Hormonal stimulation before eco advice. In vitro fertilization. Step by step. What should you do?

Preparing for the IVF procedure consists, first of all, of leading a healthy lifestyle, eating right, taking medications prescribed by a fertility specialist, passing the necessary tests and undergoing prescribed examinations.

How to prepare for in vitro fertilization

Naturally, several months before the IVF procedure, it is necessary to give up bad habits - smoking and drinking alcohol. Saunas and hot baths are not recommended.

How should you eat? You can't go on unbalanced diets. Nutrition should be complete and varied, include a sufficient amount of vitamins and proteins: fruits, vegetables, herbs, chicken, eggs, fish, cheese. Boil the dishes, cook in a double boiler or bake in the oven. Limit your consumption of smoked, fatty and spicy foods.

Lead an active lifestyle, swim in the pool, run in the park or long distances. However, do not overuse physical activity.

The IVF preparation procedure is aimed at egg maturation. Before a woman should take the following medications:

• A course of antibiotics and vitamin supplements for one or both partners.
• Oral contraceptives starting 3-4 days after the basic ultrasound to exclude ovarian cysts and to program the cycle. Taking them is not mandatory, but helps in programming the cycle.

Stimulation protocols before IVF

To stimulate the ovaries to produce several eggs and, accordingly, increase the chances of pregnancy, two types of drugs are used:

• Drugs for stimulating the ovaries - gonadotropins. These hormones are usually secreted by the pituitary gland to control the number of developing follicles and eggs. They come in 2 types: FSH (follicle stimulating hormone) and HMG (Human menopausal gonadotropin). The drugs are available in 3 forms: urinary (cheapest, extracted from the urine of postmenopausal women), a highly purified version of urinary, and recombinant (more expensive, made in a genetic laboratory).
• Drugs to prevent premature ovulation. GnRH (Gonadotropin Releasing Hormone) analogs and GnRH antagonists: are prescribed to prevent the ovaries from releasing an egg early.

Long protocol

According to the long protocol, women begin injections on the 21st day of the cycle (when 4-5 contraceptive pills remain). The woman is invited to the clinic on day 2 or 3 of her next cycle to begin the actual ovarian stimulation. Before stimulation, an ultrasound and sometimes a blood test are performed.

Short protocols/protocols with antagonists

For women on the short or antagonist protocol, all injections begin on day 2 of the cycle and last 9-12 days until the eggs are mature, as determined by ultrasound.

Ovarian stimulation

Regardless of the protocol used, the patient is provided with a detailed prescription for medications with dosage and injection schedule, and the time of the next visit to the doctor is set. All conditions are case specific and may vary from cycle to cycle.

Many women prefer to have their husbands/relatives/family doctor give them injections at home or even do them themselves. However, injections usually entail minor discomfort and a number of side effects. The main side effect is hyperreaction, which can occur in 1-2 out of 100 stimulations.

Ultrasonography

An ultrasound (ultrasound examination) is mandatory in the stimulation protocol before IVF. An ultrasound with a vaginal probe is done 3-5 days after the prescription of drugs to detect the reaction of the ovaries. It determines the number and size of follicles growing in the ovaries, which gives a prediction of how many mature eggs to expect. It is then decided whether the patient needs to change the dose of the drug, and a day is set for egg retrieval. During the stimulation protocol, an average of three ultrasounds are performed; the presence of the husband is not necessary.

If the ovaries do not respond well to medication and the ultrasound predicts only one or two eggs, the cycle may be aborted as a low-performing cycle.

HCG injections

HCG injections are intended to stimulate the final maturation of eggs before IVF. Egg collection is planned 34-36 hours after the injection. Collection time depends on the number and size of follicles.

The in vitro fertilization method is considered the most effective in the treatment of infertility. With his help, a large number of couples were able to become parents. The course of a natural pregnancy is similar to that resulting from IVF. The only difference is that during artificial insemination the most suitable conditions for successful conception are specially created. Stimulation during IVF is needed to obtain the maximum number of eggs that are mature and suitable for insemination. It is impossible without stimulation of superovulation before IVF; this is one of the mandatory conditions of the procedure.

Stimulation of superovulation with the help of hormonal drugs allows you to obtain more eggs suitable for fertilization from the follicular reserve.

Why is ovulation stimulation needed during IVF?

Before giving a patient IVF, doctors conduct a series of studies to determine the causes of infertility. Most often, pregnancy does not occur due to hormonal imbalance, which negatively affects the activity of the ovaries and the condition of the endometrium. In such cases, therapy is carried out using special drugs that suppress the natural production of hormones and replace them with artificial ones. This stage is considered the most important in the in vitro fertilization program, since it ensures the correct and enhanced functioning of the ovaries.

An individual medication regimen () is developed for each patient, in accordance with the characteristics of the body. The fertility specialist decides which stimulation is best. It is important to strictly follow the dosage and take medications at the same time. The start of hormonal therapy usually coincides with days 3-5 of the menstrual cycle. Under the influence of hormones, several follicles mature at once, whereas under natural conditions everything is limited to only one or two eggs. This entire period takes place under the control of ultrasound diagnostics, which is necessary to determine the most suitable day for.

The more follicles that can be extracted using needle aspiration, the greater the chance of a successful outcome of the procedure. Fertilization of viable eggs is carried out in a special test tube.

Around the fifth day, the strongest embryos, according to doctors, are implanted into the patient’s uterine cavity.

Stimulation protocols before IVF

Fertility doctors use several different types of protocols for ovarian stimulation during IVF. The choice of treatment regimen is based on the individual characteristics of the patient:

1. Causes of deviations in reproductive health.
2. Age.
3. Tendency to allergic reactions.
4. Chronic diseases.
5. Sensitivity to certain types of medications, etc.

The impact of all types of protocols is aimed at partial or complete suppression, first of all, of follicle-stimulating and luteinizing hormones. Instead, artificial analogs begin to work, the dosage of which is selected individually. The entire process is monitored using an ultrasound machine. According to the standards, with hormonal stimulation, the endometrium increases every day by 1 mm, and the follicle - by 2. In cases where the actual indicators are lower than established, doctors increase the dosage or change the drug.

The protocols differ only up to the point of extraction. Of these, long and short protocols are distinguished, or hyper-long and ultra-short, as well as protocols with minimal stimulation. In some cases, IVF is carried out without hormonal therapy in a natural cycle, if there is normal ovulation. Before choosing a protocol, doctors carefully study all diagnostic data, features of the menstrual cycle, the activity of the endocrine system, etc. After all, the reaction of ovarian receptors to stimulation, as well as the likelihood of complications, depends on the chosen treatment tactics.

How long does it take to stimulate?

The period of hormonal stimulation during IVF is determined by a reproductologist. When chosen, stimulation lasts about 10 days. Usually, after the first home injection, the patient needs to come to the clinic for a control ultrasound and hormonal analysis. This is necessary to study the effect of the dose of drugs on the body. If there are no deviations from the norm, the reproductologist decides to start an IVF program. After this, the woman continues to receive injections and visit the clinic to monitor therapy. At the control stage, the dose of the drug can be adjusted.

If a woman is diagnosed with endometriosis, benign neoplasms, ovarian cysts, etc., then it is used, the duration of which is a month or a little more. In some cases, hyperlong stimulation is indicated, lasting about six months.

The stimulation time depends on which protocol will be prescribed by the IVF clinic doctor.

During therapy, women often experience copious, colorless discharge. This sign is considered normal, and it should not cause alarm, since it indicates normal growth of the endometrium. There should be no symptoms such as:

• pain in the lower abdomen;
• itching and discomfort in the genital area;
• greenish discharge with an uncharacteristic pungent, unpleasant odor.

All this may indicate an inflammatory process that should not exist. If such signs occur, you should immediately report them to your doctor.

What drugs are used for stimulation during IVF

Hormonal stimulation of ovulation before IVF is carried out using special synthetic drugs in the dosage prescribed by the doctor. The choice of medications depends on the stage of the intended program:

• During ovarian stimulation, medications based on follicle-stimulating hormone are used.
• Fertilization stage. The active substances of the drugs promote the release of the egg at the right time. Medicines based on human chorionic gonadotropin are used.
• For successful implantation of the embryo in the uterine cavity and its normal further development, medications with progesterone are prescribed.

IVF drugs are a combination of stimulating (at the protocol stage) and supporting hormones (after embryo transfer).

Most often, doctors use medications from the following list:

1. Puregon.
2. Orgalutran.
3. Klostilbegit.
4. Gonal.
5. Cetrotide.
6. Diferelin.
7. Menopur.
8. HCG drugs.
9. Decapeptyl, etc.

Puregon

A gonadotropic agent that promotes the maturation of several follicles at once and replenishes the deficiency of FSH and LH. It is used both as part of an IVF program and to activate natural ovulation. Contraindications to use of the product:

• hypersensitivity.
• tumors of the ovaries and mammary glands.
• uterine fibroid.
• enlarged ovaries.
• abnormalities in the structure of the genital organs that are not compatible with pregnancy.
• pregnancy and lactation.

Puregon can cause, which manifests itself in the form of nausea, abdominal pain, intestinal disorders, etc. There is a risk of an ectopic or multiple pregnancy.

Orgalutran

The drug is in the form of a solution for subcutaneous administration based on the active substance called ganirelix. Used to suppress the synthesis of FSH and LH during stimulation during IVF. The duration of therapy with this medication is five days, and only in a strictly prescribed dosage. Orgalutran is contraindicated in the following cases:

• Disorders of the kidneys and liver.
• Individual intolerance to the active substance.
• Pregnancy and lactation.
• Allergy.

Klostilbegit

The medication can be used in various protocols. The main indications are anovulatory infertility, polycystic ovary syndrome, galactorrhea, etc. The drug is most often used to collect the maximum number of eggs. But it suppresses endometrial growth, so embryo transfer is usually carried out in the next cycle. Clostilbegit has many contraindications and side effects. The entire therapy process must be carefully monitored by a gynecologist.

Gonal

The Italian drug Gonal is one of the most powerful, and its use is justified where other drugs have proven ineffective. Suitable for the treatment of both female and male infertility. Before using it, you should be thoroughly examined by an endocrinologist. It often causes ovarian hyperstimulation syndrome and also contributes to the onset of multiple pregnancies.

Cetrotide

The drug Cetrotide is intended to suppress ovulation. With IVF, this is necessary for the purpose of further superovulation, and for the regulation of the menstrual cycle, so that the follicles can fully mature. When the drug is first administered, the patient should be under medical supervision for an hour, since allergic reactions to the active substance are possible.

Diferelin

is an analogue of gonadotropin-releasing hormone. Creates optimal conditions for the growth and maturation of a large number of follicles. In addition to treating female infertility, IVF with stimulation is used to treat endometriosis, as well as prostate cancer in men.

Menopur

This drug is often used in combination with products containing hCG. It is effective in stimulating the ovaries as it promotes the maturation of follicles. In addition, it improves the condition of the mucous membrane in the uterus and activates the production of estrogen. But before using it, a comprehensive examination is necessary, including that of the sexual partner.

HCG drugs

Made from the urine of pregnant women. Urine undergoes special purification and preparation, then human chorionic gonadotropin is isolated from it. HCG-based drugs are administered two days before the planned oocyte puncture. They are necessary to prepare the follicles for the upcoming procedure. One such injection is enough, after which there are usually no complications. The most commonly used medication is called Pregnil.

Rules for self-administration of drugs

Many patients prefer to inject themselves themselves. Doctors do not object in cases where they have the appropriate skills or have a special injector pen. Some drugs should be administered subcutaneously, while others intramuscularly. Before the first injection, you should carefully read the instructions.

In this video, a girl undergoing the protocol shows how to independently prepare and administer medications at home:

Important rules:

1. The solution must be injected very slowly.
2. Injections should be given strictly at the same time of day.
3. Do not miss the time of administration of the drug, and if you miss it due to forgetfulness or other reasons, immediately notify the doctor to find out further actions.
4. Wash your hands thoroughly before the procedure and disinfect the skin at the injection site.
5. Do not change the dosage under any circumstances.

How to behave during hormonal preparation

Stimulation before in vitro fertilization is a very responsible and difficult period for a woman. At this time, mood swings and feelings of fear that everything will end unsuccessfully are normal. The support of loved ones, the absence of stressful situations and worries is very important. Doctors strongly recommend eating well and properly, often being in the fresh air, and taking long walks.

You need to forget about diets in order to lose weight; you should not allow excessive physical activity.

Nutrition should be varied and balanced. During stimulation during IVF, protein is very useful, as it helps prevent the development of hyperstimulation syndrome. Therefore, it is necessary to consume more lean meat, eggs, dairy and fermented milk products. Fiber contained in vegetables and fruits is needed to normalize digestive processes. If you have problems with the gastrointestinal tract, you need to consult a gastroenterologist to correct your diet.

Other rules that are important to follow:

• Complete cessation of active and passive smoking, as well as any alcoholic beverages.
• Preventing colds and infectious diseases, avoiding crowded places.
• It is unacceptable to take medications that have not been approved by the attending physician, even if you have chronic diseases.
• You cannot take a hot shower or bath, or go to the sauna.
• Drinks containing caffeine are harmful because they affect the hormonal system.

What complications can there be?

Stimulation of superovulation before IVF is a serious burden on the body, which does not always pass without leaving a trace. In most cases, the woman’s well-being and reproductive health are restored after completion of the procedure, but still long-term use of hormonal drugs negatively affects the patient, and often leads to serious consequences.

One of the most common complications of stimulation is ovarian hyperstimulation syndrome.

Ovarian hyperstimulation during IVF is a condition in which the sex glands greatly increase in size due to the growth of follicles. Symptoms of the pathology can occur immediately, or after the embryos are transferred and the long-awaited pregnancy occurs.

The severity of symptoms depends on the severity of the condition:

• Enlargement of the ovaries to 5-10 cm, slight swelling, pain and heaviness in the abdomen, as before menstruation, are signs of the initial degree of the syndrome.
• If the size of the ovaries reaches 12 cm, and nausea and vomiting are added to the above symptoms, then we are talking about a moderate degree.
• When the diameter of the ovaries exceeds 20 cm, arrhythmia and shortness of breath appear, and blood pressure rises, then this is a severe stage of hyperstimulation.

Possible consequences of OHSS during stimulation of superovulation during IVF:

1. Ovarian torsion.
2. Disorders of the liver and kidneys.
3. Ascites (accumulation of fluid in the abdominal cavity).
4. Diuresis disorders.
5. Increased risk of blood clots.
6. Heart failure, etc.

There is a risk group for developing hyperstimulation syndrome, which includes women diagnosed with polycystic disease, as well as those prone to allergic reactions. This complication can be prevented if all risk factors are taken into account and the optimal dose of a suitable hormonal drug is selected.

Be sure to watch the video about complications that may and may not arise during stimulation before IVF:

Multiple pregnancy

As you know, not one, but several embryos are implanted into the uterine cavity at once. This is necessary to increase the chances of a successful IVF outcome. Often two or three embryos take root at once, resulting in a multiple pregnancy, which doubles the load on the entire body and on the reproductive system in particular.

Ectopic pregnancy

This complication during in vitro fertilization occurs very rarely, but still occurs. When an embryo is implanted outside the uterine cavity, the patient feels weakness and dizziness, pain in the abdominal area, and bleeding appears. Such symptoms require immediate medical attention, since an ectopic pregnancy is a serious threat to a woman’s life.

Infertility treatment using IVF is quite complex, but effective. It is very important to contact qualified specialists with extensive experience in order to eliminate all risks and consequences, and get the opportunity to give birth to your own healthy child.

Ask questions in the comments. Tell us about your stimulation experience, what complications did you experience? Write if you liked the article? Don't forget to rate it below. Thanks for visiting. Let complications pass you by.

It is important to remember that each patient has her own individual response to the medications received during treatment, and that each subsequent treatment cycle is different from the previous one. This means that in reality your response will be different from the response of other patients to the same drugs, but your body may also respond differently to each subsequent cycle of IVF treatment, i.e., not the same as in the previous cycle ECO. In this regard, your examination, treatment and, accordingly, its results may differ from those of other patients. We kindly ask you not to compare the results of your examination and treatment, as well as planned future treatment, with the results of examination and treatment obtained from other patients. Although you may find many similarities with them, please remember that IVF and ICSI treatment is a personal matter and that most patients feel uncomfortable and embarrassed about discussing their personal problems publicly.

The information contained in this section of the site should help you undergo IVF treatment. You can find a discussion of various aspects of IVF on our forum.

If you are planning IVF treatment, we recommend that you consult a doctor approximately 1-2 months before the start of the cycle you have chosen for IVF to resolve all your questions. At the appointment, the results of the preliminary examination are re-evaluated, including: examination on a chair, ultrasound, hormonal studies, identification of pathogens of sexually transmitted infections, i.e. standard examination for patients before IVF treatment (“Pre-IVF Examination”). According to indications, additional examination methods are carried out.

You will be given an agreement for IVF treatment (including ICSI methods, assisted hatching, fragmentation removal) for review and subsequent registration. All forms of agreement between the parties for each procedure must be signed by you and your partner before the start of the treatment cycle. You will be informed when you will meet with your doctor to review all the collected documents, receive answers and clarifications to any questions that remain not fully clear to you or your partner.

One of the main requirements for starting IVF treatment is protection from pregnancy in the cycle in which treatment begins using not hormonal, but barrier methods of contraception (condom).

How to increase your chances of IVF success

For women:

• Avoid, if possible, taking any medications other than regular aspirin. If you are prescribed any medications by another doctor, you must inform your doctor before starting treatment.
• Avoid smoking and drinking alcohol.
• Limit your intake of coffee and caffeinated drinks as much as possible (no more than 2 cups per day).
• Avoid dietary changes and weight loss diets during your IVF cycle.
• Refrain from sexual intercourse for 3-4 days before follicle puncture, and subsequently after embryo transfer until the day of the pregnancy test (detailed recommendations will be given to you in the statement on the day of embryo transfer).
• Ordinary physical activity, as well as physical exercise, are not contraindicated until the enlarged ovaries as a result of treatment do not create some discomfort.
• Avoid hot baths, baths and saunas.
• Try to avoid contact with patients with acute respiratory viral infections (ARVI), avoid hypothermia. If your body temperature rises or cold symptoms appear, tell your doctor.

For men:

• An increase in body temperature above 38° C 1-2 months before the IVF / ICSI procedure can negatively affect sperm quality; If you are sick, please measure your body temperature and report any increase (any illness or illness accompanied by an increase in body temperature).
• Visiting baths and saunas is not recommended, as elevated temperatures can adversely affect sperm quality; please refrain from visiting them for at least 3 months before you are due to start treatment.
• Taking medications, drinking alcohol and smoking cigarettes should be avoided before starting IVF/ICSI treatment.
• Do not start any new sports or strenuous activities for 3 months prior to starting IVF/ICSI. If you run, please try to switch to walking without overload.
• Refrain from wearing tight underwear.
• Avoid sexual intercourse for at least 3 days, but no more than 7 days before sperm collection (on the day of follicular puncture).

For both spouses:

If you have a genital herpes infection, you must report the appearance of symptoms preceding the disease (general malaise, general weakness, unmotivated fatigue), acute manifestations of the disease or healing rashes. Regardless of whether a man or a woman suffers from genital herpes, any of the indicated stages of herpes infection will require immediate cessation of IVF/ICSI treatment.

Start of the IVF program

On the eve of the start of the IVF program, 7-10 days before menstruation, you need to make an appointment with your attending physician to conduct an ultrasound of the pelvic organs and assess the condition of the ovaries and the thickness of the endometrium (uterine mucosa). After the doctor verifies the normal condition of the ovaries (absence of ovarian cysts) and endometrium, in the presence of the necessary official documents (a contract for the provision of medical services, an agreement for this method of treatment, signed by both partners) and the results of examinations (“Examination before IVF”) , the doctor enters the patient into the program (IVF treatment cycle).

The patient is given an individual prescription sheet, the rules for administering medications and the “lifestyle” during the IVF treatment cycle are explained in detail. The patient should come to each subsequent appointment with an appointment sheet. The prescription sheet indicates the patient’s name, her age, outpatient card number and describes in detail the entire treatment regimen: the name of the drugs, daily doses, frequency, route and sequence of their administration and the date of each subsequent appearance at the doctor’s appointment. During the treatment cycle, both spouses must strictly follow all prescriptions and recommendations of the attending physician and appear for examination at the appointed time.

The patient is given directions (vouchers) to pay for each stage of IVF treatment. Before each stage of treatment begins, it must be paid in advance.

The ongoing treatment can be stopped at any stage if, in the opinion of the doctor, the chances of successful completion and obtaining good results are extremely low.

The first stage of IVF is stimulation of ovulation

Its goal is to increase the chances of pregnancy. To do this, a woman is prescribed hormonal drugs that cause the simultaneous maturation of several follicles in her ovaries. In each of the follicles, one egg matures, which is collected during puncture. After their fertilization, several embryos are obtained. The more embryos were obtained, the greater the chances of successful development of pregnancy after their transfer to the patient’s uterus.

Drugs to stimulate superovulation:

• GnRH agonists (a-GnRH) – “Diferelin” or “Decapeptyl”;
• GnRH antagonists (anti-GnRH) – “Orgalutran”, “Cetrotide”;
• Preparations of human menopausal gonadotropins (HMG) - “Menopur”;
• FSH preparations – “Puregon”, “Gonal-F”;
• Preparations of human chorionic gonadotropin (hCG) – “Pregnil”.

All these drugs are prescribed according to developed treatment regimens or “protocols for stimulating superovulation.” Currently, several such “stimulation protocols” have been developed and successfully used all over the world, providing for the joint or sequential use of drugs from these groups to achieve the main goal of ovarian stimulation in IVF cycles - the growth of several follicles. Before stimulation begins, your doctor will discuss with you the stimulation protocol that is most suitable for you.

As a rule, a GnRH agonist, Diferelin or Decapeptyl, is first prescribed for 10-14 days from the middle of the second phase of the previous cycle (21 days of the menstrual cycle) to suppress spontaneous ovarian activity. This is not the stimulation itself, but only the preparation of the ovaries for its implementation with HMG or FSH drugs. It is very important because... increases the effectiveness of subsequent stimulation and allows you to reduce the dose of prescribed HMG (FSH) drugs and, accordingly, the cost of treatment. This is an important argument, since all stimulation protocols used in IVF are carried out exclusively with expensive hormonal drugs.

The start of administration of a - GRG usually occurs on the 21st day in a 28-day cycle or the 23rd in a 30-day cycle and lasts, on average, 10-14 days, but possibly longer if the need arises. This scheme for stimulating superovulation is the most traditional, most widespread and effective of all those proposed today. It is called the “long” stimulation protocol.

There are other stimulation schemes (“short” and “ultra-short” protocols), but they are used much less frequently and, mainly, when standard “long” modes are ineffective.

During the 10-14 days of ovarian preparation, the patient needs to come to the doctor only twice: before the start of the administration of a-GnRH (1st appointment, that is, directly entering the IVF program) and after this period (2nd appointment). Of course, if there are no unforeseen reasons for an additional visit to the doctor.

After the required degree of ovarian suppression is achieved under the influence of a-GnH (as judged by the doctor at the 2nd appointment by the decrease in the concentration of estradiol in the blood and the characteristic ultrasound picture), the doctor makes additional prescriptions for the patient. The dose of a-GnRH is halved and a new drug is prescribed directly to stimulate the “suppressed” ovaries - drugs of gonadotropic hormones - "Menopur" or "Puregon" ("Gonal-F") in addition to a-GrH for 12 - 14 days.

The scheme described above - the α-GRG + HMG (FSH) complex - can significantly increase the number of follicles in the ovaries. This, in turn, improves the quantity and quality of the resulting embryos and allows you to plan the treatment cycle taking into account the wishes and needs of the patient: “bring closer” or, conversely, “pushing back” the puncture of the follicles for several days to obtain the eggs that have matured in them without fear that this will worsen treatment results.

This stimulation continues until a single appointment in the middle of the cycle of the hCG drug, which causes the maturation of the eggs in the follicles, which allows them to be prepared for puncture at the second stage of treatment (the stage of puncture of the resulting follicles).

To stimulate ovulation, as a rule, three types of gonadotropins are used: HMG - "Menopur" and FSH - "Puregon" or "Gonal-F".

The first day of administration of gonadotropins is considered the first day of the cycle, and further counting is carried out from this day. This makes IVF treatment cycles different from other stimulated cycles used in assisted reproduction (intrauterine insemination or insemination with donor sperm), in which stimulation begins on the 3rd to 5th day of the menstrual cycle and without prior administration of a-GnRH.

The drugs act on the ovaries and stimulate the maturation of follicles. The dose of the administered drug to stimulate follicular growth is selected individually, taking into account the woman’s age, her weight and the initial state of the ovaries (their functional reserve) and depends on the response of the ovaries to the IVF treatment. This reaction is assessed periodically by the level of sex hormones in the blood serum (estradiol) and the ultrasound picture (the number and size of follicles in each of the ovaries, as well as the thickness of the endometrium).

Carrying out an ultrasound and determining the concentration of estradiol during treatment with hormonal drugs is called “Ultrasound and hormonal monitoring”.

Ultrasound and hormonal monitoring

Ultrasound monitoring is carried out by the attending physician at the appointment, and a blood test for estradiol is taken upon the doctor’s direction in a diagnostic laboratory. Monitoring is not paid separately, since its cost is included in the cost of this stage of treatment. The frequency of monitoring is set by the doctor depending on the results obtained (ultrasonic picture and estradiol concentration). The date and time of each subsequent visit to the doctor for monitoring is entered on the appointment sheet held by the patient. As a rule, the number of visits does not exceed 4 or 5. The time must be chosen taking into account the wishes of the patient, because most of them continue to work.

In our company, ultrasound is performed with a vaginal sensor (abdominal ultrasound), which is significantly more informative than conventional ultrasound through the abdominal wall. Before performing a abdominal ultrasound, you will need to empty your bladder to improve the quality of the resulting image.

The nurse invites you to the monitoring room. You will be asked to undress as if for a gynecological examination, after which you lie down on a prepared gynecological chair and your attending physician is invited. The sensor is inserted by the doctor into the patient’s vagina; a sterile condom is first put on it, which is discarded after use.

The ultrasound procedure is completely painless and safe. Some patients may experience a feeling of discomfort or embarrassment, and there may be slight vaginal discharge after the end of the ultrasound procedure, mainly due to the use of a special gel to improve the quality of the resulting image.

What is assessed during ultrasound monitoring?

The first ultrasound monitoring is usually carried out on the 5th or 6th day of stimulation with gonadotropins to assess the response of the ovaries (dynamics of follicle growth) and endometrial thickness in order to select the most optimal dose of the drug and determine the date of the next visit. Before the active growth of follicles begins (until they reach sizes of 10 mm and above), an ultrasound scan is performed once every 4-5 days, then the ovaries are examined more often - once every 2-3 days. Blood tests for estradiol are taken either with the same frequency or somewhat less frequently (depending on the specific situation).

Depending on the dynamics of follicle growth and hormonal levels, the attending physician determines the frequency of attendance for monitoring individually for each patient and selects the exact dose of drugs.

At each monitoring, the doctor determines the number of follicles in each ovary, measures the diameter of each follicle, and evaluates the thickness of the uterine mucosa.

Finally, when your doctor decides that you are ready for follicle puncture (more precisely, the follicles are mature enough for puncture to collect oocytes), you will be given an injection of hCG. As a rule, this drug is prescribed 35 - 36 hours before the puncture itself for the final maturation of the eggs. If the puncture is not performed, ovulation occurs 42 - 48 hours after the time of injection.

The main and mandatory conditions for prescribing hCG are a certain degree of follicular development according to ultrasound (at least 3 mature follicles). A potentially mature follicle against the background of stimulation is a follicle measuring 18-20 millimeters.

Second stage of IVF - follicle puncture

The purpose of this stage is to obtain eggs from the follicles of stimulated ovaries by puncturing them with a hollow needle (puncture). This intervention is performed under ultrasound guidance, in sterile conditions (operating room) and under intravenous anesthesia.

The time for the puncture is scheduled by the doctor in advance and according to the standard schedule: 35-36 hours after the administration of hCG. The date and time of the proposed puncture are recorded on the patient’s appointment sheet.

The contents of the follicle (follicular fluid with eggs) are transported to the embryology laboratory in special sterile disposable plastic containers made of non-toxic polymer. The entire follicle puncture procedure lasts, on average, 15-20 minutes.

Before follicular puncture

In order to avoid vomiting during and after anesthesia, you must:

• In the evening, on the eve of the puncture, refrain from eating after 18-00 and from taking any liquids after 24-00.
• On the day of the procedure, refrain from eating or drinking any liquids until the procedure begins.

We strongly ask that you come to the puncture without makeup, contact lenses, manicure or jewelry. You don't have to take off your wedding ring. You must come to our hospital 30 minutes before the time for which your puncture is scheduled (the corresponding date and time are indicated on your appointment sheet). By the time the puncture is completed, your husband must donate sperm for subsequent analysis, special processing and fertilization of the resulting eggs. Therefore, he should come with you on the day of the puncture and go to the reception desk, informing him of the purpose of coming (puncture for your wife). The IVF laboratory nurse accompanies the spouse to a special room for sperm donation. The spouse must remain in our company until the results of the puncture and spermogram are received.

The hospital nurse invites you to a special changing room. Then your body temperature and blood pressure are measured, your general health is determined, and you are asked to completely empty your bladder. You are escorted to the operating room, where they prepare you for the puncture: they help you lie down in a gynecological chair, and the external genitalia are treated.

An anesthesiologist and your attending physician are invited to the operating room. After the administration of drugs for anesthesia (that is, when you fall asleep), the procedure itself is carried out.

After the puncture, you are under the supervision of hospital medical personnel for 1.5-2 hours. Once the anesthesiologist is satisfied that your condition is satisfactory and you are feeling well, you will be allowed to stand up. The IVF laboratory nurse will accompany you and your husband to the attending physician. We do not allow patients to leave after the puncture unaccompanied, so your spouse or any other accompanying person must be with you.

After follicle puncture

The doctor informs you about the results of the puncture, makes new appointments, and sets the date and time for embryo transfer. The day after the puncture, you can speak directly with the embryologist who is working on your cells. You will receive a comprehensive answer from a specialist to your questions about the quality of eggs, sperm, their fertilization, and a little later (a day after the puncture) you can find out about the quantity and quality of the resulting embryos. The embryologist's phone number and the time of the call are included in your doctor's appointment sheet.

After the puncture, you can eat and drink as you see fit, depending on how you feel. In order to prevent the occurrence of an infectious process after puncture, you will be recommended to take antibiotics (a single loading dose of a broad-spectrum antibiotic - 1 capsule of doxycycline).

After the procedure, you may experience some soreness in the pelvic area, a feeling of fatigue, or even drowsiness (the latter is associated with the use of anesthesia). Slight bleeding from the genital tract after puncture is also possible, associated with a puncture of the vaginal wall during puncture. As a rule, they are scanty and vary in color from red to dark brown.

When to tell your doctor about problems

Please tell your doctor if you experience the following symptoms after the puncture:

• High temperature (over 37 degrees C).
• Severe bleeding from the vagina.
• Unusual or severe pain in the pelvic area.
• Difficulty urinating or bowel movements.
• Nausea, vomiting, or diarrhea.
• Sharp or shooting pain.
• Pain or sting when urinating.
• Unusual back pain.
• Increase in abdominal circumference.

Support corpus luteum function

In place of the punctured follicles, yellow bodies are formed. Normally, at the site of a mature follicle that “bursts” during ovulation in a woman of reproductive age, a corpus luteum is also formed, the main function of which is the production of the hormone progesterone, which “prepares” the uterine mucosa for the attachment of the embryo. However, in IVF cycles, α-GnRH drugs are used to stimulate ovulation, which reduce the function of the corpus luteum. Moreover, levels of the hormone estradiol in stimulated cycles are disproportionately increased compared to progesterone. Therefore, drug support for the function of the corpus luteum and normalization of the ratio of estrogen and progesterone are necessary, starting from the day of follicle puncture. This improves the condition of the uterine mucosa - the endometrium and thereby increases the chances of successful implantation (attachment) of embryos.

In most cases, we prescribe the natural hormone progesterone in the form of the pharmaceutical drug Utrozhestan or synthetic progesterone Duphaston.

"Utrozhestan" is available in the form of capsules for oral administration (oral) or vaginal administration. The vaginal method of administering the drug is preferable, since in this case it immediately goes to the uterus, bypassing the systemic (general) blood flow. Duphaston is available in tablet form and is taken orally only.

In some cases, after follicular puncture, the drugs Proginova or Estrofem are prescribed until the day of the pregnancy test. Both drugs contain another female hormone, estradiol, which also takes part in preparing the uterine lining for implantation. The drugs are available in tablet form, but Proginova is taken orally, and Estrofem is inserted into the vagina.

The type and dosage of the drug is selected individually. All prescriptions are recorded by your attending physician on the prescription sheet immediately after the puncture, and then after the embryo transfer the dosage of the drugs is adjusted.

The third stage of IVF - fertilization of eggs and cultivation of embryos

After the follicular fluid arrives at the laboratory, the embryologist conducts a “search” for eggs, which are then placed in an incubator. Fertilization is carried out with concentrated sperm 4-6 hours after receiving the eggs. For normal fertilization, approximately 50 thousand sperm are used for each egg. If sperm parameters do not meet the requirements of standard IVF or previous IVF attempts have been unsuccessful, further treatment tactics are discussed (possibly ICSI or IVF using donor sperm). The ICSI technique is used to fertilize mature eggs in the case of sperm abnormalities in the spouse (“ICSI”).

If it is difficult to obtain sperm on the day of puncture or there are no sperm in the ejaculate, a special procedure is provided - testicular biopsy.

The day of puncture is considered day zero of embryo culture; The first day of cultivation is the day following the puncture. It is on this day that most eggs show the first signs of fertilization. They are already noticeable 16 - 18 hours after the union of eggs with sperm (insemination). Fertilization is re-evaluated 24-26 hours after insemination. Fertilization control is carried out by an embryologist when viewing dishes with cultured cells under a microscope.

One of the reasons for IVF failure is the lack of fertilization of eggs. Often the reason for this is not possible to establish, despite the extensive knowledge of scientists in this area. No one is immune from this, and such an outcome is often difficult to predict, but it must be remembered. If your couple did not have eggs fertilized using the standard IVF method, you and your husband need to visit a doctor to decide on further management tactics for your couple. Possible options: repeat donation of sperm and performing the ICSI procedure or performing ICSI with sperm already obtained on the day of puncture (if it is of good quality). It is advisable from the very beginning, even before the puncture, to discuss the possibility of switching to ICSI if the standard IVF procedure fails.

Stages of embryo development

A fertilized egg is called a zygote - it is a one-cell embryo that already contains a double set of chromosomes, that is, from the paternal and maternal organism. However, the presence of zygotes is not yet sufficient to resolve the issue of the possibility of embryo transfer into the uterine cavity. First you need to make sure that the embryos are splitting and developing normally. This can only be judged based on the quantity and quality of the dividing cells of the embryo and not earlier than one day after fertilization, when the first signs of fragmentation appear. They appear most clearly only on the second day of cultivation. Every day, an embryologist evaluates embryos, recording all parameters: the number and quality of embryonic cells (blastomeres), the rate of fragmentation, the presence of abnormalities, etc.

Only good quality embryos can be transferred. Embryo transfer is carried out on the 2nd - 5th day of cultivation, depending on the rate of their development and the quality of the embryos.

Until recently, embryos were cultured for three days and then transferred into the uterus and/or frozen. Nowadays, so-called extended culturing of embryos for five or six days until they reach the blastocyst stage is common. Blastocysts have a higher implantation success rate, allowing us to transfer fewer embryos and reduce the risk of multiple pregnancies while increasing pregnancy rates.

The fourth stage of IVF - embryo transfer

As mentioned above, embryo transfer is carried out on the 2nd - 5th day of cultivation, depending on the stage of their development. On the day of embryo transfer, you must arrive 30 minutes before the appointed time. The presence of the husband is possible, but not required. On the day of the transfer, we allow patients a light breakfast, but liquid intake should be limited. This will reduce the discomfort associated with a full bladder.

Immediately before embryo transfer, the doctor, embryologist and couple decide on the number of embryos to be transferred. The embryologist demonstrates in photographs the embryos selected for transfer and answers questions of interest to the couple.

After receiving information about the doctor’s readiness to carry out the embryo transfer procedure, the embryologist collects the embryos into a transfer catheter, which is a thin plastic tube with an attached syringe, and hands it over to the doctor performing the transfer.

The embryo transfer procedure is technically simple. The patient lies down on the gynecological chair. The doctor exposes the cervix in the speculum, and then inserts a catheter through the cervical canal into the uterine cavity. The catheter contains embryos that enter the uterine cavity. The doctor then passes the catheter to an embryologist, who examines its contents under a microscope for any embryos remaining in the catheter.

Embryo transfer usually does not take long (5-10 minutes). The procedure is painless, although sometimes the patient may experience slight discomfort.

If, after embryo transfer, a couple has “extra” embryos of good quality, the couple is offered to freeze them for further storage and subsequent transfer after thawing in the event of no pregnancy after this IVF attempt (“Embryo Cryopreservation”).

After embryo transfer, you are in a horizontal position for 40 - 45 minutes, after which you get dressed and are invited to see your doctor to discuss further details of treatment and lifestyle.

How to behave after embryo transfer?

Your attending physician will provide a detailed statement in 2 copies (to you and your attending physician at your place of residence) about the IVF treatment performed. The extract indicates: lifestyle recommendations, timing of pregnancy tests and ultrasound examinations, dosages and duration of medication use. In addition, if necessary (working patients), a certificate of incapacity for work (sick leave) is issued. Nonresident patients are issued an open sick leave certificate, which they can extend at their place of residence.

After embryo transfer, the dose of progesterone drugs (Utrozhestan or Duphaston) is usually doubled, and their use can continue until 12-14 weeks of pregnancy, when the placenta (baby place) is formed and releases “its” progesterone in sufficient concentration.

After the transfer, some patients report slight spotting or the release of air bubbles from the genital tract. Please don't worry about this. This does not mean that at this time your embryos are expelled from the uterine cavity.

Immediately after embryo transfer, it is very useful to come home, lie down and try to relax. From the moment of transfer until the pregnancy test, you can safely return to most of your daily activities and responsibilities with the exception of excessive physical activity.

It is considered absolutely normal that if the pregnancy test results are negative, you will blame yourself for doing something or, conversely, not doing something during this period of time - the waiting time.

In this regard, try not to do anything that you will reproach yourself for if pregnancy does not occur, and adhere to the recommendations below:

• Do not take a bath or swim for the first 24 hours after the transfer.
• Do not shower or splash yourself with water.
• Don't use tampons.
• Do not be sexually active until you receive your first pregnancy test.
• Do not engage in running, aerobics, tennis, skiing, mountaineering or other similar sports.
• Do not start other sports or physical activities.
• Don't lift heavy things.

You can return to "work" after 24 hours in bed and one or two days of moderate physical activity.

Try to do something to distract yourself from waiting for the pregnancy test results, which will help you survive these 12 - 14 days.

You may have some spotting or spotting from your vagina before taking a pregnancy test. Approximately 50% of our pregnant patients after IVF had similar discharge before the test and even after receiving a positive result! Don't lose optimism! You should definitely get your blood tested, even if you think that this discharge is menstruation and pregnancy has not occurred. A quantitative pregnancy test must be done - determination of hCG in the blood.

Diagnosis of pregnancy

A quantitative hCG pregnancy test must be done 14 days after embryo transfer. If this time falls on a Sunday day off, the test can be done on Monday

To donate blood for analysis, you need to come to the laboratory in the morning between 8:00 and 11:00. The results will be ready after 15:00. You can receive a referral for analysis immediately from your attending physician after embryo transfer.

A blood test for hCG determines the hormone (human chorionic gonadotropin) released by the embryo when it implants in the uterine cavity. As a rule, the concentration of this hormone is comparable to the result of IVF treatment: the presence of pregnancy, the number of embryos in the uterine cavity, etc.

Most pregnancy tests give either positive or negative results. However, sometimes there are “weakly positive” results - a low concentration of hCG in the blood.

If you were given exactly this result, it may indicate the following:

• Delayed but normal embryo implantation.
• Interrupted pregnancy.
• Ectopic pregnancy.
• Laboratory error.

Further monitoring of hCG is extremely important in each of the above situations. 2-3 days after the weakly positive result, you need to repeat this study. Repeated blood testing for hCG will give us the opportunity to determine whether your pregnancy is progressing and whether it is developing normally.

The first ultrasound is recommended to be performed one week after the day of the pregnancy test (or 3 weeks after the embryo transfer). This ultrasound at such an early stage is extremely important in terms of the possibility of termination of pregnancy (miscarriage), ectopic pregnancy and multiple pregnancies. Ectopic tubal pregnancy can occur in 2-3% of IVF pregnancies.

Timely, early diagnosis of ectopic pregnancy and laparoscopic surgery allows one to avoid serious complications that threaten the woman’s life.

The second ultrasound examination is carried out 10 days after the first to confirm the normal development of pregnancy - to determine the fetal heartbeat. As soon as we detect a fetal heartbeat, we recommend that you contact your obstetrician-gynecologist for early pregnancy registration. The approximate pregnancy period at the moment will be 6-7 weeks.

If the pregnancy test is negative, you stop taking progesterone medications. It will take 3 or 5 days before your period arrives, if it has not arrived earlier. Your menstrual flow may be different from your usual periods (heavier, lighter, shorter or longer). If menstruation does not come within the next week, inform your attending physician at our center and repeat the hCG blood test.

Your IVF treatment cycle was not successful - do not despair! You can visit your doctor to talk about your treatment and your future prospects. All that will help us in this case is time and a repeat IVF program.

Ovulation stimulation drugs

The active principle of such medications are the two main gonadotropic hormones of the pituitary gland, which are necessary for the normal functioning of a woman’s ovaries. FSH - follicle-stimulating hormone is responsible for the growth and development of the follicle in the ovary, and LH - luteinizing hormone ensures the final maturation of the egg and ovulation in the middle of the cycle (rupture of the leading follicle and release of the mature egg into the abdominal cavity).

There are two types of gonadotropic hormone drugs: HMG drugs - contain both hormones - FSH and LH; FSH preparations contain only the FSH hormone. In our clinic, the most commonly used HMG drugs are Menopur (Ferring, Germany), and the FSH drugs are Puregon (Organon, Holland) and Gonal-F (Serono, Italy). . These medications differ not only in composition, but also in their production technology.

"Menopur" is obtained from the urine of menopausal women using special highly purified technology. The drugs "Puregon" and "Gonal-F" are created by genetic engineering - the drugs contain only a certain section of the FSH molecule, which directly ensures the growth of the follicle.

The use of all drugs is safe from the point of view of the risk of developing an immune reaction against “foreign” hormones.

Side effects of these drugs are infrequent and include abdominal discomfort, flatulence (bloating), mood swings, fatigue or restlessness, which in most cases improve or disappear completely after follicular puncture. One of the possible complications of therapy with gonadotropic hormones is multiple growth of follicles and the development of ovarian hyperstimulation (“Ovarian hyperstimulation syndrome”).

The drugs are available in the form of a dry substance (powder) and an accompanying solvent (in ampoules) and are administered intramuscularly once a day. In this case, 2-4 ampoules of dry substance are diluted with the contents of one ampoule of solvent.

Usually patients give themselves injections, sometimes they involve their relatives or friends who know how to do intramuscular injections.

In any case, you can always count on our help - injections can be done by a nurse in the treatment room. We strongly recommend that she give the first injection in order to teach the patient or whoever will be injecting her how to administer the drug. It is important to administer the drugs in the dose prescribed by the doctor, at the same time of day, preferably in the 2nd half of the day.

Instructions for IVF patients on the administration of drugs "Menopur", "Puregon" and "Gonal-F"

• Prepare in advance: one sterile syringe with a needle for intramuscular injection, 2 cotton balls moistened with 70% alcohol, one ampoule of solvent and 3 or 4 ampoules of the drug (in accordance with the prescription sheet).
• Treat the index and thumb of your right hand with an alcohol ball and quickly (in one motion) uncork the ampoules.
• Remove the cap from the needle and draw 1 or 2 ml of water (the proposed sterile solvent) into a syringe and dissolve this amount of solvent alternately in each of 2 to 4 ampoules with a dry substance, sequentially transferring the contents of the previous ampoule (already dissolved) into the next ampoule (with the dry substance not yet dissolved). The substance dissolves almost instantly; the needle should be inserted into the ampoule as deeply as possible.
• Draw the dissolved contents of all ampoules into the syringe; Hold the syringe vertically and lightly press the plunger to remove all air bubbles from the syringe.
• Select the injection site; preferably, it does not coincide with the site of the previous (yesterday) injection. Gently grab the skin in this area with your left hand. Take a comfortable position and, leaning on the leg opposite to the one where the injection is to be made, try to relax the muscles of the latter as much as possible.
• Apply an alcohol ball to the injection site and hold the ball under your left thumb.
• Holding the drawn syringe like a “throwing spear,” pierce the skin with the needle (the depth of penetration should be at least 1/2 the length of the needle) and quickly insert the needle into the muscle.

GnRH agonists

To prevent a woman’s own pituitary hormones from interfering with the stimulation of superovulation, their production is blocked by analogues (agonists) of the hormone GnRH (a - GnRH). The active principle of the drugs is the compound triptorelin, a synthetic analogue of GnRH. The latter causes the release of gonadotropic hormones in the female body, which, in turn, have a direct effect on the production of female sex hormones, the growth of follicles and the maturation of eggs in the ovaries. GnRH agonists prepare the ovaries and thereby “unify” the conditions for subsequent maturation of follicles during stimulation. In addition, these drugs prevent premature ovulation, that is, rupture of follicles before puncture.

Of the agonists in our clinic, the most commonly used are Decapeptyl-Daily (Ferring, Germany) and Diferelin-Daily (Ipsen, France).

The drugs are available in the form of daily injections (daly - from the English word “daily” - daily) and deposited forms (the drug is administered once every 4 weeks). In the IVF program, drugs with daily administration are most often used. Most drugs are available for subcutaneous injection, some drugs are administered intramuscularly.

"Decapeptyl Daily"

The drug is available in the form of ready-made syringes of 2 types: “Decapeptyl - daily 0.5 mg” - and “Decapeptyl - daily 0.1 mg”. Each such syringe looks very much like an insulin syringe, which is used by patients with diabetes - a very thin needle (no thicker than a hair for painless subcutaneous administration of medication). We usually prescribe Decapeptyl Daily 0.1 mg as a daily subcutaneous injection. One package contains 7 or 28 syringes with the drug. The drug is stored in the refrigerator. One syringe is enough for one injection (if prescribed in the first 10-14 days of treatment); when the doctor reduces the daily dosage (the next 12-14 days of administration of a-GRG - already together with gonadotropin preparations), it is enough to administer not the entire syringe, but only half of its contents per day, and it is recommended to store the remaining medicine in the syringe (0.5 ml) in refrigerator until the next dose (after putting the cap on the needle). Immediately before administering the drug, there is no need to further warm it up.

Instructions for administration of "Decapeptyl-Daily 0.1 mg"

• When you start administering Menogon or Puregon, the dose of Decapeptyl-Daily is reduced by exactly half; the syringe is not thrown away, and the second half of the contents of the syringe remaining after injection is stored in the refrigerator until the next injection, for which the cap is put back on the needle.

Diferelin Daily

Diferelin-Daily is available in the form of a dry substance (powder) and an attached solvent (in ampoules) and is administered subcutaneously once a day. In this case, the contents of an ampoule of dry substance are diluted with the contents of one ampoule of solvent.

Instructions for administration of Diferelin-Daily 0.1 mg

• Wash and dry your hands thoroughly.
• Prepare in advance: one sterile syringe with a needle for intramuscular injection, 2 cotton balls moistened with 70% alcohol, one ampoule of solvent and a bottle of dry substance.
• Treat the index and thumb of your right hand with an alcohol ball and quickly (in one motion) open the ampoule with the solvent. Spray the cap of the bottle with an alcohol ball and open it.
• Remove the cap from the needle and draw 1 or 2 ml of water (the proposed sterile solvent) into the syringe and dissolve this amount of solvent in the vial with the dry substance; The substance dissolves almost instantly; the needle should be inserted into the ampoule as deeply as possible.
• Draw the dissolved contents of the bottle into the syringe; Hold the syringe vertically and lightly press the plunger to remove all air bubbles from the syringe.
• Take the syringe and the new alcohol ball in your right hand.
• Select a subcutaneous injection site (on the shoulder or on the anterior abdominal wall); It is advisable to change injection sites daily. Gently clean the injection site with a cotton ball moistened with alcohol.
• Holding the syringe in your right hand like a “throwing spear” at an angle relative to the surface of the skin, quickly insert the syringe needle under the skin.
• Smoothly, without jerking, squeeze out the entire contents of the syringe, then remove the needle, treat the injection site with a new cotton ball with alcohol and throw away the used syringe.

When you start administering Menogon or Puregon, the dose of Diferelin-Daily is reduced by exactly half; the syringe is not thrown away, and the second half of the contents of the syringe remaining after injection is stored in the refrigerator until the next injection, for which the cap is put back on the needle.

GnRH agonists must be administered at the same time, preferably in the evening. If the time of administration of the drug changes (the difference is more than an hour), you must inform your doctor about this and discuss with him the time of the next injection.

Each drug is accompanied by detailed instructions from the manufacturer about the features of use and storage of this drug, its side effects, which greatly facilitates their administration by the patients themselves. However, due to the fact that these drugs have their own characteristics of administration, we recommend that patients receive their first injection in our treatment room. The nurse in the treatment room teaches the patient all the rules for administering the drug.

Side effects of agonists do not occur often and are associated mainly with a decrease in the level of sex hormones in the blood: a decrease in sexual desire, rapid mood changes, hot flashes, and rarely depression are possible. But all of these manifestations are transient in nature and indicate the effectiveness of the drug, paradoxically, because they are associated with a temporary decrease in the level of sex hormones (estradiol) in the body. All of these symptoms associated with a decrease in estrogen saturation disappear after the start of gonadotropin administration due to increased estrogen production in the woman’s stimulated ovaries.

The drugs do not accumulate in the body, and all side symptoms disappear without a trace. Sometimes there is slight soreness, redness or, less commonly, itching at the injection site (injection site). This is a local allergic reaction, which usually does not require the prescription of additional medications and discontinuation of the drug, but it, like other possible side effects of the drug, should be reported to your doctor in a timely manner.

GnRH antagonists

GnRH antagonists (ant-GnRH), like agonists, block the functioning of the pituitary gland, and thereby provide conditions for stimulating follicular growth. Antagonists are prescribed at the final stage of stimulating follicular growth to prevent premature ovulation (usually from the 6-7th day of stimulation, that is, the use of Menopur or Puregon). During the stimulation process, as a rule, no more than 4-5 injections are required.

Medicines in this group include Orgalutran (Organon, Holland) and Cetrotide (Serono, Italy). Our company uses the drug "Orgalutran".

The drug is available in the form of ready-made syringes “Ogralutran 0.25 mg”. Each such syringe looks very much like an insulin syringe, which is used by patients with diabetes - a very thin needle (no thicker than a hair for painless subcutaneous administration of medication).

The drugs are prescribed as subcutaneous injections at the same time of day, which is indicated by your doctor.

Instructions for administering the drug "Orgalutran 0.25 mg"

• Open the package and take the syringe from the package.
• Remove the plastic cap from the syringe needle.
• Take the syringe in your left hand and a cotton ball soaked in 95% alcohol in your right hand.
• Select a site for subcutaneous injection (on the shoulder or on the anterior abdominal wall); It is advisable to change injection sites daily. Gently clean the injection site with a cotton ball moistened with alcohol.
• Holding the syringe in your right hand like a “throwing spear” at an angle relative to the surface of the skin, quickly insert the syringe needle under the skin.
• Smoothly press the plunger to squeeze out the contents of the syringe, then quickly remove the needle.
• Treat the injection site with an alcohol ball.
• All used material (cotton balls, used syringes, etc.) is thrown away (in regular waste containers - no special equipment required).

Chorionic gonadotropin (hCG)

Human chorionic gonadotropin is a hormone similar to luteinizing hormone (LH), which causes ovulation of the leading follicle in the middle of the menstrual cycle.

The hCG injection is intended to prepare the follicles for puncture and the final maturation of the eggs. Ovulation occurs 42-48 hours after hCG administration. Therefore, follicular puncture must be performed before ovulation, otherwise the follicles will be empty. HCG is prescribed 35 - 36 hours before the puncture. The time for prescribing the drug is recorded in the prescription sheet and is once again clarified by your doctor immediately before the puncture.

Many patients experience discomfort in the lower abdomen after an HCG injection due to an increase in the size of the ovaries and believe that they are ovulating. In fact, careful monitoring of patients during treatment and the drugs used (a-GnRH or antagonists) almost completely eliminate the risk of premature ovulation, i.e., ovulation before follicle puncture.

HCG is produced by different companies under different commercial names. The most commonly used drug is Pregnil (Organon, Holland). The drug looks like a white powder. Each ampoule of dry substance is accompanied by 1 ampoule of solvent. The drug is administered intramuscularly.

The hCG injection is performed only once during the entire treatment cycle, the injection is painless and, as a rule, the patient gives it to herself. Before the scheduled puncture time (written down on the appointment sheet), the patient does not need to visit the doctor or take blood tests for hormones.

Instructions for administering the drug "Pregnil"

The timing of hCG administration is a decisive factor in treatment, so the drug must be administered exactly at the calculated time!

• Wash and dry your hands thoroughly.
• Prepare in advance: a disposable syringe with a needle, 2 cotton balls moistened with 70% alcohol, and medicine (ampule with dry substance).
• Take the ampoule with the dry substance from the package; remove all plastic protective coverings.
• Treat each ampoule with an alcohol ball.
• Remove the cap from the needle, insert the needle straight and firmly into the center of the rubber cap of the solvent ampoule.
• Turn the ampoule upside down.
• Lower the plunger of the syringe to withdraw sterile solvent (in an amount of 3 ml), and then disconnect the empty ampoule.
• Remove air bubbles from the syringe by lightly flicking it or shaking it with your fingers, then squeezing out the air with the syringe plunger.
• Select the site for the intramuscular injection. Stretch the skin in the selected area with your left hand.
• Take the ready-to-use syringe and a cotton ball soaked in alcohol in your right hand. Treat your skin with alcohol and hide the used ball under your left hand.
• Holding the syringe like a “throwing spear”, insert the needle into the muscle at an angle, then with sharp pressure on the piston, squeeze out the entire contents of the syringe, remove the needle, and treat the injection site with a new cotton ball with alcohol.
• Place used instruments and medications in a waste container.

In vitro fertilization provides a real opportunity for infertile couples to become parents. The procedure is not as simple as it seems, and the woman often has to undergo ovarian stimulation to induce superovulation. What it is and how it happens, we will tell you in this article.

What it is?

Stimulation of the ovaries before IVF is carried out only in a stimulated cycle. With normal ovarian function without the use of any medications, a woman matures one egg in one menstrual cycle, or less often - two.

Stimulation of the ovaries allows you to obtain several eggs in one cycle, which significantly increases the chances of selecting the highest quality oocytes, their fertilization and subsequent transfer to the uterine cavity of the expectant mother. Ultimately, the likelihood of pregnancy increases.

After the couple contacts a reproductive specialist, taking into account the true cause of infertility, an individual scheme is prescribed - an “action plan” for the next month. This plan, drawn up for a specific woman, providing a detailed description of the stages, their order, as well as hormonal drugs to stimulate ovulation and their dosage, is called a protocol.

Starting the next menstrual cycle in which IVF is planned, the woman “enters the protocol.” This introduction begins precisely with stimulating the increased work of the ovaries, so that by the middle of the cycle the doctor can obtain not one, but several oocytes suitable for fertilization.

Stimulation of the ovaries completely changes the biological rhythm of life of the female body. The ovaries do not work as usual, but in emergency mode. Stimulation before IVF is most often required during the first protocol. If you manage to obtain a large number of eggs, then in the next protocol (provided that the first does not bring a positive result) you can do without drug “shock” hormone stimulation; the doctor will be able to use cryopreserved (frozen) eggs or embryos.

You can, of course, try to get pregnant in a natural cycle, without stimulation. In this case, an embryo obtained from a single egg is transferred to a woman without drug support, but the predicted effectiveness of such IVF is several times lower than with the stimulated protocol.

The state of the female body that the doctor strives for when prescribing ovarian stimulation is called superovulation. This term means multiple ovulation, in which 3-4-5 or even more follicles mature.

Sources:

1. Losos, Jonathan B.; Raven, Peter H.; Johnson, George B.; Singer, Susan R. Biology. New York: McGraw-Hill. pp. 1207-1209.
2. Campbell N. A., Reece J. B., Urry L. A. e. a. Biology. 9th ed. - Benjamin Cummings, 2011. - p. 1263
3. Tkachenko B. I., Brin V. B., Zakharov Yu. M., Nedospasov V. O., Pyatin V. F. Human physiology. Compendium / Ed. B. I. Tkachenko. - M.: GEOTAR-Media, 2009. - 496 p.
4. https://ru.wikipedia.org/wiki/Ovulation

How is stimulation carried out?

Usually the stimulation process begins on the 3rd or 5th day of the menstrual cycle. The countdown is from the first day of the next menstruation. Therapy lasts until approximately the middle of the cycle, when, according to ultrasound estimates, the size of the follicles reaches a sufficient size. Then the procedure of “ovarian puncture” is prescribed. It is carried out in a hospital setting under general or local anesthesia. A thin and long hollow needle is inserted into the woman’s ovary through the back wall of the vagina, which “pumps out” the contents of the dominant follicles along with the eggs.

The eggs undergo microscopic examination, and the best of them are considered suitable for fertilization. The oocytes are placed in a nutrient medium, and the sperm of the husband or donor is added there.

Fertilized eggs remain to “ripen” in the laboratory for several more days, after which they are again subjected to strict selection. Only the most viable and strong embryos will be implanted into the uterine cavity of the expectant mother.

The more eggs were obtained, the more of them successfully passed the fertilization stage and were found suitable for transfer, the higher the likelihood of a successful IVF outcome. If after transfer there are “extra” embryos left, in agreement with the attending physician, they can be frozen and will be stored in a cryobank until required. The woman will be able to use them in the next protocol or in a few years, when she wants to give birth to another baby.

From the moment the hormones are prescribed, which in the first phase of the cycle should ideally lead to superovulation, control over the growth of the endometrium of the uterus and follicles begins. Normally, the endometrium should “grow” by 1 mm, and the follicles by 2 mm every day.

If growth exceeds these normative values, the regimen is revised to adjust for the likelihood of developing a dangerous complication - ovarian hyperstimulation syndrome. If the growth rate of the endometrium and follicles is not up to normal, the doctor may increase the dosage of hormones or change one drug to another. The ovarian response may vary.

Impact doses of hormones, which are completely unusual for the female body outside of IVF, can have quite noticeable negative consequences for the entire body, and therefore stimulation with minimal hormonal support is sometimes recommended in order to minimize the harmful effects. However, in such protocols, for the most part, only follicles grow, the endometrium grows slightly, and its thickness is very important so that fertilized eggs can implant and take root.

In protocols with minimal stimulation, doctors often set the goal only to collect biomaterial - eggs and freeze them until the next protocol, when the endometrium is ready to accept the fertilized egg.

Stimulation in a short protocol lasts approximately ten days. The entire protocol takes one menstrual cycle. In a long protocol, stimulation can last more than 30 days.

When choosing the type of protocol, the doctor focuses on the cause of infertility and related problems. So, with endometriosis, it will take quite a long time to “build up” the endometrium, so a long protocol is chosen. In particularly difficult cases, the duration of stimulation can reach up to six months.

Feelings during stimulation

A woman usually begins to feel the consequences of hormonal stimulation during the stimulation process itself. The hormonal background changes, natural hormones are replaced by an excessive concentration of those introduced from the outside, and the state of health noticeably worsens. A woman can literally be plagued by severe headaches, nausea, dizziness, nagging pain in the lower back and lower abdomen.

Due to changes in the hormonal balance, a woman’s psycho-emotional state is disturbed, she becomes nervous, intolerant, whiny, irritable, she is overcome by attacks of severe anxiety, night sleep is disturbed, and bloating and appetite disturbances may occur.

If, during the stimulation period, clear, rather abundant discharge from the genital organs appears, this is a good sign, indicating that the endometrium is growing at a fairly rapid pace, and the chances of implantation of embryos into the functional layer of the uterus after embryo transfer increases.

Drugs

To stimulate superovulation, exclusively synthetic hormonal drugs are used. The doctor chooses the dosage based on the patient’s own hormone levels, the state of the reproductive system, the cause of infertility, the woman’s age and a host of other factors, including the response of the ovaries to stimulation.

In the first phase, follicle-stimulating hormone (FSH) drugs are taken; when the follicles enlarge and ovulation approaches, the woman is given drugs based on LH, which helps the egg to quickly mature. After about 36 hours, a puncture is scheduled - and the eggs, ready to meet the sperm, are removed from the ovaries.

If a woman is planning to undergo insemination (not to be confused with IVF), then when the follicles mature, drugs based on human chorionic gonadotropin (hCG) are administered, which provokes rupture of the follicle membranes and the release of a mature egg. After which the woman’s sperm is injected into the uterine cavity from her husband or donor. Conception, unlike IVF, does not take place in a test tube, but in the body of the expectant mother.

At the final stage after embryo transfer, the woman is prescribed drugs containing synthetic progesterone. It is this hormone that prevents the onset of the next menstruation, and also creates the most comfortable conditions for the developing embryo - it thickens and makes the endometrium of the uterus more loose, improves metabolic processes, partially suppresses maternal immunity so that embryo rejection does not occur, and also maintains the smooth muscles of the uterus in a calm state , preventing hypertension and possible miscarriage.

The most popular and common drugs used during ovarian stimulation include the following.

"Orgalutran". This remedy allows you to suppress the production of follicle-stimulating and luteinizing hormones, which is very important for controlled superovulation in the IVF protocol. The drug exists in the form of syringes with an injection solution. At the recommended dose, it is injected subcutaneously into the thigh area. It is important not to forget to take the drug at certain time intervals, otherwise the pituitary gland will quickly restore its ability to synthesize FSH and LH. Usually the drug is taken for five days.

• "Pugeron." This is a drug with a follicle-stimulating effect. It promotes the maturation of not one, but several follicles in the first phase of the menstrual cycle. Puregon therapy is prescribed not only in the IVF protocol, but also before intrauterine insemination, as well as in IVF + ICSI protocols. The drug is administered from 2-3 days of the menstrual cycle, duration is from 7 to 12 days, until the preovulation stage is detected by ultrasound results. Stimulation with Puregon is considered effective over four protocols. Then the effect decreases and the drug needs to be changed.

• "Gonal-F". This drug exists both in the form of a lyophysilate for preparing injections after dissolution, and in the form of a ready-made solution for subcutaneous injection in the so-called “syringe pen”. The dose of the drug per day should not exceed 450 IU. Every day, from day 2-3 of the cycle, the drug is injected subcutaneously into different places. It is strongly not recommended to inject the product into the same place. Usually, 12-13 days after the start of use, the follicles reach adequate size and can be extracted by puncture.

• "Menopur." Reviews of stimulation with this drug are mostly positive. The product is obtained from the urine of women in a state of natural age-related menopause. The drug affects the activity of the pituitary gland to suppress all follicles except the dominant one, and therefore it becomes possible to obtain several eggs that are mature and suitable for fertilization. The drug also increases the thickness of the endometrium.
• "Meriofert". This drug also has a pronounced follicle-stimulating effect, promotes endometrial growth, and also increases estrogen levels. The drug can be administered subcutaneously and intramuscularly.

• "Klostilbegit." This drug is usually used in “soft” IVF schemes. With its help, the ovaries quickly cope with the growth of several follicles, which will be fertilized not in this cycle, but a little later. The dosage of the drug is purely individual. The ovarian response to the drug is not always adequate.

How to give injections yourself?

Usually, doctors do not object to a woman doing the necessary daily injections on her own; before that, she will receive detailed instructions on where and how to administer the drug. The general requirements for independently fulfilling doctor’s orders are as follows:

• subcutaneous injections are best done with special injector pens;
• any hormonal drug should be administered extremely slowly and deliberately;
• Injections should be given at the same time every day;
• if one injection is missed for some reason, you should call the doctor and get further recommendations;
• It is strictly prohibited to increase or decrease the recommended doses.

If a woman falls ill with a cold, flu or acute respiratory viral infection during stimulation, or if she has been prescribed antibiotics, she should definitely contact her doctor to decide on the advisability of continuing stimulation or postponing the egg retrieval procedure to another menstrual cycle.

Possible complications

One of the most dangerous complications of stimulation as a stage of IVF is considered to be ovarian hyperstimulation syndrome. With this syndrome, the ovaries increase in size due to the growth of a large number of follicles.

Symptoms of hyperstimulation most often manifest as ascites (accumulation of fluid in the abdominal cavity), in which a woman feels bloated. Pain in the lower abdomen can have varying intensity; it directly depends on how much the woman’s ovaries have enlarged relative to the normal size.

Breathing becomes heavier and more difficult, and nausea, vomiting and diarrhea may occur. The fingers, legs, and lower abdomen swell greatly, blood pressure drops, and the woman’s well-being noticeably deteriorates. The volume of urine excreted by the kidneys decreases markedly. In a state of hyperstimulation, embryo transfer is highly undesirable, since the likelihood of carrying a pregnancy to term, even if it occurs, will be minimal.

The most at risk of hyperstimulation of the gonads are fair-haired women under the age of 35, women suffering from polycystic disease, as well as women who are prone to allergies and receive hormonal support with hCG in the second phase of the cycle.

The danger of hyperstimulation lies in the possibility of death, the development of heart and kidney failure, and the likelihood of rapid depletion of the gonads.

The highly qualified doctor who conducts the protocol and his willingness to quickly respond to changes in the woman’s well-being and ovarian response will help to avoid ovarian hyperstimulation. If the follicles grow too slowly, the dose of the hormonal drug should not be increased sharply; after identifying the cause of the unsatisfactory growth of the follicles, sometimes it is necessary to change the drug altogether. During puncture, in order to avoid the development of hyperstimulation in the second phase, it is important to aspirate all accessible large follicles.

In most cases, such an unpleasant complication can be avoided, so do not panic. A trusting relationship with the doctor will ensure that the process of stimulating follicle growth will proceed without dangerous complications and the remaining stages of IVF will proceed similarly, ending in complete success.

Other possible complications of ovarian stimulation before IVF include the possibility of multiple pregnancies, as well as the possibility of ectopic pregnancy after embryo transfer, but this is extremely rare. During stimulation, especially if it is carried out over several protocols, a woman can gain a lot of weight. Also, some sources indicate the likelihood of early menopause after pregnancy, which became possible thanks to IVF precisely because of the previous hormonal stimulation of the ovaries.

How to behave during the stimulation period?

Of course, it is quite difficult for a woman to remain calm and measured, because hormones leave their mark on almost everything - well-being changes (not for the better), libido decreases, the woman experiences not only emotional instability, but is also in a state of severe stress due to fears that the attempt may fail. Nevertheless, doctors strongly recommend trying to pull yourself together and cope with your negative emotions, because stress clearly does not contribute to the successful implantation of embryos and the onset of such a long-awaited pregnancy.

It is important for a woman to walk in the fresh air and eat well. Trying to stick to a diet or vegetarianism should be a thing of the past. Diet and successful IVF are incompatible. A woman’s diet should contain many vitamins and minerals. The menu must contain animal proteins - meat, fish, dairy products.

The amount of fat in the menu should be somewhat limited. Proteins are extremely important because consuming them in sufficient quantities somewhat reduces the likelihood of such an unpleasant complication as hyperstimulation syndrome.

It is important for a woman who has entered into the protocol and started stimulation to change her lifestyle. She should get a good night's sleep and take care of her health. Immunity, which inappropriately can be undermined and weakened by a viral infection, influenza, or high fever, is now necessary so that the female body can cope with a more important task. Therefore, it is important to stay away from sick people; during epidemic seasons, it is better to take several days off or part of a vacation and save yourself from the need to meet sneezing and coughing people on the bus, subway, or at work.

Smoking and drinking alcoholic beverages during ovarian stimulation, as well as drinking coffee, cocoa, and strong tea can have a negative impact on hormonal levels. It is better to refuse all this.

A woman should not go to a bathhouse or sauna, visit a solarium, or be exposed to direct sunlight for a long time. You should not take any medications without the knowledge and approval of your fertility specialist.

If you have a headache, do not immediately grab painkillers, and if you are vomiting, take antiemetics. It is better to endure some unpleasant sensations and symptoms - they are temporary.

If during the stimulation process unusual discharge appears, for example, bleeding or “smearing”, you should definitely consult a doctor without delay. If your joints hurt, and many women, according to reviews, note that this also happens, you should also consult a doctor.

The most common cause of infertility is the lack of egg maturation. Therefore, to help a woman give birth to a child, drugs are used as a treatment method to stimulate ovulation, which activate the production of natural hormones in the woman’s body that are responsible for her reproductive process.

What drugs exist to stimulate ovulation?

Treatment begins only after a thorough examination of both spouses, when the final cause is determined. The course of medication is selected by the doctor individually for each expectant mother in the absence of contraindications.

Hormonal drugs

Let's take a closer look at which ovulation stimulation drugs are most often used:

• medications based on menopausal gonadotropin (HMG) - menoghan, pergonal, menopur, etc., they contain follicle-stimulating and luteinizing hormones in equal parts;
• FSH-based drugs - puregon, gonal, etc., which are similar in action to their natural analogue;
• clostilbegit, serofen, clomid inhibit estrogen production, and therefore hormones that affect follicle growth increase their level to normal;
• choreonic gonadotropin (hCG), prophase, ovitrel, choragon, pregnyl, etc., are necessary to stimulate the rupture of the follicle membrane for the release and timely release of the egg.

These hormonal drugs for stimulating ovulation in properly selected combinations and dosages are effective in treating various types of infertility.

Drug regimens

There are various schemes for using stimulant drugs.

Scheme 1

Most often used. Treatment here is carried out with clostilbegit. It is used from 5 to 9 days from the date of bleeding and with mandatory ultrasound monitoring. Initially, the study is done after a couple of days and then repeated at the same interval until the growing follicle reaches a size of 17-18 mm. After this, the woman is given an injection of hCG so that the reproductive cell is released within 24 hours. The day of the injection and the day after it are the most favorable times for conception.

Ultrasound not only monitors the growth of the egg, but also the thickness of the endometrium, therefore, when its thinning is noticed, one of the estrogen-containing drugs is added in parallel with clostilbegit - proginova, devigel, estrogel, etc.

Scheme 2

Involves the use of gonadotropins (gonal, puregon, menogon). The drug chosen by the doctor is prescribed from day 2-3 of the cyclic process. The first ultrasound is done on days 6-7. The duration of taking this group of drugs depends on the growth rate of the follicle, monitored by ultrasound. The frequency of this study is also determined by the gynecologist, but usually it is once every 2-3 days. When the egg has reached the desired size, as in the first case, the use of hCG is indicated.

Scheme 3

Provides the possibility of using any gonadotropin as a drug to stimulate ovulation initiated by clostilbegit. In this case, a combined course of taking hormones is calculated. Clostilbegit is taken for 5 days from day 2-5, then gonal or another medicine from this group for another 5-7 days, after which an ultrasound is indicated at the appropriate time and an hCG injection is given again.

At the end of the first phase and successfully completed ovulation, regardless of the medications and regimen taken during it, from the 16th day of the cycle, the doctor will definitely prescribe the use of the hormone of the second period - progesterone (duphaston or utrogeston), regardless of its level, to maintain the formation of the corpus luteum and the normal process implantation (uterine preparation). This is a necessary measure for the hormonal balance of both phases.

Features of stimulation during IVF

Drugs used to stimulate ovulation during IVF are similar to those used during the natural process (clostilbegit, menopur, gonal, etc.). Doses and course of treatment are prescribed individually, and the entire process takes place with ultrasound monitoring under the supervision of a physician.

The goal in this case is to achieve superovulation - the maturation of several full-fledged cells at once in one period. Ultrasound is performed every other day, starting from the 5th day of treatment. When the follicles reach maturity, an hCG injection is given and at the right time the germ cells are removed from the ovary using a puncture. They are artificially fertilized and after 2-5 days the embryos are transferred to the uterus, where they are implanted into the endometrial wall for further growth.

Taking progesterone drugs during this procedure is also relevant.

conclusions

The use of drugs to stimulate ovulation helps correct hormonal imbalances in a woman’s body and conceive a child, both during the natural process of conception and during IVF.