Neuroactive steroids in the neuroendocrine control of food intake, metabolism, and reproduction.

Neuroactive steroids are a type of steroid hormones produced within the nervous system or in peripheral glands and then transported to the brain to exert their neuromodulatory effects. Neuroactive steroids have pleiotropic effects, that include promoting myelination, neuroplasticity, and brain development. They also regulate important physiological functions, such as metabolism, feeding, reproduction, and stress response. The homoeostatic processes of metabolism and reproduction are closely linked and mutually dependent. Reproductive events, such as pregnancy, bring about significant changes in metabolism, and metabolic status may affect reproductive function in mammals. In females, the regulation of reproduction and energy balance is controlled by the fluctuations of oestradiol and progesterone throughout the menstrual cycle. Neurosteroids play a key role in the neuroendocrine control of reproduction. The synthesis of neuroestradiol and neuroprogesterone within the brain is a crucial process that facilitates the release of GnRH and LH, which in turn, regulate the transition from oestrogen-negative to oestrogen-positive feedback. In addition to their function in the reproductive system, oestrogen has a key role in the regulation of energy homoeostasis by acting at central and peripheral levels. The oestrogenic effects on body weight homoeostasis are primarily mediated by oestrogen receptors-α (ERα), which are abundantly expressed in multiple brain regions that are implicated in the regulation of food intake, basal metabolism, thermogenesis, and brown tissue distribution. The tight interplay between energy balance and reproductive physiology is facilitated by shared regulatory pathways, namely POMC, NPY and kisspeptin neurons, which are targets of oestrogen regulation and likely participate in different aspects of the joint control of energy balance and reproductive function. The aim of this review is to present a summary of the progress made in uncovering shared regulatory pathways that facilitate the tight coupling between energy balance and reproductive physiology, as well as their reciprocal interactions and the modulation induced by neurosteroids.

Resveratrol and Reproductive Health.

Resveratrol (RSV), a plant-derived polyphenol, demonstrates broad-spectrum health benefits, including anti-proliferative, anti-inflammatory, antidiabetic, anti-ischemic and antioxidant effects. The aim of this review is to give an important heads-up regarding the influence of RSV as a phytoestrogen, RSV effects on most common pregnancy-related complications, as well as its impact on the embryogenesis, spermatogenesis, and women's reproductive health. Considering the important implications of RSV on human reproductive health, this overview could provide a groundwork, encouraging more detailed research at the clinical level.

Prevalence, Risk Factors, and Pathophysiology of Nonalcoholic Fatty Liver Disease (NAFLD) in Women with Polycystic Ovary Syndrome (PCOS).

Background: Polycystic Ovary Syndrome (PCOS) is one of the most common endocrine disorders in women's reproductive period of life. The presence of nonalcoholic fatty liver disease NAFLD, one of the leading causes of chronic liver disease in the Western world, is increased in women with PCOS. This review aims to present current knowledge in epidemiology, pathophysiology, diagnostics, and treatment of NAFLD in PCOS with an emphasis on the molecular basis of development of NAFLD in PCOS women. Methods: Authors investigated the available data on PCOS and NAFLD by a MEDLINE and Pub Med search during the years 1990-2021 using a combination of keywords such as "PCOS", "NAFLD", "steatohepatitis", "insulin resistance", "hyperandrogenaemia", "inflammation", "adipose tissue", and "obesity". Peer-reviewed articles regarding NAFLD and PCOS were included in this manuscript. Additional articles were identified from the references of relevant papers. Results: PCOS and NAFLD are multifactorial diseases, The development of NAFLD in PCOS women is linked to insulin resistance, hyperandrogenemia, obesity, adipose tissue dysfunction, and inflammation. There is the possible role of the gut microbiome, mitochondrial dysfunction, and endocannabinoid system in the maintenance of NAFLD in PCOS women. Conclusions: There is a need for further investigation about the mechanism of the development of NAFLD in PCOS women. New data about the molecular basis of development of NAFLD in PCOS integrated with epidemiological and clinical information could influence the evolution of new diagnostic and therapeutic approaches of NAFLD in PCOS.

Maternal glycoregulation in pregnancies complicated by diabetes mellitus in the prediction of fetal echography findings and perinatal outcomes.

AIM: We aimed to determine maternal hemoglobin A1c (HbA1c) levels and pregestational body mass index (BMI) as the predictors of glycemic control and its importance for fetal echography findings and perinatal outcomes in pregnancies complicated by diabetes mellitus (DM). METHODS: Our intention was to evaluate how BMI and HbA1c levels might be used to predict fetal interventricular septum (IVS) thickness, atrioventricular inflow early diastole (E)/ atrial systole (A) velocity ratio, and perinatal outcomes. Patients in the 38th gestational week were divided into three groups according to their insulin therapy: (i) patients with gestational diabetes mellitus (GDM) treated only with dietary changes (GDM group, n = 32); (ii) patients with GDM treated with insulin therapy (DM2 group, n = 27); and (iii) patients with type 1 DM (DM1 group, n = 22). RESULTS: In the DM1 group, we found statistically significant correlations between BMI and IVS thickness (P = 0.036), HbA1c and IVS thickness, as well as the mitral E/A velocity ratio (P = 0.013 vs P = 0.007). In this group, HbA1c showed a statistically significant correlation to neonatal birth weight (P = 0.037) and BMI influenced on appearance respiratory distress syndrome in neonates in DM1 group (P = 0.027). The values of HbA1c predict neonatal respiratory distress syndrome in DM2 and GDM groups (P = 0.036). CONCLUSION: As good predictors of maternal glycoregulation, BMI and HbA1c levels determine fetal echography findings as well as neonatal outcomes in pregnancies complicated by DM.

[Poor Ovarian Response to Stimulation for In Vitro Fertilization].

The term "poor respond (POR) patients" is used for the group of women who respond badly to usual doses of gonadotropins in in vitro fertilization (IVF) treatments; the consequence is low pregnancy rate. A consensus was reached on the minimal criteria needed to define POR. At least two of the following three features must be present: 1. advanced maternal age (40 years or more) 2. previous POR (3 or less oocytes with a conventional stimulation protocol) 3. abnormal ovarian reserve (AMH 0.5-1.1 ng/ml or AFC 5-7).The aim is to find better therapeutic options for these patients. Increased levels of day 3 follicle stimulating hormone (FSH) and estradiol (E2), as well as decreased levels of anti-Müllerian hormone (AMH) and antral follicle count (AFC), can be used to assess ovarian reserve, as indirect predictive tests. A larger number of well designed, large scale, randomized, controlled trials are needed to assess the efficacy of different management strategies for poor responders: flare up gonadotropin releasing hormone (GnRH) agonist protocols, modified long GnRH agonist mini-dose protocols, luteal initiation GnRH agonist stop protocol, pretreatment with estradiol--GnRH antagonist in luteal phase, natural cycle aspiration or natural cycle aspiration GnRH antagonist controlled, adjuvant therapy with growth hormone or dehydroepiandrosterone (DHEA). The results of up to now used protocols are unsatisfactory and stimulation of the ovulation in poor responders remains a challenge, especially when bearing in mind that in the majority of cases the patients will be menopausal in relatively short period of time.

The Role of Potassium Channels in the Vasodilatation Induced by Resveratrol and Naringenin in Isolated Human Umbilical Vein.

Preclinical Research Potassium (K+ ) channels have a key role in the maintenance of smooth muscle tone; a variety of agonists can modify the tone by altering K+ -channel activity. The aim of this study was assess the effects of the phenols, resveratrol, and naringenin on K+ -channels of the vascular smooth muscle. Segments of human umbilical vein (HUV) without endothelium were precontracted using serotonin (100 µM) or 100 mM K+ to derive cumulative concentration-response curves using increasing concentrations of resveratrol or naringenin. K+ -channel inhibitors were added in the bath before resveratrol (1-100 µM) or naringenin (0.01-1 mM) in assess the role of K+ -channels in their effects on HUV precontracted by serotonin. 4-Aminopiridine (4-AP; 1 mM), a nonselective blocker of voltage-dependent, tetraethylammonium (TEA; 1 mM) and barium chloride (1 mM), a nonselective blocker of Ca2+ -dependent and inward rectifier K+ -channels (respectively) induced significant shifts to the right (P < 0.05) of resveratrol. concentration-response curves. The effect of naringenin was antagonized by 4-AP (1 mM). 4-AP-, TEA-, and barium chloride-sensitive K+ -channels are probably involved in the resveratrol vasodilatatory effect, while naringenin seems to affect 4-AP-sensitive K+ -channels. However, other mechanisms of vasodilation induced by polyphenols could not be excluded. Drug Dev Res, 2015. © 2015 Wiley Periodicals, Inc.

Fetal and maternal plasma homocysteine levels during the second half of uncomplicated pregnancy.

OBJECTIVE: To measure fetal and maternal plasma homocysteine (Hcy) concentrations in uncomplicated pregnancies. METHODS: Paired maternal venous and fetal umbilical cord blood (n = 81) samples were evaluated for plasma Hcy and vitamin B12 levels, in addition to eight neonatal umbilical cord blood samples obtained immediately following delivery. RESULTS: Both fetal and maternal Hcy concentrations were positively correlated with advancing gestational age (ρ = 0.44, p < 0.0001; and ρ = 0.27, p < 0.05, respectively). Fetal plasma Hcy concentrations [2.2 µmol/l (IQR: 2.0-3.2)] were significantly lower than both neonatal umbilical vein [5.0 µmol/l (IQR: 4.4-6.5); p < 0.001] and maternal plasma Hcy levels [4.4 µmo/l (IQR: 3.4-5.4); p < 0.001]. In addition, Hcy values at term were higher in the umbilical vein compared with the umbilical artery [5.0 µmol/l (IQR: 3.4-5.4) versus 4.2 µmol/l (IQR: 3.7-5.5), respectively; p = 0.016]. Significant correlation was noted and between fetal and maternal Hcy levels (ρ = 0.50, p < 0.0001), while fetal Hcy was negatively correlated with maternal B12 concentrations (ρ = -0.32, p < 0.001). CONCLUSIONS: Fetal Hcy levels were significantly lower than maternal and neonatal levels and correlated with gestational age across the second half of pregnancy.

The different effects of resveratrol and naringenin on isolated human umbilical vein: the role of ATP-sensitive K⁺ channels.

The blood flow from the placenta to the fetus depends on human umbilical vein (HUV) vascular tone. ATP-sensitive K(+) (K(ATP)) channels link the metabolic state of the cell to membrane potential, and their activation in the HUV represents protection against hypoxia. The aims of our study were to assess the effects of resveratrol and naringenin on the HUV and to define the roles of K(ATP) channels in their effects. Serotonin or 100 mM K(+) were used for precontraction of the HUV without endothelium. The cumulative concentration-response curves were obtained by adding increasing concentrations of resveratrol or naringenin. Glibenclamide was used, in order to test the role of K(ATP) channels in its effect. Resveratrol induced more potent vasodilatation of serotonin- and 100 mM K(+)-precontracted HUV than naringenin. Glibenclamide induced significant shift to the right of the concentration-response curves of resveratrol and P1075 (a specific opener of K(ATP) channels). Western blotting showed that HUV expressed protein Kir6.1. Thus, resveratrol and naringenin produce dilatation of HUV. It seems that K(ATP) channels are involved in the relaxation of HUV induced by resveratrol, while naringenin seems to interact with other ion channels. The K(+) channel-independent mechanism(s) of these polyphenols could not be excluded.

Fetal free thyroxine concentrations in pregnant women with autoimmune thyroid disease.

CONTEXT: Fetuses from mothers with autoimmune thyroid disease (AITD) may be affected by antithyroid antibodies, antithyroid drugs, and iodine. OBJECTIVE: The study correlated fetal free T(4) (fT4) with fetal ultrasound parameters and maternal thyroid function, thyroid antibodies, and medication dose from mothers with AITD. DESIGN AND SETTING: The study was designed as a prospective cohort study and conducted in an academic referral center. PATIENTS: Eighty-three of 85 women with AITD completed the study; 38 were treated for hyperthyroidism and 25 for hypothyroidism, and 20 were euthyroid. MAIN OUTCOME MEASURES: Outcomes were as follows: 1) fetal-fT4, TSH, ultrasound parameters (morphology, biometrics, heart rate); and 2) maternal-fT4, TSH, antithyroid drug dose, and antithyroid antibodies, thyroid peroxidase and TSH receptor (TRAK). Parameters were determined at the same time, between the 22nd and 33rd wk gestation. RESULTS: A total of 48.3% of fetuses from hyperthyroid mothers, 60% of fetuses from hypothyroid mothers, and 10% of fetuses from euthyroid mothers had elevated fT4 levels (P = 0.006). In hypothyroid mothers, the presence of both thyroid antibodies was related to fetal hyperthyroidism, whereas absence was related to fetal euthyroidism (P = 0.019). Hyperthyroid mothers (TRAK-positive, thyroid peroxidase-negative) with hyperthyroid fetuses had significantly higher mean TRAK than hyperthyroid mothers with euthyroid fetuses (13.7 vs. 3.7 IU/liter; P = 0.02). Fetal fT4 correlated weakly negatively with maternal TSH within the normal range, but not with ultrasound parameters or with antithyroid drug dose. CONCLUSION: High fetal fT4 levels were unexpectedly frequent in women with AITD, including maternal autoimmune hypo- and hyperthyroidism. Further studies are needed, as well as noninvasive methods to assess fetal thyroid function.

Altered response of human umbilical artery to 5-HT in gestational diabetic pregnancy.

The aim of this investigation was to evaluate serotonin (5-HT) action on isolated human umbilical arteries (HUA) from normal and gestational diabetes mellitus (GDM) pregnancies. 5-HT caused HUA contraction in a concentration-dependent manner in both investigated groups but with lower efficacy in GDM. After endothelial denudation or in the presence of indomethacin (cyclooxygenase inhibitor), the 5-HT-evoked response was comparably augmented, but only in arteries from uncomplicated pregnancies. 5-HT contractions were unchanged by L-NOARG (NO-synthase inhibitor) or glibenclamide (K(ATP) channel blocker) in both investigated groups. Whereas nifedipine (Ca(2+) channel blocker) reduced the contractile effect of 5-HT and was more potent in GDM, ouabain (Na(+)/K(+)-ATPase inhibitor) caused the contraction of HUA prior to 5-HT addition in both groups, but with a significantly reduced effect in GDM. In vascular rings from GDM, methiothepin (a 5-HT(1)/5-HT(2) receptor antagonist) significantly reduced 5-HT-induced contraction to a similar extent as compared to uncomplicated pregnancies. Ketanserin (a 5-HT(2A) receptor antagonist) produced a concentration-dependent inhibition of the 5-HT effect in GDM. In conclusion, in normal pregnancies, 5-HT produced a concentration- and endothelium-dependent contraction of HUA, most probably via endothelial prostacyclin. In contrast, the contractile effect of 5-HT in GDM was reduced with apparent endothelial dysfunction. In both normal and diabetic pregnancies, voltage-gated Ca(2+) channels and Na(+)/K(+)-ATPase contribute to the 5-HT-evoked contraction, as well to the regulation of basal vascular tone, but those actions were notably impaired in GDM. In uncomplicated and diabetic pregnancies, the transduction mechanism of 5-HT involves activation of mixed population of 5-HT(1) and 5-HT(2A) receptors in the HUA.

[Quantitative analysis of lamellar bodies in amniotic fluid as fetal pulmonary maturity indicator].

BACKGROUND/AIM: Although lamellar bodies have been the center of interest over the last years, the published results of fetal pulmonary maturity determination according to their concentration in amniotic fluid are controversial. The aim of this study was to determine the significance of lamellar bodies, as well as the ratio lecithin/sphingomyelin (L/S) in amniotic fluid for the assessment of fetal pulmonary maturity. METHODS: This prospective 2-year study included 102 female examinees, ranging from 17 to 44 years of age, in whom lamellar bodies concentrations in amniotic fluid were determined to check the efficacy of the applied therapy for obtaining arteficial fetal pulmonary maturity. The shake test was applied as a comparative test for determining a quantitative L/S ratio. To determine a fetus maturity and development stage we followed up biparietal diameter, abdominal circumference, femure length, ponderal index at birth and body mass. RESULTS: Out of a total of 102 amniocenteses within a period from 26th to 40th gestation week only 70 results were considered due to 32 unknown neonatal outcomes. Biparietal diameter was 224-362 mm, femur length 56 - 78 mm, ponderal index 1.22-2.84, fetus body mass 1300-4 350 g. There was found a significant relation between gestation age and lamellar bodies concentration (R = 0.396398, p < 0.01), as well as between gestation age and the ratio L/S (R = 0.691297, p < 0.01). Also, there was a significant correlation of lamellar bodies concentration to the ratio L/S determined (R = 0.493609, p < 0.01). CONCLUSION: Determination of lamellar bodies concentration values is a reliable method to confirm fetal pulmonary maturity.

The role of antioxidant vitamins in hypertensive disorders of pregnancy.

Preeclampsia (PE) is an important and a leading cause of both maternal morbidity and adverse perinatal outcomes. Despite progress in perinatal medicine for patients with an established diagnosis of PE, a therapeutic approach other than termination of pregnancy was unsuccessful. Women predisposed to PE begin pregnancy with a certain degree of endothelial dysfunction, a lesion that precedes shallow placentation. The proposed sequence of events comprises endothelial dysfunction, defective trophoblast invasion, and consequential impaired placental perfusion, immune maladaptation and inflammation. The possible link between these could be oxidative stress by excessive production of reactive oxygen species coupled with inadequate or overwhelmed antioxidant defense mechanisms. These defense mechanisms, involving antioxidant vitamins and enzyme systems, may restrain the extent of damage caused by oxidative stress. Markers of oxidative stress in women with established PE were confirmed. Accordingly, these findings support an expected beneficial effect of antioxidant therapy in the prevention of PE and other pregnancy-related disorders. Numerous studies have been carried out in order to investigate this possible and simple prophylactic and/or therapeutic approach in prevention of oxidative stress and eventual reduction of PE and its perinatal complications. In this review the role of vitamin antioxidants in prevention and treatment of PE is discussed. Despite the logic behind using antioxidant vitamins, the data, thus far, are at best conflicting.

Chorionic villus sampling significantly affects fetal cardiovascular function.

OBJECTIVE: To assess the effects of chorionic villus sampling (CVS) on fetal heart rate (FHR). METHODS: A prospective longitudinal study was conducted among 300 patients undergoing transabdominal CVS between 8 and 13 weeks of gestation. Duration of the procedure, number of needle passes, sample weight, maternal age, fetal gender, and FHR response to CVS were recorded. RESULTS: The FHR before but not after CVS was inversely correlated with gestational age (r = -0.406, p < 0.001). Conversely, following CVS, no correlation was observed between FHR and gestational age (r = -0.06, p = 0.27). The difference between FHR after CVS and that obtained before CVS (delta FHR) increased with increasing gestational age at sampling (r = 0.372, p < 0.0001), decreased with increasing specimen weight (r = -0.16, p = 0.01) and increased with increasing maternal age (r = 0.22, p < 0.0001). Duration of the procedure, fetal gender and number of needle passes did not affect delta FHR. Multiple logistic regression indicated that gestational age at CVS and maternal age but not the other variables significantly affected delta FHR and together they accounted for over 22% of the variance (R(2) = 0.224, p < 0.0001). CONCLUSIONS: In summary, our results suggest that acute fetal hemodynamic changes accompany CVS and that these changes vary with gestational age.

Pharmacological evaluation of bradykinin effect on human umbilical artery in normal, hypertensive and diabetic pregnancy.

The objective of this investigation was to compare bradykinin (BK) action on isolated intact or denuded human umbilical artery (HUA) in normal pregnancy, pregnancy-induced hypertension (PIH) and gestational diabetes mellitus (GDM). Bradykinin contracted HUA in a concentration-dependent manner in all investigated groups. Control BK contractions were unchanged by L-NOARG (NO-synthase inhibitor), glibenclamide (K(ATP) channel blocker), or des-Arg(9)(leu(8))-BK (B(1) antagonist), while were reduced by indomethacin (cyclooxygenase inhibitior) or nifedipine (Ca(2+) channel blocker). After endothelial denudation in GDM, concentration-response curve for BK was shifted to the left in relation to control HUA from normal pregnancy. OKY-046 (thromboxane A(2) -synthase inhibitor) displaced concentration-response curve for BK to the right in PIH, whereas reduction in maximal contraction was obtained in HUA from GDM. Ouabain (Na(+)/K(+)-ATPase inhibitor) contracted HUA prior to BK addition in all groups. Apamin (small conductance K(Ca) channel blocker), TEA (non-selectve K(+) channel blocker) or Ba(++) (K(IR)(+) channel blocker) augmented maximal BK contractions in normal pregnancy, PIH and GDM, respectively. HOE 140 (B(2) antagonist) produced concentration-dependent inhibition of BK effect in all groups. Collectively, in HUA from all groups BK evoked vasoconstriction via smooth muscle B(2) receptors. Intact endothelium provided additional modulation of BK contraction in GDM. Contribution of contractile cyclooxygenase products to BK action was demonstrated, and in PIH and GDM thromboxane A(2) was also involved. Voltage-gated Ca(2+) channels and Na(+)/K(+)-ATPase contribute to the BK contraction, and to the regulation of basal vascular tone, respectively. Diverse K(+) channels modulate BK contraction in HUA by preventing excessive vasoconstriction.

[Gross characteristics of placentas from an assisted reproduction program].

INTRODUCTION: Even though placentas from assisted reproduction programs often differ from placentas of women who conceived naturally, they are rarely examined. The aim of our investigation was to determine some gross characteristics of placentas of women who conceived with assisted reproduction. MATERIAL AND METHODS: We examined 30 placentas from an assisted reproduction program (20 from in vitro fertilization and 10 from intrauterine insemination) and 30 placentas of women who conceived naturally. All women were age matched. All the women were at term. RESULTS: The mean weight of placentas from assisted reproduction program was 573 g and of those after natural conception--582.67g. The mean length of the umbilical cords was 64.3cm after assisted reproduction and 66.3cm after natural conception. The mean placenta thickness after assisted reproduction was 2,22 cm and after natural conception 2.28 cm. Eight placentas of the study group had a marginal insertion of the umbilical cord, which lead to a statistically significant difference when compared to placentas of women who conceived naturally: chi-square = 7.07; p>0.01. DISCUSSION: Marginal cord insertion into the placenta after assisted reproduction is also often described in the literature (as a possible "consequence" of embryo-transfer). CONCLUSION: There were no statistically significant differences in the mean weight and dimensions of placentas, length of the umbilical cord, gross pathological features of placentas and cords, mean birth weight of babies and placental/fetal ratios between women from assisted reproduction program and those who conceived naturally.

Micronutrients in women's reproductive health: I. Vitamins.

Proper nutritional status of women before, during, and after pregnancy is an important element of reproductive health. It maintains maternal health and reduces the risk of adverse pregnancy outcome, birth defects and chronic disease in children later in postnatal life. Pregnancy creates a special metabolic demand for high-quality nutrients. With careful food selection, it is possible to obtain most of the recommended levels of nutrients. Apart from the dietary intake, nutrition is highly dependant on economic status, social and cultural environment, and personal habits of the mother. Nutritional imbalance could cause detrimental effects to the pregnant woman, influence pregnancy outcome, and impair breast milk composition. Despite the extensive research, we still do not have a complete understanding how nutritional status of the mother influences her health as well as fetal growth and development. It is well known that fetal growth and development is strongly linked with maternal supply of essential nutrients, e.g. vitamins. The exact role of the variety of micronutrients in fetal growth and development has yet to be explored in detail. It is estimated that up to 30% of pregnant women suffer from a vitamin deficiency. Without supplementation, about 75% would show a deficit of at least one vitamin. Moreover, multivitamin deficit combinations often co-exist, and subclinical depletations are probably common; consequences could be severe. Studies carried on in developing countries have shown that improving micronutrient intake in deficient women can reduce maternal morbidity and mortality. Also, proper maternal intake of important micronutrients directly enhances the quality of breast milk. To meet the increasing demands during pregnancy and the breastfeeding period women should not be dependent only upon the dietary intake: adequate reserve is essential for the successful pregnancy outcome.

Micronutrients in women's reproductive health: II. Minerals and trace elements.

It is widely accepted that micronutrients have a major function in many periods of women's life, particularly during pregnancy and lactation. Inadequate stores or intake of micronutrients might have adverse effects both to the mother (hypertension, anemia, complications of labor) and the fetus (congenital malformations, pre-term delivery, intrauterine growth retardation). The effect of improper nutrition is influenced by gestational age, severity of deficiency, or both. Generally, the daily requirements in minerals and trace elements are easily met in women having a balanced diet. Such diet during pregnancy should provide the recommended daily allowance of all nutrients except elemental iron. Consequently, deficiency states are supposed to be rare in developed countries, and supplementation should be made on an individual basis. On the other hand, nutritional deficiencies during pregnancy might be difficult to detect. Studies from developing countries where micronutrient malnutrition is common during pregnancy gave us strong evidence that supplementation of certain trace elements and minerals could prevent some of the most severe adverse pregnancy outcomes. While some micronutrients have been studied extensively (e.g. calcium, iron, zinc, iodine), much less is known about others. It has been shown that multiple micronutrient deficiencies, rather than single deficiencies, are common. Our knowledge about the significance of interactions between micronutrients in relation to pregnancy outcome is limited. The role of these interactions in improving pregnancy outcome need to be investigated more precisely. According to the summarized data, the potential benefits of routine supplementation seem to outweigh any potential adverse reaction that can be attributed to their consumption.

[Medicamentous abortion with mifepristone and misoprostol in Serbia and Montenegro].

BACKGROUND/AIM: Medicamentous abortion was first introduced in Serbia and Montenegro in September 2001. The aim of this study was to assess the efficiency, side effects, and acceptability of medicamentous abortion using mifeprostone orally (600 mg), and 48 hours later, misoprostol both orally and vaginally in different regiments in our population (400 mcg, 600 mcg, 800 mcg). METHODS: A total of 235 consecutive women with pregnancies up to 49 days of gestational age were assigned to 4 groups according to the different misoprostol regiment (group I 400 mcg, group II 600 mcg, group III 800 mcg orally, and group IV 800 mcg both orally and vaginally). The principal outcome measure was a successful abortion defined as a complete expulsion of intrauterine contents without a need for surgical intervention 14 days after the procedure. Other outcome measures were the following: drug related effects, and adverse effects related to the abortion process. RESULTS: In general, the success rate was 50%, 89.48%, 75% and 92.11% in the groups I, II, III, and IV, respectively, as judged by the complete expulsion of the intrauterine contents without surgical intervention (t1:4 = 7.005; t2:4 = 0.3872, t3:4 = 2.9784, p < 0.01). The incidence of adverse effects (vomiting, abdominal pain, bleeding, and fever) was low in general, but among our groups it occurred mostly with the higher doses of orally applied misoprostol (800 and 600 mcg). Only one case required urgent curettage for heavy vaginal bleeding, and two blood transfusions, as well. No cases of intact pregnancies were recorded in the study. CONCLUSION: Our study showed that a mifepristone dose of 600 mg orally, and misoprostol 400 mcg orally and 400 mcg vaginally were most effective. Thus, a combination of mifepristone and misoprostol for medicamentous abortion should take a higher proportion in the termination of early pregnancy in our population.

Preterm and premature rupture of membranes in pregnancies after in vitro fertilization.

Women conceiving by assisted reproduction are at higher risk for preterm and premature rupture of membranes. The aim of our study was to estimate and compare incidence of preterm premature rupture of membranes in singleton pregnancies of women who conceived by intrauterine insemination and in vitro fertilization, from 1999 to 2003. We investigated 87 women from the intrauterine insemination, and 102 from the in vitro fertilization program. There were no statistically significant differences in regard to preterm and premature rupture of membranes: p > 0.75 in two groups. The incidence of premature rupture of membranes was 2.30% (after intrauterine insemination) and 2.94% (after in vitro fertilization). There was no statistically significant differences in regard to preterm and premature rupture of membranes in women who conceived by insemination and in vitro fertilization. Estimated incidence of preterm and premature rupture of membranes was similar to the literature data and also similar to incidence after natural conception.