No 3 (2023)

The paper analyzes the data available in the literature on pregnancy and delivery complications in endometriosis. A high percentage of women with endometriosis experience infertility and have a higher risk of adverse pregnancy outcomes. Pregnant women with endometriosis are much more commonly noted to have placenta previa and placental abruption, preterm labor, to need a caesarean delivery, and to have gestational hypertension and preeclampsia, fetal death, and stillbirth. At the same time, the increased risk of pregnancy complications does not depend on the type of reproduction (spontaneous or using assisted reproductive technologies). The complicated course of pregnancy in women with endometriosis points to an interdisciplinary problem and justifies the need to follow up these patients in third-level healthcare facilities.

Conclusion: To prevent and minimize the risk of pregnancy complications, it is necessary to adhere to personalization tactics for both pregravid preparation and pregnancy management.

The data available in the modern scientific literature on the role of the uterine and embryonic factors in failed euploid embryo implantation were systematically analyzed. The keywords “microRNA”, “small non-coding RNA”, “embryo implantation”, “implantation failure”, “implantation window”, “infertility treatment”, “thin endometrium”, “endometrial receptivity”, “molecular mechanisms”, and “gene expression” were used to search for literature sources in the Russian and foreign databases eLibrary, Medline/PubMed, and Embase. Differential expression of certain blastocyst microRNAs is shown to be associated with implantation failure. The paper describes the molecules involved in the transmission of maternal signals that are activated in the blastocyst trophectoderm. It reflects the mechanism of molecular regulation in endometrial receptivity and that of formation of a thin endometrium and genes identified in the networks that may play a certain role in the development of the thin endometrium.

Conclusion: The current evidence supports the promise of studying the molecular mechanisms of embryo implantation. Further investigations are needed to search for new biomarkers to select embryos with their good implantation potential, to assess endometrial receptivity for improving the outcomes of assisted reproductive technology programs, to reduce reproductive losses, and to give birth to healthy babies.

Objective: To determine the content of the adhesion molecule E-cadherin in the plasma and placenta of women with preeclampsia (PE) and assess its involvement in the development of PE.

Materials and methods: This study included 55 pregnant women. Thirty-five of them had pregnancies complicated by PE (Group I), and 20 had uncomplicated pregnancies (Group II, control). Blood plasma levels of the soluble form of E-cadherin were determined using enzyme immunoassay. Placental E-cadherin expression was studied by the Western blot method.

Results: The plasma soluble form of E-cadherin was higher in patients with PE than in controls, 8.0 ng/ml and 3.87 ng/ml, respectively (p<0.001). Placental tissue analysis showed a significantly higher content of the soluble form of E-cadherin in PE.

Conclusion: The increased level of the soluble form of E-cadherin in the plasma and placental tissue in PE reflects the abnormal proliferation and differentiation of trophoblasts, which is typical of this pathology.

Objective: To compare two surgical techniques for placenta increta management at delivery.

Materials and methods: The study included 57 (100%) patients with placenta increta who delivered at the Rostov Regional Perinatal Center from 2019 to 2021. Group 1 included 32/57 (56%) patients with a placental defect <120 mm in the largest diameter and no bladder dissection difficulties, who underwent intraoperative ultrasound navigation to find the upper edge of the placenta. Subsequently, a caesarean section was performed in the lower uterine segment with an incision above the upper edge of the uterine aneurysm with application of distal hemostasis (Foley catheter), followed by metroplasty. Group 2 included 25/57 (44%) patients with a placental defect >120 mm in the largest diameter who underwent cesarean section to extract the fetus (the placenta remains in situ), suturing the uterine incision, followed by dissection of the vesical-uterine fold with excision and distal lowering of the bladder followed by distal hemostasis (Foley catheter), a second uterine incision above the herniated bulge, and metroplasty.

Results: The total blood loss was 1200 (900; 1700) and 2500 (1400; 4000) ml in groups 1 and 2, respectively (p=0.001). Blood loss > 2000 ml occurred in 4/32 (12%) and 15/25 (60%) patients in groups 1 and 2, respectively (p<0,001). Intraoperative autologous blood transfusions were performed more frequently in Group 2 (22/57 (88%)) than in Group 1 (16/57 (50%)) (p=0,004). Their volumes and the frequency and volume of blood component transfusions did not differ significantly.

Conclusion: Organ-sparing surgery is an acceptable treatment option for patients with placenta increta. Surgical treatment of patients in Group 1 showed the best hemostatic effect; however, under certain conditions, a surgical technique involving two uterine incisions should be used.

Objective: Assessment of medical and social aspects of the prevalence and the structure of infertility causes in Russia.

Materials and methods: We used the data of questionnaire survey of 7004 infertile couples. The questionnaire included the questions about education, social and marital status, as well as information from medical documentation about the age, reproductive and medical history of partners. To perform comparative assessment of the studied characteristics, all participants of the study were divided into 2 groups, depending on the period of seeking treatment in fertility clinics. Group 1 consisted of 3509 couples who sought infertility treatment from January 1, 2010 to December 31, 2015. Group 2 comprised 3495 couples, who sought infertility treatment from January 1, 2016 to December 31, 2020.

Results: Over the past 5 years, the age of infertile couples seeking treatment increased by 4 years on average and was 34 (4.8) years for women and 35.5 (5.9) years for men. At the same time, the proportion of women over 40 increased by 4 times. The proportion of rural residents increased. Introduction of the IVF program into Compulsory Medical Insurance (CMI) system has made it more accessible to a wide range of people with different incomes. The number of HIV-infected infertile couples planning treatment of infertility has increased.

Tubo-perioneal factor (24.2% and 23.5% in groups 1 and 2) ranked first as the only cause of infertility. The second most common factor of infertility was male infertility (17% and 19.4%). The third factor was endocrine origin of infertility (5.1% and 7.6%). Regardless of the estimated period of time, the combined types of infertility prevailed in the structure of infertility causes – 39.6% in group 1 and 39.5% in group 2.

Conclusion: The results of the study demonstrated the influence of medical and social factors on health-seeking behavior of patients with infertility, as well as the frequency of various causes of reproductive disorders.

Objective: To determine management tactics for patients with diffuse and nodular adenomyosis, by assessing the their functional state of the endometrium.

Materials and methods: Examinations were made in 104 patients who were ranged by groups Group 1 comprised 58 examinees with diffuse adenomyosis; Group 2 included 46 examinees with the nodular form. All the patients underwent three-dimensional ultrasound of pelvic organs. The investigators studied the thickness, volume and echostructure of the endometrium, indicators of volumetric blood flow: vascularization index (VI%); flow (FI) and vascular flow (VFI).

Results: The diffuse and nodular forms of adenomyosiosis are associated with the changes in the the thickness, the endometrial pattern, as well as with the hemodynamic parameters in the terminal branches of uterine arteries (hypovascularization, an increase in the angle-independent indices of blood flow velocity curves. The obvious uterine mucosal thinning particularly in patients with nodular adenomyosis, and which means the association with the disturbed endometrial functional state accompanied by a reduction in the implantation potential.

Conclusion: The patients with obvious endometrial thinning and the nodular form of adenomyosis, it is advisable to recommend a a reproductologist’s consultation to decide whether assisted reproductive technologies should be used. Three-dimensional ultrasound is an additional objective method for estimating the volume of the endometrium and hemodynamics in volume at the level of the basal and spiral arteries.

Background: The HLA class I system controls the interaction of all immunocompetent cells of the body and determines the recognition of its own and foreign (including altered own) cells, by triggering and realizing an immune response: during the implantation process, in the transplantation of foreign organs and tissues, in autoimmune diseases, and in the development of cancers. Thus, the data available in the world and Russian literature have demonstrated the ability of protein products of HLA-G gene expression to modulate the proliferation of immune system cells, as well as the strength and specificity of the immune response.

Objective: To conduct a molecular biological study of nine HLA-G gene polymorphic alleles in the group of pregnant women in the first trimester and in the population of the North-West Region of the Russian Federation and to identify the relationship to their family obstetric history.

Materials and methods. In 2019 to 2022, the D.O. Ott Research Institute of Obstetrics, Gynecology, and Reproductology (Saint Petersburg) examined DNA samples from 180 dwellers in the North-West Region of the Russian Federation. Group 1 consisted of 33 pregnant women with reproductive disorders (one or more miscarriages, non-developing pregnancy, ART failures); Group 2 (control) included 29 pregnant women without their family obstetric history; a comparison group comprised 118 people from the population of the North-West Region of the Russian Federation, in which the investigators carried out an associative analysis of HLA-G gene polymorphic alleles (725*C/G, 3741*ins/del 14 bp) and HLA-G*01 alleles (01, G*01:02, G*01:03, G*01:04, G*01:05N, G*01:06 and G*01:07).

Results: The analysis of 3741*ins/del 14 bp polymorphism showed that the Del/Del genotype frequency was 13/33 (39.40%) in pregnant women with a history of reproductive losses, 5/29 (17.24%) in the control group; p = 0.052), and the allele Ins was detected 1,4 times more often in the group without a family obstetric history (20/33 (60.6%) and 24/29 (82.8%), respectively; p=0.056). According to the calculated odds ratio, the carriers of the combined Del/Del and C/C genotype were detected 9 times more frequently among patients with a history of reproductive losses compared to the controls (OR=8.96, CI 1.05;76.74). In Group 1, the HLA-G*01:05N allele was noted to be detected 3.5 times more often than in the population sample.

Conclusion: The findings may judge an association between HLA-G gene alleles and a family obstetric history and may be important in assessing the risk of early reproductive losses and in developing new prevention and treatment strategies for this pregnancy complication.

Objective: To study the effect of 0.1% activated glycyrrhizic acid spray on the relief of vulvar discomfort and pathological leucorrhoea in women with nonspecific (aerobic), vulvovaginal candidiasis and bacterial vaginosis.

Materials and methods: The study was conducted under the supervision of the principal investigator with the participation of outpatient healthcare facilities providing obstetric and gynecological care in the cities: Moscow, Saint Petersburg, Voronezh, Belgorod, Krasnodar, Rostov-on-Don, Stavropol, Yekaterinburg, Chelyabinsk, Ufa, Novosibirsk, Krasnoyarsk, Irkutsk, Samara, Saratov, Kazan, and Nizhny Novgorod. The investigation enrolled 8,249 patients aged 18 to 45 years who complained of pathological vaginal discharge, discomfort in the external genital area with a clinical diagnosis of nonspecific (aerobic) vaginitis, vulvovaginal candidiasis, or bacterial vaginosis. All the patients underwent a comprehensive examination, including a physical and gynecological examination, bacterioscopy of vaginal smears, and comprehensive quantitative assessment of the vaginal microflora using a real-time polymerase chain reaction assay. All the patients were prescribed etiotropic therapy depending on the pathogen and clinical diagnosis at the discretion of an attending physician, by adding 0.1% activated glycyrrhizic acid (Epigen Intim) spray.

Results: The combination therapy resulted in a reduction of discomfort symptoms, such as itching (from 1.45 to 0.35 scores), burning (from 1.44 to 0.35 scores), unpleasant odor (from 1.31 to 0.51 scores), profuse discharge (from 1.8 to 0.30 scores), vulvar and vaginal mucosal dryness (from 0.44 to 0.16 scores), painful urination (from 0.37 to 0.14 scores), and dyspareunia (from 0.71 to 0.16 scores). The nature of discharge and its volume were stated to normalize (the proportion of patients with an abnormal discharge volume decreased from 3,812/8,249 (46.6%) to 101/8,249 (1.1%)).

Conclusion: When included in the combination treatment of patients with clinical manifestations of aerobic vaginitis, vulvovaginal candidiasis, and bacterial vaginosis, the drug based on 0.1% activated glycyrrhizic acid spray for local and topical application was found to relieve (cease) complaints of pathological vaginal discharge and vulvovaginal discomfort and to be safe and well tolerated.

The paper reviews the data available in the literature and those obtained by the authors on the surgical treatment of 78 women with genital prolapse in the Gynecology Unit, Simferopol Perinatal Center, in 2019 to 2022. The common complaints in patients who visited the healthcare facility were external genital organ discomfort, periodic aching pains in the lower abdomen and lower back, and vaginal foreign body sensation. The most common comorbidities were lower extremity varicosities (56%), coronary heart disease (38%), obesity (35%), and hypertension (34%). The mean duration of surgery was slightly longer, as well as blood loss was slightly greater and bed days were slightly more in the vaginal hysterectomy group. The results of assessing the quality of life a year after surgery indicate the high efficiency of treatment in all the four groups; however, the patients who underwent laparoscopic promontofixation show the best results.

Conclusion: In the authors’ opinion, the use of laparoscopic promontofixation is a preferred technique for surgical correction of genital prolapse. However, the analysis allows the authors to judge that all methods for correction of genital prolapse continue to be actively used in practical healthcare.

The paper analyzes the modern literature data on estetrol, a native fetal estrogen that has been proposed as an estrogen component in the combined oral contraceptives, where only ethynyl estradiol has been traditionally used. a number of preclinical and clinical trials have provided evidence that estetrol is an estrogen that has unique properties since it does not affect hepatic parameters and hemostasis, has an antiestrogen effect on breast tissue and in high doses demonstrates an antitumor effect in breast and prostate cancers. Due to the above properties, estetrol has become an estrogen that become potentially safe as a component of the combined oral contraceptive containing 15 mg of estetrol and 3 mg of drospirenon in one tablet to be used in the 24/4 regimen, which have been now completed and shown the high efficacy of the contraceptive agent, as well as due to the minimal side effects: a good patient compliance with its usage. All phases of clinical trials of the new combined hormonal contraceptive containing 15 mg of estetrol and 3 mg of drospirenone in one tablet to be used in the 24/4 regimen, which have now been completed and shown the high efficacy of the contraceptive agent, a high safety, as well as due to the minimal side effects: a good patient compliance with its usage. Phase III trials of the new combined hormonal contraceptive, which have now been completed and shown that the new agent esterette is already available for patients and physicians.

Conclusion: The new hormonal combined oral contraceptive with a fetal estrogen, estetrol in combination with drispirenone ensures effective contraception, predictable presentations of hemorrhage, and a favorable safety profile.

Background: The effect of pregnancy on the course of endometrioid disease is ambiguous and can be implemented in both curbing the progression of the disease and activating the pathological process with the development of life-threatening conditions, particularly spontaneous intra-abdominal hemorrhage, which requires complex differential diagnosis and timely surgical tactics.

Case report: A female patient at 32 weeks of gestation was admitted to the perinatal center with complaints of lower abdomen pain. Her medical history showed that she had undergone laparoscopic enucleation of right ovarian endometrioid cyst, cauterization of single endometriotic foci, and adhesiolysis two years before this pregnancy. Threatened preterm birth was diagnosed; a thorough examination was performed. A differential diagnosis was made between acute appendicitis, pelvic vascular thrombosis, ileus, pyelonephritis, renal colic, uterine rupture, preterm placental abruption, and threatened preterm birth. Following an examination by a surgeon, a council of physicians made a decision for surgical treatment due to suspected intra-abdominal hemorrhage. Intraoperatively, there is blood in the abdominal cavity; the source of bleeding was varicose vein wall perforation in the region of the right broad ligament of the uterus; a biopsy was done. A histological examination revealed that there were foci of external genital endometriosis. A hemostatic sponge was applied to control bleeding. A caesarean section was performed. The mechanism of tissue perforation is related to rejection of highly vascularized endometrioid tissue foci with hemorrhages and necrosis in the presence of an impaired estrogen/progesterone ratio in the third trimester of pregnancy, with the development of spontaneous hemoperitoneum. To overcome diagnostic difficulties, interdisciplinary interaction was needed to achieve a favorable gestational and perinatal outcome in a pregnant woman with a life-threatening condition.

Conclusion: The accumulation of knowledge and experience in managing pregnant women with endometrioid disease will be able to optimize medical tactics and to avoid critical obstetric conditions and deaths. Each confirmed clinical observation of the course of endometrioid disease in pregnant women, which is complicated by spontaneous hemoperitoneum, is undoubtedly of scientific and practical value.