Ovarian hyperstimulation is a reaction of the ovaries to a high dose of a hormonal drug that is prescribed to the patient in order to increase the number of mature eggs for IVF.

Ultrasound image of an ovary with hyperstimulation syndrome

The main reason that contributes to the occurrence of ovarian hyperstimulation is an increase in the dosage of the drug administered for in vitro fertilization.

Due to the high concentration of the resulting hormone after puncture, changes begin to occur in the female body: the production of estradiol increases, the blood becomes thicker, the fluid is poorly excreted and is retained in the tissues, thereby causing swelling. As a result, the ovaries are 10-20 cm.

Forms and symptoms

Ovarian hyperstimulation syndrome (OHSS) is one of the common complications of in vitro fertilization. It can occur both during the period of embryo transfer into the uterus and after pregnancy has occurred.

Attention! There is an opinion among experts that the more painful and earlier the symptoms appear, the longer the recovery will be.

There are the following forms of violation:

• light;
• heavy.

Each form of ovarian hyperstimulation syndrome has its own signs and intensity of their manifestation.

Symptoms of ovarian hyperstimulation:

1. Easy shape:

• causeless increase in abdominal size/waist size by 3 cm or more;
• pain in the lower abdomen;
• aching, nagging pain in the ovarian area, a feeling of fullness;
• weight gain;
• urinary disturbance.

Important! The appearance of the above symptoms is explained by an increase in the size of the ovaries, poor circulation, the development of cystic neoplasms, inflammation (,), and accumulation of fluid in the body.

1. Average:

• painful sensations in the ovarian area, which become more acute when bending the body or other sudden movements;
• pain in the lower abdomen is constant and radiates to the leg or sacrum;
• swelling of the arms, legs, external reproductive organs (labia, clitoris);
• dizziness, darkening of the eyes;
• dysbacteriosis;
• weight gain.

1. Heavy:

Severe ovarian hyperstimulation syndrome is characterized by an increase in ovarian size of more than 12 cm and sudden impairment of kidney function. In this case, the patient requires urgent medical care and hospital treatment.

At-risk groups

Unfortunately, it is impossible to say with certainty which patients will develop OHSS. However, doctors say that the likelihood of the disorder occurs in women who:

• suffer from an allergic reaction;
• thin build and fair haired;
• have neoplasms on the ovaries (cystic,);
• undergo GnRg-a stimulation and support the luteal phase with human chorionic gonadotropin preparations;
• have high levels of estradiol in the body.

That is why, in order to prevent possible risks and complications of IVF, each patient is prescribed a full examination and a series of tests.

Treatment methods

Treatment for ovarian hyperstimulation depends on the severity of the disease. Let's take a closer look at each form and the corresponding treatment methods.

Light form

Treatment for mild forms of ovarian hyperstimulation involves lifestyle changes and not taking any medications.

First of all, the patient is recommended to introduce protein into her daily diet. However, the best option would be a high-protein diet. Nutrition for OHSS also involves eating large amounts of greens, boiled fish, lean meat, fruits and vegetables.

A woman with this disorder should drink at least 3 liters of fluid per day. The most useful and effective will be rosehip tincture, green tea, fruit drinks, compotes, and still mineral water.

Remember! Drinking alcohol and coffee during OHSS is strictly prohibited!

Treatment of mild forms also involves regular monitoring of weight and measuring the amount of urine per day. Thus, frequent urination may indicate a deterioration in the body’s condition and the transition of OHSS to a severe form.

The patient is prohibited from any physical activity, training, heavy lifting, overwork, stress and nervousness. Sex should also be avoided until complete recovery.

Moderate and severe form

Moderate and severe ovarian hyperstimulation syndrome requires constant monitoring and monitoring of the general condition of the patient’s body, so treatment takes place only in a hospital.

Upon admission to the hospital, the woman is initially measured for abdominal size, weight, diuresis, an ultrasound of the kidneys and liver, a cardiogram and a blood test for Ht (hematocrit). Based on the results of the examination, the doctor chooses a treatment method - medication or surgery.

Drug therapy consists of taking corticosteroids, antiprostaglandins, antihistamines and thromboembolic prophylactic drugs (Clexane, Fraxiparine, etc.). Sometimes the patient undergoes blood purification (plasmapheresis).

Surgical intervention for ovarian hyperstimulation is carried out only as a last resort. Everything depends not only on the degree of the disease, but also on the presence of tumors on the ovaries and internal bleeding. So, if a large size, rupture or malignancy is detected, the doctor prescribes laparoscopy or laparotomy. At the same time, he prescribes conservative therapy, which consists of:

• relieving painful symptoms by taking painkillers;
• balancing blood circulation with plasma, albumin and protein, which are administered intravenously;
• eliminating nausea, dizziness, vomiting;
• normalization of water and electrolyte balance.

Remember! Early diagnosis and timely treatment allows you to get rid of OHSS within 3-6 weeks!

Consequences of OHSS

Among the main consequences of ovarian hyperstimulation are:
ie:

1. Exacerbation of chronic diseases.
2. Poor implantation of embryos during IVF.
3. Necrosis of the ovary, which threatens complete removal of the organ or part thereof (oophorectomy, resection).
4. Rupture of the cyst, torsion of its stem or the ovary itself.
5. Thrombosis.
6. Acute renal and liver failure.

Important! If conception occurs, the patient’s general condition worsens and will last until the 12th week of pregnancy.

Preventive measures

How to avoid ovarian hyperstimulation? First of all, you need to reduce the dosage of gonadotropin (hCG) during IVF or completely eliminate hormone stimulation. Of course, the chances of conceiving a child are greatly reduced, but the expectant mother’s body is not subjected to any unusual stress.

Prevention of OHSS during stimulation also implies timely disposal of cystic neoplasms on the ovaries. To do this, a specialist regularly performs ultrasound of the pelvic organs.

If a woman is at risk of developing a disease directly during pregnancy, then most often the doctor suggests freezing the embryos and transferring them in the next favorable cycle.

Remember! Prevention of ovarian hyperstimulation involves constant monitoring of the growth and development of follicles and proper dosage of hormones.

Ovarian hyperstimulation syndrome during IVF

As a result of intense hormonal stimulation carried out to obtain the maximum number of eggs during IVF, a rather unpleasant condition can occur - syndrome ovarian hyperstimulation(OHSS).

Causes of ovarian hyperstimulation

The main cause of ovarian hyperstimulation syndrome is a side effect of the drugs used in the IVF protocol. The trigger mechanism is recognized as hormonal drugs containing hCG. It is these drugs that are administered 36 hours before puncture to ensure complete maturation of the eggs. Doctors are fully aware of the possible consequences; IVF is iatrogenic.

But without prescribing an hCG injection, the opportunity to obtain oocytes capable of fertilization will be missed.

Changes in the body with OHSS

The origin of OHSS is complex and not fully established. It is believed to trigger biochemical reactions that negatively affect the vascular system. Control over the functioning of the ovaries is lost. They increase in size (sometimes reaching 10 cm or more in diameter). .

The level of prostaglandins, histamine, and estradiol increases in the blood. These substances have a negative effect on blood vessels. The result is an increase in the permeability of the vascular wall. The liquid fraction of blood enters the extravascular space and accumulates in the abdominal, pleural cavities, pericardium (pericardial sac) and tissues. The blood thickens. The liver and kidneys are involved in the process.

How to avoid ovarian hyperstimulation during IVF?

A risk group has been identified for hyperstimulation syndrome. This includes patients:

• young age (up to 35);

• with a reduced body mass index;

• having a history of allergic reactions;

• who have had this syndrome before;

• in which a very large number of follicles mature;

• having high estradiol activity in plasma (determined in a blood test);

• stimulation of which occurs with the use of GnRH agonists.

Be sure to monitor membership in a risk group in the preparatory stage. With IVF, ovarian hyperstimulation syndrome occurs in almost all women, but it only occurs in a mild form (and this cannot be avoided). The attention of doctors and their prescriptions are aimed at preventing the development of moderate and severe degrees of the pathological process.

Ovarian hyperstimulation: symptoms

Symptoms of ovarian hyperstimulation do not appear simultaneously with the administration of drugs, but after several days (2–4).

In many ways, the course of OHSS depends on:

• drugs used in the IVF protocol;

• individual characteristics of the body;

• number of mature eggs.

A mild degree of the syndrome includes the following symptoms:

• the appearance of edema in the lower extremities and slight weight gain;

• pain, discomfort in the lower abdomen;

• general health decreases;

• bloating.

There is no drug treatment for mild ovarian hyperstimulation. Help is limited to bed rest, a protein diet and increased fluid intake.

The average degree of OHSS consists of the following symptoms:

• nausea;

• abdominal pain spreading to the sacral, lumbar regions, lower back;

• the appearance of tension in the anterior abdominal wall, increasing bloating;

• diarrhea;

• constipation;

• headache;

• symptom of “appearance of floaters before the eyes”;

• decrease in diuresis (volume of urine excreted);

• weight gain 2–3 kg;

• the appearance of edema in the upper extremities and genitals.

If you experience such symptoms, you need to contact your doctor and begin treatment in a hospital to alleviate your condition and prevent the development of a severe form. You can't delay!

Treatment of moderate severity of ovarian hyperstimulation syndrome

Before starting therapy, it is necessary to determine the severity. To do this, a number of additional studies need to be done.

Treatment for ovarian hyperstimulation syndrome depends on the results obtained and the severity of symptoms. Depending on the condition, treatment can be carried out under conditions of complete or partial hospitalization (after completing the prescribed procedures, you can return home daily).

Therapeutic measures:

• Volume replenishment and blood thinning. Sweating of plasma from the vascular bed leads to dehydration, blood volume decreases, blood density increases, and the risk of blood clots increases. To overcome these processes, intensive infusion therapy is necessary: ​​intravenous drip administration of large volumes of colloid-crystalloid solutions.

• To reduce swelling and fluid accumulation in the cavities, albumin solutions and plasma are administered intravenously.

• Pain therapy.

• Blood thinners.

• Medicines to relieve vomiting.

Surgical treatment is used in severe cases:

• Laparocentesis. It is aimed at removing accumulated fluid from the abdominal cavity. A puncture is made in the abdominal wall and the fluid is allowed to drain.

• Thoracentesis. Through a puncture of the chest wall, the fluid that is compressing the lungs is removed.

• Hemodialysis is extrarenal (using a machine) blood purification in case of renal failure. This method is known as “artificial kidney”.

A successful recovery from hyperstimulation syndrome during IVF does not guarantee its return after pregnancy. The fact is that during pregnancy the body independently produces hCG, which can trigger the development of such a symptom complex as ovarian hyperstimulation. But there is no need to be afraid. The main thing is that you are aware of the possible development of such a condition. And you already know what to do when it appears.

Induction of ovulation, or artificial stimulation of follicle maturation through hormonal drugs, the indications for which are constantly expanding, is one of the achievements of modern reproductology.

As the main component of a number of reproductive technologies, ovarian hyperstimulation is used during IVF, during artificial insemination, in case of luteal phase deficiency, transfer of zygotes or gametes into the fallopian tubes, etc. However, the possible negative consequences of this procedure (for their prevention, timely diagnosis and providing qualified assistance) require the knowledge and experience of doctors.

What is the danger of ovarian hyperstimulation and what is it?

Its rather serious, although not common, complication is ovarian hyperstimulation syndrome (OHSS). It can occur with varying degrees of severity and sometimes be fatal.

Definition of pathology and its statistics

The disease is currently considered as a systemic inflammatory process of the endothelial layer of blood vessels, representing an excessive systemic reaction of the body. OHSS is manifested by a complex of clinical symptoms, syndromes and laboratory parameters. It develops, as a rule, in response to the sequential administration of gonadotropic hormones (follicle-stimulating hormone in the first phase of the menstrual cycle and human chorionic hormone in an ovulatory dose) in accordance with classical programs or stimulation of superovulation.

Due to the lack of a single, generally accepted classification, statistical assessment is difficult and is based mainly only on cases of moderate and severe severity that required assistance to women in a hospital setting. On average, the frequency of the syndrome is 0.5-33% (with various stimulation schemes), and the frequency of its severe forms is 0.2-10%.

There are isolated cases of self-occurring hyperstimulation syndrome in the first trimester of spontaneous pregnancy, as well as rare cases of spontaneously occurring recurring familial episodes of the syndrome that are not associated with ovulation stimulation and reproductive technologies. It is believed that they may be the result of mutations in the follicle-stimulating hormone receptors, resulting in significantly increased sensitivity to human chorionic gonadotropin.

In most cases, this complication is a consequence of the use of gonadotropins in the form of injections in IVF programs; sometimes it occurs as a result of the use of Clomiphene citrate.

Pathogenesis and predisposing factors of the disease

The final mechanism of development of the pathology remains unclear, however, a prerequisite for adequate intensive treatment is taking into account the main features of the pathogenesis of the disease.

Physiological for the female body is the maturation of, as a rule, one, less often two oocytes at the same time, which are at the preovulation stage. The menstrual cycle is associated with the production of fluid into the abdominal cavity by the ovaries and peritoneum. Its volume, insignificant during the follicular phase, increases towards the period of ovulation, reaches its maximum value after it, then gradually decreases by the first day of menstruation.

This is explained by cyclic changes in the permeability of ovarian vessels during the growth of the dominant follicle, the formation of it and the corpus luteum. All processes are associated with changes in the levels of sex hormones, in particular estradiol and progesterone, as well as prostaglandins, cytokines, vascular epithelial growth factor, histamine and other biologically active substances that contribute to an increase in the permeability of the vascular wall and, accordingly, a change in the volume of fluid in the abdominal cavity.

The meaning of the mechanism of development of ovarian hyperstimulation syndrome comes down to the fact that artificial superovulation in assisted reproductive technology programs is a deliberate violation of the physiological principle aimed at the simultaneous maturation of 10-20 or more follicles in order to select the best egg. As a result of this, multiple cysts form in the ovaries and the first ones increase in volume.

It is assumed that the introduction of an ovulatory dose of human chorionic gonadotropin and the formation of a large number of follicles with the formation of a correspondingly increased total volume of intrafollicular fluid, which contains large quantities of macrophages and cytokines involved in immune reactions, is a trigger factor for the development of the disease.

Under its influence, abnormally high amounts of sex steroids and biologically active substances enter the blood. Activation of the body's renin-angiotensin-aldosterone system occurs, which is one of the links in the development of the pathological process. Of particular importance is the excessive secretion of vascular endothelial growth factor by the ovaries, leading to damage to the endothelial cells of the inner lining of blood vessels.

As a result of these mechanisms, the permeability of the walls of the capillary network of tissues of many organs for proteins that carry water with them increases. Massive sweating of varying degrees of severity occurs and a significant redistribution of a significant volume of the liquid part of the blood from the bloodstream into the organ cavities occurs. These are the pleural, pericardial, abdominal (from the vessels of the omentum and peritoneum) cavities. Hydrothorax, hydropericardium, ascites and, less commonly, anasarca are formed.

A decrease in intravascular blood volume leads to hypovolemia, a decrease in blood pressure, a compensatory increase in the number of heart contractions, a decrease in renal blood supply and a decrease in renal filtration, disturbances in the water-electrolyte balance and the acid-base state of the blood, as well as thickening of the blood and an increase in its coagulability. Blood thickening and increased coagulability are the cause of the formation of blood clots and associated complications.

Thus, the secondary consequences of the mechanisms of ovarian hyperstimulation syndrome are dysfunction of the heart, liver and kidneys, the development of adult respiratory distress syndrome, hypovolemic shock, disseminated intravascular coagulation syndrome with the formation of thrombosis and thromboembolism. In addition, less dangerous complications are possible, such as intra-abdominal bleeding, torsion of the uterine appendages, and exacerbation of long-term chronic diseases.

There are two types of hyperstimulation syndrome depending on the time of its development:

1. Early.
2. Late.

Early syndrome extremely rarely begins against the background of direct stimulation of hyperovulation. This usually occurs immediately after follicular puncture or during the first 7-10 days before transfer of the embryo into the uterine cavity. It is associated with the introduction of an ovulatory dose of drugs (mainly human chorionic gonadotropin), which have a stimulating effect on the growth and maturation of follicles. The early development of pathology is the cause of a high frequency of spontaneous miscarriages.

Late syndrome is explained by a significant increase in the level of human chorionic gonadotropin during implantation and early pregnancy. If, after transfer of the embryo into the uterine cavity, implantation of a fertilized egg occurs, then in most cases there is a deterioration in the general condition of the woman, which lasts until approximately 12 weeks of pregnancy. The earlier the symptoms of the syndrome appear, the more severe its course.

If pregnancy does not occur after ovarian hyperstimulation, then (most often) the symptoms of the pathology that arise disappear at the onset of menstruation. Only in rare cases, in the absence of pregnancy, signs of OHSS may persist or even increase for some time.

The planning of hyperovulation induction by a fertility specialist takes into account the initial risk factors. These include:

• The woman's age is less than 36 years.
• Cases of ovarian hyperstimulation syndrome in the past.
• Body type of asthenic type and very low body weight (BMI less than 18.5).
• Availability.
• High levels of total estradiol in the blood - more than 4,000 pg/ml.
• Anti-Mullerian hormone concentration more than 3.6 ng/ml
• The number of follicles after stimulation is more than 35.
• Use (for induction purposes) of urinary gonadotropins - Menogon, Humegon, etc.
• Stimulation with GnRH agonists such as human menopausal gonadotropin or Clomiphene citrate.
• Supporting the second phase of the menstrual cycle and/or stimulating hyperovulation using human chorionic gonadotropin preparations such as Pregnil, Ovitrel, etc.
• High dosages of gonadotropic hormones, although the dependence of the development of the pathological condition on the dose is questionable.
• Support through progesterone of the luteal phase.
• Development of an infertile pregnancy cycle.

The least danger of the disease is observed when:

• woman's age is less than 36 years;
• overweight;
• weak ovarian response to stimulation;
• the formation of single mature follicles in response to the induction of superovulation.

Symptoms of ovarian hyperstimulation

Depending on the severity of the clinical picture and the nature of laboratory changes, 4 degrees of severity of the disease are distinguished:

1. Easy.
2. Average.
3. Heavy.
4. Critical.

Mild severity

Almost always accompanies ovulation induction procedures. The general condition of the woman is usually satisfactory. The main sensations during ovarian hyperstimulation are discomfort and heaviness in the abdomen, moderate thirst. A slight nagging pain appears in the abdomen. Its swelling and slight tension are noted, and upon palpation of the lower sections, the ovaries can be identified.

When performing an ultrasound, multiple follicles and luteal cysts are determined in the ovaries; the diameter of the ovaries is less than 8 cm. In addition, a small amount of fluid may sometimes be present in the pelvis. Hematocrit values ​​are normal.

Average degree

The general condition sometimes remains relatively satisfactory, but is more often regarded as moderate. The intensity of abdominal pain increases, which is associated with increasing irritation of the peritoneum by enlarged ovaries and an increase in the volume of exudate in the abdominal cavity. The subjective symptoms mentioned above are more pronounced compared to mild severity. These are accompanied by symptoms of gastrointestinal disorders - nausea, vomiting, and sometimes diarrhea. There is a moderate increase in abdominal circumference and body weight due to increased fluid consumption and its redistribution into free cavities.

The pulse rate and number of respirations increase slightly. The size of the abdominal circumference and body weight increase even more. Ultrasound reveals the presence of ascitic (exudate) fluid in the abdominal cavity and an increase in the diameter of the ovaries to 12 cm. Hematocrit values ​​do not exceed 45%. Signs of moderate pathology in most women persist for 10 days after administration of hCG in an ovulatory dose.

Severe degree

Most often, the criteria for distinguishing it from the moderate severity of hyperstimulation syndrome are ambiguous. The general condition is assessed as serious. Subjective symptoms may include a feeling of fear, dizziness and headache, a feeling of “floaters” before the eyes. Due to the development of respiratory and heart failure, the woman’s position in bed is forced - sitting or with the head end of the bed significantly raised. Shortness of breath, rapid pulse and decreased blood pressure, increased body temperature (in 80% of women) are noted against the background of the development of a respiratory infection, urinary tract infection, abscesses at injection sites, etc.

The abdomen is dense on palpation and significantly increased in volume due to ascites. When performing radiography or ultrasound, fluid is sometimes detected in the pleural and pericardial cavities; the diameter of the ovaries exceeds 12 cm - up to 25 cm. With echocardiography, cardiac output and venous return of blood are reduced, the end-diastolic volume is reduced, and fluid is sometimes detected in the pericardial cavity. Sometimes swelling of the face and lower extremities is possible, and in rare cases, anasarca. Due to poor circulation in the pelvic organs, swelling of the external genitalia may appear.

Laboratory tests - a decrease in daily diuresis (the amount of urine per day), blood tests indicate an increase in hematocrit of more than 45%, the number of leukocytes more than 15x10 9 / l, an increase in hepatic aminotransferases and a decrease in total blood protein, an increase in the specific gravity of urine and an increase in protein in it .

Critical degree

Characterized by severe or extremely severe general condition. Complaints and subjective sensations are the same as in severe cases. The amount of urine excreted is significantly reduced. Daily diuresis is less than 1,000 ml.

On external examination of the patient - shortness of breath, rapid pulse, low blood pressure, symptoms of peritoneal irritation, enlarged liver, tense and even more enlarged abdomen due to significant accumulation of ascitic fluid (up to 5-6 l), easily palpable in its lower parts enlarged ovaries. X-ray or echography often reveals a large amount of fluid in the pleural cavities. Symptoms of respiratory and heart failure are expressed.

In blood tests, the hematocrit exceeds 55%, the number of leukocytes exceeds 25x10 9 g/l, electrolyte imbalance and hemocoagulation disorders are determined. Symptoms of respiratory distress syndrome and acute renal failure develop, thrombosis and thromboembolism appear, and severe multiple organ failure develops with corresponding indicators of laboratory and instrumental studies.

Treatment of ovarian hyperstimulation syndrome

In mild cases of OHSS, observation and treatment are carried out on an outpatient basis. Restriction of sexual intercourse and physical activity, a diet high in protein and limited in fiber-rich foods are recommended; fluid intake is allowed depending on need. The liquid should be mainly in the form of mineralized water - to prevent disturbances in water-electrolyte balance.

Considering the possibility of a rapid increase in the severity of a woman’s condition, treatment of moderate and severe disease is carried out only in specialized specialized hospitals with intensive care and resuscitation departments or wards. This allows for a thorough examination and monitoring of body weight, functions of vital organs, acid-base status, water and electrolyte balance, as well as hematocrit indicators, which are one of the most important criteria for assessing the severity of the disease. Observation and treatment should be carried out by doctors who have experience in managing patients with this pathology.

The main medications for ovarian hyperstimulation syndrome are drugs that help restore the volume of circulating blood (circulating blood volume). They are necessary to reduce blood clotting and maintain renal filtration. They are administered intravenously. Therapy begins with balanced crystalloid solutions in the form of Ringer's solution, isotonic sterofundin, Trisol, ionosteril. In some cases (hyperkalemia), an isotonic sodium chloride solution is used.

The choice of crystalloid solutions is carried out in accordance with the indicators of the balance of electrolytes in the blood. At the same time, the clinical guideline for their sufficiency is monitoring of hematocrit, central venous pressure and laboratory data of renal function.

After infusion of crystalloids for severe ovarian hyperstimulation, colloidal plasma-substituting solutions based on hydroxyethyl starch (HES) are prescribed: Infucol, Volutenz, Voluven, Volucam, Refortan. They remain in the bloodstream for a long time, improve the rheological properties of the blood, help normalize central and peripheral circulation, microcirculation, vascular wall permeability, oxygen delivery to tissues, reduce the inflammatory response, activate the immune system, etc.

In addition, unfractionated and low molecular weight types of heparin (Fraxiparin, Dalteparin, etc.) are prescribed to prevent the formation of blood clots, immunoglobulins and antibacterial drugs to prevent secondary infections, antispasmodics and paracetamol to reduce abdominal pain, etc.

In the presence of progressive tense ascites and associated disorders of the general condition, breathing, and cardiac activity, fluid is evacuated from the abdominal cavity through an abdominal or transvaginal puncture. A critical degree of pathology is an indication for artificial termination of pregnancy.

How to avoid the development of a pathological condition

Currently, a unified approach to preventing the development of complications has not yet been developed. The first and important condition for prevention is the individual determination of early and late risk factors in a particular patient. The main prevention of ovarian hyperstimulation syndrome is:

• reducing the dosage of gonadotropic hormones, especially when introducing a starting dose;
• refusal to use an ovulatory dose of human chorionic gonadotropin;
• the use of carbegoline (Dostinex) as a powerful agonist of type 2 dopamine receptors on the day of use of the drug that triggers ovulation and/or after transfer of the embryo into the uterine cavity;
• later initiation of the use of gonadotropic hormones or early administration of human chorionic gonadotropin, which helps reduce the stimulation time;
• performing aspiration of accessible follicles;
• the use of progesterone instead of human chorionic gonadotropin to maintain the luteal phase.

This pathology, associated mainly with the development of assisted reproduction technologies, is relatively new. It can lead to serious complications that pose a danger not only to a woman’s health, but also to her life. Treatment methods are mainly syndromic and symptomatic. In this regard, their use requires the presence of experienced reproductive specialists, anesthesiologists and resuscitation specialists and careful development of the principles of preventive measures.

) involves several successive stages. The first stage is the stimulation of superovulation, so that the woman’s follicles produce many more eggs than usual. The maturation of several follicles in the ovary is achieved by taking special medications. Typically, after taking them, 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 follicle puncture and egg collection. During the third stage, the doctor fertilizes them with sperm “in vitro”. If everything goes well, on about 3-5 days, one (maximum two) is selected from the already formed embryos, 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 can’t get pregnant, she’ll do IVF and that’s it! In most cases, this is true. But, as with any issue, there is another side to the coin. Unfortunately, not very pleasant.

What is hyperstimulation during IVF?

It turns out that in some women, drugs that are used to stimulate superovulation provoke hyperstimulation syndrome. Each woman experiences this condition differently. There are also very difficult cases. They are especially often recorded 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 does become pregnant as a result of IVF, then the pregnant woman’s condition is further aggravated due to physiological hormonal changes. In some cases, symptoms of hyperstimulation persist for 10 or even 12 weeks. By the way, it has been established that the earlier hyperstimulation manifests itself, the more difficult it will be.

Who may experience hyperstimulation during IVF?

Although hyperstimulation syndrome is a disease that is caused by medical intervention, no doctor can answer a patient with 100% accuracy whether she is at risk of hyperstimulation syndrome. However, there are certain factors that can contribute to the occurrence of ovarian hyperstimulation. Among them: genetic predisposition of women under the age of 35 (fair-haired and not prone to obesity), polycystic ovary syndrome, increased amount of estradiol in the blood, allergic reactions, use of GnRH a-for the purpose of superstimulation, support of 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, increased abdominal volume, feeling of heaviness, pain, as during menstruation, frequent urination. The diameter of the ovaries increases to 5-10 cm.

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

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

Complications of ovarian hyperstimulation include ectopic pregnancy, rupture of ovarian cysts, and torsion of the uterine appendages. Ovarian torsion can happen because the enlarged ovaries become very mobile. Torsion leads to poor circulation followed by necrosis (the ovary dies). When a woman is torsioned, she feels a sharp pain that does not subside, but on the contrary, intensifies. In this case, the woman needs urgent surgery. If irreversible processes have already occurred, the entire ovary or part of it has to be removed.

The most common complications of ovarian hyperstimulation are ascites (fluid accumulation in the abdomen) and hydrothorax (fluid accumulation in the chest). This happens because fluid from the bloodstream is not removed through the kidneys or through 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 during in vitro fertilization

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

To date, the mechanism of development of hyperstimulation is unknown, so there is no special specific treatment. The only sure way to cure is to eliminate the pregnancy. But this is hardly the right solution, since it was for the sake of pregnancy that in vitro fertilization was performed, which provoked ovarian hyperstimulation syndrome. Therefore, in a hospital setting, all actions come down to alleviating the woman’s condition and maintaining the pregnancy.

In mild forms of hyperstimulation syndrome, medications are not used. The woman is prescribed rest and proper nutrition, which includes drinking plenty of fluids and eating a nutritious and balanced diet. A woman should monitor her weight and daily urine output.

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 is monitoring her breathing, the functioning of the cardiovascular system, liver, and kidneys. Electrolyte balance is monitored (abdominal size, weight, diuresis,). To treat 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 abdominal puncture and surgery.

After the last stage of IVF - embryo transfer - it is necessary to carefully monitor the woman’s condition. She is prescribed rest and sexual relations with her husband are prohibited. 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 their dream, experiences strong emotional stress. If serious complications are observed, psychological stress is possible. Some women fear, for example, that using stimulant drugs will cause ovarian cancer. But, in fact, studies have proven that there is no connection between taking such drugs and ovarian cancer (as well as other organs).

Especially for Olga Rizak

Ovarian hyperstimulation is an artificially induced dangerous condition, accompanied by physical and moral discomfort for a woman. Occurs, as a rule, when using methods of assisted reproductive technologies (IVF). Pathology has different forms and can be characterized by signs that differ in intensity.

It is dangerous to become pregnant with overstimulated ovaries. If conception does occur, then the threat to the fetus remains throughout the entire gestational period.

Ovarian hyperstimulation syndrome is a condition in which multiple enlargement of the gonads occurs due to the growth of several follicles. Depending on the severity of the pathology, these pelvic organs increase several times from 3-4 cm. The gonads can grow up to 20 cm.

Hyperstimulated ovaries appear in women who use assisted reproductive technologies. Isolated cases of OHSS occurring in the natural cycle, without the use of hormonal agents, have also been documented. Hyperstimulation during IVF occurs most often, since the protocol necessarily uses drugs that stimulate follicle growth. This condition can be determined by the characteristic clinical picture:

• ascites – accumulation of aqueous substance in the peritoneal cavity (the abdomen “swells”);
• pain in the lower abdomen (the severity of the symptom depends on the severity of the pathology);
• difficulty breathing resulting from the effect of fluid on the diaphragm in the pleural area;
• nausea accompanied by vomiting and diarrhea (appears due to irritation of the digestive tract);
• anasarca - accumulation of fluid in the lower part of the body, manifested by severe swelling of the arms, fingers, legs and peritoneum;
• decrease in pressure indicators;
• impaired diuresis (less urine is produced).

After puncture, hyperstimulation may worsen, as a corpus luteum forms in place of the former follicles. Transfer of fertilized eggs in such situations is not recommended. However, medical practice shows that at the discretion of the doctor and after assessing the stage of the pathological process, in isolated cases the protocol ends with planned implantation.

With a pronounced stage of hyperstimulation, the prognosis is usually unfavorable, since the production of hCG aggravates ovarian hyperstimulation during IVF, and pregnancy is complicated.

In vitro fertilization must be approached taking into account the individual characteristics of the female body in order to prevent a condition such as hyperstimulation.

Risk factors for developing OHSS

For some women, it is possible to predict in advance the likelihood of multiple enlargement of the gonads. The following groups of patients are prone to pathology:

• fair-haired under the age of 35;
• with a diagnosis of polycystic disease and frequent formation of functional cysts on the ovaries;
• with an increase in the amount of secreted estradiol;
• prone to allergic reactions;
• with prior administration of gonadotropin-releasing hormone agonists;
• with the support of the second phase with hCG drugs.

Ovarian hyperstimulation syndrome can be prevented by addressing risk factors. Based on the available information about the patient, the doctor will select the best dose of hormonal drugs. Thanks to the knowledge, qualifications and ability of reproductive specialists to evaluate prognoses, ovarian hyperstimulation during IVF occurs only in exceptional cases. Doctors usually manage to avoid such a complication.

What are the dangers of ovarian hyperstimulation?

The consequences of ovarian hyperstimulation can be very different. Much depends on the stage and form of the pathological process, as well as the timeliness of the assistance provided. The main and most dangerous complication of enlarged gonads will be death. With active fluid intake, cardiac and renal failure occurs, as well as acute thromboembolism. The mechanism of development of pathology is as follows:

1. under the influence of drugs, the work of the sex glands is activated, as a result of which massive growth of follicles begins;
2. plasma and proteins penetrate from the blood vessels of the gland into the peritoneal cavity;
3. the blood thickens greatly, increasing the risk of blood clots;
4. due to an increase in blood viscosity and a decrease in its volume, acute failure of some organs occurs (the heart and kidneys are at risk).

After embryo transfer (if the manipulation was considered acceptable and carried out), symptoms of hyperstimulation may persist for several months. During this period, a serious threat to the fetus arises. The likelihood of miscarriage with OHSS is many times higher than without it. Pregnancy and ovarian hyperstimulation together can seriously complicate the patient’s condition. Throughout the entire gestation period, the risk of fetoplacental insufficiency, the threat of premature birth, hormonal imbalance, circulatory disorders and hypoxia for the child remains. According to statistics, a baby born after OHSS is more likely to have health problems in the first days of life.

During pregnancy, after IVF, and even several years after childbirth, ovarian depletion may occur against the background of OHSS. The culmination of this complication is early menopause.

Stages of ovarian hyperstimulation

Symptoms of ovarian hyperstimulation have different intensities, which characterize the stages of enlargement of the gonad: mild, moderate, severe. Pathology is also divided into two forms:

• early - signs of hyperstimulation appear immediately after the follicle matures and go away on their own with the beginning of a new menstrual cycle (if pregnancy occurs, OHSS requires mandatory therapy, as it risks developing into a late form);
• late - symptoms appear from 4-5 weeks of pregnancy and persist for several months, are severe and require mandatory treatment.

The severity of symptoms gives the doctor the opportunity to understand how serious the pathological process is and whether it requires intervention.

Light degree

Early hyperstimulation syndrome occurs in almost all women undergoing IVF. At the same time, the size of the ovaries increases by one and a half to two times. Multiple follicles and cysts are visualized in the ovaries on ultrasound. The woman feels a slight nagging pain and bloating. During an ultrasound examination, a small accumulation of fluid in the abdominal cavity may be detected. This condition can be considered normal in the IVF protocol.

Average degree

Moderate ovarian hyperstimulation is characterized by pain in the lower abdomen and a slight increase in its volume. Ultrasound data show the presence of fluid in the abdominal cavity, and the gonads are enlarged to 12 cm. A characteristic difference between moderate and mild is the inclusion of the digestive tract in the process, which is manifested by nausea, vomiting and diarrhea.

Severe degree

One of the characteristic signs of the syndrome is swelling of the legs.

To characterize the severe form of OHSS, the main symptoms can be noted: significant enlargement of the abdomen due to fluid accumulation, pain and discomfort, swelling of the lower extremities. There are also disturbances in the functioning of the heart, which causes tachycardia and shortness of breath. The woman is forced to adhere to bed rest. Breathing becomes easier when you take a semi-sitting position with your torso elevated.

Diagnostic measures show that the ovaries are enlarged in volume up to 25 cm, the number of leukocytes in the blood is increased, the density of blood and urine is increased. The total amount of urine excreted decreases. Additionally, body temperature may increase.

Critical degree

The most severe degree of OHSS is critical. The total volume of urine excreted is reduced to 1 liter. The pulse is rapid, breathing is difficult. Blood pressure is reduced. The abdomen swells greatly (up to 6 liters of fluid accumulates there). There are symptoms of thrombosis and thromboembolism. This condition requires urgent medical intervention.

Treatment of ovarian hyperstimulation syndrome

In the mild stage of hyperstimulated ovaries, outpatient treatment is carried out, which does not involve the use of medications. The patient is recommended bed rest and psycho-emotional rest. The diet for ovarian hyperstimulation is protein. It is necessary to limit the consumption of salt, bran and completely eliminate alcohol. You should drink as needed, mainly mineral water.

In the case of a moderate condition, therapy is carried out in a hospital due to the likelihood of rapid progression of the pathology. Continuous monitoring allows the patient’s well-being to be assessed: indicators of water and electrolyte balance, hematocrit, functionality of vital organs. Constant supervision of medical personnel specializing in such pathologies is necessary.

• Treatment of ovarian hyperstimulation involves the use of medications aimed at replenishing the volume of circulating blood. They help improve kidney filtration and reduce blood density. Physiological solutions are administered intravenously or drip.
• An important aspect in the treatment of OHSS is the prevention of thrombosis. For this purpose, the drugs Fraxiparin or Dalteparin are administered.
• If necessary, the patient is provided with anti-inflammatory, painkillers and antipyretic medications. If possible, Paracetamol, Ortofen, Nurofen are taken orally. In emergency cases, analgesics are administered intramuscularly.
• Antibacterial therapy is prescribed in some cases to prevent infection of the abdominal and pelvic organs. Preference is given to broad-spectrum drugs.

If ovarian hyperstimulation syndrome develops during pregnancy, then the expectant mother must be prescribed maintenance hormonal therapy with progesterone-based drugs. It is also recommended to take antispasmodics, sedatives, and vitamin complexes. Sexual contact should be avoided for the entire period of treatment.

How to avoid ovarian hyperstimulation during IVF

Prevention of ovarian hyperstimulation syndrome begins even before the prescription of stimulant medications. Today there is no specialized unified method for preventing pathology. It is important at all stages of planning to assess the likelihood of early or late risks and calculate the prospects in advance. You can prevent OHSS by the following methods:

• use gonadotropic hormonal agents in the minimum effective dosage for the procedure;
• refuse to administer human chorionic gonadotropin in an ovulatory dose or completely eliminate it;
• take type 2 dopamine receptor agonists from the day of using the medication that triggers the ovulation process;
• reduce stimulation time;
• carry out aspiration of all accessible follicles;
• use progesterone preparations to maintain the second phase instead of drugs based on human chorionic gonadotropin.

It is possible to avoid ovarian hyperstimulation syndrome during IVF in most protocols. OHSS is becoming the exception rather than the rule in the method of assisted reproductive technologies.

It is important that the doctor knows all the characteristics of the patient’s body. If a woman has already had stimulation or had problems with the functioning of the reproductive system, for example, PCOS, all the nuances should be told to the doctor. While taking hormones, you need to carefully monitor your well-being, and if unusual signs appear, notify your fertility specialist.