Abstract
BackgroundOvarian hyperstimulation syndrome (OHSS) is a common and severe complication for patients undergoing IVF/ICSI-ET. Melatonin widely participates in the regulation of female reproductive endocrine activity. However, whether melatonin participates in the progression of OHSS is largely unknown. This study aims to identify the predictive value of follicular fluid (FF) melatonin for OHSS establishment and the underlying mechanism.MethodsAll participants of this case-control study were enrolled at the Reproductive Medicine Center located in the First Affiliated Hospital of Zhengzhou University in China from January to October in 2017. Quantitative real-time PCR and western blot were used to examine the mRNA and protein levels. Primary granulosa cells were extracted and cultured for in vitro studies. Melatonin concentration was measured by ELISA. Logistic analysis and receiver-operating characteristic (ROC) curves were used to evaluate the predicting value of melatonin on OHSS occurrence.Main outcome measuresThe expression level of melatonin receptor 2 (MT2), P450 aromatase cytochrome (aromatase), vascular endothelial growth factor (VEGF), and inducible nitric oxide synthase (iNOS) mRNA in human primary granulosa cells. The concentration of melatonin in FF. The predicting value of melatonin on OHSS and the cut-off value of the prediction.ResultsFF melatonin concentrations were significantly higher in patients with OHSS compared to non-OHSS group (35.94 ± 10.18 ng/mL vs 23.93 ± 10.94 ng/mL, p<0.001). The expression of MT2 mRNA (p = 0.0459) and protein in granulosa cells was also significantly higher in the OHSS group. When using a cut-off level of 27.52 ng/ml, the sensitivity and specificity of FF melatonin to predict OHSS was 84.6 and 74.0%, respectively (p < 0.0001). We also found that melatonin could up-regulates aromatase mRNA, VEGF mRNA expression and down-regulates iNOS mRNA expression in the granulosa cells.ConclusionOHSS patients have higher melatonin in the FF as well as higher MT2 expression in the granulosa cells. The melatonin in FF might be used as an effective predictor for the occurrence of OHSS.
Highlights
Melatonin (N-acetyl-5-methoxytryptamine) is a compound extracted from pineal glands and peripheral nerve [1]
The melatonin in follicular fluid (FF) might be used as an effective predictor for the occurrence of Ovarian hyperstimulation syndrome (OHSS)
No significant difference was found in age, BMI, antral follicle count (AFC), basal follicle stimulating hormone (FSH), E2, P4, prolactin (PRL) and testosterone (T) levels as well as duration of infertility between OHSS and non-OHSS groups
Summary
Melatonin (N-acetyl-5-methoxytryptamine) is a compound extracted from pineal glands and peripheral nerve [1]. Melatonin participates in the regulation of hypothalamic-pituitary-gonadal axis function and reproductive endocrine activity [2, 4]. Earlier studies have demonstrated that MT1 and MT2 are widely distributed in the female reproductive system, such as the uterus, ovaries, the epithelial cells of the mammary gland, and the granulosa cells [8]. According to a single-nucleotide polymorphisms (SNP) study, rs10830963 in MT2 gene may predispose the polycystic ovarian syndrome (PCOS) in the Chinese population [9], which indicate that MT2 might regulate follicle development and ovary reactivities. Melatonin widely participates in the regulation of female reproductive endocrine activity. Whether melatonin participates in the progression of OHSS is largely unknown. This study aims to identify the predictive value of follicular fluid (FF) melatonin for OHSS establishment and the underlying mechanism
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