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

Abstract

Objective: To 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.

Design: Randomized, double-blind, placebo-controlled study.

Setting: Academic 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.

Conclusions: This 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.