Efficacy of Interventions to Reduce Risk for Ovarian Hyperstimulation Syndrome

A study done with support from the New England Fertility Society and the Boston University Clinical and Translational Science Institute examined how effective risk interventions aimed at reducing the risk of ovarian hyperstimulation syndrome are. Ovarian hyperstimulation syndrome (OHSS) is a relatively rare occurrence, but the chance for it does increase when women are undergoing IVF treatment. OHSS is the excessive response of the ovaries to taking medicines to make eggs grow. Fluid can leak in the abdomen as a result of a large amount of growing follicles and high levels of estradiol.

There are different classifications of OHSS, ranging from mild to severe, and one out of three women report to have mild symptoms during controlled IVF procedures. As a precaution, women who exhibit moderate symptoms are routinely examined to measure the size of the ovaries and their fluid levels are monitored as well. In severe cases, blood clots can form but this is rare since most women are treated before receive treatment before OHSS gets to this stage.

OHSS only occurs in 1-5% of IVF cycles, and women who are younger than 35 or who have a risk of polycystic ovarian syndrome (PCOS) are at a greater risk of OHSS as well.

This article will present data from this study to find out:

• Are OHSS risk reduction strategies effective?
• If they are, which ones are most effective?
  

Objective and Methods

This study was conducted utilizing a five year chart review of patients from the eIVF database. This included patients who were 35 and younger, with PCOS, and who were already undergoing their first IVF cycle. These patients underwent three types of data collection for this study.

• Personal data such as age, BMI, gravidity/parity, and smoking status were all considered in this study.
• OHSS risk reducing strategy. There were a number of strategies studied for this test to discern which one would result in the greatest risk reduction. These strategies included: metformin use, cabergoline use, GnRHa trigger, and a freeze-all of embryos.
• Finally, cycle data was collected for each patient as well. This included the protocol type, maximum FSH dose, peak estradiol level, number of follicles, number of oocytes, number of MII oocytes, and number of 2PN embryos.
  

The data was analyzed to show the results of what a single OHSS intervention strategy would yield, as well as a combination of methods for intervention.

Results and Conclusions

Were any interventions successful?

The group of patients used in the study were all at a higher risk of OHSS, so these results should be taken in this context. The researchers found that GnRHa, when was singularly used as an intervention method, proved to be successful in reducing the risk of OHSS. It is interesting to note that when GnRHa was combined with other intervention strategies, it did not result in any better outcome than that which was reached by the GnRHa alone. Because these findings confirm the role of hCG in causing OHSS in the first place, the authors of the study recommend more testing to confirm the effectiveness of the other intervention strategies used.

This study also found that the use of cabergoline-- either solely or combined with another intervention method-- actually increased the risk of OHSS in the patient group. It is known that ovarian granulosa cells have the ability to express dopamine receptors. Treatment with a dopamine agonist would result in intracellular calcium mobilization, thus making it possible for cabergoline to drive granulosa cell activity and actually make OHSS worse for the patient.

When the GnRHa was administered by itself, it was able to reduce the overall risk of OHSS to 0.476 percent, while freeze-all reduced it to 0.57 percent, metformin to 0.51 percent, and using no risk reduction strategy reduced it to 0.55 percent. The cabergoline actually increased the risk to 0.75 percent.

The combination of metformin and GnRHa yielded a reduction of 0.48 percent risk of OHSS, which is still not as low as the GnRHa alone. The combination of metformin and cabergoline increase the risk of OHSS to 0.767 percent, and is higher than just the cabergoline alone.

These results show that there are interventions that can successfully lower the risk of OHSS in women who are at high risk for the condition. However, after studying the results, there are also some interventions that can actually increase the risk for the syndrome. Although the researchers conducted both single method interventions and combination intervention methods, it appears that the most successful was the GnRHa intervention given alone. More tests would be needed to determine if there are other triggers that can reduce the risk of OHSS, but for now it the efficacy of GnRHa to lower the risk of OHSS is a supported conclusion.