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Administration of low-dose LH induces ovulation and prevents vascular hyperpermeability and vascular endothelial growth factor expression in superovulated rats

¹ IVI foundation, (fIVI), C/Guadassuar no. 1, 46015 Valencia, Spain, ² Department of Obstetrics and Gynaecology, School of Medicine, Valencia University, C/Blasco Ibañez, 17, 46010 Valencia, Spain and ³ Hospital Dr Peset, c/Gaspar Aguilar no. 15, 46020 Valencia, Spain

Correspondence should be addressed to A Pellicer, C/Guadassuar no. 1, 46015 Valencia, Spain; Email: apellicer{at}ivi.es

The administration, to rats, of a combination of pregnant mares serum gonadotrophin (PMSG) and human chorionic gonadotrophin (hCG) in high doses induces the ovarian hyperstimulation syndrome (OHSS) which is characterized by increased vascular permeability (VP) and simultaneous overexpression of vascular endothelial growth factor (VEGF) in ovarian cells. hCG has a longer half-life than LH and a greater biological activity, expressed in a higher incidence of complications such as OHSS. Similarly, FSH may also be related to the ovulatory changes within the follicle as there is a simultaneous surge in spontaneous cycles. The aim of this study was to compare the capacity of hCG, FSH and LH to induce ovulation and simultaneously prevent OHSS in the animal model. Immature female rats were treated with 10 IU PMSG for 4 days, and ovulation was triggered with saline, 10 IU hCG, 10 IU FSH, 10 IU LH or 60 IU LH. The number of oocytes ovulated into the tubes, VP and mRNA VEGF expression were evaluated and compared.

All the hormones employed were as effective at triggering ovulation, with similar significant P values when compared with the control for which saline was used. The use of 10 IU LH resulted in significantly lower VP and VEGF expression than that seen in the groups treated with 10 IU hCG, 10 IU FSH or 60 IU LH. In conclusion, FSH and hCG, as well as a sixfold increase in LH, displayed similar biological activities, including increased VP due to excessive VEGF expression. The use of lower doses of LH produced similar rates of ovulation, while preventing the undesired changes in permeability. These experiments should therefore encourage clinicians to determine the optimal dose of LH to be employed in women in order to trigger ovulation and, at the same time, avoid the risk of OHSS.

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				S. R. Soares, R. Gomez, C. Simon, J. A. Garcia-Velasco, and A. Pellicer Targeting the vascular endothelial growth factor system to prevent ovarian hyperstimulation syndrome Hum. Reprod. Update, April 2, 2008; (2008) dmn008v1. [Abstract] [Full Text] [PDF]