Ovarian hyperstimulation syndrome (OHSS) incidentally occurs in controlled ovarian stimulation protocols and is associated with
human chorionic gonadotropin (hCG) administration. OHSS is caused by increased vascular permeability (VP) and thought to be mediated by hypersecretion of
vascular endothelial growth factor (
VEGF) by granulosa cells. Low molecular weight (LMW)-LH agonists have a similar mode of action but a shorter half-life compared with hCG, which could potentially lead to a clinical benefit in reducing the risk for OHSS in controlled ovarian stimulation protocols. The objective of this study is to investigate the role of an orally active LMW-LH agonist in OHSS induction compared with recombinant LH (rec-LH) and hCG. Immature rats were hyperstimulated with pregnant mare serum
gonadotropin, and ovulation was induced by hCG, rec-LH or a LMW-LH agonist. The degree of VP was determined by
Evans Blue in the abdominal cavity. Ovaries were weighed, and
VEGF concentration in the ovary was determined. Pregnant mare serum
gonadotropin stimulation followed by single-dose hCG or rec-LH resulted in clear enlargement of the ovaries and increased VP and
VEGF levels. However, ovulation induction with a single dose of the LMW-LH agonist did not result in increased VP and
VEGF levels, and even multiple dosing to mimic a longer exposure did not induce OHSS symptoms. In conclusion, we demonstrated that the oral LMW-LH agonist did not induce VP in rat, indicative for OHSS, possibly due to reduced
VEGF production. If this is translatable to human, this could potentially represent a clinical benefit in reducing the risk for OHSS when using these compounds in controlled ovarian stimulation protocols.