Ovarian Hyperstimulation Syndrome - Pathophysiology

Pathophysiology

OHSS has been characterized by the presence of multiple luteinized cysts within the ovaries leading to ovarian enlargement and secondary complications, but that definition includes almost all patients undergoing ovarian stimulation. The central feature of clinically significant OHSS is the development of vascular hyperpermeability and the resulting shift of fluids into the third space,;

As hCG causes the ovary to undergo extensive luteinization, large amounts of estrogens, progesterone, and local cytokines are released. It is almost certain that vascular endothelial growth factor (VEGF) is a key substance that induces vascular hyperpermeability, making local capillaries "leaky", leading to a shift of fluids from the intravascular system to the abdominal and pleural cavity. Supraphysiologic production of VEGF from many follicles under the prolonged effect of hCG appears to be the specific key process underlying OHSS. Thus, while the patient accumulates fluid in the third space, primarily in the form of ascites, she actually becomes hypovolemic and is at risk for respiratory, circulatory, and renal problems. Patients who are pregnant sustain the ovarian luteinization process through the production of hCG.

Avoiding OHSS typically requires interrupting the pathological sequence, such as avoiding the use of hCG. One alternative is to use a GnRH agonist instead of hCG. While this has been repeatedly shown to "virtually eliminate" OHSS risk, there is some controversy regarding the effect on pregnancy rates if a fresh non-donor embryo transfer is attempted, almost certainly due to a luteal phase defect. There is no dispute that the GnRH agonist trigger is effective for oocyte donors and for embryo banking (cryopreservation) cycles.