Stimulation of ovulation of PCOS. Part 2.

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


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.

PCOS

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…

Stimulation of ovulation of polycystic ovary syndrome

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.

ovulation stimulation

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…