Management of Severe Ovarian Hyperstimulation Syndrome

Peter Kovacs, MD, PhD


March 01, 2006


A 24-year-old woman with polycystic ovaries on urinary follicle-stimulating hormone (FSH) for controlled ovarian stimulation who did ovulate and was following a planned protocol developed severe ovarian hyperstimulation syndrome (OHSS) 7 days after ovulation. Her beta human chorionic gonadotropin (hCG) is 76 IU/mL. Paracentesis has been done twice. Her ascites have yet to resolve, and she has developed pleural effusion. Olguria and a hematocrit of 46% have complicated the matter. Any suggestions regarding further course of action?

Shyam Kulkarni, MBBS, DNB

Response from the Expert

Peter Kovacs, MD 
Clinical Reproductive Endocrinologist, Research and Scientific Coordinator, The Kaali Institute-IVF Center, Budapest, Hungary


OHSS is the most severe complication of controlled ovarian stimulation and complicates 3% to 8% of in vitro fertilization (IVF) cycles; severe OHSS is rare and complicates 1% to 2% of cycles. Young, thin women with high steroid levels during stimulation and with the simultaneous growth of > 10 follicles are at particular risk. The syndrome is characterized by ovarian enlargement, abdominal/gastrointestinal discomfort, and fluid shift into the third space with intravascular volume depletion. The severity is graded on the basis of the size of the ovaries, subjective complaints, and laboratory/radiologic findings.

Once OHSS develops it cannot be treated; only supportive measures can be offered. There are 2 types of OHSS: Early-onset OHSS develops after the pre-retrieval hCG injection, whereas late-onset OHSS develops when the treatment is successful and pregnancy follows. If the treatment does not lead to pregnancy, early-onset OHSS usually resolves on its own within a few days.

Late-onset OHSS, on the other hand, can persist for weeks during early pregnancy. HCG seems to plays an important role in the pathomechanism of both types of OHSS. Vasoactive substances (eg, vascular endothelial growth factor) are released into the circulation in response to hCG. They increase vascular permeability and, as a result, fluid and colloids leave the circulation, resulting in ascites, pleural/pericardial effusion, or edema.

Specific treatment cannot be offered; thus, one's best bet is to try to avoid OHSS. Those at risk need to be identified and an appropriate stimulation protocol needs to chosen for them. If the patient still hyper-responds, the dose of medication can be reduced or withheld ("coasting") during stimulation; or embryos can be frozen instead of being transferred and the cycle can be canceled.

If, despite all these efforts, OHSS still develops, various supportive measures can be undertaken. First, the severity of the condition needs to be assessed. The grade of severity is determined on the basis of subjective complaints, laboratory testing, and ultrasound/radiologic findings. The most important task is to maintain adequate circulation to all organs. Milder cases can be followed on an outpatient basis, but severe cases should be hospitalized. Although patients with OHSS have excess fluid in the body, they still have intravascular volume depletion, so it is very important to closely monitor the fluid intake and output.

Women who are managed as outpatients should measure their weight and abdominal circumference daily and should keep a record of their fluid intake and urinary output. For hospitalized patients, fluid intake (oral and intravenous) should be charted and, if needed, a Foley catheter should be inserted to follow urinary output. Albumin infusion (25 mg every 6 to 12 hours) or hydroxyethyl starches (HES) may be necessary to mobilize the extravascular fluid. Diuretics should only be used when the body starts moving the extra fluid on its own (a good marker of this is to follow the hematocrit; once it starts to decrease, very small doses of diuretics could be given). If, despite these efforts, the fluid status is still inadequate, monitoring central pressures by a central line may become necessary. This would require an intensive care setting.

It is also important to monitor changes in the laboratory values (eg, blood count, liver/renal function, electrolytes) as these provide information about the function of the individual organs. If too much ascites/pleural fluid is accumulated and it interferes with breathing -- and if conservative methods are not sufficient to mobilize the extra fluid -- surgical aspiration (eg, paracentesis, thoracentesis) may be necessary. This will often result in temporary improvement of pain and breathing, but the fluid is likely to accumulate again.

It is very important to use measures for thrombosis prevention (elastic stockings, sequential compression devices, aspirin, low-dose heparin). Meanwhile, one should not forget about the pregnancy itself. HCG levels need to be monitored, and progesterone supplementation should be used instead of hCG for the support of the luteal phase. In extreme cases, such as in patients with renal failure or those experiencing thromboembolic events, the termination of pregnancy might be necessary.

The patient described in this case appears to have severe OHSS. She should be managed as an inpatient. Her laboratory values and fluid status require close attention. Paracentesis can be repeated several times. Thoracentesis should also be performed if indicated on the basis of her clinical status. Albumin and HES can offer temporary relief, but they also eventually leave the circulation, potentially making things worse. The patient should receive a fluid volume that maintains adequate urinary output (about 30 mL/hr). Thromboprophylaxis is an important part of her care. As some of these patients become very frightened, they should receive emotional support as well. Pregnancy termination should only be considered if the patient develops any life-threatening complication.


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