Age Group-specific Reference Intervals for the Elecsys Anti-Müllerian Hormone Assay in Healthy Korean Women: a Nationwide Population-based Study.

Background: Anti-Müllerian hormone (AMH) is one of the most reliable markers of ovarian reserve. Automated AMH assays are widely used in clinical laboratories, but reference intervals for the Elecsys AMH assay for Asian populations have not yet been determined. We aimed to determine reference intervals in healthy Korean women. Methods: The study included 1,450 women aged 19 to 54 years who participated in the Korea National Health and Nutrition Examination Survey between 2013 and 2016. The study participants were divided into seven 5-year age groups. AMH and progesterone concentrations were measured using Roche Elecsys assays, and bone morphogenetic protein-15 (BMP15) was genotyped for the detection of major variants. Age group-specific reference intervals for AMH were established as recommended by the CLSI EP28-A3c guidelines. Results: The mean age was 37.4 years. AMH concentrations decreased with increasing age, especially after 40 years, with the median AMH decreasing from 30.9 pmol/L in participants of 19-24 years to 0.071 pmol/L in participants of 50-54 years. The mid-95 percentile AMH reference intervals decreased from 7.93-81.21 pmol/L in participants of 19-24 years to 0.07-3.86 pmol/L in participants of 50-54 years. Disease-associated BMP15 variants were not detected. Conclusions: We determined Elecsys AMH assay reference intervals in healthy Korean women. The results may provide basic information for the interpretation of AMH concentrations and assessment of ovarian reserve in Korean women.

Body fluid concentrations of bisphenol A and their association with in vitro fertilization outcomes.

Bisphenol A (BPA) is an endocrine-disrupting chemical thought to mimic the action of oestrogens. There have been reports suggesting an association between BPA exposure and infertility in humans. In this prospective cohort study, 146 couples undergoing in vitro fertilization (IVF) were recruited. Total BPA concentrations were measured in urine, plasma, follicular fluid and semen samples using LC-MS/MS. Pregnancy (serum ß-HCG >1.2 mIU/mL) was observed in 67 (45.9%) out of 146 couples. The mean of urine BPA for all participants was 3.7 ng/mL. In the logistic regression models, BPA concentrations of body fluids (female/male urine, female/male plasma, follicular fluid, and semen) did not significantly affect the outcomes such as pregnancy, presence of good quality embryo, or the proportion of normally fertilized oocytes. In the multiple linear regression models, BPA concentrations of body fluids did not significantly affect the parameters such as number of retrieved oocytes, peak E2 level, sperm concentration, and sperm motility. In conclusion, BPA concentrations in body fluids were not significantly associated with IVF outcomes such as pregnancy, good quality embryo, normally fertilized oocytes, number of retrieved oocytes, peak E2 level, sperm concentration, and sperm motility. Therefore, we could not find the evidence that the non-occupational low-dose exposure to BPA affects IVF outcomes.

Genetic Polymorphism of CYP2D6 and Clomiphene Concentrations in Infertile Patients with Ovulatory Dysfunction Treated with Clomiphene Citrate.

CYP2D6 is primarily responsible for the metabolism of clomiphene citrate (CC). The purpose of the present study was to investigate the relationship between CYP2D6 genotypes, concentrations of CC and its major metabolites and drug response in infertility patients. We studied 42 patients with ovulatory dysfunction treated with only CC. Patients received a dose of 100 mg/day CC on days 3-7 of the menstrual cycle. CYP2D6 genotyping and measurement of CC and the major metabolite concentrations were performed. Patients were categorized into CC responders or non-responders according to one cycle response for the ovulation. Thirty-two patients were CC responders and 10 patients were non-responders with 1 cycle treatment. The CC concentrations were highly variable within the same group, but non-responders revealed significantly lower (E)-clomiphene concentration and a trend of decreased concentrations of active metabolites compared to the responders. Nine patients with intermediate metabolizer phenotype were all responders. We confirmed that the CC and the metabolite concentrations were different according to the ovulation status. However, our results do not provide evidence for the contribution of CYP2D6 polymorphism to either drug response or CC concentrations.