ISOLATED MATERNAL HYPOTHYROXINEMIA AND ITS PERINATAL OUTCOME IN NORTH MACEDONIA.

Isolated maternal hypothyroxinemia (IMH) is defined as the presence of low maternal total thyroxine (TT4) level in conjunction with normal maternal thyroid-stimulating hormone (TSH) level. The aim was to investigate whether IMH is associated with adverse pregnancy outcome in North Macedonia. Dried blood spot samples were obtained from 359 pregnant women meeting the inclusion criteria and analyzed for TT4 and TSH. Postpartum data were entered from their medical histories. Out of 359 women, 131 (37.42%) belonged to IMH group. There were statistically significant differences in birth weight (p=0.043), intrauterine growth restriction (IUGR) (p=0.028), Apgar score at 1 min <7 (p=0.018) and cesarean section for dystocia/disproportion (p=0.024) between the IMH and normal thyroid function (NTF) groups. In regression analysis, TSH was a significant variable predicting Apgar score (ßst=0.05597, p=0.047), body mass index predicting birth weight (ßst=0.02338, p=0.045) and TT4 predicting small for gestational age/IUGR (ßst=-0.089834, p=0.029) in IMH group. TT4 was a strong predictor of birth weight (ßst=-0.004778, p=0.003) and premature delivery (ßst=0.028112, p=0.004) in NTF group. The impact of IMH in pregnancy remains controversial. IMH was associated with an increased maternal BMI and higher birth weight of neonates. Overweight could be a potential risk factor for thyroid dysfunction in pregnant women, and specifically IMH. The worst fetal outcome was seen in IMH mothers examined in second trimester. We found TSH, TT4 and BMI to be strong predictors of perinatal outcomes.

Prevalence of Specific Types of Human Papiloma Virus in Cervical Intraepithelial Lesions and Cervical Cancer in Macedonian Women.

INTRODUCTION: Cervical cancer is a malignancy originating in the transformation zone of the cervix, most commonly in the squamous cells. It is the fourth most common cancer in women worldwide, and the third most common cause of female cancer death. Genital human papilloma viruses (HPV) are sexually transmitted and approximately 630 milion people worldwide are infected. More than 200 genotypes, subtypes and variants have been reported, 13-15 being oncogenic type, which could be responsible for cervical intraepithelial lesions (CIN) or cancer. AIM: Aim of this study was to evaluate the prevalence of this infection and to identify specific types of human papiloma virus in cervical intraepithelial lesions and cervical cancer in Macedonian women. MATERIAL AND METHODS: The study was conducted at the University Clinic for Obstetrics and Gynecology, Skopje, Macedonia, in a period of four years. The study was performed on a cohort of 1895, 18 - 73 year old patients who during primary examination had already abnormal PAP smear test. Cervical cells were collected in the lithotomy gynecological position of the patient, using endocervical cytobrush and cotton-tipped swab, and both were placed in sterile test tube with phosphate buffered saline. Samples were stored at temperature of 2 - 8 °C and Human Pappiloma Virus (HPV) genotyping was analyzed within 7 days by multiple Polymerase Chain Reaction (PCR) methods. RESULTS: The mean age of enrolled women was 40,8 years±10.36 SD(minimum of 18 and maximum 73 years. Among the patients, the presence of HPV by using PCR was detected in 40,68 % (769 patients) and was highly associated with cervical abnormalities. The prevalence of HPV was highest (82,1%) in women aged 20-years or less and it decreased with age and was lowest (19,9%) among patients older than 50 years. The prevalence of oncogenic types of the virus was higher if the cytologic diagnosis is CIN 3/Carcinoma in situ (CIS). In these patients detection of high risk HPV was in 79,1% females with CIN 3 and 97,5 % in females with CIS. The lowest prevalence was detected in patients with atypical squamous cells of undetermined significance (ASCUS) (23,9%) and CIN 1-25 (6%). Results of HPV typing show that genotypes were found either single or multiple in both single and multiple infections. We have seen that HPV 16, 18 and 31 were the most common types detected among the patients from Macedonia. HPV 16 was present even in 52,1 % of women with CIS and in 41,2% in women with CIN 3. HPV type 31 ranked second in patients wit CIN1, CIN2, CIN3 but HPV 18 ranked second in patients with CIS with (12,8%). Surprisingly, patients with mixed infection had more low grade intraepithelial squamous lesions (LSIL) and high grade squamous intraepithelial lesions (HSIL) then CIS. CONCLUSION: Among Macedonian women, HPV 16, 31 and 18 were HPV types strongly associated with intraepithelial cervical lesions and cervical cancers. The prevalence of high risk HPV was highest in youngest women, but the risk was highest among patients with invasive cervical cancer (ICC). Surprisingly, patients with mixed infection had more LSIL and HSIL then CIS.

HPV status after cold knife conization.

INTRODUCTION: The aim of this study was to determine whether HPV DNA test after cold knife conization is a predictive factor for CIN persistence or recurrence. The study also investigated whether HPV DNA test results should influence post cold knife excision surveillance. MATERIALS AND METHODS: A retrospective observation study was performed on 738 patients who underwent cold knife conization for CIN or microinvasive cervical cancer at the University Clinic of Obstetrics & Gynecology, Medical Faculty, Ss. Cyril and Methodius University, Skopje from 1st June 2007 to 1st June 2009. A total of 217 patients met the inclusion criteria and were with complete data. The follow-up HPV DNA testing was performed at 8 months after cold knife conization, after which the patients were followed-up every 4 months till 24 months postoperatively. RESULTS: HPV DNA testing after 8 months after conization showed that 44 patients were HPV DNA positive and 199 were HPV DNA negative. Recurrent cytological abnormalities were found in 26 of the 44 HPV DNA positive patients, and in 12 of the 199 HPV DNA negative patients. Analysis showed that a positive HPV DNA result was a risk factor for recurrent/persistent cervical intraepithelial neoplasia. CONCLUSION: HPV DNA testing 8 months after conization is important for predicting the risk of disease: persistence or recurrence. In addition, such testing can assist in designing patient management, since HPV DNA negative patients should undergo routine surveillance, while HPV DNA positive patients should undergo frequent and meticulous surveillance.

Thyroid Function of Pregnant Women and Perinatal Outcomes in North Macedonia.

OBJECTIVE: Thyroid diseases are the second most common endocrine disorders in the reproductive period of women. They can be associated with intrauterine growth restriction (IUGR), preterm delivery, low Apgar score, low birthweight (LBW) or fetal death. The aim of the present study is to explore thyroid dysfunction and its relationship with some poor perinatal outcomes (Apgar Score, low birthweight, and preterm delivery). METHODS: Dried blood spot samples from 358 healthy pregnant women were analyzed for thyroid stimulating hormone (TSH), total thyroxine (TT4), and thyroglobulin (Tg). Neonatal data were collected upon delivery. Four groups were formed based on thyroid function tests (TFTs). RESULTS: Of the 358 tested women, 218 (60.72%) were euthyroid. Isolated hypothyroxinemia was present in 132 women (36.76%), subclinical hyperthyroidism in 7 women (1.94%), and overt hypothyroidism in 1 (0.28%). The perinatal outcomes IUGR (p = 0.028) and Apgar score 1 minute (p = 0.015) were significantly different between thyroid function test [TFT]-distinct groups. In the multiple regression analysis, TT4 showed a statistically significant inverse predictive impact on LBW (p < 0.0001), but a positive impact of Tg on LBW (p = 0.0351). CONCLUSION: Thyroid hormones alone do not have a direct impact on neonatal outcomes, but the percentage of their participation in the total process cannot be neglected. Based on the regression analysis, we can conclude that TT4 and Tg can be used as predictors of neonatal outcome, expressed through birthweight and Apgar score. The present study aims to contribute to determine whether a test for thyroid status should become routine screening during pregnancy.

OBJETIVO: As doenças da tireoide são as segundas doenças endócrinas mais comuns no período reprodutivo das mulheres. Elas podem estar associadas à restrição de crescimento intrauterino (RCIU), parto prematuro, baixo índice de Apgar, baixo peso ao nascer (BPN) ou morte fetal. O objetivo do presente estudo é explorar a disfunção tireoidiana e sua relação com alguns resultados perinatais insatisfatórios (índice de Apgar, baixo peso ao nascer e parto prematuro). MéTODOS: Amostras secas de sangue em 358 gestantes saudáveis foram analisadas para hormônio estimulador da tireoide (TSH), tiroxina total (TT4) e tireoglobulina (Tg). Os dados neonatais foram coletados no momento do parto. Quatro grupos foram formados com base em testes de função tireoidiana (TFT). RESULTADOS: Das 358 mulheres testadas, 218 (60,72%) eram eutireoidianas. Hipotiroxinemia isolada estava presente em 132 mulheres (36,76%), hipertireoidismo subclínico em 7 mulheres (1,94%) e hipotireoidismo evidente em 1 (0,28%). Os resultados perinatais RCIU (p = 0,028) e índice de Apgar de 1 minuto (p = 0,015) foram significativamente diferentes entre os grupos distintos de TFT. Na análise de regressão múltipla, TT4 mostrou impacto preditivo inverso estatisticamente significativo no BPN (p < 0,0001), mas impacto positivo da Tg no BPN (p = 0,0351). CONCLUSãO: Isoladamente, os hormônios tireoidianos não têm impacto direto no desfecho neonatal, mas o percentual de sua participação no processo total não pode ser desprezado. Com base na análise de regressão, podemos concluir que TT4 e Tg podem ser usados como preditores do resultado neonatal, expressos por meio do peso ao nascer e do índice de Apgar. O presente estudo tem como objetivo contribuir para que um teste para verificar o estado da tireoide deva se tornar um rastreamento de rotina durante a gravidez.

The Connection between the Endometrial Thickness and the Risk of Endometrial Malignancy in Postmenopausal Women.

BACKGROUND: Postmenopausis is a period that starts one year after the last menstruation. Late menopause, after 70 years, is called senile. AIM: To examine the correlation between endometrial thickness and the risk of endometrial malignancy in postmenopausal. MATERIAL AND METHODS: Prospective clinical study involving 120 postmenopausal patients treated at the University Clinic for Gynecology and Obstetrics - Skopje, divided into two groups: control and examination. The control group included 40 postmenopausal patients, hospitalised and operated due to urogenital pathology. The examined group consisted of 80 patients divided into three subgroups according to the ultrasound verified thickness of the endometrium: from 5-8 mm; > 8-11 mm and above 11 mm. A detailed history and intervention were taken in the patients from both groups, and the material was sent for histopathological analysis to determine eventual malignancy. RESULTS: The probability of endometrial malignancy significantly increased by 1.012 times in the group with a thickness of the endometrium from 5-8 mm, 1.769 times in the endometrial thickness group > 8-11 mm and 4.737-fold in the group over 11 mm compared to the control group. CONCLUSION: In postmenopausal patients, the likelihood of endometrial cancer significantly increases with the thickness of the endometrium.

Comparison Between HPV DNA Testing and HPV E6/E7 MRNA Testing in Women with Squamous Cell Abnormalities of the Uterine Cervix.

INTRODUCTION: The aim of the study was to compare the results of two human papillomavirus (HPV) diagnostic techniques: human papillomavirus deoxyribonucleic acid (HPV DNA) testing and human papillomavirus E6/E7 messenger ribonucleic acid (HPV E6/E7 mRNA) testing in women with squamous cell abnormalities of the uterine cervix. MATERIAL AND METHODS: Comparative prospective study, conducted in the period from January 2016 to June 2017 of 128 sexually active women, age groups of 20 to 59 years (40.50 ± 10.85) with squamous cell abnormalities on the cervical cytology. All patients were subject to: HPV DNA testing, HPV E6/E7 mRNA testing and colposcopic cervical biopsy with endocervical curettage for histopathologycal analysis. HPV DNA testing was done using multiplex polymerase chain reaction (PCR) and reverse hybridization methods. HPV E6/E7 mRNA testing was done using real-time PCR method. RESULTS: Data analysis showed an association between the results of HPV DNA testing and HPV E6/E7 mRNA testing (p˂0.0001). The concordance between the results of both tests was moderate (55.47%). The results show that HPV E6/E7 mRNA testing had a higer specificity 88.89% and positive predictive value (PPV) 93.59% for HSIL + invasive squamous cell carcinoma compared to HPV DNA testing that had specificity of 55.56% and PPV 84.61%, respectively. CONCLUSION: The results of our study suggested that HPV E6/E7 mRNA testing is more specific and has a higher positive predictive value than HPV DNA testing and that viral oncoproteins E6 and E7 are superior biomarkers for the detection of high-risk HPV-associated squamous intraepithelial lesions of the uterine cervix.

Thyroid Function of Pregnant Women and Perinatal Outcomes in North Macedonia / Função tireoidiana de mulheres grávidas e resultados perinatais na Macedônia do Norte

Abstract Objective Thyroid diseases are the second most common endocrine disorders in the reproductive period of women. They can be associated with intrauterine growth restriction (IUGR), preterm delivery, low Apgar score, low birthweight (LBW) or fetal death. The aim of the present study is to explore thyroid dysfunction and its relationship with some poor perinatal outcomes (Apgar Score, low birthweight, and preterm delivery). Methods Dried blood spot samples from 358 healthy pregnant women were analyzed for thyroid stimulating hormone (TSH), total thyroxine (TT4), and thyroglobulin (Tg). Neonatal data were collected upon delivery. Four groups were formed based on thyroid function tests (TFTs). Results Of the 358 tested women, 218 (60.72%) were euthyroid. Isolated hypo thyroxinemia was present in 132 women (36.76%), subclinical hyperthyroidism in 7 women (1.94%), and overt hypothyroidism in 1 (0.28%). The perinatal outcomes IUGR (p = 0.028) and Apgar score 1 minute (p = 0.015) were significantly different between thyroid function test [TFT]-distinct groups. In the multiple regression analysis, TT4 showed a statistically significant inverse predictive impact on LBW (p < 0.0001), but a positive impact of Tg on LBW (p = 0.0351). Conclusion Thyroid hormones alone do not have a direct impact on neonatal outcomes, but the percentage of their participation in the total process cannot be neglected. Based on the regression analysis, we can conclude that TT4 and Tg can be used as predictors of neonatal outcome, expressed through birthweight and Apgar score. The present study aims to contribute to determine whether a test for thyroid status should become routine screening during pregnancy.

Resumo Objetivo As doenças da tireoide são as segundas doenças endócrinas mais comuns no período reprodutivo das mulheres. Elas podem estar associadas à restrição de crescimento intrauterino (RCIU), parto prematuro, baixo índice de Apgar, baixo peso ao nascer (BPN) ou morte fetal. O objetivo do presente estudo é explorar a disfunção tireoidiana e sua relação com alguns resultados perinatais insatisfatórios (índice de Apgar, baixo peso ao nascer e parto prematuro). Métodos Amostras secas de sangue em 358 gestantes saudáveis foram analisadas para hormônio estimulador da tireoide (TSH), tiroxina total (TT4) e tireoglobulina (Tg). Os dados neonatais foram coletados no momento do parto. Quatro grupos foram formados com base em testes de função tireoidiana (TFT). Resultados Das 358 mulheres testadas, 218 (60,72%) eram eutireoidianas. Hipotiroxinemia isolada estava presente em 132 mulheres (36,76%), hipertireoidismo subclínico em 7 mulheres (1,94%) e hipotireoidismo evidente em 1 (0,28%). Os resultados perinatais RCIU (p = 0,028) e índice de Apgar de 1 minuto (p = 0,015) foram significativamente diferentes entre os grupos distintos de TFT. Na análise de regressão múltipla, TT4 mostrou impacto preditivo inverso estatisticamente significativo no BPN (p < 0,0001), mas impacto positivo da Tg no BPN (p = 0,0351). Conclusão Isoladamente, os hormônios tireoidianos não têm impacto direto no desfecho neonatal, mas o percentual de sua participação no processo total não pode ser desprezado. Com base na análise de regressão, podemos concluir que TT4 e Tg podem ser usados como preditores do resultado neonatal, expressos por meio do peso ao nascer e do índice de Apgar. O presente estudo tem como objetivo contribuir para que um teste para verificar o estado da tireoide deva se tornar um rastreamento de rotina durante a gravidez.

Current status of human papillomavirus vaccination implementation in central and eastern Europe.

We present a review of the current implementation status of vaccination against human papillomaviruses (HPV) and available data concerning the burden of HPV infection and HPV type-specific distribution in 16 central and eastern European countries: Albania, Bosnia and Herzegovina, Bulgaria, Croatia, the Czech Republic, Estonia, Montenegro, Poland, Romania, Serbia, Slovakia, Slovenia, and The Former Yugoslav Republic of Macedonia. At least one current HPV prophylactic vaccine is registered in all central and eastern European countries except Montenegro. Six counties-Bulgaria, the Czech Republic, Latvia, Romania, Slovenia, and Former Yugoslav Republic of Macedonia-have integrated the HPV vaccination into their national immunization program and currently provide routine vaccination free of charge to the primary target population. Ten countries have not integrated HPV vaccination into the national immunization program. The key reasons for lack of implementation of HPV vaccination into the national immunization program are the high vaccine cost and negative public perception. Vaccination of males is not recommended in any country in the region.

Cervical cancer screening practices in central and eastern Europe in 2012.

The burden of cervical cancer in central and eastern Europe is generally higher compared to western or northern Europe due to a history of mostly opportunistic cervical cancer screening practices and due to the strong influence of political and economic changes in post-communist transition. This article describes the current cervical cancer screening practices, organizational plans for the future, and main obstacles that need to be overcome in 16 countries in central and eastern Europe: Albania, Bosnia and Herzegovina, Bulgaria, Croatia, the Czech Republic, Estonia, Hungary, Latvia, Lithuania, Montenegro, Poland, Romania, Serbia, Slovakia, Slovenia and The former Yugoslav Republic of Macedonia. Unfortunately, only a few countries have managed to establish an organized and well-functioning cervical cancer screening program in recent years, whereas most countries in the region are still struggling with implementation-related issues of organized cervical cancer screening. Encouragingly, even in the countries where only opportunistic screening is performed, well-prepared plans and strategies have been established for switching to organized screening in the near future.

The influence on coagulation of transdermal estrogen hormone replacement therapy as a preoperative preparation of the tissue before vaginal hysterectomy.

In 32 postmenopausal patients who underwent vaginal hysterectomy due to the presence of uterine prolapse at the Department of Uro-gynaecology and Pelvic Floor Disorders in the Clinic of Gynaecology and Obstetrics, Medical School, Skopje in the period from 1st January 2002 to 1st January 2003, and who were preoperatively treated with transdermal estradiol 50 microg/day during 14 days the following parameters of the coagulating status were estimated: prothrombin time (PT) that is expressed in: absolute value, percentage and INR; activated partial thromboplastin time (aPTT Pathrombin SL); thrombin time and platelets number before and after hormone replacement therapy. After 14-day transdermal estrogen therapy, the parameters: PT, PT%, PT INR, aPTT Pathrombin SL didn't expressed significant changes, the thrombin time expressed significant extension, and the platelets expressed a significant decrease. According to our results, the transdermal estrogens might not have any influence on the hepatic synthesis of coagulating factors till the step of prothrombin formation. They might have an essential influence on the step of prothrombin transformation into thrombin, as well as on the process of megacaryocytes segregation into platelets.