Which IVF Treatment Has a Lower Risk for OHSS?

Peter Kovacs, MD, PhD


June 30, 2016

Risk of Severe Ovarian Hyperstimulation Syndrome in GnRH Antagonist Versus GnRH Agonist Protocol: RCT Including 1050 First IVF/ICSI Cycles

Toftager M, Bogstad J, Bryndorf T, et al
Hum Reprod. 2016;31:1253-1264


One of the most severe, potentially life-threatening complications of in vitro fertilization (IVF) is ovarian hyperstimulation syndrome (OHSS).[1] As part of the syndrome, patients may experience nausea, vomiting, abdominal distension, and pain. In addition, OHSS can cause ascites and hemoconcentration resulting in decreased urine output and can lead to enlarged ovaries with multiple cysts. In more severe cases, it may cause hydrothorax, pericardial fluid accumulation, respiratory difficulty, and circulatory problems.[1]

There is no treatment for OHSS; it resolves eventually on its own. Supportive therapy can be offered until symptoms resolve. There are certain risk factors for OHSS, and the best method of "treatment" is prevention by selecting proper stimulation, drug dose, and management of the cycle.

Reports suggest that the risk is lower with protocol, but the literature is not universally supportive of this finding.[2,3,4] This randomized controlled trial (RCT) compared the risk for OHSS and clinical outcome with long gonadotropin-releasing hormone (GnRH) agonist vs short GnRH antagonist stimulation.

The Study

For this study, 1099 women under the age of 40 years undergoing their first IVF/intracytoplasmic sperm injection cycle were randomly assigned to either GnRH agonist or GnRH antagonist stimulation. Baseline parameters were well balanced.

The stimulations on average lasted 2 days fewer with the antagonist approach, and the amount of gonadotropins used was less too. There were an average of 1.6 fewer eggs in the GnRH antagonist group.

Pregnancy rates, ongoing pregnancy rates, and live birth rates (22.8% vs 23.8%) were similar.

Moderate (15.6% vs 10.2%) and severe (8.9% vs 5.1%) OHSS was more frequent in the GnRH agonist group, while there was no difference in the risk for mild OHSS. Almost twice as many women using the GnRH agonist protocol had changes in their treatment plan due to OHSS. Cycle cancellation for OHSS and need for ascites aspiration as part of OHSS management were more frequent in the GnRH agonist group.

The authors concluded that the risk for OHSS was significantly lower with the use of GnRH antagonist, while the chance of pregnancy was similar with the two approaches.


OHSS is characterized by ovarian enlargement and a shift of fluid from the intravascular compartment to the extravascular space. This occurs in response to the vasoactive substances that are secreted following human chorionic gonadotropin (hCG) trigger used prior to the egg retrieval. OHSS is graded based on the severity of the subjective symptoms as well as the clinical or laboratory findings. Mild OHSS requires no treatment, but supportive therapy is needed for the more severe cases.[1]

This large RCT in a heterogeneous patient population found a reduced OHSS risk with GnRH antagonist with no negative impact on clinical outcome. Safety has to be a top priority with elective treatments. During IVF, the stimulation has to be planned in order to provide us with a sufficient number of eggs with no iatrogenic complications. For those at risk for OHSS, low-dose gonadotropins with GnRH antagonist should be the first-line treatment. This also allows the final hCG trigger to be replaced by GnRH agonist, which further lowers the risk for OHSS.[5] One also has to consider elective cryopreservation with delayed transfer, should all efforts to eliminate hyperresponse fail.



Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.