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Vol 69, No 5 (2020)

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Actual Health Care Problems
Differential diagnosis of the uterine septum: problems and solutions
Kazantseva E.V., Shelayeva E.V., Rusina E.I.

The article presents literature data on the peculiarities of diagnosing different types of uterine abnormalities. The main topic of the publication is the role and effectiveness of three-dimensional ultrasound in the differential diagnosis of the uterine septum.

Journal of obstetrics and women's diseases. 2020;69(5):5-12
Possibilities for predicting abnormal labor at the present stage
Mudrov V.A.

Hypothesis/aims of study. Labor abnormalities can lead to dangerous complications for both the mother and the fetus. There are currently no effective ways to prevent abnormal uterine contractile activity. Therefore, the timeliness of diagnosis, which largely determines labor outcome, depends on the effectiveness of assessing the likelihood of the development of abnormal labor. The aim of this study was to examine the possibilities for predicting abnormal labor progression at the present stage of the development of science.

Study design, materials and methods. A systematic analysis and synthesis of the literature data presented by domestic and foreign authors in the period from 1985 to 2020.

Conclusion. A comprehensive approach to assessing the likelihood of the development of abnormal labor will optimize the tactics of labor management, which in the long-term will reduce the frequency of surgical delivery.

Journal of obstetrics and women's diseases. 2020;69(5):13-26
Original Researches
Gas chromatography-mass spectrometry-based metabolic profiling of androgens, progestins and glucocorticoids in women with polycystic ovary syndrome
Vorokhobina N.V., Velikanova L.I., Glavnova O.B., Malevanaya E.V., Galakhova R.K., Matezius I.Y.

Hypothesis/aims of study. Polycystic ovary syndrome (PCOS) is a common disease. Depending on the diagnostic criteria, the disease is seen in 10-20% of women of reproductive age and accounts for 70-80% of all forms of hyperandrogenic syndrome. PCOS is a heterogeneous condition of multifactorial etiology characterized by various clinical, endocrine and metabolic disorders. Therefore, it is important to clarify the specific features of steroid hormone biosynthesis and metabolism and steroidogenesis enzyme activity, as well as to search for new laboratory criteria for early diagnosis and prompt treatment. The aim of this study was to perform metabolic profiling of androgens, progestins and glucocorticoids using gas chromatography-mass spectrometry (GC-MS) in obese and non-obese women with PCOS.

Study design, materials and methods. We examined 53 women of reproductive age diagnosed with PCOS. The first group included 30 women aged 22 to 29 years with normal body weight. The second group comprised 23 obese patients aged 25 to 33 years with an average body mass index (BMI) of 35.3 ± 0.4 kg/m2. The control group consisted of 25 healthy women aged 26 ± 0.6 years having a normal BMI without clinical and biochemical signs of hyperandrogenism. Immunoassay methods were used to determine the serum levels of luteinizing hormone, follicle-stimulating hormone, free testosterone, 17-hydroxyprogesterone, and sex hormone-binding globulin. A glucose tolerance test was performed to determine glucose and insulin levels before and after load. Urine steroid profiles were studied by GC-MS with the optimization of the sample preparation schedule. Statistical data processing was performed using the STATISTICA for WINDOWS software system (version 10). The main quantitative characteristics of the patients are presented as the median (Me), the 25th percentile and the 75th percentile (Q25Q75). To compare the results obtained in the study groups, the nonparametric Mann-Whitney test was used. The 95% confidence interval was considered statistically significant.

Results. The article presents a metabolomics analysis of androgens, glucocorticoid hormones and progestins in women with PCOS compared to the control group. It was revealed that non-obese patients with PCOS had increased urinary excretion of androstenedione metabolites, dehydroepiandrosterone and its metabolites, 17-hydroxypregnanolone, pregnantriol, and 5-ene-pregnenes, while obese patients with PCOS had increased that of androsterone and dehydroepiandrosterone metabolites (16-oxo-androstenediol and androstenediol-17β) compared to the control group findings. Decreased ratios of cortisol and cortisone tetrahydro metabolite amount to the levels of 11-oxo-pregnanetriol, pregnanetriol and 17-hydroxypregnenolone, when compared to the control group, was obtained in non-obese patients with PCOS, which indicates 21-hydroxylase deficiency. In obese patients with PCOS, four signs of increased 5α-reductase activity were obtained, and in PCOS patients with a normal BMI, three signs were obtained, which indicates varying 5α-reductase activity in PCOS patients depending on the BMI.

Conclusion. Quantitative evaluation of androgen and progestin metabolites, as well as 5α- and 5β-metabolites of androstenedione and glucocorticoids in the study of urine steroid profiles by GC-MS method opens new opportunities for PCOS diagnostics.

Journal of obstetrics and women's diseases. 2020;69(5):27-38
Morphological evaluation of the hypoplastic endometrium in women with ineffective art protocols
Tolibova G.K., Tral T.G., Kogan I.Y.

Hypothesis/aims of study. The hypoplastic endometrium has a significant negative impact on the probability of pregnancy and is one of the adverse factors influencing on the effectiveness of assisted reproductive technology (ART) protocols. Violation of the structural and functional characteristics of the endometrium associated with hypoplasia leads to endometrial dysfunction. In this regard, the relevance of a morphological study of the hypoplastic endometrium is beyond doubt. This study was aimed to determine the morphofunctional pattern of the hypoplastic endometrium in patients with a history of ineffective ART protocols.

Study design, materials and methods. Histological and immunohistochemical studies of the endometrium were performed in 340 patients. The endometrial receptor profile (estrogen receptors, ER; progesterone receptors, PR) and pro-inflammatory markers (CD8+, CD20+, CD4+, CD138+) were evaluated by immunohistochemical method.

Results. The morphological pattern of the hypoplastic endometrium in patients with ineffective ART protocols was characterized by polymorphic transformation variants with impaired endometrial receptor profile. This impaired proliferative and secretory transformation of the hypoplastic endometrium is underlain by damage to the endometrium basal layer resulted from intrauterine interventions and chronic endometritis with components of stromal fibrosis, sclerosis of the spiral arteries, and increased number of pro-inflammatory markers that led to endometrial dysfunction.

Conclusion. This article first describes the morphological variants of the hypoplastic endometrium in women with ineffective ART protocols. Integration of comprehensive morphological diagnostics with verification of the transformation variant of the hypoplastic endometrium can serve as the basis for rehabilitation therapy.

Journal of obstetrics and women's diseases. 2020;69(5):39-48
Specific interactions between genes of the hemostasis system, folate cycle and background comorbid pathology in the prognosis of preeclampsia
Belotserkovtseva L.D., Kovalenko L.V., Kasparova A.E., Mordovina I.I., Donnikov M.Y., Telitsyn D.P.

Hypothesis/aims of study. The search for early predictors of preeclampsia currently remains relevant. There is still a need to study maternal factors affecting the development of preeclampsia such as intergenic interactions in a pregnant woman with single nucleotide polymorphisms (SNPs) in genes associated with hemostasis system and folate cycle, as well as predictors. The aim of this study was to assess the role of comorbid pathology and gene polymorphism associated with the hemostasis system and folate cycle in predicting preeclampsia in a pregnant woman.

Study design, materials and methods. We examined 158 pregnant women in two study groups, including 92 women with preeclampsia and 66 healthy subjects. Somatic anamnesis of the patients was studied, with the course and outcomes of pregnancy analyzed. The carriage of SNPs in genes involved in hemostasis and the folate cycle was studied once by the method of polymerase chain reaction in real time with amplification of polymorphic loci and restriction analysis using specific endonucleases. The analysis of intergenic interactions was performed using the MDR 3.0.2 program.

Results. Seven genes involved in hemostasis and three genes involved in the folate cycle were studied. The highest entropy of the case-control status for preeclampsia is associated with the locus of coagulation factor F7 10976G>A — 9.49% and that of methylenetetrahydrofolate reductase MTHFR 677C>T (A223V) — 5.35%. The combination of loci of the tissue plasminogen activator inhibitor-1 gene SERPINE1 (PAI-1) and the platelet glycoprotein integrin 1α-2 gene ITGA2 (SERPINE1 (PAI-1) (5G>4G) + ITGA2 (807C> T)) account for 18.28%, and SERPINE1 (PAI1) (5G>4G) + MTHFR (677C>T) 14.26% of results. A three-locus synergy model SERPINE1 (PAI-1) (5G>4G) + MTHFR (677C>T) + ITGA2 (807C>T) responsible for the development of preeclampsia was obtained, which has a reproducibility of 10/10 and an accuracy of predictions of 84.3%.

Conclusion. Our data indicate a high contribution of the ITGA2, SERPINE1 (PAI-1), and MTHFR mutations combination to the prediction of preeclampsia.

Journal of obstetrics and women's diseases. 2020;69(5):49-58
Blood serum and follicular fluid relaxin: a pilot study of the hormone effects on ovarian function and fertilization efficiency
Bespalova O.N., Zagaynova V.A., Kosyakova O.V., Gzgzyan A.M., Kogan I.Y., Milyutina Y.P., Tkachenko N.N., Borodina V.L., Lesik E.A., Mekina I.D., Komarova E.M.

Hypothesis/aims of study. To date, one of the most important avenues of research in the field of reproductive medicine is the searching for new biochemical markers of oocyte quality and the prediction of the effectiveness of in vitro fertilization (IVF) protocols. The aim of this study was to assess the effect of relaxin levels in blood serum and follicular fluid on the efficiency of ovulation stimulation, fertilization, and characteristics of the embryos.

Study design, materials and methods. This prospective randomized cohort study included 11 patients undergoing infertility treatment in a superovulation stimulation protocol using gonadotropin-releasing hormone antagonists. Age, body mass index, hormonal status, ovarian response, endometrial thickness and structure, the number and quality of oocytes and embryos, as well as fertilization efficiency were assessed. The level of relaxin in blood serum and follicular fluid samples was determined on the day of transvaginal follicle puncture using enzyme immunoassay.

Results. A correlation between follicular fluid relaxin levels and body mass index, age, the number of oocytes, and their fertilization efficiency (p < 0.05) was established. Changes in follicular fluid relaxin level were revealed depending on the gonadotropin preparations (p < 0.05) and triggers of final maturation of oocytes (p < 0.05). The tendency of the effect of gonadotropin doses on circulating relaxin levels, and of the hormone itself on endometrial thickness and the quality of oocytes was determined.

Conclusion. Determination of the relaxin concentration can be considered as a promising method for predicting the result of ovarian stimulation and the efficiency of fertilization in IVF protocols.

Journal of obstetrics and women's diseases. 2020;69(5):59-68
Pregnancy outcomes in patients with uterine junctional zone thickening
Orekhova E.K., Zhandarova O.A., Kogan I.Y.

Hypothesis/aims of study. Overcoming infertility and miscarriage in adenomyosis is a complex practical problem in obstetrics and gynecology. It is likely that one of the signs of the disease is a thickening of the transitional zone between the endometrium and the myometrium (J-zone), which can be visualized using magnetic resonance imaging (MRI). The data on the influence of the biometric characteristics of the J-zone on the course and outcome of pregnancy in patients with adenomyosis is ambiguous. This study was aimed to assess the effect of J-zone thickness on pregnancy outcomes in patients with adenomyosis.

Study design, materials and methods. This is a prospective study, which included 102 patients aged 22-39 years with ultrasound signs of adenomyosis who were going to conceive. The patients were divided into two groups: Group 1 (n = 58) consisted of nulliparous patients with no history of previous intrauterine interventions; Group 2 (n = 58) comprised multiparous women with any of those, such as curettage of the uterine cavity for a non-developing or unwanted pregnancy and separate diagnostic curettage for a reason not related to pregnancy. Using MRI, J-zone maximum thickness was measured at the thickest part. We evaluated the relationship between J-zone thickness and pregnancy outcomes, while estimating J-zone thresholds for subfertility outcomes in the both groups.

Results. The average value of J-zone maximum thickness in Group 2 was significantly higher than that in Group 1 and amounted to 12.1 ± 4.2 mm and 10.3 ± 3.9 mm, respectively (p < 0.05). The pregnancy rate in the both groups did not differ significantly and amounted to 43.1% in Group 1 and 38.6% in Group 2 (p > 0.05). The frequency of retrochorial hematoma was diagnosed in 13.8% and 22.7% of cases, respectively, and did not differ significantly in the both groups (p > 0.05). The frequency of spontaneous miscarriage in Group 1 and Group 2 did not differ, either (6.9% and 6.8%, p > 0.05). The J-zone thresholds for unfavorable pregnancy outcomes were determined with a probability of 60% in Group 1 (9.1 mm) and Group 2 (10.0 mm).

Conclusion. J-zone thickness may be used as a prognostic marker of pregnancy outcome in patients with adenomyosis.

Journal of obstetrics and women's diseases. 2020;69(5):69-75
Conservative therapy of interstitial pregnancy in deep infiltrative endometriosis
Khachaturyan A.R., Yarmolinskaya M.I., Tsypurdeyeva A.A., Popov E.N., Rudikova A.I.

This article summarizes data on the prevalence, risk factors and the role of external genital endometriosis in the development of ectopic pregnancy. The existing algorithms for the use of conservative therapy of ectopic pregnancy of rare localizations are discussed. The authors presented a clinical case of using methotrexate in the treatment of a patient with infiltrative endometriosis and trophoblast persistence after laparoscopic removal of interstitial tubal pregnancy.

Journal of obstetrics and women's diseases. 2020;69(5):77-86
Experience in surgical correction of genital prolapse caused by abdominoperineal operations for colon cancer in anamnesis
Plekhanov A.N., Bezhenar V.F., Karachun A.M., Bezhenar F.V., Tsypurdeyeva A.A., Epifanova T.A.

In recent studies, it has been established that extralevator abdominoperineal extirpation (ELAPE) of the rectum can improve the oncological results of treatment of distal rectal cancer compared to standard abdominoperineal extirpation. As a result of extralevator dissection, a large defect of the perineum is formed, which requires plastic closure. While performing ELAPE, the structures that form the pelvic diaphragm are affected. This increases the risk of pelvic organ prolapse in women and significantly affects the quality of life of these patients, which requires subsequent surgical treatment. Despite the fact that pelvic organ prolapse develops as a consequence of previous surgical treatment by an oncologist, they do not consider it as a complication in the long-term postoperative period. Such patients are not referred to the operating gynecologist. Currently, this problem is poorly understood and there are no standardized approaches to the surgical treatment of pelvic prolapse in this category of patients.

Journal of obstetrics and women's diseases. 2020;69(5):87-97
Use of assisted reproductive technologies in euthyroid women with antibodies to the thyroid gland. A literature review
Gorelova I.V., Prikhodko K.A., Rulev M.V., Zazerskaya I.E.

The presence of antibodies to thyroid peroxidase and thyroglobulin of the thyroid gland in women with infertility is more common than in the population. Some studies describe the negative effect of autoantibodies on reproductive function and the results of assisted reproductive technology (ART) programs even in the absence of impaired thyroid function. This article presents a review of literature data on the possible mechanisms of this negative influence. To date, there are no data on a significant decrease in the quality of oocytes, embryos and pregnancy rates in ART cycles in such patients. The negative effect of autoantibodies on the frequency of live births can be realized through such complications of pregnancy as miscarriage and premature birth. Currently, the possibilities for preventing these complications are poorly understood. According to recent meta-analyses, the use of levothyroxine in euthyroid patients with autoantibodies who are treated for infertility using ART methods does not result in a decrease in the frequency of miscarriage and premature birth.

Journal of obstetrics and women's diseases. 2020;69(5):99-104
Features of the course of pregnancy in women with polycystic ovary syndrome
Nikolayenkov I.P., Kuzminykh T.U., Tarasova M.A., Seryogina D.S.

Polycystic ovary syndrome is one of the most common pathologies in the practice of an obstetrician-gynecologist. Overcoming infertility characteristic of this syndrome is an important problem of endocrinology, gynecology, and reproductive medicine. Innovative therapeutic and surgical methods of treatment can correct hormonal and metabolic disorders, induce ovulation and achieve a long-awaited pregnancy. Early gestation periods in patients with polycystic ovary syndrome often occur with miscarriage, and the risks of developing gestational diabetes mellitus, cervical insufficiency, gestational arterial hypertension, preeclampsia, and placental insufficiency increase. We have analyzed modern ideas about the effect of various pathogenetic links of polycystic ovary syndrome on the course of pregnancy.

Journal of obstetrics and women's diseases. 2020;69(5):105-112
Uterine fibroids: the role of signaling pathways in the pathogenesis. A literature review
Yarmolinskaya M.I., Polenov N.I., Kunitsa V.V.

Uterine fibroids are one of the most common benign tumors of the female reproductive system, originating from smooth muscle cells of the cervix or uterine body. The controversial issues of the pathogenesis of the disease make equal the various theories of its development and approaches to therapy. To date, there is no single and unambiguous opinion on the causes of the onset and recurrence of uterine fibroids, but thanks to the modern level of molecular medicine, much progress has been made in the study of hormonal and molecular genetic mechanisms of the initiation, formation and growth of the myoma node. The aim of this work was to review the modern aspects of the pathogenesis of uterine fibroids. We analyzed book chapters, original and review articles deposited in the PubMed database and related to the study of the pathogenesis of uterine fibroids from 2000 to 2019. This review presents modern data on the role of sex steroid hormones and their enzyme regulation, as well as growth factors and vitamin D in the pathogenesis of the disease. Particular attention was paid to signaling pathways involved in the regulation of basic cellular processes, in the onset and progression of the disease. It was noted that the activation of signaling pathways such as Wnt / β-catenin, MAPK / ERK, and TGF-β / SMAD plays a significant role in the development of uterine fibroids. Further study of the pathogenesis of the disease is needed for new strategies to design targeted therapy of uterine leiomyoma.

Journal of obstetrics and women's diseases. 2020;69(5):113-124
Theory and Practice
Clinical case of pregnancy and preterm labor in a woman with stage III genital prolapse
Ziganshin A.M., Mudrov V.A.

This article presents a clinical case of pregnancy and preterm labor at 31-32 weeks of pregnancy in a woman with stage III genital prolapse. This pregnancy occurred spontaneously within three years after a seven-year period of taking combined oral contraceptives. The birth was complicated by premature outpouring of amniotic fluid and ended with the birth of premature fetus.

Journal of obstetrics and women's diseases. 2020;69(5):125-130

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