REPRODUCTIVE ENDOCRINOLOGY

Laboratory manifestations of fetal inflammatory response syndrome in extremely premature newborns

V.V. Bila — 2024-10-18

Background. Fetal inflammatory response syndrome (FIRS) is a pathological response to changes in the chorion and is manifested by inadequate cytokine production and endothelial dysfunction.
Objective of the study: to investigate laboratory changes in extremely premature newborns depending on the presence of FIRS criteria.
Materials and methods. The prevalence of umbilical cord blood leukocytosis and leukopenia, anemia and thrombocytopenia, as well as increased levels of C-reactive protein and procalcitonin in 403 premature newborns was analyzed depending on the presence of FIRS laboratory criteria. Newborns were divided depending on the gestational age (I and II groups – 24–27 weeks, III and IV groups – 28–34 weeks), and the presence of prenatal rupture of the fetal membranes (I and III groups) or the onset of labor with intact membranes (II and IV groups).
Results. FIRS increases the frequency of leukopenia, anemia, and thrombocytopenia in extremely premature newborns, and the frequency of leukocytosis and the appearance of young forms of leukocytes in premature infants from early preterm labour. Elevated levels of C-reactive protein and procalcitonin were more common in cases of premature rupture of membranes than in cases of labor with intact amniotic sac. This frequency did not depend on the presence of FIRS in extremely premature newborns; such dependence was outlined for premature infants from early preterm labour.
Conclusions. Leukopenia is more often found in premature babies from very early premature births than from early premature births. More than 20 × 109/ml leukocytosis and an increased proportion of young forms of neutrophils of more than 10% were found in the case of premature rupture of the fetal membranes, more often than during childbirth with intact membranes. In extremely premature newborns FIRS was accompanied by an increased frequency of leukopenia, thrombocytopenia, and anemia. FIRS do not increase levels of C-reactive protein and procalcitonin in extremely premature newborns.

Resolution of the I Ukrainian forum on miscarriages

T.F. Tatarchuk — 2024-10-18

Today, there is an urgent need to develop and implement a regulatory document on abortion. This is due to the catastrophic state of reproduction of the Ukrainian population – the annual decrease in the number of labor, birth rates and the demographic crisis in Ukraine in general. Pregnancy loss not only causes obstetric complications, but also causes significant damage of the mental health of the woman and her partner, including depression and post-traumatic stress disorder.
This resolution is a joint position of the leading specialists of Ukraine on the issue of miscarriages based on domestic experience, results of randomized controlled trials and meta-analyses, as well as clinical recommendations of scientific societies of the world. The presented information is designed to help improve clinical approaches to the management of miscarriage in today’s conditions, in order to save every pregnancy and to not lose a baby.
During the Forum, the practical issues of diagnosis and treatment of miscarriage, modern management of threatened and habitual miscarriage, hormonal support of pregnant women and the use of progestogens, the influence of the first half of pregnancy on the birth of a healthy child, the impact of liver diseases on the choice of therapy in a pregnant woman, and others issues were considered.
World clinical experience has convincingly proven the high effectiveness of progestogens in the therapy of threatened and repeated miscarriages. However, not all progestogens are equally effective in reducing the risk of miscarriage and live birth in case of threatened miscarriage. Micronized progesterone and dydrogesterone are the most effective. Dydrogesterone differs from progesterone in its mechanism of action and affinity for progesterone receptors. A strong evidence base has been accumulated about a high profile of effectiveness and a low frequency of maternal and fetal complications for dydrogesterone, the use of which is approved by leading foreign associations.
Drug interactions and their effects on the liver should also be taken into account. Drugs that are indicated for pregnant women should be prescribed in the smallest therapeutic dose, which should be effective.

The “brain-sparing” effect and thromboelastometric features of newborns with growth retardation

S.S. Leush — 2024-10-18

Background. The phenomenon of «brain-sparing» is usually seen as a protective response to placental insufficiency. However, there are many reasons to consider the protectiveness insufficient, even questionable. For example, due to the high incidence of hemorrhagic complications
in newborns. Increased cerebral perfusion may be associated with postnatal functional and structural complications. A deficient intrauterine environment increases the risk of coronary heart disease, hypertension, stroke, and metabolic syndrome.
Objective of the study: to investigate an elastometric blood coagulation and fibrinolysis parameters in newborns with intrauterine growth retardation.
Materials and methods. 42 children born at 28–34 weeks and 20 full-term babies with spectral dopplerometric blood flow in maternal and fetal vascular pools (uterine, umbilical and middle cerebral arteries) performed within 24–48 hours before birth were divided into three groups. The main group (group I) included 24 newborns in the period of 28-34 weeks with growth retardation. Comparison groups: 18 premature infants of the appropriate term without growth retardation (group II), 20 healthy full-term infants (group III).
Blood samples from umbilical arteries were examined by the method of rotational thromboelastometry with the feb-tem® reagent. The parameters of volumetric blood flow in the specified vascular basins were determined by the Doppler ultrasound examination.
Results. Synchronous acceleration of blood flow and a moderate decrease in resistance were observed in all the examined basins, except for the middle cerebral artery in fetuses with growth retardation, which fits into the definition of «brain spare». They also showed elastometric signs of increased coagulation ability – increased blood clot density and delayed blood lysis.
Conclusions. The appearance of Doppler signs of the middle cerebral artery dilation and slowing of blood flow in its basin should be regarded as an advanced violation of the blood supply. The tendency to increase coagulation and slow fibrinolysis in neonates with growth retardation further complicates their neonatal prognosis. Such newborns require monitoring of the blood coagulation system and fibrinolysis in the early neonatal period.

Criteria for predicting early neonatal adaptation of newborns in women who had COVID-19 infection during pregnancy

G.S. Manasova — 2024-10-18

Objective of the study: to investigate the possibility of predicting the early neonatal adaptation of newborns based on clinical and instrumental data that assesses the status of pregnant woman with COVID-19 infection and the fetus.
Materials and methods. The participants of the study were 58 pregnant women with a diagnosis of COVID-19 (group A) and 40 women with a physiological course of pregnancy (group B), as well as their newborns. In addition to the analysis of standard examinations results, perinatal consequences for the mother and the fetus/newborn, the association between the saturation level (SрO2) in the pregnant woman, the short-term heart rate variability (STV) according to cardiotocography data of the fetus and the assessment of the newborn according to the Apgar scale was studied.
Results. The SрO2 level was 95% or more in 87.9% of infected pregnant women, in 12.06% it was 90–94% (critical for pregnant women). 10.3% of pregnant women needed intensive therapy and respiratory support, 69% of women had inflammatory changes in the chest organs (pneumonia, etc.). Cardiotocography showed a significant difference in the type of basal heart rate between the groups (χ2 = 14.9055, p = 0,00058) and STV (7.78 ± 2.56 vs 8.39 ± 2.03 ms) in groups A and B, respectively
(U = 687, p = 0.00022).
The Apgar scale index in groups A and B was 6.48 ± 2.39 and 8.05 ± 0.54 points, respectively (χ2 = 21.933, df = 4). 20% of newborns in group B had 7 points in the first minute, 80% had 8 points or more. 51.85% of newborns in group A had scored 7 points or less (F = 0.00246, p < 0.05, odds ratio 4.308, 95% CI 1.681 – 11.037). 10.34% of newborns required intensive care, 5.17% – administration of surfactant, 1.72% – artificial lung ventilation. Regression analysis showed that the Apgar scale indicator at the first minute of life in newborns in group A depends on the SрO2 level of the pregnant woman (Y = 0.89X1 – 79.19), as well as on the STV (Y = 0.89X1 + 0.028X2 – 79.53), where Y is the score on the Apgar scale, X1 is the SрO2 in a pregnant woman, X2 is the STV.
Conclusions. Assessment of the hypoxemia degree in pregnant women with COVID-19 infection and the cardiotocographic assessment of the fetus state require special attention: there is a direct association between these indicators and the assessment of the newborn according to the Apgar scale, which allows predicting the course of the period of early neonatal adaptation. It is recommended that these newborns be classified as a risk group with a violation of the adaptation period and possible long-term consequences.

Short cervix: modern perspectives on known problems

I.A. Zhabchenko — 2024-10-18

The article provides modern literature data on terminology, diagnostics and new approaches to the treatment of short cervix syndrome. The term «short cervix» combines the concept of short cervix and isthmic-cervical insufficiency in most of the guiding documents of the world obstetrics and gynecology societies. However, the issues of diagnosis and correction of these conditions remain relevant and debatable: sonographic criteria, the use of progesterone, cerclage, obstetric pessaries, their various combinations, and the question of their effectiveness.
It is necessary to measure the cervix length by transvaginal cervicometry in the 20 weeks of pregnancy in the absence of previous reproductive losses and in the period of 14–16 weeks if there were previous reproductive losses. Therapeutic interventions should be started (vaginal micronized progesterone, cerclage, obstetric pessary) when the cervix is shortened to 25 mm or less at 20 weeks. Urgent cerclage should be performed when the umbilical cord is shortened to 20 mm or less. The effectiveness of cerclage, according to most experts, is comparable to the effectiveness of vaginal progesterone, unlike obstetric pessaries, the effectiveness of which is currently considered unproven.
For our country today, in addition to the generally recognized risk factors of this pathology, the factors associated with improper conditions for providing medical care and their consequences are especially relevant. Childbirth in inappropriate places without observing the rules of asepsis and antiseptics, often without qualified medical personnel, can lead to undiagnosed and lack of suturing of cervical tears), their infection, subsequent deformation and functional failure of the cervix.
There is also a need to support the micronutrient status of pregnant women in wartime conditions in Ukraine (vitamins of group B, vitamin D, magnesium, polyunsaturated fatty acids) in combination with progestins (micronized progesterone Luteinа) and/or cerclage in case of short cervix.

Morphofunctional features of isthmocele complicated by abnormal uterine bleeding

Z.I. Hladchuk — 2024-10-18

Background. The frequency of cesarean section remains high, and in some countries it exceeds 40% of all deliveries. The prevalence of isthmoceles as a consequence of cesarean section according to different authors ranges from 19 to 84%. Symptomatic isthmoceles is most often accompanied by abnormal uterine bleeding in 30-55% of women.
Objective of the study: to determine the functional, morphological and immunohistochemical features of isthmocele complicated by abnormal uterine bleeding.
Materials and methods. A prospective study was conducted, 68 patients were under observation: 38 patients of reproductive age with isthmocele after cesarean section who sought medical care for abnormal uterine bleeding (group 1, the main) and 30 practically healthy women of the same age with a normal uterine scar (group 2, the control). Immunohistochemical examination was performed in paraffin sections. Primary and secondary antibodies were used to detect CD34, CD68 and CD138 markers.
Results. Patients with isthmocele complicated by abnormal uterine bleeding have an increased body mass index, a higher frequency of dysmenorrhea, excessive menstruation, heavy menstrual bleeding, intermenstrual bleeding, anemia, compared with women with a complete uterine scar (p < 0.01). Isthmoceles in 84.2% of cases was associated with ultrasonographic and pathologic signs of adenomyosis, with insufficiently effective treatment of abnormal uterine bleeding noted in 78.9% of cases, and no effect of conservative treatment in 21.1% of cases. The high expression of CD34, CD68, CD138 markers in the areas of the isthmoceles complicated by abnormal uterine bleeding indicates the activity of adenomyosis and the presence of chronic endometritis, which determines the specificity of the clinical picture and requires improvement of treatment approaches.
Conclusions. Accounting the functional, morphological and immunohistochemical features of isthmocoele complicated by abnormal uterine bleeding will improve the effectiveness of treatment of symptomatic isthmocoele.

Problems of access to healthcare services in the armed conflict zones

M.I. Malachinska — 2024-10-18

Background. Ongoing military conflicts in various regions of the world have a significant negative impact on women’s health, including access to health services, maternal mortality and general well-being.
Objective of the review: to provide a comprehensive understanding of the multifaceted impact of war on refugee women, highlighting key areas such as physical health, mental health, reproductive health and access to basic services.
Analysis of literary data. Numerous barriers faced by women in armed conflict are considered. The main problems include insufficient transport connections, financial constraints, poor quality of medical services and cultural norms. The destruction of the health care infrastructure, the lack of medicines and personnel significantly limit the availability of reproductive health care services. These factors contribute to an increase in the number of home births without qualified support, which increases the risk of maternal and child mortality. Also important is the psychological impact of war, including stress, depression and post-traumatic stress disorder, which are common among pregnant women.
In addition, malnutrition and environmental toxins further complicate the situation, undermining the health of women and newborns. Thus, conflict-induced food insecurity leads to malnutrition among pregnant and lactating women, causing adverse health outcomes such as anemia, low birth weight, and increased susceptibility to infections. Exposure to environmental toxins from modern weapons, such as heavy metals, poses long-term health risks to pregnant women and their babies. In particular, toxins can affect the emotional and cognitive development of children.
Conclusions. This review highlights the urgent need for comprehensive health services, integrated medical and psychosocial support, and targeted interventions to address these challenges. Improving access to quality health care, ensuring food security and mitigating environmental risks are critical to improving maternal and child health.

The right to sexual and reproductive health of adolescents: problems of achieving the goals of sustainable development

M.M. Blikhar — 2024-10-18

The article proves that the range of issues related to reproductive and sexual health is an important area that requires a separate scientific review. At most, the current demand for analysis of adolescent reproductive health issues is due to the needs of the formation of the future generation, procreation and national prosperity of the state and nation.
Objective of the study: to analyze the trends in achieving the Sustainable Development Goals regarding the appropriate level of provision and protection of reproductive and sexual health of adolescents and to identify social and cultural-legal obstacles in achieving the specified task.
Materials and methods. The results of the research are based on the analytical information of international bodies and the data of the author’s survey, which was conducted during 2023–2024 in different regions of Ukraine, the respondents were 346 teenagers. Three groups of key problems in the field of ensuring the right to reproductive health of adolescents were formed and analyzed: problems caused by socio-cultural trends (early marriages, early sexualization and the tradition of genital mutilation); environmental problems and trends in the negative state of the nation’s health; shortcomings of the health care system and informing the population about contraception.
Results. It was found that the health care system often provides information in a form that is not accessible to adolescents, does not provide an adequate level of sexuality education. The insufficient number of specialized and adapted reproductive health programs for adolescents disrupts the system of early disease prevention, contributes to an increase in the level of child pregnancies, sexually transmitted infections, and other types of negative consequences.
Conclusions. Shortcomings in the health care system, in particular, limited access to medical services, lack of specialists with appropriate qualifications, gaps in financing, etc., are a significant gap for the implementation of the studied right. Attention is drawn to the duty of a democratic state to create a system of providing medical services adapted for adolescents, which includes information and a mechanism of access to contraception, providing medical and preventive services.

Vitamin D for the prevention of disease: an Endocrine Society clinical practice guideline (2024)

Editor Editor — 2024-10-18

Background. Numerous studies demonstrate associations between serum concentrations of 25-hydroxyvitamin D (25[OH]D) and a variety of common disorders, including musculoskeletal, metabolic, cardiovascular, malignant, autoimmune, and infectious diseases. Although a causal link between serum 25(OH)D concentrations and many disorders has not been clearly established, these associations have led to widespread supplementation with vitamin D and increased laboratory testing for 25(OH)D in the general population. The benefit-risk ratio of this increase in vitamin D use is not clear, and the optimal vitamin D intake and the role of testing for 25(OH)D for disease prevention remain uncertain.
Objective. To develop clinical guidelines for the use of vitamin D (cholecalciferol [vitamin D3] or ergocalciferol [vitamin D2]) to lower the risk of disease in individuals without established indications for vitamin D treatment or 25(OH)D testing.
Materials and methods. A multidisciplinary panel of clinical experts identified and prioritized 14 clinically relevant questions related to the use of vitamin D and 25(OH)D testing to lower the risk of disease. The panel prioritized randomized placebo-controlled trials in general populations (without an established indication for vitamin D treatment or 25[OH]D testing), evaluating the effects of empiric vitamin D administration throughout the lifespan, as well as in select conditions (pregnancy and prediabetes). The panel defined “empiric supplementation” as vitamin D intake that exceeds the Dietary Reference Intakes (DRI) and is implemented without testing for 25(OH)D. Systematic reviews queried electronic databases for publications related to these 14 clinical questions. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology was used to assess the certainty of evidence and guide recommendations. The approach incorporated considered patient values, costs and resources required, acceptability and feasibility, and impact on health equity of the proposed recommendations.
Results. The panel suggests empiric vitamin D supplementation for children and adolescents aged 1 to 18 years to prevent nutritional rickets and because of its potential to lower the risk of respiratory tract infections; for those aged 75 years and older because of its potential to lower the risk of mortality; for those who are pregnant because of its potential to lower the risk of preeclampsia, intra-uterine mortality, preterm birth, small-for-gestational-age birth, and neonatal mortality; and for those with high-risk prediabetes because of its potential to reduce progression to diabetes.
Because the vitamin D doses in the included clinical trials varied considerably and many trial participants were allowed to continue their own vitamin D–containing supplements, the optimal doses for empiric vitamin D supplementation remain unclear for the populations considered. For nonpregnant people older than 50 years for whom vitamin D is indicated, the panel suggests supplementation via daily administration of vitamin D, rather than intermittent use of high doses. The panel suggests against empiric vitamin D supplementation above the current DRI to lower the risk of disease in healthy adults younger than 75 years.
No clinical trial evidence was found to support routine screening for 25(OH)D in the general population, nor in those with obesity or dark complexion, and there was no clear evidence defining the optimal target level of 25(OH)D required for disease prevention in the populations considered; thus, the panel suggests against routine 25(OH)D testing in all populations considered.
The panel judged that, in most situations, empiric vitamin D supplementation is inexpensive, acceptable to both healthy individuals and health care professionals, and has no negative effect on health equity.
Conclusions. The panel suggests empiric vitamin D for those aged 1 to 18 years and adults over 75 years of age, those who are pregnant, and those with high-risk prediabetes. Due to the scarcity of natural food sources rich in vitamin D, empiric supplementation can be achieved through a combination of fortified foods and supplements that contain vitamin D. Based on the absence of supportive clinical trial evidence, the panel suggests against routine 25(OH)D testing in the absence of established indications. These recommendations are not meant to replace the current DRIs for vitamin D, nor do they apply to people with established indications for vitamin D treatment or 25(OH)D testing. Further research is needed to determine optimal 25(OH)D levels for specific health benefits.

Features of correction of metabolic disorders in women with polycystic ovary syndrome

O.V. Bulavenko — 2024-10-18

Background. A significant proportion of couples worldwide suffer from infertility associated with polycystic ovary syndrome (PCOS). PCOS is characterized by increased androgen synthesis in the theca cells of the ovaries, hyperandrogenemia and ovarian dysfunction in women. Most of the clinical symptoms and altered levels of blood biomarkers in PCOS patients point to metabolic dysregulation and adaptive changes as key underlying mechanisms of disease development. Since the liver is the metabolic center of the body and participates in steroid-hormonal detoxification, pathological changes in it can contribute to endocrine disorders through the liver-ovary axis. Of particular interest is hyperglycemia, changes in secretory proteins of the liver and insulin sensitivity, which affect the maturation of ovarian follicles and can potentially lead to female infertility.
Objective of the review: to provide an understanding of the new metabolic mechanisms underlying PCOS, which lead to the disease and its exacerbation, as well as to summarize therapeutic approaches to the correction of PCOS complications, in particular, liver function disorders using the drug Hepatomunil.
Analysis of literary data. This review presents the relationship and underlying mechanistic basis between PCOS and metabolic disorders in women by summarizing the main pathologic features of the disease. Most symptoms of PCOS are associated with insulin resistance, type II diabetes, decreased levels of sex hormone-binding globulin, increased levels of alanine aminotransferase and aspartate aminotransferase, which may indicate liver dysfunction. The metabolic profile and function of the ovaries can be affected by any pathological changes in the levels of systemic metabolism and/or in peripheral organs, in particular the liver, which serves as the metabolic center of the body, mediating its effects through the liver-ovary axis.
Conclusions. Despite the lack of a clear protocol for the correction of liver function disorders and non-alcoholic fatty liver disease in PCOS patients, lifestyle modification should be the basis. Drugs that improve metabolism, as well as hepatoprotectors with immunomodulatory properties (the drug Hepatomunil) may have positive prospects for use.