Ovarian Hyperstimulation Syndrome (OHSS)

The most serious complication of pharmacological stimulation in IVF is severe ovarian hyperstimulation syndrome (OHSS), which can develop after oocyte retrieval. In these cases the woman requires several days in hospital and may develop conditions that endanger her health.

How common is severe OHSS?

Under protocols with GnRH agonists, it occurred in about 2% of women — and in 10-38% of those with polycystic ovaries or OHSS in a previous attempt. Under modern protocols with a GnRH antagonist the risk is halved; with the strategy described below it is practically eliminated.

What happens to the body in severe OHSS?

In women with severe OHSS, a significant volume of fluid leaks out of the blood vessels and accumulates in the abdominal cavity, around the lungs and/or the heart. This fluid, which can reach 2-3 litres, causes marked abdominal discomfort, difficulty breathing, or impaired cardiac function. At the same time, the reduction in circulating blood volume can in severe cases lead to liver and kidney failure.

Can we predict which woman will develop severe OHSS?

Our ability is limited. There are women with a large number of follicles after stimulation who will not develop the syndrome, and others with a normal number who will. This uncertainty is one of the reasons modern practice favours complete prevention over prediction-based strategies.

How is it treated once it has developed?

Treatment of established severe OHSS is mainly supportive: rehydration, thromboprophylaxis, and drainage of abdominal or pleural fluid where required. Administration of a GnRH antagonist in the luteal phase can accelerate symptom resolution. In any case, recovery takes several days and the experience is markedly burdensome for the woman.

It is not acceptable for a woman to be hospitalised for days in her effort to have a child, when severe OHSS can today be practically avoided.

Can we eliminate the risk of severe OHSS?

Yes, by combining three measures — without reducing the chance of pregnancy. First, an antagonist (or PPOS) protocol instead of an agonist. Second, the final injection 36 hours before retrieval is given as a GnRH agonist (Gonapeptyl, Suprefact, Arvecap) instead of hCG (Ovidrelle, Pregnyl) — this avoids the prolonged hormonal stimulation that causes OHSS. Third, all embryos are cryopreserved and transferred in a later cycle, once the ovaries and the endometrium have recovered.

Why is embryo transfer performed in a later cycle?

The endometrium during the stimulation cycle has been exposed to supraphysiological levels of oestradiol and progesterone, so its receptivity is reduced. In a subsequent cycle the endometrium is physiological, and live-birth rates from frozen-thaw transfer are equivalent — and in certain groups higher — than those from fresh transfer. The couple therefore wins twice: avoiding severe OHSS and preserving the chance of pregnancy.

IVF can today be performed with practically zero risk of severe OHSS. Anything less should no longer be accepted.