Effect of varying doses of tamoxifen on ovarian histopathology, serum VEGF, and endothelin 1 levels in ovarian hyperstimulation syndrome: an experimental study

Abstract

ObjectiveTo 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.Materials and methodsA 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.ResultsDespite 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).ConclusionTamoxifen 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.

EGR1 Promotes Ovarian Hyperstimulation Syndrome Through Upregulation of SOX9 Expression

“…VEGF is a key mediator involved in OHSS, which can be induced by hCG and elevates vascular hyperpermeability 33 . Agents or factor commonly regulate OHSS progression through modulation of VEGF expression 41 , 42 . Yang et al 43 have reported that EGR1 inhibits the migration and angiogenesis of HTR-8/SVneo cells through downregulation of VEGF.…”

Aflibercept suppresses ovarian hyperstimulation syndrome: an experimental study in rats

“…Pala et al, focused on the antiproliferative effect of tamoxifen by blocking the mitogenic effect of estrogen. Zhai et al, focused on the suppression of VEGF expression through the Kisspeptin / KISS1R (KISS1 receptor) system 2,13,14 . In our study, OHSS rats showed higher VEGF levels.…”

Efficacy of Dan’e Fukang Soft Extract in Moderate Ovarian Hyperstimulation Syndrome for Concurrent Treatment of Blood and Fluid Guided by the “Triple Prevention” Principle

“…Besides, the increased secretions of some cytokines or mediators (eg including vascular endothelial growth factor [VEGF], platelet-derived growth [PDGF], insulin-like growth factor‐1 [IGF‐1]) also been demonstrated to occupy an important role in increased capillary permeability as well as the fluid accumulation in the third space, which may be responsible for the inflammatory response associated with follicular maturation, ovulation, corpus luteum function and embryo implantation. 3 , 4 …”

“…Besides, the increased secretions of some cytokines or mediators (eg including vascular endothelial growth factor [VEGF], platelet-derived growth [PDGF], insulin-like growth factor-1 [IGF-1]) also been demonstrated to occupy an important role in increased capillary permeability as well as the fluid accumulation in the third space, which may be responsible for the inflammatory response associated with follicular maturation, ovulation, corpus luteum function and embryo implantation. 3,4 Several strategies have been suggested to prevent or relieve the progression of OHSS according to the results obtained from clinical practice and experimental findings, for example, cycle cancellation, antagonist protocol, withholding gonadotropin administrations and stopping injecting human chorionic gonadotropin (hCG) until hCG drops to a safe level as well as embryos freezing. However, none of these strategies mentioned above are fully effective in preventing OHSS, except for cycle cancellation.…”