Fibrinogen and cytokines as biomarkers of ovarian hyperstimulation syndrome in women undergoing assisted reproductive technology treatment: A prospective cohort study

Abstract

BackgroundOvarian hyperstimulation syndrome is the most severe and life-threatening iatrogenic complication of controlled ovarian stimulation during assisted reproductive technology procedures. Its diagnosis and severity grading are complex. Despite its debilitating and sometimes fatal consequences, there is a paucity of data on early predictors of ovarian hyperstimulation syndrome.ObjectiveThis study aimed to identify early predictors of ovarian hyperstimulation syndrome among women undergoing controlled ovarian stimulation for assisted reproductive technology treatment.MethodsThis prospective cohort study included 46 women undergoing assisted reproductive technology treatment from 1 April to 30 November 2023 at Hallmark Medicals, Kumasi, Ghana. Participants were conveniently recruited and received a standard controlled ovarian stimulation protocol. A structured questionnaire was used to collect sociodemographic and clinical data. Approximately 10 mL of venous blood was collected for laboratory analysis of fibrinogen and cytokine markers as well as hepatic and renal function tests. Statistical analyses were performed using R version 4.3.2 and Statistical Package for the Social Sciences version 26.0. A <i>p-</i>value of <0.05 was considered significant.ResultsThe incidence of ovarian hyperstimulation syndrome among the study cohort was 10.9%, with a higher prevalence (60%) among the 18-24 year age group (<i>p </i>><i> </i>0.05) than among other age groups. Fibrinogen and cytokine levels did not differ significantly between the ovarian hyperstimulation syndrome and non-ovarian hyperstimulation syndrome groups; moreover, there was no significant difference in their levels measured before and after controlled ovarian stimulation (<i>p</i> > 0.05). However, receiver operating characteristic analysis revealed that elevated baseline (pre-controlled ovarian stimulation) levels of fibrinogen (area under the curve = 0.567, <i>p </i>=<i> </i>0.604), interleukin-8 (area under the curve = 0.628, <i>p </i>=<i> </i>0.337), tumour necrosis factor-alpha (area under the curve = 0.615, <i>p</i> = 0.337) and interleukin-10 (area under the curve = 0.633, <i>p </i>=<i> </i>0.334) were associated with an increased risk of ovarian hyperstimulation syndrome. Women with elevated baseline interleukin-10 (≥33.5 ng/L) were at higher risk of ovarian hyperstimulation syndrome, with a sensitivity of 80.0%, specificity of 71.8%, area under the curve of 63.3% and an accuracy of 72.7%.ConclusionInterleukin-10 may serve as an early predictor of ovarian hyperstimulation syndrome among women undergoing controlled ovarian stimulation, with high sensitivity, specificity and accuracy. Further large-scale studies are warranted to confirm these findings.