The Impact of Laparoscopic Treated Endometrioma on the Live Birth Rate in IVF/ICSI Cycles Compared with Unexplained Infertility: A Prospective Randomized Study

BACKGROUND: It is estimated that 30–70% of patients who undergo treatment for infertility are afflicted with endometriosis. AIM: The objectives of this study are to evaluate the impact of laparoscopic treated endometrioma compared to unexplained subfertility on the live birth rate in women undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). METHODS: This randomized prospective study included 120 women who contacted the department of IVF in the period from 2010 to 2015. Women were divided into two groups according to the findings obtained by laparoscopy. The treated endometrioma group (n = 60) with unilateral ovarian endometriomas and the non-endometriosis group (n = 60) with unexplained infertility undergoing the first cycle of IVF-embryo transfer (IVF-ET) were included in the study. In all participants, ICSI was used and all had fresh embryo transfer per cycle. The primary outcome was to live birth. RESULTS: Our results demonstrated that clinical pregnancy rates (p = 0.54) and live birth rate (p = 0.63) are similar. The preservation of a good ovarian response to stimulation by gonadotropins after laparoscopic ovarian cystectomy was presented. Laparoscopic cystectomy is followed by good IVF/ICSI outcome into the level expected in women with unexplained subfertility. CONCLUSION: Therefore, operative treatment is justified by not altering the live birth rate. Additional study is needed to be considered cystectomy before IVF as an effective approach for managing endometriosis-associated infertility

REGULATORY CONSIDERATIONS OF BIOSIMILARS AND CLINICAL DILEMA OF THEIR USE

Biomedical products are complex molecules, produced by living cells. More accurately, they are molecules that are naturally produced in the human body, like hormones or growth factors, monoclonal antibodies, blood products, immunological medicinal products, sera and vaccines, allergens, and advanced technology products such as gene and cell therapy products. Copies of these drugs, known as biosimilars, are comparable but not identical and are not generic version of innovator biological products. Specific regulatory requirements and abbreviated registration process apply in the case of biosimilars, in order to demonstrate efficacy and safety profile and to prove that product is similar to the original biomedical product. Like all medicines, biological medicines work by interacting with the body to produce a therapeutic outcome, but the mechanisms by which they do this may vary from product to product and through indications. Therefore the role of the physicians in treatment of patients with these complex medicinal products is particularly important. Regulatory issues, manufacturing, safety, physicians have part in develop use of biosimilars as much as generic drugs. Even though, the most important factor for market of biosimilar are commercial factor, still, real clinical dilemma of use are present, so it is necessary to have clear regulatory framework and postmarketing data on the use of biosimilar

Indicators of Preeclampsia in Correlation with Maternal Cytokines in Pregnancy

Aim: the purpose of the actual study was to evaluate, in the third trimester of pregnancy, the relationship between the formation of anti-inflammatory IL-10 cytokine and several indicators of moderate and severe preeclampsia. Materials and methods: in the third trimester of gestation, examination of the biochemical markers of preeclampsia (PE) and maternal IL-10 levels was conducted in 100 women with pregnancies complicated by varying degrees of preeclampsia and in 100 normotensive patients, hospitalized at the University Clinic of Gynecology and Obstetrics, Skopje, Republic of Macedonia. Patients with preeclampsia were categorized into moderate and severe preeclampsia groups according to the degree of preeclampsia. Logistic regression of the different parameters for the occurrence of severe preeclampsia analysis was used to determine the predictive value. Results: the regression analysis detected systolic blood pressure of 160 mmHg or higher, diastolic blood pressure of 100 mmHg or higher, persistent proteinuria in pregnancy, serum LDH concentration of 450 U/L or higher, and reduced serum concentrations of IL-10 as significant predictors of severe preeclampsia. Conclusion: significantly, lower IL-10 concentrations in maternal serum in patients with severe preeclampsia in comparison with respective concentrations in patients with moderate preeclampsia can be considered as major pathognomonic laboratory sign of severe form of preeclampsia

Efficiency of trichloroacetic acid in the tretment of subclinical HPV infections of the uterine cervix

Cervical cancer is the fourth leading cause of death among the female population worldwide and represent 6,5% of all female cancers. According to World health organization our country, North Macedonia is among the countries with middle high age standardized rate of 7,5. Statistical review of Institute of public health of North Macedonia showed that in average there are 150 new diagnosed cases of cervical cancer per year in our country, and one third of them died. Papillomaviruses are ubiquitous and more than 200 types were recognized by DNA sequence data showing genomic differences.There are over 200 types of human papilloma virus (HPV), 40 of which are specific to the anogenital region, while 14 are high-risk types , which are the most common causes of cervical cancer. The most important viral proteins that affect gene regulation and cell transformation are the E6 and E7 prooncogenes, which bind to p53 and retinoblastoma (Rb) proteins , thus cell apoptosis and cause immortalization of the cells is prevented. The period from infection to the onset of an intraepithelial lesion is three weeks to three months, that is the time needed for basal keratinocytes to move through the cervical epithelium, to differentiate, and to desquamate. And the time that is usually needed for high squamous intraepithelial lesions to progress to microinvasive cancer usually takes decades. Because there is no cytolysis or cytological death due to viral replication, there is no inflammation throughout the life cycle of HPV and the production of cytokines is absent or they are produced in a very small amount. Therefore, the virus can be tolerated by the host for a a longer period of time, thus it would be able to persist without causing an immune response. Persistent high-risk types are the most common cause of high-grade cervical intraepithelial lesions and cervical cancer. Over time, the greater the viral load or the infection is , the greater the possibility of progression of the subclinical infection to a cervical intraepithelial lesion is. The topical action of trichloroacetic acid (TCA) on eradication of HPV is well established. The results of this procedure are promising, and the procedure is easy, inexpensive, does not require specific and special training of the staff performing it. This treatment and therapy with TCA protects the cervical mucosa from long-term exposure to HPV, thereby reducing the risk of developing high-grade intraepithelial lesions. In this way, patients avoid the surgical treatment and intervention that is necessary for higher degrees of cervical lesions caused by HPV. This is very important because the patients affected by high squamous intraepithelial lesions caused by HPV that require a surgical treatment, are often in reproductive age and this noninvasive treatment can indirectly reduce the risk of preterm delivery. Keywords:TCA, treatment, HPV infection, cervix, neoplasia, preventio

Улогата на некои инфламаторни маркери, цитокини и тумор маркери во дијагноза на ендометриозата

Endometriosis is a multifactorial disease which etiopathogenesis has not been elucidated. One of the theories of etiopathogenesis is the inflammatory theory. Aims of the study: To develop a practical non-invasive test for the diagnosis of endometriosis by examining some inflammatory markers and cytokines; to compare the highly sensitive C-reactive protein (hsCRP), cytokines (interleukin-6-IL-6 and tumor necrotizing factor alpha) and the tumor marker cancer antigen 125 (CA-125) among healthy patients and patients with endometriosis; to determine the sensitivity and specificity of each biomarker separately in the diagnosis of endometriosis and to determine their role in the diagnosis of endometriosis. Materials and methods: In a prospective study conducted at the University Clinic for Gynecology and Obstetrics, Ss. Cyril and Methodius University in Skopje, North Macedonia 138 patients were included of a reproductive age between 18-50 years (83 with diagnosis endometriosis operated laparoscopically or with laparotomy) and a control group of 55 healthy women, in a period between 01.09.2018 to 01.05.2021. Serum levels of IL-6, TNF-α, hs-CRP and tumor marker CA-125 were evaluated in both groups. Results: Serum levels of CA-125, IL-6 and TNF-α and hs-CRP were significantly higher in patients with endometriosis compared to the control group. The surface under the ROC curve (AUC) for IL-6, CA-125, hs-CRP, and TNF-α has shown that as individual markers they all have a discriminatory capacity to diagnose patients with endometriosis. Conclusions: Results obtained in our study showed statistically significantly higher serum concentrations of CA-125, IL-6 and TNF-α and hs-CRP in patients with endometriosis compared to the control group of patients. However, none of these biomarkers showed a high sensitivity for diagnosis of endometriosis. It is necessary to find a panel combination of biomarkers with a high sensitivity of about 100% that will enable early diagnosis of endometriosis.Ендометриозата е мултифакторно заболување, чија етиопатогенеза не е разјаснета. Една од теориите за етиопатогенезата е инфламаторната теорија. Цели на истражувањето: Да се развие практичен неинвазивен тест за дијагноза на ендометриозата со иследување нанекои инфламаторни маркери и цитокини; да се направи споредба на  високосензитивниот Ц-реактивен протеин  (hsCRP), цитокините (интерлеукин 6 –IL-6 и тумор-некротизирачки фактор алфа - TNF-α) и туморскиот маркер cancer antigen 125 (CA-125) кај здрави пациентки и пациентки со ендометриоза; да се утврди сензитивноста и специфичноста на секој биомаркер посебно во дијагнозата на ендометриозата и да се утврди нивната улога во дијагноза на ендометриозата. Материјал и методи: Во проспективна студија спроведена на Универзитетската клиника за гинекологија и акушерство, Универзитет „Св. Кирил и Методиј“ во Скопје, Северна Македонија беа вклучени 138 испитанички на репродуктивна возраст помеѓу 18-50 години (83 со дијагнозa ендометриоза, оперирани со лапароскопија или лапаротомија) и контролна група од 55 здрави жени, во период од 01.09.2018 година до 01.05.2021. Серумските вредности на интерлеукин 6 (IL-6), тумор-некротизирачки фактор алфа (TNF-α), високоспецифичен Ц-реактивен протеин (hsCRP) и туморскиот маркер CA-125 беа евалуирани во двете групи. Резултати: Серумските вредности на CA-125, IL-6 и TNF-α и hsCRP беа сигнификантно повисоки кај пациентките со ендометриоза во споредба со оние во контролната група. Површината под ROC кривата (AUC) за IL-6, CA-125, hs-CRP и TNF-α покажа дека како поединечни маркери сите имаат дискриминаторен капацитет за дијагноза на пациентки со ендометриоза. Заклучоци: Иследувањата во нашата студија покажаа статистички сигнификантно повисоки концентрации на CA-125, IL-6 и TNF-α и hs-CRP кај пациентките со ендометриоза во однос на контролната група пациентки. Меѓутоа, ниту еден од овие биомаркери не покажа висока сензитивност за дијагноза на ендометриозата. Потребно е да се најде панел комбинација на биомаркери со висока сензитивност од околу 100% кои ќе овозможат  рана дијагноза на ендометриозата

2D/3D Ultrasound Findings of Uterine Carcinosarcoma: A Case Report and Literature Review

Uterine carcinosarcoma is an infrequent, yet an invasive malignant tumor of the uterus. We presented the case of a 76-yearold menopausal woman with the first sparse bleeding and ultrasound findings of a large polypoid formation filling the uterine cavity. Ultrasound, specially more advanced techniques as 3D ultrasound and 3D Color Doppler ultrasound provide very useful data not only in the recognition of tumor mass, but also in terms of the structure, differentiation and stage of the malignancy. Keywords: 2D ultrasound, 3D color Doppler transvaginal ultrasound, Uterine carcinosarcoma. Donald School Journal of Ultrasound in Obstetrics and Gynecology (2022): 10.5005/jp-journals-10009-192

Efficacy of trichloroacetic acid in treatment of HPV related infections of the uterine cervix

Objective: To establish the efficacy of single topical 85% trichloroacetic acid (TCA) treatment of the subclinical Human papillomavirus (HPV) infections of the uterine cervix. Methods: This is a retrospective study including patients with HPV infection of the uterine cervix established by HPV DNA PCR assay. All the patients were treated with 85% TCA, applied topical and treatment response was followed up by HPV DNA PCR assay in various groups of patients, two, three, four, six and twelve months after the treatment with TCA. Remission was defined as complete clearance of HPV. Results: In total, 173 patients with HPV specific type were included in the study. Unfortunately 70 patients didn’t return for following check up after the treatment and in 103 patients follow up HPV DNA PCR was made, which showed that 70 of them had complete HPV clearance. In addition, 68% and 33 patients were confirmed as positive, 32% and 10 of the HPV positive group still had the same type of HPV, 30% and 23 of them were typed with new type of HPV, 70%. Conclusion: A single treatment of topical TCA for subclinical HPV infections is associated with high HPV clearance, especially two, three and four months after the treatment. The HPV clearance six and twelve months after the treatment, decreases progressively. This gives us the right to think of TCA as an effective agent for subclinical HPV infection treatment. Key words: human papillomavirus, trichloroacetic acid, cervical intraepithelial neoplasia, cervical cance

KONCENTRACIJA JODA U MOKRAĆI: PREDSKAZATELJ POROĐAJNE TEŽINE ILI BIOLOŠKI BILJEG ZA PROCJENU JODNOG STATUSA SAMO U ZDRAVIH TRUDNICA?

Introduction: This study determined urine iodine concentration (UIC) during gestation, assessed the maternal iodine nutrition status and correlated it with gestational age at birth (GAB) and birth weight (BW).The measurement of UIC provides the best single measurement of the iodine nutritional status in population. Objective: Determination of UIC in pregnant women in North Macedonia. Methods: This prospective study assessed the iodine nutrition status during the course of pregnancy with reference of median UIC among 364 healthy pregnant women in different gestational age (in trimester and 5-week intervals). Results: The overall and the 1st to the 3rd trimester median UIC were: 183.7, 207, 189.75 and 169.28 [μg/L], respectively. The median UIC (μg/L) results according to 5-week interval in advancing gestation were: 232.34, 200.13, 152.81, 194.39, 181.28, 160.28, 169.41 and 175.24, respectively. We detected 5.22% (19/364) and 74.72% (272/364) with the median UIC < 50 μg/L and UIC ≥ 100 μg/L, respectively. In multiple regression, the median UIC (β = 0.0000767, P = 0.929) had no statistically signifi cant prediction to the GAB. Disease prevalence results for mean UIC in detecting BW had no statistical signifi cance: area under curve (AUC) = 0.521, z-statistic (0.340), sensitivity (45.83%), specifi city (66.27%), predictive (6.59%) and P value (0.734). Conclusion: Iodine status of pregnant women in our study is generally suffi cient by World Health Organization recommendations. The median UIC in each trimester and 5-week interval has statistically insignifi cant decrease in accordance to the advancing gestation. The median UIC has no signifi cance in predicting GAB and BW.Uvod: Ova je studija utvrdila koncentraciju joda u mokraći (UIC) tijekom trudnoće, procijenila prehrambeni status joda kod majke i povezala ga s gestacijskom dobi pri rođenju (GAB) i porođajnom težinom (BW). Mjerenje UIC-a omogućava najbolje pojedinačno mjerenje prehrambenog statusa joda u populaciji. Cilj: Određivanje UIC-a trudnicama u sjevernoj Makedoniji. Metode: Ova prospektivna studija procjenjivala je prehrambeni status joda tijekom trudnoće, pozivajući se na medijan UIC 364 zdrave trudnice u različitoj gestacijskoj dobi (u intervalima tromjesečja i 5 tjedana). Rezultati: Ukupna i prosječna UIC od 1. do 3. tromjesečja bila su: 183,7, 207, 189,75 i 169,28 [μg / L]. Srednji rezultati UIC (μg / L) prema intervalu od 5 tjedana u napredovanju trudnoće bili su: 232,34, 200,13, 152,81, 194,39, 181,28, 160,28, 169,41 i 175,24. Otkrili smo 5,22 % (19/364) i 74,72 % (272/364) s medijanom UIC <50 μg / L, odnosno UIC ≥ 100 μg / L. U višestrukoj regresiji, medijan UIC (β = 0,0000767, P = 0,929) nije imao statistički značajno predviđanje za GAB. Rezultati prevalencije bolesti za srednji UIC u otkrivanju BW nisu imali statističku značajnost: područje ispod krivulje (AUC) = 0,521, z-statistika (0,340), osjetljivost (45,83 %), specifi čnost (66,27 %), prediktivna (6,59 %) i P vrijednost (0,734). Zaključak: Jodni status trudnica u našem istraživanju u pravilu je dovoljan prema preporukama Svjetske zdravstvene organizacije. Medijan UIC-a u svakom tromjesečju i intervalu od 5 tjedana statistički je beznačajno smanjen u skladu s napredovanjem trudnoće. Medijan UIC nema značenje u predviđanju GAB i BW

Role of the nurse in gynecological endoscopic operations

Gynaecology is the branch of medicine that studies the disease and the treatment of the treatment of the female reproductive system (uterus, ovaries and vagina), and is responsible for the overall health of women. Translated from the Latin meaning "the science of women", as opposed to andrology, which deals with health issues specific to the male reproductive system.An important role in the development of this industry has medical prevention and education of women

Human Papillomavirus infection in cervical precancerous lesions

Infection with high-risk HPV genotypes increases the risk for persistent or progressive cervical lesions. The aim of this study was to determine the frequency and correlation of the HPV infection with the cytological or histopathological diagnosis. A total of 6988 samples were analysed and after exclusion of the repeated samples and/or those containing degraded DNA, 4421 patients were included in the study group. PCR-RFLP technique was used as a method for HPV typing. HPV infection was detected in 1819 out of 4421 patients. The frequency of infection was 23% in the patients’ group with cytological and 60% in the group with histopathological diagnosis. The HPV frequencies in precursor lesions were as follows: 51% in patients with mild; 75% in patients with moderate; 91% in patients with severe dysplasia and 93% in carcinoma in situ lesions. The most prevalent HPV types in descending order were: HPV 16, 31, 53, etc. HPV infection was the most frequent in patients under 19 years old. In 169 out of 1253 samples with determined viral genotype, a multiple infections were found. This data for the prevalence and distribution of the HPV infection in Macedonian women accentuates the need for the establishment of organized screening programs