Ovarian hyperstimulation syndrome

Introduction to ovarian hyperstimulation syndrome Ovarian hyperstimulation syndrome (OHSS) is one of the main complications of in vitro fertility-assisted fertility. It is an over-reaction of human ovulation-promoting drugs. It has multiple follicular development, ovarian enlargement, and capillary permeability in both ovaries. Sexual abnormalities, abnormal body fluids and protein extravasation enter the third gap of the human body characterized by a series of complications of clinical symptoms. The main clinical manifestations of OHSS are cystic enlargement of the ovary, increased capillary permeability, and accumulation of body fluids in the interstitial space, causing peritoneal effusion, pleural effusion, and local or systemic edema. In recent years, the occurrence of OHSS is on the rise, which has increasingly attracted the attention of clinical medical workers. basic knowledge The proportion of illness: 0.001% Susceptible people: women Mode of infection: non-infectious Complications: pleural effusion, pericardial effusion, thrombosis, intracranial hypertension syndrome, cerebral infarction

Causes of ovarian hyperstimulation syndrome

OHSS can occur after various stimulations of follicles. The main risk factors associated with OHSS are:

Drug sensitive (40%):

Common in polycystic ovary patients and young (age <35 years old) small and thin; ovarian hypersensitivity is characterized by a significant increase in serum estrogen concentration (> 10000 pmol / L) and a large number of follicles (> 20), often medium size Follicles (diameter <14mm), it is generally believed that the presence of excessive follicles is an important marker of OHSS. Many data indicate that PCOS is the most important risk factor for OHSS. Recently, it has been found that patients with hyperinsulinemia PCOS have a high risk of OHSS. Some people compared PCOS with follicle stimulating hormone (FSH) and found that the incidence of OHSS in hyperinsulinemia was significantly higher than that in the control group. The ovarian growth rate and the number of immature follicles in the hyperinsulinemia group were also higher than those in the control group. Plasma E2 levels during ovulation are also high in the high insulin group, so it is believed that insulin and FSH may have synergistic effects, and the ovarian sensitivity to FSH is significantly improved.

Succession history (25%):

In vitro fertilization (IVF), HCG is often used as a follicle-stimulating and ovulation-promoting agent. Compared with endogenous luteinizing hormone (LH), HCG is more likely to cause OHSS due to:

The half-life of 1HCG preparation is longer, and the follow-up effect after ovulation is more obvious.

The affinity of 2HCG preparation to LH receptor is stronger than that of endogenous LH and the action time is long. The data show that the affinity of HCG to its receptor is 2 to 4 times stronger than that of LH, and the half-life is 24 to 36 h (LH half-life is 60 min). Generational kinetic studies have shown that after intramuscular injection of HCG 5000U or 10000U, the increase of HCG level can last for 6 to 10 days. Therefore, when HMG/FSH superovulation, HCG injection can cause further enlargement of ovaries and form multiple corpus luteum cysts. Super-physiological blood F2 and progesterone (P) levels are likely to cause multiple pregnancies and OHSS in patients with ovarian hyperreactivity.

3HCG preparation has both LH and FSH-like effects, which can stimulate the ovary and promote the luteinization of granulosa cells. In addition, HCG plus endogenous HCG aggravates OHSS during pregnancy, so successful pregnancy occurs during IVF or ovulation induction therapy. The risk of severe OHSS is higher.

Use HCG to promote ovulation or maintain the gestational corpus luteum.

Endogenous HCG secretion during early pregnancy.

Pathogenesis

Ovarian hyperstimulation syndrome (OHSS) is one of the main complications of in vitro fertility-assisted fertility. Assisted reproduction, in vitro fertilization, artificially over-stimulated ovary can have three common complications:

1OHSS and polycystic ovary syndrome (PCOS), its mechanism is unknown, may be mainly associated with vascular endothelial growth factor (VEGF) overexpression, excessive prostaglandin synthesis, inflammatory factors and angiotensin-2 (AT-2) Related factors such as release.

2 thromboembolic lesions, especially for those who have hypercoagulable state, assisted fertility over-stimulated ovarian can cause severe thromboembolic lesions.

3 multiple pregnancies and ectopic pregnancy, mainly because multiple eggs mature at the same time, and caused by pregnancy, clinical use of ovulation inducers, such as human chorionic gonadotropin (HCG), human menopausal gonadotropin (human menopausal gonadotropin, HMG) and clomiphene, a series of clinical manifestations caused by excessive stimulation of the ovaries, severe cases can be life-threatening.

Ovarian hyperstimulation syndrome prevention 1. Maintain an optimistic and happy mood. Long-term mental stress, anxiety, irritability, pessimism and other emotions will make the balance of the cerebral cortex excitatory and inhibition process imbalance, so you need to maintain a happy mood. 2, life restraint pay attention to rest, work and rest, life orderly, maintain an optimistic, positive, upward attitude towards life has a great help to prevent disease. Do the regularity of tea and rice, live daily, not overworked, open-minded, and develop good habits. 3, reasonable diet can eat more high-fiber and fresh vegetables and fruits, balanced nutrition, including protein, sugar, fat, vitamins, trace elements and dietary fiber and other essential nutrients, meat and vegetables, diversified food varieties, Giving full play to the complementary role of nutrients in food is also helpful in preventing this disease.

Ovarian hyperstimulation syndrome complications Complications, pleural effusion, pericardial effusion, thrombosis, intracranial hypertension, cerebral infarction

1. Pulmonary complications: characterized by non-lung tissue substantial, restrictive pulmonary dysfunction, which is at least associated with ascites formation, increased intra-abdominal pressure, limited diaphragmatic activity (decline), and limited thoracic expansion, due to the above reasons Insufficient lung dilatation, decreased pulmonary ventilation, dysregulation of ventilatory/blood flow ratio, leading to ventilatory dysfunction hypoxemia, such as pulmonary infection, pulmonary thromboembolic lesions can lead to severe adult respiratory distress and lung Functional failure, Howat et al reported that 1 case of adjuvant ARDS and sepsis in patients after in vitro fertilization, long-term treatment, and methotrexate (MTX) to prevent future ectopic pregnancy, successful.

2. Pleural effusion, pericardial effusion, cholestasis syndrome, deep vein thrombosis or arterial suspension thrombosis, benign intracranial hypertension syndrome, multiple cerebral infarction (due to hypercoagulable state cerebral embolism), pseudo Cholinesterase deficiency.

Symptoms of ovarian hyperstimulation syndrome Common symptoms Diarrhea, abdominal distension, abdominal pain, weight gain, ascites, abdominal discomfort, edema, abdominal muscle tension, abdominal fluid, irritability

1. Clinical classification of OHSS: The main clinical manifestations are cystic enlargement of the ovary, increased capillary permeability, accumulation of body fluids in the interstitial space, causing ascites, pleural effusion, and local or systemic edema. Generally, OHSS can be divided into light and medium. , weighs 3 degrees.

(1) Mild OHSS: manifested as weight gain, thirst, abdominal discomfort, slight swelling of the lower abdomen, mild nausea and vomiting, physical examination without loss of water and abdominal positive signs, B-ultrasound showed ovarian enlargement (diameter > 5cm) There are a number of corpus luteum, showing a small amount of fluid in the abdominal cavity.

(2) Moderate OHSS: nausea and vomiting, abdominal distension, abdominal pain, shortness of breath, but no significant fluid loss and electrolyte imbalance. Physical examination showed abdominal distension but no abdominal muscle tension, ascites may be positive, sputum and swelling The ovary, B-ultrasound showed cystic enlargement of the ovary (>7 cm) and moderate amount of peritoneal effusion.

(3) Severe OHSS: The symptoms of moderate OHSS are further aggravated, and there are a lot of clinical manifestations of fluid loss (such as irritability, rapid pulse, low blood pressure), third interstitial fluid accumulation, peritoneal effusion and even intestinal effusion, Low blood volume shock, blood concentration, oliguria, water and electrolyte balance disorder, physical examination showed abdominal tension, ascites sign positive, ovary increased significantly, B-ultrasound showed ovarian diameter > 10cm, extremely severe cases may be due to massive ascites, pleural effusion, Acute respiratory distress syndrome occurs in pericardial effusion, and complications such as liver, renal failure and thrombosis may occur, such as blood cell volume 45%, white blood cells 15 × 109 / L, massive ascites, oliguria, mild liver, Renal dysfunction can be diagnosed as severe OHSS, such as blood cell volume 55%, white blood cells 25 × 109 / L, a large number of ascites, renal failure, thromboembolism, and the development of respiratory distress syndrome is extremely serious.

Some patients have ovarian torsion, ovarian cyst rupture and other acute abdomen due to ovarian ovarian disease. Recently, some people have divided the light, medium and severe OHSS into 5 grades, mild: grade I, and obvious abdominal distension. Grade II, grade I symptoms and nausea, vomiting and/or diarrhea, ovarian enlargement but diameter <5cm, moderate: grade III, symptoms same as before, B-ultrasound with ascites. Severe: Grade IV, the above symptoms and difficulty in breathing, clinically detect ascites and/or pleural effusion; Grade V, in addition to the above symptoms, blood volume changes, manifested as blood concentration, increased blood viscosity, abnormal blood coagulation mechanism And renal blood flow reduction.

2. Laboratory and ultrasonography: suspected OHSS should be used for whole blood cell analysis, liver and kidney function tests, water and electrolyte tests, pelvic ultrasound, body weight measurement, E2 level determination, etc. Monitoring the observation of ovarian response to gonadotropins is prevention Important measures of OHSS, OHSS can be expressed as blood cell volume and white blood cell elevation, low sodium, hypoproteinemia, ovarian enlargement by ultrasound, follicular flavin cyst, mild ovarian enlargement to 5 ~ 7cm, moderate 7 ~ 10cm, the severity is more than 10cm, at the same time can be seen as peritoneal effusion, pleural effusion or pericardial effusion, severe OHSS can appear liver dysfunction (expressed as hepatocyte damage) and cholestasis, alkaline phosphatase, alanine aminotransferase, Aspartate aminotransferase, bilirubin, creatine kinase increased, usually returned to normal within 1 month, some patients with liver biopsy showed hepatic steatosis, Kuffer cell proliferation, ascites exudate, containing a higher concentration of protein.

3. Disease observation and prediction

(1) Prediction of ovarian hyperstimulation: serum E2 and ovarian morphological changes can reflect the degree of ovarian stimulation. B-ultrasound monitoring and E2 determination are performed every day from 7 to 8 days after stimulation. Brinsden et al believe that IVF or gametes are involved. Intrauterine transplantation (GIFT), serum E210000pmol/L (3000pg/ml), ovarian diameter12mm, follicle number20 is the threshold index of ovarian hyperstimulation, the risk of OHSS exceeding this threshold Significantly increased, so the ovarian response should be closely monitored during the pregnancy, but the E2 level should be considered different depending on the experimental method used. It is suggested that the increase in blood estrogen is more responsive to the ovarian stimulation than the absolute level. Sensitivity.

Ellenbogen proposed to predict OHSS by follicular ultrasound scoring. They used vaginal ultrasound to detect 63 ovulation cycles (HMG plus HCG) in 34 patients with PCOS. The scoring method was as follows: the average diameter of follicles was 5 to 8 mm, and the score was 9 to 12 mm. 1.5 points, 13 ~ 16mm for 2 points, 17mm for 3 points, and cumulative total ovarian follicles, and found that the total score <25 did not occur OHSS, the total score > 30 points were OHSS, in addition, the total score Parallel to the blood E2 level.

(2) Selective precautions based on estrogen levels: Brinsden et al. believe that appropriate measures can be taken to prevent the occurrence of OHSS according to estrogen levels during the pregnancy.

1 serum E2 10000pmol / L (3000pg / ml), no OHSS performance can be directly used for embryo transfer.

When 2E2 needs luteal support after 5000-10000 pmol/L (1500-3000 pg/ml) transplantation of blastocyst, progesterone should be used.

3 serum E2 17000pmol / L (5500pg / ml), the total number of follicles 40 banned HCG ovulation, at this time can continue to use gonadotropin-releasing hormone agonist (GnRH agonist, GnRH-A) to inhibit ovarian hyperstimulation ( The mechanism is as follows: After the normal size is restored, the ovary is stimulated with a small dose of gonadotropin.

4 serum E2 in 10000 ~ 17000pmol / L (3000 ~ 5500pg / ml), the number of follicles in the case of 20 ~ 40, HCG can still be used, but blastocyst should be used for freezing, not for fresh blastocyst transplantation, so as to avoid OHSS deterioration, Recently, Thinen et al. performed blastocyst freezing treatment on 23 high-risk cases of OHSS. Only 2 cases developed OHSS, 1 case was mild, and the other 1 case was severe. The success rate of freeze-thaw blastocyst transplantation was higher (22.7%).

5 In the process of ovulation induction, serum E2>1000pg/ml, when there are more than 4 follicles with diameter 14mm, there is a risk of multiple pregnancy, multiple pregnancy is easy to cause OHSS, and HCG should be avoided to promote ovulation.

(3) Selection of ovulation-promoting drugs: The data on GnRH-A study showed that GnRH-A instead of HCG can induce follicular maturation and ovulation, and effectively reduce the occurrence of OHSS. Compared with HCG, ovulation rate and pregnancy rate are similar. The multiple birth rate is reduced, but has no effect on the number and quality of the egg, but the blood E2 and progesterone levels in the luteal phase are low, and the luteal function may be insufficient, resulting in increased abortion rate. The corpus luteum support treatment should be properly performed, which may be caused by:

1GnRH-A regulates the pituitary gonadotropin-secreting cell autoreceptor and reduces LH secretion.

The 2GnRH-A induced LH/FSH peak down regulates the corresponding receptors of the ovarian corpus luteum, reducing its reactivity.

The role of 3GnRH-A in directly dissolving the corpus luteum cannot be ruled out. Therefore, GnRH-A must be artificially supplemented with progesterone after ovulation induction. Some scholars advocate simultaneous supplementation to support corpus luteum function. Progesterone support corpus luteum function significantly reduces OHSS occurrence compared with HCG. However, if E2 is not very high, it can also supplement HCG. GnRH-A induced ovulation is beneficial to reduce the occurrence of OHSS in the luteal phase. Although multiple enlarged luteinized cysts are still seen, its function is poor, blood E2, progesterone. The level is low, so the clinical symptoms are mild. Lewitt used GnRH-A instead of HCG for ovulation induction in patients with a history of severe OHSS induced by HCG. The results showed that no severe OHSS occurred after GnRH-A, pregnancy rate and HCG. Similar to ovulation induction, GnRH-A long-term regimen should be used for ovarian hyperstimulation (ie, from the luteal phase to the HCG injection day before the treatment cycle), and GnRH-A should be used for 1 cycle before PCOS superovulation, which can reduce OHSS. Occurrence, but also treatment of its androgen excess, GnRH-A induction of ovulation indications: high sensitivity to HMG / FSH ovulation or fertilization technology superovulation treatment, patients with high risk of OHSS.

Aboulghar et al. advocated that patients with PCOS who had a history of severe OHSS with FSH could be treated with HMG or recombinant human FSH (small-dose escalation). They compared HMC with recombinant human FSH (dose 75 U/d, 37.5 per week) U), the results showed no severe OHSS in both groups, and the pregnancy rates were 20% and 15.4%, respectively.

Examination of ovarian hyperstimulation syndrome

Suspected OHSS should be used for whole blood cell analysis, liver and kidney function tests, water and electrolyte tests, body weight measurement, E2 level determination, etc. Monitoring the observation of ovarian response to gonadotropins is an important measure to prevent OHSS. OHSS can be expressed as blood cell volume and Increased white blood cells, low sodium, hypoproteinemia, severe OHSS can occur liver dysfunction (expressed as hepatocyte damage) and cholestasis, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, bilirubin, creatine kinase increased It usually returns to normal within 1 month. In some patients, liver biopsy shows hepatic steatosis, Kuffer cell proliferation, ascites is exudate, and contains a higher concentration of protein.

1. Abdominal, pelvic ultrasound examination showed ovarian enlargement, follicular flavin cyst, mild ovarian enlargement to 5 ~ 7cm, moderate 7 ~ 10cm, severe more than 10cm, at the same time visible ascites.

2. Chest X-ray, pleural effusion or pericardial effusion.

3. Severe OHSS can cause liver dysfunction. In some patients, liver biopsy shows hepatic steatosis and Kuffer cell proliferation.

Diagnosis and differentiation of ovarian hyperstimulation syndrome

diagnosis

1. According to medical history and clinical manifestations, weight gain, thirst, abdominal discomfort, slight swelling of the lower abdomen, mild nausea and vomiting.

2. B super-oval enlargement (diameter > 5cm), there are multiple corpus luteum, showing a small amount of effusion in the abdominal cavity.

3. Blood cell volume and white blood cell elevation, low sodium, hypoproteinemia, severe OHSS may appear liver dysfunction (expressed as hepatocyte damage) and cholestasis, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, bilirubin , creatine kinase increased.

4. Patients with suspected OHSS should have complete blood cell analysis, liver and kidney function tests, water and electrolyte tests, pelvic ultrasound, body weight measurement, E2 level determination, etc.

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