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No 11 (2021)

Articles

Pregnancy outcomes after maternal COVID-19 vaccination during pregnancy: preliminary data

Sukhikh G.T., Dolgushina N.V., Shmakov R.G., Klimov V.A., Yarotskaya E.L., Petrova U.L.
Obstetrics and Gynecology. 2021;(11):5-8
pages 5-8 views

Vaccination during pregnancy: present and future

Shipitsyna E.V., Shirshova N.Y., Kogan I.Y.

Abstract

Vaccination during pregnancy, which is finding increasing use worldwide, is one of the most effective and promising strategies for preventing morbidity and mortality from infectious diseases among pregnant women and newborn babies. Vaccination for pregnant women has been shown to be highly effective and safe in a number of important infections, such as influenza, pertussis, and tetanus. As there is more evidence that vaccination during pregnancy against the novel coronavirus infection is effective and safe, an increasing number of countries include it in priority vaccination programs. In recent years, progress has been made to design new vaccines against Group B streptococcus, respiratory syncytial virus, and cytomegalovirus, which are designed mainly for pregnant women. According to many studies, an obstetrician/gynecologist’s vaccination recommendation with sufficient information on the need and safety of vaccination for a woman and a newborn baby is a key factor for a pregnant woman’s decision to get vaccinated. Conclusion: This review analyzes the literature on the main aspects of vaccination during pregnancy: the efficacy and safety of currently recommended vaccines and the factors influencing the attitude of pregnant women to vaccination. It discusses the issues of pregnant women’s vaccination against the novel coronavirus infection and the promising areas and developments in vaccination during pregnancy.
Obstetrics and Gynecology. 2021;(11):9-16
pages 9-16 views

Search for the causes of reproductive system disorders: a research review

Kirakosyan E.V., Nazarenko T.A., Pavlovich S.V.

Abstract

The continuous development of assisted reproductive technologies (ART) has led to the fact that all types of male and female infertility have now been overcome; however, the effectiveness of using ART methods remains limited and is approximately 30%. What is the reason for this? The paper reviews the world literature sources available in the databases Scopus, Web of Science, MedLine, Cochrane CENTRAL, Cochrane Database of Systematic Reviews (CDSR), Database of Abstracts of Reviews of Effectiveness (DARE), EMBASE, Global Health, CyberLeninka, and Russian Science Citation Index (RSCI) for a comprehensive study of the contribution of various factors to the development of reproductive system disorders. It considers the possible role of genetic and immunological causes, abnormal intra-ovarian steroidogenesis and folliculogenesis, leading to oocyte defects and mitochondrial disorders, which can in turn contribute to impaired early embryogenesis. The analyzed findings are promising, but further investigations of the etiopathogenesis of reproductive system disorders are needed to optimize the algorithm for patient examination and treatment. Particular attention is paid to the most demonstrative clinical model of reproductive system disorders, such as infertility of unknown origin, as an investigation object, when the reproductive system appears anatomically and functionally normal; however, conception does not occur. Conclusion: The information on the role of genetic and immunological causes, abnormal intra-ovarian steroidogenesis and folliculogenesis, leading to oocyte defects and mitochondrial disorders, which can in turn promote impaired early embryogenesis is summarized and analyzed. The algorithm for the diagnosis and treatment of patients with infertility of unknown origin, which is currently relevant from a clinical point of view, is given.
Obstetrics and Gynecology. 2021;(11):18-25
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The follicular fluid metabolomic profile as a marker for oocyte quality in assisted reproductive technology programs

Gaponenko A.A., Mityurina E.V., Frankevich V.E.

Abstract

One of the leading factors in determining the success of assisted reproductive technologies is to obtain an embryo with a high implantation potential, which in turn depends more on the quality of gametes. The main criterion for assessing the quality of oocytes is their morphological characteristics. Recent studies are aimed at searching for more accurate and non-invasive markers that determine the egg ability to be fertilized and to subsequently develop to a normal embryo. Follicular fluid is a unique investigation object, as it carries information about the features of the metabolic activity of the oocyte, and hence its competence. A study of biological fluid metabolomes has become possible due to the technologies based on the use of mass spectrometry and nuclear magnetic resonance. This review presents studies that discuss whether the follicular fluid metabolomic profile can be investigated to assess the quality of an oocyte and the feasibility of using a number of metabolites as additional markers. It also gives the results of a number of studies of the complete metabolomic profile of follicular fluid from patients of different age groups and according to the values of anti-Mullerian hormone. There are data on the composition of follicular fluid in women with polycystic ovary syndrome and other metabolic disorders. The review describes the studies of follicular fluid metabolomes in patients with ovarian endometrioid cysts and in those with recurrent implantation failures. Conclusion: The results of the studies conducted have confirmed the prospects and relevance of further investigation of the follicular fluid metabolic profile, which may allow one to create predictive oocyte quality model in the future.
Obstetrics and Gynecology. 2021;(11):26-31
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Uterine fluid analysis as a new opportunity to increase implantation ratesin assisted reproductive technology programs

Babayan A.A., Makarova N.P., Kondakova N.V., Gokhberg Y.A., Nepsha O.S., Kalinina E.A.

Abstract

A significant proportion of ineffective cycles of assisted reproductive technologies (ART) prompt investigators to continue to search for new approaches to defining endometrial receptivity. Most modern methods for evaluating the functional state of the endometrium are invasive and cannot be performed in one cycle with embryo transfer in the ART programs. The introduction of new-generation technologies (epigenomics, transcriptomics, proteomics, and metabolomics) makes it possible to better understand the complex biological processes that contribute to the successful outcome of ART programs. The possibility of obtaining uterine fluid directly in the embryo transfer cycle, on the one hand, and the use of omix technologies that allow the search for prognostic and diagnostic markers, on the other hand, open up new perspectives for studying the endometrium during the implantation window. Endometrial secretion analysis will be able to identify the molecular profile of uterine fluid to detect window of displacement or disruption. This review describes the possibilities of applying modern omix technologies in identifying the molecular profile of uterine fluid during the implantation window for the elaboration of an individual treatment approach in the ART programs. Conclusion: The results of the studies conducted confirm the prospects and relevance of investigating the protein, metabolomic and transcriptomic profiles to determine the most favorable time period for embryo transfer, which can be used to enhance the effectiveness of ART programs.
Obstetrics and Gynecology. 2021;(11):32-40
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Preimplantation genetic testing for embryo aneuploidy: opportunities, problems, and prospects

Savostina G.V., Perminova S.G., Ekimov A.N., Veyukova M.A.

Abstract

Human embryo aneuploidies make a substantial contribution to the etiology of implantation failures and early reproductive losses in assisted reproductive technology (ART) programs. The currently available methods for the morphological assessment of embryo quality cannot rule out aneuploid embryo transfer into the uterine cavity. The most common method for assessing the ploidy of an embryo is preimplantation genetic testing for aneuploidy (PGT-A). The introduction of PGT-A into clinical practice could considerably reduce the likelihood of aneuploid embryo transfer into the uterine cavity and enhance the effectiveness of ART programs. However, the expediency of using PGT-A in various groups of patients at high risk for aneuploid embryo formation, as well as in married couples with a good prognosis requires discussion. The paper gives a detailed analysis of the literature data from the studies evaluating the effectiveness of using PGT-A for embryos in patients of older reproductive age, in those with recurrent implantation failures or recurrent miscarriage, as well as in couples in whom the male partner had severe spermatogenic failure. The paper discusses the expediency of routine use of PGT-A in married couples with a good prognosis, as well as when using donor oocytes. It presents the stages of PGT-A, advantages and disadvantages of various methods of PGT-A and material sampling methods for analysis, as well as the possible reasons for of false positive and false negative results of PGT-A. Conclusion: PGT-A is a modern high-hrly informative method for assessing the chromosomal status of an embryo before its transfer in the ART programs. Currently, the most common method of PGT-A is high-throughput next-generation sequencing (NGS), whereas trophectoderm biopsy is a procedure to obtain material.
Obstetrics and Gynecology. 2021;(11):42-49
pages 42-49 views

Consulting gamete and embryo donors and surrogate mothers: problems and their solution ways in world practice

Bashmakova N.V., Polyakova I.G., Symaniuk E.E., Khramtsova A.Y.

Abstract

Today, reproductive donation is one of the successful methods to solve infertility problems and is frequently the only chance for many people to become parents. The assisted reproductive technology (ART) procedures have not only medical aspects; a special role in them is played by both the mental state of all participants and their awareness about the social and legal consequences of ART. This paper analyzes the world practice of consulting reproductive donors. The authors consider how the need for advice given to donors is legislatively regulated or recommended in the documents of the responsible organizations, as well as how the goals and scope of consulting services are defined. Reproductive donor counseling varies from country to country and according to the reproductive material. But there are general trends. Most of the consultations with donors discuss their motives, the consequences of donation, both physical and psychological ones, future expectations, and legal issues, which is extremely important for signing their informed consents. Particular attention is paid to the consequences of donation for the current or future family of the donor, discussion of expectations and requirements for the exchange of information between all the parties concerned. Conclusion: Timely information, legal, and psychological consultations to donors are a guarantee of their conscious signing of informed consent form and can dismantle many problems before donation. The favorable prognostic factors for effective ART are a conscious decision to become a reproductive donor, a high level of motivation, a willingness to cooperate with a physician and a recipient, and the stable mental state supported by a psychologist throughout the entire process.
Obstetrics and Gynecology. 2021;(11):50-55
pages 50-55 views

Molecular markers for endometrial receptivity in assisted reproductive technology programs

Gokhberg Y.A., Timofeeva A.V., Kalinina E.A.

Abstract

Despite the increasing effectiveness of assisted reproductive technology (ART) programs, the frequency of successful embryo implantations remains low. The lack of implantation may be associated with impaired endometrial receptivity during the implantation window. To determine the receptivity of the endometrium, various diagnostic methods, such as histological analysis, electron microscopy, immunohistochemical examination, and molecular genetic analysis, have been developed and used; however, many of them depend on contributing factors and are of ow functional significance in solving this problem. The search for an ideal marker is now ongoing to determine the best moment for embryo transfer into the uterine cavity for an in vitro fertilization (IVF) cycle. The use of omix technologies to study the embryo culture medium could predict not only the quality, but also implantation potential of the embryo itself, as well as optimize the selection of embryos for transfer to the uterine cavity. However, to enhance the effectiveness of ART programs, it is advisable not only to study the embryonic profile, but also to assess endometrial receptivity. Conclusion: In this connection, analyzing the literature sources has shown that the study of the small non-coding RNA (sncRNA) in the endometrial samples is a promising and relevant analysis that will be able to personalize the approach to implementing ART programs.
Obstetrics and Gynecology. 2021;(11):56-62
pages 56-62 views

In vitro oocyte maturation

Mikhailova N.D., Mishieva N.G., Kirillova A.O., Martazanova B.A., Dzhincharadze L.G.

Abstract

In vitro maturation (IVM) is an assisted reproductive technology (ART) that implies aspiration of immature oocytes and their subsequent in vitro maturation. This technology is of particular importance for patients with polycystic ovary syndrome, as it prevents a formidable complication, such as ovarian hyperstimulation syndrome, as well as for those with resistant syndrome of the ovaries that are unresponsive to gonadotropin stimulation, and for those with cancers due to the possibility to completely abandon any stimulation. Nevertheless, IVM ranks below classical in vitro fertilization (IVF) in efficiency. To enhance the latter of classical IVM, an innovative embryological procedure, a two-stage capacitation in vitro maturation (CAPA-IVM) system that includes a preparatory (pre-IVM) step, has been developed, which contributes to the acquisition of competence by oocytes, and their further cultivation and maturation in the IVM media. This technology has shown to be effective, but it has a rather limited application and at this stage requires further investigation. Conclusion: This literature review describes the experience and efficiency of IVM and CAPA-IVM procedures including those in comparison with classical IVF in different categories of patients on the basis of Russian and international publications on this topic from the Pubmed system. The choice of the optimal treatment policy for such patients also requires further investigation.
Obstetrics and Gynecology. 2021;(11):64-70
pages 64-70 views

Genes involved in premature ovarian failure

Chernukha G.E., Tabeeva G.I., Rshtuni S.D., Mashaeva R.I., Chernykh V.B., Marchenko L.A.

Abstract

Premature ovarian failure (POF) is a clinical syndrome characterized by secondary amenorrhea in the presence of high FSH levels in women under the age of 40 years. The incidence of this pathology is progressively rising and currently amounting for 3-4%. Premature depletion of the ovarian reserve may be related to both genetic and environmental factors and their combination, including infectious, toxic, and autoimmune damage to the ovaries, as well as to chromosomal abnormalities, genetic variants, and epigenetic factors. This review identifies a panel of the most significant candidate genes involved in the genesis of POF, such as NANOS3, FIGLA, FOXO3, NR5A1, NOBOX, BMP15, GDF9, PGRMCI, PTEN, and BRCA1,2. These genes are responsible for a key role in early folliculogenesis, including for the formation of primary follicles and for the production of the zona pellucida, for their growth to the FSH-dependent stage, for the inhibition of FSH receptor mRNA expression in granulosa cells, thereby preventing the premature luteinization of follicles, as well as for early steroidogenesis and regulation of apoptotic processes in primordial follicles. Conclusion: Knowledge of candidate genes underlying the genesis of POF, as well as the possibility of performing whole exome sequencing in clinical practice will be of def ined value not only in understanding the physiology of the ovaries, but also for genetic counseling to make an early (preclinical) diagnosis of POF.
Obstetrics and Gynecology. 2021;(11):71-80
pages 71-80 views

Chloramphenicol: new possibilities of the old drug

Zyryanov S.K., Butranova O.I., Chenkurov M.S.

Abstract

One of the central problems of pharmacotherapy for infectious diseases is the active rise of antibiotic resistance to the most commonly used drugs, which leads to a shortage of effective patient management strategies. A possible alternative in this situation can be an evaluation of the modern abilities of antibacterial drugs, the use of which in clinical practice has been minimized over the past decades. An example of such a drug is chloramphenicol, the systemic application of which has been sharply limited since the 1960s because of reports on toxic reactions (aplastic anemia, gray baby syndrome). Topical chloramphenicol is characterized by the low level of systemic absorption and by the absence of its ability to cause a range of side effects typical for systemic use. The high antibacterial activity of chloramphenicol against a wide range of gram-negative and gram-positive pathogens (Morganella morganii, Empedobacter brevis, Burkholderia cepacia, Bacteroides spp., H. influenzae, Salmonella typhi, Staphylococcus aureus (including MRSA), Streptococcus pneumonia, Streptococcus pyogenes, Gardnerella vaginalis, Mycoplasma pneumoniae, Mycoplasma hominis, and Ureaplasma spр.), including resistant strains, allows its use in a variety of infectious diseases. The mechanism of action and structure of the drug, which distinguish it from other classes of antibacterial agents, make it possible to produce an effective effect, including on pathogens that do not contain penicillin-binding proteins (mycoplasma) in the cell wall. According to the published data, a comparative analysis of the safety profile of systematically used chloramphenicol has revealed no signif icant differences in that of representatives of other groups of antibacterial drugs, with the exception of anemia cases. The studies on the application of topical chloramphenicol in pregnant women have not revealed its teratogenic potential of the drug when used during 2-3 months of pregnancy. Conclusion: The pooled data suggesting that chloramphenicol has high activity against a broad range of pathogens, therapeutic efficacy, and a satisfactory safety profile when applied topically in various fields (clinical studies in ophthalmology and gynecology) indicates that its intravaginal formulation can be used to treat bacterial vaginosis.
Obstetrics and Gynecology. 2021;(11):81-94
pages 81-94 views

The place of alternative therapy in the algorithms for managing patients with climacteric syndrome in the context of personalized medicine

Andreeva E.N., Absatarova Y.S.

Abstract

Many women experience various climacteric manifestations. Despite the fact that menopausal hormone therapy is the gold standard for relieving hot flushes, as many as 80% of patients have used at least one alternative method in an effort to alleviate their condition. It is today known that vasomotor symptoms are a serious risk factor for cardiovascular diseases, such as coronary heart disease, hypertension, and hyperlipidemia. It is the cardiovascular mortality that holds the lead in women; therefore, therapeutic measures aimed at relieving menopausal syndrome become not only the struggle for their quality of life, but also for a reduction in all-cause mortality. This topic is especially relevant for patients with contraindications to estrogen therapy, which forces physicians to look at evidence-based medicine for a safe treatment that is adequate to the severity of manifestations. The paper provides an overview of the current drug and non-drug methods that can relieve climacteric syndrome, by evaluating their efficiency and safety: exercises, diet therapy, psychological procedures, herbal remedies, amino acids, antidepressants (selective serotonin reuptake inhibitors), gabapentin, and neurokinin-3 receptor antagonists. Conclusion: Thus, the modern possibilities of alternative therapy allow a physician and a patient to sufficiently widely and adequately choose drugs on the requests of a woman so that she can go through the menopausal transition comfortably and safely, by maintain her quality of life.
Obstetrics and Gynecology. 2021;(11):96-102
pages 96-102 views

Preimplantation genetic testing of embryos in assisted reproductive technology programs in patients with external genital endometriosis

Kulakova E.V., Nepsha O.S., Ekimov A.N., Drapkina Y.S., Makarova N.P., Ibragimova L.K., Sysoeva A.P., Kalinina E.A.

Abstract

According to published data, external genital endometriosis (EGE) leads to decline of oocyte quality/quantity and the effectiveness of ART programs. In patients with EGE, oocytes may be chromosomally unstable. This may affect the incidence of embryonic aneuploidy. Aim: To assess the incidence of aneuploid embryos in women with EGE versus women of appropriate age without EGE, who underwent fertility treatment with ART programs. Materials and methods: The group of women with EGE included 113 women, and the control group included 211 women. The group of women with endometriosis consisted of 113 patients, the control group comprised 211 women. Each group was divided into three subgroups depending on the age (<35 years, 35-37years, >37 years). To assess whether an embryo was aneuploid, high-resolution next-generation sequencing (NGS) was performed after trophectoderm. Results: There were no statistically significant differences in embryonic parameters, aneuploidy rates in embryos, and the outcomes of ART programs in patients with EGE versus the control when comparing the subgroups of appropriate age. Conclusion: It was shown, that there is no obvious impact of EGE on the effectiveness of ART programs after embryo transfer. However, a potential effect of endometriosis on the number of removed MII oocytes, as well as the rate of aneuploid embryos cannot be ignored. For detailed study of the effect of EGE on the incidence of aneuploidy further prospective research is necessary.
Obstetrics and Gynecology. 2021;(11):104-112
pages 104-112 views

Metabolomic profile of follicular fluid and embryo culture media in patients with extragenital endometriosis

Ibragimova L.K., Smol'nikova V.Y., El'darov C.M., Bobrov M.Y., Agadzhanyan D.S., Romanov E.A., Kalinina E.A.

Abstract

Objective: To identify specif ic markers in follicular fluid (FF) and embryo culture media to assess embryo quality and implantation potential in patients with extragenital endometriosis (EGE). Materials and methods: We performed comparative genomic hybridization to analyze FF and embryo culture media samples from patients with EGE and control subjects undergoing the IVF (ICSI) with preimplantation genetic testing. Spent culture medium metabolites from individually cultured embryos were detected using the HPLC-MS in the positive ion detection mode. After identifying chromatographic peaks and aligning chromatograms, partial least squares discriminant analysis was performed to better visualize the metabolite prof iles of the compared samples. Results: Metabolite profiling revealed differences in FF and culture medium compositions of patients with EGE and control subjects. Comparative analysis of metabolites showed changes in lipid metabolism and decreased antioxidant levels in patients with EGE. These findings suggest an essential role of oxidative stress and lipid metabolism regulation, especially fatty acids performing structural, nutritional, and signaling functions in EGE pathogenesis. Conclusion: Further analysis of the study findings and the search for markers attributable to embryonic development features, characteristic of EGE, remain relevant.
Obstetrics and Gynecology. 2021;(11):114-124
pages 114-124 views

Value of embryonic mitochondrial DNA in predicting the effectiveness of assisted reproductive technologies

Nepsha O.S., Kulakova E.V., Ekimov A.N., Drapkina Y.S., Makarova N.P., Kraevaya E.E., Kalinina E.A.

Abstract

Research evidence suggests that a sufficient level of mitochondrial DNA (mtDNA) in cumulus cells and oocytes is associated with the high potential of female germ cells for fertilization and is an essential factor contributing to the pre-implantation embryonic development. Several studies have shown that a reduced mtDNA copy number is associated with a higher pregnancy rate. Objective: To investigate if mtDNA content in trophectoderm (TE) cells during preimplantation genetic testing for aneuploidy (PGT-A) could be a new marker for an embryo's implantation potential. Materials and methods: The mtDNA content of trophectoderm cells was analyzed in 244 euploid embryos after OGT-A using the NGS technique. Results: Analysis of euploid embryo transfer results showed that the mtDNA content in TE blastocyst cells was not associated with ART outcomes. Also, there was no association between the mtDNA level and embryo sex. A relationship was noted between the degree of early blastocyst expansion and mtDNA level. Blastocysts with TEs corresponding to excellent grade A had higher mtDNA content. The mtDNA copy number was significantly lower in embryos biopsied on day six after fertilization compared to biopsied embryos on day 5 of culture. The mtDNA content in all TE cells in euploid embryos was statistically insignificantly correlated with maternal age. Conclusion: The study findings suggest that mtDNA content in TE cells is not predictive for the embryo implantation potential and ART effectiveness. It should be emphasized that blastocysts with an increased mtDNA levels in TE cells was associated with the birth of healthy children in the ART program. These results confirm that the quantitative mtDNA content is one of the critical factors associated with blastocyst development and depends on the day of embryo culture.
Obstetrics and Gynecology. 2021;(11):125-134
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Morphological abnormalities in oocytes in patients with HIV infection receiving antiretroviral therapy

Mityurina E.V., Perminova S.S., Kravchenko A.V., Kozyrina N.V., Veyukova M.A., Gaponenko A.A.

Abstract

Aim: To study the prevalence of oocyte dysmorphisms in HIV-infected women receiving antiretroviral therapy (ART). Materials and methods: The retrospective study included 210 married couples who underwent IVF. The main group included 113 HIV-infected patients, and the control group included 97 women without HIV infection, who underwent 163 and 123 ovarian stimulation cycles, respectively. Morphological assessment of 2321 mature MII oocytes was performed, of them 1228 oocytes were obtained in the main group and 1093 in the control group.. Results: The median age of patients with HIV infection was 34 (31;37) years; duration of the diseases and Art WAS 8 (5;11) and 3.6 (2;6) years, respectively. 65 of 113 women (57.5%; 95% CI: 47.8- 66.4) had subclinical stage 3 of the disease, 43 women (38.1%; 95% CI: 29.2-47.8) had stage 4A, 2 women (1.8%; 95% CI: 0-4.4) had stage 4B, and 3 women (2.7%; 95% CI: 0-6.2) had stage 3C of HIV infection (Russian HIV classification). The average CD4+ lymphocytes count was 582 (432;807) cells/pl, and immunoregulatory index (IRI) was 0.87. All patients received ART and had had an undetectable viral load in the blood beforee IVF treatment. The prevalence of various types of oocyte dysmorphisms in HIV-infected women was significantly higher versus the women in the control group and was 29.5% (362/1228) and 14.1% (154/1093), respectively (р<0.001, RR 2.0; 95% CI: 1.765-2.480). Among ocyte cytoplasmic abnormalities in both groups, centrally located cytoplasmic granulation (CICG) prevailed. Detection rate of this type of dysmorphisms was 17.3% (213/1229) in the main group, and 10% (109/1093) in the control group. The difference was statistically significant (р<0.001; RR 2.26; 95% CI: 1.8-2.7). The prevalence of extracytoplasmic abnormalities of oocytes, as well as combination of their types in HIV-infected patients was comparable with HIV-seronegative control. Conclusion: The higher prevalence of oocyte dysmorphisms in HIV-infected patients who received ART versus healthy women, indicates deterioration of the morphological features of oocytes in this group of patients.
Obstetrics and Gynecology. 2021;(11):135-142
pages 135-142 views

Assessment of the expression level of hsa_pir_020497 piRNA in the follicular fluid of patients with different in vitro fertilization outcomes

Shamina M.A., Timofeeva A.V., Fedorov I.S., Kalinina E.A.

Abstract

Objective: To determine the relationship between morphological and molecular biological criteria for assessing the quality of oocytes retrieved from the women on the day of transvaginal puncture of follicles. Materials and methods: We used deep sequencing method with its subsequent validation by real-time RT-PCR to identify the spectrum of small non-coding RNAs (sncRNAs) present in the follicular fluid of the left and right ovaries of 25 patients; among them, three patients underwent IVF program again after a negative result of selective embryo transfer into the uterine cavity and preconception care (administration of myo-inositol in combination with folic acid, vitamin D and omega-3). Results: We identified 86 piRNAs and 79 microRNAs by deep sequencing of sncRNA of the ovarian follicular fluid; expression level of hsa_pir_020497piRNA was statistically significantly (p=0.01) higher in the group of patients with a positive ART treatment outcome (n=14) compared to the group of patients with a negative ART treatment outcome (n=8) according to real-time RT-PCR data. After preconception care, all three patients showed an increase in the expression level of hsa_piR_020497in the follicular fluid in one or two ovaries to the expression level of hsa_piR 020497 which is characteristic of pregnant women. Protein products of potential target genes hsa_piR_020497participate in signaling pathways mediated by the epidermal growth factor receptor (ErbB), mitogen-activated protein kinase (MAPK), transforming growth factor beta (TGFP), insulin-like growth factor 1 (IGF-1), phosphatidylinositol-3-kinase/Akt pathway and in the regulation of cytosolic calcium and metabolism of vitam ins and cofactors. Conclusion: Since the protein products of the target genes hsa_piR_020497 are involved in the main signaling pathways responsible for follicle formation and egg maturation, it is relevant to conduct further studies on a large sample of couples to determine its impact on IVF outcomes.
Obstetrics and Gynecology. 2021;(11):143-153
pages 143-153 views

Impact of preimplantation genetic testing on assisted reproductive technology outcomes in couples with male factor infertility

Makarova N.P., Lobanova N.N., Kulakova E.V., Nepsha O.S., Ekimov A.N., Kalinina E.A.

Abstract

Background: In recent years, considerable attention has been focused on the association between severe male factor (SMF) and the incidence of embryonic aneuploidy, including whether SMF should be considered an indication for preimplantation genetic testing for aneuploidy (PGT-A). Objective: To investigate the impact of men's age and form of male infertility on the rate of embryonic aneuploidy and the outcomes of assisted reproductive technology (ART). Materials and methods: This retrospective study analyzed 2915 ART cycles (2225 stimulation cycles, including 371 cycles with PGT-A and 690 cryopreserved cycles). The ejaculate was evaluated based on the sperm quality criteria of the WHO reference values. The SMF group consisted of patients with oligoasthenoteratozoospermia and patients with testicular biopsy. Patients with teratozoospermia were divided into two groups, categorized by the percentage of morphologically abnormal spermatozoa. On day five after fertilization, the embryo trophectoderm was biopsied, followed by PGT-A. Results: Comparison of ART outcomes in stimulation cycles and a fresh embryo transfer and in cryopreserved cycles with and without PGT-A showed statistically significantly lower pregnancy and birth rates in patients with the sperm morphology score of 0-2% and 3% in cryopreserved cycles without PGT-A. Patients with SMF undergoing ART with PGT-A showed a trend towards increasing pregnancy and birth rates. Conclusion: PGT-A can improve pregnancy outcomes for couples with SMF with fewer embryos transferred due to reducing early pregnancy losses.
Obstetrics and Gynecology. 2021;(11):154-164
pages 154-164 views

Improvement of the embryological stage in assisted reproduction treatment with hyaluronan-enriched culture medium in couples using preimplantation genetic testing for aneuploidy

Drapkina Y.S., Kulakova E.V., Nepsha O.S., Ekimov A.N., Makarova N.P., Kalinina E.A.

Abstract

Background: During the transfer of an euploid embryo, implantation failure can result from the inadequate formation of the embryo-endometrial adhesion. According to the studies, hyaluronic acid culture media have a positive effect on the outcomes of assisted reproduction programs due to a better embryo-endometrial communication. Such media can also influence the processes of endometrial decidualization and embryo development. Objective: To evaluate pregnancy and delivery rates in patients undergoing infertility treatment with IVF/ ICSI with preimplantation genetic testing for aneuploidy (PGT-A) when an euploid embryo is transferred in hyaluronan-enriched culture medium. Materials and methods: This was a retrospective analysis of the data of309 couples undergoing IVF/ICSI cycles with gonadotropin-releasing hormone (GnRH) antagonist protocol. Cyclic hormone therapy was administered to prepare the endometrium for the subsequent transfer of an euploid embryo. Hyaluronan-enriched culture medium was used in embryo transfer of 53 patients and a standard culture medium was used in 256 cases. Results: Depending on the age, all patients were divided into three subgroups: subgroup 1 (24-30 years, 72 women), subgroup 2 (31-36 years, 148 women), subgroup 3 (37-43 years, 89 women). Unlike the results of other studies, we did not find any statistically significant effect of the hyaluronan-enriched culture medium on the outcomes of ART programs in patients of different age subgroups. Conclusion: The absence of statistically significant results may be associated with a small sample of patients in the group with hyaluronic acid, as well as the criteria for selecting patients in the comparison and control group. Further research should be done to investigate the optimal use of hyaluronan-enriched culture medium and to determine the indications for its use in different groups of patients.
Obstetrics and Gynecology. 2021;(11):166-174
pages 166-174 views

Molecular genetic predictors and ovarian reserve in women with deep infiltrating endometriosis

Melkozerova O.A., Okulova E.O., Mikhelson A.A., Tretyakova T.B.

Abstract

Objective: To investigate molecular genetic predictors and ovarian reserve in patients with infiltrating extragenital endometriosis. Materials and methods: This is a case-control study including 70 patients of reproductive age with deep infiltrating endometriosis (study group) and 50 fertile women (control group). All patients underwent testing for ovarian reserve. The molecular genetic analysis included testing for polymorphic variants of genes encoding proteins involved in the regulation of apoptosis [C-KIT: 2600 G>A, KITLG: 80441 C>T, TP53: Ex4+119 G>C (Arg72Pro)] and angiogenesis ((VEGF-A: +12143 C>A, VEGF-A: -2578 C>A, VEGF-A: -634 G>C, VEGF-A: +936 C>T). Results: The AMH level was significantly lower in patients with deep infiltrating endometriosis [2.4 (2.0) ng/ ml] than in the control group [3.8 (3.2) ng/ml], p<0.05. Antral follicle counts were also significantly lower in women in the study group [8.3 (4.5)] than in the control group [11.8 (4.1)], p<0.001. Women in the study group had a statistically significantly higher frequency of the polymorphic allele Ex4+119 G>C of the TP53 gene [OR 2.43 (95% CI1.12; 5.27)], p<0.03. Carriage of the polymorphic allele +12143 C>A of the VEGF-A gene in a homo- or heterozygous state increases the risk of deep infiltrating endometriosis [OR 2.18 (95% CI 1.03; 4.61)], p<0.05. Trilocus model constructed by multivariate analysis suggested the involvement of a combination of single nucleotide polymorphisms of genes regulating apoptosis (C-KIT: 2600 G>A, TP53: Ex4+119 G>C) and angiogenesis (VEGF-A: -2578 C>A) in the pathogenesis of endometriosis. Conclusion: Deep infiltrating endometriosis without visible affection of the ovaries may be associated with a significant decline in ovarian reserve. Dysregulation of apoptosis and angiogenesis in deep infiltrating endometriosis may be a critical mechanism undelaying diminished ovarian reserve due to the premature activation of primordial follicles and their early depletion.
Obstetrics and Gynecology. 2021;(11):175-186
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Fertility outcomes in women after therapy for non-Hodgkin lymphoma

Dmitrieva I.Y., Nazarenko T.A., Burduli A.G., Polushkina E.S., Khokhlova S.V.

Abstract

Aim: To assess menstrual and reproductive function in women, who underwent treatment non-Hodgkin (NHL) lymphoma. Materials and methods: The study included 39 female patients diagnosed with NHL. All patients still had remission by the end of the study. To collect retroaspective data, a telephone survey of the women under the study was conducted, or the data were collected from their medical records. Results: Before conception, the patients underwent 3-4 or even more than 11 chemotherapy cycles. In one patient, menses never resumed after 14 cycles of chemotherapy. However, a single observation was not enough for making statistically significant conclusion. Most treatment regimens included highly gonadotoxic substances (Cyclophosphan in 94.87% of the cases, Doxorubicin and platinum-based drugs in 89.74%). R-CHOP was the most common regimen, which was used among the studied cohort. Regular menstrual cycle resumed after treatment in 82.05% of patients. Of them, 46.88% of women received combined oral contraceptive pills (COCP), and 9.38% received depot GnRH agonist (aGnRH) for ovarian protection. After treatment with COCP, 16.66% of patients had permanent amenorrhea. None of the patients, who were treated with depot aGnRH, had persistent amenorrhea. The median period of menstrual cycle restoration was 2.41 months. In 62.07% of women, who received COCP, menstruation restored immediately or 1 month after treatment. Restoration period was longer (1-2 months) in patients, who received depot aGnRH. In 34/48% of women, the episodes of ovarian dysfunction (oligomenorrhea) was observed. Spontaneous pregnancy rate was 82.76% among those who had menses. Pregnancy occurred in a period from 24 to 54 months after the completion of chemotherapy treatment. Infertility rate increased from 10.26 to 23.07%. Two patients got pregnant after undergoing ART treatment. 82.76% of women with restored menses spontaneously conceived 24 to 54 months after polychemotherapy. The rate of infertility among the treated women increased from 10.26% to 23.07%. Two patients became pregnant after IVF. Conclusion: The critical factors for restoration of menstrual function after treatment for non-Hodgkin lymphoma were; the age of patients, high ovarian reserve, chemotherapy duration and regimens. Recovery of menstrual cycle does not always result in restoration of fertility. Medical ovarian protection does not completely protect from gonadotoxic impact of polychemotherapy. Due to this, it is important that the patients with oncologic diseases should undergo examination by a gynecologist not only after being diagnosed with the oncologic disease, but also after treatment. Only cooperation between oncologists and gynecologists may contribute to correct prognosis, reduction of reproductive losses women’s understanding of their reproductive prospective.
Obstetrics and Gynecology. 2021;(11):187-193
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Experience with Intralipid in early reproductive losses

Bespalova O.N., Zhernakova T.S.

Abstract

The fat emulsion Intralipid containing ω-6 and ω-3 fatty acids has been the gold standard of parenteral nutrition for 60 years. To date, there have been thirty years of experience with Intralipid in the immunological factor of early reproductive losses; ω-6 and ω-3 polyunsaturated fatty acids (PUFA) have been proven to play a role in oocyte maturation and embryo implantation, in the balance of synthesis of pro- and anti-inflammatory cytokines, and in the reduction of natural killer (NK) cytotoxicity. Considering the comparable efficacy of Intralipid and intravenous immunoglobulins, the fat emulsion was presented as a promising and affordable method for the treatment of recurrent abortion and implantation failures in IVF programs. Scientific sources have contradictory data on the eff icacy of Intralipid in repeated implantation failures. This is due to the determination of indications for its prescription and to the choice of criteria for evaluating the efficiency of this therapy. The paper includes data from 25 original investigations from 1991 to 2021, which present different results of Intralipid therapy. It describes the proposed mechanism of its action in the early stages of pregnancy and presents materials on the history of the discovery, classification, and metabolism of fat emulsions. Conclusion: The accumulated depot of essential a-3 PUFA during the pre-conception period contributes to the optimal development of the fetal brain and visual organs and, as shown by numerous studies, prevents the development of great obstetric syndromes. Thus, the intravenous administration of fat emulsions has a positive effect on the onset and prolongation of pregnancy.
Obstetrics and Gynecology. 2021;(11):194-201
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Efficiency and acceptability of two-stage therapy for recurrent bacterial vaginosis

Uruimagova A.T., Prilepskaya V.N., Mezhevitinova E.A., Donnikov A.E., Abakarova P.R., Dovletkhanova E.R., Gusakov K.I., Odyvanova A.A.

Abstract

Objective: To evaluate the clinical and laboratory efficiency, acceptability, and safety of anti-relapse therapy with a cream containing acidophilic bacteria (Lactobacillus acidophilus), vitamin-mineral protein-peptide complex (Superlimflife) in patients with bacterial vaginosis (BV) Materials and methods: One hundred and sixteen women aged 18 to 49 years with recurrent BV were examined. The diagnosis was based on Amsel’s criteria. After assessing the inclusion and exclusion criteria, 100 women were included in the study. The patients were divided into 2 groups: 1) 50 patients with recurrent BV who were prescribed one-stage therapy; 2) 50patients with recurrent BV who were prescribed two-stage therapy using Acylact DUO cream. The urogenital tract microflora was comprehensively studied using real-time PCR. The expression profiling method was used to evaluate the state of local (mucosal) immunity by the mRNA expression levels of the key immune response genes. The expression level of 8 genes, such as IL-1fi, IL-10, IL-18, TNFa, TLR4, GATA3, CD68, and B2M, was taken into account in the epithelial cell sample, by using the ImmunoQuantex kit. Results: The findings suggest that the number of complaints in the patients who received two-stage therapy at Visit 4, while their recurrence occurred after one-stage therapy. Microscopic examination of vaginal smears by Visit 4 revealed that the predominance of the Lactobacillus spp. morphotype and the absence of key cells were more common in the patients receiving anti-relapse therapy than in those having one-stage therapy (p<0.05). In Group 2 women who received two-stage therapy by Visit 4, the number of lactobacilli in 45 (90%) women corresponded to the normal value, moderate and significant decreases in lactobacilli were found in 2 (4%) and 3 (6%) patients, respectively; while in Group 1 by Visit 4, the normal number of lactobacilli was observed in 22 (44%) women; moderate or significant decrease were seen in 16 (32%) and 12 (24%) patients, respectively. Analyzing the time course of changes in the expression level of proinflammatory and anti-inflammatory cytokines in each of the groups during 4 visits revealed that the women in the two-stage group had a tendency to decrease proinflammatory markers and to increase anti-inflammatory ones (p<0.05). On the contrary, the women having one-stage therapy showed a decrease in the expression level of anti-inflammatory markers and an increase in that of TLR4 and TNFA compared to the screening stage; while the expression level of IL8, IL10, and TLR2decreased (p < 0.05). Conclusion: Two-stage therapy using the Acylact DUO cream enhances the efficiency of antibacterial therapy in combined use due to the normalization of a local immune response, contributes to a more stable restoration of the normal representative ratio for the vaginal microbiota and to a decrease in the rate of the recurrent process.
Obstetrics and Gynecology. 2021;(11):202-212
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Effect of hormone replacement therapy with estradiol in frozen embryo transfer on estrogen metabolism in women with various polymorphisms of catechol-O-methyltransferase gene

Kvashnina E.V., Tutakov M.A., Vakhlova O.S., Tomina E.V., Shilova N.V.

Abstract

Objective: To compare the content of estradiol metabolites in the urine of women with various catechol-O-methyltransferase (COMT) rs4680 gene polymorphisms, who underwent natural frozen embryo transfer cycle andgonadotrophin-releasing hormone (GnRH) agonist long protocol with hormone replacement therapy (HRT). Materials and methods: We analyzed 28 assisted reproductive technology (ART) cycles with vitrified embryo; each of them was assessed for the level of estrone and estradiol metabolites in the urine and polymorphisms of the COMT rs4680 gene. Ultrasound monitoring of the endometrium and biochemical monitoring of estrogen and progesterone levels in blood serum were conducted. Levels of hydroxy- and methoxyestrone and estradiol in urine of women who had a frozen embryo transfer (FET) cycle were evaluated depending on COMT rs4680 gene polymorphism. A comparative analysis of the indicators was carried out depending on the FET type (progestogens in the natural cycle or GnRH agonist long protocol with HRT using 0.1% transdermal gel with estradiol). Results: GGpolymorphism of the COMTgene has been shown to be associated with a higher level of methoxylated forms of estrogens in the urine compared to that in women with AA and GA polymorphism of the COMT gene. Indicators of methoxylated estrogens in women with AA polymorphism in GnRH agonist long protocol were found to be better than those in women in the natural cycle, according to the content of non-dangerous methoxy forms in the urine of the patients. There was no increase in pro-oncogenic hydroxylated forms of estrogens in women who had a long protocol with HRT. Conclusion: The level of methoxylated estrogens formation is associated with COMT gene polymorphism: the lower level of methoxy forms is associated with AA and GA variants. At the same time, none of the polymorphism variants are associated with the increase of potentially dangerous metabolites of estrogen in women who had GnRH agonist long protocol. Therefore, the FET cycle with GnRH agonists combined with the use of 0.1% transdermal gel with estradiol does not result in a rise of pro-oncogenic estrogen metabolites and does not lead to an increase of oncological risks in ART programs compared to those with embryo transfer in a natural ovulatory cycle.
Obstetrics and Gynecology. 2021;(11):213-220
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Evaluation of patients’ satisfaction with Angeliq Micro in real clinical practice after 13 cycles of treatment in Russia

Yureneva S.V., Prokofieva S.V., Spiridonova N.V., Yurasova E.A., Ilyina L.M.

Abstract

A decrease in estrogen production during the menopausal transition leads to the appearance of various symptoms that differ in intensity and duration and can have a significant impact on the quality of life. Hot flushes and night sweats are the most common symptoms of the menopause. The most effective treatment for menopausal symptoms is menopausal hormone therapy. Objective: To assess patients’ satisfaction with Angeliq Micro in real clinical practice during 13 cycles of treatment and to evaluate changes in menopausal symptoms and quality of life after 3-4 and 13 cycles of treatment, as well as the reasons for early discontinuation of treatment. Materials and methods: This is a prospective multicenter non-interventional cohort study on the assessment of patients’ satisfaction with Angeliq Micro in real clinical practice. The study included 1570patients aged 50-65 years who experienced moderate or severe vasomotor symptoms and needed treatment with ultra-dose drugs. Results: The patients with moderate to severe intensity of menopausal vasomotor symptoms were satisfied with ultra-dose Angeliq Micro. The proportion of such women exceeded 99% after 13 cycles of treatment. Conclusion: The results of treatment with Angeliq Micro in real clinical practice demonstrate high patients’ satisfaction rate with this method of treatment and provide a modern doctor with more opportunities to help middle-aged women.
Obstetrics and Gynecology. 2021;(11):222-228
pages 222-228 views

Experience in the use of low-dosed levonorgestrel-containing intrauterine system LCS16 and combined oral contraceptive containing 30 mcg ethinyl estradiol and 3 mg drospirenone in young women

Suturina L.V., Dikke G.B.

Abstract

Objective: To assess the satisfaction of young nulliparous and parous women using low-dosed levonorgestrel-releasing intrauterine system (LNG-IUS) or taking a combined oral contraceptive (COC) containing 30 mcg ethinyl estradiol and 3 mg drospirenone for 12 months. Materials and methods: The study included women aged 18-29 years (n=147) who used LNG-LUS LCS16 (n=74) or took COC (30 mcg ethinyl estradiol and 3 mg drospirenone) (n=73). We studied general satisfaction of the patients using the contraceptive method and the Likert scale 6 and 12 months after applying one of the contraception methods. We assessed the satisfaction using the bleeding and pain profile, treatment-emergent adverse events (TEAE), preferences in contraception method and attrition rate. Results: The percentage of patients who considered themselves to be ‘very satisfied’ and ‘satisfied’ with the contraception method was 90.3% (65/72) in the group using the LUD, and 97.3% (71/73) in the group taking the COC for 12 months. There was a decrease in bleeding and pain when patients used both methods and a decrease in the number of days of blood loss in the LUD group after 12 months. Amenorrhea was observed in 7.7% (5/72) of the participants of the LUD group and in no cases in the COC group. The patients’ responses about the bleeding profile were ‘very satisfied’ or ‘rather satisfied’ in 94.3% (66/72) and 95.8% (69/73) of the cases, respectively. TEAE were revealed in 50% (36/72) of women in the LNG-LUS group and in 38.4% (28/73) of women in the COC group. After 12 months, 81.4% and 79.2% (57/73) women respectively wanted to continue using their method of contraception. Conclusion: Both contraception methods, LNG-LUS and COC, are characterized by high satisfaction rates.
Obstetrics and Gynecology. 2021;(11):230-236
pages 230-236 views

Iron deficiency in Russia: main problems and possible solutions

Stuklov N.I., Basiladze I.G., Kisly N.D.

Abstract

The paper reviews the current epidemiological problems of iron deficiency and anemia in Russia. The authors place emphasis on women of reproductive age and pregnant women who represent the most socially signif icant group of the population. Morbidity rates and population characteristics of the problem are presented in detail. The paper examines the signif icance of global medical and social issues and the consequences of iron def iciency, issues related to the quality of life, clinical manifestations, the impact on reproductive function and the consequences of pregnancy. The authors give a detailed description of the modern understanding of iron metabolism, its regulation, mechanisms of absorption and transportation, and possible schemes for the development of iron deficiency. The authors explain the role of such iron regulatory proteins as divalent metallotransporter, ferroportin, hepcidin and their interaction, the values of other metals involved in iron metabolism, such as copper and manganese. The pathogenetic aspects of sideropenic and anemic syndromes, their significance in reproductive function and fetal formation are considered in detail. Both classical and novel algorithms and approaches are given. The paper presents modern algorithms for the treatment of latent iron deficiency and iron deficiency anemia, possible approaches and recommendations of various medical specialists. This paper attempts to show the most effective medications and approaches to their use in women with iron deficiency anemia. The advantages of liquid medications are described; the most effective doses, regimens, and duration of their use are discussed. As a result, the authors summarize all the information, present the simplest schemes for the diagnosis and treatment of different stages of iron def iciency and suggest a new approach to the treatment of iron def iciency, using the previous solution of the problem. Conclusion: Iron deficiency remains a serious problem in Russia. However, there is a possibility that incidence of iron deficiency will be reduced in our country in the near future.
Obstetrics and Gynecology. 2021;(11):237-244
pages 237-244 views

Review of the results of clinical studies of follitropin delta in ovarian stimulation protocols. The first experience of its use in Russia

Kalugina A.S., Boyarsky K.Y., Makolkin A.A., Zvereva I.O., Voznesenskaya J.V., Kholodov D.V.

Abstract

The paper presents the results of the clinical studies ESTHER-1, ESTHER-2, MARCS, STORK, and GRAPE, which have evaluated the efficacy of follitropin delta for ovarian stimulation (OS) in infertility programs with assisted reproductive technologies (ART). The ESTHER-1 and ESTHER-2 studies have been conducted on 1,326 women from several countries around the world. The studies have evaluated the effectiveness of individual calculation of the dosage of the OS drug, as well as its safety profile, especially in terms of the development of ovarian hyperstimulation syndrome (OHSS), one of the most common and serious complications of controlled OS. The ESTHER-2 study has assessed the safety profile of the second and third OS cycles. The STORK and GRAPE studies of 347 patients from Japan and 1009 women from several Asian countries have evaluated the efficacy of follitropin delta, taking into account the ethnic characteristics of the patients. The MARCS study enrolling 110 patients has analyzed the efficacy of a mixed protocol of follitropin delta and a highly purified urine-derived menopausal gonadotropin. The conducted clinical studies have shown that individual calculation of the dosage of follitropin delta offers benefits in a significant reduction in the risks of OHSS with comparable or better indicators for the number of oocytes collected, in the frequency of pregnancy, etc., which also allow the use of smaller total follitropin delta doses than those in the standard regimens. Following a review of the studies examples of clinical experience with follitropin delta in mono- and mixed protocols for women with low, normal, and high ovarian reserves are given. Conclusion: The gained experience with follitropin delta confirms its eff icacy in both mono- and mixed protocols in patients with low, normal and high ovarian reserves. Follitropin delta helps achieve a predictable ovarian response while minimizing the risk of OHSS, including patients with endocrine factor infertility (including polycystic ovary syndrome).
Obstetrics and Gynecology. 2021;(11):246-264
pages 246-264 views

HPV-associated diseases: questions and answers

Kostava M.N.

Abstract

Human papillomavirus (HPV) is the most common sexually transmitted infection. Two thirds of women become infected within 2 years after the onset of sexual activity. HPV genetic material can be found in almost all forms of cervical cancer and in some cancers of the anogenital region and oropharynx. The problem of HPV-associated diseases and cervical cancer is very serious, due to the fact that the prevalence of HPV is extremely high. The total number of people infected with HPV is approaching 700 million. According to the available statistical data, favourable outcome of HPV-associated diseases can be observed mainly in young women, however, the diseases may run for quite a long period of time. Taking into account the characteristics of HPV-associated diseases, it is possible to use immunomodulatory drugs, such as inosine pranobex (Groprinosin). It can contribute to the activation of local immunity, as well as the creation of more favorable conditions for surgical treatment and prevention of relapses.
Obstetrics and Gynecology. 2021;(11):267-276
pages 267-276 views

Monochorionic-triplet pregnancy with twin reversed arterial perfusion syndrome

Pribushenya O.V., Lazarevich N.A.

Abstract

Background: Monochorionic-tripletpregnancies are rare clinical cases and thisplacentation type concurrent with congenital malformations in one of the fetuses causes difficulties in choosing obstetric tactics. Case report: The paper describes three clinical cases of monochorionic-triplet pregnancy with twin reversed arterial perfusion syndrome. In one case, the pregnancy occurred after in vitro fertilization and transfer of two five-day embryos, which made it difficult to timely diagnose. The pregnancy was spontaneous in the other two cases. Two other pregnancies were spontaneous. All pregnancy cases were terminated due to the high risk of adverse obstetric complications. Pathological examination of the post-abortion material confirmed the prenatally established diagnosis. A molecular genetic study of the zygosity of the twins revealed that they were monozygotic. Conclusion: Twin reversed arterial perfusion syndrome is associated with the high risk of adverse perinatal outcomes and the high rate of diagnostic errors for twins. In triplet pregnancies, the prognosis is poorer due to the high incidence of obstetric complications.
Obstetrics and Gynecology. 2021;(11):278-285
pages 278-285 views

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