Vol 67, No 2 (2018)

Composition of endometrial microbiota and chronic endometritis severity in patients with in vitro fertilization failures. Is there any connection?
Tsypurdeeva N.D., Shipitsyna E.V., Savicheva A.M., Gzgzyan A.M., Kogan I.Y.

Background. Pelvic inflammatory disease (PID), including chronic endometritis (CE), is a factor leading to endometrial receptivity disorder and in vitro fertilization (IVF) failures. The role of microorganisms in colonizing the endometrium, the pathogenesis of chronic inflammation, and associated infertility require further study.

Aims: To determine the taxonomic profile of the endometrial microbiota in different grades of CE in patients with a history of IVF failure.

Materials and methods. This study included 107 patients with ≥ 1 IVF failures. Depending on the severity of CE, and according to the morphological analysis of endometrial biopsy, the patients were categorized into three groups: group I (n = 14), patients without signs of CE; group II (n= 20); patients with signs of mild CE; and group III (n = 73),patients with signs of moderate and severe CE. All the patients underwent Pipelle biopsy of the endometrium according to our modified technique on days 18–23 of the menstrual cycle. Species and quantitative composition of the endometrial microbiota were investigated using real-time polymerase chain reaction (PCR).

Results. Compared to groups II and III, Lactobacillus spp. (50% and 46.6% versus 85.7%) and Eubacterium spp. (25% and 35.6% versus 78.6%) were detected significantly more frequently in the endometrial microflora of group I patients, respectively. Simultaneously, significantly more bacteria of the families Enterobacteriaceae (50% and 64.4% versus 35.7%, respectively) and Streptococcus spp. (55% and 56.2% versus 7.1%, respectively) were found in the patients of groups II and III compared to group I. The abundance of lactobacilli and Eubacterium spp. have also been shown to be significantly higher in the endometrial samples of women in group I than in those of the women in groups II and III, whereas the abundance of enterobacteria and streptococci are significantly higher in women with CE than in women without CE.

Conclusions. In patients without signs of CE, Lactobacillus spp. and Eubacterium spp. prevail in the endometrial microbiota. Chronic inflammation in the endometrium is associated with an increase in the frequency and abundance of Streptococcus spp., Staphylococcus spp., and bacteria of the family Enterobacteriaceae.

Journal of obstetrics and women's diseases. 2018;67(2):5-15
Prognostic possibilities of relaxin as a marker of preterm birth
Kosyakova O.V., Bespalova O.N.

Premature birth is one of the most important problems of modern obstetrics because it is a leading cause of childhood morbidity and mortality in all countries. Annually, > 1 million premature newborns worldwide die from various types of complications, and most of the survivors become disabled. Moreover, according to WHO analysis, most of these children can be saved by developing measures for the early identification of preterm births, which will provide additional time for effective intervention. Currently, available diagnostic methods do not adequately assess the risks of premature delivery owing to the low predictive value of the methods. This makes it necessary to search for predictors of preterm labor that can improve the accuracy of diagnostic techniques. The desired predictors should have a pathogenetic basis, and most importantly, they must contribute to the early detection of life-threatening premature births. The hormone relaxin could be considered to be a promising marker of premature birth because its role in the pathogenesis of premature birth is unquestionable, and the evaluation of its levels is possible during the early stages of pregnancy.

Journal of obstetrics and women's diseases. 2018;67(2):16-25
Systematization of obstetric bleeding and preeclampsia “near-missˮ opportunity reasons
Davlyatova G.K., Kamilova M.Y., Ishan-Khodzhaeva F.R.

The results of the systematization of reasons for obstetric bleeding and preeclampsia near-miss opportunities established during an audit in 20 delivery homes in Tajikistan are presented in this article. The following reasons were reported: knowledge (45%), organizational problems (38%), and necessity for the correction of National Standards of obstetric bleeding and preeclampsia (13%). Therefore, determining recommendations for this country is a practical step to realize “near-miss” opportunities to prevent obstetric bleeding and preeclampsia.

Journal of obstetrics and women's diseases. 2018;67(2):26-31
The effect of excess body weight and obesity on the effectiveness of assisted reproductive technologies programs
Mahmadaliyeva M.R., Kogan I.Y., Niauri D.A., Mekina I.D., Gzgzyan A.M.

The purpose of the study. To determine the main indicators of the effectiveness of IVF programs in over-weight and obese patients. Based on the Research Institute of obstetrics, gynecology, and reproductology D.O. Ott, we conducted an analysis involving women aged 18–39 years who were treated in the IVF program in the department of assistive technologies in infertility treatment. The study included 97 patients who met the selection criteria. The patients were categorized into three groups: group I, 33 obese women (body mass index (BMI) ≥ 30.8 kg/m2); group II, 34 overweight women (BMI = 25 to 29.9 kg/m2); and the control group, 30 normal weight patients (BMI = 18 to 24.9 kg/m2). As a result, the efficiency of ART programs decreased significantly in women of group I, owing to the weaker response of the ovaries to the stimulation of superovulation, which causes an increased gonadotropin demand to stimulate  ovulation.

Journal of obstetrics and women's diseases. 2018;67(2):32-39
Clinical efficiency of desmopressin and cyclooxygenase inhibitor use in incontinent women
Osipova N.A., Niauri D.A., Gzgzyan A.M.

Hypothesis/aims of study. Questions regarding the pathogenesis of urine incontinence and methods of treatment are acti vely discussed by gynecologists, urologists, and neuropathologists. Urine incontinence often has multifactor origins: the causes of urine incontinence are connected, as a rule, with the violation of urine continence functional mechanisms, anatomotopographical features of the lower urinary tract, or an premature ovarian failure. Simultaneously, changes in kidney function play a role in the pathogenesis of urine incontinence. In some cases, urine incontinence is combined with urine overproduction or inversion of the circadian rhythm of renal function owing to a decrease in the reabsorption of sodium ions in the thick ascending limb of the loop of Henle. In some patients, we successfully normalized ion transport, diuresis, and circadian rhythm of urine production by desmopressin or diclofenac administration. The present analysis was undertaken to evaluate the clinical efficiency of desmopressin and diclofenac in incontinent patients with nocturnal polyuria and polyuria.

Study design, materials, and methods. In total, 130 patients with complaints of urinary incontinence, polyuria (24-h urine volume of 40 mL/kg bodyweight or above), or nocturnal polyuria (nocturnal volume/24-h urine volume of 0.33 or above); 30 incontinent women without polyuria or nocturnal polyuria (comparison group); and 14 control subjects were included. The mean patient age was 43.6 ± 4.5 years (41.8 ± 3.7 years in the comparison group and 39.4 ± 6.3 years in the control group, p > 0.05). All the participants performed seven days of urine collection to determine the voided volumes. Patients with polyuria or nocturnal polyuria performed the 3-fold 24-h pad-test. Patients with polyuria and nocturnal polyuria were examined twice: in the initial state and one month after the start of treatment with the optimal dose of diclofenac or desmopressin (Minirin).

Results. The use of both diclofenac or desmopressin in patients with various types of urine incontinence, polyuria, or nocturia decreased the volume of voided urine because of the normalization of diuresis and an increase in cystometric bladder capacity.

Journal of obstetrics and women's diseases. 2018;67(2):40-51
The efficacy of selective cyclooxygenase 2 inhibitors in the treatment of genital endometriosis
Samoshkin N.G., Yarmolinskaya M.I., Polyakova V.O.

External genital endometriosis is characterized by the processes of angiogenesis, neurogenesis, impaired apoptosis, local inflammation of the tissues, secretion of estradiol, and cell proliferation. In a similar manner, prostaglandin E2 affects  tissues. The safest drugs that overwhelm COX-2 activity and inhibit the expression of prostaglandin E2 are selective COX-2 inhibitors. As a mediator of inflammation, prostaglandin E2 is involved in all inflammatory processes. It induces the expression of local P450 aromatase and the anti-apoptotic gene Bcl-2. E2 also possesses immunosuppressive-mediated activity and inhibits the synthesis of cytokines IFNγ, TNFα, and IL-12, IL-1β-mediated expression of chemokines, the proliferation of T- and B-cells and reduces the cytotoxic activity of NK cells, creating a background of the immunosuppressive characteristic of endometriosis [1–3].

This study included 100 patients of reproductive age (aged 22−35 years) with a confirmed diagnosis of external genital endometriosis of degree II–IV. Fifty patients received 100 mg of celecoxib in monotherapy and in combination with 2 mg of dienoguest. The control group included 50 people receiving monotherapy with 2 mg of dienogest. The effectiveness of therapy was assessed using the visual analog scale (VAS) and on the basis of the dynamics of algodismenorrhea, pain during coitus, clinical examination, and the patient’s subjective assessment of the degree of irritability and severity of depressive syndrome. The effectiveness of the treatment was evaluated according to MRI and ultrasound of the pelvic organs throughout the study. To control for possible complications of the therapy, the patients performed a comprehensive dynamic survey assessing the indicators of general blood analysis and the blood coagulation system. In the group with the combined application of celecoxib and dienoguest, a clinically significant reduction in pain syndrome and a decrease in the degree of irritability and depressive syndrome were noted relative to the control group. No side effects of celecoxib on the body systems were identified throughout the study. Thus, celecoxib can be recommended as a safe and effective combination therapy for endometriosis.

Journal of obstetrics and women's diseases. 2018;67(2):52-60
Ovarian aromatase activity: evaluation methods and the clinical significance in IVF protocols
Yakovlev P.P., Krylova J.S., Mekina I.D., Polyakova V.O., Kvetnoy I.M., Tarasova M.A., Kogan I.Y., Gzgzyan A.M., Rodichkina V.R.

Introduction. Cytochrome P450 aromatase is a key enzyme in the biosynthesis of estrogens from androgens. Some gynecological diseases are accompanied with changes in the activity of ovarian aromatase. Moreover, changes in the acti vity of ovarian aromatase are associated with the response to standard gonadotrophin stimulation in women undergoing in vitro fertilization. A new effective method determining the activity of ovarian aromatase without using ovarian tissue biopsy has been developed.

The purpose of the present study was to compare the detection of ovarian aromatase activity using the ratio of estradiol to AMH on the second day of the menstrual cycle through the immunocytochemical evaluation of aromatase expression in cumulus cells.

Methods. Depending on the activity of the ovarian aromatase, calculated on the second day of the menstrual cycle, 16 patients undergoing IVF protocols were categorized into three groups: eight patients with low activity, four with normal activity, and four with high activity. The patients did not differ in age and BMI. The expression of aromatase in cumulus cells obtained through transvaginal puncture was investigated by the immunocytochemical method.

Results. The fluorescence intensities in the low, normal, and high activity groups were 134 (122–161), 238 (201–251), and 259 (240–299), respectively. Differences between these groups were statistically significant (p = 0.008). There was a pronounced positive correlation between the activity of ovarian aromatase, calculated on day two of the menstrual cycle, and the intensity of aromatase fluorescence in cumulus cells (Spearman, r = 0.75, p = 0.001, n = 16).

Journal of obstetrics and women's diseases. 2018;67(2):61-69
Intestinal dysbiosis is a risk factor or a cause of miscarriage?
Bezmenko A.A., Kislitsyna N.D.

The number of spontaneous abortions continues to increase despite the new methods of diagnosis and treatment. A total of 15%–23% of confirmed pregnancies end in spontaneous miscarriages. Of the causes of reproductive losses, approximately 7% are chromosomal abnormalities, and the remaining are conditionally preventable.

This article discusses the role of intestinal dysbiosis in the pathogenesis of miscarriage. Focus on this issue and the evaluation of the effectiveness of the treatment of gastrointestinal tract diseases may be a primary way to prevent early reproductive losses.

Journal of obstetrics and women's diseases. 2018;67(2):70-78

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