P-610 Elevated/high-normal TSH on day of beta-hCG in sub-clinical hypothyroid patients on levothyroxine associated with better odds of pregnancy in IVF cycles: a nested case-control study
Authors: Ghoshdastidar B , Ghoshdastidar S 
Published: July 2024

Abstract

Study question
Is there an association between odds of achieving pregnancy and high-normal/elevated TSH levels in sub-clinical hypothyroid (SCH) patients on levothyroxine replacement who are undergoing IVF?

Summary answer
Odds of achieving pregnancy are significantly greater when TSH on day of beta-hCG is elevated/high-normal despite levothyroxine replacement in sub-clinical hypothyroid (SCH) patients undergoing IVF.

What is known already
TSH levels are known to increase following ovarian stimulation (OS). A 2023 Nature publication reported that in euthyroid patients undergoing fresh embryo transfer following OS and IVF, elevated/high-normal TSH levels (&gt;2.5 mIU/mL) are associated with better pregnancy rates. Another recent study found no differences in IVF outcomes between SCH patients whose TSH was maintained=/&lt; 4.2 mIU/mL on levothyroxine vs euthyroid controls. To the best of our knowledge, there are no prospective studies investigating possible association between pregnancy outcome and elevated TSH levels following OS within a cohort of SCH patients on levothyroxine replacement, using 2.5 mIU/mL as a strict cut-off.

Study design, size, duration
Nested case-control study performed between July-December 2023. PCOS and other endocrinopathies excluded. 100 SCH patients booked for fresh, blastocyst eSET cycles initially recruited after thyroxine replacement. 79 patients completed the study following 5 drop-outs and 16 cases of cycle cancellation/failure, cleavage-stage transfers and freeze-all. Odds of achieving pregnancy (‘cases’) in patients with elevated/high-normal TSH (‘exposure’) on day of beta-hCG determined by Odds Ratio, with beta-hCG negative patients serving as ‘controls’. First IVF cycle data analysed/presented.

Participants/materials, setting, methods
Study performed at an university-affiliated ART institute. Following institutional ethical clearance, patients with SCH (TSH&gt;2.5 mIU/mL) recruited after informed consent. Levothyroxine replacement initiated to achieve TSH:0.5-2.5 mIU/mL and continued; followed by OS, antagonist IVF/ICSI cycles, hCG trigger and fresh blastocyst eSET. TSH measured again on day of beta-hCG (blinded). Odds Ratio calculated (IBM SPSS V.26) to determine odds of achieving pregnancy in high-normal/elevated group (TSH&gt;2.5 mIU/mL) compared to low-normal group (TSH =/&lt; 2.5 mIU/mL).

Main results and the role of chance
Baseline demographic characteristics of the single starting cohort of sub-clinical hypothyroid patients undergoing IVF/ICSI (n = 79) are summarized as mean±SD- age: 31.7±4.9 years, BMI: 27.9±14.2 kg/m2, AMH: 3.1±2.4 ng/mL, TSH before levothyroxine replacement: 5.5±2.7 mIU/mL. Data analysis showed that out of 63 patients in whom TSH level elevated &gt; 2.5 mIU/mL on day of beta-hCG, 33 became pregnant (P.R- 52.4%); and out of 16 patients in whom TSH remained =/&lt; 2.5 mIU/mL on day of beta-hCG, 3 became pregnant (P.R- 18.8%). Statistical analysis further revealed that odds of achieving pregnancy in elevated/high-normal TSH group was almost 5 times compared to odds of achieving pregnancy in low-normal TSH group (OR = 4.77, C.I= 1.24-18.37, at 95% confidence), considering TSH values on day of beta-hCG. Mean TSH in pregnant group (n = 36) was also found to be higher (4.2±1.6 mIU/mL) than mean TSH (3.9±1.9 mIU/mL) in those who did not get pregnant (n = 43).

Limitations, reasons for caution
Our study is limited by its modest sample size and adequately powered, larger prospective studies are needed before definite conclusions can be drawn from our data. Moreover, being an ongoing study, we do not yet have miscarriage and live-birth data for all patients and thus have not reported the same.

Wider implications of the findings
To our knowledge, this is the first prospective study documenting association between positive pregnancy outcome and high-normal TSH (using TSH&gt;2.5 mIU/mL as cut-off) in SCH patients having fresh blastocyst eSET. Further investigation is required to determine if high-normal TSH following OS has protective impact on IVF, and its underlying mechanism.

Trial registration number
not applicable