Ovarian hyperstimulation syndrome (OHSS) is a pathological condition that develops after the use of hormonal agents to stimulate ovulation. Clinical manifestations of this syndrome include respiratory and cardiovascular insufficiency, ascites, anasarca, oligoanuria, gastrointestinal disorders. The diagnosis of ovarian hyperstimulation syndrome is established on the basis of physical examination, general laboratory tests, ultrasound, chest radiography. Treatment involves normalization of rheological properties of blood, if necessary – oxygen support and evacuation of ascitic, pleural or pericardial fluids.
Ovarian hyperstimulation syndrome is a systemic pathology in obstetrics and gynecology that develops as a result of excessive activation of the synthesis of steroid hormones by the ovaries against the background of stimulation of superovulation. This syndrome was first described in 1943. The overall prevalence of ovarian hyperstimulation syndrome, according to various data, ranges from 0.4% to 35% of cases from all the stimulation schemes carried out. Severe forms are much less common – in 0.1-10%. The mortality rate in this case is 1 case per 45,000- 50,000 women. The main cause of death in OHSS is adult respiratory distress syndrome or thromboembolism, less often acute renal failure or gastrointestinal tract damage.
The immediate cause of ovarian hyperstimulation syndrome is the body’s reaction to hormonal drugs that affect ovulation. As a rule, such funds are used in in vitro fertilization or egg donation, in the treatment of infertility and anovulatory cycles, etc. As a result, the ovaries produce excessively large amounts of steroid hormones (progesterone and estrogen). A high concentration of hormones leads to systemic damage to the endothelium and increased permeability of the vascular wall. Against the background of generalized release of protein-rich fluid outside the vessels, fluid accumulates in the body cavities and interstitial.
Ovarian hyperstimulation syndrome is also manifested by hyperdynamic type of blood circulation. This concept includes a decrease in blood pressure, an increase in cardiac output and an increase in the tone of the sympathetic part of the peripheral nervous system. Stimulation of the renin-angiotensin-aldosterone system plays a leading role in the genesis of ovarian hyperstimulation syndrome, which causes a high level of interleukins and TNF fractions α and β in the blood. Experts admit the existence of a genetic tendency to ovarian hyperstimulation syndrome. Separately, there are risk factors that increase the likelihood of its development. These include incorrect selection of the dose of drugs for stimulation or its non-compliance, deficiency of body weight, episodes of OHSS in the anamnesis.
Based on clinical and laboratory characteristics, four degrees of severity of ovarian hyperstimulation syndrome are distinguished:
- Mild. The general condition is not disturbed. Blood pressure and heart rate are within normal limits. Complaints of minimal discomfort, a feeling of heaviness in the hypogastrium. The diameter of the ovaries according to ultrasound scanning is up to 8 cm. Hematocrit is less than 40%.
- Medium degree. There is an increase in mild symptoms, nausea, vomiting, less often diarrhea. The general condition remains normal. Heart rate and BH may slightly increase, and blood pressure may decrease. There is an increase in body weight and abdominal circumference. On ultrasound, the ovaries are more than 8 cm, signs of ascites. Ht – 40-45%.
- Severe degree. Complaints are similar, but more intense and may be accompanied by fear. The general condition is moderate or severe. There is a significant decrease in blood pressure, tachycardia, fever, shortness of breath of a mixed or inspiratory nature. There is a pronounced increase and tension of the abdomen. The first signs of hydropericardium and hydrothorax, anasarca are possible. The diameter of the ovaries on ultrasound is over 12 cm. Laboratory determines leukocytosis over 15×109 / l, oliguria, hypo- and dysproteinemia. Ht – 45-55%.
- Critical degree. The complaints are similar. Massive ascites and hydrothorax are detected. The development of respiratory distress syndrome (RDS), acute respiratory failure and thromboembolism is characteristic. Anuria, leukocytosis of 25×109/l or more is determined in the laboratory. Ht – more than 55%.
Symptoms of ovarian hyperstimulation syndrome
Usually, clinical manifestations of ovarian hyperstimulation syndrome occur on 2-5 days after the use of stimulant drugs. Their combination and intensity vary depending on the severity of the pathology. The woman is in a forced position (half-sitting). The general condition ranges from normal to severe. An increase in body weight is often observed. The skin acquires a pale shade, becomes dry. Acrocyanosis often develops. There are swelling of the arms and legs or anasarca. Fever with ovarian hyperstimulation syndrome is a sign of infectious complications, most often from the genitourinary or respiratory system. Less often it occurs against the background of internal pyrogenic reactions.
The defeat of the respiratory and cardiovascular systems in OHSS is manifested by tachypnea, shortness of breath of an inspiratory or mixed nature, tachycardia, a feeling of increased heartbeat or rhythm disturbances. Gastrointestinal disorders in ovarian hyperstimulation syndrome include nausea, repeated vomiting, and rarely diarrhea. There is pronounced discomfort or pain in the hypogastric region. Pain syndrome with OHSS of a pulling or stabbing nature of varying intensity with possible irradiation in the groin and amplification during movements or turns of the body. Against the background of hypovolemia and hypotension, the work of the kidneys is disrupted – oligoanuria and ARF occur.
Anamnestic data in favor of ovarian hyperstimulation syndrome indicate ongoing stimulation programs in this ovulatory cycle, non-compliance with dosage or the presence of other potential etiological factors. The complaints that the patient may make depend on the severity of the pathology. During physical examination of women with ovarian hyperstimulation syndrome, enlarged ovaries and signs of fluid accumulation in the body cavities are detected without hindrance. There is also tachypnea, dullness of percussion sound in the basal parts of the lungs, weakening of breathing during auscultation or its complete absence (hydrothorax), tachycardia, muffled heart tones, hypotension, expansion of the boundaries of cardiac dullness, (hydropericardium), abdominal enlargement and tension, bulging of the navel, ascites.
In the blood test for ovarian hyperstimulation syndrome, leukocytosis of varying severity and symptoms of hemoconcentration (relative erythrocytosis, increased Hb and Ht, thrombocytosis) are determined. Urine tests can reveal the presence of protein (proteinuria) and a decrease in the amount of urine (oligoanuria). In the biochemical analysis of blood with OHSS, there is an increased concentration of potassium and a reduced concentration of sodium, hypo– and dysproteinemia, an increase in C-reactive protein.
Instrumental diagnostics in ovarian hyperstimulation syndrome is realized by means of chest rengenography, ultrasound and ECG. The first technique allows to determine the presence of fluid in the thoracic and pericardial cavities, as well as the development of RDS. An ECG may show ventricular extrasystole, a decrease in the amplitude of the teeth, massive electrolyte changes in the myocardium. Ultrasound examination makes it possible to visualize enlarged ovaries, study their structure, determine the presence of free fluid in the abdominal cavity, pleural sinuses and pericardium, and evaluate the dynamics of the heart.
The essence of conservative treatment for ovarian hyperstimulation syndrome is to replenish the CBV, normalize the rheological properties of the blood, prevent the development of multiple organ failure, thromboembolism and ARF. Hypovolemia is relieved by infusion therapy with crystalloids (NaCl 0.9%, combined saline solutions) with further addition of colloids. Pain syndrome in ovarian hyperstimulation syndrome is eliminated by antispasmodic drugs and non-narcotic analgesics. Prevention of thromboembolic complications is carried out with the help of unfractionated heparin or low molecular weight heparins.
With RDS, oxygen support or ventilation is mandatory. In case of severe hemodynamic disorders or critical condition of the patient, antibacterial therapy is carried out in order to prevent bacterial complications. Surgical treatment for ovarian hyperstimulation syndrome may consist in evacuation of accumulated fluid (laparocentesis and thoracocentesis, pericardial puncture), median laparotomy for internal bleeding, torsion or rupture of the ovary, etc.
Prognosis and prevention
The prognosis for a woman with ovarian hyperstimulation syndrome is usually favorable. With successful fertilization, there is a risk of miscarriage in the I and II trimesters, fetoplacental insufficiency and premature birth – in the III trimester. Prevention of ovarian hyperstimulation syndrome includes detailed compliance with the instructions of the attending obstetrician-gynecologist, the use of smaller doses of drugs in the presence of risk factors for OHSS, balanced nutrition with the use of a large volume of fluid, prevention of physical or psychoemotional overload, a full examination before ovulation stimulation, abstinence from sexual activity.