Regulation of vascular endothelial growth factor-A and its soluble receptor sFlt-1 by luteinizing hormone in vivo: implication for ovarian follicle angiogenesis

Guy Gutman, Vivian Barak, Sharon Maslovitz, Ami Amit, Joseph B. Lessing, Eli Geva
In: Fertility and Sterility · 2008 · vol. 89(4) , pp. 922–926 · doi:10.1016/j.fertnstert.2007.03.097 · PMID:18343373 · W2147775371
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Luteinizing hormone was found to regulate vascular endothelial growth factor-A and its soluble receptor sFlt-1 in vivo, suggesting a role in ovarian follicle angiogenesis.

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Abstract

ObjectiveTo determine in vivo whether LH supplementation during the late follicular phase induces ovarian follicle angiogenesis in humans, as reflected by vascular endothelial growth factor (VEGF)-A, its soluble receptor sFlt-1, and placental growth factor (PlGF) expression.DesignRandomized, double-blind, placebo-controlled study.SettingAcademic tertiary care medical center.Patient(s)Twenty infertile, healthy women (aged 18-39 years) undergoing IVF.Intervention(s)Administration of recombinant FSH after down-regulation and equal randomization of subjects to receive recombinant LH 75 IU/day or placebo when two or more follicles reached a mean diameter of 14 mm.Main outcome measure(s)Serum and follicular fluid (FF) VEGF-A, sFlt-1, and PlGF protein levels were measured.Result(s)Recombinant LH increased both the FF VEGF-A/sFlt-1 ratio statistically significantly and PlGF/sFlt-1 insignificantly. Recombinant LH did not affect the serum VEGF/sFlt-1 ratio. Plasma levels of PlGF were undetectable.ConclusionsThis in vivo study demonstrates for the first time in humans that LH induces ovarian follicular angiogenesis via modulation of VEGF-A and its soluble receptor sFlt-1 expression. A constant VEGF-A/sFlt-serum ratio may prevent adverse effects of VEGF-A. Because angiogenesis is essential during the periovulatory period, recombinant LH supplementation during the late follicular phase may improve ovulation induction outcome.

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