Signs of hypera after puncture. Embryo transfer during ovarian hyperstimulation. Prevention of ovarian hyperstimulation. Potential complications. Treatment of moderate and severe forms of OHSS

Every woman strives to become a mother with all the forces of her nature and, when it does not work out naturally, she is ready to try again and again with the help of medicine. The procedure of in vitro fertilization has long been heard, because thanks to it, the dream of motherhood becomes a reality. Discussing with the patient the features and nuances of the method, the doctor is obliged to inform her about the possible risks. The most difficult and unpredictable "turn" of IVF is considered ovarian hyperstimulation syndrome (OHSS). We will discuss it in our article.

This disease is iatrogenic. This is the name of the negative state, the cause of which was the invasion of doctors into the human body. OHSS is a reaction to high doses of hormonal drugs, through which, during the IVF procedure, the normal functionality of the ovaries is restored. The first death of a woman from hyperstimulation was recorded in 1951. Since then, the pathology has been under the close attention of scientists and physicians, because a certain degree of the disease manifests itself in almost all women who use IVF to get pregnant.

IVF features

In vitro fertilization is an assisted technology of reproductive medicine, which is carried out in several stages. Let's look at them all briefly.

1. The first stage - with the help of hormones, they act on the ovaries to achieve superovulation. This is the name of the phenomenon when, against the background of exposure to stimulant drugs, much more eggs are formed in the follicles than nature intended. As a result of medical intervention, 10-12 follicles are formed in the ovary, which, of course, makes conception quite real. At the same time, the production of the hormone estradiol also increases, which certainly affects the health of a woman.
2. The second stage is the extraction of eggs ready for fertilization from the follicles.
3. The third stage - from the body of a woman, the field of activity of a specialist is transferred to a test tube, where mature eggs are artificially fertilized with spermatozoa. If the operation is successful, within 4-5 days embryos are formed, one or two of which are implanted in the patient's uterus. The remaining biomaterial is frozen: these embryos will be needed in the case when the first ones do not take root.

Upon closer examination, IVF technology cannot be called very complicated. Some might even think that women who fail to conceive naturally are needlessly upset when there is such a wonderful reproductive technology as IVF. In most cases, this procedure really allows you to achieve an excellent result, but you should not forget about the possible unpleasant complications, the effect of which every woman who agrees to in vitro fertilization has to experience for herself to a certain extent.

Ovarian hyperstimulation in IVF

As a side effect of hormonal drugs, using which achieve the onset of superovulation, ovarian hyperstimulation syndrome is recognized. Everyone expresses it individually. Extremely difficult cases in terms of correction are noted in patients with polycystic ovaries. If the patient's history includes this diagnosis, the dosage of drugs is calculated taking into account this factor (usually the amount of hormones is reduced).

Pathology develops already during the period of ovulation stimulation, however, its symptoms make themselves felt only after the embryo is fixed in the uterus. If, in the presence of ovarian hyperstimulation syndrome, the artificial insemination procedure is successful and pregnancy occurs, the patient becomes even worse due to natural hormonal changes. Painful signs of a painful condition of the ovaries can persist for 9 to 12 weeks. As a rule, the earlier this syndrome manifested itself, the more complications develop later.

The Importance of Hyperstimulation for IVF Success

When a woman's reproductive system undergoes any pathological metamorphosis, the process of egg formation in the ovarian follicles stops. In order for the eggs to reappear and mature there, the body is given an impetus with the help of hormone therapy. On the basis of stimulation with large doses of these biologically active substances, one cycle brought about 20 eggs. Such conditions greatly increase a woman's chances of becoming pregnant through in vitro fertilization.
The reverse side of the medal of this assisted reproductive technology is an increase due to hyperstimulation of estradiol in the blood plasma, as a result of which the blood thickens and vascular permeability deteriorates. This state of affairs causes the concentration of excess fluid in the natural cavities of the body and severe swelling. This condition makes pregnancy extremely difficult.

How does ovarian hyperstimulation syndrome develop?

Nature provides that in one monthly cycle only one egg cell appears in the ovary of a woman. But when stimulated by hormones in the follicles, much more eggs mature at a time - only in this case, one can count on successful fertilization as a result of assisted reproductive technology.

In parallel with the increase in fertility in the body, the level of the hormone estradiol increases, which affects the throughput of the walls of blood vessels (it increases sharply), as a result of which the liquid plasma leaves the bloodstream, and the tissues of various organs and systems in the body swell greatly. On this ground develops:

• ascites - in this case, the fluid fills the abdominal cavity;
• hydrothorax - the chest cavity is filled with fluid;
• hydropericardium - fluid fills the space around the heart muscle (the so-called pericardial sac).

With a complication of hyperstimulation, the ovaries greatly increase, so the membrane protecting them experiences significant stretching, and pains of varying intensity occur in the lower abdomen.

In the course of research, it was found that, depending on the severity of the syndrome, the ovaries in diameter increase to the following sizes:

• the initial stage - from 5.5 to 10 cm;
• middle stage - from 7 to 11.5 cm;
• the last stage is from 12.5 to 25 cm.

The early manifestation of ovarian hyperstimulation syndrome has an unpromising prognosis for the course and treatment.

The chances of becoming a mother in women predisposed to this pathology are 1.5 - 2 times less than in those who bypass the complication. If the fertilized egg does not take root in the uterus, then all signs of hyperstimulation completely disappear with the start of a new menstrual cycle. If pregnancy develops, the woman's well-being is aggravated even more.

OHSS and its symptoms

Symptoms of ovarian hyperstimulation differ depending on the intensity of the disease. Pathology of initial severity manifests itself:

• not too pronounced discomfort in the lower abdomen, from physical exertion, discomfort increases;
• a feeling of petrification and fullness of the abdominal cavity;
• subtle swelling of the lower extremities;
• deterioration in general well-being.

The average severity of the disease is expressed:

• well-defined pains in the lower abdomen, which are aggravated by sudden movements and spread to the sacrum and groin;
• a feeling of fullness and severe bloating;
• dizziness, visual disturbances in the form of "flies" before the eyes;
• a decrease in the daily volume of urine and a decrease in the frequency of urging to the toilet;
• dysbacteriosis;
• visible swelling of the arms and legs;
• swelling of the external genital organs;
• extra kilos.

Ovarian hyperstimulation syndrome of the last, most dangerous stage is accompanied by:

• severe fatigue, headaches, visual disturbances;
• excruciating pains in the abdomen, which seem to burst it from the inside and become stronger if you change the position of the body, and spread to the coccyx, groin and sacrum;
• a strongly swollen abdomen due to ascites;
• decrease in the daily volume of urine;
• high body temperature;
• frequent vomiting;
• hypotension;
• difficulty inhaling and exhaling;
• severe swelling of the whole body;
• heart rhythm disorder;
• hydrothorax.

Hyperstimulation syndrome manifests itself on the 3rd - 4th day after the start of hormonal therapy, which stimulates superovulation in the woman's body.

Forms of ovarian hyperstimulation syndrome

Pathology can have an early and late form.

An early form of the disease is said to occur when a woman's health deteriorates during the luteal phase of the menstrual cycle. It begins after ovulation is completed, when the egg is released from the ruptured follicle. If the embryo does not attach in the uterine cavity, all manifestations of the pathological syndrome disappear.

Late hyperstimulation syndrome manifests itself at 5-12 weeks of the "interesting" position. The condition of the pregnant woman is extremely difficult.

OHSS and risk factors

As a result of many years of practice, factors have been established that increase the risk of developing this pathology. We list the main ones:

• high sensitivity of the ovaries to the active ingredients of hormonal drugs that stimulate ovulation;
• errors in determining the individual dosage for a particular patient;
• low body weight of a woman, asthenic body shape;
• age up to 35 years;
• elevated levels of estradiol in the patient's blood;
• a woman's tendency to an allergic reaction;
• the presence of polycystic ovary syndrome in the patient's history;
• cases of development of OHSS in the past.

Diagnosis of ovarian hyperstimulation syndrome

During the diagnostic examination, the doctor first of all analyzes the patient's complaints: poor health, pain in the lower abdomen, nausea, swelling. Then the specialist studies the history of the disease and the history of the patient's life: what did she have before, what bad habits did she have, hereditary factor, whether there were similar cases, if this is not her first IVF.

The next stage of the examination is a gynecological examination and palpation of the abdomen, during which the specialist can detect swelling and even feel the ovaries if they are greatly enlarged.

The ultrasound procedure allows you to give the current situation a more reasonable assessment: to assess how much the ovaries have enlarged, to confirm or deny pregnancy, to see if there is excess fluid in the abdominal cavity.

As a result of a laboratory analysis in the blood, a high concentration of sex hormones is detected, a general thickening of the blood is recorded against the background of a decrease in the volume of its liquid part. When examining urine, its high density and protein in its composition are detected.

Electrocardiography and echocardiography procedures help to analyze the nature of the work of the heart.

The presence of excess fluid in the chest cavity and the cavity around the heart can be confirmed during the x-ray procedure.

At the end of the examination, the woman is consulted by a reproductive specialist.

Features of the treatment of ovarian hyperstimulation syndrome

A mild form of pathology is treated on an outpatient basis. The patient is shown prolonged rest and bed rest, plentiful and frequent drinking, and obligatory observation by a gynecologist.

In most cases, the signs of uncomplicated OHSS can be managed by adhering to a number of simple rules regarding the patient's lifestyle:

• eat healthy and varied food. The diet must contain lean meat, low-fat dairy products, various cereals, raw vegetables and fruits;
• drink plenty of water, give up "soda" and alcohol;
• give up intimate life for a while;
• do not overwork at work;
• control weight;
• monitor the quality and volume of diuresis.

The average and severe form of the disease is subject to correction in a hospital setting. Complex therapy includes the following activities:

• the introduction of large volumes of water-salt solutions (intravenously);
• taking medications that make the walls of blood vessels more dense;
• the introduction of drugs that prevent the formation of blood clots (blood clots);
• taking antibacterial drugs to avoid additional infectious inflammation with major complications;
• taking medications on a protein nutritional basis;
• ridding the patient of excess fluid in the abdominal cavity. To do this, laparocentesis is done: during the operation, the abdominal wall is pierced to ensure the outpouring of fluid;
• thoracocentesis. Through this operation, excess fluid is removed from the chest through a puncture in the chest wall;
• resort to hemodialysis in case of severe renal dysfunction.

Treatment prognosis for OHSS

Eliminating or alleviating the symptoms of ovarian hyperstimulation syndrome, of course, takes time. Even the treatment of pathology of an easy degree takes several days, or even weeks. However, experienced specialists can, fortunately, predict the features of the course of the disease and intervene in time if it deviates from the planned “scenario”.

Sequelae of ovarian hyperstimulation syndrome

If measures to eliminate the pathology are not taken on time, the patient's health is in great danger. Consider the most serious complications:

1. Ascites (up to 25 liters of fluid can accumulate in the abdomen).
2. Rupture of the ovary with the appearance of severe bleeding.
3. Complicated respiratory failure (excess fluid accumulated in the chest cavity prevents the lungs from moving freely).
4. Severe heart failure (on the basis of the hydropericardium, the heart muscle works fully).
5. Serious kidney dysfunction due to blood clotting.
6. Development of an ectopic pregnancy.
7. Torsion of the ovary, as a result of which the vessels supplying the organ with the necessary nutrients are pinched, and the ovary dies.
8. Accelerated aging of the ovaries - despite the age of a woman suitable for motherhood, she cannot become pregnant due to the fact that the ovulatory mechanism of her body is out of order, and the hormonal background of the reproductive system is irrevocably disturbed.

How to avoid OHSS

Out of 100 cases of IVF, only 10-15 cases end in serious ovarian pathology as a result of artificial insemination. Fatal outcomes as a complication of the IVF procedure are extremely rare and occur mainly due to cerebral infarction and acute liver or kidney failure. To protect yourself from the possible development of pathology, you must first of all carefully follow all the doctor's recommendations during the IVF procedure. Also, do not forget about the following rules:

1. Refuse food with a pronounced taste (spicy, salty, fried foods), give preference to foods high in protein, drink plenty of water and drinks.
2. Refuse from intense physical exertion, avoid potentially dangerous situations for the mental state.
3. Plan pregnancy well in advance and avoid obligatory examination before stimulating superovulation.

The doctor, for his part, is obliged to choose the right hormonal drug for stimulation, correctly calculate the minimum but effective individual dose for the patient, based on her age, weight and obstetric and gynecological history.

How to determine individual disposition to OHSS. Video

ICD-10 CODE N98.1 Ovarian hyperstimulation.

Ovarian hyperstimulation syndrome (OHSS)- an iatrogenic complication, which is based on a hyperergic uncontrolled response of the ovaries to the administration of gonadotropins in ovulation stimulation cycles and ART programs. In some cases, the syndrome may manifest after ovulation induction with clomiphene or when pregnancy occurs in a spontaneous cycle.

Ovarian hyperstimulation syndrome (OHSS) is a consequence of hormonal stimulation of the ovaries.

EPIDEMIOLOGY OF OVARIAN HYPERSTIMULATION SYNDROME

The frequency of OHSS varies from 0.5% to 14% with various schemes of ovulation stimulation and does not tend to decrease. Severe forms of the syndrome, which require hospitalization, are diagnosed in 0.2-10% of cases. According to the Russian National Registry, when using ART methods, the frequency of severe OHSS in 2004 was 5.6%. The disease proceeds with varying degrees of severity and can be fatal due to advanced thromboembolic complications or RDS in adults. The expected lethality is 1 per 450-500 thousand women. With the development of OHSS, which poses a threat to the life of a woman, a complex of therapeutic measures is carried out, which must be carried out quickly and with minimal errors, in accordance with the algorithm adopted today. In addition, it must be taken into account that the most severe forms of OHSS occur against the background of the onset of pregnancy.

PREVENTION OF OVARIAN HYPERSTIMULATION SYNDROME

*♦ careful selection of patients for ovulation induction, taking into account the initial level of estrogen and the size of the ovaries;
♦ the use of individual doses of gonadotropins, starting with the minimum;
♦ shortening of the period of hyperstimulation by earlier prescription of CG;
♦ reduction of the ovulatory dose of hCG or refusal to administer it; the use of GnRH agonists and clomiphene citrate instead of hCG;
♦ daily monitoring of the general condition of patients, the size of the ovaries during the treatment period and within 2-3 weeks after its cancellation;
♦ control of the level of estrogen in the blood plasma and the size of the ovaries and follicles.

More:

• Identification of high-risk groups for the development of OHSS before the start of ovarian stimulation. Clinically reliable:
  ♦young age combined with a low body mass index (<25);
  ♦PCOS;
  ♦multifollicular ovaries (the presence of more than 10–12 antral follicles with a diameter of 2–5 mm);
  ♦ large volume of ovaries;
  ♦basal level E2 more than 400 pmol/l;
  ♦high doses of gonadotropins;
  ♦presence of OHSS in anamnesis.
• Preventive measures before the start of ovarian stimulation (preferential choice of recombinant FSH preparations and their administration in low doses).
• Determination of risk factors during the period of stimulation of superovulation:
  ♦development of more than 20 follicles >12 mm in size;
  ♦rapid growth of follicles;
  ♦E2 more than 10,000 pmol/ml.
• Preventive measures during the period of stimulation of superovulation with the threat of developing OHSS:
  ♦ use of daily GnRH agonists at a dose of 0.1 mg as an ovulation trigger if stimulation is carried out according to a protocol with antagonists;
  ♦ early aspiration of follicles in one ovary;
  ♦aspiration of all follicles during puncture;
  ♦ delayed introduction of trigger ovulatory dose of hCG;
  ♦ refusal to administer the ovulatory dose of hCG;
  ♦ refusal to support the luteal phase with hCG preparations.

One of the alternative solutions for IVF and ET patients with a high risk of developing moderate and severe OHSS as an early preventive measure and increasing the effectiveness of the IVF program is the abolition of ET, cryopreservation of all “good” quality embryos and subsequent transfer in a stimulated or natural menstrual cycle.

The pregnancy rate during the transfer of embryos thawed after cryopreservation is 29.5% and does not depend on the scheme for preparing the endometrium of patients for transfer, however, the presence of ovulation is the optimal condition for pregnancy.

The cumulative pregnancy rate per patient with cancellation of transfer in a stimulated cycle, freezing of all embryos with their subsequent transfer is 37.1% and does not significantly differ from the same indicator when transferring "native" embryos (47.5%). At the same time, it should be noted that in the presence of risk factors for the development of OHSS, the choice of superovulation stimulation protocols (with GnRH agonists or antagonists), as well as the starting and course doses of the gonadotropin preparations used, are not considered decisive.

The use of modified schemes of ovarian function stimulation, consisting in the delayed introduction of the ovulation trigger or its replacement with a GnRH, is not advisable, since their use does not reduce the risk of developing OHSS, and the effectiveness of the treatment cycle decreases significantly.

For patients at risk of developing OHSS, ovarian function stimulation schemes with the presence of “small” doses of hCG (250 IU per day) at the stage of final maturation of follicles (when the dominant follicles reach a diameter of 14–16 mm) can be considered promising, and with the start of hCG administration, it is advisable to stop administration of FSH. With this treatment regimen, the effectiveness can reach 36%, and the incidence of OHSS is 4%. In the case of the combined appointment of FSH and hCG, the risk of developing this syndrome and multiple pregnancy increases.

SCREENING

Screening is not done.

CLASSIFICATION OF OVARIAN HYPERSTIMULATION SYNDROME

There is no single classification of OHSS. Based on clinical and laboratory symptoms, 4 degrees of severity of the syndrome are distinguished (Table 19-2).

Table 19-2. OHSS classification

* Ovarian size may not correlate with severity of OHSS in ART cycles due to follicular puncture.

Distinguish between early and late OHSS. If OHSS develops into the luteal phase and implantation does not occur, the syndrome disappears spontaneously with the onset of menstruation, rarely becoming severe. If implantation occurs, most often a deterioration in the patient's condition is observed, lasting up to 12 weeks of pregnancy. Late OHSS is caused by a significant rise in plasma hCG and is associated with implantation and early pregnancy. The spontaneous development of OHSS is always associated with pregnancy. The syndrome develops at a gestational age of 5–12 weeks. The severity of OHSS can be regarded as moderate to severe.

ETIOLOGY AND PATHOGENESIS OF OVARIAN HYPERSTIMULATION SYNDROME

The pathophysiology of ovarian hyperstimulation syndrome is the subject of scientific research, the main goal of which is to improve the tactics of managing this group of patients. Ovarian hyperstimulation syndrome develops against the background of abnormally high concentrations of sex steroid hormones in the blood plasma, which negatively affect the functions of various body systems. The starting factor for the development of the syndrome is the introduction of an ovulatory dose of hCG. The development of the syndrome is based on the phenomenon of "increased vascular permeability", leading to a massive release of a protein-rich fluid into the "third space" - the interstitium, and the formation of ascites, hydrothorax and anasarca. However, the "factor X" leading to fluid extravasation remains unknown. Ovarian hyperstimulation syndrome is characterized by the development of a hyperdynamic type of hemodynamics, manifested by arterial hypotension, an increase in cardiac output, a decrease in peripheral vascular resistance, an increase in the activity of the reninangiotensinaldosterone system and the sympathetic nervous system. A similar type of circulatory disorders is also formed in other pathological conditions accompanied by edema (heart failure with a high ejection fraction, liver cirrhosis).

The pathophysiology of the syndrome is studied in three directions: the role of activation of the reninangiotensin system, the relationship between the immune system and the ovaries, and the role of vascular endothelial growth factor. Currently, ovarian hyperstimulation syndrome is considered from the standpoint of a systemic inflammatory response syndrome, against which massive damage to the vascular endothelium occurs. In patients with OHSS, high concentrations of IL1, IL2, IL6, IL8, tumor necrosis factor α and β were found in the peritoneal transudate. Under the action of pro-inflammatory cytokines, systemic activation of coagulation processes occurs. Severe hypercoagulability is an integral part of the pathogenesis of systemic inflammatory response syndrome.

The role of the microbial factor in OHSS and its contribution to the development of the systemic inflammatory response syndrome are discussed. It is assumed that microorganisms that colonize the intestines, the genitourinary tract, can penetrate beyond their habitat and have an effect on the body similar to that of sepsis. The pathophysiology of OHSS spontaneously occurring during pregnancy, as well as familial recurring episodes of this syndrome in subsequent pregnancies not associated with the use of ART methods and ovulation induction, are associated with FSH receptor mutation.

*Etiology of ovarian hyperstimulation syndrome: when ovulation is stimulated with clomiphene, OHSS occurs 4 times less often and proceeds more easily than with the use of gonadotropic drugs.

*Pathogenesis of ovarian hyperstimulation syndrome: after ovulation stimulation, the amount of follicular fluid containing vasoactive substances (estradiol, progesterone, prostaglandins, cytotoxins, histamine, metabolic products) increases significantly. It is these substances that play a leading role in the development of ascites, hydrothorax, anasarca.
Under the influence of estrogens, the permeability of the vascular wall of the veins of the ovaries, vessels of the peritoneum, omentum, and pleura changes. Rapid filtration of the liquid part of the blood into the abdominal and / or pleural cavities, the pericardium leads to hypovolemia and hemoconcentration. Hypovolemia causes a decrease in renal perfusion with the development of oliguria, electrolyte imbalance, hyperkalemia and azotemia; there is hypotension, tachycardia, an increase in hematocrit, hypercoagulability. Angiotensins activate vasoconstriction, biosynthesis of aldosterone, prostaglandins, increase vascular permeability and neovascularization.
The role of the ovarian immune system in the induction of OHSS is very large: the follicular fluid contains macrophages, which are a source of cytokines that play a role in steroidogenesis, luteinization of granulosa cells, and neovascularization of developing follicles.

CLINICAL PICTURE OF OVARIAN HYPERSTIMULATION SYNDROME

* As mentioned above, there are 3 degrees of severity of ovarian hyperstimulation syndrome:
1. Light: a feeling of heaviness, tension, bloating, pulling pains in the abdomen. The general condition is satisfactory. The diameter of the ovaries is 5-10 cm, the level of estradiol in the blood is less than 4000 pg / ml. Ultrasound of the ovaries: many follicles and luteal cysts.
2. Medium: the general condition is slightly disturbed. Nausea, vomiting and/or diarrhea, discomfort and bloating. There is an increase in body weight. The diameter of the ovaries is 8-12 cm, ascitic fluid is detected in the abdominal cavity. The level of estradiol is more than 4000 pg / ml.
3. Severe: the general condition is moderate or severe. Appears shortness of breath, tachycardia, hypotension. The abdomen is tense, enlarged (ascites). Fluid may appear in the pleural, pericardial cavities, and anasarca may develop. Possible swelling of the external genitalia. The diameter of the ovaries is more than 12 cm, they are palpable through the abdominal wall.

OHSS is characterized by a wide range of clinical and laboratory manifestations:

• an increase in the size of the ovaries, sometimes up to 20–25 cm in diameter, with the formation of follicular and luteal cysts in them against the background of a pronounced edema of the stroma;
• an increase in vascular permeability, leading to a massive release of fluid into the "third space" and its deposition with the development of hypovolemia, with signs of hypovolemic shock, hemoconcentration, oliguria, hypoproteinemia, electrolyte imbalance or without them;
• increased activity of liver enzymes;
• the formation of polyserositis.

In severe cases, anasarca, acute renal failure, thromboembolic complications, RDS in adults develop.

There are no clear criteria to differentiate between moderate and severe OHSS. In moderate and severe OHSS, the general condition is assessed as moderate and severe. The severity of the syndrome is directly related to the severity of hemodynamic disorders that cause the clinical picture. The onset of the development of the syndrome can be either gradual with an increase in symptoms, or sudden - “acute”, in which a sharp redistribution of fluid in the body occurs within a few hours with the formation of polyserositis. With the manifestation of the syndrome appear:

• weakness, dizziness, headache;
• flashing "flies" before the eyes;
• respiratory disorders;
• dry cough, aggravated by lying down;
• dry mouth, nausea, vomiting, diarrhea;
• bloating, a feeling of fullness, tension, pain in the abdomen, often without a clear localization;
• infrequent urination;
• increase in body temperature;
• swelling of the external genitalia and lower extremities.

The ovaries are enlarged and easily palpated through the abdominal wall. At the time of manifestation of OHSS, the vast majority of patients show symptoms of peritoneal irritation. Respiratory failure in patients with OHSS usually occurs as a result of limited respiratory mobility of the lungs due to:

• ascites;
• enlargement of the ovaries;
• the presence of effusion in the pleural or pericardial cavities.

In the stage of manifestation of severe OHSS, it can be complicated by acute hydrothorax, RDS in adults, pulmonary embolism, pulmonary edema, atelectasis, and intraalveolar bleeding. Pleural effusion is diagnosed in approximately 70% of women with moderate to severe OHSS, and the effusion can be unilateral or bilateral in nature and occurs against the background of ascites. In some cases, the syndrome occurs only with signs of unilateral hydrothorax, and most often right-sided. Ascitic fluid is able to penetrate into the pleural cavity along the thoracic lymphatic duct, which follows into the mediastinum through the aortic slit of the diaphragm. A clinical case of the development of shock in a patient with OHSS and massive right-sided pleural effusion, which caused displacement and compression of the mediastinal organs, as well as a fatal outcome in a woman with OHSS and hydrothorax due to pulmonary edema, massive hemorrhage into the lumen of the alveoli in the absence of pulmonary embolism, is described.

Fever accompanies the course of OHSS in 80% of patients with a severe form of the syndrome, while the temperature rise occurs against the background of:

• urinary tract infections (20%);
• pneumonia (3.8%);
• upper respiratory infections (3.3%);
• phlebitis at the site of the catheter (2.0%);
• inflammation of the subcutaneous fat at the puncture site of the abdominal wall for laparocentesis (1.0%);
• infection of the postoperative wound (1.0%);
• buttock abscess at the site of intramuscular injections of progesterone (0.5%).

Fever of non-infectious origin in every second patient with OHSS is probably associated with endogenous pyrogenic mechanisms. Isolated cases of sepsis in severe OHSS have been described. Against the background of the development of the syndrome, latent chronic somatic diseases become aggravated. Clinical manifestations of spontaneous OHSS are formed in the first trimester of pregnancy with a gestational age of 5 to 12 weeks and are characterized by a gradual increase in symptoms. The first clinical sign, forcing to pay close attention to the patient, is polyserositis, accompanied by weakness, abdominal discomfort.

Ultrasound reveals enlarged ovaries with multiple cysts and normal progressing pregnancy. OHSS can occur with the development of thromboembolic complications. The cause of thrombosis in OHSS remains unknown, but the main role in the pathogenesis of this condition is assigned to high concentrations of estrogens, hemoconcentration, and a decrease in circulating plasma volume. Long periods of hospitalization, limitation of motor activity, decreased venous return due to ovarian enlargement, increased activity of coagulation factors, fibrinolysis inhibitors and platelets make an additional contribution to the high risk of developing thrombotic complications due to OHSS. It was shown that in women with thromboembolic complications that arose after superovulation stimulation, ovulation induction and in ART programs, their development in 84% occurred during pregnancy. In 75% of cases, thrombus formation in the venous bed was noted with predominant localization in the vessels of the upper limb, neck and head (60%), however, in a number of patients spontaneous arterial thrombosis was diagnosed with localization in the vessels of the brain. The formation of blood clots in the femoral popliteal, carotid, subclavian, iliac, ulnar, mesenteric arteries and aorta was less commonly noted. The literature describes a case of a woman with OHSS developing occlusion of the central retinal artery with loss of vision that did not recover later. The incidence of pulmonary embolism in patients with OHSS and deep vein thrombosis of the lower extremities is 29%, while in women with OHSS and deep vein thrombosis of the upper extremities and arterial thrombosis, the risk of this complication is significantly lower and amounts to 4% and 8%, respectively.

Complications: intra-abdominal bleeding due to rupture of ovarian cysts, torsion of the uterine appendages, concomitant ectopic pregnancy. The development of OHSS is often accompanied by an exacerbation of chronic somatic diseases.

DIAGNOSIS OF OVARIAN HYPERSTIMULATION SYNDROME

The diagnosis of OHSS is established on the basis of anamnesis, a comprehensive clinical, laboratory and instrumental examination that reveals enlarged ovaries with multiple cysts, pronounced hemoconcentration and hypercoagulation in a patient who used ART methods or controlled ovulation induction in this cycle to achieve pregnancy. Typical errors in the diagnosis of OHSS entail an emergency surgical intervention for malignant ovarian tumors accompanied by ascites or peritonitis with the scope of the operation: bilateral oophorectomy or bilateral resection of the ovaries and sanitation of the pelvic cavity and abdominal cavity.

ANAMNESIS

The use of ART methods or controlled ovulation induction in this cycle to achieve pregnancy with infertility.

PHYSICAL EXAMINATION

• The general condition of the patient is moderate or severe. The skin is pale, acrocyanosis is possible. In some cases, icteric sclera, subicteric skin are found. Mucous membranes are clean and dry. Edema of the anterior abdominal wall, external genitalia, upper and lower extremities may develop, in especially severe cases - anasarca. Pay special attention to the condition of the limbs, head, neck area in order to exclude deep vein thrombosis.
• In the study of the cardiovascular system, tachycardia, hypotension, heart sounds are muffled.
• In the study of the respiratory system: tachypnea during exercise or at rest. On percussion: dullness of pulmonary sound in the projection of the lower parts of the lungs on one or both sides due to pleural effusion. On auscultation, there is a weakening of respiratory sounds in the area of ​​pulmonary sound dullness; with severe hydrothorax, respiratory sounds are not heard.
• Examination of the abdominal organs: the abdomen is swollen, often tense due to the formation of ascites, painful in all parts, but more often in the lower parts in the area of ​​the projection of the ovaries. The abdomen participates in the act of breathing or lags behind a little. At the time of manifestation of OHSS, weakly positive symptoms of peritoneal irritation may be detected. The ovaries are easily palpable through the anterior abdominal wall, their size is increased. The liver may protrude from under the edge of the costal arch.
• Urinary system: urinary retention, daily diuresis<1000 мл, олигурия, анурия. Симптом Пастернацкого отрицательный с обеих сторон. Дизурия при отсутствии патологических изменений в анализах мочи может быть обусловлена давлением увеличенных яичников на мочевой пузырь.
• CNS: the patient is conscious, contact, adequate. The appearance of neurological symptoms indicates thrombosis of cerebral vessels.
• Gynecological examination: Bimanual gynecological examination should be avoided due to the high risk of enlarged ovarian apoplexy and intra-abdominal bleeding. Assessment of the size and condition of the uterus and its appendages should be carried out according to ultrasound.

LABORATORY RESEARCH

• Clinical blood test: hemoconcentration (hematocrit > 40%, hemoglobin > 14 g/l); hematocrit >55% indicates a potential threat to life; leukocytosis reflects the severity of the systemic inflammatory response: in some cases it reaches 50x109/l without a shift to the left, thrombocytosis up to 500–600x106/l.
• Biochemical analysis of blood: electrolyte imbalance, including hyperkalemia and hyponatremia, leading to a decrease in plasma osmolarity. Hypoproteinemia, hypoalbuminemia, high levels of C reactive protein, increased activity of AST and ALT, in some cases - γ-glutamine transferase or alkaline phosphatase, in some patients - an increase in creatinine and urea.
• Hemostasiogram: increase in fibrinogen concentration up to 8 g/l, von Willebrand factor up to 200–400%, decrease in antithrombin III concentration below 80%, increase in Ddimer by more than 10 times. Normal APTT, prothrombin index, INR.
• Blood immunoglobulins: a decrease in the concentration of IgG and IgA immunoglobulins in the blood plasma.
• General urinalysis: proteinuria.
• Analysis of the composition of ascitic fluid: high content of protein and albumin, low number of leukocytes, relatively high number of erythrocytes, high concentrations of all pro-inflammatory cytokines, C-reactive protein, globulin fraction of proteins.
• Oncomarkers in blood plasma: the concentration of CA 125 reaches its maximum values ​​up to 5125 U/ml by the second week of development of OHSS, when both ovaries are most enlarged. The increased content of the tumor marker persists up to 15–23 weeks after the onset of signs of OHSS, despite the ongoing treatment.
• Serum procalcitonin is determined in 50% of patients in the range of 0.5–2.0 ng/ml, which is regarded as a moderate systemic inflammatory reaction.
• Microbiological examination of urine discharged from the vagina and cervical canal reveals atypical pathogens in 30% of women: Pseudomonas, Proteus, Klebsiella, Enterobacter, E. coli.

INSTRUMENTAL STUDIES

• Ultrasound of the pelvic organs: enlarged ovaries from 6 to 25 cm in diameter with multiple cysts, uterus of normal size or enlarged, free fluid in the pelvic cavity and normal progressive singleton or multiple pregnancy.
• Ultrasound of the abdominal organs: the presence of free fluid in the abdominal cavity in an amount of 1 to 5–6 liters. Normal size and structure of the liver or hepatomegaly. Echo-signs of biliary dyskinesia. When examining the kidneys, the pelvicalyceal complex was not changed.
• Ultrasound of the pleural cavities: free fluid on one or both sides.
• Echocardiography: against the background of hemodynamic disorders - a decrease in ejection fraction, a decrease in end-diastolic volume, a decrease in venous return, in some cases - free fluid in the pericardial cavity.
• Electrocardiography: heart rhythm disturbance by type of ventricular extrasystole, tachycardia; diffuse changes in the myocardium of a metabolic and electrolyte nature.
• X-ray of the chest (carried out with suspicion of adult RDS and thromboembolism): infiltrates.

DIFFERENTIAL DIAGNOSIS

Differential diagnosis is carried out with ovarian cancer. The following approaches are applied:

• Together with the oncogynecologist, the study of the history data, the results of the examination of the patient at the time of her inclusion in the IVF program, as well as the clinical picture of the disease at the present time, since ascites in ovarian cancer is the final stage of the disease. In patients with signs of OHSS, before the onset of superovulation stimulation, the normal size of the ovaries is noted according to ultrasound, the absence of ascites, the concentration of CA 125 does not exceed 35 U / ml.
• Dynamic ultrasound using transvaginal and transabdominal sensors (with OHSS, a gradual regression of all symptoms and normalization of the size of the ovaries are noted; this does not happen with ovarian cancer).
• OHSS is always a hormone-dependent condition. In plasma - high concentrations of estradiol and progesterone. In the presence of pregnancy - a high content of βhCG. In ovarian cancer, the concentrations of estradiol, progesterone, and βhCG are normal (in ovarian cancer and pregnancy, βhCG is increased).
• An important diagnostically significant event is the cytological examination of the aspirated fluid during paracentesis and thoracocentesis. In patients with OHSS, there are no cytological changes characteristic of ovarian cancer.
• Taking into account that the clinical picture of OHSS in a number of ways is similar to the clinical picture of the terminal stage of ovarian cancer, when there are multiple metastatic lesions of the gastrointestinal tract and other body systems, ultrasound is necessary to detect metastatic tumors. According to indications - CT and MRI.
• Determination of the dynamics of the concentration of CA 125, cancer embryonic Ag and other tumor markers in the blood plasma: with OHSS, their concentrations gradually return to normal; with ovarian cancer - increase. However, tumor markers are not specific to ovarian cancer. Their high concentrations were noted in inflammatory processes of the genital organs, MM, endometriosis, DOT, in early pregnancy.
• Diagnostic laparoscopy with biopsy of the peritoneum and greater omentum is the final stage in the differential diagnosis of OHSS and ovarian cancer. As noted, hemorrhagic ascites in combination with enlarged ovaries is the final stage of ovarian cancer. During laparoscopy in such patients, millet-like rashes are found on the peritoneum and the greater omentum, an increase in the lymph nodes of the greater omentum. A biopsy of these formations and lymph nodes of the greater omentum is a criterion for the diagnosis of ovarian cancer. In patients with OHSS, the ascitic fluid is usually transparent, with laparoscopy the peritoneum and the greater omentum are not visually changed, the entire pelvic cavity is occupied by enlarged ovaries of a bluish-purple color with multiple hemorrhagic cysts and cysts with transparent contents. In severe stages of OHSS, the ovaries protrude beyond the small pelvis and may reach the edge of the liver and stomach. It is better to refrain from an ovarian biopsy, since the risk of bleeding is very high even with a pinpoint biopsy, which can lead to tragic consequences.
• In the process of monitoring the patient, dynamic ultrasound and hormonal monitoring is mandatory. In the absence of regression of the described symptoms of OHSS and ovarian cysts within 8–12 weeks, a repeated comprehensive examination of the patient with specialist advice should be carried out in order to exclude the diagnosis of ovarian cancer.

INDICATIONS FOR CONSULTATION OF OTHER SPECIALISTS IN OHSS

• In view of the involvement of all organs and systems in the pathological process, an examination by a therapist is mandatory.
• If thrombotic complications are suspected, consult a vascular surgeon.
• With severe hydrothorax - consultation of a thoracic surgeon to resolve the issue of performing a puncture of the pleural cavity.
• Consultation with an anesthesiologist and resuscitator in severe and critical OHSS.

EXAMPLE FORMULATION OF THE DIAGNOSIS

Infertility I. 11th day after PE in the uterine cavity. Severe OHSS in the IVF program. Ascites. Right-sided hydrothorax. DIC syndrome.

* OHSS is diagnosed on the basis of clinical data and ultrasound (stromal hyperplasia, more than 10 small follicles with a diameter of 5-10 mm along the periphery of the ovaries) and laparoscopy.

Laboratory examination: hypovolemia, hemoconcentration, hematocrit > 45%, leukocyte count > 15x109/l, increased levels of AST, ALT, bilirubin, alkaline phosphatase, decreased albumin concentration. Oliguria, creatinine clearance< 50мл/мин, повышенная концентрация тестостерона в крови, соотношения ЛГ/ФСГ >2 in the middle of the follicular phase.

TREATMENT OF OVARIAN HYPERSTIMULATION SYNDROME

The lack of a clear concept of the pathophysiology of OHSS makes it impossible to carry out effective, pathogenetically substantiated treatment, which allows effectively and in a short time to stop the development of the syndrome and multiple organ disorders that accompany severe forms of OHSS.

GOALS OF TREATMENT

Prevention of the development of multiple organ dysfunction by restoring the central circulatory system, eliminating hemoconcentration, electrolyte imbalance, preventing acute renal failure, RDS in adults and thromboembolic complications. Treatment is carried out until the moment of spontaneous regression of the syndrome as the concentration of hCG in the blood plasma decreases for 7 days in cycles where pregnancy has not occurred, or 10-20 days with a successful pregnancy. Outpatient treatment for mild OHSS: daily assessment of weight and diuresis, limiting excessive physical activity and sexual activity, drinking plenty of fluids with the addition of solutions rich in electrolytes.

Tactics for the treatment of ovarian hyperstimulation syndrome

*1. Mild form: bed rest; plentiful drinking of mineral water; observation of the patient's condition.
2. Moderate and severe forms (only in a hospital setting):
control over the function of the cardiovascular system, respiratory system, liver, kidneys, electrolyte and water balance (diuresis, weight dynamics, changes in abdominal circumference);
hematocrit control;
crystalloid solutions in / in drip (to restore and maintain BCC);
intravenous drip colloidal solutions 1.5-3 l / day (while maintaining hemoconcentration) and persistent oliguria;
hemodialysis (with the development of renal failure);
corticosteroid, antiprostaglandin, antihistamine drugs (to reduce capillary permeability);
with thromboembolism - low molecular weight heparins (fraxiparin, clexane);
plasmapheresis - 1-4 sessions with an interval of 1-2 days (improvement of the rheological properties of blood, normalization of CBS and blood gas composition, reduction in the size of the ovaries); paracentesis and transvaginal puncture of the abdominal cavity with ascites.

INDICATIONS FOR HOSPITALIZATION

Hospitalization is required for moderate to severe OHSS.

MANAGEMENT TACTICS ON ADMISSION TO THE HOSPITAL

The first stage: upon admission of the patient to the hospital, it is necessary to correctly collect an anamnesis, which allows one to assume the development of OHSS, to conduct a complete clinical, laboratory and instrumental examination, on the basis of which to evaluate:

• parameters of hemodynamics, respiration, urination;
• the presence and nature of electrolyte disturbances;
• liver function;
• plasma protein concentration;
• coagulation potential of blood;
• the presence of polyserositis; exclude intra-abdominal bleeding and torsion of the uterine appendages.

An ultrasound of the abdominal cavity and small pelvis is performed to determine the degree of ovarian enlargement and the presence of ascites. The use of CT is not always advisable, since it requires additional transportation of the patient and increases the risk of adverse outcomes. When performing chest x-ray or CT in patients with OHSS, it is necessary to be aware of the possibility of pregnancy and conduct these studies according to strict indications (suspicion of ARDS, thromboembolism).

The second stage: setting a peripheral venous catheter. The issue of using a central venous catheter is decided individually. The most appropriate catheterization of the subclavian vein, since the risk of thrombosis in this case is the smallest. One of the advantages of placing a central catheter is the ability to monitor CVP and adjust the volume of infusion therapy. A bladder catheter can be used to assess diuresis, but given the associated risk of ascending urinary infection, the need for bladder catheterization should be considered on an individual and daily basis.

The third stage: medical treatment of patients with OHSS should be aimed at maintaining hemodynamics and mobilizing the fluid contained in the abdominal cavity by creating a negative balance of sodium and water. The primary task of this stage is the reimbursement of the BCC in order to:

• decrease in hemoconcentration;
• normalization of renal filtration;
• maintaining adequate systemic perfusion.

After the introduction of the initial dose of crystalloid, and then colloidal solutions, the volume of further infusion therapy depends on:

• echocardiography data;
• the presence of urination;
• blood pressure values;
• hematocrit values;
• CVP values.

With the normalization of these parameters, infusion therapy is stopped. Failure to comply with this approach leads to the development of hemodilution, which provokes a rapid increase in polyserositis and worsening of the patient's condition.

NON-DRUG AND DRUG TREATMENT OF OVARIAN HYPERSTIMULATION SYNDROME

• The choice of crystalloid solution depends on the degree of electrolyte imbalance. The most commonly used is 0.9% sodium chloride solution with or without added glucose. Caution should be exercised in the use of solutions containing potassium due to the risk of hyperkalemia. When determining the amount of injected crystalloids, it should be taken into account that under conditions of generalized damage to the endothelium, the volume of these solutions should be 2–3 times less than the volume of colloidal solutions, since the predominance of crystalloids aggravates the development of polyserositis, and in some cases leads to the development of anasarca. Infusion therapy begins with the introduction of 500-1000 ml per 1 hour of isotonic sodium chloride solution, followed by the appointment of colloids.
• When choosing a colloid solution, one should be guided by the notion that OHSS is an iatrogenic condition characterized by generalized damage to the endothelium against the background of a systemic inflammatory response. In this regard, the basis of basic infusion therapy should be a solution that can work most effectively under these conditions. These requirements are best met by a HES solution with a low molecular weight of 130,000 D and a degree of substitution of 0.4.

A solution of HES 6% (molecular weight 130 / 0.4) is used in a daily volume of 25–30 ml per kilogram of body weight. The positive properties of HES, which justify its predominant use in patients with OHSS, include the ability to:

• quickly replenish and retain the VCP in conditions of generalized damage to the endothelium;
• stay in the bloodstream for a long time;
• effectively increase colloid osmotic pressure;
• not have a negative effect on the vascular endothelium;
• inhibit the release of von Willebrand factor from endothelial cells;
• improve the rheological properties of blood, microcirculation;
• reduce tissue swelling;
• easily metabolized and excreted by the kidneys;
• do not cause allergic reactions.

A solution of HES 6-10% (200/0.5) in a daily volume of 20 ml per kilogram of body weight can also be used in the basic therapy of OHSS. However, the property that limits the use of this solution in the treatment of OHSS is its ability to accumulate in the body with prolonged use (more than 7 days), cause liver dysfunction and increase the activity of AST and ALT up to 800 U / l.

Solutions of HES 6% (450/0.7) are not advisable to use in this group of patients due to the negative impact on the function of the kidneys, liver and deterioration of hemocoagulation parameters.

Dextran solutions cannot be used in the complex therapy of OHSS, as they:

• increase the release of the von Willebrand factor;
• induce a pro-inflammatory cascade;
• do not improve the rheological properties of blood in the doses used;
• increase the risk of allergic reactions.

Infusion of dextrans in conditions of increased capillary permeability can lead to the development of the so-called dextran syndrome, accompanied by pulmonary edema, impaired liver and kidney function, and the development of coagulopathy.

Side effects of gelatin solutions are comparable to those of dextran solutions, which also limits their use in OHSS.

The indication for the administration of albumin solutions in conditions of generalized endothelial damage in OHSS is hypoalbuminemia (serum albumin less than 25 g/l or protein less than 47 g/l). A 20% solution is used in a daily volume of 3 ml per kilogram of body weight, followed by the introduction of furosemide, the use of which is justified by the notion that the protein under conditions of "endotheliosis" easily penetrates through the pores of the endothelium and "pulls" water into the interstitium, increasing the risk of developing interstitial pulmonary edema.

FFP is used in the complex therapy of OHSS only with a confirmed deficiency of blood clotting factors.

• Respiratory disorders: with the development of shortness of breath, it is necessary to determine the saturation of O2 using pulse oximetry, to examine blood gases. With a deterioration in respiratory parameters or the development of respiratory failure, tracheal intubation and transfer to mechanical ventilation are performed.
• In patients with hydrothorax against the background of OHSS, expectant management is justified. When forming a hydrothorax, a puncture of the pleural cavity is carried out only in case of severe respiratory failure. With the development of RDS in adults and the need to transfer to mechanical ventilation, sparing regimens are used, which reduces the likelihood of deaths and shortens the time spent on mechanical ventilation. Due to the high risk of developing infectious complications in OHSS, the infectious etiology of RDS in adults is excluded.
• Diuretics are ineffective in evacuating fluid from the third space and are contraindicated in hypovolemia and hemoconcentration due to an even greater decrease in intravascular fluid volume. Their limited use is justified when hematocrit values ​​of 36–38% are reached, hemodynamics are closely monitored, against the background of persistent oliguria and peripheral edema.
• There is evidence of the efficacy and safety of low-dose dopamine in the treatment of patients with severe OHSS to increase renal blood flow and glomerular filtration. At the same time, in a multicenter placebo-controlled study of 328 critically ill patients with clinical signs of initial renal failure, no protective effect of continuous intravenous infusion of low doses of dopamine was found.
• Pain relief: paracetamol, antispasmodics. NSAIDs should not be used due to possible negative effects on the fetus in early pregnancy.
• The basis for the prevention of thrombotic complications in OHSS is the elimination of hemoconcentration. Antithrombotic therapy is indicated when laboratory signs of hypercoagulability appear. Drugs used: NG and LMWH. A necessary condition for the appointment of NG is the normal value of antithrombin III. The daily dose is 10–20 thousand units subcutaneously. Laboratory control - APTT, determination of platelet count on the 7th day of treatment. LMWH: calcium nadroparin (daily dose of 100 antiXa IU/kg 2 times subcutaneously), dalteparin sodium (100–150 antiXa IU/kg 2 times subcutaneously), enoxaparin sodium (1 ml/kg per day 1–2 times subcutaneously). Laboratory control - determination of plasma anti-Xa activity 3 hours after LMWH administration allows maintaining the effective dose of the drug within the safe therapeutic range and thus minimizing the likelihood of bleeding. The appointment of antithrombotic drugs is continued until the normalization of coagulation parameters of the blood. Thrombinemia monitoring is carried out by determining the concentration of D-dimer in blood plasma by a quantitative method. The duration of the appointment of LMWH is determined individually, if necessary, it can exceed 30 days.
• The advisability of parenteral administration of glucocorticoids, antihistamines, NSAIDs, angiotensin-converting enzyme inhibitors continues to be discussed in the literature, however, there are no reliable results confirming the effectiveness of the use of these drugs. The use of angiotensin-converting enzyme inhibitors is limited in pregnant women due to their teratogenic effects on the fetus.
• Taking into account the positive effect of prescribing immunoglobulins for the prevention of secondary infections in other diseases accompanied by protein loss, such as nephrotic syndrome, one can count on the effectiveness of this therapy in patients with OHSS. However, for the final confirmation or refutation of this hypothesis from the standpoint of evidence-based medicine, research is needed.
• The indication for empiric antibiotic therapy is the risk of secondary infection in critically ill or hemodynamically unstable patients. The change of the empirically selected drug is carried out according to the results of a bacteriological study. When prescribing empirical antibiotic therapy, it is necessary to be guided by information about the severity of the disease, risk factors for infection, and the characteristics of antibiotic resistance in this department. To reduce the risk of infectious complications in these patients, invasive manipulations, in particular, abdominal paracentesis, thoracocentesis, laparoscopy, laparotomy, should be performed only under strict indications.
• Nutritional support with oral protein preparations is provided to all patients with OHSS who are in the hospital.
• Indications for laparocentesis in women with OHSS:
  ♦ progressive intense ascites;
  ♦oliguria;
  ♦an increase in creatinine or a decrease in its clearance;
  ♦hemoconcentration, not amenable to drug correction.

A decrease in intra-abdominal pressure after removal of ascitic fluid leads to an increase in blood flow in the renal veins, an increase in venous return and cardiac output. For laparocentesis, a transabominal or transvaginal approach may be chosen. Enlarged ovaries create a technical difficulty, in connection with this, the use of ultrasound control is mandatory. Prolonged drainage of the abdominal cavity for 14-30 days with batch removal of peritoneal transudate with a pyrogen-free catheter "Cystofix" has advantages, as it allows:

• avoid simultaneous evacuation of a large volume of peritoneal transudate and thereby eliminate sharp fluctuations in intra-abdominal pressure that cause hemodynamic disturbances;
• stabilize the patient's condition;
• to avoid repeated punctures of the abdominal cavity to remove ascitic fluid in this category of patients.

The one-time volume of the evacuated fluid is about 3.5 liters, for each patient it is determined individually. The total volume of evacuated ascitic fluid during the period of treatment of severe OHSS can range from 30 to 90 liters. TVP is possible only in the conditions of specialized hospitals of IVF clinics under ultrasound control by a specialist doctor who owns this manipulation, due to the high risk of injury to the ovaries and the development of intra-abdominal bleeding.

The biochemical composition of the peritoneal fluid is similar to the blood plasma of a particular patient and is a transudate with a high protein content. The color of the peritoneal fluid can vary from amber yellow to hemorrhagic. The hemorrhagic nature is due to the "sweating" of erythrocytes into the third space in severe OHSS or an admixture of blood. To exclude intra-abdominal bleeding, it is necessary to determine the hematocrit and erythrocytes in the peritoneal fluid.

Refusal of autotransfusion of ascitic fluid is due to the high content of anti-inflammatory cytokines in it, the repeated introduction of which into the bloodstream from the abdominal cavity aggravates the course of OHSS, enhancing the systemic inflammatory response syndrome. In the absence of indications for laparocentesis, ascites gradually regresses spontaneously after reaching a negative sodium balance by limiting salt intake and / or prescribing diuretics.

Dynamic monitoring of patients with severe OHSS includes:

• daily assessment of fluid balance in the body;
• daily study of clinical blood test indicators, blood plasma electrolytes, creatinine, protein, albumin, liver enzyme activity, coagulogram parameters.

The study of the prothrombin index, INR and APTT does not provide information for assessing the risk of thrombotic complications.

A typical mistake in the treatment of women with OHSS is the unreasonable prolongation of infusion therapy in the absence of hemodynamic disorders and an attempt to completely stop the development of OHSS as an iatrogenic condition.

SURGICAL TREATMENT OF OVARIAN HYPERSTIMULATION SYNDROME

Surgical treatment for OHSS is justified only in the presence of acute gynecological diseases: torsion of the epididymis, rupture of an ovarian cyst, bleeding from an ovarian cyst. A sign of bleeding in patients with OHSS is a sharp drop in hematocrit without improvement in urination, reflecting the degree of blood loss, and not a decrease in hemoconcentration. Adnexal torsion manifests with acute pain in the lower abdomen and vomiting. In this case, laparoscopic ovarian untwisting is considered the most effective operation, and early diagnosis and adequate surgical treatment determines a favorable prognosis. Late diagnosis entails the need to remove the necrotic ovary using laparotomy access. Unfortunately, in Russia, the strategy for the treatment of patients with uncomplicated OHSS in general gynecological hospitals consists in emergency surgery and resection of about 30–50% of the ovarian tissue or bilateral oophorectomy in connection with a presumptive diagnosis of ovarian cancer and/or developed peritonitis. Such tactics in the world are regarded as a medical error with corresponding legal consequences.

In extremely rare cases, with an increase in the severity of OHSS and a deterioration in the patient's condition, despite adequate therapeutic measures being taken in full, the question of abortion is raised, which reduces the concentration of hCG in the blood plasma and leads to a gradual regression of OHSS.

*Complications of OHSS:

1. Thromboembolism, coagulopathy.
2. Acute renal failure due to insufficient renal perfusion.
3. Adult respiratory distress syndrome (ARDS).

APPROXIMATE TIMES OF INABILITY TO WORK

If not pregnant: 7-14 days. In case of pregnancy - from 14 days to 2-3 months. A long period of disability is due to the period of time necessary for spontaneous regression of the syndrome, which lasts up to 8–12 weeks of pregnancy, as well as the complicated course of the first trimester of pregnancy, often multiple.

FURTHER MANAGEMENT

• Dynamic monitoring during pregnancy.
• Control of thrombinemia according to coagulogram data. The appointment of LMWH is stopped when the standard values ​​of Ddimer are reached.
• Dynamic assessment of the state of liver function.

FORECAST

When pregnancy occurs, its complicated course due to the threat of interruption in the I and II trimesters and the development of placental insufficiency and the risk of premature birth in the III trimester. There are no data on the quality of life of women who have had severe OHSS and their risk of developing cancer in the available literature.

When a woman is unable to conceive naturally, she opts for in vitro fertilization. One of the stages of the protocols is the stimulation of the follicles for the production of eggs, which in some cases has negative consequences. In order to psychologically prepare for the IVF procedure, you should know what ovarian hyperstimulation is and why it is dangerous.

Mechanism of ovulation

For conception to occur, a sperm must meet a mature egg. The follicle is responsible for its production, but it is active only on certain days of the menstrual cycle. In a healthy woman, the mechanism functions clearly, as programmed by nature.

It is worth the system to fail, and the follicles drastically reduce the production of eggs or give a weak (immature) material. Problems with conception begin. In this situation, a woman is prescribed stimulant drugs (for example, Dostinex), which should improve the quality of ovulation. As a result, the follicles simply begin to "gush" with biological material.

Ovarian hyperstimulation syndrome during pregnancy is the body's response to interference with natural processes.

Hyperovulation is a phenomenon when the production of a much larger number of eggs in one cycle begins than was laid down by nature. This increases the chances of conception. It is not difficult to identify the symptoms of hyperovulation - pains in the lower abdomen appear and sexual desire increases.

The basal temperature rises, which the patient must monitor daily. The consistency of the mucus secreted from the cervix changes. Confirmation of the alleged ovulation will be a special test and ultrasound diagnostics.

GSS degrees

Ovarian hyperactivity does not pass without a trace for the patient, because there was a violent intrusion into the system. She needs to understand that exposure to hormonal drugs during IVF gives an impetus not only to the production of eggs. There is also a side effect - the production of estradiol. This hormone negatively affects the health of the patient, provoking the development of hyperstimulation.

Under the influence of drugs, a large number of eggs will develop, but the effect of hormone therapy will also affect other aspects, worsening the woman's well-being.

Studies show that hyper with eco is accompanied by thickening of the blood, thinning of blood vessels and poor excretion of fluid from the body. This condition is considered pathological, but in each woman it manifests itself in different ways. In this case, the degree of severity and the stage at which the syndrome manifested itself are important.

Varieties of pathology

Early is observed immediately after ovulation. If pregnancy does not occur, menstruation will begin in due time and the syndrome will decline. Late manifests itself 2-3 months after pregnancy after ovarian hyperstimulation. It manifests itself severely and is difficult to treat.

Ovarian hyperstimulation during pregnancy after IVF has 3 degrees of severity, and each of them can give complications.

The severity of HSS. In a mild form, deterioration in well-being is not always noticeable - only a slight swelling of the abdomen and some discomfort. The average degree manifests itself as severe pain in the abdomen and large swelling due to fluid accumulated in the peritoneum. The condition of the pregnant woman worsens, she develops nausea and vomiting. In severe form, abdominal pain becomes quite sharp. Weakness, shortness of breath appear, pressure drops (even if the woman had hypertension before).

It can be observed both after egg retrieval and after embryo transfer. Therefore, a woman at all stages of IVF should monitor her condition.

IVF stages

Having achieved increased ovulation with the help of stimulants, they collect mature eggs, resorting to ovarian puncture. In this case, punctures of the walls of the vagina are made. Their number depends on the number of mature follicles from which the material is taken. All this leads to damage to blood vessels, the formation of hematomas and blood clots.

Signs of ovarian hyperstimulation after puncture are manifested by spotting, accumulation of fluid in the peritoneum, cramps in the lower abdomen, or stabbing pains. Puncture of ascitic fluid during ovarian hyperstimulation can cause bloating, which not only causes discomfort, but also has serious consequences in case of late help.

In such a situation, it is not allowed to transfer embryos without eliminating the problems. If at this stage the woman felt relatively normal, the protocol is continued. But ovarian hyperstimulation may develop after embryo transfer when the woman is already pregnant.

What is hypera after replanting? For some women, complications in IVF begin after the transfer of embryos, preventing them from settling normally in the uterus. Even if pregnancy has occurred, the symptoms of ovarian hyperstimulation after embryo transfer will soon appear.

The severity will depend on the individual characteristics of the body of the woman herself (in other words, on the response of her system). But even a mild form sometimes has serious consequences of ovarian hyperstimulation during IVF.

Why is ovarian hyperstimulation dangerous during IVF? Up to 20 liters of fluid can accumulate in the abdominal cavity, which will provoke the development of ascites. Fluid sometimes seeps into the chest cavity, making breathing difficult. Due to thickening of the blood, kidney dysfunction develops. Enlarged ovaries may rupture. OHSS often causes ectopic pregnancy.

Even in a young woman, overovulation leads to premature aging of the ovaries, thus disrupting the hormonal balance irrevocably. At the same time, hyperstimulation can not only complicate the course of pregnancy, but also cause miscarriages and the development of pathologies in the baby. Moms who have had hyperstimulation are more difficult to rebuild after childbirth and may even have problems with lactation.

Treatment

You should not leave for later the treatment of ovarian hyperstimulation syndrome with IVF, taking measures at the first signs, since the process develops quite quickly.

How to treat ovarian hyperstimulation? Moderate and severe forms are best treated in a hospital under the constant supervision of physicians. You will need droppers with the introduction of various drugs that ensure the normal function of all organs, excluding the development of thromboembolism, reducing vascular permeability. So, "Voluven" can drip for several weeks.

For large edema, clinical guidelines focus on removing fluid from the abdominal cavity through surgery. In case of problems with the ovaries, they can be removed. In especially severe cases, you will have to resort to hemodialysis and antibiotics.

In a mild form, you can treat ovarian hyperstimulation at home. Here the recommendations are reduced to the observance of the normal rhythm of life. A special diet is introduced for ovarian hyperstimulation and fluid intake is exclusively on schedule.

In most cases, the prognosis is good if treatment is started in a timely manner. But it is better to know how to avoid ovarian hyperstimulation during IVF so that there are no undesirable consequences.

Prevention. Reduce or stop the ovulatory dose of certain drugs. Take your time with the embryo transfer by moving the protocol to the next menstrual cycle. Avoid the formation of cysts during ovulation. All other actions will depend on the woman herself, her lifestyle and health.

Ovarian hyperstimulation with IVF is a serious problem that can become an obstacle to bearing a baby. But, nevertheless, the GSN is not a reason to refuse the opportunity to become a mother. If hyperstimulation occurs, it must be eliminated in time.

Ovarian hyperstimulation (ovarian hyperstimulation syndrome) is a gynecological disease, the occurrence of which is caused by excessive intake of hormonal agents in order to stimulate ovulation to conceive a child.

Ovarian hyperstimulation syndrome during IVF is a rather dangerous pathological process, as it is characterized by increased blood clotting, excessive hormone production, and ovarian enlargement. It should be noted that ovarian hyperstimulation can develop immediately after the IVF procedure or already during pregnancy.

The clinical picture is characterized by a general deterioration in well-being, pain in the lower abdomen, in some cases present. Diagnosis is carried out by conducting a physical examination with the collection of a personal history, laboratory and instrumental research methods.

Treatment is carried out using conservative methods, as well as minimally invasive surgical interventions. It should be noted that ovarian hyperstimulation during pregnancy is a dangerous disease, as there is a high risk of death.

The prognosis is exclusively individual in nature, since everything will depend on the severity of the pathological process and the general health indicators of the patient.

Etiology

The reasons for the development of such a disease are an excessive amount of hormonal steroid drugs that are used to stimulate the ovaries.

The risk group includes women for whom the following indicators are true:

• age less than 36 years;
• in history;
• previous ovarian hyperstimulation during IVF;
• low body weight, asthenic type physique;
• if after the procedure the number of follicles is less than 35;
• the use of urinary gonadotropins;
• high dosages of gonadotropic hormones;
• use of luteal phase progesterone;
• development of an infertile pregnancy cycle;
• the presence in a personal history of endocrine diseases, hormonal disorders.

Somewhat less, but still there is a risk of developing such a pathological process if:

• there is the formation of single mature follicles;
• there is a weak ovarian response to stimulation;
• excess body weight;
• no personal history of pregnancy.

It is possible to avoid ovarian hyperstimulation during IVF if the procedure is carried out correctly and all the recommendations of doctors are followed.

Classification

According to the severity, the following forms of the pathological process are distinguished:

• Light - this form is almost always present after the puncture, and the general condition of the woman is characterized as satisfactory.
• Medium - the clinical picture is more pronounced, an ultrasound examination may reveal fluid in the abdominal cavity. Most often, this condition of a woman is classified as moderate, and the clinical picture lasts about 10 days.
• Severe - formed, an increase in the ovaries in diameter up to 25 centimeters, the general condition is characterized as severe. There is a pronounced clinical picture.

The critical stage is considered separately, when there is practically no diuresis, the general condition of the patient is characterized as extremely life-threatening. In this case, there is a high risk of death.

Symptoms

The nature of the clinical picture will depend on the stage of development of the pathological process.

So, the mild stage of OHSS is characterized as follows:

• palpation of the lower abdomen can detect the ovaries;
• moderately increased thirst;
• pulling pain in the lower abdomen;
• discomfort and heaviness in the abdomen;
• bloating, slight tension.

Symptoms of ovarian hyperstimulation syndrome with moderate severity of the pathological process are as follows:

• abdominal pain may radiate to the groin area, becomes more pronounced;
• an increase in the abdomen, which will be due to a large amount of exudate in the abdominal cavity;
• increase in abdominal circumference, body mass index may increase;
• nausea, which is often accompanied by vomiting;
• diarrhea;
• dizziness, weakness, increasing malaise;
• general deterioration of well-being.

Diagnostically, an excess of hematocrit by almost two times will be established.

The severe stage of the pathology will be characterized by the following clinical picture:

• the above-described clinical picture will proceed in a more pronounced form;
• lowering blood pressure;
• increase in body temperature;
• increased sweating;
• a feeling of fear, a state close to fainting, loss of consciousness;
• a woman is forced to take an uncomfortable position due to;
• the diameter of the ovaries is 12-25 centimeters;
• swelling of the external genital organs;
• a critical decrease in daily urine output.

The critical stage in the development of the pathological process will have the same symptoms as described above, but in a more severe form.

In addition, the symptoms will be supplemented by the following clinical signs:

• enlarged liver;
• accumulation of fluid in the abdominal cavity - up to 5-6 liters;
• low blood pressure;
• shortness of breath, shallow breathing;
• rapid pulse, increased cold sweating;
• pronounced symptoms of acute respiratory and.

This condition of a woman is extremely dangerous for her life, so medical care should be provided urgently.

Diagnostics

The diagnostic program includes the following laboratory and instrumental diagnostic methods:

• general and detailed biochemical blood test;
• general urine analysis;
• X-ray of the OGK.

Based on the results of diagnostic measures, as well as taking into account the current clinical picture, the doctor determines further therapeutic measures.

Treatment

Treatment will depend on the severity of OHSS. So, with a mild form, specific therapeutic measures are not required, it is enough to follow the general recommendations of the doctor, eat right and observe bed rest.

In all other cases, hospitalization of the patient is mandatory.

Treatment is usually based on the following activities:

• restoration of water and electrolyte balance;
• the introduction of plasma preparations, albumin;
• elimination by taking painkillers;
• elimination of nausea and vomiting.

Fraxiparine is also administered to prevent thrombosis. Therapeutic measures are determined by the doctor on an individual basis.

Complications

The consequences of ovarian hyperstimulation can be expressed in the following complications:

• ovarian necrosis;
• cyst rupture;
• poor ovarian implantation in IVF;

At a severe and critical stage of development of OHSS, there is a high risk of death. Prevention consists in the controlled administration of hormonal drugs and monitoring the patient's condition.

Is everything correct in the article from a medical point of view?

Answer only if you have proven medical knowledge

Diseases with similar symptoms:

It is no secret that microorganisms are involved in various processes in the body of each person, including the digestion of food. Dysbacteriosis is a disease in which the ratio and composition of the microorganisms inhabiting the intestines are disturbed. This can lead to serious disorders of the stomach and intestines.

) involves several successive stages. The first stage is the stimulation of superovulation so that many more eggs are produced in the woman's follicles than usual. The maturation of several follicles in the ovary is achieved by taking special preparations. Usually, after taking them, from 10 to 12 follicles are formed. Naturally, an increased number of simultaneously mature follicles significantly increases the chances of conception, but also increases production, which leads to certain consequences. The next stage is the puncture of the follicles, the taking of eggs. During the third stage, the doctor fertilizes them with "in vitro" spermatozoa. If everything goes well, on about 3-5 days, one (maximum two) of the already formed embryos is selected, which are transplanted into the woman's uterus. Those embryos that remain are frozen to be used if pregnancy does not occur this time.

It seems that the mechanism is clear and, at first glance, not so complicated. It seems, well, a woman cannot get pregnant, she will do IVF and that's it! In most cases, it is. But, as in any matter, there is another side to the coin. Unfortunately not very pleasant.

What is hyperstimulation in IVF?

It turns out that in some women, drugs that are used to stimulate superovulation provoke hyperstimulation syndrome. Every woman experiences this condition in her own way. There are also very difficult cases. They are especially common in women diagnosed with polycystic ovary syndrome (PCOS). If a woman is diagnosed with PCOS, she needs to reduce the dose of the drug.

Ovarian hyperstimulation syndrome is the most serious and very dangerous complication that can occur during in vitro fertilization. Hyperstimulation develops already at the stage of superovulation, but, as a rule, it manifests itself a little later - after it enters the woman's uterine cavity.

If a woman with ovarian hyperstimulation still becomes pregnant as a result of IVF, then the condition of the pregnant woman, due to physiological hormonal changes, is even more aggravated. In some cases, the symptoms of hyperstimulation persist for 10 or even 12 weeks. By the way, it has been established that the earlier hyperstimulation has manifested itself, the more difficult it will be to proceed.

Who can experience hyperstimulation during IVF?

Although hyperstimulation syndrome is a disease that is caused by medical intervention, no doctor can answer the patient with absolute accuracy whether hyperstimulation syndrome threatens her. However, there are certain factors that can contribute to the occurrence of ovarian hyperstimulation. Among them: the genetic predisposition of women under the age of 35 (fair-haired and not prone to fullness), polycystic ovary syndrome, an increased amount of estradiol in the blood, allergic reactions, the use of a-GnRH for the purpose of superstimulation, support for the luteal phase with drugs.

Symptoms of ovarian hyperstimulation during IVF

The development of hyperstimulation may be indicated by several symptoms, which depend on the severity of the disease.

Light degree: slight swelling, an increase in the volume of the abdomen, a feeling of heaviness, pain, as during menstruation, frequent urination. The diameter of the ovaries increases to 5-10 cm.

Average degree: added nausea, vomiting, loss of appetite, diarrhea, bloating, weight gain. The ovaries increase to 8-12 cm.

Severe degree: shortness of breath, heart rhythm disturbances, high blood pressure, a very strong increase in the volume of the abdomen. The ovaries become more than 12 cm in diameter. In some cases, they reach 20-25 cm in diameter.

Complications of ovarian hyperstimulation are ectopic pregnancy, rupture of ovarian cysts, torsion of the uterine appendages. Ovarian torsion can happen because the enlarged ovaries become very mobile. Torsion leads to impaired circulation, followed by necrosis (the ovary dies). A woman with torsion feels a sharp pain, which does not subside in any way, but, on the contrary, intensifies. In this case, the woman needs urgent surgery. If irreversible processes have already occurred, it is necessary to remove the entire ovary or part of it.

The most common complications of ovarian hyperstimulation are ascites (fluid accumulation in the abdomen) and hydrothorax (fluid accumulation in the chest). This happens because the fluid from the bloodstream is not excreted through the kidneys or with breathing, but sweats into the cavity. There are other complications: the formation of blood clots (up to thromboembolism), impaired liver and (or) kidney function.

Treatment of ovarian hyperstimulation in in vitro fertilization

Most doctors are familiar with this problem only in practice. Sometimes a doctor in his entire practice never encounters something like this.

To date, the mechanism for the development of hyperstimulation is unknown, so there is no special specific treatment. The only sure way to be cured is to eliminate the pregnancy. But this is hardly the right way out, since it was for the sake of the onset of pregnancy that in vitro fertilization was carried out, which provoked ovarian hyperstimulation syndrome. Therefore, in a hospital, all actions are reduced to alleviating the condition of the woman and maintaining the pregnancy.

With a mild form of hyperstimulation syndrome, medications are not used. A woman is prescribed peace and proper nutrition, which provides for abundant drinking, a complete and balanced diet. A woman should monitor her weight and daily amount of urine.

In the case of moderate and severe forms of ovarian hyperstimulation syndrome, home treatment will not work. The woman is admitted to the hospital. The hospital monitors her breathing, the work of the cardiovascular system, liver, kidneys. Monitor electrolyte balance (abdominal size, weight, diuresis,). For the treatment of OHSS, drugs are used that reduce capillary permeability, as well as those used to prevent thromboembolism.

In severe cases, with ruptured cysts and internal bleeding, the woman will undergo a puncture of the abdominal cavity and surgery.

After the last stage of IVF - embryo transfer - it is necessary to carefully monitor the condition of the woman. She is prescribed peace and forbidden sexual relations with her husband. Sometimes, after embryo transfer, a woman may develop an inflammatory process.

Any married couple who dreams of a child, but encounters various difficulties on the way to a dream, experiences strong emotional stress. If serious complications are observed, psychological stress is possible. Some women are afraid, for example, that the use of stimulant drugs will provoke ovarian cancer. But, in fact, studies have shown that there is no connection between taking such drugs and ovarian cancer (however, like other organs) does not exist.

Especially for Olga Rizak