Richard Scott Lucidi
History of present illness
A 28-year-old gravida 0 woman is brought into the emergency department by her husband with complaints of abdominal pain, abdominal distension, nausea, and difficulty breathing.
Her symptoms began that afternoon and have become pro- gressively worse. She states that her pain is on both sides of her lower abdomen and that it is difficult to breathe, especially when lying down. She has mild nausea but denies vomiting, diarrhea, or fever. She cannot remember the last time she urinated.
Her history is significant for anovulatory infertility due to polycystic ovary syndrome. She has been undergoing in-vitro fertilization (IVF) treatment. A phone call to her reproductive endocrinologist reveals that her egg retrieval was 7 days prior and 32 oocytes were obtained. Her peak estradiol level was 4231 pg/mL. She had a single embryo transferred to her uterus two days ago.
Her only medications are prenatal vitamins and vaginal progesterone. She has no other medical problems, and has never had surgery.
Physical examination
General appearance: Well-developed, well-nourished woman in mild discomfort and mild respiratory distress Vital signs:
Temperature: 37.0°C Pulse: 115 beats/min
Blood pressure: 102/62 mmHg Respiratory rate: 24 breaths/min Oxygen saturation: 99% on room air Height: 66 inches
Weight: 124 lb
Cardiovascular: Tachycardic, regular rhythm, no murmur, no jugular venous distention
Pulmonary: Tachypneic, breaths are shallow, lungs are clear
Abdomen: Distended,fluid wave is present, diffusely tender Extremities: No edema is seen
Laboratory studies:
WBCs: 16 100/μL (normal 3900–11 700/μL) Hb: 15.3 g/dL (normal 12–15 g/dL) Ht: 46% (normal 34.8–45.0%)
hCG: 22 mIU/mL (normal<5 mIU/mL) Sodium: 131 mEq/L (normal 135–145 mEq/L)
Potassium: 5.5 mEq/L (normal 3.7–5.2 mEq/L) Creatinine: 1.1 mg/dL (normal 0.5–1.0 mg/dL) Imaging: A pelvic ultrasound is obtained (Fig. 62.1) Intravenous analgesics and anti-emetics were administered.
How would you manage this patient?
This patient has ovarian hyperstimulation syndrome (OHSS).
Her history of a recent IVF treatment and her constellation of symptoms support the diagnosis. Although abdominal pain and a positive pregnancy test would usually prompt consider- ation of ectopic pregnancy in the differential diagnosis, that would not be likely in this case. Her embryo transfer was only two days ago, so it would be too early for her to have symp- toms from an ectopic pregnancy. It would also be too early for a pregnancy to have detectible human chorionic gonadotropin (hCG) levels. Her positive pregnancy test is due to the exogen- ous hCG used in the IVF stimulation.
Her laboratory abnormalities of hyponatremia, hyperkale- mia, leucocytosis, and hemoconcentration, as well as her respiratory difficulty, indicate severe disease and the need for inpatient management. She should be admitted for pain man- agement, intravenous volume replacement, venous thrombosis prophylaxis, and correction of her electrolyte abnormalities.
Since this patient had nausea but no vomiting, oral opiates, such as oxycodone, are a goodfirst option for pain manage- ment. Intravenous opiates may be required if vomiting
Fig. 62.1 Transvaginal ultrasound of the right ovary.
Acute Care and Emergency Gynecology, ed. David Chelmow, Christine R. Isaacs and Ashley Carroll. Published by Cambridge University Press.
© Cambridge University Press 2015.
develops. Fluid replacement and correction of the electrolyte abnormalities can be achieved with a 1 L bolus of normal saline followed by continuous infusion at 150 mL/h. Heparin 5000 U SQ BID should be started for venous thrombosis prophylaxis.
Ovarian hyperstimulation syndrome
Ovarian hyperstimulation syndrome (OHSS) is a potential complication of in-vitro fertilization treatment and other ovarian stimulation treatments involving gonadotropins.
In its severe form, OHSS affects approximately 1% of women undergoing ovarian hyperstimulation [1].This patient has a number of risk factors for OHSS, including treatment with exogenous gonadotropins, young age (<35 years), low body weight, polycystic ovary syndrome, high estradiol levels, larger number of follicles stimulated, and use of hCG. Although not present in this patient, prior OHSS is also a risk factor.
Although the pathophysiology of OHSS is not clear, increased capillary permeability and extravasation offluid into the peritoneal cavity are the hallmarks of the disease [2]. The third-spacing offluid results in an increase in total-body water, decreased intravascular volume, and the symptoms, signs, and laboratory abnormalities of the disease (Table 62.1). Although the increased capillary permeability begins in the ovaries, it can spread to other tissues resulting in pulmonary and peripheral edema. The risk of thromboembolic disease is also increased in women with severe OHSS. This may be due to the hemocon- centration and inactivity associated with abdominal discomfort [2], or it may be that underlying thrombophilias are predispos- ing factors for the development of severe OHSS [3]. In addition to thromboembolism, other life-threatening complications of OHSS include adult respiratory distress syndrome (ARDS), renal failure, and hemorrhage from ovarian rupture [2].
OHSS typically presents in patients following gonadotropin treatment for infertility and is rare in patients not treated with gonadotropins or in patients treated with other medications such as clomiphene. It typically presents 3–7 days following hCG treatment but can present as late as 17 days after hCG [4].
Most patients initially develop abdominal discomfort (99%) and other symptoms and signs are often present (Table 62.1).
Ultrasound will often show enlarged ovaries that are typically 5–12 cm but may measure up to 25 cm. Ovarian rupture can occur with aggressive abdominal or pelvic examination so these should be avoided in favor of ultrasound examination.
The initial laboratory evaluation should include a complete blood count and metabolic panel to assess sodium, potassium, creatinine, aspartate aminotransferase (AST) and alanine ami- notransferase (ALT). Abnormal results of these tests are shown inTable 62.1and inpatient management should be considered for patients with abnormal results.
OHSS is a common complication of ovarian stimulation and is usually a self-limiting disorder that resolves spontan- eously within a few days. The duration and severity can worsen, especially in patients who conceive. This worsening is likely from continued hCG exposure.
The American Society for Reproductive Medicine Practice Committee [2] points out that, while OHSS has traditionally been classified as mild, moderate, or severe, the signs and symptoms of the disease represent a continuum not amenable to a specific classification system. However, management is dictated by the severity. Mild OHSS can usually be managed in the outpatient setting with oral hydration using at least 1 L of sports drinks or other electrolyte-supplemented beverages, oral analgesics, and daily weights with instructions to monitor for signs of progressive disease (weight gain of >2 lb daily, increasing abdominal girth or discomfort, urine output<1 L/
day). Acetaminophen or opiates should be used for analgesia.
Nonsteroidal anti-inflammatory drugs should be avoided while pregnancy is a possibility. Patients should continue monitoring for two weeks or until menses occurs.
Hospitalization should be considered if the diagnosis is unsure, vomiting prevents oral hydration, or pain is severe enough to require intravenous analgesics. Hospitalization should also be considered if any sign or laboratory abnormal- ity of severe disease is present. In this case, the patient’s tachypnea, tachycardia, oliguria, electrolyte abnormalities, and hemoconcentration merit inpatient management.
Inpatient management of OHSS is primarily supportive and consists of intravascular volume replacement and correc- tion of electrolyte abnormalities. Normal saline is
Table 62.1 Symptoms, signs, and laboratory abnormalities of OHSS
Symptoms Signs Lab. abnormalities
Mild Abdominal discomfort Nausea/vomiting Abdominal distension
Enlarged ovaries on ultrasound
Severe Shortness of breath
Rapid weight gain Tachypnea Tachycardia Hypotension Tense ascites Oliguria
Hyponatremia (<135 mEq/L) Hyperkalemia (>5 mEq/L) Hemoconcentration (Hct>45%) Leukocytosis (WBCs>15 000/μL) Creatinine>1.2
Elevated liver enzymes OHSS, ovarian hyperstimulation syndrome.
recommended instead of lactated Ringer’s due to the hypona- tremia that is often present. Plasma expanders such as 25%
albumin (50–100 g over 4 hours) may be used when normal saline infusion fails to maintain normal hemodynamic status and urine output. Thromboembolic prophylaxis with heparin (5000 U SQ every 12 hours) or low-molecular-weight heparin (Lovenox®40 mg SQ daily) is also recommended for patients with intravascular hemoconcentration until the hematocrit normalizes (Ht <38%). Diuretics such as furosemide can be used, but their use should be avoided until after the intra- vascular volume has normalized. Inpatient monitoring should continue until pain improves, electrolytes are within the normal range and the hemoconcentration has resolved.
A falling hematocrit indicates mobilization of fluid into the intravascular space and is usually not an indication of hemor- rhage. If hyperkalemia is present, an ECG should be obtained.
If peaked T waves, ST segment depression, or prolonged PR or QRS intervals are present, prompt treatment with calcium gluconate is indicated. If no ECG abnormalities are present, the hyperkalemia can be corrected more slowly with sodium polystyrene sulfonate USP (Kayexelate®).
Paracentesis may be required to alleviate abdominal pain or respiratory symptoms. This can be accomplished under ultrasound guidance using either a transabdominal or transva- ginal approach. In otherwise healthy women with OHSS, large volumes can usually be safely removed.
Prevention of OHSS involves careful monitoring during ovarian stimulation and the recognition of risk factors. Since prior OHSS is a risk factor, this patient will be at high risk should she undergo similar treatment in the future.“Coasting”
for up to three days has been shown to decrease the risk of OHSS without lowering pregnancy rates. Coasting involves delaying hCG and withholding gonadotropin stimulation until estradiol levels fall below 2500 pg/mL. Gonadotropin-releasing hormone (GnRH) agonists (leuprolide) can be used to induce an endogenous luteinizing hormone (LH) surge instead of hCG to reduce the risk. Using a lower dose of hCG (5000 mIU instead of 10 000 mIU) will also reduce the risk of OHSS [4].
Key teaching points
Mild ovarian hyperstimulation syndrome (OHSS) is a common complication of ovarian stimulation with gonadotropins.
Severe OHSS is an uncommon but potentially life-threatening complication.
OHSS is self-limited and treatment is primarily supportive to alleviate symptoms and prevent complications of the disease.
Risk factors for OHSS include gonadotropin ovarian stimulation, prior OHSS, young age, low body weight, polycystic ovary syndrome, high estradiol levels, large follicle counts, and human chorionic gonadotropin (hCG) (during stimulation or from a resulting pregnancy).
Common symptoms and signs of OHSS include abdominal pain and bloating, shortness of breath, ascites,
hyponatremia, hyperkalemia, and hemoconcentration.
Potential life-threatening complications of OHSS include pulmonary embolism, ovarian rupture and hemorrhage, hypovolemic shock, and electrolyte-induced arrhythmias.
References
1. Schenker JG. Clinical aspects of ovarian hyperstimulation syndrome.Eur J Obstet Gynecol Reprod Biol1999;85:13–20.
2. Practice Committee of the American Society for Reproductive Medicine.
Ovarian hyperstimulation syndrome.
Fertil Steril2008;90(Suppl 3):
S188–93.
3. Dulitzky M, Cohen SB, Inbal A, et al.
Increased prevalence of thrombophilia among women with severe ovarian
hyperstimulation syndrome.Fertil Steril 2002;77:463–7.
4. Lucidi RS.Ovarian Hyperstimulation Syndrome. Available athttp://
emedicine.medscape.com/article/
1343572-overview.
Case 62: Abdominal pain and distension seven days after egg retrieval for planned IVF