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I’ve read about ovarian hyperstimulation syndrome, but how common is it really? Is this something to worry about?
—Julie
Ovarian hyperstimulation syndrome ( OHSS) is a rare, but potentially serious complication of in vitro fertilization. The risk is highest after stimulation and retrieval (so within the first week following your retrieval).
The primary issue with OHSS is that fluid (plasma) shifts from the vascular system (your arteries and veins) into your abdomen and pelvis. With your ovaries already enlarged from the IVF cycle stimulation, you can imagine that this could be very uncomfortable, to put it mildly. Symptoms of OHSS can range from mild to severe. Patients with mild OHSS have abdominal bloating, discomfort, and mild nausea. Symptoms of more serious cases include having so much abdominal bloating that it is difficult to breathe, having little fluid in the veins, putting you at risk for a blood clot (deep vein thrombosis), and severe nausea and vomiting.
Historically, the rates of moderate to severe OHSS were approximately 1–5% of IVF cycles. Today, rates are much lower due to changes we can make in IVF stimulation cycle protocols and adjunctive treatments we can use to mitigate risk. A 2021 analysis of over 1 million IVF cycles in Japan found the risk of moderate to severe OHSS was less than 1%.
Patients at risk of OHSS include those with a lot of growing follicles and potential for a large number of eggs retrieved, usually over 15 eggs or more. Each growing follicle creates estrogen, and a high estrogen level at time of trigger increases risk of OHSS. While no strict consensus exists for a cutoff value that predicts risk of OHSS, generally accepted criteria are more than 25 developing follicles or eggs retrieved and estradiol levels over 3500 pg/mL at time of trigger.
If you are someone who is at risk of OHSS, your doctor can make certain decisions regarding your care that help decrease that risk. One of the biggest advances in decreasing the risk of OHSS has been the utilization of a GnRH-agonist trigger (also called Lupron trigger) prior to the egg retrieval rather than an hCG trigger. Historically, hCG was used as it is molecularly similar to the hormone your brain makes to trigger ovulation (LH). However, using this type of trigger stimulated the ovaries longer after retrieval than LH produced by your brain would, which increased the risk of OHSS. With a GnRH-agonist trigger, your own LH is used as the trigger for final maturation of the oocytes, which does not last as long in your body as hCG does. A Cochrane review of 17 randomized controlled trials found that using a GnRH-agonist trigger reduces the risk of moderate to severe OHSS to essentially zero.
There are some additional therapies that can help mitigate OHSS symptoms in specific groups. Metformin can decrease the risk of developing OHSS in those patients with PCOS. Another medication, called cabergoline, can help decrease the risk for any patient at risk of OHSS. Your doctor may prescribe these if they think you are at risk of developing moderate to severe OHSS based on your IVF cycle response.
Fortunately, the risk of developing OHSS is low, around 1%. Before your cycle, it may be helpful to talk to your physician regarding your case and potential risk.
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