Meta-analysis of ART outcomes in women with different preconception TSH levels

Abstract

BackgroundTo assess whether elevated thyroid-stimulating hormone (TSH) levels before conception can predict poor outcomes of assisted reproductive technology (ART).MethodsPrior to July 2018, we searched the PubMed, EMBASE, COCHRANE, Google Scholar, and CNKI databases for studies. Retrospective or prospective reports that compared ART results in patients with subclinical hypothyroidism (SCH) with normal thyroid function were selected. Two reviewers separately reviewed each potential article for qualification, analyzed the quality of the studies according to the Newcastle-Ottawa scale, and extracted the data. The PRISMA guidelines were adopted.ResultsWe selected a total of 18 publications that included 14,846 participants for this meta-analysis. When the TSH cut-off value for SCH was set at 2.5 mIU/L, no significant differences were observed in ART-related outcomes between SCH patients and normal women. The evaluated outcomes included the live birth rate (LBR) (OR: 0.93; 95% CI (0.77,1.12), P = 0.43), clinical pregnancy rate (CPR) (OR:1.02; 95% CI (0.90,1.17); P = 0.74), pregnancy rate (PR) (OR: 1.00; 95% CI (0.89,1.12); P = 0.99), and miscarriage rate (MR) (OR:1.24; 95% CI (0.85, 1.80); P = 0.26). Furthermore, when a higher TSH level was used as the cut-off value to diagnose SCH (i.e., 3.5–5 mIU/L), a significant difference was found in the MR (OR: 1.91; 95% CI (1.09, 3.35); P = 0.02) between the two groups of ART-treated women. However, when a broader cut-off value was used to define SCH, no significant differences were observed in the LBR (OR: 0.72; 95% CI (0.47,1.11); P = 0.14), CPR (OR: 0.82; 95% CI (0.66,1.00); P = 0.052), or PR (OR: 1.07; 95% CI (0.72,1.60); P = 0.74) between the two groups of ART-treated women.ConclusionNo difference was observed in ART outcomes when a TSH cut-off value of 2.5 mIU/L was used. However, when a broader TSH cut-off value was used, preconception SCH resulted in a higher miscarriage rate than in normal women.Electronic supplementary materialThe online version of this article (10.1186/s12958-018-0424-0) contains supplementary material, which is available to authorized users.

2021 European Thyroid Association Guideline on Thyroid Disorders prior to and during Assisted Reproduction

“…The most commonly used commercial assays in Europe have an ULRR for serum TSH between 3.60 and 4.31 mIU/L [20]. In a recent meta-analysis, altered ART outcomes were present from TSH levels of 3.5 mIU/L and upwards, but in 2 interventional trials with LT4, an increased LBR was present only when TSH levels exceeded 4.0 and 4.5 mIU/L, respectively [13, 14, 21]. Based on these factors, therefore, we propose to define SCH (and to initiate treatment with LT4) from a TSH cutoff >4.0 mIU/L or >ULRR if the latter is >4.0 mIU/L.…”

“…Furthermore, women with PCOS, POI, and idiopathic subfertility have a higher prevalence of TAI and serum TSH levels compared with fertile women [6, 9, 25]. Serum TSH levels >3.5 mIU/L are associated with impaired ART outcomes, and LT4 treatment can increase LBRs in women with TSH levels >4.0 mIU/L [11, 14].…”

“…The impact of thyroid dysfunction before ART on the live birth rate (LBR) seems to emerge at TSH levels >3.5 mIU/L and upwards [14]. In a meta-analysis mainly including women with TSH levels >4.0 mIU/L, LT4 treatment increased LBR to comparable rates to those in women without elevated TSH [11].…”

MANAGEMENT OF ENDOCRINE DISEASE: Thyroid and female infertility: more questions than answers?!

“…The most commonly used commercial assays in Europe have a ULRR for serum TSH between 3.60 and 4.31 mIU/L (89). In a recent meta-analysis, altered ART outcomes were present from TSH levels >3.5 mIU/L on, and based on this and the few interventional trials with LT4 that showed an increased LBR when TSH levels exceeded 4.0 and 4.5 mIU/L, respectively, guidelines propose to initiate treatment with LT4 from a TSH cutoff >4.0 mIU/L or >ULRR if the latter is >4.0 mIU/L (16,90,91,92). According to the (strict) Cochrane systemic review criteria, only one study could be included, in which 64 women were scheduled for IVF/ICSI with TSH levels >4.5 mIU/L (>80% of the women had TAI) and randomised to LT4 or no treatment.…”

The impact of TSH levels on clinical outcomes 14 days after frozen-thawed embryo transfer

“…Most importantly, this study observed a higher clinical pregnancy rate when basal TSH levels were less than 2.5 mIU/L. However, whether moderately elevated TSH levels compromise ART clinical outcomes remains controversial [4][5][6][7]. Experts suggest that TSH concentrations < 2.5 mIU/L should be maintained during the ART procedure in infertile patients, especially in those with overt hypothyroidism [8][9][10][11].…”