The OHSS woes

There is an adage in medicine that "problems come in 3s" and having now dealt with three recent potential cases of ovarian hyperstimulation syndrome (OHSS) this seems quite appropriate. OHSS is no fun. It is tough on the patient and tough on the doctor. It is hard to counsel a patient about a possible outcome whose prevention requires her to derail the chance of getting pregnant after working so hard to reach that point. However, I have NEVER regretted canceling a cycle or freezing all embryos to avoid OHSS, but I have been surprised to see OHSS arise in a patient in whom I was not anticipating it to develop (kinda tortured english there, but I was a biology major). So with OHSS on my mind here is the Question of the Day:


67. My doctor said that I might get ovarian hyperstimulation syndrome. What is ovarian hyperstimulation syndrome, and what can I do to prevent it?

Ovarian hyperstimulation syndrome (OHSS) is a complication associated with the use of fertility drugs. As the ovarian follicles grow, they secrete a wide range of substances, the most important of which is estrogen. Estrogen causes the lining of the uterus to thicken, enabling the embryo to implant there after ovulation and embryo transfer. After a woman receives an HCG injection, her follicles eventually collapse, releasing the eggs within; the follicles may also be aspirated with a needle to harvest the eggs for IVF.

Within a few days, the fluid within the follicles is restored. Each follicle is now called a corpus luteum (Latin for “yellow body”), referring to the fact that it contains large stores of cholesterol that are used to produce the steroid hormones estrogen and progesterone. In addition, the follicle begins to produce a host of other growth factors—including vascular endothelial growth factor (VEGF), a protein that is likely responsible for the emergence of OHSS.

Mild OHSS results in enlarged, tender ovaries but usually only minimal free fluid in the abdominal cavity. By contrast, moderate and severe forms of OHSS are associated with fluid accumulation in the abdominal cavity or sometimes even in the pleural cavity surrounding the lungs. In its severe form, OHSS can result in nausea, vomiting, shortness of breath, and dehydration. As the fluid builds up in the abdomen, the woman becomes increasingly uncomfortable, and diminished blood flow to the kidneys may lead to decreased urine production. This situation can spiral downward rapidly, and complications of blood clot formation and kidney damage can occur if OHSS is left untreated.

Patients with severe OHSS are best managed in the hospital, where they can receive intravenous resuscitation and the fluid can be removed via paracentesis. Occasionally, the fluid around the lungs may need to be removed if the woman is suffering from respiratory difficulties. However, most of the respiratory complaints associated with OHSS result from the inability of the diaphragm to move appropriately given the marked amount of fluid present within the abdomen.

Prevention of OHSS is always the best strategy. This syndrome can best be avoided by judicious use of fertility medications, which is why most physicians individualize gonadotropin doses based on the patient’s history, the appearance of her ovaries on ultrasound, and her previous response (if any) to fertility medications. Patients older than age 35 in whom fewer than 12 eggs are retrieved rarely develop significant hyperstimulation. In contrast, patients with polycystic ovarian syndrome are at the highest risk for developing OHSS. Other high-risk patients include women who have many small and medium-size follicles associated with estrogen levels of more 4000 pg/dL at the time of HCG administration.

However, not all patients who fall into this category will develop OHSS, and some women who might not otherwise seem to be at risk for it will, in fact, go on to develop the syndrome. This randomness of OHSS makes the decision-making process somewhat problematic when trying to prevent this complication. A woman who exhibits an excessive response to fertility medications associated with a large number of follicles and a high estrogen level should be counseled regarding OHSS prevention strategies.

The first option is to withhold the HCG trigger shot, cancel the cycle, and avoid any attempt at pregnancy. Alternatively, a reduced amount of HCG (5000 units) can be given, followed by follicle aspiration, egg fertilization, and freezing of the embryos with no fresh transfer in that cycle. In such cases, the severe form of hyperstimulation is rarely encountered. In our practice, we have experienced outstanding pregnancy rates during subsequent FET cycles in these patients. Even if no transfer is performed, the woman may still require a brief hospitalization or drainage of the abdominal fluid. Ultimately, it is the HCG trigger shot or the HCG produced by a successful pregnancy cycle that induces the ovarian production of VEGF and the other substances that are the cause of OHSS. In patients who are stimulated without GnRH agonists (Lupron), an alternative method to reduce the risk of hyperstimulation is to use Lupron itself as a trigger rather than HCG. Given that the majority of women undergoing IVF are already taking Lupron, however, this strategy would apply to only a small percentage of the patients pursuing infertility treatment. Furthermore, this strategy would simply eliminate the initial symptoms of OHSS associated with the HCG trigger shot; if pregnancy subsequently occurs, the patient would still be at risk for the OHSS associated with a successful cycle.

OHSS is an unpleasant experience for patients, but fortunately the incidence of severe OHSS is low (only 1% to 2%) and the vast majority of patients recover quickly with no long-term problems. In cases where OHSS is associated with pregnancy, this problem can last 2 to 3 weeks and may require several procedures to drain the excess fluid. In addition, because of the dehydration associated with OHSS, patients with this syndrome are at risk for the formation of blood clots in the leg or lung. To prevent this complication, most hospitalized patients receive prophylactic daily doses of a blood thinner such as heparin or Lovenox.