endothelin-1 and Ovarian-Hyperstimulation-Syndrome

Ovarian hyperstimulation syndrome (OHSS) is a serious complication affecting ovulation induction. Its most severe manifestation takes the form of massive ovarian enlargement and multiple cysts, haemoconcentration and third-space accumulation of fluid. The full-blown clinical syndrome may be complicated by renal failure and oliguria, hypovolaemic shock, thromboembolic episodes, adult respiratory distress syndrome (ARDS), and death. Although the pathophysiology of this syndrome has not been completely elucidated, it seems likely that the increased capillary permeability triggered by the release of vasoactive substance secreted by the ovaries under human chorionic gonadotrophin (HCG) stimulation plays a key role in this syndrome. Several factors such as histamine, serotonin, prostaglandins, prolactin, and a variety of other substances have been implicated in this process in the past. At present, factors belonging to the renin-angiotensin system, cytokines including the interleukins, tumour necrosis factor alpha, endothelin-1 and vascular endothelial growth factor (VEGF) are thought to be involved in triggering increased vascular permeability after ovulation induction treatment. This manuscript summarizes the current knowledge of the pathophysiology of ovarian hyperstimulation syndrome with emphasis on the correlation of the various factors with the clinical phenomena of this iatrogenic syndrome.

Topics: Adult; Chorionic Gonadotropin; Endothelial Growth Factors; Endothelin-1; Female; Histamine; Humans; Iatrogenic Disease; Interleukins; Lymphokines; Models, Biological; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Prostaglandins; Renin-Angiotensin System; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

To examine the effects of low-to-high doses of tamoxifen on ovarian histopathology, serum VEGF, and endothelin 1 levels in ovarian hyperstimulation syndrome (OHSS) in an experimental setting.. A total of 20 female Wistar albino rats, 22 days of age, were randomly divided into four groups. Follicle-stimulating hormone 10 IU was administered subcutaneously in 15 rats on 4 consecutive days, with OHSS induction on day 5 by 30 IU of human chorionic gonadotropin. Group 1 (n=5) comprised 35-day-old control rats, group 2 (n=5) 35-day-old OHSS rats, group 3 (n=5) 27-day-old OHSS rats receiving 1 mg/kg of oral tamoxifen for 7 days, group 4 (n=5) 27-day-old OHSS rats receiving 3 mg/kg of oral tamoxifen for 7 days. All rats were decapitated on day 35. Serum VEGF, endothelin 1, and ovarian follicular reserve were assessed in all rats. Kruskal-Wallis variance analysis and the Mann-Whitney U-test were used for statistical comparisons. A Bonferroni correction was performed to control the inflation of significance, with a significance level set at a P-value of less than 0.025.. Despite higher serum VEGF, endothelin 1, follicular reserve, and angiogenesis and fibrosis of the corpus luteum in the OHSS group compared to controls, these differences were not significant (P>0.025, Mann-Whitney U-test). There was a significant reduction in the ovarian follicular reserve in tamoxifen groups compared to controls (P<0.025, Mann-Whitney U-test), while angiogenesis of the corpus luteum, number of atretic follicles, fibrosis, and serum VEGF were significantly higher in rats receiving tamoxifen (P<0.025, Mann-Whitney U-test). Also, significantly lower follicular reserve and fibrosis were observed among rats in the low-dose tamoxifen group in comparison with rats in the high-dose tamoxifen group (P<0.025, Mann-Whitney U-test). No groups had a significant change in endothelin 1 levels (P>0.025, Mann-Whitney U-test).. Tamoxifen 1 g and 3 g resulted in a dose-dependent increase in VEGF and endothelin 1 levels, and ovarian follicle reserves were significantly reduced in our experimental model.

Topics: Administration, Oral; Animals; Disease Models, Animal; Dose-Response Relationship, Drug; Endothelin-1; Female; Gonadotropins; Humans; Ovarian Hyperstimulation Syndrome; Rats; Rats, Wistar; Tamoxifen; Vascular Endothelial Growth Factor A

To investigate the short and long-term effects of ovarian hyperstimulation syndrome (OHSS) on serum levels of vascular endothelial growth factor (VEGF) and endothelin-1 and ovarian follicular reserve (OFR).. An experimental case-control study was conducted on a university animal laboratory with 20 immature (22-day-old) virgin female Wistar Albino rats. Firstly, rats were divided into two groups. Group 1 (n = 10): control and Group 2 (n = 10): experimental OHSS induced rats. Secondly, Group 2 was randomly divided into two groups on the day of OHSS development (27th day) as follows: Group 3 (n = 5): 27-day-old OHSS induced rats and Group 4 (n = 5): 27-day-old OHSS induced rats supervised for seven days. Group 1 was divided into two groups to constitute age-matched controls as follows: Group 5 (n = 5): 27-day-old rats, Group 6 (n = 5): 35-day-old rats. The comparisons of Group 3 vs Group 5 and Group 4 vs Group 6 were performed. Main outcome measures were OFR, serum levels of VEGF, and endothelin-1.. While the OFR and primordial follicle number (PFN) of Group 3 were significantly lower than those of Group 5 (p < 0.05); VEGF and endothelin-1 levels and atretic follicle number (AFN) were significantly higher in Group 3 compared to Group 5 (p < 0.05). In Group 4, PFN was significantly lower (p < 0.05) and AFN was significantly (p < 0.05) higher than Group 6. However, there were no statistically significant difference between Group 4 and Group 6 regarding the parameters of OFR, serum levels of VEGF, and endothelin-1.. This experimental OHSS model revealed increased serum VEGF and endothelin-1 levels and decreased OFR during short-term of OHSS. OHSS showed detrimental effect on PFN of rats during long-term.

Topics: Animals; Disease Models, Animal; Endothelin-1; Female; Ovarian Hyperstimulation Syndrome; Ovarian Reserve; Rats; Rats, Wistar; Time Factors; Vascular Endothelial Growth Factor A

To assess the markers of destabilization of homeostasis in women with ovarian hyperstimulation syndrome (OHSS), the investigation of the levels of cortisol, markers of renin-angiotensin-aldosterone system, endothelin, proinflammatory cytokines, acute phase proteins, and parameters of hemostasis was performed. Our survey involved 105 women who became pregnant after IVF: 21 women with symptoms of the early moderate and severe OHSS, 28 women with the late moderate and severe OHSS, and 56 pregnant women undergoing IVF without symptoms of OHSS. It was found significant increase of levels of cortisol, interleukins, the number of leucocytes, concentration of fibrinogen and D-dimers in patients with early and late OHSS. The development of late OHSS is associated with the lower level of IL-8 and ceruloplasmin. The OHSS is characterized by leukocytosis, higher level of IL-6, TNF-α, fibrinogen, D-dimers, thus reflecting the homeostasis imbalance. The determination of the level of fibrinogen, D-dimers, leukocytes can be an important screening test of the intensity of the inflammatory process in patients with OHSS.

Topics: Adult; Aldosterone; Angiotensin II; Ceruloplasmin; Endothelin-1; Female; Haptoglobins; Homeostasis; Humans; Hydrocortisone; Interleukins; Ovarian Hyperstimulation Syndrome; Pregnancy; Prospective Studies; Renin-Angiotensin System; Statistics, Nonparametric; Tumor Necrosis Factor-alpha