Free Estriol Research Articles

Особенности гормональной регуляции индуцированного полового цикла овцематок

The purpose of the study is to identify patterns of changes in the content of progesterone, FSH, LH and free estriol under various options for inducing the reproductive cycle of ewes with hormonal drugs. Objectives: during the period of spring anaphrodisia, to stimulate sexual oestrus in ewes using a double injection of estrofan; during the same period, to stimulate sexual estrus in ewes according to the follimag-progestamag, surfagon scheme; to study the nature of changes in the content of sex hormones in the blood serum of ewes during the implementation of the specified schemes for stimulating sexual heat; to identify the pattern of dynamics of sex hormones in ewes during an induced sexual cycle. The study was conducted in the Orenburg Region in April 2022 on Romanov breed ewes. Three groups of ewes of 12 heads each were formed. The age of the sheep is 3–5 years, live weight is 30–35 kg. The experiment was carried out against the background of fortification of sheep with E-selenium. In groups I (control) and II, animals were administered E-selenium on the 1st and 11th days of the experiment, in group III – on the 1st and 8th days. Hormonal stimulants were not used in the control; in group II, sheep were administered estrofan on days 1 and 11 and surfagon on the 13th day of the experiment; in group III, follimag was used on the 1st day, progestamag and surfagon on the 8th day. To determine the hormone content, blood was taken from the jugular vein from all animals on the 1st, 8th, 11th, 13th, and 14th days of the experiment. When stimulating sexual heat in ewes during seasonal anaphrodisia, the most pronounced hormonal response was obtained using injections of follimag and progestamag with surfagon at weekly intervals. When using this regimen, the levels of free estriol and LH reached their maximum values by the 11th day from the start of stimulation, creating optimal conditions for ovulation. After stimulating sexual heat in ewes, it is advisable to begin mating or insemination on the 10th–11th day.

P-39 Fictitious hyperestrogenism in perimenopause: Difficulties in diagnosis by laboratory pitfalls

Abstract Introduction Laboratory errors related to interfering substances can cause significant morbidity related to unnecessary investigations and interventions and patient anxiety. Estradiol (E2) is quantified mainly with competitive immunoassays. The prevalence of analytical interference can be up to 6% and is due to the impairment of the interaction between test antibody and analyte, causing falsely elevated levels. Nevertheless, interference due to heterophile antibody is extremely rare. Clinical Case A 51-year-old woman, normal weight, nulliparous, irrelevant previous medical history, menarche at 12 years old and regular menstrual cycles, was referred to the Endocrinology Department due to elevated E2 level. She was followed 4 years before in another institution with no formal diagnosis complaining of severe vasomotor symptoms, vaginal dryness and menometrorrhagias. She was on combined oral contraceptives for 10 years as a method of contraception, which she stopped two years ago. The first two E2 random values were 2362 and 3121 pmol/L, respectively when she had 47 and 49 years old. During our evaluation in January 2021, at the age of 51 years old, in the 4th day of her menstrual cycle, the laboratory evaluation revealed: FSH 9.56 mUI/mL (2.5-10.2), LH 5.43 mUI/mL (1.9-12.5), Prolactin 18.12 ng/mL (2.8-29.2), E2 3530.51 pmol/L (71.6-529.2), 17-Hydroxiprogesterone 0.52 ng/mL (0.32-1.47), DHEA-SO4 75.9 ug/dL (35-430), 4-Androstenedione 1 ng/mL (0.3-3.3) and SHBG 137 nmol/L (18-144). Transvaginal pelvic ultrasonography performed 15 days after menstrual period revealed 2 subserous leiomyomas, a 12 mm endometrial line and a right ovary with a pre-ovulatory follicle. CT scan of adrenal glands was unremarkable and a sellar MRI revealed a 4mm area of hypocaptation in the left region of the adenohypophysis. During this period the patient was treated with escitalopram 10 mg od, with vasomotor symptoms improvement. Two years later, after a 6-month period of amenorrhea, she repeated the analytical evaluation that revealed raised gonadotropins levels (FSH 102.12 mUI/mL, LH 25.37 mUI/mL), low progesterone 0.91 mUI/mL (< 4.45) but maintained a largely elevated estradiol level (1128.01 pmol/L) with undetectable free Estriol (< 0.10 ng/mL). This pattern motivated laboratorial review of blood samples by mass spectrometry and not by chemiluminescence as before. The value was substantially lower (447 pmol/L) hypothesizing the presence of heterophilic antibodies. Conclusion Although false E2 elevation due to analytical interference is rare, it must be suspected when results are discordant with the clinical picture and there is no evidence of neoplastic disease. Here, we report a case of falsely elevated E2 that led to prolonged investigation and major impact on a female's quality of life during the challenging period of perimenopause.

The early predictive value of maternal serum PAPP-A concentration at 11-14 weeks of pregnancy for preeclampsia.

To determine the expression and clinical significance of maternal serum pregnancy-associated plasma protein A (PAPP-A) in pregnant women with different degrees of preeclampsia at 11-14 weeks of gestation. The clinical data of 65 pregnant women with preeclampsia admitted to our hospital from January 2020 to October 2022 were retrospectively analysed. Another 45 normal pregnant women who came to our hospital for prenatal examination and delivery during the same period were selected as the healthy control group. The serum contents of PAPP-A, a-fetoprotein (AFP) and free estriol (uE3) in each group were compared. The correlation between PAPP-A and AFP as well as uE3 was analysed by Pearson analysis. The clinical value of serological indexes in diagnosing preeclampsia was analysed using ROC curve. The levels of PAPP-A and uE3 in pregnant women in the preeclampsia group were lower, while the contents of AFP were higher than these in the healthy control group ( p < 0.01). The pregnant women with severe preeclampsia had lower levels of PAPP-A and uE3 with higher levels of AFP compared to these with mild preeclampsia ( p < 0.001). Pearson correlation analysis showed that serum PAPP-A was negatively correlated with AFP ( r = -0.246, p < 0.05) and positively correlated with uE3 ( r = 0.398, p < 0.01) in preeclampsia patients. ROC curve analysis demonstrated that the area under the curve (AUC) of PAPP-A, AFP and uE3 to assist in the diagnosis of preeclampsia was 0.740, 0.738 and 0.806, respectively. The AUC of the combination of PAPP-A, AFP and uE3 to assist in the diagnosis was 0.912, with a sensitivity of 90.38% and a specificity of 80.33%. The clinical assisted diagnostic value of combined detection was high. The serum level of PAPP-A in pregnant women with preeclampsia in the early pregnancy was significantly lower and related to the severity of the disease. The combination of routine detection for AFP and uE3 had a good predictive value for preeclampsia, which was helpful to take relevant interventions to reduce the incidence of preeclampsia as early as possible, and had a positive impact on protecting maternal and infant health.

Clinical assessment of the placenta function in women at risk and threat of premature delivery

Premature birth, despite the significant achievements of perinatal medicine in recent decades, remains an urgent global and national medical and social problem, as it is the leading cause of perinatal morbidity and mortality. According to modern views, placental dysfunction can be one of the causes of premature birth, and its frequency, according to randomized studies, can be from 78 to 91%, depending on the gestational age. At the same time, the research conducted to date does not provide a clear understanding of the role of timely diagnosis and prevention of placental dysfunction in preventing premature birth.The objective: to perform clinical evaluation of the prevalence of placental dysfunction in women at risk of preterm birth and with threat of preterm birth.Materials and methods. 180 pregnant women were took part in the study. To achieve the research aim, three research groups were formed. I group – 73 pregnant women with threat of premature birth; II group – 77 pregnant women with risk factors for premature birth. Women with risk factors for premature birth were included in the study at the stage of pregnancy planning (IIA subgroup, 39 women) or from the moment of applying to a women’s outpatient clinic to monitor the course of pregnancy (IIB subgroup, 38 pregnant women). The control group included 30 pregnant women with an uncomplicated course of pregnancy.Transabdominal ultrasound examination with color Doppler mapping, determination of free estriol, progesterone and placental lactogen levels in blood serum were performed at 18–21+6 and 28–30 weeks of gestation.Results. Analysis of the prevalence of risk factors for placental dysfunction and preterm birth in patients of the studied cohort showed that in pregnant women with preterm birth (I group), the combination of risk factors was 5.2; in pregnant women who received pre-gravid training (IIA subgroup) – 3.2; in pregnant women who were included in the study in the I trimester of pregnancy (IIB subgroup) – 4.7, while in pregnant women of the control group – only 0.8 (p&lt;0.05).The threat of early spontaneous miscarriage with the formation of a retrochorial hematoma as a clinical manifestation of primary placental dysfunction was determined in 43.8% of pregnant women whose premature delivery was carried out for medical reasons. Placenta abruption in these patients can be considered as decompensation of the primary dysfunction of the placenta with the transition to acute placental insufficiency.The formation of chronic placental dysfunction, clinically manifested by the syndrome of fetal growth retardation, was most often observed in patients whose pregnancy ended in spontaneous premature birth at 34–36+6 weeks in the presence of an untouched amnion, – 68.6% compared to births at 28–33+6 weeks of gestation – 25.9% and with childbirth at 22–37+6 weeks – 13.3%.Conclusions. Clinical manifestations of placental dysfunction were detected in 30.6% of patients with premature birth, with morphological signs in 60.4% of cases, which indicates the hidden course of placental insufficiency before the development of premature birth.Morphological signs of placental dysfunction were determined in 87.5% of cases of premature births for medical reasons and in 100.0% of cases of spontaneous births at 22–27+6 weeks of gestation (with a combination of risk factors from 2.1 to 3.0), in 66.7% – with premature births at 28–33+6 weeks of pregnancy, in 40.0% – with premature births at 34–36+6 weeks of pregnancy and only in one (5.6%) case – with term births.The frequency of fixation of morphological characteristics of placental dysfunction correlates with the frequency of early pregnancy complications, primarily with the formation of retrochorial hematomas in the first half of pregnancy.

Оцінка показників комплексної стратифікації ризиків розвитку прееклампсії в пацієнток із ретрохоріальними гематомами

Purpose - to assess the prognostic value of a comprehensive study of the influence of indicators of angiogenic/antiangiogenic profile in women with retrochorial hematoma (RCH) in the І trimester, uterine artery (UA) dopplerometry data in stratifying the risks of developing placental dysfunction in these women. Materials and methods. A prospective analysis of the course of pregnancy was carried out in 137 women with a threat of miscarriage aged 20 to 47 years, who made up two comparison groups: the Group I - 60 patients with RCH, the Group II - 77 patients with a threat of abortion without hematoma. Results. The average age of women of the Group I was 31.2±0.6 years, of the Group II - 32.2±0.6 years. The gestational age at enrollment was equal 6.1±0.55 weeks in the Group I and 7.2±0.61 weeks in the Group II. A direct, reliable correlation of weak strength was established in pairs: the presence of the human chorionic gonadotropin (hCG) and the pulsatility index (PI) in UA &gt;95 percentile, hCG and a higher level of hCG in the I and II trimesters of pregnancy. A reduced level of PAPP-A was significantly associated with cases of preeclampsia (PE) in the anamnesis, increased Body Mass Index, a high level of PI in UA, including with PI levels &gt;95 percentile, as well as with a reduced level of free estriol. Significant inverse correlations were established between the level of PLGF and indicators of PE in history, the level of PI in UA and the content of hCG. At the same time, the level of alpha-fetoprotein in the studied patients was directly associated with increased levels of PI in UA and hCG. It was established that the risk of early PE was more inherent for women with the presence of PCH in the І trimester of pregnancy, while the percentage of the development of late PE with and/or without fetal growth retardation was more often higher in women with a threat of termination of pregnancy in the І trimester trimesters without the formation of RHG. Conclusions. The occurrence of RHG at the stage of early placentation increases the risks of developing placental dysfunction and obstetric complications associated with it. PRISCA-1, PLGF, PI of UA, as well as the calculation of the risk of developing PE in the trimester І using the FMF calculator should be used to form a risk group for the development of placenta-associated complications. Indicators of PI of UA &gt;99 percentile in the І trimester of pregnancy in combination with a decrease in PAPP-A ˂0.45 MoM should be considered critical. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patients was obtained for conducting the studies. No conflict of interests was declared by the authors.

EVALUATION OF CERTAIN BIOCHEMICAL AND ANGIOGENIC MARKERS IN THE FIRST TRIMESTER OF PREGNANCY IN WOMEN WITH UMBILICAL CORD PATHOLOGY

At the stage of formation of fetoplacental complex, various factors of the external and internal environment create prerequisites for subsequent unfavorable course of pregnancy and childbirth. Their influence falls on the period of formation and differentiation of extraembryonic structures in the first trimester of pregnancy. That is why umbilical cord pathologies are considered to be one of the main causes of the development of fetal distress, low birth weight and post-hypoxic states of newborns.&#x0D; The purpose of the research: to analyze changes in the parameters of certain biochemical and angiogenic markers in patients with umbilical cord pathology.&#x0D; Research materials and methods. Medical documentation of 56 patients (the main group) with umbilical cord pathology and abnormalities of its insertion (27 pregnant women with a single umbilical artery and 29 women with velamentous insertion) was processed. The comparison group included 30 patients with normal structural components of the umbilical cord. The level of free ȕ-hCG, PAPP-A, free estriol, AFP, placental lactogen, certain growth factors PIGF and sFlt-1 was evaluated using the method of immunoenzymatic analysis. “Astraia Obstetrics” software (“Astraia software gmbH”, Germany) was used to determine the risk of preeclampsia, chromosomal abnormalities, fetal growth retardation, and premature birth.&#x0D; Research results and their discussion. An imbalance in the concentration of PAPP-A and β-hCG, when its low levels corresponded to high levels of β-hCG, was revealed in the main group. An increase in the average values of the level of PAPP-A MoM was established in almost half of the observations (42.9%), a significantly higher level of free ȕ-hCG was noted in 28.6 % of samples. The combined indicators of the concentration of PlGF in women with umbilical cord pathology were significantly lower (by 1.6 times) compared to the data of the comparison group; placental lactogen has a tendency to decrease. The combined values of the concentration of PlGF in women with umbilical cord pathology were significantly lower (by 1.6 times) compared to the data of the comparison group, and the indicators of the level of sFlt-1 – by 1.5 times (p&lt;0.05). This made it necessary to evaluate the calculated parameters of the angiogenic coefficient, which reflects the depth of vascular disorders and the severity of vascular imbalance.. At the same time, this ratio was found to be 2.0 times lower in the patients of the comparison group compared to the combined total indicator in the main group - in pregnant women with umbilical cord pathology - 155.7 units. (p&lt;0.05)&#x0D; Conclusions. Among pregnant women with umbilical cord pathology, a high proportion of the increased PAPP-A indicator, probably a lower level of free β-chorionic gonadotropin subunit, and low parameters of placental lactogen in the third trimester of pregnancy were observed. The combined indicators of the concentration of PlGF in women with umbilical cord pathology were significantly lower (by 1.6 times), and the indicators of sFlt-1 level – by 1.5 times higher compared to the data of the comparison group, which can be a marker of the abnormal formation of fetoplacental complex with the deterioration of the intrauterine fetal condition, as well as an increase in the angiogenic factor. The use of “Astraia Obstetrics” module in combination with prenatal biochemical screening made it possible to assign 23.2 % of examined patients with umbilical cord pathology to the risk group for the development of chromosomal abnormalities, preeclampsia, fetal growth retardation and premature birth.

Placental dysfunction in women at risk and threat of premature delivery

Premature birth remains one of the most urgent problems of modern obstetrics. It is not possible to reliably establish the cause in 70–80% of premature births, so the search for risk factors and markers of premature termination of pregnancy is justified. According to many authors, 25–30% of women at risk of premature birth have placental dysfunction.The objective: was to assess the prevalence of placental dysfunction in women at risk of preterm birth and with preterm birth.Materials and methods. 80 pregnant women were under observation. The criteria for inclusion in the study were the presence of risk factors for premature birth – Group I (30 women) or the threat of premature birth – Group II (30 women). The control group consisted of 20 conditionally healthy pregnant women. Transabdominal ultrasound examination with color Doppler mapping, determination of free estriol, progesterone and placental lactogen levels in blood serum was performed at 18–21+6 and 28–30 weeks of gestation.Results. The average age of the patients was 31.4±2.5 years, there was no significant difference in age, life history, social status, somatic pathology between the formed groups. Pregnant women of groups I and II probably had a history of pelvic inflammatory disease more often than in controls; colpitis; sexually transmitted infections; pathology of the cervix and operations on the uterus and appendages. The course of this pregnancy in most of the women of the studied cohort was complicated by the threat of termination of pregnancy, 36.7% of pregnant women of the I group and 46.7% of the II group had premature births. Signs of premature ripening of the placenta were detected in 13 (43.3%) pregnant women of the experimental cohort and in 1 (5.0%) of the control group (Р&lt;0.0001), which was accompanied by changes in parameters during dopplerometry of utero-placental blood flow. Clinical manifestations of placental dysfunction occurred in 36.7% of patients in the risk group of premature birth and pregnant women with a threat of premature birth, and were manifested by a decrease in the level of progesterone, a plateau in the increase in the level of placental lactogen. Morphological signs of placental dysfunction were found in 43.3% of cases of premature birth, which correlates with the frequency of early complications of pregnancy, primarily with the formation of retrochorial hematoma.Conclusions. Clinical manifestations of placental dysfunction (fetal growth retardation, preeclampsia) occur in a third of patients of the risk group and pregnant women with a threat of premature birth, which correlates with changes in the hormone-producing function of the placenta.

Predictive value analysis of Down's screening serological indicators in the second trimester for gestational hypertension

Objective: To discuss the prediction efficacy of Down's screening serological indicators in the second trimester of gestational hypertension (GH). Methods: 64 849 pregnant women who had undergone regular check-ups at the Beijing Obstetrics and Gynecology Hospital from June 2013 to June 2019 and finally gave birth were the subjects of the study. There were 3 808 cases of the GH group (including patients with GH, preeclampsia, and eclampsia diagnosed) and 61 041 cases of non-GH group respectively. 3 ml of fasting venous blood was drawn during 14-19 weeks of pregnancy, and body weight, serum β-human chorionic gonadotropin (β-HCG), free estriol (uE3) and alpha fetal protein (AFP) were obtained through physical check and laboratory testing. β-HCG, AFP, uE3 were analyzed by using the corresponding median times of gestational age (MOM value), and multivariate logistic regression model and receiver operating characteristic curve (ROC curve) were used to analyze the predictive efficiency of serological indicators. Results: Among 64 849 research subjects, the GH group (3 808 cases) and the non-GH group (61 041) were (29.51±2.72), (29.38±2.68) years old, the weights were (65.46±12.17), (58.73±9.13) kg, gestational age of blood collection were (16.53±0.89) and (16.58±0.90) weeks respectively. The analysis of multivariate logistic regression model showed that the risk of GH increased with the increase of body weight, β-HCG and AFP concentration, OR (95%CI) values were 1.059 (1.056-1.062), 1.329 (1.188-1.487) and 1.195 (1.125-1.269); so did when the concentration of uE3 decrease, OR (95%CI) value was 0.527 (0.464-0.599). ROC curve analysis results show that age, weight, serum AFP, β-HCG, uE3 and multivariate diagnosis all have predictive efficiency for GH (P values<0.05); combined diagnosis of multiple indicators and weight AUC (95%CI) were 0.684 (0.675-0.693) and 0.673 (0.663-0.682), but the Youden index, sensitivity, and specificity of the two were relatively small. Conclusion: The β-HCG, AFP and uE3 of Down's screening in the second trimester of pregnancy were relatively low in predicting GH.

Preterm Delivery: Predictive Value of Salivary Estriol, and Alpha Feto Protien

Background: Preterm labor is defined by the presence of painful uterine contractions that lead to progressivechanges in the cervix that allow descent and delivery of the newborn before the 37th week of gestation.Objective: To assess the predictive value of salivary estriol and Alpha feto protein in preterm delivery.Patients and Method: A prospective study were carried out in our hospital during the period from 1/1/2020to the 30/8/2020 among the patients who attended for consultation, 120 patients with gestational age between16 and 18 weeks were selected and divided into two groups. Results: The serum level of Alpha-feto proteinwas (338. 15 ± 182.55 in case group vs. 239. 68 ± 112. 51 in control group) with significant association(p=0.01). In spite of the decrease of the estriol level in preterm group we found no significant differenceswere found between both groups regarding the estriol level (P&gt;0.05)Conclusion: The increase in free estriol in saliva in this study was not significantly associated with pretermdelivery in asymptomatic patients at risk, and there is a significantly increase in AFP concentration inpreterm pregnant patients.

SONOGRAPHIC MARKERS OF ASSOCIATION OF FOLATE CYCLE POLYMORPHIC GENES AND EPIGENETIC FACTORS

Reproductive losses in Ukraine are about twice the European average, but have the same causes: miscarriage, abortion, malformations, parental infertility, death of women of childbearing age and children under six days of age. The study focuses on genetically determined reproductive losses associated with folate cycle polymorphism, some other polymorphisms, and epigenetic factors that increase the risk of adverse pregnancy outcomes. Methods of systematic and demographic analysis studied the indices of medical and statistical observation of the population of the Kharkiv region within the period of 2008−2018 with an emphasis on the results of biochemical, molecular genetic and sonographic examinations of pregnant women. Data on the number of examined pregnant women were analyzed using ultrasonographic and biochemical studies at the level of alpha−fetoprotein, chorionic gonadotropin and free estriol in the framework of selective screening programs for pregnant women. Statistical data on the number of fetuses and newborns who died during the first − sixth day after birth, with a distribution on the basis of full−term have been studied. The data are compared with similar national indices. The directions of reducing the reproductive losses are offered, including complex inspection of pregnant women with use of ultrasonography, biochemical and molecular−genetic methods of diagnostics of genetic diseases and defects of fetus development. Among the epigenetic factors we have identified obesity and old age of pregnant women, among the types of abortions we did medical abortions associated with stillborn pregnancies, as well as miscarriages. The findings of the study can be used to minimize the effects of risk factors for reproductive loss in the activity of general practitioners. Key words: polymorphism of folate cycle genes, reproductive losses, miscarriage, congenital malformations of fetus, ultrasonography.

The experience of L-arginine using in placental insufficiency

Objective. To evaluate the effectiveness of the use of L-arginine in the treatment of placental insufficiency (PI) in pregnant women.&#x0D; Materials and methods. We examined 49 pregnant women with PI at 22-34 weeks of gestation. The women were divided into two groups. The 1st group included 27 patients who, as part of the standard complex treatment, were injected intravenously with L-arginine (Tivortin®, “Yuria-Pharm”, Ukraine) 4.2 % solution for infusion at a dose of 100 ml a day for 5 days. The 2nd group included 22 women in which standard basic therapy was used for PI treatment. To study the state of the fetoplacental complex in the blood serum of pregnant women, the level of human placental lactogen (hPL) and free estriol (E3) was determined by direct competitive enzyme immunoassay (ELISA).&#x0D; Results and discussion. All patients included in the study were comparable in somatic and obstetric status. The age of pregnant women in both groups ranged from 22 to 39 years, averaging 26±3.2 years in the 1st and 31±2.4 years in the 2nd group. The level of hPL before therapy was reduced in 10 (37.03 %) patients in the 1st group and in 8 (29.62 %) patients in the 2nd group. The concentration of free E3 was reduced in 12 (44.44 %) patients of the 1st group and in 9 (40.9 %) patients of the 2nd group. In the main group, the average concentration of free E3 was 18.8±13.3 ng/ml, and the hPL was 7.1±2.6 mg/L. In the comparison group, the level of free E3 averaged 19.1±10.2 ng/ml and hPL was 6.9±3.9 mg/L. After adjustment of PI in all patients of the 1st group, and in 19 (86.36 %) of the 2nd group, the concentration of hPL and free E3 corresponded to the norm. Thus, in the main group, the average concentration of free E3 was 22.7±14.1 ng/ml, and the hPL was 8.1±2.9 mg/L. In the comparison group, the level of free E3 averaged 22.1±14.6 ng/ml and hPL – 8.3±3.9 mg/L. Only in 3 (13.63 %) patients of the comparison group, the level of hormones was still reduced.&#x0D; Conclusions. The inclusion of L-arginine (Tivortin) in therapeutic regimens in order to correct placental dysfunction leads to a regression of fetoplacental circulatory disorders and reduces the risk of unfavorable perinatal outcomes.

Особливості гормонального балансу та метаболічного профілю у вагітних з різними типами ожиріння

Maternal obesity has become one of the main factors influencing obstetric and perinatal outcomes. Obesity in pregnant women increases the risk of complications during pregnancy, childbirth and the postpartum period. The newborns of obese women also have higher rates of perinatal morbidity and an increased risk of long-term health problems. The objective: to learn hormonal and metabolic peculiarities in pregnant women with different obesity types during full-term pregnancy. Materials and methods. We examined 61 pregnant women with android type and 57 pregnant women with gynoid type of obesity at 39.6–40.6 weeks of gestation and 57 pregnant women without obesity and overweight. The concentration of estradiol, free estriol, insulin, placental lactogen, free testosterone, cortisol, dehydroepialdosterone sulfate (DHEA sulfate), and serum progesterone by enzyme-linked immunosorbent method and glucose rate by glucose-oxydase method were determined. The HOMA index was determined. Results. In pregnant women with gynoid obesity type, the level of progesterone was 41.15 (34.6–48) ng/ml, with android type – 35.7 (32.6–40.6) ng/ml and with physiological body weight 35.4 (33.2–40) ng/ml (p&lt;0.05). While determining the concentration of placental lactogen in three groups there were no significant differences. There was a decrease (p&lt;0,05) in the level of free estriol in groups of pregnant women with android and gynoid type of obesity in comparison with the control group, respectively 13.9 (13.1–14.9) ng/ml, 13.6 (12, 4–15.4) ng/ml and 14.7 (13.6–15.8) ng/ml. The concentration of estradiol in second group was 24 925.3 (20 206.6–30 400.5) pg/ml, which is 1.2 times (p&lt;0.05) higher as in the control group and 1.4 times higher as in first group. In pregnant women with android-type obesity, estradiol levels were 1.2 times lower (p&lt;0.05) compared with the control group. The concentration of cortisol in pregnant women with android type was 812.1 (599–1235.15) nmol/l, which is 2.7 times higher (p&lt;0.05) compared to the women with gynoid type of obesity and 1.5 times higher (p&lt;0.05) than in the control group. In pregnant women with gynoid type of obesity, 1.7 times lower (p&lt;0.05) cortisol levels were observed in comparison with control group. The level of free testosterone was 2.4 (1.7–3.1) nmol/l in pregnant women of first group, what was higher (p&lt;0.05) than in second group and in control group, respectively 1 (0.8–1.5) nmol/l and 1.9 (1.6–2.3) nmol/l. Pregnant women in group 1 had 2.4 times higher (p&lt;0.05) testosterone levels compared to group 2 and 1.2 times higher (p&lt;0.05) than in control group. In women with android type, the concentration of DHEA sulfate was 2.4 times higher (p&lt;0.05) than in pregnant women with gynoid type and 2.1 times higher (p&lt;0.05) compared with the control group. Pregnant women with android type of obesity have a significantly higher (p&lt;0.05) serum insulin concentration of 67 (40–94.5) μIU / ml compared to women with gynoid type of obesity 33.3 (25.6–43) μIU/ml. When determining the glucose concentration no significant difference between three groups was found. The HOMA index in pregnant women with android type of obesity was 2.1 times higher than in pregnant women with gynoid type and 2.3 times higher than in control group (p&lt;0.05). Conclusions. The results of a study indicate that the type of distribution of adipose tissue is important during pregnancy and childbirth because the hormonal and metabolic activity of adipose tissue in android and gynoid obesity types are different. Keywords: android type of obesity, pregnancy, gynoid type of obesity, hormonal balance, metabolic profile.

Effects of Psychological Stress during Pregnancy on FE3 in Maternal Serum

Objective: to investigate the effect of psychological stress during pregnancy on serum FE3. Method: symptom self-rating scale (scl-90) was used to evaluate the degree of psychological stress of pregnant women.The Free estriol (FE3) level in maternal serum was detected by particle chemiluminescence. Result: serum FE3 levels in pregnant women in the stress group were significantly lower than those in the control group (P < 0.05). Conclusion: psychological stress during pregnancy can reduce serum FE3 level.

The Ratios of Estradiol and Progesterone to Testosterone Influence the Severity of Facioscapulohumeral Muscular Dystrophy

Background: Facioscapulohumeral muscular dystrophy (FSHD) occurs as a consequence of genetic deletion of D4Z4 repeats on chromosome 4q35. Onset of FSHD is earlier in males, suggesting that testosterone may trigger the disease. In accordance, the rapid progression of disease in women after menopause suggests a protective role for estrogen and progesterone. No studies have examined levels of all these hormones in relation with the severity of FSHD. Aims: To evaluate the possible correlation between the severity of FSHD with sex hormones, age, and genetic deletion on chromosome 4q35. Subjects and Methods: D4Z4 repeat units were investigated in 33 patients (19 males/14 females) with FSHD. In the blood samples, luteinizing hormone, follicle-stimulating hormone, free estriol, estradiol, free testosterone and total testosterone, progesterone, 17-OH progesterone, prolactin, albumin, and fibrinogen were measured. The severity of FSHD was identified using a Clinical Severity Score (CSS) scaling system. Spearman's correlation and regression analyses were performed as statistical analyses. Results: Age (P = 0.001, r = 0.541) and total testosterone (P = 0.045, r = 0.351) were positively correlated, and the progesterone/total testosterone (P = 0.025, r = −0.390) and estradiol/total testosterone ratios (P = 0.025, r = −0.389) were negatively correlated with the severity of FSHD. Conclusions: Our results indicate that age, total testosterone, ratios of estradiol and progesterone to total testosterone, but not deletion on chromosome 4q35, have a significant relation with the severity of FSHD. Given that both estrogen and testosterone treatment are considered in therapy, our results suggest that estrogen and progesterone but not testosterone are likely to be more effective on the severity of FSHD.

Differences in serum steroid hormones concentrations in Spontaneously Hypertensive Rats (SHR) - an animal model of Attention-Deficit/Hyperactivity Disorder (ADHD).

Spontaneously hypertensive rats are the most common animal model used to study attention deficit hyperactivity disorder (ADHD). The present study investigated the levels of steroid hormones in the bloodstream of hypertensive rats and its normotensive control strain, Wistar-Kyoto rats, to check if there are any hormonal differences between both strains at the onset of ADHD. Plasma samples were collected from young (5-week-old) and mature (10-week-old) male hypertensive and normotensive rats to determine the serum level of testosterone, 17beta-estradiol, free estriol, progesterone, corticosterone and cortisol using ELISA kits. The results showed statistically significant increases in serum levels of testosterone and free estriol in 10-week-old hypertensive and normotensive rats when compared to 5-week-old animals. Moreover, the concentrations of progesterone, corticosterone and cortisol were significantly elevated in 10-week-old hypertensive rats when compared to 5-week-old animals of both strains as well as 10-week-old normotensive rats. Hormonal differences observed between 10-week-old hypertensive and normotensive rats were also accompanied by differences in the volumes of lateral ventricles as well as the third ventricle and cerebral aqueduct. In conclusion, elevated contents of progesterone, corticosterone and cortisol in hypertensive rats may be associated not only with ADHD but also with developing hypertension. This question needs further study.

CHANGES OF THE SLEEP, HORMONAL BALANCE AND PROFILE OF CYTOKINES IN PREGNANT WOMEN WITH PLACENTAL INSUFFICIENCY

Objective – to establish the correlation between the placental insufficiency, sleep disorders and pro- and anti-inflammatory part of the immune system by questioning, studying of the levels of melatonin, placental hormones and pro- and anti-inflammatory cytokines in pregnant women with placental insufficiency.Materials and methods. 80 pregnant women with placental insufficiency, manifesting as intrauterine fetal growth restriction (IUGR) of II-III degree in the 3rd pregnancy trimester (study group) and 30 women with normal clinical flow of pregnancy (control group) were questioned. 46 patients from study group and 20 patients from control group women were examined further: the studying of the blood plasma concentrations of melatonin, placental hormones (placental lactogen, free estriol), pro-inflammatory cytokines, such as tumor necrotizing factor-α (TNF-α), interleukin-1-β (IL-1-β), interleukin-6 (IL-6), and anti-inflammatory cytokines, such as interleukin-4 (IL-4) and interleukin-10 (IL-10), was conducted.Results and the discussion. Questioning showed that pregnant women with placental insufficiency (PI) in 86% cases experience the sleep disorders starting from pregnancy term 12-22 weeks (healthy pregnant women – mostly after 30 weeks, 57% cases), more commonly wake up 2 or more times per night (71% of positive answers, in control group – 23%), and 3 or more times per week (78% of positive answers, in control group – 17%). It also has been established that concentration of melatonin significantly decreases, if the pregnancy is complicated by intrauterine fetal growth restriction (study group – 126,87±14,87 pg/ml, control group – 231,25±21,56 pg/ml, p&lt;0,001). The levels of pro-inflammatory cytokines in the study group were significantly higher, comparing with the control group (TNF-α: study group – 10,05±1,35 pg/ml, control group – 5,60±1,50 pg/ml, p&lt;0,05; IL-1-β: study group – 14,67±2,13 pg/ml, control group – 3,96±0,92 pg/ml, p&lt;0,001; IL-6: study group – 6,91±0,99 pg/ml, control group – 2,69±0,99 pg/ml, p&lt;0,05). The same is true about anti-inflammatory cytokines (IL-4: study group – 5,97±0,50 pg/ml, control group – 3,74±0,62 pg/ml, p&lt;0,05; IL-10: study group – 11,40±1,50 pg/ml, control group – 4,70±3,20 pg/ml, p&lt;0,001). We did not find significant difference in hormonal concentrations between groups.Conclusions. Sleep disorders in pregnant women with placental insufficiency appear earlier and seem to be more expressed then in healthy pregnant women. The blood level of melatonin significantly decreases in case of placental insufficiency, manifested as intrauterine fetal growth restriction. The strengthening of the pro-inflammatory immunity, shown as the increasing of the levels of TNF-α, IL-1-β and IL-6, is also present in case of IUGR. The rising of the plasma concentration of the anti-inflammatory cytokines, such as IL-4 and IL-10, in our opinion, can be explained by activation of the mechanisms of compensation, which decrease the risk of premature labor.

ҰРЫҚ ДАМУЫНЫҢ АҚАУЛАРЫНА БИOХИМИЯЛЫҚ СКРИНИНГТІҢ НӘТИЖЕЛЕРІ

The leading cause of malformations of the human fetus is chromosomal abnormalities. In connection with this, one of the main tasks of medical genetics is to reduce the incidence of chromosomal pathology in the human population. To solve this problem, invasive and non-invasive methods of prenatal diagnosis are used. The article presents the results of biochemical screening of blood serum of pregnant women and, in particular, the results of a cytogenetic study of the fetus of pregnant women at risk. Biochemical screening was conducted for 30335 pregnant women. The screening was conducted in the I and II trimester at 11-13 and 14-20 weeks of pregnancy. In the first trimester, a double test was used to determine the level of the β-subunit of the hCG hormone and the pregnancy-related plasma protein RAPP-A. In the second trimester, a triple test was used - determination of the level of AFP, hCG and free estriol E3. Based on the use of the enzyme immunoassay, the results of the indices of these biomarkers determined the possibility of the presence of chromosomal abnormalities in the fetus. According to biochemical screening, a risk group was identified from 662 (2.2%) pregnant women who underwent invasive diagnosis. Cytogenetic studies of metaphase cells of villi chorion were carried out. Fetal development disorders were detected in 41 cases, which was 6.2%. In two cases, cystic gigrum and spina bifida were identified. Karyotype disorders were found in 39 (5.9%) of the fetuses. Among them, the karyotype of Down syndrome was revealed in 29 cases, which was 74.4%. Comparative analysis by age factor showed an increase in the frequency of fetuses with Down's syndrome by 2.2 times in pregnant women 30 and older. Key words: biochemical screening, biomarkers, enzyme immunoassay, chromosomal abnormalities, fetal karyotype.

Does Active Smoking Influence the Second Trimester Biochemical Markers Concentrations?

Cigarette smoke contains over 7000 different substances some of them exerting harmful effects on embryo and pregnant woman. Nowadays 15 % of adult people and around 10-15% of pregnant women smoke. Previous studies showed that cigarette smoke compounds could exert pharmacodinamic effects and influence some of the second trimester biochemical markers concentration. Therefore there is a need to adjust the reference values of second trimester markers depending of the smoker status. The aim of our study was to analyse which of the markers are influenced by smoking and whether the software used to calculate the risk for aneuploidies is able to counterbalance this influence. Alpha-fetoprotein (AFP), chorionic gonadotropin hormone (hCG) and free estriol (uE3) values were measured in second trimester sera of 1242 pregnant women: 1089 non-smokers and 153 smokers. Only hCG second trimester values were influenced by smoking whereas AFP and uE3 values were not. The correction of medians according to the smoking status was able to counterbalance this effect.

Is there a Need for Own Median Calculation in the Second Trimester Biochemical Markers Screening?

Screening of fetal aneuploidies in early pregnancy is a well-established method in the materno-fetal medicine. The aim of our study was to analyze if the medians recommended by the manufacturers are adequate to perform an accurate screening or if there is a need for own laboratory medians calculation in second trimester biochemical marker screening.Sera were collected between 14 wp and 22 wp from 3374 singleton pregnancies. We analyzed three second trimester biochemical markers (AFP, hCG and free Estriol) concentration in all pregnant women and in a subgroup of pregnant women in which gestational age was determined based on crown-rump length. Our results showed that for all biochemical markers the difference between the manufacturer and the own calculated median was lower than 10% excepting the hCG value in the group of pregnant women in which the gestational age was determined on basis of crown-rump-length. Our results show it is recommended to replace the values of the median for hCG measurement with the own laboratory calculated medians. This does not seem to be necessary in the case of AFP and free Estriol measurement.

Changes in cervical cancer course under the influence of HPV/chlamydia trachomatis co-infection.

e17018 Background: The purpose of the study was to analyze the effect of HPV/Chlamydia trachomatis co-infection on the hormonal status of tumor and visually unchanged cervical tissues in cervical cancer patients. Methods: We studied levels of estrone (E1), estradiol (E2), free estriol (E3), free (fT) and total (T) testosterone, progesterone (P4) and prolactin (PRL) by the ELISA in tumors and visually unchanged cervical tissues of 49 patients with cervical cancer T1b-2aN0M0 with endophytic (25 patients) and exophytic (24 patients) patterns of tumor growth. 13 patients with endophytic tumors and 12 patients with exophytic ones were infected with HPV and Сhlamydia trachomatis (Ch.tr.). HPV infection was determined by Е7 protein expression, Ch.tr. – by IgG and IgА and antigen/DNA in ELISA and PCR. Intact cervical tissues obtained during hysterectomy from 22 non-infected women with endometrial cancer were used as the control. Results: Tumor tissues of the cervix without infection demonstrated increased levels of all sex steroids: estrogens by 3 times, androgens by 3.1 times and progestins by 1.8 times. Co-infected tissues were characterized by the sex-steroid imbalance. We observed reduced coefficients of estrogens to T and fT by 1.6 and 6 times, respectively, compared to intact tissues (most significant in a tumor with endophytic growth pattern) and an increase in the estrogens to P4 ratio by 1.5 times – only in endophytic growth pattern. Androgenic status in co-infected tumor tissues increased by 1.7 in endophytic and by 3.1 times in exophytic growth pattern. PRL level was increased only in co-infected tumors (by 2.5 times). Unchanged co-infected tissues, unlike non-infected samples, showed E2 increase by 2.6 times in exophytic and by 1.5 times in endophytic growth pattern, T increase by 1.6 times only in endophytic tumors and P4 decrease by 1.5 times and PRL increase by 1.8 times regardless the tumor growth pattern. Conclusions: Hormonal profile of both tumor and unchanged cervical tissues was dependent on HPV/Ch. tr. co-infection and tumor growth patterns. The changes could result from HPV and Ch. tr. interaction triggering malignant processes.