Abstract
BackgroundThe objective of this investigation was to determine if kinase insert domain/vascular endothelial growth factor receptor 2 (KDR/VEGFR2) genetic variation was associated with the development of ovarian hyperstimulation syndrome (OHSS) in patients undergoing controlled ovarian hyperstimulation (COH).MethodsThis was a case–control study of 174 patients who underwent controlled ovarian stimulation. Patient blood samples were genotyped for single nucleotide polymorphisms (SNPs) spanning the KDR locus. OHSS development, clinical outcome variables, SNP and haplotype frequencies were compared between control (n = 155) and OHSS (n = 19) groups.ResultsPatients who developed OHSS had significantly higher response markers (estradiol levels of the day of hCG administration, number of follicles developed, number of eggs retrieved) than control patients. When adjusted for age and self-identified race, the rs2305945 G/T genotype was associated (P = 0.027) with a decreased risk (OR = 0.30; 95% CI = 0.10, 0.93) of developing OHSS using an overdominant model. The rs2305945 G/T variant was also associated with decreased COH response (number of follicles, number of eggs retrieved) in an overdominant model. The rs2305948, rs1870378, rs2305945 (C-T-G) haplotype was associated with both decreased COH response and OHSS risk (unadjusted OR = 0.10; 95% CI = 0.01, 0.80, P = 0.031).ConclusionsThe KDR receptor is believed to play a central role OHSS development and is a target for pharmacological prevention of OHSS. These results indicate that genetic variation in the KDR gene may impact individual risk of developing OHSS from COH. In addition, the rs2305948 SNP and C-T-G haplotype might serve as potential biomarkers for poor ovarian response to COH.
Highlights
The objective of this investigation was to determine if kinase insert domain/vascular endothelial growth factor receptor 2 (KDR/Vascular endothelial growth factor receptor 2 (VEGFR2)) genetic variation was associated with the development of ovarian hyperstimulation syndrome (OHSS) in patients undergoing controlled ovarian hyperstimulation (COH)
Given that the pathophysiology of OHSS involves increased vascular permeability (VP), these results suggest that C-T-G haplotype could potentially result in a Kinase insert domain receptor (KDR) receptor with decreased function
We found that the rs2305945 Single nucleotide polymorphism (SNP) and the C-T-G haplotype were both associated with diminished ovarian response to COH
Summary
The objective of this investigation was to determine if kinase insert domain/vascular endothelial growth factor receptor 2 (KDR/VEGFR2) genetic variation was associated with the development of ovarian hyperstimulation syndrome (OHSS) in patients undergoing controlled ovarian hyperstimulation (COH). COH is associated with some degree of risk for the iatrogenic complication ovarian hyperstimulation syndrome (OHSS). Life threatening, OHSS leads to hospitalization in 1.9% of IVF cases [7]. In cases of severe OHSS, myocardial infarction and/or stroke can lead to death [9,10]. Onset OHSS occurs within 3–5 days after oocyte retrieval and is related to the hyperresponse of the ovaries to COH followed by the use of hCG for oocyte maturation. Late onset OHSS appears 9– 12 days after oocyte retrieval and results from COH and the endogenous hCG produced by a developing embryo [11]. Spontaneous cases of OHSS have been reported with the supra-physiologic hCG levels seen with multiple gestations or molar pregnancy [12]. Regardless of severity, the development of OHSS is associated with significant physical, psychological and financial implications [14]
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