Abstract
Study question
TSH blood levels play a role in terms of ovarian stimulation and pregnancy? Do we need to treat patients with TSH out of range?
Summary answer
Euthyroid patients with negative autoantibodies during COS should not be treated even if basal TSH is higher than 2.5 U/L
What is known already
Abnormal thyroid function is associated with adverse pregnancy outcomes, being essential during embryo implantation and early pregnancy. TSH receptors can be found in endometrial and ovarian tissues and during controlled ovarian stimulation TSH levels suffer modifications because of hyperestrogenemia. Subclinical hypothyroidism is defined as a TSH level greater than 4.5 mIU/L with normal FT4 levels. It is controversial whether or not to use first-trimester pregnancy and infertility thresholds for upper limit of 2.5 mIU/L TSH. However, neither American Thyroid Association nor the American Society Reproductive Medicine recommendations have clearly defined how infertile patients need to be treated.
Study design, size, duration
Between April 2016 and December 2019, we performed a retrospective observational study at the University Hospital of Padua, including patients who underwent IVF/ICSI treatments. We included patients with idiopathic or tubal infertility or with poor ovarian reserve, in presence of basal TSH≤ 4,5 U/L and negative anti-TPO Ab and anti-Tg Ab. Exclusion criteria were severe male factor, TSH<0,2 or > 4,5 U/L, BMI higher than 30, oncologic patients, uterine disease.
Participants/materials, setting, methods
We enrolled a total of 389 patients. We checked TSH blood levels on the day before starting stimulation (T0). We divided our patients according to TSH level < 2,5U/L (group A) or ≥ 2,5U/L (group B). We then checked TSH on the day of hCG trigger (ThCG). Delta TSH (ThCG-T0) was calculated and correlated to endometrial thickness, number of occytes retrieved, embryos obtained and frozen, Clinical Pregnancy Rate (CPR) and Live Birth Rate (LBR).
Main results and the role of chance
Group A (251) and group B (138) were homogeneous for age, body mass index, AMH levels, antral follicular count. Short ovarian stimulation cycle with GnRH antagonist and long cycle with GnRH agonist proportions were similar in both groups. Also, FSH recombinant and hMG gonadotropin use and total amount were similar for the two groups. No statistically significant difference was found between the groups in terms of endometrial thickness, follicles greater than 14 mm as medium diameter, number of oocytes retrieved, number of mature oocytes (MII), embryos obtained, number of embryos cryopreserved, CPR and LBR. However, when considering the Delta TSH, we found possible correlations in group A. In particular, the number of oocytes retrieved was higher in Delta TSH positive (3.4±2.2) rather than in Delta negative women (2.6±1.7) with a p value of 0.002. Moreover, mature oocytes (MII) were retrieved more frequently in Delta TSH positive (5.7±3.8) rather than in Delta negative women (4.5±3) with a p value of 0.008. Group B Delta TSH did not show any possible statistically significant correlations.
Limitations, reasons for caution
This is a retrospective study and results must be confirmed on a well-designed randomized controlled study. Moreover, since we use strict eligibility criteria, we enrolled few patients. Correlations must be considered with caution since the role of TSH is under study, especially when considering LBR outcome.
Wider implications of the findings: Our results are congruent with previous studies. In particular, we suggest not to treat patients with TSH levels on range (between 0.2mIU/L and 4.5 mIU/L). TSH increase during COS in euthyroid patients could be interpreted as a positive physiological response and it is associate with better COS outcomes.
Trial registration number
N/A
Are STATS Arginine-methylated?
