Prevention and Management of Ovarian Hyperstimulation Syndrome (OHSS)

·   It is recommended to counsel patients with elevated anti-müllerian hormone levels, polycystic ovary syndrome (PCOS), and anticipated high oocyte yields that they are at increased risk for ovarian hyperstimulation syndrome (OHSS). Interventions to reduce OHSS risk should be focused on this patient population.

(Strong Recommendation).

·   It is recommended to dose gonadotropins based on individualized ovarian reserve testing to decrease the risk of OHSS (Strong Recommendation).

·  Consider lowering the starting dose of gonadotropins and/or supplementing with oral ovulation-inducing medications (clomiphene citrate and/or letrozole) to decrease the risk of OHSS (Conditional Recommendation).

·  Use a GnRH agonist to trigger oocyte maturation as a first-line strategy to reduce the risk of moderate-to-severe OHSS (Strong Recommendation).

·  Coasting is generally not recommended as a primary strategy to reduce the risk of moderate-to-severe OHSS. However, when other more effective strategies are not available, coasting in combination with cabergoline and a freeze-only strategy may mitigate the risk (Conditional recommendation).

·  Provide adequate luteal support when using a GnRH agonist as a trigger and planning a fresh embryo transfer (Strong Recommendation).

·  In patients at risk for moderate-to-severe OHSS, start a dopamine agonist such as cabergoline on the day of the hCG trigger or soon after that and continue for several days (Strong Recommendation).

·  Consider a freeze-only cycle and subsequent frozen embryo transfer in patients at risk for OHSS based on a high ovarian response or elevated serum estradiol levels. Multiple high-quality studies have reported a significant reduction in rates of moderate or severe OHSS when this strategy is employed (Strong Recommendation).

·  Do not use a lower dose for the human chorionic gonadotropin (hCG)-only trigger as a strategy to reduce the risk of moderate-to-severe OHSS (Conditional Recommendation).

·  Do not administer letrozole as an intervention to reduce rates of moderate-to-severe OHSS (Conditional Recommendation).

·  Do not administer a luteal GnRH antagonist alone to reduce rates of moderate-to-severe OHSS. Most studies report no reduction in rates of moderate-to-severe OHSS or associated signs or symptoms. Some low-quality evidence suggests modest symptomatic improvement in women with OHSS who received a GnRH antagonist after the hCG trigger (Conditional Recommendation).

·  Do not use aspirin as a primary strategy to reduce the incidence of OHSS (Conditional Recommendation).

·  Do not administer metformin for the sole purpose of reducing the incidence of OHSS in GnRH antagonist cycles. Most studies do not report a significant reduction in OHSS rates in women with PCOS who were given metformin. However, metformin may be considered for OHSS risk reduction among women with PCOS using a GnRH-agonist protocol (Conditional Recommendation).

·  Do not administer medications such as mifepristone, myoinositol, D-chiro-inositol, or glucocorticoids to reduce rates of OHSS as studies have shown these interventions to be ineffective (Conditional Recommendation).

·  Do not use volume expanders such as albumin, hydroxyethyl starch, or mannitol in patients at high risk of developing moderate or severe OHSS (Conditional Recommendation).

· Clinicians need to be aware of the symptoms and signs of OHSS, as the diagnosis is based on clinical criteria. (Conditional Recommendation). Table 4

· Women presenting with symptoms suggestive of OHSS should be assessed face-to-face by a clinician. In women presenting with severe abdominal pain or pyrexia, extra care should be taken to rule out other causes of the patient’s symptoms. The input of clinicians experienced in the management of OHSS should be obtained in such cases. (Conditional Recommendation).

·  It is recommended that once the diagnosis of OHSS is established, the severity of the disease should be classified as mild, moderate, severe, or critical according to the standardized classification scheme included. (Conditional Recommendation). Table 5

· Outpatient management is recommended for women who have mild or moderate OHSS and only in selected cases with severe OHSS when the physician can ensure that the patient can follow clinical guidelines and ensure that a system is in place to assess the condition every 1 to 2 days. (Conditional Recommendation).

· Women undergoing outpatient management of OHSS should be appropriately counselled and provided with information regarding fluid intake and output monitoring. In addition, they should be provided with contact details to access advice. (Conditional Recommendation)

· Fluid replacement by the oral route, guided by thirst, is the most physiological approach to correcting intravascular dehydration. (Conditional Recommendation)

·  Women with moderate OHSS should be evaluated for predisposing risk factors for thrombosis and prescribed either antiembolism stockings or LMWH if indicated. (Conditional Recommendation).

·  Women with severe OHSS being managed on an outpatient basis should receive thromboprophylaxis with low molecular weight heparin (LMWH). The duration of treatment should be individualised, taking into account risk factors and whether or not conception occurs. (Conditional Recommendation).

·  Women with OHSS being managed on an outpatient basis should be reviewed urgently if they develop symptoms or signs of worsening OHSS. In the absence of these, a review every 2–3 days is likely to be adequate. (Conditional Recommendation).

·  Baseline laboratory investigations should be repeated if the severity of OHSS is thought to be worsening. Haematocrit is a useful guide to the degree of intravascular volume depletion. (Conditional Recommendation) Table 6

·  Outpatient paracentesis/culdocentesis of ascitic fluid by the abdominal or transvaginal route under ultrasound guidance may be considered for prevention of disease progression in cases of moderate to severe OHSS. (Conditional Recommendation).

·  Hospital admission should be considered for women who:

·   are unable to achieve satisfactory pain control

·  are unable to maintain adequate fluid intake due to nausea

·  show signs of worsening OHSS despite outpatient intervention

·  are unable to attend for regular outpatient follow-up

·  have critical OHSS.
(Conditional Recommendation).

·  Women with severe and critical OHSS should be hospitalized for intravenous hydration and observation. (Conditional Recommendation)

·  Intravenous hydration with crystalloid solution should be implemented to prevent hemoconcentration and provide adequate organ perfusion targets. When the use of a crystalloid solution does not allow the maintenance of such an infusion, an alternative colloidal solution should be administered. (Conditional Recommendation).

·  Women admitted with OHSS should be assessed at least once daily. More frequent assessment is appropriate for women with critical OHSS and those with complications. (Conditional Recommendation).

·  Antiemetics may be used in women with OHSS, avoiding medicines contraindicated in pregnancy. (Conditional Recommendation).

·  Women with persistent haemoconcentration despite volume replacement with intravenous colloids may need invasive monitoring, and this should be managed with anaesthetic input. (Conditional Recommendation) (40).

·  Features of critical OHSS should prompt consideration of the need for intensive care. Multidisciplinary assistance should be sought for the care of women with critical OHSS and severe OHSS who have persistent haemoconcentration and dehydration. A clinician experienced in the management of OHSS should remain in overall charge of the woman’s care. Intravenous colloid therapy should be considered for women who have large volumes of fluid removed by paracentesis. (Conditional Recommendation)

·  In hospitalized patients, pain relief should be conducted with acetaminophen and/or opioid analgesics. (Conditional Recommendation).

·  Prophylactic doses of anticoagulants should be considered in women who have severe ovarian hyperstimulation syndrome. The duration of LMWH prophylaxis should be individualized according to patient risk factors and outcome of treatment. (Conditional Recommendation).

· Paracentesis should be performed to alleviate discomfort in hospitalized patients with tense ascites. (Conditional Recommendation)

Indications for paracentesis include the following:

-   severe abdominal distension and abdominal pain secondary to ascites

-  shortness of breath and respiratory compromise secondary to ascites and increased intra-abdominal pressure

-  oliguria despite adequate volume replacement, secondary to increased abdominal pressure causing reduced renal perfusion.

·  In addition to the usual symptoms and signs of venous thromboembolism (VTE), thromboembolism should be suspected in women with OHSS who present with unusual neurological symptoms, even if they present several weeks after apparent improvement in OHSS. (Conditional Recommendation)

·  Surgery is only indicated in patients with OHSS if there is a coincident problem such as adnexal torsion, ovarian rupture, or ectopic pregnancy, and should be performed by an experienced surgeon. (Conditional Recommendation)

·  Non-steroidal anti-inflammatory drugs with antiplatelet properties shouldn't be used for pain relief as they may compromise renal function. (Conditional Recommendation)

·  Diuretics should be avoided as they further deplete intravascular volume, but they may have a role in a multidisciplinary setting if oliguria persists despite adequate fluid replacement and drainage of ascites. (Conditional Recommendation)

·  There is insufficient evidence to support the use of gonadotrophin-releasing hormone antagonists or dopamine agonists in treating established OHSS. Those drugs should not be used as routine management of OHSS. (Conditional Recommendation).