Premature ovarian insufficiency - novel hormonal approaches in optimizing fertility.

Premature ovarian insufficiency (POI) is a delicate medical problem in young women. This condition is not unchangeable and permanent but is associated with intermittent and unpredictable ovarian activity, resulting in low conception rate. Over the period of 8 years, the evaluation of secondary amenorrhea was conducted in 90 patients below the age of 40 who wished to restore fertility. Having confirmed the diagnosis and investigated the etiology of POI, hormone replacement therapy was applied (sequential administration of estradiol and norethisterone acetate) in the first 30 patients (group A). Estrogen-progestogen therapy with daily supplementation of 25 mg of micronized oral dehydroepiandrosterone (DHEA) was conducted in 44 patients (group B), whereas a combined regime (estrogen-progestogen therapy, DHEA supplementation in daily dose of 25 mg, and melatonin supplementation in daily dose of 3 mg) was conducted in 16 patients (group C). In the course of our study, 16 pregnancies were realized (18% of all cases: 17% in group A; 18% in group B; 19% in group C) 6 to 20 months after the initiation of hormone therapy, and there have been 13 completed term pregnancies so far with normal fetal growth and development. We concluded that estrogen-progestogen therapy combined with DHEA and melatonin could optimize fertility and lead to successful pregnancy in POI patients.

Clinical features of lung cancer in patients with connective tissue diseases: a 10-year hospital based study.

BACKGROUND: Connective tissue diseases (CTD) might be associated with various malignancies, and one of the most frequent is lung cancer (LC). Despite our understanding of pathogenesis, this association remains still unclear. The aim of the present study is to describe the clinical characteristics of patients with CTD who developed LC. METHODS: Of 375 successive patients with CTD followed up to University Hospital between 1995 and 2004, 24 patients were diagnosed with LC: 11 (46%) had systemic sclerosis (SSc), 6 (25%) rheumatoid arthritis (RA), 6 (25%) systemic lupus erythematosus (SLE), and 1 (4%) dermatomyositis. We analyzed LC stage, radiological presentation, histological type, patients' smoking status, method of diagnosis, treatment applied, and disease outcome. RESULTS: Average duration of CTD was 13.95 (range 0-30) years. Non-small cell lung cancer (NSCLC) was significantly more frequent than small-cell lung cancer (SCLC). Among patients with NSCLC, 21 patients (85%) presented with stage III or IV. With regard to treatment, 13% patients underwent surgery, 25% chemotherapy, 4% patients combined chemo- and radiotherapy and 58% patients had only supportive therapy. The median survival was 5 months (range 1-96 months). CONCLUSION: The majority of CTD patients who developed LC were diagnosed at advanced stage and had poor survival. Efforts for early detection of LC in CTD patients' group are warranted.

Development of a risk index for prediction of abnormal pap test results in Serbia.

BACKGROUND: Serbia is one of the countries with highest incidence and mortality rates for cervical cancer in Central and South Eastern Europe. Introducing a risk index could provide a powerful means for targeting groups at high likelihood of having an abnormal cervical smear and increase efficiency of screening. The aim of the present study was to create and assess validity ofa index for prediction of an abnormal Pap test result. MATERIALS AND METHODS: The study population was drawn from patients attending Departments for Women's Health in two primary health care centers in Serbia. Out of 525 respondents 350 were randomly selected and data obtained from them were used as the index creation dataset. Data obtained from the remaining 175 were used as an index validation data set. RESULTS: Age at first intercourse under 18, more than 4 sexual partners, history of STD and multiparity were attributed statistical weights 16, 15, 14 and 13, respectively. The distribution of index scores in index-creation data set showed that most respondents had a score 0 (54.9%). In the index-creation dataset mean index score was 10.3 (SD-13.8), and in the validation dataset the mean was 9.1 (SD=13.2). CONCLUSIONS: The advantage of such scoring system is that it is simple, consisting of only four elements, so it could be applied to identify women with high risk for cervical cancer that would be referred for further examination.

Differences in risk factors for cervical dysplasia with the applied diagnostic method in Serbia.

BACKGROUND: In the etiology of cervical cancer not only HPV infection is important, but also other factors such as demographic influences and sexual and reproductive health attitudes, as well as others related to preventive measure usage (or non usage). The aim of this study was to examine factors associated with cervical dysplasia in asymptomatic women who were examined by routine cytology and cervical biopsy for early detection of cervical cancer. MATERIALS AND METHODS: Socio-demographic and other characteristics were obtained from medical files of 85 examinees with pathologic cytologic findings (Pap test) and histopathologic (HP) findings after biopsy. RESULTS: According to the Pap test result, a greater probability for development of cervical dysplasia was noted with examinees having a larger number of sexual partners (OR= 5.01, 95% CI 1.04-24.10), and those who are afraid of the Pap finding. Risk factors for development of cervical dysplasia according to the bioptic finding were early beginning with sexual activities, presence of any STD in personal medical history and fear of the Pap test finding. CONCLUSIONS: The only risk factor found to be important for both methods was fear of the Pap testing finding.

Doppler parameters of the maternal hepatic artery blood flow in normal pregnancy: maternal hepatic artery blood flow in normal pregnancy.

OBJECTIVE: Objective of our study was to evaluate changes in Doppler resistance indices in the common hepatic artery during normal pregnancy. STUDY DESIGN: Cross-sectional study included 210 healthy pregnant women gestational age 6-40 weeks, 40 healthy non-pregnant women and 30 women after delivery. We divided all pregnant women by pregnancy trimester. We registered pulsatility index (PI) and resistive index (RI) in the common hepatic artery and compared the evaluated values among non-pregnant women and women in first, second and third trimester and post partum and tested correlation of both parameters with gestational age. Statistical analysis was done by Chi square test, one-way ANOVA followed by post-hoc test and two-tailed Pearson and Spearman correlation. The difference was considered to be significant if p<0.05. RESULTS: We found lower values of PI and RI in the third trimester compared to control group and first and second trimester (p<0.01). There is negative correlation between the values of PI and RI with the gestation (p<0.01). CONCLUSION: Hepatic artery resistance indices decrease during the third trimester of pregnancy. This decrease may be the result of systemic arterial vasodilatation in normal pregnancy. The arterial resistance indices may be more useful for the evaluation of liver blood flow over the total blood flow as they are more reliable, being angle independent, easier to obtain, reflect vascular changes and might help in quick orientation about liver blood flow in pregnancies complicated by preeclampsia and HELLP syndrome. Our study is a pilot one, and further studies are needed to establish nomograms for the PI and RI during the gestation.

[Comparison of two different types of hormone therapy effects on haemostatic parameters in early postmenopausal women].

INTRODUCTION: Most postmenopausal women have some of menopausal symptoms due to oestrogen deprivation. Many therapeutic options are available for managing menopausal problems. However, hormone therapy is associated with a heightened risk for thromboembolic events. OBJECTIVE: To investigate the effects of different types of hormone therapy on some haemostatic parameters. METHODS: This randomized, controlled study included 56 healthy, early postmenopausal women aged 46-58 years on different types of hormone therapy (tibolone 2.5 mg/day, 25 women, or CCHT 2 mg estradiol plus 1 mg norethisteron acetate, 31 women) and 20 healthy postmenopausal women of the same age receiving placebo. Effects of these 2 medicaments on some haemostasis parameters were measured 3 and 6 months after the onset of treatment. RESULTS: Short-term use (3 months) of both tibolone and CCHT had a detrimental effect on antithrombin, protein C and protein S levels (decreased), and even more so in the group treated with CCHT. Plasminogen-activator inhibitor type 1 levels were decreased by both tibolone and CCHT, but more so by CCHT; thrombin-antithrombin complex were increased in both groups. There were no changes in haemostatic parameters between 3-month and 6-month treatment in any group. CONCLUSION: Both therapeutic options are associated with an activation of thrombogenic and fibrinolytic markers within 3 months of use. Tibolone appears to produce a better balance between thrombogenesis and fibrinolysis. Since our results show a lower incidence of thrombotic events, further studies are required.

[Fetal cerebral-umbilical Doppler ratio in prediction of fetal distress in patients with preeclampsia].

BACKGROUND/AIM: The use of color Doppler ultrasonography provides noninvasive observation, confirmation and quantification of pathophysiological processes in fetoplacental circulation in pregnant patients. By blood vessel mapping and the obtained waves spectral analysis it is posible to evaluate vascular resistency of the fetus blood vessels. The aim of the study was to evaluate cerebral-umbilical pulsatility index ratio in fetal circulation in prediction of fetal distress in patients with preeclampsia. METHODS: By measurement of pulsatility indices in medial cerebral and umbilical arteries in 400 patients with uncomplicated pregnancy, normal values were calculated for fetuses from 15-40 weeks. In our study group 70 patients with preeclampsia were included. Cerebral-umbilical (C/U) ratio was calculated after pulsatility indices in medial cerebral artery and umbilical artery determining by the spectral Doppler analysis of flow velocity waveforms in these vessels. Fetal outcome was analyzed by measurement of the Apgar score at the 5th minute and fetal pH at birth. RESULTS: The mean C/U ratio values in the third trimester of normal pregnancy were between 1.8 and 1.9. The mean C/U ratio values in the patients complicated with preeclampsia were significantly lower comparing to normal pregnancies (ANOVA, p < 0.05). The mean 5th minute Apgar score in the study group was 6.35 +/- 1.58, and the mean fetal pH at birth was 7.16 +/- 0.15. Linear regression test showed a highly significant correlation between low C/U ratio and fetal pH at birth in patients with preeclampsia (r = 0.49, p < 0.01). CONCLUSION: The C/U ratio values obtained from spectral Doppler analysis in fetal vessels showed a highly significant correlation with fetal pH at birth in the patients with preeclampsia. The results of our study confirmed the reliability of C/U ratio in estimation of fetal condition in preeclamptic patients. Very low C/U ratio values in patients with preeclampsia indicate that in these fetuses fetal acidosis and fetal distress may be expected.

[The effect of anogenital warts on life quality of affected patients].

INTRODUCTION: Anogenital warts represent a clinical manifestation of the infection of the lower female genital tract, human papilloma viruses types 6 and 11. They belong to the group of sexually transmitted diseases and then may be localized either on the female or male genitalia. The aim of the study was to show the effect of anogenital warts on life quality of the affected patients. MATERIAL AND METHODS: The study was conducted on 200 female patients using the standardized questionnaire filled in by patients under the researcher's supervision immediately before laser wart removal. Each question out of 15 could be answered by one of the suggested answers: always, almost always, sometimes, rarely and never. The answer "always" was worth one point, "almost always" two points, "sometimes" three points, "rarely" four points and never "five" points. Life quality was categorized as bad, tolerable, good, very good and excellent. The lower number of points in the questionnaire indicated the worse life quality and the higher number of points demonstrated a better life quality. RESULTS: The study results showed that the highest number of subjects was in the third and fourth decade of life. The presence of anogenital warts had an effect on life quality in most patients. 5% of subjects assessed their life quality as bad, 16% as tolerable, 45% as good and 23% as very good. Only in 11% of patients the presence of anogenital warts did not have any effect on life quality (chi2 = 121.680, p < 0.001). CONCLUSION: The presence of anogenital warts has a significant effect on life quality of affected patients, indicating the significance of their early detection and treatment.

Treatment of heterotopic cervical pregnancy after in vitro fertilization-embryo transfer by using transvaginal ultrasound-guided aspiration and instillation of hypertonic solution of sodium chloride.

OBJECTIVE: To report a case of successful treatment of heterotopic cervical pregnancy resulting from IVF-embryo transfer. DESIGN: Case report. SETTING: Tertiary university clinical center. PATIENT(S): A 31-year-old patient, treated for heterotopic cervical pregnancy, diagnosed in the 6th gestational week. INTERVENTION(S): Transvaginal ultrasound-guided aspiration of cervical pregnancy and instillation of hypertonic solution of sodium chloride, upon ligation of descending cervical branches of the uterine arteries. MAIN OUTCOME MEASURE(S): Patient recovery and further maintenance of intrauterine twin pregnancy. RESULT(S): The cervical pregnancy was successfully aborted, and the intrauterine twin pregnancy was successfully maintained. CONCLUSION(S): The intervention applied may be used in treatment of heterotopic cervical pregnancy.

[The significance of the ovarian arteriolar vasodilatation in pathogenesis of the ovarian hyperstimulation syndrome].

Ovarian hyperstimulation syndrome is a complication of the ovulation stimulation, most commonly by gonadotrophins. It frequently occurs in patients included in in vitro fertilization program. The exact mechanism of development of this syndrome has not been elucidated yet. The basic pathogenic mechanism of development of this syndrome is vasodilation of the ovarian blood vessels. Dilated ovarian blood vessels become permeable. Permeability of dilated ovarian blood vessels is more increased by released ovarian mediators. Due to increased permeability of the blood vessels, there is leakage of the intravascular fluid into the extravascular areas resulting in hypovolemia, edema and ascites. Hypovolemia leads to renal perfusion decrease. Increased salt and water reabsorption occurs in the renal tubules so oliguria develops. Decreased arterial blood volume results in stimulation of the renin-angiotensin-aldosterone system, the sympathetic nervous system as well as the antidiuretic hormone. The activation of the sympathetic nervous system via beta adrenergic receptors stimulates renin release and aldosterone secretion. Renin stimulates release of angiotensin I which transforms into angiotensin II. Angiotensin II increases the pressure and stimulates aldosterone secretion. In patients with this syndrome, there is an elevated plasma endothelin and natriuretic peptide level. Endothelin is an important vasoconstrictor. It increases secretion of renin, aldosterone, catecholamines, antidiuretic hormone, and atrial natriuretic peptide, and enhances the vasoconstrictive effect of norepinephrine and angiotensin II. The platelet number increase together with the elevated factor of blood coagulation and hyperviscosity in a severe form of this syndrome may result in development of intravascular thrombosis. The treatment consists of maintenance of circulatory function, i.e. the increase of effective arterial blood volume by applying the plasma volume expanders.

[Noninvasive diagnosis of fetal anemia in Rh-alloimmunized pregnancies by color Doppler].

UNLABELLED: INTRODUCTION Fetal anemia is usually diagnosed by invasive procedures, such as amniocentesis and cordocentesis. As these procedures carry a substantial risk for pregnancy loss, a nonivasive method for diagnosing fetal anemia is needed. Doppler allows measurement of blood flow velocity in fetal vessels. In anemic fetuses increased velocities in medial cerebral artery (MCA) are registered. The aim of our study was to evaluate if there were changes in blood flow waveforms in anemic fetuses' MCA, and if these changes correlated with values of fetal hematological parameters. MATERIAL AND METHODS: A clinical study evaluated 172 pregnancies of gestational age between 28 and 32 weeks, in which cordocentesis was performed due to maternal Rh-alloimmunization. During sonographic examination we evaluated blood flow velocities and pulsatility index (Pi) in MCA. We registered hematological parameters such as hemoglobin and hematocrit. Based on hemoglobin levels, all fetuses were divided into four groups: nonanemic (140 g/l); mild anemia (120-139.9 g/l); moderate anemia (100-119.9 g/l) and severe anemia requiring intrauterine transfusion (99.9 g/l). We compared mean systolic velocities and Pi between groups and studied the correlation between MCA mean systolic velocities and hemoglobin and hematocrit values. Statistical analysis was done using ANOVA test and parameter linear correlation. The difference was considered to be significant if p < 0. 05. RESULTS: Out of 172 fetuses, 60 (34.09%) were nonanemic, 56 (31.82%) showed mild anemia, 56 (31.82%) moderate anemia and 24 (13.64%) fetuses had severe anemia. Anemic fetuses had significantly higher MCA flow velocities compared to nonanemic fetuses. Values of Pi decreased in severe forms of fetal anemia, but the difference wasn't significant. Levels of hemoglobin and hematocrit showed inverse correlation with the values of MCA mean systolic velocities, while correlation with the values of Pi wasn't observed. DISCUSSION: Cerebral blood flow velocity in medial cerebral artery was assessed to diagnose fetal anemia. MCA mean systolic velocity is increased in anemic fetuses and correlates with the degree of anemia. The main advantage of this parameter is that advanced software programs are not necessary. We can conclude that in cases of Rh-alloimmunization in anemic fetuses increased MCA mean systolic velocities are registered. There is an inverse correlation between MCA mean systolic velocities and hemoglobin and hematocrit values. We suggest that measurements of MCA mean systolic velocities should be used in fetuses at risk for anemia and in selection of fetuses requiring invasive procedures.

[Assessment of maternal cerebral blood flow in patients with preeclampsia].

INTRODUCTION: Systemic vasoconstriction in preeclamptic patients increases vascular resistance, and is manifested by increased arterial blood flow velocity. The aim of the study is to evaluate if there is a change of Doppler indices in maternal medial cerbral artery (MCA) in severe preeclampsia due to: 1) severity of clinical symptoms, 2) the begining of eclamptic attack and 3) the application of anticonvulsive therapy. MATERIAL AND METHODS: A prospective clinical study included 92 pregnant women, gestational age 28-36 weeks. They were divided into three groups: normotensive (n=30), mild preeclampsia (n=33), and severe preeclampsia (n=29). We investigated maternal cerebral circulation by assessing the MCA. We registrated: pulsatility index (Pi), resistance index (Ri), systolic/diastolic ratio (S/D), and the maximum systolic, end diastolic and medium velocity. Patients with severe preeclampsia were divided into two subgroups. subgroup 1 included patients without symptoms of threatening eclampsia (n=18; 62.06%); while subgroup 2 included those with symptoms of preeclampsia (n=11; 37.94%). All patients with severe preeclampsia were treated with magnesium sulfate (MgSO4), and cerebral blood flow was measured before and after the treatment. Statistical analysis was done by oneway ANOVA, Student t-test and t-paired sample test. The difference was considered to be significant if p<0.05. RESULTS: Significantly increased Pi, Ri and all velocities were established in the group of patients with severe preeclampsia compared with the other two groups. In the group with severe preeclamsia we registrated significantly increased values of all velocities (patients with signs of threatening eclampsia). After MgSO4 treatment in patients with severe preeclampsia significantly decreased values of Pi, Ri, S/D ratio and all velocities were registered. DISCUSSION: In the studied group of patients with severe preclampsia we found increased velocity values, Pi and Ri, especially in patients with signs of threatened eclampsia, suggesting that blood vessels changes are most prominent in severe preeclampsia. Cerebral blood flow meassurements can be used as a clinical test for the prediction of eclampsia. Magnesium-sulfate (MgSO4) has a signifficant role in prophylaxis and treatment of eclampsia, and, therefore, positive influence on reduction of cerebral ishemic lesions can be expected. CONCLUSION: We can conclude that changes of the cerebral blood flow can be evaluated by evaluating blood flow velocities in the medial cerebral artery. Velocities tend to increase in severe preeclampsia, especially with signs of threatening eclampsia, and decrease after treatment with mgnesium sulfate. Serial measurements of blood flow in medial cerebral artery in patients with severe preeclampsia may be used in prediction of eclampsia and in evaluation of magnesium sulfate therapy effects.