编号 10 (2024)

Pregnancy, childbirth and the appearance a newborn are associated with significant psychoemotional stress for women. A number of researchers have demonstrated a correlation between depression during pregnancy and adverse perinatal outcomes.

The article presents an analysis of the studies conducted by the Russian and foreign scientists in the field of research into the psychological state of pregnant women. There is evidence for the association of depression during pregnancy with various obstetric and perinatal complications (preterm labor, hypertensive disorders, developmental delay and risk of autism in early childhood, etc.). Additionally, the relationship between exposure to maternal prenatal stress and subsequent physical, psychological and psychiatric outcomes in later life has been identified, including emotional instability, behavioral abnormalities, cognitive impairment, chronic metabolic disease and congenital heart disease. The present study considers the interrelation of psychological state with neuroendocrine regulatory mechanisms and the state of the autonomic nervous system. Psychoprophylactic preparation for childbirth is demonstrated to be important.

Conclusion: The literature review proves the necessity to continue research aimed at diagnosing and correcting the psychoemotional state of pregnant women. When a pregnant women experiences anxiety, the obstetrician-gynecologist should refer the patient to a psychologist. Targeted screening for psychiatric disorders as possible clinical markers of risk of obstetric and perinatal complications can help to correct and monitor the development of psychoemotional disorders on time and reduce the risk of complicated pregnancy and childbirth.

Asherman’s syndrome (AS) is an acquired endometrial condition defined by the presence of nonvascular myofibrous intrauterine adhesions and at least one of the following symptoms: history of decreased fertility, recurrent miscarriages, dysmenorrhea, noncyclic pelvic pain, aberrant placentation, or menstrual disorders (amenorrhea, hypomenorrhea, or oligomenorrhea). The review presents a comprehensive analysis and summary of studies on AS, considering the etiology, pathogenesis, diagnosis, advantages and disadvantages of the treatment methods, as well as the latest therapeutic possibilities for intrauterine adhesions. The existing medical literature on the subject accessible via open sources was studied. These sources included the eLibrary (a scientometric database), PubMed (an English-language text database of medical and biological publications), and CyberLeninka (a scientific electronic library). It is essential to consider the findings of the anamnesis, clinical and instrumental studies when selecting an appropriate treatment and prevention of AS. Treatment methods should certainly be aimed at correcting the pathogenetic mechanisms involved in the development of intrauterine adhesions. Hysteroscopy, hormone therapy and the use of intrauterine contraceptives are the traditional methods. Modern techniques such as the use of biomaterials and stem cells are important components of regenerative medicine. The description of treatment, recurrence prevention, and the incidence of AS is a challenging and clinically significant task.

Conclusion: It is worth noting that if uterine surgery is indicated, the risk of developing intrauterine adhesions should be minimized.

Relevance: Conducting extended genetic testing based on whole exome sequencing allows for the diagnosis of Noonan syndrome in pregnant women with nonimmune hydrops fetalis (NIHF). The data obtained may help to revise the management strategy for the current pregnancy and assist in determining the risk of recurrence of Noonan syndrome in this parental couple.

Materials and methods: Pregnant women with NIHF underwent invasive prenatal diagnostics, followed by genetic testing using molecular karyotyping on DNA microarrays and whole exome sequencing.

Results: The study presents the clinical observations of three cases of NIHF associated with Noonan syndrome in the fetus. Married couples were examined and the inheritance pattern of variants associated with Noonan syndrome was determined. Genetic counseling was provided to the families, and a method for planning subsequent pregnancies was established.

Conclusion: Whole exome sequencing enables the diagnosis of Noonan syndrome in patients with NIHF, provides an estimation of fetal prognosis, and expands the scope of genetic counseling for the couple.

Objective: To analyze clinical and anamnestic risk factors and develop prediction models for early- and late-onset fetal growth restriction.

Materials and methods: A cross-sectional study was conducted at the V.I. Kulakov NMRC for OG&P of Minzdrav of Russia, involving 382 pregnant women. Group 1 included 110 pregnant women with fetal growth restriction, whereas Group 2 included 272 women with pregnancies without fetal growth restriction. An analysis of the somatic and obstetric-gynecological history and course of the current pregnancy in both groups was performed. Prediction models for the likelihood of developing early- and late-onset fetal growth restriction were developed.

Results: In group 1, a history of arterial hypertension [10/110 (9.1%) vs. 6/272 (2.2%), p=0.045, OR=0.226 (95% CI 0.052–0.979)], chronic pyelonephritis [8/110 (7.3%) vs. 2/272 (0.7%), p=0.025, OR=0.094 (95% CI 0.010–0.865)], chronic endometritis [8/110 (7.3%) vs. 58/272 (21.3%), p=0.02, OR=0.82 (95% CI 0.015–10.353)], and a history of giving birth to children with growth restriction in previous pregnancies [8/110 (7.3%) vs. 2/272 (0.7%), p=0.025, OR=0.094 (95% CI 0.010–0.865)] were significantly more common than in group 2. During the current pregnancy, the following complications were significantly more prevalent in group 1 than in group 2: threatened miscarriage [35/110 (31.8%) vs. 64/272 (23.5%), p=0.04, RR=1.97 (95% CI 1.03–3.75)], preeclampsia [11/110 (10%) vs. 9/272 (3.3%), p=0.01, RR=3.53 (95% CI 1.37–9.08)], chronic arterial hypertension [11/110 (10%) vs. 11/272 (4.0%), p=0.02, RR=2.84 (95% CI 1.15–7.01)], and placenta previa [5/110 (4.5%) vs. 5/272 (1.8%), p=0.01, RR=0.84 (95% CI 0.42–1.68)]. Significant predictors of fetal growth restriction included a history of having a child with growth restriction, placenta previa, obesity, and preeclampsia. Based on the identified predictors, mathematical predictive models were developed to determine the likelihood of fetal growth restriction.

Conclusion: The developed predictive models for early- and late-onset fetal growth restriction can help reduce the incidence of pregnancy complications and improve perinatal outcomes.

Relevance: Glucagon-like peptide-1 (GLP-1) is an incretin hormone that regulates insulin secretion, and elevated GLP-1 level is in fetal growth restriction. GLP-1 can bind to its membrane receptors on leukocytes and change their phenotype.

Objective: To study the impact of GLP-1 on the phenotypic profile of peripheral blood mononuclear cells in pregnant women with fetal growth restriction and identify potential diagnostic markers.

Materials and methods: The study was conducted in two stages. In stage one, the impact of the GLP-1 receptor agonist liraglutide on the phenotypic profile of peripheral blood mononuclear cells in 12 pregnant women (6 patients with fetal growth restriction and 6 patients with normal pregnancy) was assessed using flow cytometry. In stage two, 56 pregnant women were enrolled in the study, and divided into two groups. The main group consisted of 32 women with fetal growth restriction. The comparison group consisted of 24 patients with normal pregnancy.

The diagnostic significance of the obtained markers (CD4, CD8, CD86 and CD163) was evaluated by measuring their counts and expression levels in the peripheral blood of pregnant women.

Results: In vitro assessment of the effect of liraglutide on mononuclear cells in the peripheral blood of pregnant women showed statistically significant decrease in CD8⁺ lymphocyte number (p=0.03), reduction in CD8 expression in lymphocytes (p=0.03) and elevated expression of CD163 on monocytes (p=0.05). In the blood of pregnant women with fetal growth restriction, statistically significant relatively high levels of CD4⁺ (p=0.02) and CD163⁺ (p=0.001) monocytes and relatively low levels of CD8⁺ lymphocytes (p=0.006) were found. At the same time, the levels of CD163 expression in the main group were significantly elevated (p=0.02), while the levels of CD86 expression on monocytes was reduced (p=0.02). The ROC analysis showed the potential diagnostic value of the relative level of CD163⁺ monocytes in the blood of pregnant women for the diagnosis of fetal growth restriction (AUC=0.83).

Conclusion: The obtained data showed that in fetal growth retardation glucagon-like peptide-1 triggers a specific cellular response, which is manifested by activation of a pronounced anti-inflammatory effect in women’s blood. Studying this signaling pathway may help to understand new mechanisms of fetal growth restriction and identify potential markers that will enable to verify this pregnancy complication at the antenatal stage.

Objective: The objective of the study was assessment of relationship between the prognostic values of laboratory serum markers and histopathological changes in early pregnancy loss.

Materials and methods: The study included 269 women of reproductive age seeking healthcare in hospital due to reproductive loss before 12 weeks of pregnancy. Histomorphological structural changes were evaluated followed by comparative analysis of these changes and laboratory parameters, such as fibrinogen, leukocytes, interleukin-6 (IL-6), platelets, thrombomodulin (TM), and plasminogen activator inhibitor 1 (PAI-1), which are most often used in predicting reproductive losses.

Results: Our study found statistically significant difference between the group of inflammatory changes versus the group of hemorrhagic/ischemic changes. The interquartile ranges for IL-6 were 5730–8840 ng/ml and 3540–6910 ng/ml, respectively, that can serve as a prerequisite for determination of reference values for prediction of inflammatory factors at the pre-gravid stage. Also, there was statistically significant difference in TM levels. The interquartile range of TM in the group of inflammatory changes was 5430–6510 ng/ml versus 7120–9030 ng/ml in the group of hemorrhagic/ischemic changes, that indicated a significant correlation between laboratory markers and the results of histological analysis of hemorrhagic changes. There were no statistically significant differences between the other laboratory parameters.

Conclusion: According to analysis of histopathological changes before 12 weeks of pregnancy and two or more adverse pregnancy outcomes in history in female population in Kazakhstan, the main causes of reproductive losses are inflammatory and hemorrhagic disorders. The study showed that IL-6 as a predisposing factor of the causes of reproductive losses and TM as the gold standard for identification of coagulation and hemorrhagic defects, that cause miscarriage, can be considered to be the most significant prognostic laboratory criteria.

Objective: To evaluate the association between xenobiotic detoxification system gene polymorphisms and hormone replacement therapy (HRT) efficacy in patients with premature ovarian insufficiency (POI).

Materials and methods: This study included 83 women with POI who exhibited persistent symptoms of estrogen deficiency while receiving HRT E2/DYD 2 mg/10 mg. The participants were divided into two groups: group 1 (n=23) included patients with signs of severe estrogen deficiency (GCS score > 20 and E2 blood level <150 pmol/l) and group 2 (n=60) included those with a GCS score < 20 and an E2 blood level >150 pmol/l. Genotyping was performed by real-time PCR. The distribution frequencies of alleles and genotypes for the polymorphisms were analyzed in both groups. The χ² test assessed the significance of the differences (p). The strength of the association between features was evaluated using the odds ratio (OR).

Results: Allele A of the A313G polymorphism of GSTP1 and allele C of the C341T polymorphism of GSTP1 were associated with severe estrogen deficiency in patients receiving HRT E2/DYD 2 mg/10 mg (OR=2.99, 95% CI 1.07–8.33, p=0.03; OR=7.43, 95% CI 0.96–57.52, p=0.03). The AC haplotype (risk haplotype) for the GSTP1 A313G (Ile105Val) and GSTP1 C341T (Ala114Val) polymorphisms was significantly more frequently detected in patients with severe estrogen deficiency during HRT (69.6% in group 1 versus 43.3% in group 2, p=0.049, OR=2.99, 95% CI 0.97–9.80). The -341 C/C genotype was identified as a marker of the risk haplotype based on haplotype and individual genotype correspondence assessment.

Conclusion: GSTP1 gene polymorphisms play a significant role in the response to HRT in patients with POI, likely due to their influence on the regulation of E2 detoxification processes.

Background: The choice of the optimal medication for post-transfer support in fresh embryo transfer in vitro fertilization (IVF) programs is an important issue in the choice of personalized therapy which is mainly aimed at improving perinatal outcomes.

Objective: To evaluate pregnancy outcomes after IVF programs with fresh embryo transfer depending on the type of progestogen used for the post-transfer support.

Materials and methods: This was a retrospective study conducted at the Urals Scientific Research Institute for Maternal and Child Care, Yekaterinburg in the period from February 2019 to December 2022. The study included 390 pregnant patients with a history of infertility who had stimulated IVF cycles with fresh embryo transfer. All women were divided into two groups: group 1 included 143 patients who received dydrogesterone 30 mg/day orally as luteal phase (LP) support after transvaginal puncture until 12–20 weeks gestation, and group 2 included 247 patients who received micronized vaginal progesterone (MVP) 600 mg/day vaginally as supportive therapy until 20 weeks gestation. The primary outcome measure was live birth rate, while the secondary outcome measure was the rate of early pregnancy termination (miscarriage), preterm and term labor, and pregnancy complications.

Results: Among gynecological diseases, polycystic ovary syndrome was statistically significantly more frequent in patients with LF dydrogesterone support than in patients with MVP support (20/143 (14%) and 18/247 (7.3%) respectively, p=0.020). Pregnancy outcomes were analyzed according to the type of progestogen used for the post-transfer support. The rate of term delivery was 84/143 (58.7%), the rate of pregnancy termination before 22 weeks was 34/143 (23.8%), and the rate of preterm delivery was 25/143 (17.5%) in the group of patients who took dydrogesterone. The rate of term delivery was 153/247 (61.9%), the rate of pregnancy termination was 50/247 (20.2%), and the rate of preterm delivery was 44/247 (17.8%) in the group of patients who received MVP. There were no statistically significant differences in the rate of pregnancy outcomes depending on the type of progesterone used for the post-transfer support (dydrogesterone or MVP) (p>0.05). Pregnancy-induced hypertension with or without proteinuria was statistically significantly more frequent in patients who took MVP for the post-transfer support, 24/247 (9.7%), compared to 6/143 (4.2%) in the dydrogesterone group (OR=2.457, 95% CI: 0.98-6.164, p=0.045).

Conclusion: The results of the analyses showed comparable effectiveness of progestogens used for the post-transfer support (dydrogesterone or MVP) on pregnancy outcomes in the IVF cycle; the data did not reach statistically significant differences. According to the results obtained in the study, it can be concluded that the use of dydrogesterone helped to reduce late pregnancy complications such as pre-eclampsia. It is necessary to conduct further studies to evaluate perinatal outcomes of pregnancies after IVF programs depending on the type of progestogen used for the post-transfer support.

Objective: To study the effect of a prolonged course of topical therapy with fenticonazole for the prevention of recurrent vulvovaginal candidiasis in patients with the chronic recurrent course of the disease and to evaluate the recurrence-free course of vulvovaginal candidiasis during the following 6 months.

Materials and methods: The study included 206 female patients with recurrent vulvovaginal candidiasis. The patients received the following treatment: fenticonazole 600 mg topically was prescribed twice at 72 h intervals to the patients of the main group (n=96); then the patients of the 1st subgroup (n=36) received fenticonazole 600 mg once every 10 days for 3 months; the patients of the 2nd subgroup (n=30) received fenticonazole 600 mg twice at 72 h intervals once a month for 3 months; the patients of the 3rd subgroup (n=30) received fenticonazole 600 mg once every 10 days followed by two courses of PRP-therapy. The patients in the control group (n=110) were prescribed fluconazole 150 mg orally on days 1, 4 and 7, then 150 mg once a week for 3 months. The patients of the groups were comparable in age, body mass index, somatic and gynecologic diseases. The women were followed up for 3 months of maintenance therapy and then 6 months after the end of the treatment.

Results: There were no significant differences in the rate of recurrent vulvovaginal candidiasis in patients receiving systemic and topical therapy (p=0.66), but during a 3-month follow-up the rate of recurrence was considerably higher in the group of patients who received systemic treatment with fluconazole (p=0.043). The efficacy of therapy was 92.71% in the main group and there were no subsequent recurrences during the next 3 months in 87.5% of the patients. The efficacy of therapy was 94.55% in the control group, and there were no recurrences in 76.36% of the patients during the next 3 months. Recurrences were noted in 34.3% (33/96) of patients in the main group in 6 months after the end of the course of maintenance therapy, and recurrences were observed in almost every second case in the control group, namely, in 46.4% (51/110), respectively (p=0.039).

Conclusion: Topical and systemic therapy are equally effective in the treatment of recurrent vulvovaginal candidiasis. The rate of recurrence after the end of the treatment was significantly lower after topical use of fenticonazole compared to systemic administration of fluconazole.

To optimize the surgical treatment of patients with rare benign vulvar tumors on the basis of clinical characteristics of the disease.

This article presents clinical cases of benign vulvar tumors such as superficial angiomyxoma, papillary hidradenoma, fibroangiolipoma, and vulvar fibropapilloma.

The article describes patients’ complaints, case history, clinical picture, and the type of pathologic focus in the vulva area. It emphasizes the main clinical characteristics which are necessary for timely diagnosis of the disease.

Rare benign vulvar tumors are often difficult to diagnose. A thorough examination of the inguinal-femoral lymph nodes is essential for an accurate diagnosis. The absence of enlarged lymph nodes, absence of tumor infiltration of the underlying tissues, expansive growth, and clear boundaries with healthy tissues are indicative of a benign tumor. The doctor can frequently be confused by the large size of the mass; however, a long history of the disease in combination with the above-mentioned characteristics also suggests that the process is benign. Meanwhile, the presence of enlarged, dense, painless regional lymph nodes can be indicative of a malignant tumor, even if the primary focus is small.

Conclusion: When choosing a surgical and postoperative treatment option, one should consult the physician and the morphologist; additional clinical data presented to the morphologist can help make the final diagnosis easier and exclude suboptimal surgery.

Background: Endogenous heparin-like syndrome (HLS) in obstetrics is a rare complication most practicing physicians are unfamiliar with. Glycosaminoglycans (GAGs) circulating in the bloodstream, mostly of endothelial origin, play the role of endogenous heparins. Liver disease, systemic inflammatory response, and infectious diseases are associated with the HLS development. The incidence of HLS varies according to pathology; for instance, it is 5% in trauma, and in liver transplantation it can be as high as 100%. The incidence of HLS in obstetrics remains unclear. The difficulty in the correction of the hemorrhagic syndrome associated with HLS is the lack of a uniform approach to therapy.

Case report: This article presents the first clinical observation of the HLS development in a pregnant woman after intrauterine correction of fetal spina bifida by open fetal surgery. Severe HLS was detected by thromboelastometry (CT_INTEM /CT_HEPTEM ratio >2); Laboratory parameters (activated partial thromboplastin time, thrombin time) showed hypocoagulation due to the presence of GAGs in the blood.

Conclusion: Monitoring of the hemostasis system in the perioperative period in obstetric patients can help timely recognize HLS and reduce the incidence of bleeding caused by the presence of endogenous GAGs. Further study is required to better understand how to diagnose and treat HLS effectively.

Background: Androgen-producing tumors represent an extremely rare group of hormonally active adrenal neoplasms. Their clinical course is characterized by hirsutism, menstrual irregularities, acne, virilization and other manifestations of hyperandrogenism. This condition should be differentially diagnosed with diseases such as polycystic ovary syndrome (PCOS), congenital adrenal hyperplasia (CAH), Itsenko–Cushing syndrome and adrogen-producing ovarian tumors, which are also characterized by androgen excess.

Case report: The presented clinical case is an example of long-term observation of a reproductive-aged woman with a clinical picture of hyperandrogenism and reproductive dysfunction; she received ineffective treatment for CAH and PCOS at different periods of her life. Multisteroid hormone analysis of blood serum by high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS), genetic testing combined with high-precision imaging techniques made it possible to establish the diagnosis of androgen-producing adrenal mass as the underlying cause of the disease more than 20 years after the appearance of the first symptoms. After performing adrenalectomy for the tumor, the level of androgens and their metabolites became normal, and the menstrual cycle restored.

Conclusion: Patients with manifestations of hyperandrogenism should have laboratory evaluation of possible hormonal disorders, imaging of the adrenal glands and ovaries (pelvic MRI, MSCT of the retroperitoneal space), and genetic testing for CYP21A2 gene mutations, when necessary, to exclude the excessive androgen production or adrenocortical tumorigenesis. In order to identify the source of hyperandrogenism, multisteroid blood analysis may be performed as an additional method using HPLC-MS/MS.