Safety Cut-off Point Of TSH In Women Preparing For Assisted Reproduction Before Controlled Ovarian Stimulation

Objective:Controlled ovarian stimulation（COS）is an important step of in vitro fertilization-embryo transfer,but COS can affect the thyroid function of women,and even increase thyrotropin（TSH）beyond the ideal range,which can last throughout the early pregnancy,potentially affecting the outcome of assisted reproduction and even the development of fetal nervous system.If COS had previously controlled baseline TSH within the appropriate range,the risk of TSH elevations beyond the ideal range after COS medication would undoubtedly have been reduced.The purpose of this study was to explore the safe cut-off point for the baseline TSH.Methods:The women who planned to enter the COS process for pregnancy preparation in assisted reproduction center of our hospital and whose baseline TSH had been in the appropriate range were followed up and treated with Gn RH antagonist program.The following two outcomes were established:a.The thyroid autoimmunity（TAI）was≥2.5m U/L after the thyroxine（LT4）supplementation or thyroid autoimmunity（TAI）supplementation before pregnancy;b.Patients with negative TAI before pregnancy and no need to take LT4 had TSH≥4.0m U/L after COS.Baseline thyroid function and thyroid autoantibodies were obtained from routine screening within 1 month prior to COS cycle entry（TSH₁）;The dynamic monitoring time points of serum TSH after COS administration were the day when ovulation was triggered by chorionic gonadotropin（h CG）injection after COS administration（TSH₂,hereinafter referred to as h CG）,and the14-16 days after h CG injection（TSH₃）.Considering that TSH was the most concerned index in this study and the index with the greatest influence on COS.In addition,the negative feedback speed is much faster than that of thyroid hormone,so only the TSH and sex hormone levels of subjects need to be measured in the two rechecks.The levels of TSH,FT3,FT4,TPOAb and Tg Ab were detected by Abbott ARCHITECT ci16200automatic biochemical immunoassay system（chemiluminescent particle immunoassay）.The levels of Progesterone（P）,Estradiol（E2）,luteinizing hormone（LH）and FSH were determined by chemiluminescence immunoassay.Levels of 25-hydroxyvitamin D,25（OH）D3 were determined by competitive electrochemiluminescence immunoassay.The levels of triglycerides（TG）,Low-density lipoprotein cholesterol（LDL-C）and fasting blood glucose（FPG）were determined by enzymatic method.The ferritin level was determined by chemical immunoassay.Results:（1）The study eventually included 138 women who had been treated at the assisted reproductive center of our hospital from July 2021 to December 2022 and completed at least two TSH tests,of which 114 women completed all three TSH tests.In the TAI+group of 38 patients,10 women were receiving LT4 with an unadjusted dose throughout the treatment.The mean dose of LT4 for 10 women was 43.75ug/day.There were 100 patients in the TAI-group,excluding those receiving LT4 treatment,with no difference in baseline characteristics between the two groups（P>0.05）.（2）TSH levels varied with time during COS treatment,but not with TAI+/-.The TSH level increased first and then decreased,that is,TSH₂was the peak of TSH level.（3）TSH₂was positively correlated with baseline TSH in both groups（all P<0.01）,and TSH₂was positively correlated with h CG day E2 in TAI+group（P<0.01）,but not in TAI-group.（4）After adjusting for confounders,the risk of TSH exceeding 2.5m U/L after COS increased by 3.31 times for per SD（0.78 m U/L）increase in baseline TSH in the TAI-group.In the TAI+group,for per SD increase（0.57 m U/L）in baseline TSH,the risk of TSH exceeding 2.5m U/L after COS increased by 2.97 times.（5）The baseline cut-off point was 1.92m U/L for group TAI-with TSH<4.0m U/L,and 2.11m U/L for group TAI+with TSH<2.5m U/L.Conclusion:1.In the process of controlled ovarian stimulation in assisted reproduction,the TSH level of women increased first and then decreased.The risk of peak TSH exceeding the ideal range increases with baseline TSH.2.The baseline cutoff value for TPOAb or Tg Ab positive individuals with TSH<2.5m U/L is 2.1m U/L,while the baseline cutoff value for TPOAb and Tg Ab negative individuals with TSH<4.0m U/L is1.9m U/L.