P-627 Does artificial hormonal therapy increase the TSH levels in frozen embryo transfer?
Authors: Diego Domenico F , Mariani G , Galliano D , Pellicer A , De Angelis F , Pellegrini L , Cozzolino M 
Published: July 2024

Abstract

Study question
Does administration of estradiol valerate for frozen embryo transfer (FET) increase the TSH value and the risk of miscarriage?

Summary answer
TSH is increased at the time of endometrial thickness and pregnancy test in HRT cycles. Women with higher TSH have an increased risk of miscarriage.

What is known already
Several studies describe the correlation between estradiol and TSH levels during menstrual cycles. The circulated TSH is upregulated by estradiol, in fact, TSH increases in the periovulatory phase and in women taking oral contraceptive therapy. A higher estradiol in the first trimester is correlated with an increased risk of thyroid dysfunction in offspring. TSH is also correlated to beta-Human Chorionic Gonadotropin (b-HCG) levels, many studies reported an increase of TSH values at b-HCG peak during 10-12 weeks of gestation.

Study design, size, duration
This is a retrospective, single-center, observational study enrolling 607 patients at IVI Roma from April 2022 to June 2023.Patients with 30-47 years old with single blastocyst transfer were included in the study. Both euploid frozen embryo transfer (FET) from autologous oocyte ICSI-PGT-A cycles and FET from ICSI cycles using donated oocytes were considered. FET performed under artificial endometrial preparation with HRT using exogenous estradiol and progesterone (vaginal, subcutaneous and intramuscular) were included in the study.

Participants/materials, setting, methods
TSH was evaluated before estradiol valerate administration (T0), at the control for endometrial thickness (T1), the day of embryo transfer (T2), and the day of b-HCG evaluation (T3). Accordingly, the patients were divided into two groups based on their TSH levels (low-normal group, ≤ 2.5 mIU/L; high group, &gt; 2.5 mIU/L). The primary outcome was TSH values at different times. The secondary outcome evaluated the miscarriage rate (MR) calculated for FET.

Main results and the role of chance
TSH mean at T0 was 1.65 ± 0.87. The mean value of TSH after estradiol valerate administration was 1.97 ± 1.28. TSH value increased during the estradiol valerate administration with a mean increase of 0.29 mIU/L reaching statistical significance (p &lt; 0.0001). No statistical differences were reported between T0-T2 (p = 0.64) while the statistical difference was reported in time T0-T3 with a mean increase of 0.40 mIU/L (p &lt; 0.0001). Women with T1-TSH value &gt; 2.5 mIU/L were 18.95%. The miscarriage rate in the group with TSH value &gt;2.5 mIU/L was 17.81%. The univariate analysis showed that T1-TSH values &gt;2.5 mIU/L did not affect the miscarriage rate OR 0.79 (95 CI% 0.37-1.67), p = 0.54. The multivariate analysis considering age, BMI and source of oocytes showed no statistical significance on the miscarriage rate OR 0.82 (95 CI% 0.39-1.72), p = 0.62. T2-TSH values did not affect the miscarriage rate in the univariate and multivariate analyses. Regarding T3-TSH, the univariate analysis showed that THS &gt;2.5 mIU/L affects the miscarriage rate OR 1.97(95 CI% 1.07-3.65), p = 0.03. Multivariate analysis considering possible confounders showed that women with THS &gt;2.5 mIU/L have a higher risk of miscarriage OR 1.96 (95 CI% 1.02-3.78), p = 0.04.

Limitations, reasons for caution
The retrospective design and patients with different female infertility factors for IVF were included in the study, leading to a possible biased population. The T1-TSH assessment was not scheduled at the same time for each patient. Women with TSH &gt;2.5 mIU/L at the T1-TSH value were treated with levothyroxine.

Wider implications of the findings
This study emphasizes the correlation between estradiol valerate administration and TSH values and the possible relation with increasing risk of miscarriage in women with higher TSH. Patients undergoing FET with HRT should consider thyroid supplementation or increasing dosage to reduce the risk of miscarriage.

Trial registration number
not applicable