Metabolite Biomarkers for Early Ischemic-Hypoxic Encephalopathy: An Experimental Study Using the NeoBase 2 MSMS Kit in a Rat Model.

Hypoxic-ischemic encephalopathy (HIE) is one of the most common causes of childhood disability. Hypothermic therapy is currently the only approved neuroprotective approach. However, early diagnosis of HIE can be challenging, especially in the first hours after birth when the decision to use hypothermic therapy is critical. Distinguishing HIE from other neonatal conditions, such as sepsis, becomes a significant problem in diagnosis. This study explored the utility of a metabolomic-based approach employing the NeoBase 2 MSMS kit to diagnose HIE using dry blood stains in a Rice-Vannucci model of HIE in rats. We evaluated the diagnostic fidelity of this approach in a range between 3 and 6 h after the onset of HIE, including in the context of systemic inflammation and concomitant hypothermic therapy. Discriminant analysis revealed several metabolite patterns associated with HIE. A logistic regression model using glycine levels achieved high diagnostic fidelity with areas under the receiver operating characteristic curve of 0.94 at 3 h and 0.96 at 6 h after the onset of HIE. In addition, orthogonal partial least squares discriminant analysis, which included five metabolites, achieved 100% sensitivity and 80% specificity within 3 h of HIE. These results highlight the significant potential of the NeoBase 2 MSMS kit for the early diagnosis of HIE and could improve patient management and outcomes in this serious illness.

Hormonal profile in early luteal phase after triggering ovulation with gonadotropin-releasing hormone agonist in high-responder patients.

The major limitations associated with gonadotropin-releasing hormone agonist (GnRHa) triggering are inferior clinical outcomes in fresh embryo transfer cycles caused by luteal phase insufficiency following the GnRHa triggering. We included 153 high-risk patients in this study. In group I, the patients received gonadotropin-releasing hormone agonist (GnRHa) trigger + 1,500 IU human chorionic gonadotropin (hCG) support on the oocyte pick-up (OPU) day; in group II, the patients had a dual trigger (GnRHa + 1,500 IU hCG); and in group III (control), 10,000 IU hCG trigger was prescribed for the final oocyte maturation. The levels of LH, estradiol, and progesterone were evaluated in serum on the stimulation starting day, day 6 of stimulation, on the day of the trigger administration, OPU day, days 3 and 5 post-OPU, and day 14 post-ET, as well as in follicular fluid. Progesterone concentration was significantly lower in group I on OPU+5 compared to the hCG group (I vs. III, р = 0.0065). Progesterone levels were significantly lower in group II in serum on OPU+5 compared to groups I and III (I vs. II, р = 0.0068; II vs. III, р = 1.76 × 108). The progesterone levels were significantly higher in follicular fluid in group III compared to the study groups (I vs. III, р = 0.002; II vs. III, p = 0.009). However, no significant differences in clinical outcomes were found between the groups. Then, we divided all women into pregnant and non-pregnant groups and found that estradiol (p = 0.00009) and progesterone (p = 0.000036) on the day of the pregnancy test were significantly higher in the pregnant women group. Also, progesterone on OPU day was significantly higher in the non-pregnant group (p = 0.033). Two cases of moderate ovarian hyperstimulation syndrome (OHSS) late-onset occurred in group I (3.5%, 2/56), no case of moderate/severe OHSS late-onset in group II, and three cases of moderate late-onset in group III (5.7%, 3/53). The low-dose hCG supplementation improves the luteal phase insufficiency after GnRHa triggering, which is confirmed by the comparable pregnancy rates in fresh transfer cycles between the groups. However, low-dose hCG carries a similar risk of OHSS as the full dose of hCG in high-responder patients.

Angiogenic cytokine and interleukin 8 levels in early luteal phase after triggering ovulation with gonadotropin-releasing hormone agonist in high-responder patients.

PROBLEM: Interleukin 8 (IL-8), vascular endothelial growth factor A (VEGFA), its receptors 1 (VEGFR1) and 2 (VEGFR2) are associated with ovarian hyperstimulation syndrome (OHSS) pathophysiological mechanisms. The aim of this study was to evaluate the concentrations of these cytokines depending on the way of ovulation triggering. METHOD OF STUDY: A total of 51 high-responder patients underwent IVF program and received gonadotropin-releasing hormone agonists (GnRHa) trigger + 1500 IU human chorionic gonadotropin (hCG) support on the oocyte pick-up (OPU) day (group I), dual trigger (GnRHa + 1500 IU hCG; group II), or hCG trigger 10,000 IU (group III) for the final oocyte maturation. The concentrations of cytokines were evaluated in serum by the enzyme-linked immunosorbent assay kit. RESULT(S): VEGFR2 levels were significantly lower in groups I and II than in group III in serum on the OPU (I vs. III, p = .0456; II vs. III, p = .0122) and OPU + 5 day (I vs. III, p = .0004; II vs. III, p = .0082). VEGFA levels were lower in group I than in group III (p = .0298) on the OPU day, however, were similar in all groups on the OPU + 5 day. CONCLUSION(S): A small dose of hCG elicits similar concentrations of VEGFA to a full dose of hCG; however, GnRHa triggering reduces the concentrations of VEGFR2, which could lead to the OHSS prevention.