Prorenin and active renin concentrations in plasma and ascites during severe ovarian hyperstimulation syndrome

Abstract

The pathophysiology of ovarian hyperstimulation syndrome (OHSS) remains unclear. Several lines of evidence indicate that OHSS is associated with a stimulation of the renin-angiotensin system (RAS), but its functional significance as well as its role in the pathogenesis of the syndrome are not yet determined. OHSS is associated with high plasma and ascitic concentrations of total renin, renin activity (RA) and angiotensin II (Ang II). Their ovarian or renal origin is, however, still a matter of debate. To clarify these issues further, total renin, active renin, prorenin, RA and aldosterone were measured in plasma and ascites of nine patients who developed severe OHSS after in-vitro fertilization. Blood and ascites were sampled simultaneously during therapeutic paracentesis. Total renin and prorenin concentrations were significantly higher in the ascites (mean concentration +/- SE respectively of 5920 +/- 1430 mIU/l and 5250 +/- 1350 mIU/l) than in the plasma (respectively 3060 +/- 740 mIU/l and 2000 +/- 460 mIU/l) (P = 0.020 and 0.017 respectively). Conversely, active renin and RA concentrations tended to be lower, although not statistically significantly so in the ascites (respectively 670 +/- 190 mIU/l and 47 +/- 11 ng Ang I/ml/h) than in the plasma (respectively 1060 +/- 370 mIU/l and 75 +/- 21 ng Ang I/ml/h). Aldosterone concentrations were significantly higher in the serum (2609 +/- 374 pg/ml) than in the ascites (2025 +/- 347 pg/ml) (P = 0.015). The concentration gradient between plasma and ascites for total renin and prorenin supports the hypothesis of their ovarian origin in ascites and, to a large extent, in plasma, while it is likely that the high plasma active renin and RA concentrations reflect a peripheral activation of the RAS. In conclusion, the present findings are consistent with a marked stimulation of both ovarian and renal RAS during OHSS.

Dual renin-angiotensin blockage and total embryo cryopreservation is not a risk-free strategy in patients at high risk for ovarian hyperstimulation syndrome

“…But currently available secondary preventive measures, described below, are far from being ideal. These are [1] delaying hCG injection (coasting), [2] canceling the cycle and withholding hCG injection with or without continuation of GnRHa/GnRH antagonist, [3] aspirating some of the follicles before hCG injection or shortly after hCG injection, [4] decreasing the dose of hCG, [5] use of GnRHa instead of hCG to trigger ovulation in antagonist cycles, [6] use of recombinant LH to trigger ovulation, [7] IV macromolecule administration at the time of oocyte collection, [8] cryopreserving all embryos and postponing ET to a subsequent cycle, and [9] avoiding hCG for luteal phase support. None of the above measures other than cycle cancellation eliminate the risk of OHSS.…”

“…Plasma renin level, renin activity, and aldosterone levels have been shown to be increased in OHSS (4,5,11). Chang et al reported a patient with OHSS with internal jugular vein thrombosis who had plasma renin activity nearly 30 times above normal range who returned to normal upon resolution of the syndrome (28).…”

“…There are case reports indicating increases in renin, Ang-II, and ACE activity in OHSS in humans (4,38,39). However, to the best of our knowledge there is only one study evaluating the role of ACE inhibition with regard to OHSS development in humans (17).…”

“…Enhanced capillary permeability is believed to cause the acute shift of body fluids that results in ascites and pleural effusion (2). The ovarian renin-angiotensin system (RAS) (3)(4)(5) as well as estrogens (6), P (7), and vascular endothelial growth factor (VEGF) (8) have been proposed and investigated as mediators of increased vascular permeability. Despite intensive research, no single mechanism or factor is universally accepted to cause the syndrome.…”

“…There are several studies on the role of ovarian RAS in OHSS (3)(4)(5)(9)(10)(11). The ovary was shown to secrete prorenin (12), and follicular fluid levels of renin-like activity and angiotensin II (Ang-II) were found to be relatively high when compared with plasma levels in OHSS (13)(14)(15).…”