Ovarian hyperstimulation syndrome (OHSS) is a dramatic complication of ovulation induction. In its most severe form, OHSS is characterized by massive cystic enlargement of the ovaries associated with third space fluid shift, resulting in the formation of ascites and pleural effusion. Ascites developes because of increased peritoneal capillary permeability. In this study we examined the role of vascular endothelial growth factor (VEGF) and interleukins in the pathogenesis of increased capillary permeability. VEGF is a member of the family of heparin binding proteins that act directly on endothelial cells to induce proliferation and angiogenesis. VEGF mRNA and protein are expressed by human ovarian granulosa and theca cells late in follicular development and subsequent to ovulation by granulosa and theca cells. Therefore, VEGF is ideally positioned to provoke the increased permeability of theca blood vessels that occurs shortly before ovulation. Hybridization studies in the rat and primate ovary have demonstrated VEGF mRNA expression predominantly after the luteinizing hormone (LH) surge known to be essential for OHSS. The gonadotrophin-releasing hormone antagonist results in a decreased mRNA expression, implying such expression is dependent on LH. The expression of VEGF mRNA has been recently shown to be enhanced by human chorionic gonadotrophin (HCG) in a dose- and time-dependent fashion. These studies confirm the timely association between VEGF and HCG that has been clinically known for many years to be integral in the development of OHSS. VEGF concentrations in serum, peritoneal fluid and follicular fluid of patients at risk for OHSS have been shown to be significantly related to the development of the syndrome. Furthermore, the kinetics of VEGF in the plasma of patients who actually develop severe OHSS are closely correlated with the clinical course of the syndrome and with certain biological characteristics of OHSS and of capillary leakage, such as leukocytosis and increased hematocrit. Studies on ascitic fluid from patients with sever OHSS have proved that VEGF is the major capillary permeability agent. Incubation with VEGF antiserum decreased the vascular permeability activity by 70%. Interleukin-2 (IL-2) is the first of a series of lymphocytotrophic hormones to be recognized as pivotal for the regulation of immune response. However, hard data to confirm its central role in the pathogenesis of OHSS are still lacking, despite the fact that some preliminary studies suggest a positive association between the pooled follicular fluid IL-2 concentration and the development of OHSS. IL-6 is a mediator of the acute phase response to injury, a systemic reaction characterized by leukocytosis, increased vascular permeability and increased synthesis of acute phase proteins by the liver. Significantly higher serum and ascites IL-6 concentrations were seen in OHSS patients. The immunohistochemical localization pattern suggested that IL-6 is LH or HCG dependent. However, the use of IL-6 as a predictor for the occurrence o...
The perinatal outcome and congenital malformations in children born between 1978 and 1987 in Great Britain after in-vitro fertilization (IVF) at Bourn Hall Clinic and the Hallam Medical Centre are presented. The average maternal age was 34.2 years. Multiple births were frequent, constituting 23% of all deliveries; 19% were twins and 4% triplets. There were no quadruplet or higher order multiple births during that period. Twenty-five per cent of all deliveries were preterm. The mean birth weight was 2793 g and was strongly related to multiplicity of pregnancy and gestational age. Overall, 32% of babies had a low birthweight (less than 2500 g) with 6% having a very low birthweight (less than 1500 g). The overall stillbirth and infant mortality rates were two to three times higher than those of infants born after natural conception in England and Wales; this is attributed to the high incidence of multiple births. The stillbirth rates were 5.07, 20.8 and 24.7 per thousand total births in singletons, twins and triplets respectively. The corresponding figures for perinatal mortality were 13.5, 38.2 and 37 per thousand. Overall, 2.5% of the babies had one or more major congenital malformations diagnosed within one week of life. This was within the range of expected values in the United Kingdom and there was no significant increase in any specific malformation.
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