Ivan Verdenik

Uterine electrical activity as predictor of preterm birth in women with preterm contractions

OBJECTIVE To estimate the risk of preterm birth in women admitted to the tertiary maternity hospital for preterm contractions by measuring electrical uterine activity. STUDY DESIGN The study included 47 patients with contractions between the 25th and 35th week of gestation and additional risk factors for preterm delivery. Uterine electrical activity was recorded using bipolar electrodes placed on the abdominal surface. A logistic model with the electromyographic and obstetric data was built, preterm delivery before 37th week of gestation being the outcome measure. RESULTS Seventeen patients (36%) delivered before term. Logistic regression model suggested only the intensity of electrical uterine activity and womans body weight to be significant predictors of preterm delivery, with high values related to preterm birth. They predict preterm delivery with the sensitivity of 47% and specificity of 90%. CONCLUSION We propose uterine EMG as a simple, non-invasive means to estimate the risk of preterm birth in a high-risk population with multiple risk factors present.

Septate, subseptate and arcuate uterus decrease pregnancy and live birth rates in IVF/ICSI

A retrospective matched-control study to evaluate the effect of uterine anomalies on pregnancy rates after 2481 embryo transfers in conventionally stimulated IVF/intracytoplasmic sperm injection (ICSI) cycles. The study group of 289 embryo transfers before and 538 embryo transfers following hysteroscopic resection of a uterine septum was compared with two consecutive embryo transfers in the control group. Groups were matched for age, body mass index, ovarian stimulation, embryo quality, IVF or ICSI and infertility aetiologies. Number of embryos transferred, embryo quality and absence of uterine anomalies significantly predicted the pregnancy rates in the study group: odds ratios (OR) 1.7, 2.6 and 2.5, respectively (P<0.001). Pregnancy rates after embryo transfer before hysteroscopic metroplasty were significantly lower, both in women with subseptate and septate uterus and in women with arcuate uterus compared with controls. If two or three embryos with at least one best-quality embryo were transferred, the differences were 9.6% versus 43.6%, OR 7.3 (P<0.001) and 20.9% versus 35.5%, OR 2.1 (P<0.03), respectively. Differences in terms of live birth rates were even more evident: 1.9% versus 38.6%, OR 32 (P<0.001) and 3.0% versus 30.4%, OR 14 (P<0.001). After surgery, the differences disappeared. This retrospective matched control study evaluated the influence of septate, subseptate and arcuate uterus on pregnancy and live birth rates after 2481 in conventionally stimulated IVF/intracytoplasmic sperm injection (ICSI) cycles. The study group included 827 embryo transfers (289 embryo transfers before and 538 embryo transfers following hysteroscopic resection of uterine septum ans was compared with two consecutive mebryo transfers in the control group. Both groups were matched by age, body mass index, stimulation protocol, quality of embryos, use of IVF or ICSI, and infertility aetiologies. Multivariate logistic regression analysis of the study group showed that the number of embryos, embryo quality and the absence of uterine anomalies significantly predicted the pregnancy rates: odds ratios (OR) 1.7, 2.6, and 2.5, respectively (P<0.001). The pregnancy and live birth rates before surgery were lower compared with controls, both in women with subseptate or septate uterus and in women with arcuate uterus. If two or three embryos with at least one best quality embryo were transferred, the differences in terms of pregnancy rates were 9.6% versus 43.6%, OR=7.3 (P<0.001) and 20.9% versus 35.5%, OR=2.1 (P<0.03), respectively. The differences in terms of live birth rates were even more evident: 1.9% versus 38.6%, OR=32 (P<0.001) and 3.0% versus 30.4%, OR=14 (P<0.001). After surgery, the differences disappeared. Negative impact of uterine anomalies on pregnancy and on live birth rates are two important arguments for treating uterine anomalies in infertile women.

The outcome of singleton pregnancies after IVF/ICSI in women before and after hysteroscopic resection of a uterine septum compared to normal controls

OBJECTIVE(S) To evaluate the effect of hysteroscopic resection of a large uterine septum (Class V according to the American Fertility Society (AFS) classification) and of a small partial uterine septum (Class VI according to AFS classification or arcuate uterus) on the abortion rate in pregnancies after IVF and ICSI. STUDY DESIGN The retrospective matched control study included 31 women who conceived following IVF or ICSI before hysteroscopic resection of a large (12 women) or small partial (19 women) uterine septum and 106 women who conceived following IVF or ICSI after hysteroscopic resection of a large (49 women) or small partial (57 women) uterine septum. For each pregnancy in the study group, we found two consecutive pregnant control women from the IVF/ICSI registry who had a normal uterus and were matched for age, BMI, stimulation protocol and the use of IVF or ICSI and for various infertility causes. The abortion/pregnancy rate was the main outcome measure. Data on the septum length were obtained during hysteroscopic resection by comparing the length of the 1.4 cm long yellow tip of the electric knife to the length of the resected septum. RESULTS The abortion rate before hysteroscopic metroplasty was significantly higher, both in women with a small partial septum (78.9% before resection vs. 23.7% in the normal controls, OR 12.08) and a large septum (83.3% before resection vs. 16.7% in normal controls, OR 25.00) compared to women with a normal uterus. After the surgery, the abortion rate was comparable to the abortion rate in women with normal uterus: in both women with a small partial and women with a larger septum. CONCLUSION(S) Similar to a large uterine septum, a small partial uterine septum is an important and hysteroscopically preventable risk factor for spontaneous abortion in pregnancies after IVF and ICSI.

Cross-Country Individual Participant Analysis of 4.1 Million Singleton Births in 5 Countries with Very High Human Development Index Confirms Known Associations but Provides No Biologic Explanation for 2/3 of All Preterm Births.

Background Preterm birth is the most common single cause of perinatal and infant mortality, affecting 15 million infants worldwide each year with global rates increasing. Understanding of risk factors remains poor, and preventive interventions have only limited benefit. Large differences exist in preterm birth rates across high income countries. We hypothesized that understanding the basis for these wide variations could lead to interventions that reduce preterm birth incidence in countries with high rates. We thus sought to assess the contributions of known risk factors for both spontaneous and provider-initiated preterm birth in selected high income countries, estimating also the potential impact of successful interventions due to advances in research, policy and public health, or clinical practice. Methods We analyzed individual patient-level data on 4.1 million singleton pregnancies from four countries with very high human development index (Czech Republic, New Zealand, Slovenia, Sweden) and one comparator U.S. state (California) to determine the specific contribution (adjusting for confounding effects) of 21 factors. Both individual and population-attributable preterm birth risks were determined, as were contributors to cross-country differences. We also assessed the ability to predict preterm birth given various sets of known risk factors. Findings Previous preterm birth and preeclampsia were the strongest individual risk factors of preterm birth in all datasets, with odds ratios of 4.6–6.0 and 2.8–5.7, respectively, for individual women having those characteristics. In contrast, on a population basis, nulliparity and male sex were the two risk factors with the highest impact on preterm birth rates, accounting for 25–50% and 11–16% of excess population attributable risk, respectively (p<0.001). The importance of nulliparity and male sex on population attributable risk was driven by high prevalence despite low odds ratios for individual women. More than 65% of the total aggregated risk of preterm birth within each country lacks a plausible biologic explanation, and 63% of difference between countries cannot be explained with known factors; thus, research is necessary to elucidate the underlying mechanisms of preterm birth and, hence, therapeutic intervention. Surprisingly, variation in prevalence of known risk factors accounted for less than 35% of the difference in preterm birth rates between countries. Known risk factors had an area under the curve of less than 0.7 in ROC analysis of preterm birth prediction within countries. These data suggest that other influences, as yet unidentified, are involved in preterm birth. Further research into biological mechanisms is warranted. Conclusions We have quantified the causes of variation in preterm birth rates among countries with very high human development index. The paucity of explicit and currently identified factors amenable to intervention illustrates the limited impact of changes possible through current clinical practice and policy interventions. Our research highlights the urgent need for research into underlying biological causes of preterm birth, which alone are likely to lead to innovative and efficacious interventions.

Risk factors for preeclampsia in twin pregnancies: a population-based matched case-control study.

Abstract Objective: To evaluate associated factors for preeclampsia in twin gestations and to compare incidences of pregnancy complications among twin pregnancies with vs. without preeclampsia. Patients and methods: We performed a case-control study using a population dataset of twin pregnancies delivered after 24 weeks of gestation, in Slovenia, between 1997 and 2009. Cases were twin gestations complicated by preeclampsia and controls were cases matched by gestational age, parity, and chorionicity. Results: We identified 181 cases (4.7%) of preeclampsia among 3885 twins and 542 matched controls. High pre-pregnancy body mass index (BMI) and gestational diabetes were significantly associated with preeclampsia [odds ratio (OR) 1.8, 95% CI 1.26, 2.77 for overweight (BMI 25.0–29.9); OR 4.72, 95% CI 2.83, 7.89 for obese (BMI≥30), and OR 2.19, 95% CI 1.03, 4.68 for gestational diabetes]. The association was not significant for preexisting hypertension, maternal age, smoking, and pregnancy following assisted reproduction. Placental complications (previa, abruption, or adherent placenta) were more common, and low birth weight less common in the preeclampsia group (P=0.03 and P=0.01, respectively). Conclusions: High pre-pregnancy BMI carries an especially high risk for the development of preeclampsia and its complications in twin gestation.

Variations in Multiple Birth Rates and Impact on Perinatal Outcomes in Europe

Objective Infants from multiple pregnancies have higher rates of preterm birth, stillbirth and neonatal death and differences in multiple birth rates (MBR) exist between countries. We aimed to describe differences in MBR in Europe and to investigate the impact of these differences on adverse perinatal outcomes at a population level. Methods We used national aggregate birth data on multiple pregnancies, maternal age, gestational age (GA), stillbirth and neonatal death collected in the Euro-Peristat project (29 countries in 2010, N = 5 074 643 births). We also used European Society of Human Reproduction and Embryology (ESHRE) data on assisted conception and single embryo transfer (SET). The impact of MBR on outcomes was studied using meta-analysis techniques with random-effects models to derive pooled risk ratios (pRR) overall and for four groups of country defined by their MBR. We computed population attributable risks (PAR) for these groups. Results In 2010, the average MBR was 16.8 per 1000 women giving birth, ranging from 9.1 (Romania) to 26.5 (Cyprus). Compared to singletons, multiples had a nine-fold increased risk (pRR 9.4, 95% Cl 9.1–9.8) of preterm birth (<37 weeks GA), an almost 12-fold increased risk (pRR 11.7, 95% CI 11.0–12.4) of very preterm birth (<32 weeks GA). Pooled RR were 2.4 (95% Cl 1.5–3.6) for fetal mortality at or after 28 weeks GA and 7.0 (95% Cl 6.1–8.0) for neonatal mortality. PAR of neonatal death and very preterm birth were higher in countries with high MBR compared to low MBR (17.1% (95% CI 13.8–20.2) versus 9.8% (95% Cl 9.6–11.0) for neonatal death and 29.6% (96% CI 28.5–30.6) versus 17.5% (95% CI 15.7–18.3) for very preterm births, respectively). Conclusions Wide variations in MBR and their impact on population outcomes imply that efforts by countries to reduce MBR could improve perinatal outcomes, enabling better long-term child health.

Activity of smooth muscles in human cervix and uterus.

OBJECTIVE To find the similarities and dissimilarities between the activity of the human smooth muscles in the cervix and in the uterine corpus at the onset of induced labour. STUDY DESIGN Electromyographic activity was measured in 14 primiparous women after amniotomy. The data were sampled and stored digitally in real time. For statistical analysis, the first 20 min of recordings following amniotomy were analyzed. The ratio between the mean activity at a given time and the mean activity over the whole 20 min was used for the comparison between the cervical and uterine activity. RESULTS The analysis of correlation showed that the electromyographic activity in the cervix differed from that in the uterine corpus in the majority of the enrolled cases. CONCLUSIONS The muscular activity in the cervix is independent of that in the uterine corpus at the onset of induced labour.

Singleton Pregnancy Outcomes after In Vitro Fertilization with Fresh or Frozen-Thawed Embryo Transfer and Incidence of Placenta Praevia

The aim of the study was to compare the single pregnancy and neonate outcome after fresh and frozen-thawed embryo transfer in the in vitro fertilization programme (IVF). The study focused on clinical and laboratory factors affecting the abnormal placentation, especially placenta praevia, in patients conceiving in the IVF programme. The results confirm that neonates born after frozen-thawed embryo transfer had significantly higher mean birth weight than after fresh embryo transfer (ET). Moreover, the birth weight distribution in singletons was found to shift towards “large for gestation” (LGA) after frozen-thawed ET. On the other hand, the pregnancies after fresh ET were characterized by a higher incidence of placenta praevia and 3rd trimester bleeding. Placenta praevia was more common in IVF patients with fresh ET in a stimulated cycle than in patients with ET in a spontaneous cycle. It occurred more frequently in patients with transfer of 2 embryos. From this point of view, single ET and ET in a spontaneous cycle should be encouraged in good prognosis patients in the future with more than two good quality embryos developed. An important issue arose of how the ovarian hormonal stimulation relates to abnormal placentation and if the serum hormone levels interfere with in the IVF treatment results.

Follicular oestradiol and VEGF after GnRH antagonists or GnRH agonists in women with PCOS

The aim of this study was to determine whether follicular oestradiol and vascular endothelial growth factor (VEGF) concentrations in women with polycystic ovarian syndrome (PCOS) differ according to the use of gonadotrophin-releasing hormone (GnRH) antagonists or GnRH agonists. Furthermore, the effect of follicular oestradiol and VEGF concentrations on oocyte and embryo quality was investigated. In this prospective clinical study, 20 women with PCOS undergoing intracytoplasmic sperm injection for male factor infertility were included using a GnRH antagonist or a GnRH agonist protocol. In each follicle, oestradiol and VEGF concentrations were determined. In the GnRH antagonist group 254 follicles and in the GnRH agonist group 245 follicles, were aspirated. Fewer metaphase II (MII) and more immature and degenerative oocytes were registered in the GnRH antagonist group. Follicular oestradiol and VEGF were lower in the GnRH antagonist group (P = 0.014 and P < 0.001, respectively). Moreover, higher oestradiol concentrations were related to embryos of higher quality (P = 0.037). It is concluded that GnRH antagonists decrease follicular oestradiol and VEGF concentrations and the number of retrieved MII oocytes in women with PCOS.

Adverse effects of thyroid dysfunction on pregnancy and pregnancy outcome: epidemiologic study in Slovenia.

Objective. To evaluate the consequences of maternal thyroid dysfunction for pregnancy outcome. Methods. A retrospective analysis involving all pregnant women who delivered in Slovenia in the 1997–1999 triennium; those having a medical history of thyroid dysfunction and/or taking thyroid medications were allotted to the study group (n = 748) and the remaining ones to the control group (n = 52 253). Results. Significantly higher incidences of infertility (5.5% vs. 3.7%, p < 0.05), menstrual cycle irregularities (3.2% vs. 1.9%, p < 0.05), hypertensive disorders (7.0% vs. 4.2%, p < 0.05), threatened preterm delivery (9.1% vs. 5.6%, p < 0.001), and delivery before 32 weeks (2.7% vs. 1.5%, p < 0.05) were found in the study than in the control group. There were no significant differences in the incidences of miscarriage, non-gestational diabetes mellitus, proteinuria, hyperemesis, intrahepatic cholestasis of pregnancy, intrauterine growth restriction, placental abruption, preterm delivery, small for gestational age newborns (SGA), and stillbirths. Conclusions. This is the first study to evaluate the incidence of thyroid dysfunction for the whole population of pregnant women in Slovenia using a retrospective analysis. Thyroid dysfunction adversely affects pregnancy and pregnancy outcome but to a lesser extent than presented in previous studies. An evaluation of thyroid function in the women who experience menstrual cycle irregularities, infertility, and complications during pregnancy, labor and delivery would be advisable.