Clomiphene ™

One of the reasons for infertility in women is the lack of ovulation, when there is no exit from the follicle of a mature egg, which, in fact, should be fertilized by spermatozoa. This condition is called anovulation. What drugs for ovulation stimulation exist today?

Treatment of anovulation is carried out by stimulating ovulation, for which drugs aimed at activating ovarian function are used, the most popular of which are clomid, clomiphene citrate, pregnil and clostylbegit.

Clomid – drugs for ovulation stimulation

Other names of Clomid: Ardomon, Biogen, Blesifen, Clofert, Clomhexal, Clomifeencitraat cf, Clomifen, Clomifene, Clomifeno, Clomifenum, Clomifert, Clomipheni, Clomivid, Clomoval, Clostilbegyt, Clovul, Dufine, Duinum, Dyneric, Fensipros, Fermid, Fermil, Fertab, Fertil, Fertilan, Fertin, Fetrop, Genoclom, Genozym, Gonaphene, Gravosan, Ikaclomin, Indovar, Klomen, Klomifen, Kyliformon, Milophene, Ofertil, Omifin, Orifen, Ova-mit, Ovinum, Ovipreg, Ovofar, Ovuclon, Ovulet, Pergotime, Phenate, Pinfetil, Pioner, Profertil, Prolifen, Provula, Reomen, Serofene, Serpafar, Siphene, Spacromin, Tokormon, Zimaquin.

Initially, clomid was developed to treat such a serious disease as breast cancer. However, the drug was not widely used in this area of treatment, as it did not meet the inflated expectations. Later, it was used as a drug that helps stimulate ovulation for women who have problems with the onset of conception due to a violation of the ovulatory cycle. Clomid is prescribed in the following cases:

• if the development of anovulation occurred due to the presence of polycystic ovary syndrome (PCOS);
• with infertility of unclear genesis: if, from a medical point of view, a woman has no obstacles to the onset of conception, but pregnancy does not occur. It is recommended to supplement the use of clomid with metformin, which helps to increase insulin levels and stimulate ovulation;
• for additional guarantees during ovulation stimulation before in vitro fertilization (clomid increases the chances of a successful pregnancy).

The optimal course of use of this drug should be six months, unless, of course, pregnancy occurs earlier than this period, which happens in 30% of cases.

Clomid has minor side effects, in the process of taking it, painful sensations in the lower abdomen, sleep disturbance and weight gain can be observed. In extremely rare cases, taking clomid threatens the development of a cyst or ovarian tumor.

Pregnil

Pregnil is a drug based on human chorionic gonadotropin (hCG). Its use is prescribed to women of any age, however, depending on various factors, clomid has different effects. The purpose of its use as a therapeutic agent in the treatment of infertility is to stimulate the activity of the ovaries as part of the artificial insemination program.

The highest concentration of hCG in a woman’s body is observed 20 hours after the first intake of the drug. The excess of the drug is excreted from the body independently after a few days.

Clomiphene Citrate

Clomiphene citrate is not very popular among medical professionals due to its notoriety associated with the side effects of the drug. Against the background of taking clomiphencitrate, the size of the ovaries may increase, urination becomes more frequent, visual function is impaired, and vasomotor symptoms often occur. However, clomiphene citrate is indispensable in cases where there is no possibility of folliculometry. Clomiphene citrate has contraindications: it cannot be used for ovarian cysts.

Drugs for ovulation stimulation: Clostylbegit

Clostylbegit is rightfully considered one of the most popular drugs that promote ovulation stimulation. Its effectiveness especially increases against the background of taking other drugs with a similar effect. Clostylbegit increases the level of FSH (follicle-stimulating hormone) in the female body, provided that medications are taken simultaneously to reduce prolactin levels during ovulation stimulation, which ensures its effectiveness.

The dosage of clostylbegit should be calculated by a doctor in accordance with the patient’s medical indicators and the individual characteristics of her body. The absence of ovulation after several courses of taking the drug may signal the presence of certain pathologies of the reproductive system. A side effect of clostylbegitis may consist in thickening of cervical mucus, which prevents the movement of spermatozoa.

Today we will talk about the rules for the use of hormonal ovulation stimulation drugs. Hormonal drugs are drugs obtained synthetically. They act like natural hormones produced in the body.

Types of hormonal drugs for women

In the treatment of female infertility, hormonal drugs are always used, as a rule. Women can be prescribed combined oral contraceptives, tablet or transdermal (through the skin) drugs containing estrogens, progesterone preparations, as well as the well-known clomid.

During ovulation and superovulation stimulation (IVF protocols), antiestrogens (Clostylbegit), recombinant (purified), urinary preparations containing FSH and/or LH are used.

In IVF protocols, Gnrh agonists (Diferelin, Decapeptil), Gnrh antagonists (Orgalutran, Cetrotide) are prescribed. The trigger of follicle maturation is the hormone – chorionic gonadotropin.

Thyroid preparations (synthroid) or medications that reduce prolactin production, as well as many others, can be used for treatment.

Hormonal ovulation stimulation: side effects

For the safe and effective use of the necessary hormonal drugs, the doctor first needs to examine patients, collect anamnesis and additional examinations (ultrasound, blood tests for hormones).

There are practically no medications without side effects at all. But it is necessary to distinguish side effects that do not require withdrawal of the drug. For example, breast swelling when taking contraceptive hormones is considered a normal phenomenon.

Headache, dizziness, fluctuations in weight (plus or minus 2 kg) — all this is possible and, as a rule, passes quickly.

Most medications containing hormones have a large list of contraindications. The main ones are: malignant neoplasms or suspicion of their presence, hereditary or acquired risks of thromboembolic complications (changes in blood test parameters, identified genetic mutations of hemostasis that previously occurred in patients with thromboembolism, smoking, etc.).

! It is very important to inform at the reception of all the transferred diseases, the results of the examination and follow all the recommendations of the attending physician.

Rules for the use of hormonal drugs in IVF protocols:

Regularity and dosage. Hormonal drugs should be taken at the appointed time, with a clear regularity. If you miss an appointment or have doubts about the need to continue treatment, be sure to consult your doctor. Self-cancellation or dose change can lead to negative consequences.

The frequency of appearance for follicle growth monitoring is determined individually for each patient and depends on the follicle growth rate, the specifics of the stimulation protocol.

If the patient could not get to the appointment due to unforeseen circumstances, then it is necessary to coordinate further actions by phone with the attending physician. Ovulation stimulation is carried out with daily doses of hormones, missed days can affect the result achieved.

The dosage of hormonal drugs is prescribed by the doctor individually and must be strictly observed. Any deviation in the direction of increasing or decreasing the dosage can completely disrupt the entire treatment process.

Introduction of a trigger (hCG). As soon as the ultrasound picture shows that the ovulation stimulation process is completed successfully, i.e. the follicles are ripe enough for puncture, the patient is prescribed a single injection of hCG. This drug is administered 35-36 hours before the puncture.

Ovulation may occur after 37 hours. If less than 34 hours pass after hCG administration and puncture, the oocytes will not have time to mature. In such situations, the follicles will be empty during puncture.

That is why it is so important to inject hCG at exactly the appointed time. In those situations when the patient accidentally changed the time of the trigger injection, he should immediately inform the attending physician in order to coordinate a possible change in the time of the operation.

During intrauterine insemination, the principle of the introduction of a trigger (hCG), as a rule, changes. After the introduction of the final ovulation drug, insemination is prescribed a day later, and a repeat procedure is performed 1-2 days after the first one. So it is planned to carry out insemination before and after ovulation.

The average age of American women deciding to give birth to their first child is 26.7 years. In New York, they become mothers even later — on average, at 28.5 years. Representatives of the fair sex are no longer in a hurry to start a family, preferring the development of business, career, and motherhood issues are trying to postpone. But does the female body agree with such attitudes and what are the chances of getting pregnant after 30? The gynecologist listed the factors affecting female fertility and told about the possibilities of its preservation.

What is female fertility?

The term has a Latin origin – “fertilis”, which means fertile, fertile. That is, fertility is the ability to conceive, bear and give birth to healthy offspring.

Is it true that fertility is divided into low, normal and high?

Yes, although the division is very conditional:

Low fertility is the inability of a woman to conceive and/or give birth to a healthy child without medical care.

Normal fertility is the ability to get pregnant on your own, to carry and give birth to a healthy child without medical care.

High fertility is the ability to get pregnant independently and give birth several times in a short period of time, as conceived by nature. In this case, the woman does not even need clomid to stimulate ovulation.

Chances of getting pregnant. Factors affecting fertility

Age

By the 20th week of intrauterine development, there are about 7 million immature germ cells in the girl’s ovaries. By the time of the onset of the first menstruation, only 300-400 thousand eggs remain under the influence of strong hormonal changes.

Do you think that every month in case of non-pregnancy you lose only 1 egg? That’s not so. The processes of death of follicles (structural components of the ovary, consisting of an egg and its “environment”) occur constantly under the influence of various factors, especially stressful.

Usually, fertility decreases after 30-35 years: at this time, the number of follicles not only significantly decreases, tending to 25 thousand, but also the rate of their disappearance increases and the quality of the oocytes themselves (immature eggs located in the ovary, from which mature ones are subsequently formed) significantly deteriorates.

Weight

Adipose tissue is an endocrine organ that has a hormonal function. Insufficient or excessive accumulation of estrogens in adipose tissue can cause ovulation block, menstrual cycle failure and, as a consequence, the absence of a successful pregnancy.

Overweight women have a large symptom complex of pathological adaptive mechanisms that combine under one diagnosis – metabolic syndrome. All this increases the risk of infertility, polycystic ovary syndrome, hyperandrogenism and miscarriages in the first trimester. During pregnancy, such women have a higher risk of diabetes in pregnant women, increased blood pressure and the development of preeclampsia (pregnancy complication), and the risk of operative delivery (cesarean section) is also higher.

With a lack of body weight, the body experiences extreme stress and directs all its efforts to survival, not to maintain reproductive function. That is why skinny girls, as a rule, do not have menstruation or they manifest themselves with very scanty secretions. Problems with menstruation indicate a low reproductive capacity.

Excessive physical activity

Naturally, physical activity is useful. But the good thing is that in moderation. Any intensive training puts an excessive load on the adrenal glands, so stress hormones are released: adrenaline and norepinephrine, and a cascade of biochemical reactions is triggered that increases androgens in the blood, which, in turn, can lead to ovulation block.

The lack of physical activity leads to stagnation of blood in the pelvis, lymphostasis, which means that the metabolism in the reproductive organs worsens and their nutrition is disrupted.

Chances of getting pregnant: sleep

Sleep is very important for women’s health. The production of melatonin, responsible for reparative processes in the body, the development of immunity, the restoration of basic biochemical processes, falls precisely at night.

Sex

During intimacy, a lot of blood flows to the pelvic organs, a generous cocktail of hormones and neurotransmitters is thrown into the blood, undoubtedly, this has a beneficial effect on fertility. Having an orgasm, achieving peak pleasure is a real medicine that prolongs female youth and increases the chances of successful conception.

We will not mention such obvious things as smoking or alcohol. They negatively affect fertility, ovulation and significantly reduce the chances of getting pregnant.

What affects the reduction of follicular reserve?

• bad habits (sedentary lifestyle, non-compliance with work and rest, smoking, abuse of harmful foods);
• ecology, electromagnetic radiation (I hope you don’t carry a mobile phone in your pants pockets and don’t put a laptop on the pelvic area);
• chronic stress;
• ovarian surgery (in particular, resection);
• autoimmune diseases;
• genetic features;
• chronic inflammatory diseases of the pelvic organs;

Menstrual cycles are caused by the growth of the follicle and the release of the egg from it. This phenomenon is called ovulation. Then the egg enters the lumen of the fallopian tube, where it can be fertilized by a sperm. Conception cannot occur if the meeting of these two germ cells does not take place. Therefore, not every sexual act ends with fertilization. It is necessary to simultaneously match several conditions, one of which is ovulation that occurred the day before. What could be the reasons for the absence of ovulation?

Absence of ovulation: anovulation is a condition in which, for various reasons, the egg does not exit. The onset of pregnancy in a natural way is impossible. But this does not mean that a healthy woman must conceive after a month of sexual life without protection. The moment of rupture of the follicle is theoretically calculated, but in practice ovulation can occur both earlier and later (may depend on external factors), there may be cycles without ovulation (4 times a year such cycles are the norm), not every egg is capable of fertilization. It is believed that in healthy couples of 25 years planning pregnancy, the percentage of its occurrence (precisely because of the unpredictability of the cycle) is about 30-35%, which is slightly different from the percentage with IVF under the same conditions. The cause may be more significant deviations associated with pathologies. Infertility can be discussed if pregnancy does not occur during the year of life with a partner without the use of contraception until the age of 35 and within 6 months if the partner is over 35 years old.

One of the reasons may be anovulation. This diagnosis is made after a targeted examination.

Physiological reasons for the absence of ovulation

There are a number of conditions in which a healthy female body does not provide an egg during one or a number of cycles. And this is completely normal from the point of view of physiology. So, ovulation stops immediately after pregnancy and resumes only after the end of lactation. The restructuring of the body occurs due to the natural reaction of the endocrine system.

Ovulation does not always occur simultaneously with the onset of menstruation in teenage girls. The postponement of puberty can last up to two years. And this is also considered a physiological norm.

In childbearing age, outside the periods of pregnancy and lactation, women may experience pauses of so-called rest, during which ovulation does not occur for physiological reasons. Such states occur periodically and may have a length of several cycles. Normally, during the year there is from one to 5 times skipping the output of the oocyte.

The number of eggs in women is limited, so when their limit is exhausted, natural menopause occurs. By the end of childbearing age, ovulation may occur irregularly.

What diseases can cause anovulation

Diseases of the endocrine system lead to pathological anovulation, first of all. The so–called brain glands – the pituitary gland and hypothalamus – play an important role in controlling the processes occurring in the ovaries. They produce important hormones that affect the maturation of germ cells. A violation of the blood circulation of the brain or its tumors often cause anovulation. For the normal functioning of the ovaries , the danger is:

• pituitary tumor lesion;
• hypothalamic dysfunction;
• increased prolactin levels;
• increased androgen levels;
• stress.

The absence of ovulation can also occur against the background of:

• inflammation of the appendages;
• polycystic ovaries;
• thyroid disorders;
• liver diseases;
• injuries and pathologies of internal genitalia;
• underweight or overweight;
• taking hormonal contraception medications;
• uncontrolled use of steroid drugs.

These diseases and pathological conditions are not necessarily accompanied by a complete absence of ovulation. But if anovulation takes place, then it is associated with one of these reasons or their complex.

Symptoms and diagnosis

With a normal menstrual cycle that lasts 28-30 days, ovulation occurs between the 9th and 14th day. The output of the egg can be tracked at home using an ovulatory test, which can be purchased at any pharmacy. If the test is positive, it means that the most favorable moment for conception has come. Indirect signs of the approach and onset of the moment of maturation and release of the oocyte include changes in the nature of vaginal secretions – they become transparent. If a woman has a lowered pain threshold, then she may feel a pulling pain in the ovary area at the moment of rupture of the dominant follicle.

The absence of ovulation can be indicated by many disorders of ovarian function, including polycystic. They manifest themselves as a cycle failure, menstruation delays or their complete absence. Obvious signs of anovulation:

• the absence of a natural increase in rectal temperature observed in the middle of the cycle;
• the nature of vaginal discharge does not change in the period between menstruation;
• a sharp deterioration in the condition of the skin and hair;
• negative ovulation test on probable days.

To more accurately establish the fact of anovulation, it is necessary to monitor 3-4 menstrual cycles in a row.

Even if a woman is not planning pregnancy in the near future, with symptoms of anovulation, she needs to consult a gynecologist to prevent the development of primary diseases.

The diagnosis of anovulation can only be made by a doctor. To do this, he needs to conduct a dynamic analysis of menstrual cycles based on observations.

Treatment in the absence of ovulation

Based on the results of the examination, the reason for the absence of ovulation in a woman of childbearing age is established. But often this violation is associated with lifestyle, stress, unhealthy diet and various abuses. In this case, it is enough to come to a healthy lifestyle, eliminate stress factors (perhaps undergo a course of psychotherapy) and ovulation is restored. If hormonal disorders were detected during the examination, then the treatment consists in its stabilization. The doctor may prescribe hormonal or metabolic drugs (for example, clomid).

With polycystic ovaries, they increase in size and thicken, which makes it difficult for the egg to exit. In addition, they begin to produce an excess of androgenic hormones, which suppresses the maturation of female germ cells inside the follicles. Infertility resulting from polycystic fibrosis is treated therapeutically or surgically, by resection of the ovaries.

With various pathologies that have led to a condition when the egg does not come out, an appropriate treatment strategy is chosen in gynecology. In itself, the absence of ovulation is just a symptom of a primary disease or a whole complex. Therefore, diagnosis is a very important step in restoring ovarian function and normalizing the menstrual cycle.

Prevention of problems associated with anovulation

The reasons for the absence of normal maturation and release of eggs, which are not related to congenital pathologies and hereditary factors, can be prevented with the help of prevention. Every woman should keep a menstrual diary. In cases of cycle failures, it is necessary to consult a gynecologist unscheduled. A timely examination will help determine the cause of the failure and prevent complications. A woman should monitor her diet, prevent deviations of body weight from her age norm. Obesity or anorexia are conditions in which the hormonal system fails, which certainly affects the function of the reproductive organs. Having a normal body mass index is useful not only for conception, but also for normal fetal gestation.

Women are not recommended to choose hormonal drugs on their own and take them uncontrollably. This can lead to a whole range of problems, including infertility due to ovarian dysfunction.

Poor nutrition is one of the reasons why some women can not get pregnant. Such conclusions were made by scientists on the basis of large-scale studies conducted. On their basis, a fertile diet was compiled, designed to increase the ability to conceive a baby.

The fact that the use of a certain set of products helps to get pregnant (we also remind you that clomid copes with this task perfectly) became known in the early 90s. Scientists have developed a special nutrition system after a long eight-year study in which more than 18 thousand women took part. The diet, called fertile, increases the chances of getting pregnant, and also affects the development of the fetus.

By the way, other studies conducted on animals have shown that a certain type of nutrition of parents before conception has a serious impact on the health of offspring.
Of course, when planning a pregnancy, you should not rely only on a diet, but as studies show, it can really increase the chances of conception. But of course, if a woman does not have serious problems like infection, clogged fallopian tubes, or if the cause of infertility is not any irreversible painful processes. What should be the nutrition of future parents?

What foods can not be consumed if you want to get pregnant

First of all, it is important to exclude from the diet coffee and products containing caffeine-Coca-Cola, Pepsi, etc. The fact is that caffeine suppresses the reproductive function of the body. Caffeine stimulates the production of androgens by the liver, adrenal glands, and ovaries. The increased amount of androgens does not have time to turn into sex hormones, as a result, the endocrine balance is disturbed. As a result, there is a lack of ovulation, an incompetent egg or sperm, polycystic ovary syndrome. Nicotine has the same effect.

You should also give up sugar and flour products. After consuming sugar and products with it, the glucose level increases. To reduce it, the body produces insulin, which can cause polycystic ovary syndrome, which is one of the most common causes of female infertility, problems with conception and even carrying a child.

Products with preservatives and dyes are also on the black list, since they directly affect the viability of the egg and sperm cells. In addition, settling in the liver, they disrupt its proper functioning, causing increased production of androgens.

Fertile diet: What does a woman have to get pregnant faster

The diet of the expectant mother should be rich in healthy fats, whole-grain products, vegetable proteins. All these products support the eggs in working condition, contribute to regular ovulation, normalization of sugar levels, and as a result, the onset of a long-awaited pregnancy.

Meat consumption should be reduced in favor of vegetable proteins – legumes, nuts, as well as fish and seafood. The researchers note that the use of excessive amounts of protein can negatively affect the attachment of the embryo to the uterine wall or interfere with its early development.

The diet should also contain a sufficient amount of vitamin E (vegetable oils).

As for dairy products, they should not be decontaminated. When following a fertile diet, it is recommended to consume fatty milk, cheese and yogurt. Dairy products with normal fat levels contribute to the production of a hormone associated with ovulation and fertility.

A distinctive feature of the fertile diet from others is the high level of folic acid. As is known, this acid plays a special role not only in conception, but also in the development of the embryo.

Fruits, nuts and greens are especially rich in folic acid.

Foods rich in vitamin C also contribute to the improvement of reproductive functions in women. In this regard, it is necessary to increase the consumption of citrus fruits, kiwis, apples, pears, wild berries, tomatoes, bell peppers and broccoli.

Experts recommend eating five servings of vegetables and fruits a day: three vegetables and two fruits. One fruit or vegetable is equal to one serving. It is also necessary to take vitamins.

These studies of the influence of nutrition on the probability of conception were conducted by scientists at the Harvard Medical Institute in Boston

We continue our articles about pregnancy with a diagnosis of PCOS. You can read the first part here.

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In Chile, a plenary session was held in 2002, the result of which was the first summation of data on the use of CC for ovulation induction, including in PCOS. It was noted that CC can be used in PCOS as monotherapy, in combination with gonadotropins, and in case of detected insulin resistance (IR) (using Caro and HOMA indices) — with metformin (MF). The main side effects of CC remain-the risk of multiple pregnancies, ovarian hyperstimulation syndrome and ovarian cancer. Later, studies began to appear in which it was noted that CC is most often ineffective at low doses in women with PCOS and obesity, and at higher doses (> 150 mg) it is often accompanied by hyperstimulated ovarian syndrome. And in such cases, a combination of CC and MF is more effective.

The important question remains, what is the percentage of pregnancy in women with PCOS during CC treatment? It was found that the restoration of ovulation with the use of CC occurs in 80%, and pregnancy-only in 35-40% of patients. The authors themselves associated this with the antiestrogen effect of CC at the level of the endometrium and cervical mucus. In addition, 20-25% of women with PCOS are clomiphene-resistant, and, as a rule, these are women with obesity, IR and severe hyperandrogenism.

Due to the need to discuss issues and summarize data on the treatment of PCOS in Greece, an ESHRE/ASRM consensus was held in 2007, which resulted in a synthesis of the data available at that time. The first-line drug was called CC, the second-line drug was gonadotropins, the next step in case of ineffectiveness of conservative therapy is the surgical method of treatment-electrocauterization of both ovaries (ECOI). The use of MF in women with PCOS should be limited and used only in those who have been diagnosed with a violation of glucose tolerance (HTH). The insufficient number of studies conducted in the field of biguanide use does not give a complete picture of this group of drugs for ovulation induction.

In 2009, the data of a comparative study on the use of CC, MF and their combination for ovulation induction were published. The randomized study involved 115 women who were divided into three groups. In the MF group, ovulation was achieved in 23.7%, in the CC group-in 59%, and in the combination of these drugs — in 68.4%, the birth rate was 7.9%, 15.4%, 21.1%, respectively.

Due to the lack of algorithms for the treatment of women with PCOS (taking into account age, anamnesis of the disease, the presence or absence of IR, etc.), the age of initiation of CC therapy is determined individually for each patient. In 2009, Badawy et al. published the results of a study in which they showed that the earlier a CT scan is prescribed in women with PCOS, the more pronounced the follicular growth in the ovaries, the thickness of the endometrium will be and, thus, the percentage of pregnancy will increase.

to be continued…

Today we are starting a series of articles about the ovulation stimulation of polycystic ovary syndrome, we are publishing the first part.

Polycystic ovary syndrome (PCOS) is the most common form of endocrinopathy, it occurs in 5-10% of women of reproductive age and accounts for 80%, and according to some data, even 90% of all forms of hyperandrogenism.

The classic picture of PCOS, or sclerocystic ovaries, was described by Stein and Leventhal in 1935 as a syndrome of amenorrhea and enlarged ovaries, combined in 2/3 of cases with hirsutism and in every second case with obesity. However, later it was noted the existence of a wide variety of forms of the syndrome, manifested by a significant variation in the clinical picture of the disease, the endocrine profile and morphological features of the classic syndrome, in connection with which the term “polycystic ovary syndrome”was proposed. In recent years, the concept has been put forward, which has received universal approval, that the clinical manifestations associated with PCOS should be interpreted precisely as a syndrome, and not as a disease, this is a more accurate and specific term.

The etiology and pathogenesis of PCOS are still not fully understood, despite the huge number of studies devoted to this problem.

Ovulation stimulation and the Rotterdam Consensus

The final document of the Rotterdam Consensus (2003) stated that PCOS remains a diagnosis that requires the exclusion of other known disorders that manifest themselves as universal clinical signs of hyperandrogenism, and therefore can mimic and occur “under the mask” of PCOS. While PCOS itself is a syndrome of ovarian dysfunction (irregular menstruation, anovulation, infertility), the specific manifestations of which include not only hyperandrogenism, but also the “polycystic” morphology of the ovaries. Thus, for the first time, an agreement was reached on the need to give an ultrasound assessment of the size and structure of ovarian tissue a significant diagnostic criterion.

According to the consensus, the presence of at least two of the three criteria makes it possible to verify the diagnosis of PCOS after excluding other conditions. Thus, on the one hand, in terms of examination, PCOS remains a syndrome (a complex of symptoms), the identification of which is impossible and unacceptable on the basis of the isolated presence of any single diagnostic criterion. On the other hand, a simple analysis of the pairwise combination of modern criteria allows us to draw a fundamental conclusion about the need for an expanded interpretation of the term PCOS. This is due to the additional inclusion of new clinical forms in its definition, namely: in the absence of another hyperandrogenic pathology, the diagnosis of PCOS is permissible not only in the classical course (a complete triad of signs), but also in the presence of one of three incomplete (non-classical) clinical and instrumental duets.

It is known that PCOS accounts for 56.2% of all forms of endocrine infertility. Currently, it is believed that the main ways to restore fertility in patients with PCOS should be considered assisted reproductive technologies( ART), the purpose of which is not to treat a woman, but to achieve pregnancy in a specific cycle of ovulation stimulation. The concept of ART includes not only methods of in vitro fertilization (IVF), but also conception in a natural way as a result of various methods of ovulation induction.

The leading link in the structure of assisted reproductive technologies in PCOS is the induction of ovulation. For this purpose, various medications are used individually — derivatives of chlortrianisene – clomiphene citrate (CC) and its analogues, combined oral contraceptives, gonadotropins, gonadotropin-releasing hormone analogues, insulin sensitizers, aromatase inhibitors.

The drug of choice for anovulation is considered to be CC, which was first synthesized in 1956 by WS Merrell for contraceptive purposes. Initially, CC was used for endometrial cancer during the preparation of patients for surgery, but during surgical interventions, yellow bodies in the ovaries and secretory transformation of the endometrium were accidentally discovered, which served as the basis for the use of CC as an ovulation inducer, and since 1967, the use of the drug in patients with anovulatory dysfunction began. Is CC a first-line drug for the treatment of infertility in women with PCOS? This question has arisen throughout the use of this selective estrogen receptor modulator, and there is still no clear answer: whether to use it as monotherapy or in combination with other drugs.

to be continued…