1 Epithelial Cell Biology Research Center, Department of Physiology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China 2 St Mary's Maternity Hospital, Amakohia, HHTTE, Etiti, Imo State and Department of Obstetrics & Gynecology, General Hospital Mina, Niger state, Nigeria 3 Department of Obstetrics & Gynecology, Lorma Medical Centre, San Fernando, La Union, The Philippines
Email: louisca{at}cuhk.edu.hk
Sir,
We read with great interest the recent article of Garcia-Velasco et al. (2004) which reported that coasting acts through downregulation of vascular endothelial growth factor (VEGF) gene expression and protein secretion. Although it is of great clinical value to understand the mechanism(s) involved in coasting and how it reduces the incidence of ovarian hyperstimulation syndrome (OHSS), Ulug et al. (2004)
found no difference in terms of fertilization, implantation and pregnancy rates, and incidence of severe OHSS between coasted and non-coasted patients. However, there are some points we would like to raise regarding the study of Garcia-Velasco et al. (2004)
.
Garcia-Velasco and colleagues did not explain what P on the y-axis of their Figure 1 graph represents. P was not defined in the text and was not in the figure legend either.
It has been reported that estrogen (E2) upregulates the expression of VEGF and its receptors (Cullinan-Bove and Koos, 1993; Hyder et al. 1996
; Gargett et al. 2002
). Gonadotropin administration increases the serum levels of E2. Therefore, withholding gonadotropin during coasting reduces ovarian stimulation, leading to a decline in serum E2 levels. Decrease in E2 levels subsequently leads to reduction in VEGF expression and protein secretion. The phenomenon was also observed by Garcia-Velasco et al. (2004)
.
However, VEGF may not be directly involved in the pathogenesis of OHSS. Serum VEGF concentrations have been reported not to correlate with the severity of OHSS (Kransnow et al. 1996; Geva and Jaffe 2000; Chen et al. 2000
; Eskog et al. 2001; McElhinney et al. 2002
). Garcia-Velasco et al. (2004)
also showed in their Figure 1 that despite the reduction in serum VEGF concentrations to
100 pg/ml, severe OHSS was 3.5% and 2.7% for patients and donor/recipients, respectively, and 10% for moderate OHSS. These data are similar to those of general OHSS prevalence, indicating that VEGF may not be directly responsible for OHSS. No explanation was also given as to why administration of human chorionic gonadotropin (HCG) after coasting lead to sudden elevation of serum E2 to
9000 pg/ml, and the consequence was not discussed either. Naturally, not all follicles recruited during folliculogenesis make it to ovulation, and small follicles undergo apoptosis even without coasting. Could it be that administration of HCG suddenly reversed the apoptotic process and increased the number of immature follicles, leading to the observed increase in E2? This is an unlikely event that was also not discussed. Contrary to the claim of Garcia-Velasco and colleagues, the role of E2 in the pathogenesis of OHSS is gradually beginning to unfold. A serum E2 level of 12.315 pmol/l (3.354 pg/ml) on day 11 of ovarian stimulation gives a sensitivity and specificity of 85% for the detection of women at risk for OHSS (D'Angelo et al. 2004
).
Conclusively, the decline in VEGF expression and protein secretion during coasting may be due to the drop in serum E2 levels during coasting, as E2 modulates VEGF expression. Despite a significant reduction in serum VEGF levels, the percentage of OHSS in the study of Garcia-Velasco et al. (2004) was similar to that of general OHSS prevalence, strongly suggesting that VEGF may not be directly involved in OHSS, and also may not be the mechanism involved in coasting.
References
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