Ovarian hyperstimulation syndrome.

BIBLIOGRAPHIC SOURCE(S)
Ovarian hyperstimulation syndrome. Fertil Steril 2003 Nov;80(5):1309-14. [53 references] PubMed
BRIEF SUMMARY CONTENT RECOMMENDATIONS EVIDENCE SUPPORTING THE RECOMMENDATIONS IDENTIFYING INFORMATION AND AVAILABILITY Go to the Complete Summary
RECOMMENDATIONS
MAJOR RECOMMENDATIONS
Risk Factors
The following factors increase the risk independently for developing ovarian hyperstimulation syndrome (OHSS):
Young age
Low body weight
Polycystic ovary syndrome (PCOS)
Higher doses of exogenous gonadotropins
High absolute or rapidly rising serum estradiol levels
Previous episodes of OHSS
In addition, risk rises with the number of developing ovarian follicles, and the number of oocytes retrieved in assisted reproductive technology (ART) cycles. Risk increases when higher or repeated doses of exogenous human chorionic gonadotropin (hCG) are administered in superovulation and ART cycles (for ovulation induction or luteal phase support) and decreases when exogenous progesterone, rather than hCG, is used to support the luteal phase. Pregnancy increases the likelihood, duration, and severity of OHSS symptoms.
Clinical Features
The OHSS has traditionally been classified as mild, moderate, or severe. However, the clinical symptoms and signs of OHSS exhibit a continuum of scope and severity that defies attempts at specific classification or staging.
Mild manifestations of OHSS are relatively common and include:
Transient lower abdominal discomfort
Mild nausea
Vomiting
Diarrhea
Abdominal distention (observed in up to a third of superovulation cycles)
Onset of symptoms typically occurs soon after ovulation (in superovulation cycles) or after oocyte retrieval in ART cycles, but it may be delayed.
Progression of illness is recognized when symptoms persist, worsen, or include ascites that may be demonstrated by increasing abdominal girth or ultrasound evaluation. Serious illness exists when pain is accompanied by one or more of the following:
Rapid weight gain
Tense ascites
Hemodynamic instability (orthostatic hypotension, tachycardia)
Respiratory difficulty (tachypnea)
Progressive oliguria
Laboratory abnormalities
Hypotension results from extravasation of protein-rich fluid and contraction of the vascular volume, oliguria/anuria from reduced renal perfusion due to decreased vascular volume and/or tense ascites, and pulmonary compromise from an elevated diaphragm and/or hydrothorax. Risk of thromboembolism is increased as a result of hemoconcentration, diminished peripheral blood flow, and inactivity due to abdominal distension and pain. Life-threatening complications of OHSS include renal failure, adult respiratory distress syndrome (ARDS), hemorrhage from ovarian rupture, and thromboembolism.
Management
Outpatient Management
Patients with mild manifestations of OHSS can be managed on an outpatient basis. Treatment usually requires only oral analgesics and counseling regarding the signs and symptoms of progressing illness. Intercourse is best avoided as it may be painful and may increase the risk of ovarian rupture.
Treatment of worsening OHSS typically requires antiemetics and more potent analgesics. Most patients still can be effectively managed and monitored on an outpatient basis, but they require more careful evaluation including frequent physical and ultrasound examinations (to detect increasing ascites), daily weight measurements, and serial laboratory determinations of hematocrit, electrolytes, and serum creatinine. Careful monitoring is essential and should include at least daily communication, if not examination, to ensure that progression to more severe disease is promptly recognized.
Recommendations for the outpatient management of persistent and worsening OHSS include:
Oral fluid intake should be maintained at no less than 1 L per day; any of the commercially available electrolyte-supplemented drinks is preferable to other beverages.
Strenuous physical activity should be avoided as risk of ovarian torsion increases when the ovaries are significantly enlarged. Light physical activity should be maintained to the extent possible. Strict bed rest is unwarranted and may increase risk of thromboembolism.
Weight should be recorded daily, as well as the frequency and/or volume of urine output. Weight gain of >2 pounds per day or decreasing urinary frequency should prompt repeated physical examination, ultrasound, and laboratory evaluation to include hematocrit, electrolytes, and serum creatinine.
Pregnant patients with OHSS must be monitored very closely because risk of progressing to severe disease is particularly high for those further stimulated by rapidly rising serum concentrations of hCG.
In ART cycles, it may be necessary to consider cryopreserving all embryos and deferring transfer to a subsequent cycle after symptoms have completely resolved. Although pregnancy rates in frozen embryo transfer cycles are generally lower than in fresh cycles, this approach may reduce the risk for developing severe OHSS without a marked decrease in pregnancy rates per cycle.
Hospitalization
Serious illness requiring hospitalization is relatively uncommon but by no means rare. Hospitalization may be required based on severity of symptoms, analgesic requirements, and other social considerations (availability of responsible adult supervision, support, and assistance with child care).
Given the scope and severity of symptoms and the potential for complications, most women with OHSS who are seriously ill merit hospitalization for more careful monitoring and aggressive treatment. No one symptom or sign is an absolute indication, but hospitalization should be considered when one or more of the following are present:
Severe abdominal pain or peritoneal signs
Intractable nausea and vomiting that prevents ingestion of food and adequate fluids
Severe oliguria or anuria
Tense ascites
Dyspnea or tachypnea
Hypotension (relative to baseline), dizziness, or syncope
Severe electrolyte imbalance (hyponatremia, hyperkalemia)
Hemoconcentration
Abnormal liver function tests
Laboratory findings in women with serious illness resulting from OHSS include:
Hemoconcentration (hematocrit >45%)
Leukocytosis (white blood cell count >15,000)
Electrolyte imbalances (hyponatremia: sodium <135>5.0 mEq/L)
Elevated liver enzymes
Decreased creatinine clearance (serum creatinine >1.2; creatinine clearance <50>20–30 mL/h) and reverse hemoconcentration. Five percent dextrose in normal saline is preferable to lactated Ringer's solution, given the tendency to hyponatremia. Correction of hypovolemia, hypotension, and oliguria has highest priority, accepting that fluid administration may contribute to the accumulation of ascites.
Albumin (25%) in doses of 50–100 g, infused over 4 hours and repeated at 4- to 12-hour intervals as necessary, is an effective plasma expander when infusion of normal saline fails to achieve or maintain hemodynamic stability and adequate urine output. In general, albumin is the preferred plasma expander, although others (e.g., mannitol, fresh frozen plasma) may be used. Dextran has been associated with development of adult respiratory distress syndrome (ARDS) and is best avoided.
Treatment with diuretics (e.g., furosemide, 20 mg IV) may be considered after an adequate intravascular volume has been restored (hematocrit <38%).>3 days).
Given the evidence suggesting that hCG may play a pivotal role in the development of OHSS, a lower dose of hCG (e.g., 5,000 IU vs. the standard 10,000 IU dosage) may be prudent for patients judged to be at high risk for OHSS. Alternatively, a GnRH agonist (e.g., leuprolide 0.5–1.0 mg SC) rather than hCG might be used to stimulate an endogenous LH surge to promote final oocyte maturation and induce ovulation. This approach would be useful only in cycles not involving previous down-regulation with longer term agonist treatment or use of a GnRH antagonist (e.g., ganirelix, cetrorelix).
Regardless whether hCG or a GnRH agonist is administered at midcycle, the use of exogenous progesterone (e.g., 50 mg progesterone in oil IM, 100 mg progesterone vaginal suppositories, or 8% progesterone vaginal gel, daily) for luteal phase support rather than supplemental doses of hCG, may further reduce risks of OHSS. When symptoms of OHSS emerge even before administration of hCG, cycle cancellation and less aggressive stimulation in a subsequent cycle should be seriously considered.
Although evidence indicates that meticulous follicle aspiration will reduce corpus luteum P production, it cannot be relied on to prevent development or progression of OHSS in ART cycles.
Prophylactic IV administration of 25% albumin (20–50 g) at time of oocyte retrieval has been suggested as a means to reduce risk of OHSS when E2 levels are markedly elevated or there is history of a previous episode of OHSS. Studies of its efficacy have had mixed results, and albumin treatment risks exacerbation of ascites, allergic reactions, and virus/prion transmission. However, a recent meta-analysis of five randomized controlled trials demonstrated that prophylactic albumin administration significantly reduced risk of developing OHSS (odds ratio [OR] 0.28, 95% confidence interval [CI] 0.11, 0.73); albumin infusion may be expected to prevent one case of severe OHSS for every 18 women at risk who are treated.
Summary
Experience with ovulation induction therapy and knowledge of ovarian hyperstimulation syndrome (OHSS) pathophysiology, risk factors, and clinical features are key to preventing and managing OHSS.
Mild manifestations of OHSS are fairly common, occurring in up to a third of exogenous gonadotropin-induced superovulation cycles.
Worsening symptoms of OHSS can still usually be managed on an outpatient basis, but frequent monitoring and evaluation are essential.
Serious illness resulting from OHSS is much less common, but it can be life-threatening.
Hospitalization may be necessary for patients with serious illness resulting from OHSS.
CLINICAL ALGORITHM(S)
None provided
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EVIDENCE SUPPORTING THE RECOMMENDATIONS
TYPE OF EVIDENCE SUPPORTING THE RECOMMENDATIONS
The type of supporting evidence is not specifically stated for each recommendation.
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IDENTIFYING INFORMATION AND AVAILABILITY
BIBLIOGRAPHIC SOURCE(S)
Ovarian hyperstimulation syndrome. Fertil Steril 2003 Nov;80(5):1309-14. [53 references] PubMed
ADAPTATION
Not applicable: The guideline was not adapted from another source.
DATE RELEASED
2003 Nov
GUIDELINE DEVELOPER(S)
American Society for Reproductive Medicine - Private Nonprofit Organization
SOURCE(S) OF FUNDING
American Society for Reproductive Medicine
GUIDELINE COMMITTEE
The Practice Committee of the American Society for Reproductive Medicine
COMPOSITION OF GROUP THAT AUTHORED THE GUIDELINE
Not stated
FINANCIAL DISCLOSURES/CONFLICTS OF INTEREST
Not stated
GUIDELINE STATUS
This is the current release of the guideline.
GUIDELINE AVAILABILITY
Electronic copies: Available from the American Society for Reproductive Medicine Web site.
Print copies: Available from American Society for Reproductive Medicine, 1209 Montgomery Highway, Birmingham, Alabama 35216-2809; Phone 205) 978-5000; Fax 205) 978-5005; E-mail: asrm@asrm.org; Web site: www.asrm.org.
AVAILABILITY OF COMPANION DOCUMENTS
None available
PATIENT RESOURCES
None available
NGC STATUS
This NGC summary was completed by ECRI on August 23, 2004.
COPYRIGHT STATEMENT
This NGC summary is based on the original guideline, which is subject to the guideline developer's copyright restrictions.
http://www.guideline.gov/summary/summary.aspx?doc_id=4845&nbr=3486&ss=6&xl=999