Towards an Ovarian Hyperstimulation syndrome-free clinic
By Gorka Barrenetxea PhD
Since the pioneering days of in vitro fertilization (IVF), human chorionic gonadotropin (hCG) has been usually used as a surrogate LH surge to induce resumption of meiosis, final oocyte maturation and luteinization of the granulose cells and has for many years been considered the gold standard for cycles of IVF.
Although activating the same receptor, differences exist between LH and hCG, mainly in terms of a half-life of 24 hours for LH and hCG, respectively.
And this may create a predisposition to ovarian hyperstimulation syndrome (OHSS) in women who are at risk for this complication of gonadotropin stimulation. Because the hCG trigger was associated with excessive risk of OHSS in high responders, an alternative trigger agent is needed to safely induce oocyte maturation in such patients.
OHSS is, actually, one of the most frequent, serious and potentially life-threatening complications of controlled ovarian stimulation (COS) as part of assisted reproductive technologies.
The major contributor to OHSS is the presence of hCG, either endogenous or exogenous. In early OHSS, the source of hCG is exogenous owing to the administration of hCG for final oocyte maturation. In late-onset OHSS, an endogenous source is present owing to hCG produced because of early pregnancy.
It is now accepted that GnRH agonist (GnRHa) administration to induce final oocyte maturation is effective in the prevention of OHSS. The GnRHa trigger virtually eliminates the early-onset OHSS incidence and therefore the costs associated with OHSS treatment and alternative prophylaxes supporting the concept of an OHSS-free clinic.
But, the most severe form of OHSS is the late-onset one, which is promoted by the endogenous production of HCG by the trophoblast. To avoid this severe and late OHSS, segmentation of IVF cycles has been proposed. Oocyte/ embryo freezing followed by a frozen embryo transfer in a non-stimulated cycle represents a rescue strategy that completely avoids late-onset OHSS resulting from hCG production by the implanting embryo.
An additional benefit of postponing embryo transfer is avoiding embryo exposure to extremely elevated steroid concentrations. It has been demonstrated that a high ovarian response to COH and the accompanying supraphysiologic concentrations of steroids are detrimental for endometrial receptivity, as well as being embryotoxic.
Our results confirm the efficacy of this policy of GnRH-a triggering plus cryopreservation of resulting embryos with delayed embryo transfer.