The effect of growth hormone on the metabolome of follicular fluid in patients with diminished ovarian reserve.

BACKGROUND: Increasing evidence supports that the co-treatment with growth hormone (GH) enhances ovarian response and oocyte quality during controlled ovarian stimulation (COS) in patients with diminished ovarian reserve (DOR). The composition of follicular fluid (FF) plays an essential role in oocyte development and mirrors the communication occurring between the oocyte and follicular microenvironment. However, the effect of GH on the FF metabolome remains unclear. METHODS: This prospective observational study recruited DOR patients undergoing in vitro fertilization (IVF) cycles with minimal stimulation protocol for COS. Each patient receiving GH co-treatment was matched to a patient without GH co-treatment by propensity score matching. The FF was collected after isolating oocytes and assayed by gas chromatograph-mass spectrometry (GC-MS) metabolomics. The Pearson correlation was performed to evaluate the relationship between the number of oocytes retrieved and the levels of differential metabolites. The KEGG database was used to map differential metabolites onto various metabolic pathways. RESULTS: One hundred thirty-four FF metabolites were identified by GC-MS metabolomics. Twenty-four metabolites, including glutathione, itaconic acid and S-adenosylmethionin (SAM) showed significant differences between the GH and control groups (p-value < 0.05 and q-value < 0.1). In addition, the number of oocytes retrieved was significantly higher in the GH group compared to the control group (3 vs 2, p = 0.04) and correlated with the levels of five differential metabolites. Among them, the levels of antioxidant metabolite itaconic acid were upregulated by GH administration, while SAM levels were downregulated. CONCLUSIONS: The co-treatment with GH during COS may improve oocyte development by altering FF metabolite profiles in DOR patients. However, given the downregulation of SAM, a regulator of genomic imprinting, the potential risk of imprinting disturbances should not be neglected.

Adverse effect of paternal hepatitis B virus infection on clinical pregnancy after frozen-thawed embryo transfer.

PURPOSE: This study aimed to determine the effect of paternal hepatitis B virus (HBV) infection on reproductive outcomes of couples undergoing frozen-thawed embryo transfer (FET). METHODS: This retrospective cohort study included FET cycles performed between January 2014 and March 2017 in couples with a hepatitis B surface antigen (HBsAg)-positive male partner and an HBsAg-negative female partner, which was categorized as HBsAg group. The FET cycles underwent by couples with both HBsAg-negative partners were randomly selected as controls. The primary outcome was clinical pregnancy. RESULTS: A total of 117 FET cycles, comprising 39 in the HBsAg group and 78 in the control group, were included. Couples with HBsAg-positive male partners had significantly lower clinical pregnancy rate (17.9 vs 41.0%, P = 0.013), lower implantation rate (11.1 vs 24.5%, P = 0.014), and lower live birth rate (12.8 vs 30.8%, P = 0.034) compared with the control group. Moreover, the multivariate logistic regression analysis showed that paternal HBV infection was negatively associated with clinical pregnancy (odds ratio = 0.297, 95% confidence interval 0.108-0.817, P = 0.019). The miscarriage rate was not significantly different between the two groups (28.6 vs 25.0%, P = 1.000). CONCLUSIONS: Paternal HBV infection resulted in a lower frequency of clinical pregnancy after FET, a difference that was probably attributed to a detrimental effect of HBV on the ability of embryos to survive freezing and thawing.