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15
II. DIAGNOSTIC AND TREATMENT
TUBAL-PERITONEAL INFERTILITY. ETIOPATHOGENESIS AND DIAGNOSTICS. REVIEW
Toreeva Sh.M.13, Kosherbayeva L.K.1, Aldangarova G.A.23
1Al-Farabi Kazakh National University, Almaty, Kazakhstan 2Kazakh-Russian Medical University, Almaty, Kazakhstan
3National Scientific Center of Surgery named after A.N. Syzganov, Almaty, Kazakhstan
МРНТИ 76.29.48
Тореева Ш.М. -
orcid.org/0000-0003-1198-8248
Кошербаева Л.К -
orcid.org/000-0001-8376-4345
Алдангарова Г.А. -
orcid.org/0000-0001-5927-0687
Abstract
Today, in the field of modern technologies, despite successes in the field of reproductology and advanced assisted reproductive technologies (ART), the frequency of infertile marriage has not only not stabilized, but also increased over the year, reaching 25-30% in the population. Tubal peritoneal infertility is one of the leading places in the frequency of occurrence of various factors leading to the absence of an oncoming pregnancy.
TYTiKri-перитонеальды бедеулш. Этиопатогенезi жэне диагностикасы. (Эдебиет шолуы)
Keywords
infertility, tubal-peritoneal factor, proxy obstruction of the fallopian tubes, selective hysterosalpingog-raphy, transcatheter recanalization of the fallopian tubes
Тореева Ш.М.1,3, Кошербаева Л.К.1, Алдангарова Г.А.2,3
1эл-Фараби атында?ы Казак, улттык, университет 2Казак,стан-Ресей медициналык, университет
3«А.Н. Сыз?анов атында?ы Улттык fbrnb^ хирургиялык, оргаль™» АК, Алматы, Казахстан
Ацдатпа
K,a3ipri заманты технологиялар саласында, репродуктология саласындаты жетЫктер мен жетiлдiрiлген KßMerni репродуктивт технологиялар€а (КРТ) карамастан, бедеулк неке^н жишг турактандырып кана поймай, жыл сайын ecin, халыктын 25-30% курады. Tyrim перитонеальдi бедеулк - бул алдаты жуктштн болмауына экелелн эрrYрлi факторлардын пайда болу жилг бойынша жеrекшi орындардын бiрi.
Туйш сездер
бедеулк, тупкп -перитонеальдi фактор, жатыр тyriкrерiнiн проксимальдi кедергю, селективт гисrеросальпингография, жатыр т^ктер^н rранскаrеrердi реканализациясы
Трубно-перитонеальное бесплодие. Этиопатогенез и диагностика. (Обзор литературы)
Тореева Ш.М.13, Кошербаева Л.К.1, Алдангарова Г.А.23
1Казахский национальный университет им. аль-Фараби, г. Алматы, Казахстан
2Казахстанско-Российский Медицинский Университет, г. Алматы, Казахстан
3АО «Национальный научный центр хирургии им. А.Н. Сызганова», Алматы, Казахстан
Аннотация
На сегодняшний день, в век современных технологий, несмотря на успехи в репродуктологии и усовершенствований методов вспомогательных репродуктивных технологий (ВРТ), частота бесплодного брака, не только не стабилизировалась, но и увеличивается из года в год, достигнув показателей 25-30% в популяции. Трубно-перитонеальное бесплодие находится на одном из ведущих мест по частоте встречаемости различных факторов, приводящих к отсутствию наступления беременности.
Ключевые слова
бесплодие, трубно-перитоне-альный фактор, проксиальная непроходимость маточных труб, селективная гистеросальпинго-графия, чрескатетерная рекана-лизация маточных труб
Female infertility of tubal origin - the absence of the desired pregnancy due to a congenital abnormality of the fallopian tubes or tubal: obstruction, blockage, stenosis (code N97. 1 in the International classification of diseases of the 10th revision (ICD; 10) (International Classification of Diseases, ICD). [1]
Infertility is considered a marriage in which a woman of childbearing age does not become pregnant during a year of regular sexual activity without the use of contraceptives.
According to many authors, the frequency of infertile marriage in the world is 10-15%, and in Kazakhstan it reaches up to 17%. [2, 3, 4, 5]
The female factor in infertile marriage is 40%, the share of the male factor occurs in 40% of cases, and in other cases of infertility there is a combined factor, both female and male. [6]. In this regard, the search for new methods and their improvement, as well as reducing the cost of infertility treatment, are very relevant.
According to most authors, tubal obstruction is the main cause of infertility in women in 25-35% of cases. Ovcharenko D. V. came to the conclusion that more than 50% of fallopian tube obstruction is a consequence of infectious and inflammatory processes of the genitourinary and, less often, digestive systems. [3,6,7].
According to D. N. Isaikin et al., the leading place in the Genesis of reproductive disorders is occupied by the tubal-peritoneal factor (43%), genital endometriosis, endocrine infertility, and benign neoplasms of the pelvic organs are somewhat less common [8,9].
Tubal-peritoneal infertility in the modern world continues to hold a leading position in the structure of female fertility due to sexually transmitted diseases, unsafe abortions and postpartum pelvic infections. K. Vaid et al. (2014) they indicate that in the structure of female infertility, the tubal-perito-neal factor is 40-50%.
Tubal-peritoneal infertility factors in the form of impaired patency and functional failure of the fallopian tubes are detected in 29.5-83% of patients with impaired generative function. In primary infertility, the incidence of fallopian tube damage is 29.5-70%, in secondary infertility-42-83%. [10]
Inflammatory damage to the fallopian tubes is the leading cause of infertility. In a report by O. Jaiycoba et al. (2011) showed that every year 120180 women out of every 10 thousand at the age of 15-24 years, 30-90 per 10 thousand at 15-44 years, there is inflammation of the genitals. As a result of a chronic inflammatory process that occurs with damage to the fallopian tubes, the risk of tubal-peritoneal infertility is high. Every fifth woman with a history of chronic inflammation of the append-
ages suffers from infertility, while 70% of them have a fourth degree of adhesions in the pelvis, in which damage to the fallopian tubes is irreversible even with the help of surgical treatment.
Studying the causes of infertility in women, a number of experts have concluded that tubal infertility, associated with a mechanical barrier to the fusion of the sperm with the egg, has the greatest share; its frequency on average is 42.5-80.5%. The formation of connective tissue adhesions between the visceral and parietal peritoneum of the pelvis helps to change not only the anatomical but also the functional state of the internal genital organs, which is accompanied by disorders of the mechanisms of ovulation, the perception of the egg and its transport, the formation of chronic pain syndrome, dyspareunia, dysmenorrhea, dysfunction of adjacent organs. [7]
In 25% of women, tubal-peritoneal infertility was caused by previous surgical interventions. Surgical interventions for various non-inflammatory gynecological diseases, regardless of the type of surgical access, in 81% of operated women lead to the occurrence of adhesions, and the frequency of adhesions after gluttony is 89.2%, and after laparoscopic operations - slightly less - 71.5%.
H.C.Wiesenfeld et al. (2012) note that there is no decrease in the frequency of tubal-peritoneal infertility against the background of an officially registered decrease in the frequency of acute inflammatory diseases of the pelvic organs. The authors believe that in fact, there is no reduction in the incidence of acute adnexitis, but there is a change in the course of PID - the frequency of their subclini-cal course increases in women with chlamydia and gonococcal cervicitis and/or bacterial vaginosis. In addition, a significant factor that reduces the quality of PID therapy is the late start, incorrect choice, and premature cancellation of antibacterial therapy.
The main risk factors for chronic inflammatory diseases in women of reproductive age: sexually transmitted diseases, spontaneous and artificial abortions, IUD administration. The inflammatory process is one of the most frequent complications of intrauterine medical and diagnostic manipulations, including artificial termination of pregnancy.
According to F. Herrero (2009), 58% of women developed secondary tubal-peritoneal infertility after undergoing a medical abortion. The authors also concluded that the cause of fallopian tube occlusion may be not only infectious inflammation, but also adhesions after operations on the pelvic or abdominal organs, especially after destructive forms of appendicitis, myomectomy, ovarian resection, salpingectomy for tubal pregnancy. Despite the fact that endoscopic access during surgery for tubal pregnancy is more preferable in terms of postop-
erative complications and restoration of women's reproductive function, for emergency indications, many hospitals in our Republic still use laparo-tomic access and perform removal of the fallopian tube. According to many researchers, 70-80% of women experience infertility after such operations [3,11,12].
Therefore, the development and implementation of endoscopic access and organ-preserving approaches in the treatment of patients with any gynecological diseases can reduce the number of patients with infertility. In addition, complications after medical abortions, spontaneous miscarriages, and intrauterine surgeries are common causes of secondary tubal infertility. Tubal infertility can lead to tumors of the uterus and ovaries, in which either mechanical compression of the fallopian tubes occurs, or their functional state is disturbed.
According to Yakovleva N. V. (2014), tubal obstruction caused by endometriosis occurs in 1115% of cases. Lesions of the fallopian tubes can manifest themselves not only in the form of occlusion, but also in changes in their functional activity, as a result of which the promotion of sperm, the capture of an egg and its transport after fertilization to the uterus is disrupted.
Violation of the patency of the fallopian tubes is one of the leading causes of infertile marriage and according to world statistics is 35-40% [13]. The average incidence of obturation lesions of the fallopian tubes among women suffering from infertility is from 10% to 33%. [7]
The main group of patients with tubal infertility consists of patients suffering from inflammatory diseases of the genitals. Pelvic inflammatory processes account for 74-80% of all gynecological diseases and 24% of the total number of patients admitted to a gynecological hospital. Most fallopian tube diseases occur as a result of inflammatory processes, which are most often the result of postabortion and postpartum inflammation, as well as an increase in the number of sexually transmitted diseases (STDs). The frequency of post-inflammatory changes in the fallopian tubes among long-term and unsuccessfully treated patients with a regular menstrual rhythm was 60-85% [12], while more than half of them had impaired tubal patency, 27.7% [23] had hydrosalpinxes, and 3.2% had nodose salpingitis. According to E. A. Yakovleva et al. (2013), the incidence of fallopian tube damage in infertility reaches 70%. Genital inflammatory processes are diagnosed in 60% of patients with primary and 40% with secondary tubal-peritoneal infertility. [14].
Direct changes in pipes are reduced to complete or partial obstruction. According to O. V. Astafieva et al. (2012), complete fallopian tube occlusion is detected in 14.2% of women with infertility, and
post-inflammatory changes in the tubes that do not lead to complete occlusion are diagnosed in 9.2% of patients.post-Inflammatory changes developing in the interstitial, isthmic or ampullary sections lead to damage to the muscle layer, adhesions, and peri-tubar changes.
Post-inflammatory changes in the tube can cause both mechanical obstruction of the tube, and violation of the ciliary, secretory, contractile muscle activity of the fallopian tube and its innervation.
The inflammatory process often spreads to the muscle and serous membrane and causes damage to the neuromuscular fibers, thereby causing a decrease in the contractile function of the fallopian tube. In this regard, some researchers consider violations of the contractile activity of the fallopian tubes after inflammatory diseases one of the main causes of tubal pregnancy and infertility of tubal Genesis. In 40-52% of patients, the result of tubal implantation is an organic pathology of the fallopian tube in the form of scar-dystrophic changes in its muscles. Thus, dystrophic changes in the endo-salpinx (in epithelial cells and ciliated epithelium), which lead to an increase in the adhesive component, thereby enhance the interaction of the fetal egg with the mucous membrane. Endocrine, au-tocrine, and paracrine mechanisms are involved in regulating the function of the fallopian tubes. The ciliated secretory epithelium of the mucosa, smooth muscle tissue of the tube wall and its vessel, as well as the endothelium contain epidermal growth factor (EFR), transforming growth factor (TFR-a), and EFR/TFR-a receptors. The EFR/TFR-a ratio is assigned the role of a potential regulator of the movement of epithelial cilia, its secretion, peristalsis, oviduct blood circulation, and epithelial cell proliferation. Stimulation of EGF/TFR-a receptors in a woman's fallopian tube is carried out under the influence of estrogens and prostaglandins, whose imbalance negatively affects the functioning of the fallopian tubes. [12].
Morphological studies of tissues have confirmed that chronic inflammatory diseases of the uterine appendages lead to the disintegration of the muscular and serous membranes of the fallopian tubes. Electron microscopic examination revealed sharp damage to myocytes, edema of the cytoplasm of cells. All taken together, it disrupts or makes impossible both the perception and transport of the egg to the uterus, as well as some stages of its development during its stay in the fallopian tube.
According to the literature, after a single episode of salpingitis, tube obstruction is detected in 11-13%, after a double episode-in 26-35%, with three or more episodes in 54-74% of cases.
20% of patients with tubal infertility develop pelvic adhesions, i.e. there are pronounced anatomical
changes in the internal genitals [10,12].По данным Абашидзе А.А. и соавт. (2014), при лапароскопии у женщин с бесплодием, обусловленным хроническими воспалительными заболеваниями придатков матки, спаечная болезнь органов малого таза выявляется у 86,4%.
The predominant lesion of the ampullary parts of the fallopian tubes is described in all types of salpingitis-even in the experiment, and is a protective mechanism that prevents the spread of infection in ascending and descending salpingitis. A pronounced inflammatory process in these parts of the tubes, followed by fimbria sticking together at the sites of ciliated epithelium death and scarring, leads to gross anatomical changes in the tubes by the type of baggy inflammatory pseudotumors
- hydro - and sactosalpinxes. With the long-term existence of hydrosalpinxes, atrophy of the ciliated epithelium occurs, and the prognosis of healing and restoration of the tube function significantly worsens. [7,12]
Genetic determinants have a significant impact on the development of reproductive disorders. In this regard, integrins - the "biological glue of life"
- are of interest. Integrins are glycopreins-protein complexes located on the outer membrane of the cell and specifically bind to extracellular structures, consisting of two subunits a - and p -, which can non-covalently bind to each other in different combinations, forming more than 20 types of integrins. The classification of integrins is based on the presence of a certain type of p-subunit in the integrin. Each subunit can be represented by several variants that are encoded by a group of related genes. Thus, the p-subunit of type III, subtype a (glycoprotein IIIA, or GP IIIA), is represented by two allelic forms-PLAI and PLAII. The GP IIIA gene encodes the formation of specific integrin receptors responsible for intercellular contacts and vascular disorders at the cellular level. Glycoprotein IIb-IIIA (GP IIb-IIIA), a fibrinogen receptor located on the platelet surface, is a key factor in platelet aggregation. The GP IIIA gene has two allelic forms-PLAI and PLAII, respectively, each woman can be homozygous for one of them, or heterozygous. Special attention is paid to the PLAII allele, the occurrence of WHICH is associated with the transition of the thymine nucleotide to the cytisine one in position 196 of the third exon of the Gpiiia gene, and the presence of which is associated with the processes of venous and arterial thrombosis, as well as with implantation disorders, in particular, restriction of trophoblast invasion by surface layers. The frequency of occurrence of the PLAII allele of the Gpiiia gene in the population is approximately 14.5%. [12, 15]
For the first time, the genetic mechanisms of restoring fertility in patients with tubal-peritoneal
infertility, in particular, the study of the distribution of allelic forms of the Gpiiia gene, were considered in the work Of S. V. Apresyan et al. (2003). The authors found that surgical restoration of fallopian tube patency is most effective in women who carry the PLAII allele of the Gpiiia gene (heterozygotes). Later, L. A. Salimova (2005) showed that carrying the PLAII allele of the Gpiiia gene in women with inflammation of the uterine appendages increases the likelihood of reproductive disorders, in particular, increases the risk of developing chronic endo-metritis, luteal insufficiency (NLF syndrome) and infertility. [12]
In the literature there is considerable discussion about the nature of the lesion of the fallopian tubes depending on the microbial factor, which was the cause of the disease. According to the dominant point of view today, the initiators of inflammation in organs and tissues are microorganisms present in the vagina, as well as sexually transmitted. Currently, the infectious factor has the character of mainly mixed infection, while the most common pathologic foci of chronic inflammation in the genitals of women are sexually transmitted microorganisms: chlamydia, Mycoplasma, Ureaplasma, gonococci, Trichomonas, as well as gram-positive and gramnegative aerobic and anaerobic microorganisms. [14]
The cause of tubal occlusion is most often pelvic inflammatory processes caused by sexually transmitted infections (gonorrhea, chlamydia, Ureaplasma, Trichomonas). A modern feature of the course of inflammatory diseases of the uterine appendages is their erased nature, followed by the development of a severe deforming process in the fallopian tubes and tubalyperitoneal infertility. [3,7,12,16]
According to Yakovleva E. A. (2013), the most common microbial agents that cause pelvic inflammatory diseases in women are Chlamidiatracho-matis (25-30%), NeisseriaGonorrhoea(25-40%), Mycoplasmahominis and Ureaplasmaurealiticum (30-40%), polymicrobial associations of opportunistic, pathogenic aerobic and anaerobic microorganisms. All the above-mentioned microorganisms cause low-symptom and subclinical processes, the clinical severity of which does not correspond to the severity of destructive and infiltrative changes in the uterine appendages. Laparoscopy in these cases reveals effusion, obturation of the fallopian tubes, leading to infertility or predisposing to ectopic preg-nancy.Общепринято мнение, что хламидийная инфекция протекает практически бессимптомно, вызывая выраженные анатомические изменения маточных труб по типу гидросальпинксов, перитубарные спайки и перигепатит (синдром Fitz-Hygh-Curtis). [16,18]
Unanyan A. L. et al. (2014) revealed electron microscopic features of the fallopian tubes and peritoneal fluid in patients with inflammatory diseases of the uterine appendages of chlamydial etiology. Thus, violations were found in the capillary link of the microcirculatory bed in the form of loss of villi cells, involvement of individual villous epithelial cells in the autolytic process, formation of lymphoid infiltrates, and other changes. According to the authors, the combination of these processes can lead to a decrease in the patency of the fallopian tubes and a violation of the barrier function of the epithelium. The presence of destructive changes in the epithelium, loss of function of the ciliated epithelium of the tubes, violation of their peristalsis can lead to the development of infertility.
A significant influence on the development of salpingitis and tubal infertility is exerted by the state of the immune system of a woman's body. Special importance is attached today to the violation of immunological reactivity, since immune insufficiency weakens compensatory and protective mechanisms, inhibits the development of tissue regeneration processes and prevents the restoration of impaired functions of the reproductive system.
Changes in the endocrine function of the ovaries due to the inflammatory process of the uterine appendages lead to impaired motility of the fallopian tubes in 32-35% of cases. These include functional dishormonal changes-permanent or episodic pathological conditions that cause an imbalance in the hypothalamus-pituitary-ovary system and lead to inadequate secretion of estrogens and progesterone and, accordingly, to a distortion of the contractile function of the fallopian tubes. [12,19]
Petrov Yu. a. et al. (2018) noted that the degree of explication of inflammation is inversely
related to the degree of expression of estrogen (ER) and progesterone (PR) receptors. That is, the higher the degree of inflammation, the lower the expression of the ER, PR, and Ki-67 receptors (a marker of rapid proliferation) in the endometrium, which causes infertility by itself in the absence of other factors. Further study of this problem showed that the expression of ER and PR depends on the phase of the menstrual cycle (MC). On day 6-9 of MC, leukocyte infiltration of the stromal and glandular components of the endometrium occurs, resulting in increased expression of both types of receptors (Eripr), which is observed at the initial stages of inflammation.
On day 19-22 of the MC, the uterus is undergoing a proliferation stage, a decrease in PR activity is detected, and the degree of ER expression remains unchanged.
If there are local sclerotic changes in the uterine mucosa, the expression of PR decreases sharply against the background of a stable moderate expression of ER expression throughout the MC.
The problem of timely diagnosis, establishing the etiology of salpingitis, and detecting changes in the immune and endocrine systems is largely complicated by the peculiarities of the current course of the inflammatory process. Due to the multiplicity of sources of infection, a decrease in the pathogenesis of chronic salpingoophoritis of the primary pathogen of the inflammatory process, an increased role of frequent secondary infection, the primary chronic course of the disease with scant clinical symptoms and pronounced anatomical changes in the lesion.
In order to diagnose the anatomical and functional state of the fallopian tubes in infertility, a number of methods are used that are not so much competing as complementary to each other, which differ in the degree of invasiveness and information content.
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