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Sergije Marković

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Suada Tinjić, D. Abazovic, Dušica Ljubić, D. Vojvodić, T. Bozanovic, Mirza Ibrišimović, S. Marković, A. Ljubić

Background: Premature ovarian failure (POF) can be found in 1% of women at the age of 35-40, mostly due to unknown causes. PI3K-Akt signaling is associated with both ovarian function and growth of primordial follicles. In this study, we examined the effects of autologous in vitro ovarian activation with stem cells and autologous growth factors on reproductive and endocrine function in patients with ovarian impairment. Materials and Methods: The longitudinal prospective observational study included 50 patients (between 30 and 50 years) with a diagnosis of POF and infertility. This multicenter study was performed at Jevremova Special Hospital in Belgrade, Saint James Hospital (Malta), and Remedica Skoplje Hospital, between 2015 and 2018. All patients went through numerous laboratory testings, including hormonal status. The autologous bone marrow mesenchymal stem cells (BMSCs) and growth factors were used in combination for activation of ovarian tissue before its re-transplantation. The software package SPSS 20.0 was used for statistical analysis of the results. Results: Differences in follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and progesterone (PG) hormone concentrations before and after 3, 6, and 12 months post-transplantation were tested in correlation with the volume of transplanted ovarian tissue. A significant correlation (P=0.029) was found between the change in E2 level after 3 months and the volume of re-transplanted tissues. Also after re-transplantation, 64% of the patients had follicles resulting in aspiration of oocytes in 25% of positive women with follicles. Conclusion: The SEGOVA method could potentially solve many human reproductive problems in the future due to the large number of patients diagnosed with POF, as well as the possibility of delaying menopause, thus improving the quality of life and general health (Registration number: NCT04009473).

Suada Tinjić, Mirza Ibrišimović, S. Marković

Multiple pathologies of the placenta can be identified during the first trimester of pregnancy thanks to the ultrasound diagnostics, and many molecular trophoblasts defects associated with it are still poorly understood. In other words, the 3Dand 4D-ultrasound are still the golden tool in early detection of abnormal fetal development. Using placenta as a marker in diagnosis of chromosomal abnormalities has detection sensitivity of only 3%, and is not syndrome specific, as in the case of Wolf-Hirschhorn syndrome where only few cases of hypotrophic placenta were reported. We describe the case of first-trimester pregnancy with diagnosis of pathologic placental morphology and intrauterine growth restriction of the fetus, with prenatal genetic screening testing which confirmed existence of Wolf-Hirschhorn syndrome. Suspicion for chromosomal abnormalities was raised due to placenta ultrasound examination only and this case report outlines the clinical significance of the placenta as a novel marker for Wolf-Hirschhorn syndrome, since other clinical indications in this case were not present. Keywords— Placenta, Wolf-Hirschhorn Syndrome, 3D-

S. Marković, A. Cerovac, Elmedina Cerovac, Dragana Markovic, G. Bogdanovic, Suad Kunosic

Background: The aim of this study is to compare the antenatal care, body weight, and weight gain in pregnancy between the adolescent and adult pregnancies and, thus, examine the impact of adolescence on the studied parameters. Methods: This prospective study includes 300 pregnant women who were the patients of University Clinical Center Tuzla, Clinic for Gynecology and Obstetrics from January 2011 to December 2014. The women were divided into two groups: an experimental group consisted of 150 adolescent pregnant women aged 13–19 years and a control group consisted of 150 adult pregnant women aged 20–35 years. The following parameters were analyzed: age of pregnant women, number of antenatal controls in pregnancy, prepregnancy body weight, weight gain in pregnancy, parity, and obstetric history data. Results: A significantly higher number of adolescent pregnant women belongs to a subgroup from one to two examinations during pregnancy (P < 0.000013) and to subgroups from three to five examinations (P < 0.000001). A significantly smaller number of adolescent pregnant women performed their first antenatal control in the first 2 lunar months (P < 0.01). A subgroup with optimal body weight (from 51 to 69 kg) are the most prevalent among adolescent pregnant women (P < 0.000001). A significantly larger number of adolescent pregnant women had an optimal weight gain of 7.8 to 12.99 kg (P < 0.001). Conclusions: The adolescent pregnant women have suboptimal antenatal care, which could lead to adverse maternal and birth outcomes, but have optimal body weight and weight gain during pregnancy.

Aim To compare maternal, foetal and neonatal characteristics, and perinatal outcome of preterm and term deliveries in twins pregnancies in order to improve perinatal care in Bosnia and Herzegovina. Methods This retrospective cohort study included pregnant women with twin pregnancy who delivered during the period between 1 January 2012 and 31 December 2018 at the Clinic for Gynaecology and Obstetrics, University Clinical Centre Tuzla. Results During the seven-year period 26 734 deliveries were recorded, out of which 362 (1.35 %) were twin pregnancies, 226 (62.4%) preterm and 136 (37.5%) term ones. In the preterm group 38 (16.8%) pregnancies were assisted medical reproduction, and 16 (11.7%) of those were in the term group. The average birth weight was significantly higher for the first twin in both groups (p<0.00001). Incipient intrauterine foetal asphyxia was more frequent in the preterm group (p<0.05). The most common indication for Caesarean section was abnormalities of foetal presentation and lie, 176 (68.2%) for the overall sample. Conclusion Cornerstone of twin pregnancy antenatal care is to get correct data about amnionicity and chorionicity. Since majority of prenatal data did not have this information we call all obstetricians to declare about amnionicity and chorionicity in twin pregnancies during the first trimester ultrasound examination.

Aim To determine stereological structural parameters of the parenchymal part of the placenta, placental weight and volume of adolescent pregnant women and their correlation with newborns' birth weight. Methods This prospective study was conducted on a total of 60 human placentas of term pregnancy, divided into two groups according to the age of pregnant women. Experimental group consisted of 30 placentas of pregnant women aged 13-19 years. Control group consisted of 30 placentas of pregnant women aged 20-35 years. Stereological analysis was performed. Results Volumetric density of terminal villi of adolescent placentas was significantly higher than the one of control group (p <0.0001). The volumetric density of fibrinoid of adolescent placentas was significantly lower than of the control group (p <0.0001). Total volume of terminal villi of adolescent placentas was significantly higher than of the control group (p<0.0001). The total volume of fibrinoid of adolescent placentas was significantly lower than of the control group (p<0.0001). Newborns of adolescent pregnancies had in average lower birth weight of 439.01 g compared to the newborns of the control group (p <0.00001). Conclusion Adolescent pregnancy affects placental structure, weight and volume. Newborns of adolescent pregnancy have optimal body weight.

Aim To compare the prevalence of premature rupture of membranes (PROM) and preterm premature rupture of membranes (PPROM) between adolescent and adult pregnancies, and the influence of gestational age and adolescent pregnancy on the frequency of occurrence of PROM and PPROM. Methods This prospective study included 300 pregnant patients, 13 to 35 years of age, divided into two groups. The first group consisted of 150 pregnant women aged 13-19 (experimental group) and the second group consisted of 150 pregnant women aged 20-35 (control group). Results There was a statistically significant higher incidence of both PPROM and PROM in the group of adolescent pregnant women compared to adult pregnant women (p<0.000001). Preterm delivery with PPROM was significantly more common in the group of adolescent pregnant women (p<0.004). Term delivery with PROM was statistically significantly more common in the adolescent pregnancy group than in the adult pregnancy group (p<0.001). Term delivery with PROM was statistically significantly more common than preterm delivery with PPROM in the group of adolescent pregnant women (p<0.0001). Conclusion Adolescent pregnancy has a greater impact on the frequency of PROM and PPROM.

S. Marković, Z. Žigić, A. Cerovac, Suad Kunosic, M. Lelic, Fejzo Džafić

Introduction: Knowledge of the size of surfaces available for transport is important for assessing the amount of nutrients that can be transmitted to the fetus for its normal growth and development. Aim: The aim of our study, was to determine the stereological structural parameters of the parenchymal part of placenta, ratio of birth weight and placental weight, and to determine their correlation with the body length and head circumference of the newborns of adolescent pregnant women. Methods: The study was conducted on a total of 60 human placentas of term pregnancy, divided into two groups according to the age of pregnant women. The experimental group consisted of 30 placenta of pregnant women aged 13-19. The control group consisted of 30 placenta of pregnant women aged 20-35. Computer assisted morphological analysis of images of histological preparations using stereological methods was performed. Results: Surface density of terminal villi of adolescent placentas is significant higher than the control group (t = 14,179, df = 29, p <0,0001). The T-test (t = -5,868, df = 29, p <0,0001) showed statistically significant difference in the surface density of fibrinoid in two compared groups. T-test (t = 6.438, df = 29, p <0.0001) found that total surface of terminal villi was significantly higher in adolescent placentas. The T-test (t = -6,747, df = 29, p <0,0001) found that total surface of fibrinoid was significantly lower in adolescent group. The T-test (t = 4.203, df = 29, p <0.0001) found that the ratio of birth weight of newborn and adolescent placental weight was significantly higher in relation to the control group. Conclusion: Adolescent placentas was more efficient in increasing the weight of newborns, compared to the control group placentas.

Introduction: Hydatidiform moles (HM), presenting as complete (CHM) and partial (PHM) form, are rare pregnancy disorder. Diagnosis is based on clinical presentation, ultrasound imaging findings and pathological examination of products of conception. Protein p57, encoded by CKDN1C gene, is paternally imprinted and maternally expressed gene and provides quick insight in genetic basis of HM and allows distinction of CHM from all other conceptions. compare the preevacuational and pathohistological diagnosis with outcome of p57 immunostaining. Material and methods: All cases of HM diagnosed between January 2011 and December 2015 were included in this research. Maternal age, gestational age and input diagnosis data were recored. p57 immunostaining was performed in order to evaluate the diagnosis based on tissue slides examination. Results: There were 198 cases of histologically confirmed HM, 185 PHM, 12 CHM and one case of undefined HM. Mean maternal age in the CHM group was 24,7 and in the PHM group 26,9 years, with no significant differences among these two groups (p=0,27). For CHM mean gestational age was estimated at eight and for PHM 9,2 gestational weeks. Pregnant woman older than 40 years present significant earlier compared with younger woman (p<0,01), and those younger than 20 years tend to present at the beginning of the second trimester more often than older women (p<0,05). In the CHM group, 9 (75%) input diagnoses were mola in obs, and 3 (25%) of them were signed as abortion, unlike the PHM where 126 (67%) were qualified as abortion, 35 (19%) as blighted ovum, and 26 (14%) were suggestive for molar pregnancy. p57 immunostaining results confirmed all pathohistological diagnosis of CHM whereas 8% of PHM demonstrated divergent p57 expression. Conclusion: PHM, compared with CHM, represent a greater diagnostic challenge for both gynecologist and pathologist even when presenting in more advanced pregnancies.

M. Lelic, S. Ramić, Z. Žigić, G. Bogdanovic, S. Marković

Iron deficiency, causing maternal sideropenic anemia, is one of the most frequent nutritive disorder that develops during the pregnancy. We collected 30 placentas from anemic mothers and 30 placentas from mothers belonging to the control group. Terminal villi (magnification 10x) and terminal villi capillaries (magnification 40x) were stereologically analyzed and numerically determined.In the placentas from anemic mothers we noted the values a) terminal villi: volume density 0,43 mm0, surface density 24.13 mm-1, total volume 185.57 cm3 and total surface 10.27 m2; b) capillaries of terminal villi: volume density 0.53 mm0 and total volume 224.18 cm3. In the placentas from mothers belonging to the control group we observed the following values a) terminal villi: volume density 0.44 mm0, surface density 22.27 mm-1, total volume 200.17 cm3 and total surface 10.15 m2; b) capillaries of terminal villi: volume density 0.42 mm0 and total volume 197.00 cm3. Compared with the control group anemic mothers' placentas have a significant higher values of surface density of terminal villi (p<0.05), volume density (p <0.01) and absolute volume (p<0.0001) of terminal villi capillaries, and significant lower values of absolute volume of terminal villi (p<0.05).In anemic mothers' placentas, the total volume of terminal villi changes disproportionately to the total surface of terminal villi with statistically significant increase of terminal villi capillaries compared with control group. 

Objective. To describe the intrahepatic bile duct transposition (anatomical variation occurring in intrahepatic ducts) and to determine the frequency of this variation. Material and Methods. The researches were performed randomly on 100 livers of adults, both sexes. Main research methods were anatomical macrodissection. As a criterion for determination of variations in some parts of bile tree, we used the classification of Segmentatio hepatis according to Couinaud (1957) according to Terminologia Anatomica, Thieme Stuugart: Federative Committee on Anatomical Terminology, 1988. Results. Intrahepatic transposition of bile ducts was found in two cases (2%), out of total examined cases (100): right-left transposition (right segmental bile duct, originating from the segment VIII, joins the left liver duct-ductus hepaticus sinister) and left-right intrahepatic transposition (left segmental bile duct originating from the segment IV ends in right liver duct-ductus hepaticus dexter). Conclusion. Safety and success in liver transplantation to great extent depends on knowledge of anatomy and some common embryological anomalies in bile tree. Variations in bile tree were found in 24–43% of cases, out of which 1–22% are the variations of intrahepatic bile ducts. Therefore, good knowledge on ductal anatomy enables good planning, safe performance of therapeutic and operative procedures, and decreases the risk of intraoperative and postoperative complications.

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