No 8 (2023)

The problem of infertility affects millions of reproductive-aged people worldwide, and the situation is only getting worse. Modern treatment methods involve the use of assisted reproductive technologies (ART); however, the frequency of pregnancy based on the transfer of two embryos is approximately 40%.

This may be due to the unsatisfactory quality and quantity of the oocytes obtained. Since endothelial factors are involved in maintaining the homeostasis of the female reproductive system, their excessive or insufficient number leads to the disruption of adaptation mechanisms in polycystic ovary syndrome (PCOS), ovarian hyperstimulation (OHSS), endometriosis, etc.

The review shows the role of proliferative, pro-, and anti-inflammatory endothelial factors in the maturation of oocytes in the treatment of infertility caused by different reproductive system diseases: PCOS, OHSS, endometriosis, etc.

Conclusion: Impaired homeostasis due to endothelial dysfunction and to changes in the number and/or activity of proliferative, pro-, and anti-inflammatory endothelial factors is associated with reproductive system diseases: PCOS, OHSS, endometriosis, recurrent implantation failures. Induced ovulation stimulation in the treatment of infertility by ART methods can also promote endothelial dysfunction due to a high hormonal load. This may be associated with the low efficiency of therapy.

Therefore, determining the role of proliferative, pro-, and anti-inflammatory endothelial factors is relevant for practitioners in order to increase the success and personification of the treatment of female infertility by ART methods.

reproductive medicine. It is supposed that the use of dehydroepiandrosterone and testosterone before therapy in poor female responders can improve the outcomes of ART programs due to a better OS response. At the same time, there are conflicting data on the positive effect of androgen priming on OS indicators and the clinical outcomes of in vitro fertilization (IVF). This review considers the main issues regarding the efficiency and safety of adjuvant pretreatment androgen therapy (regimens, dosages, and duration) on the effectiveness of ART cycles in poor female OS responders.

Conclusion: There is a need for further relevant randomized clinical trials to confirm the benefits and safety of androgen therapy before OS in poor female OS responders in the IVF programs.

The literature on the role of placental pathology in the development of lesions in the neonatal and fetal brain is analyzed. Structural damages and placental dysfunctions can be a cause of fetal developmental disorders and neonatal diseases. The literature data indicate that implantation disorders (as preeclampsia), circulatory disorders in the maternal (accelerated placental villous maturation and infarctions, and premature placental detachment) and in the and fetal (thrombotic vasculopathy) body, infectious, inflammatory, and immune processes (acute chorioamnionitis, chronic villitis, and funisitis), as well as massive perivillous fibrin, placenta increata, as well as umbilical cord abnormalities can lead to neurological disorders and brain damage in the newborn. The aggravating factor is the multiplicity and concurrence of different types of placental disorders. The most common brain lesions are considered to be the development of ischemic injuries, intraventricular hemorrhages, periventricular leukomalacia, and cerebral palsy. The important point of a number of placental disorders is the risk of their recurrence in subsequent pregnancies.

Conclusion: Despite the fact that morphological examination of the placenta is carried out only after childbirth, the results obtained during the examination are necessary for obstetricians and neonatologists to fully diagnose diseases of the newborn, as well as to determine treatment policy for brain lesions, in particular.

Objective: To determine the level of expression of energy metabolism genes, namely visfatin (NAMPT), ghrelin (GHRL) and leptin (LEP) in maternal and umbilical cord blood and in the placenta in case of fetal growth retardation.

Materials and methods: The study included 52 pregnant women: the main group consisted of 27 patients diagnosed with fetal growth retardation postnatally; the control group included 25 women with normal course of pregnancy. Real-time PCR was used to determine the expression level of energy metabolism genes.

Results: The level of expression of the NAMPT and GHRL genes in maternal blood was found to be statistically significantly reduced in fetal growth retardation (p=0.012 and p=0.019, respectively). The level of expression of the NAMPT and GHRL genes in umbilical cord blood was also reduced in comparison with the control group, but it was not statistically significant (p=0.30 and p=0.23, respectively). LEP gene expression in maternal and umbilical cord blood was not found. The level of leptin expression in the placenta was found to be statistically significantly increased in the main group (p=0.045), though these differences were not associated with gestational age at the time of delivery.

Conclusion: The decreased levels of expression of the NAMPT and GHRL genes in maternal blood can become an objective marker for diagnosing fetal growth retardation during pregnancy. The increased expression of LEP in the placenta in fetal growth retardation may give a better understanding of its pathogenesis and new opportunities for its diagnosis.

Postpartum endometritis (PE) is the leading cause of pyoinflammatory complications in the postpartum period. At the same time, almost every second case of PE is associated with reduced contractility of the myometrium, which manifests as subinvolutive dimensions and volume of the postpartum uterus. However, uterine subinvolution (USI) is not only a nosological entity in its own right but also a pre-stage of PE and has several clinical and laboratory features that require prevention, timely diagnosis, and therapeutic intervention.

Objective: To investigate the clinical, anamnestic, laboratory, and instrumental diagnostic features of USI in women after spontaneous and operative delivery.

Materials and methods: This study retrospectively analyzed 200 records of postpartum women treated at Voino-Yasenetsky Krasnoyarsk State Medical University clinics from 2019 to 2022. Of these, 100 had mild PE, and 100 were diagnosed with uterine subinvolution. Each group was divided into two subgroups consisting of 50 postpartum women after spontaneous birth (SB) and 50 postpartum women after abdominal delivery.

Results: Significant differences were observed in the clinical course of the disease among women in the study groups. Complaints in postpartum women with USI occurred 4 days later (day 13) than those in patients with PE (day 9). After abdominal delivery, clinical manifestations were significantly more common than in the SB subgroups (p<0.05), including lower abdominal pain and bloody discharge in all postpartum women after cesarean section (CS); more than half of the patients had purulent discharge 66/100 (66%], p<0.05). In the CS subgroup, 9/50 (18%), 19/50 (38%), and 13/50 (26%) patients had lower abdominal pain, bloody vaginal discharge, and purulent vaginal discharge, respectively. More pronounced inflammatory changes in the blood tests were characteristic of postpartum women with PE (especially in the CS subgroup) due to higher levels of leukocytes, C-reactive protein, and ESR (p<0.05). Subinvolutive dimensions of the uterus were found by ultrasound in 78% of the women with PE.

Conclusion: USI has several clinical and laboratory features that can be considered as an isolated postpartum complication. The presence of inflammatory changes in the blood tests confirmed the predominance of the infectious component over the reduced contractile function of the myometrium in patients with PE after CS. In women with SB, reduced contractile function of the myometrium prevails without obvious clinical manifestations or inflammatory changes in the blood tests. The results of the present study emphasize the need for timely diagnosis of subinvolutive changes in the uterus.

Objective: To investigate the prevalence of infertility-related laparoscopic findings among patients with familial Mediterranean fever (FMF), female genital tuberculosis (FGTB), and those without FMF or FGTB.

Materials and methods: This cross-sectional study included 204 patients with infertility. The patients were divided into a group of 50 women with FMF, median age 29 (26; 31.8) years, a comparison group of 44 women with FGTB, median age 29 (25; 33) years, and a control group of 110 patients without FMF or FGTB, median age 32 (28; 36) years.

Results: Compared with control subjects, patients with FMF and FGTB had higher incidence of pelvic adhesions (RR=2.83 [95% CI: 1.97; 4.07]; p<0.001 and 3.3 [95% CI: 2.34; 4.66]; p<0.001, respectively), free fluid (RR=3.3 [95% CI: 1.93; 5.65]; p<0.001 and 3.12 [95% CI: 1.79; 5.45]; p<0.001, respectively), and peritoneal lesions (p<0.001). Conversely, they were less likely to have genital endometriosis (RR=0.46 [95% CI: 0.27; 0.78]), p=0.002 and 0.22 [95% CI: 0.09, 0.51]; p<0.001, respectively). Tubal occlusion was more common in patients with FGTB than in controls and patients with FMF (RR=5.63 [95% CI: 3.5; 9.04]; p<0.001 and 2.41 [95% CI: 1.6; 3.63]; p<0.001, respectively). In the FMF group tubal occlusion was more common than in the control group (RR=2.34 [95% CI: 1.29; 4.24], p=0.009). Tubal peritoneal infertility was predominantly diagnosed in patients with FMF (RR=2.59 [95% CI: 1.99; 3.38]; p<0.001 and FGTB (RR=2.76 [95% CI: 2.13; 3.56]; p<0.001). Repeated pelvic surgery was more common in FMF patients than in patients with FGTB (p<0.001) and in controls (p<0.001); in the FGTB group it was observed more often than among controls (p=0.006) Patients with FMF and FGTB were more likely to undergo coagulation/cauterization of polycystic ovaries (p=0.009 and <0.001, respectively) and ovarian resection (p<0.001).

Conclusion: FMF and FGTB are associated with an increased risk of pelvic adhesion, tubal occlusion, free fluid, peritoneal lesions, and tubal peritoneal infertility. Both conditions often require repeated pelvic surgery such as coagulation/cauterization of polycystic ovaries and ovarian resection.

Objective: To investigate the epidemiological situation regarding the incidence and prevalence of benign breast disease (BBD) among women in the Ural Federal District (UFD) between 2012 and 2021.

Materials and methods: This descriptive epidemiological study analyzed the incidence and prevalence of BBD in the UFD from 2012 to 2021. The study included adult women, including those older than working age.

Results: From 2012 to 2019, an increase in the incidence and prevalence of BBD was observed among adult women in the UFD. The average growth rates (AGR) of incidence and prevalence were 3.37% and 5.29%, respectively. During the same period, the incidence of BBD in women beyond working age showed a moderate upward trend and higher prevalence. The AGR was 1.91% and 6.03%, respectively. However, 2020–2021 witnessed a significant decrease in these indicators, with a negative AGR. This decline can be attributed to restrictive measures, suspended medical care, decreased preventive examinations, outpatient medical supervision, and outpatient care owing to the COVID-19 pandemic.

Conclusion: This study of the dynamics of BBD incidence and prevalence among adult women in the UFD from 2012 to 2021 provides valuable information for understanding the factors contributing to the pre-pandemic growth of these indicators. This knowledge can aid in the future planning and improvement of medical care, particularly with the aim of enhancing the quality of life of patients. It is important to consider regional characteristics, including sparsely populated and rural areas, when implementing such plans.

Objective of the study – to familiarize practicing obstetricians/gynecologists with the criteria of criminal, civil, and administrative responsibility for adverse outcomes of medical care and related reproductive losses; to show how it is possible to avoid repeating other people's mistakes; to "analyze" the most striking clinical cases of maternal and perinatal mortality through the eyes of a lawyer and a doctor at the same time; to demonstrate positive and negative foreign experience, to look into the future and to search for the best way to develop legislation (in a broad sense, including clinical recommendations) and judicial practice. When writing this paper, the authors used open sources of publication of impersonal court decisions: databases of the state automated system "Justice" (https://bsr.sudrf.ru/bigs/portal.html), the portal "Judicial and regulatory acts of the Russian Federation" (https://sudact.ru), the legal reference system "Consultant plus". The selected court decisions were evaluated according to their informative value for the medical community, the accuracy and completeness of the reflection of medical documentation, the topical belonging to obstetric issues. The literature sources were sought for, by using the Russian and foreign electronic libraries (https://www.elibrary.ru), Elsevier (https://www.elsevier.com), PubMed (https://pubmed.ncbi.nlm.nih.gov).

Conclusion: Within the framework of the stated topic, the authors do not pretend to provide detailed coverage of all aspects of the raised problem and they propose together with the participants of the First International Congress “The Right to Life” held at the V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of the Russian Federation on April 18–20, 2023, to continue a frank conversation about medical errors and their consequences on the largest scientific platforms and, above all, with the participation of the medical community.

Background: Chronic endometritis (CE) is associated with unsuccessful attempts of in vitro fertilization (IVF) in 7.7–67.5% of patients.

Objective: To increase the effectiveness of IVF in patients with infertility caused by CE.

Materials and methods: The study included 600 infertile patients with CE undergoing IVF treatment. The patients were randomized into two groups (300 people each). Treatment in groups I and II included antibacterial therapy (10 days) and progesterone (6 months); patients in group I received a complex of natural antimicrobial peptides and cytokines (Superlymph) (1–4 courses after 2–3 months). During IVF cycle, one cryopreserved embryo was transferred.

Results: Pregnancy occurred in 57.0% vs. 38.7% (RR=1.47; 95% CI: 1.24–1.75, p<0.001) as a result of treatment before cryopreservation in groups I and II, live birth was noted in 45.3 and 20.7%, respectively (RR=2.19; 95% CI: 1.70–2.83, p<0.0001). The same parameters were higher in patients aged 35 and over who received Superlymph, namely by 1.6 and 2.6 times, respectively, as well as in patients suffering from infertility for 5 years or more. Therapy with Superlymph contributed to reducing the risk of miscarriage at early stages, premature birth and low weight birth by 2 times compared to the treatment without it, preeclampsia by 2 times, hypoxia and fetal growth retardation by 3 times, antenatal fetal death by 6.7 times, respectively.

Conclusion: The use of Superlymph in combination with progesterone during preconception care improves the results of IVF in patients with uterine infertility caused by CE.

Objective: To study the effect of Mense dietary supplements on the state of the urogenital zone in patients with recurrent lower urinary tract infection during peri- and postmenopause and to evaluate the risk of recurrent urinary tract infection.

Materials and methods: The study included 86 patients in peri– and postmenopause with the symptoms of vaginal and cystourethral atrophy and recurrent cystitis. The main group consisted of 44 patients, the control group included 42 patients. The patients of both groups received standard therapy for acute urinary infection. To prevent recurrent cystitis, all patients were administered medications containing cranberry proanthocyanidins. The patients were also recommended to consume not less than 1.5L of fluid per day and to maintain the proper hygiene of the urinary tract. The patients of the main group additionally received Mense dietary supplements, 1 or 2 capsules per day during a meal for one month. The state of pelvic venous hemodynamics and microcirculation of the bladder wall were assessed with the help of Doppler sonography and laser Doppler flowmetry. Bladder microcirculation parameters were measured using laser analyser of blood microcirculation (LAKK-02, Russia).

Results: During the study all the patients of the main group noticed the considerable improvement in general well-being, decrease in tenderness, relief of pain in the lower abdomen and discomfort in the urethra area after 1 and 6 months. The use of Mense dietary supplements in women with chronic recurrent cystitis in the period of peri– and postmenopause helps to achieve higher clinical effect due to the remarkable improvement in the circulation of the bladder wall and urethra and positive dynamics in pelvic venous blood flow.

Conclusion: The complex therapy containing Mense supplements with phytoestrogens for the recurrent infection of the urinary tract during peri– and postmenopause contributes to the improvement in the state of the urogenital zone, and also considerably reduces the number of cystitis recurrences.

Objective: To evaluate the effectiveness of the treatment of genitourinary syndrome of menopause (GSM)/vulvovaginal atrophy (VVA) with a non-hormonal vaginal cream containing hyaluronic acid and phytocomplex in patients with a history of hormone-dependent tumors of the reproductive organs.

Materials and methods: Thirty patients with symptoms of GSM/VVA aged 30 to 60 years with a history of breast cancer (n=13) and endometrial cancer (n=17) were included in an observational prospective study. At the screening visit, after the women’s condition was assessed, they received a non-hormonal cream with hyaluronic acid and phytocomplex using the following scheme: one dose at night in the vagina daily for 4 weeks, then one dose every other day for 8 weeks, then one dose twice a week for 12 weeks. The efficacy and safety of therapy was assessed after 3 and 6 months using a 4-point visual analog scale (VAS), the Bachmann Vaginal Health Index (VHI), pH-meters, the state of the vaginal microbiocenosis, and diaries of adverse events.

Results: The average age of the patients was 46±7 years, the average age of menopause was 4.0±2.7 years (from 1 to 14 years). There were 73.3% of sexually active women. Therapy with a non-hormonal vaginal cream for 6 months led to a statistically significant decrease in subjective symptoms (dryness, dyspareunia, burning, etc.) by more than 4 times compared with baseline data (VAS score at baseline – 11.7, after 6 months – 2.8, p=1.23*10^-24); a significant improvement in objective symptoms and an increase in the VHI by more than 2 times compared to the baseline values (VHI initially – 9.2, after 6 months – 20.1, p=5.81*10^-20); a statistically significant decrease in vaginal pH: initially – 6.1, after 6 months – 5.1, p=4.46*10^-12), an increase in the amount of lactoflora in the vaginal biotope by more than 2.5 times (initially, the average % of total bacterial mass (TBM) was 27.33, after 6 months of therapy it was 69.27) and a more than 2-fold decrease in optionally anaerobic (initial average % of TBM was 27.13%, after 6 months of therapy it was 13.73%) and obligate anaerobic microflora (initially average % of TBM was 46.14%, after 6 months of therapy it was 17.22%).

Conclusion: Our study showed that the combined cream Estrogial with hyaluronic acid and phytocomplex effectively reduces the symptoms of VVA, improves the condition of the vaginal mucosa, increases extravasation, significantly reduces the pH of the vagina and promotes the growth of normal microflora.

Objective: To evaluate the effect of the vaginal use of progesterone on vaginal biocenosis in pregnant women with a high risk of preterm birth.

Materials and methods: Cochrane, MEDLINE, Pubmed databases were assessed. Such keywords as progesterone, vaginal biocenosis, vaginal discharge were used for the search. The search depth was 12 years (2010–2022). A total of 69 sources were identified, 49 of them met the search criteria.

Results: The analysis of bibliographic sources showed that preterm birth remains one of the most relevant issues in modern obstetrics all over the world. In 184 countries, preterm birth rate ranges from 5% to 18% of the number of children. In Russia, more than 70,000 children are born prematurely every year. Etiology of preterm birth includes a lot of factors. About 80% of preterm birth are associated with infection of the amniotic fluid before 30 weeks gestation. The source of infection can be an inflammatory process in the uterine cavity, vagina, the presence of bacterial vaginosis. Vaginal biocenosis is one of the main components of a woman's reproductive health, and therefore the question of the effect of hormone therapy on the vaginal microbial landscape is of practical interest. This is especially important in preterm birth prevention, since vaginal progesterone is recommended for preterm birth prophylaxis in the high-risk group of patients (shortening the length of the cervix, history of preterm birth). However, the studies assessing the influence of progestins on the microbiocenosis of the vagina, are limited. It is important to continue research in this direction.

Conclusion: It is necessary to carry out further in-depth studies on the effect of progesterone on the vaginal biocenosis in pregnant women.

A systematic analysis of the information available in modern literature (Medscape, Medline, PubMed, eLibrary, CyberLeninka, Google scholar databases in 2010–2022) on the safety, tolerability, efficacy and features of the use of vaginal lubricants was carried out. The main types of chemical composition and physiological characteristics of vaginal lubricants are presented; targeted lubricants are considered in the light of clinical situations. A number of studies have convincingly shown that the intrinsic toxicity of individual components of lubricants, in addition to pH and osmolality, are of great importance for the their safety. When developing lubricants, special attention is paid to safety issues, not only from the point of view of the impact on the mucous membrane and microbiota of the woman's vagina, but also compatibility with germ cells, fertilization and embryos for couples who are not protected from pregnancy, as well as for use by medical workers during manipulations in assisted reproductive technology programs. For patients with symptoms of vulvovaginal atrophy (VVA), lubricants are an alternative to hormone therapy; when applied to the tissues of the vulvovaginal region, they eliminate the effects of dryness, provide moisture to the mucosa, and increase the index of vaginal health. The osmolality of the gel does not affect the viability of lactobacilli. Lubricant microbiocides are the most convenient way to use special antiseptics against sexually transmitted infections (STIs) with proven activity. Some lubricants contain special additives enhancing the genital sexual response during sexual intercourse.

Conclusion: The analysis of scientific data confirms the feasibility of widespread use of lubricants for sexual dysfunction, as moisturizers for VVA, as well as the possibility of their using during pregnancy, for postcoital cystitis, to reduce the risk of infection with STIs during sexual intercourse.

Background: Acute intermittent porphyria is a group of rare hereditary metabolic diseases caused by a genetic defect of the enzymes involved in heme biosynthesis that leads to the excessive accumulation of porphyrins in the body. Surgical intervention and the use of various medications can result in an exacerbation of acute intermittent porphyria.

Case report: The paper describes a clinical case of a 25-year-old patient diagnosed as having 38 week’s gestation, acute intermittent porphyria, a condition after two heme arginate therapy cycles started in 2019, and clinical hematological compensation, porphyritic polyneuropathy, Stage 2 chronic kidney disease. The patient was admitted in a satisfactory condition to the V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, after a telemedical consultation to be examined and prepared for surgical delivery. There was no clinically significant polyneuropathy, neurological deficit, and autonomic nervous system dysfunction during pregnancy. Three days before the date of delivery, infusion preparation was done using a 20% glucose solution of 1000 ml per day, daily serum sodium monitoring, single determination of the urinary porphyrinogen level (69 mg/l). General balanced anesthesia was the method of choice. The postoperative period occurred without respiratory and hemodynamic disorders. The investigators monitored the levels of serum sodium and iron, blood inflammation markers, creatinine, ferritin, and urea. The administration of heme arginate was not required due to her good preoperative preparation. At 24 hours after surgery, the patient was transferred to the specialized unit. She was discharged in a satisfactory condition on 7 postoperative days.

Conclusion: The described case demonstrates that there can be a favorable course of pregnancy, childbirth and the postpartum period in porphyria compensation, optimal choice of a method for delivery and anesthesia, adequate preoperative preparation.

Background: Spontaneous ovarian arterial rupture is a rare life-threatening complication. This pathology is most commonly associated with pregnancy.

Case report: This paper describes a clinical case of a multiparous (ecundipara) patient with ovarian aneurysm rupture in the postpartum period. The patient aged 39 years has been admitted to the Gynecology Department, Republican Clinical Hospital, Ministry of Health of the Republic of Tatarstan, on the second day after term vaginal delivery with complaints in the right lumbar area and temperature rises. Contrast-enhanced computed tomography (CT) has revealed large retroperitoneal hematoma, and active extravasation of the contrast agent into the right retroperitoneal space. Embolization of uterine arteries and the right ovarian artery was successfully performed.

Conclusion: Contrast-enhanced CT allows one to detect a rare complication as ovarian arterial aneurysm rupture. Diagnostic angiography and subsequent transcatheter arterial embolization are an alternative to a surgical intervention and are considered to be very effective in this condition.