implantation rate (IR), clinical pregnancy rate (CPR) and miscarriage rate (MR). We also extracted data on mean age and basal serum concentrations of thyroid stimulating hormone (TSH) and performed a meta-regression analysis to assess the effect of these two covariates on CPR and MR.

OUTCOMES: We selected 12 studies for the meta-analysis. Six of the included studies were prospective cohort studies, and six were retrospective cohort studies. Compared with women with negative TAI, women with positive TAI had a lower LBR (odds ratio (OR) 0.73; 95% confidence interval (CI) [0.54-0.99]; P = 0.04; 9 studies; 4396 women; I2 = 41%), a higher MR (OR 1.44; 95% CI [1.06-1.95]; P = 0.02; 12 studies; 4876 women; I2  = 35%), a similar CPR (OR 0.90; 95% CI [0.77-1.06]; P = 0.22; 12 studies; 4876 women; I2  = 7%), a similar number of oocytes (standardized mean difference [SMD] 0.10; 95% CI [-0.09 to 0.29]; P = 0.28; 5 studies; 1506 women; I2  = 47%), a similar FR (OR 1.11; 95% CI [0.97-1.27]; P = 0.13; 3 studies; 1082 women; I2  = 0%) and a similar IR (OR 0.98; 95% CI [0.73-1.32]; P = 0.91; 2 studies; 918 women; I2  = 0%). Both mean age (SMD 0.96; 95% CI [0.66-1.27]; P < 0.00001; 9 studies; 3256 women; I2  = 85%) and serum TSH (SMD 0.24; 95% CI [0.15-0.34]; P < 0.00001; 6 studies; 2098 women; I2  = 59%) were higher in women with TAI. However, neither of these two covariates were significantly associated with CPR or MR.

WIDER IMPLICATIONS: TAI does not impact on IVF/ICSI outcome in terms of NOR and likelihood of fertilisation, implantation and clinical pregnancy. On the contrary, the presence of thyroid autoantibodies may have a detrimental effect on the course of a pregnancy, determining an increased risk of miscarriage and a decreased chance of live birth. However, given the possible modifying effects of age and serum TSH, further evidence is warranted prior to drawing inferences on causality.