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To investigate whether there is a relationship between TSH levels on the 14th day post embryo transfer (D14 TSH levels) and the reproductive outcomes in euthyroid women who are free from levothyroxine (LT4) treatment and undergo the first in vitro fertilization /intracytoplasmic sperm injection embryo transfer (IVF/ICSI-ET) cycles with the homogeneous ovarian stimulation protocols. This was a prospective study including a total of 599 euthyroid women undergoing the first IVF/ICSI ET cycles. Serum samples were collected and frozen on the 14th day post embryo transfer. TSH levels were measured after the confirmation of clinical pregnancy. The patients were divided into three groups (low-normal ≤ 2.5 mIU/L; high-normal 2.5–4.2 mIU/L; and high > 4.2 mIU/L) based on D14 TSH levels. Reproductive outcomes were compared among the three groups. Binary logistic regression analyses and generalized additive mixed models with smoothing splines were used to investigate the relationship between TSH levels and reproductive outcomes. D14 TSH levels were significantly elevated compared to basal TSH levels, and the degree of TSH elevation was significantly higher in pregnant women compared to that in non-pregnant women. The clinical pregnancy and live birth rates increased significantly in the high-normal D14 TSH groups, and doubled in the high D14 TSH groups compared to the low TSH groups. When adjusted by age, basal TSH, AMH, E2, endometrial thickness, type and causes of infertility, and transferred embryos, the dose-dependent relationships between D14 TSH and clinical pregnancy and live birth were observed. Obstetric outcomes in singleton or twins live birth among the different D14 TSH groups were similar. Elevated D14 TSH levels were associated with better clinical pregnancy and live birth rates, and were not associated with worse obstetric outcomes. The mechanisms to explain the phenomenon remained to be studied. [ABSTRACT FROM AUTHOR]

Bicalutamide (BCL) has been approved for treatment of advanced prostate cancer (Pca), and vitamin D is inevitably used in combination with BCL in Pca patients for skeletal or anti-tumor strategies. Therefore, it is necessary to study the effect of vitamin D application on the pharmacokinetics of BCL. We developed and validated a specific, sensitive and rapid UHPLC–MS/MS method to investigate the pharmacokinetic behaviours of BCL in rat plasma with and without the combined use of vitamin D. Plasma samples were extracted by protein precipitation with ether/dichloromethane (2:1 v/v), and the analytes were separated by a Kinetex Biphenyl 100A column (2.1 × 100 mm, 2.6 μm) with a mobile phase composed of 0.5 mM ammonium acetate (PH 6.5) in water (A) and acetonitrile (B) in a ratio of A:B = 35:65 (v/v). Analysis of the ions was run in the multiple reactions monitoring (MRM) mode. The linear range of BCL was 5–2000 ng mL−1. The intra- and inter-day precision were less than 14%, and the accuracy was in the range of 94.4–107.1%. The mean extraction recoveries, matrix effects and stabilities were acceptable for this method. The validated method was successfully applied to evaluate the pharmacokinetic behaviours of BCL in rat plasma. The results demonstrated that the pharmacokinetic property of BCL is significantly affected by combined use of vitamin D, which might help provide useful evidence for the clinical therapy and further pharmacokinetic study. [ABSTRACT FROM AUTHOR]

Background and Objectives: Hyperhomocysteinaemia (HHcy) is an independent risk factors for several disorders, including cardiovascular disease. The understanding of the relationship among genetic, epigenetic and the efficacy of folate therapy for HHcy remain unclear. This study aim to investigate whether betaine-homocysteine methyltransferase (BHMT) single-nucleotide polymorphisms (SNPs) and DNA methylation are related to the efficacy of folate therapy for HHcy and whether BHMT DNA methylation mediates the SNP-folate therapy efficacy association.Methods and Study Design: A total of 638 patients with HHcy were involved in this prospective cohort study. Logistic and linear regression was used to explore associations among SNPs, DNA methylation, and folate therapy efficacy. Finally, mediation analysis was performed to investigate whether DNA methylation of BHMT mediates the association between SNPs and folate therapy efficacy.Results: BHMT rs3733890 was significantly associated with folate therapy efficacy (p<0.05). BHMT and BHMT_1 DNA methylation level was significantly associated with folate therapy efficacy (p=0.017 and p=0.028). DNA methylation of BHMT and BHMT_1 mediated 34.84% and 33.06% of the effect of rs3733890 on folate therapy efficacy, respectively.Conclusions: There has a consistent interrelationship among BHMT genetic variants, methylation levels of BHMT, and folate therapy efficacy. BHMT and BHMT_1 DNA methylation proportionally mediated the effects of rs3733890 SNPs on the efficacy of folate therapy for HHcy. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to evaluate the associations of thyroid autoimmunity (TAI) with the number of oocytes retrieved (NOR), fertilization rate (FR), and embryo quality (EQ) in euthyroid women with infertility and diminished ovarian reserve (DOR)., Methods: This retrospective cohort study involved 1,172 euthyroid women aged 20-40 years with infertility and DOR who underwent an oocyte retrieval cycle. TAI was diagnosed in the presence of serum thyroperoxidase antibody (TPOAb) concentrations higher than 34 IU/ml and/or serum thyroglobulin antibody (TgAb) concentrations exceeding 115.0 IU/ml. Among these women, 147 patients with TAI were classified as the TAI-positive group, while 1,025 patients without TAI were classified as the TAI-negative group. Using generalized linear models (GLMs) adjusted for confounding factors, we evaluated the associations of TAI and the serum TPOAb and TgAb concentrations and NOR, FR, and EQ in this study's subjects. The TPOAb and TGAb values were subjected to log10 transformation to reduce skewness. Logistic regression models were used to estimate the effects of TPOAb and TgAb concentrations on the probabilities of achieving a high NOR (≥7) and high FR (>60%)., Results: For the whole study population, women with TAI had a significantly lower NOR and poorer EQ than women without TAI ( P < 0.001 for both). Interestingly, in the TSH ≤2.5 subgroup, the TAI-positive group also had a significantly lower NOR and poorer EQ than the TAI-negative group ( P < 0.001 for both). Furthermore, negative associations were observed between log10(TPOAb) concentrations and NOR and the number of high-quality embryos and available embryos ( P < 0.05 for all). The log10(TgAb) concentrations were inversely associated with NOR and the number of high-quality embryos ( P < 0.05 for all). In the regression analysis, the log10(TPOAb) concentrations had lower probabilities of achieving a high NOR [adjusted odds ratio (aOR): 0.56; 95% confidence interval (95% CI) 0.37, 0.85; P = 0.007]., Conclusions: TAI and higher TPOAb and TgAb concentrations were shown to be associated with reductions in the NOR and EQ in the study population. Our findings provide further evidence to support systematic screening and treatment for TAI in euthyroid women with infertility and DOR., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Zhang, Su, Ren, Yu, Li, Xu and Lou.)