Perinatal outcome of singleton pregnancies following in vitro fertilization.

PURPOSE OF INVESTIGATION: To determine whether in vitro fertilization/intracytoplasmatic sperm injection (IVF/ICSI) singleton pregnancies are at increased risk for maternal and fetal complications than spontaneous singleton conceptions. MATERIALS AND METHODS: The pregnancy outcome of 634 singleton pregnancies after IVF/ICSI delivered at the Clinic for Gynecology and Obstetrics during the period January 2006 to January 2010 were compared to 634 matched singleton controls, matched one by one by age, parity, education, and body mass index (BMI). Differences in pregnancy outcomes between the groups were assessed using Student's t-test with Yates correction for continuous variables and Chi-squared test for categorical variables. RESULTS: The mean gestational age at delivery of the IVF group was 38.13 +/- 1.72 weeks, slightly shorter than spontaneously conceived singletons at 38.65 +/- 1.79 weeks. The diagnosis of gestational diabetes mellitus (GDM) was frequently made in the IVF group (11.82% vs 8.35%, t = 2.052, p < 0.05). Total preterm delivery rate of IVF pregnancies was 9.30%, significantly higher than the controls 5.85% (t = 2.33, p < 0.05), especially at the 30-32 weeks gestation period. The predominant mode of delivery after IVF pregnancy was cesarean section (80.75% vs 31.38% at spontaneously conceived, t = 17.71, p < 0.001), while vaginal route was the choice for naturally originated pregnancies 68.6% vs 19.24% (p < 0.01). No differences were found in the average birth weights, LBW, VLBW, SGA, and LGA regarding the pregnancy origin. Perinatal mortality rates were comparable among singletons with different pregnancy origin. CONCLUSIONS: Singletons from IVF/ICSI pregnancies have poorer perinatal outcome associated with higher rates of cesarean sections, preterm birth and prematurity, fetal malpresentation (breech presentation), and the occurrence of maternal GDM in pregnancy.

Correlation of progesterone levels on the day of oocyte retrieval with basal hormonal status and the outcome of ART.

This study aimed to assess whether basal hormonal levels can predict the levels of progesterone (P4) on the day of oocyte retrieval (OR) and examine the impact of P4 levels on the day of OR on the outcome of assisted reproduction. One hundred sixty-four patients that were enrolled in the assisted reproduction procedure were classified according to their P4 levels on the OR day (< 2 ng/ml vs. ≥ 2 ng/ml). Patients who had P4 levels < 2 ng/ml had significantly higher follicle stimulating hormone (FSH) levels and significantly lower anti-Mullerian hormone (AMH) levels. More than half of patients with P4 levels < 2 ng/ml on the OR day got pregnant and delivered healthy infants. There was a significant correlation between lower FSH values and higher P4 values at OR and between higher AMH values and higher P4 values on the day of OR. Regression analysis showed that high FSH levels are the most important factor that can reliably imply lower P4 levels on OR day. Our study confirmed that lower basal FSH levels can predict the levels of P4 on the OR day. Moreover, lower levels of P4 on the day of OR are associated with a positive outcome in assisted reproduction.

Cervical and duodenal polyps and their malignant alterations--case report.

During routine examination of a 32-year-old patient, a cervical polyp was found and CIN III was confirmed by biopsy. After performing colposcopy, biopsy and establishing CIN III as well as performing gastroscopy where a duodenal polyp was found, thorough diagnostic exams and therapy were carried out. Complete duodenal resection and conization were performed. The medical board decided that neither further radiation nor chemotherapy was needed.

Effect of oxytocin as a partial agonist at vasoconstrictor vasopressin receptors on the human isolated uterine artery.

1. The effect of oxytocin on endothelium-intact and endothelium-denuded segments of the human uterine artery rings was investigated. 2. In both types of preparation oxytocin induced contraction of human uterine artery with similar potency and efficacy (pEC50 values: 6.95 +/- 0.05 vs 7.06 +/- 0.01; maximal response values: 61 +/- 4.1% vs 63 +/- 5.1% for arteries with and without endothelium, respectively). 3. In contrast, human uterine arteries, both intact and denuded of endothelium, did not respond to the addition of the selective oxytocin receptor agonist, [Thr4, Gly7]oxytocin (10 nM(-1) microM). 4. The vasopressin receptor antagonists, [d(CH2)5Tyr(Me)]AVP (10-100nM) and [d(CH2)5,D-Ile2,Ile4]AVP (300 nM-3 microM) produced parallel rightward shifts of the curves for oxytocin. The Schild plots constrained to a slope of unity gave the following -log K(B) values: [d(CH2)5Tyr(Me)] AVP vs [d(CH2)5,D-Ile2,Ile4] AVP 9.24 vs 6.91 and 9.26 vs 6.84 for human uterine artery with intact and those denuded of endothelium, respectively. In contrast, in both types of preparations the oxytocin receptor antagonist, [d(CH2)5Tyr(OMe), 2Orn8]vasotocin (1 microM), did not significantly affect oxytocin-induced contractions. 5. The calculated pK(A) values for oxytocin itself also did not differ between preparations: 6.56 and 6.43 for human uterine artery with and without endothelium, respectively. In both types of preparations, the receptor reserve (K(A)/EC50) was close to unity (intact vs denuded: 3.9 vs 3.0). 6. It is concluded that, in human uterine artery, oxytocin induces contractions that are not modulated by the endothelium. It is likely that oxytocin acts as a partial agonist on human uterine artery, regardless of the endothelial condition. On the basis of differential antagonists affinity and affinity of oxytocin itself, it is probable that receptors involved in oxytocin-induced contraction in human uterine arteries belong to the V(1A) vasopressin receptors.

Characterization of arginine vasopressin actions in human uterine artery: lack of role of the vascular endothelium.

1. The effect of arginine vasopressin (AVP) on human uterine artery rings, both intact and denuded of endothelium, was investigated. 2. Initially, AVP (63 pM-32 nM) induced concentration-dependent contraction of human uterine artery (pD2 = 8.92 +/- 0.01). Removal of the endothelium did not affect the concentration-response curve for AVP (pD2 = 8.83 +/- 0.03). 3. In contrast, human uterine arteries, both intact and denuded of endothelium, did not respond to the addition of 1-desamino-8-D-arginine vasopressin (dDAVP, 1 nM-1 microM). 4. In both types of preparations, [d(CH2)5Tyr(Me)AVP (1-10 nM) and [d(CH2)5,D-Ile2,Ile4]AVP (300 nM-3 microM) produced parallel rightward shifts of the curves for AVP. The Schild plots constrained to a slope of unity gave the following -log KB values: [d(CH2)5Tyr(Me)]AVP vs. [d(CH2)5,D-Ile2,Ile4]AVP 9.66 vs. 6.69 and 9.61 vs. 6.80 for human uterine artery, intact and denuded of endothelium, respectively. 5. The pKA values for AVP itself also did not differ between preparations: 6.56 and 6.43 for human uterine artery with and without endothelium, respectively. In both types of preparations, the receptor reserve (KA/EC50) was considerably greater than unity (intact vs. denuded: 228 vs. 244). 6. It is concluded that, in human uterine artery, AVP induces contractions that are not modulated by the endothelium. It is likely that AVP acts as a full agonist on human uterine artery, regardless of the endothelial condition. On the basis of differential antagonists affinity and affinity of AVP itself, it is probable that vasopressin receptors involved in AVP-induced contraction in human uterine arteries belong to the V1a or V1a-like subtype.

L-arginine induces relaxation of human uterine artery with both intact and denuded endothelium.

The effect of L-arginine on isolated human uterine artery rings was investigated. L-Arginine, but not D-arginine, induced concentration-dependent relaxation. Removal of the endothelium enhanced the relaxant effects of L-arginine. Methylene blue and dexamethasone non-competitively inhibited L-arginine-induced relaxation, while NG-monomethyl-L-arginine competitively antagonized the response to L-arginine. Calmidazolium did not affect relaxation evoked by L-arginine. The dissociation constants obtained for L-arginine and NG-monomethyl-L-arginine in intact rings were not significantly different from those in endothelium-denuded rings. It is concluded that the relaxation induced by L-arginine in human uterine artery is mediated by non-endothelial nitric oxide production. We suggest that the NO synthase mediating the L-arginine-induced relaxation is an inducible type.

Endothelium-dependent relaxation in response to acetylcholine in the human uterine artery.

The effect of acetylcholine on isolated human uterine artery rings was investigated. Acetylcholine induced concentration and endothelium-dependent relaxation (pD2 = 7.29 +/- 0.03) of the precontracted arterial segments. The dissociation constant (KA) for acetylcholine was 1.35 (0.92-1.77) mumol/l. The occupancy-response relationship was non-linear. Half-maximal response to acetylcholine was obtained with 5.25% receptor occupancy. Muscarinic receptor antagonists: atropine, pirenzepine, methoctramine, p-fluoro-hexahydro-sila-diphenidol (pFHHSiD) and 4-diphenyl-acetoxy-N-methyl-piperidine (4-DAMP) competitively antagonized the response to acetylcholine. The constrained pA2 values were 9.32 +/- 0.03, 7.13 +/- 0.01, 6.26 +/- 0.01, 8.17 +/- 0.01 and 9.13 +/- 0.02, respectively. A selective muscarinic M2 receptor antagonist, gallamine, had no effect on acetylcholine-induced relaxation. It is concluded that in human uterine arteries acetylcholine induces endothelium-dependent relaxation and acts as a full agonist. We suggest that the muscarinic receptors involved in the acetylcholine-induced relaxation of the isolated human uterine artery are predominantly of the M3 subtype.

Indomethacin reduces contraction of isolated non-pregnant human uterine artery induced by prostaglandin F2 alpha.

The purpose of this study was to explore whether cyclooxygenase products derived from endothelium or vascular smooth muscle participate in the response of human uterine artery to prostaglandin F2 alpha. Experiments were performed using human uterine arterial rings. Prostaglandin F2 alpha (0.4 nM-1 microM) induced contraction of human uterine arteries with both intact and denuded endothelium with similar potency and efficacy (pD2 values: 7.93 +/- 0.01 and 8.07 +/- 0.03 for vessels with and without endothelium respectively; maximal response values: 89.1 +/- 4.7% and 92.3 +/- 3.8% for vessels with and without endothelium respectively). Indomethacin (10 microM) significantly suppressed the maximum effects of prostaglandin F2 alpha and induced a shift towards the right of the prostaglandin F2 alpha concentration-response curves, regardless of the endothelial condition. On the other hand, in both types of preparations, OKY-046 (10 microM), an inhibitor of thromboxane synthesis, did not affect prostaglandin F2 alpha-induced contraction of human uterine arteries. It is concluded that in human uterine artery prostaglandin F2 alpha-induced contraction is mediated, at least in part, through constrictor prostanoid(s) of vascular smooth muscle origin that is not thromboxane A2.

Predominant role for nitric oxide in the relaxation induced by acetylcholine in human uterine artery.

The effect of acetylcholine on the isolated human uterine artery rings was investigated. Acetylcholine (10(-10) M to 6 x 10(-5) M) induced concentration- and endothelium-dependent relaxation (pD2 = 7.4 +/- 0.02, maximal response was 77.5 +/- 6.3% of relaxation induced by papaverine at 3 x 10(-4) M) of the pre-contracted arterial segments. Indomethacin (10(-5) M), diethylcarbamazine (10(-4) M) and tetra-ethylammonium (3 x 10(-4) M) had no effects on acetylcholine-evoked relaxation. Methylene blue (10(-5) M) and NG-monomethyl-L-arginine (L-NMMA) (3 x 10(-6) to 3 x 10(-5) M) antagonized relaxation induced by acetylcholine. The inhibition of endothelium-dependent relaxation by L-NMMA (10(-5) M) was reversed by L-arginine (10(-5) M) but not by D-arginine (10(-4) M). It is concluded that in uterine artery acetylcholine induces endothelium-dependent relaxation of isolated uterine artery is probably mediated via endothelial nitric oxide formation.

[Thyroid gland function during pregnancy]. / Aktivnost stitaste zlezde u trudnoci.

In order to examine the thyroid gland function we analysed healthy pregnant women (20) with normal pregnancy course and term delivery, who had normal endocrinological findings before the investigated pregnancy. In all patients TSH, T4 and T3 concentrations were radioimmunologically determined by trimester, median values with standard deviations were analysed in order to establish normal values during gravidity, as well as the possible changes in relation to non-gravid condition. We determined that T4 (29.3%) and T3 (23.5%) concentrations significantly increased and that TSH insignificantly decreased (12.1%) in the first trimester of pregnancy. In healthy pregnant women during the advance of gestation there was a significant increase of T4 and T3, which was significantly higher in the following than in the previous trimester. TSH concentrations during pregnancy gradually decreased but the decrease during the whole course of pregnancy, and in separate trimesters, was not found to be statistically significant.

Predominant role for nitric oxide in the relaxation induced by vasoactive intestinal polypeptide in human uterine artery.

It has been previously shown that vasoactive intestinal polypeptide (VIP) induces endothelium-dependent relaxation of the human uterine artery. However, the nature of the mediator of the VIP-induced endothelium-dependent relaxation of the human uterine artery has not yet been determined. Therefore these experiments were undertaken to examine the effects of VIP on human uterine arteries and to establish the role of various endothelial factors on the relaxation induced by VIP. The experiments were performed on isolated human uterine arterial rings. VIP (0.3-100 nM) induced a concentration-dependent relaxation of human uterine arteries with intact endothelium (pEC50 = 8.06+/-0.14, n = 28). After the removal of the endothelium this relaxation was abolished (n = 6). Indomethacin (10 microM), a cyclooxygenase inhibitor, and diethylcarbamazine (100 microM), a lipoxygenase blocker, had no effects on VIP-induced relaxation. In contrast, methylene blue (10 microM), a blocker of guanylate cyclase, NG-monomethyl-L-arginine (10 microM), an inhibitor of nitric oxide (NO) synthase, and 4-aminopyridine (1 mM), a non-selective blocker of K+ channels, antagonized the effect of VIP with suppression of maximal VIP-induced relaxation. Non-competitive antagonism with methylene blue revealed that the pKa value for VIP-receptor complex was 8.10+/-0.10 (n = 6) and the receptor reserve expressed as KA/EC50 was 0.89+/-0.11, where pKa = log10KA, and KA is the dissociation constant of VIP-receptor complex. Therefore, on the basis of the results presented, we can conclude that VIP induces endothelium-dependent relaxation in human uterine arteries, acting as a partial agonist on this blood vessel. It appears that endothelium-dependent relaxation induced by VIP in human uterine artery can be entirely explained by the release of NO from endothelial cells.

[Hematoma of the parametrium due to birth trauma]. / Hematom parametrija kao posljedica porodajne traume.

From 1973 to 1980, assisting 59,068 vaginally completed deliveries, the authors encountered 19 hematomas of the parametrium (0.032%). Labour was prolonged in 13 out of these 19 cases and the instruments applied were the outlet forceps in 6 and the vacuum extractor in 2 cases, while the expulsion of the child in 5 cases was helped by an intravenous injection of Syntocin. Half the parturients were in the third and half in the fourth decade of their life; a third of them were primiparae. Clinically the picture of atony or uterine rupture prevailed. In the development of the hematoma of the parametrium a large number of etiological factors are to be pointed out: birth injury, parity, age, predisposition, and others. In 6 women subtotal hysterectomy, in 4 the ligature of the uterine artery, and in 5 the evacuation of the hematoma were applied, while in the remaining ones the treatment as conservative.

[Drug therapy of Graves' disease in pregnancy]. / Medikamentozna terapija Gravesove bolesti u graviditetu.

An analysis was made of 75 pregnant patients who received medicamentous therapy for Graves' disease before the investigated pregnancy and 20 healthy pregnant women with normal pregnancies and term delivery. A severe form of hyperthyreosis was found in 35 examined persons. A separate analysis was made of the patients who had no previous therapy (17) and pregnant patients who were treated with antithyroid drugs (18), with the aim to investigate their effect on the course and outcome of pregnancy and the condition of the newborn infant. In all examined pregnant women the median values with standard deviations for TSH, T4 and T3 in each trimester of pregnancy, the dynamics of their trends, as well as the correlation of values in treated and untreated pregnant women were recorded. The analysis of the pregnancy course in patients with hyperthyreosis indicated a significantly higher incidence of gestational diabetes and EPH gestoses (p less than 0.001). A separate analysis indicated that hyperthyreoidism is one of the risk factors in the occurrence of gestational diabetes. There were 90% of pregnant women who were delivered in an euthyroid condition achieved before pregnancy and maintained during pregnancy, 85% with mild and 77.1% with severe hyperthyreosis. The comparison of treated and untreated patients indicated that the percentage of delivered patients is similar (77.8:76.4), while the incidence of spontaneous abortions was higher (16.7:11.8) and of fetal deaths lower (5.5:11.8). There was one stillbirth in an untreated patient, while the remaining infants were healthy. The authors are of the opinion that it is necessary to achieve remission before pregnancy. In patients with severe hyperthyreosis the authors suggest the administration of antithyreoid drugs.

Relaxation of human uterine artery in response to pinacidil: predominant role for ATP-dependent potassium channels.

The effect of pinacidil on human isolated uterine artery rings was investigated. Pinacidil (10 nM-300 microM) induced a concentration-dependent relaxation of the precontracted arterial segments (pD2: 6.26; maximal response: 98.5%). Apamin (1 microM) and tetraethylammonium (6 mM) had no effects on the pinacidil-evoked relaxation, while 4-aminopyridine (0.1-6 mM) and glibenclamide (1-10 microM) competitively antagonized the response to pinacidil. The dissociation constants for 4-aminopyridine and glibenclamide were 240 microM and 0.40 microM, respectively. It is concluded that, in human uterine arteries, pinacidil induces relaxation. On the basis of differential antagonist affinities, we suggest that pinacidil produces a relaxation of this blood vessel through activation of glibenclamide-sensitive, ATP-dependent potassium channels.