Adhesions at repeat cesarean delivery: is there a personal impact?

PURPOSE: The rise in the rate of cesarean deliveries highlights complications related to adhesion formation. This study evaluated whether the incidence and severity of adhesions secondary to repeat cesarean deliveries are a consequence of repeated surgeries or due to an individual's propensity to develop adhesions. METHODS: A retrospective chart review was conducted for 160 patients who had more than two repeat cesarean deliveries in a single teaching hospital. Data regarding intra-abdominal adhesions were collected. The severity, location, density and amount of adhesions were evaluated based on standard operative reports. Adhesion progression in subsequent cesarean deliveries was evaluated for each individual patient. RESULTS: 69/160 (43 %) patients developed significant adhesions following the primary cesarean delivery. Of these, 46 (67 %) had significant adhesions at the second surgery. Of the 91 (57 %) patients, who did not develop significant adhesions after the primary cesarean delivery, 34 (37 %) had significant adhesions at the third surgery. A patient presenting with significant adhesions at her second cesarean had a 1.88-fold risk for significant adhesions at her third cesarean (95 % CI 1.3-2.7). CONCLUSIONS: Our results suggest that adhesion development might be influenced by individual factors more than by the number of cesarean deliveries.

Obstetric and neonatal outcomes after preterm premature rupture of membranes among women carrying group B streptococcus.

OBJECTIVE: To evaluate whether carriers of group B streptococcus (GBS) have adverse obstetric and neonatal outcomes when preterm premature rupture of membranes (PPROM) occurs. METHODS: In a retrospective study, data were reviewed for women with a singleton pregnancy and PPROM before 34 weeks who attended the Meir Medical Center, Kfar Saba, Israel, between 2005 and 2012. All women received roxithromycin for 1 week, and ampicillin until GBS culture results were available. Ampicillin was continued to 1 week if the GBS culture was positive. The primary study outcome measure was the latency period (time from rupture of membranes to active/induced labor). RESULTS: Among 116 eligible patients, 21 (18.1%) were GBS carriers and 95 (81.9%) noncarriers. The latency period was 11.2 ± 18.1 days for GBS carriers versus 7.5 ± 9.6 days for noncarriers (P=0.93). However, there was a correlation between the length of ampicillin treatment and the latency period (Spearman correlation coefficient 0.7; P<0.001). There were no differences in early neonatal outcomes. CONCLUSION: GBS carriers with PPROM did not have adverse outcomes. Longer treatment with ampicillin among GBS carriers prolonged the latency period.

Retained placental tissue as an emerging cause for malpractice claims.

BACKGROUND: Removal of retained placental tissue postpartum and retained products of conception (RPOC) abortion is done by uterine curettage or hysteroscopy. Trauma to the endometrium from surgical procedures, primarily curettage, can cause intrauterine adhesions (Asherman's syndrome) and subsequent infertility. The incidence of malpractice claims relating to intrauterine adhesions is rising, justifying reevaluation of the optimal way of handling these complications. OBJECTIVES: To review malpractice claims regarding intrauterine adhesions, and to explore the clinical approach that might reduce those claims or improve their medical and legal outcomes. METHODS: We examined 42 Asherman's syndrome claims handled by MCI, the largest professional liability insurer in Israel. The clinical chart of each case was reviewed and analyzed by the event preceding the adhesion formations, timing and mode of diagnosis, and outcome. We also assessed whether the adverse outcome was caused by substandard care and it it could have been avoided by different clinical practice. The legal outcome was also evaluated. RESULTS: Forty-seven percent of the cases occurred following vaginal delivery, 19% followed cesarean section, 28% were RPOC following a first-trimester pregnancy termination, and 2% followed a second-trimester pregnancy termination. CONCLUSIONS: It is apparent that due to the lack of an accepted management protocol for cases of RPOC, it is difficult to legally defend those cases when the complication of Asherman syndrome develops.

Telomere shortening in intra uterine growth restriction placentas.

INTRODUCTION: Placentas from pregnancies complicated with IUGR (intrauterine growth restriction) express altered telomere homeostasis. In the current study, we examined mechanisms of telomere shortening in these placentas. METHODS: Placental biopsies from 15 IUGR and 15 healthy control pregnancies were examined. The percentage of trophoblasts with fragmented nuclei: senescence-associated heterochromatin foci (SAHF), was calculated using DAPI staining. The amount of human telomerase reverse transcriptase (hTERT) mRNA was evaluated using RtPCR levels of telomere capture using FISH in those samples were estimated. RESULTS: The percentage of trophoblasts with SAHF was higher in IUGR compared to control samples, (25±13.4% vs. 1.6±1.6%, P<0.0001), hTERT mRNA was decreased (0.5±0.2 vs. 0.9±0.1, P<0.0001) and telomere capture was increased (13.2±9.7% vs.1.3±2.5%, P<0.001). CONCLUSIONS: We suggest that IUGR placentas express increased signs of senescence as part of the impaired telomere homeostasis. One factor that mediates telomere shortening in these placentas is decreased hTERT mRNA, leading to decreased protein expression and therefore, reduced telomere elongation. Telomere capture, which is a healing process, is increased in IUGR trophoblasts as a compensatory mechanism.

Senescence in amniocytes and placentas from trisomy 21 pregnancies.

OBJECTIVE: Senescence has been described as a stable cell proliferation arrest resulting from the progression of primary human fibroblasts through a finite number of population doublings in vitro. Accelerated telomere shortening was observed in pregnancies complicated by intrauterine growth restriction, in placentas of diabetic mothers and trisomy 21 amniocytes. We hypothesized that under conditions of stress, telomeres in placentas will be shorter and there will be more cells with the senescence phenotype. METHODS: The two study groups included placental biopsies from 7 cases of trisomy 21 and amniocytes from 10 cases of trisomy 21. The control groups consisted of placental biopsies from 6 cases and amniocytes from 10 pregnancies with a normal karyotype. The samples were analyzed for the presence of senescent cells based on the number of fragments in each cell. RESULTS: A significantly higher percentage of cells in the senescent state, based on a higher percentage of cells with more fragmentations, were found in the amniocytes (20.8%) and in trophoblasts (94.3%) from placentas with trisomy 21 compared to the control groups. CONCLUSION: Among other genetic instability parameters, trisomy 21 amniocytes and trophoblasts express a higher prevalence of senescent cells than were previously reported.

Is it necessary to induce labor in cases of intrauterine growth restriction at term?

OBJECTIVES: Infants with intrauterine growth restriction (IUGR) have increased morbidity and mortality. The decision whether to induce labor at term or to expectantly manage these pregnancies is controversial. The aim of this study was to assess the outcomes of these two management strategies in term pregnancies. STUDY DESIGN: This retrospective cohort study compared neonatal and maternal morbidity and mortality of IUGR fetuses (estimated fetal weight below the 10th percentile) between induced and spontaneous labors. RESULTS: Records of 669 IUGR newborns were reviewed; 499 were delivered through spontaneous labor and 170 were delivered through induced labor. Epidemiology and early perinatal outcomes between the two groups were similar. The cesarean section rate was significantly higher (P<0.005) in the induced group. CONCLUSIONS: Expectant management for term IUGR pregnancies seems to be safe, with lower rates of cesarean deliveries. A large, prospective, randomized controlled trial with long-term neonatal follow-up is indicated.

Endoreduplication in cervical trophoblast cells from normal pregnancies.

OBJECTIVE: Fetal cells represented by extravillous trophoblasts (EVT) obtained from the cervix by a minimally invasive procedure are important for prenatal diagnosis in early pregnancies. Endoreduplication is a duplication of chromosomes without mitosis, leading to polyploidy that might represent increased cellular metabolic activity. In this study, we estimated the normal prevalence of polyploid trophoblasts exfoliated to the cervix between 5 and 13 weeks of gestation. METHODS: Cervical samples were obtained by cytobrush, between 5 and 13 weeks of gestation from 36 randomly selected, singleton pregnancies. FISH was done with X, Y and two 21 probes. RESULTS: We diagnosed 21 pregnancies with female and 15 pregnancies with male fetal karyotypes. A mean of 15.2 (0.02%) tetraploid cells were found in pregnancies with a female fetus and a mean of 2.0 (0.003%) tetraploid cells were found in pregnancies with a male fetus. The tetraploid cells (endoreduplicated trophoblasts) were two to three times larger than the normal cells usually seen in the cervix. CONCLUSIONS: Extravillus trophoblasts tend to form endoreduplication to the ploidy level of 4c-8c of DNA. Those cells may represent a typical phenomenon in the growing placenta. Extravillus trophoblasts from female fetuses tend to form higher rates of endoreduplication.

A comparison of surface acquired uterine electromyography and intrauterine pressure catheter to assess uterine activity.

OBJECTIVE: Intrauterine pressure catheter (IUPC) is the primary device used to evaluate uterine activity. In contrast to the IUPC, electrical uterine myography (EUM) enables noninvasive measurement of frequency, intensity, and tone of contractions. The aim of this study was to determine the accuracy of EUM compared to IUPC. STUDY DESIGN: EUM measured myometrial electrical activity using a multichannel amplifier and a noninvasive position sensor. In all, 47 women in labor were monitored simultaneously with an IUPC and EUM. We compared the frequency, intensity, and tone of uterine contractions between the methods. RESULTS: The correlation of the frequency, intensity, and tone of contractions between uterine electromyography and IUPC was strong with significant r values of 0.808-1 (P < .0001). CONCLUSION: Electrical uterine electromyography yields information about uterine contractility comparable to that obtained with IUPC.

TERC telomerase subunit gene copy number in placentas from pregnancies complicated with intrauterine growth restriction.

INTRODUCTION: intrauterine growth restriction (IUGR) is a significant cause of both short- and long-term morbidity and mortality. IUGR secondary to placental dysfunction is correlated with telomere shortening. Telomerase is an enzyme complex that elongates telomeres. One of its components is encoded by the telomerase RNA component gene (TERC), which serves as the RNA template for the addition of telomeric repeats. We hypothesized decreased TERC gene copy number in IUGR placentas as part of the mechanism of telomere shortening in placental dysfunction. METHODS: we estimated the gene copy number of the TERC gene at 3q26 by applying FISH to trophoblasts of placental biopsies from five pregnancies with IUGR caused by placental insufficiency and compared them to placentas from five gestational-age matched, uncomplicated pregnancies. RESULTS: significantly lower TERC gene copy number was observed in IUGR trophoblasts on the same chromosome and on other chromosomes, compared to the control samples (p<0.05). CONCLUSIONS: the TERC gene copy number is decreased in IUGR trophoblasts. These results support the observations of telomere shortening and decreased telomerase activity in IUGR placentas. We suggest that these findings might play a role in the pathophysiology of IUGR, perhaps by promoting senescence in trophoblasts of IUGR placentas.

Telomeres are shorter in placental trophoblasts of pregnancies complicated with intrauterine growth restriction (IUGR).

OBJECTIVE: Telomeres are nucleoprotein structures located at the termini of chromosomes, and protect them from fusion and degradation. Telomeres are progressively shortened with each mitotic cycle and by environmental factors. We hypothesized that antepartum stress can lead to accelerated telomere shortening in placental trophoblasts, and plays a role in intrauterine growth restriction (IUGR). METHODS: Placental biopsies were derived from 16 pregnancies complicated with IUGR and from 13 uncomplicated pregnancies. Fluorescence-in-situ protocol was used to determine telomere length. Immunohistochemistry for hTERT was performed to assess telomerase activity. Clinical and histopathological characteristics were collected to ensure that IUGR was secondary to placental insufficiency. Fluorescence-in-situ-hybridization was used to rule out aneuploidy as a reason for shortened telomeres. RESULTS: The number and intensity of telomeres staining and telomerase activity were significantly lower in the IUGR placentas. No aneuploidy was detected for the chromosomes checked in the placental biopsies. CONCLUSIONS: Telomeres are shorter in trophoblasts of IUGR placentas.

Telomere aggregates in amniocytes with karyotype of balanced chromosomal rearrangements.

Telomeres are TTAGGG repetitions at the ends of chromosomes. Functioning telomeres are essential for normal segregation and maintenance of chromosomes during mitotic and meiotic divisions. Dysfunctional telomeres support the survival of aneuploid cells, a characteristic of many human malignancies. In contrast to the non-overlapping nature of telomeres in normal nuclei, telomeres of tumor nuclei tend to form aggregates. In this study, our objective was to evaluate the number of telomere aggregates (TAs) in karyotype-balanced structural rearrangements. This is an additional parameter of genetic instability, which might suggest a possible increased risk for diseases related to genomic instability, such as cancer. Twenty-six amniotic fluid cell cultures were established following genetic amniocentesis. Telomere FISH protocol was applied to the samples. Telomere aggregates were counted using a 2D microscope. The results were statistically tested by analysis of variance (ANOVA) and Kruskal-Wallis tests. More telomere aggregates in the structural balanced rearrangements were found in both study groups (balanced translocations and inversions) compared to the control group (P < 0.05). The persistence of TAs in cells is probably related to Breakage-Bridge-Fusion (BBF) cycles, a mechanism of TAs described by Muller and McClintock, resulting in end-to-end fusion that contributes to the onset of genomic instability. BBF cycles contribute to deletions, gene amplification, non-reciprocal translocations, and overall genetic changes associated with tumor genesis. According to our studies, the individuals who are carriers of balanced structural chromosomal rearrangements show some of the genetic instability parameters that appear in other circumstances, such as premalignant and malignant conditions.

Prenatal diagnosis of trisomy 21 through detection of trophoblasts in cervical smears.

BACKGROUND: Fetal cells exfoliate in the uterine cavity during early pregnancy and are a potential source of material for NIPD. AIMS: This study was designed to test the hypothesis that fetal cells obtained from the uterine cervix during the first trimester of pregnancy could be utilized for prenatal diagnosis of chromosomal aneuploidy. STUDY DESIGN: Fetal cells retrieved from the distal endocervical canal during the first trimester of pregnancy were hybridized with chromosome 21 specific FISH probes and analyzed with an automated fluorescence microscope. SUBJECTS AND OUTCOME MEASURES: Cells with 3 copies of chromosome 21 were detected in 5 out of 5 trisomy 21 pregnancies. RESULTS: The number of trisomic cells detected ranged from 1 to 27 with a median value of 5. CONCLUSIONS: FISH-based scanning can identify trisomy 21 pregnancies by analysis of routine cervical brushings. The approach offers the potential for non-invasive prenatal diagnosis as early as 5 weeks gestation.

Short telomeres may play a role in placental dysfunction in preeclampsia and intrauterine growth restriction.

OBJECTIVE: Telomeres shorten and aggregate with cellular senescence and oxidative stress. Telomerase and its catalytic component human telomerase reverse-transcriptase regulate telomere length. The pathogenesis of preeclampsia and intrauterine growth restriction involves hypoxic stress. We aimed to assess telomere length in trophoblasts from pregnancies with those complications. STUDY DESIGN: Placental specimens from 4 groups of patients were studied: severe preeclampsia, intrauterine growth restriction, preeclampsia combined with intrauterine growth restriction, and uncomplicated (control). Telomere length and human telomerase reverse-transcriptase expression were assessed by using quantitative fluorescence-in-situ protocol and immunohistochemistry. RESULTS: Telomere length was significantly lower in preeclampsia, intrauterine growth restriction, and preeclampsia plus intrauterine growth restriction placentas. More aggregates were found in preeclampsia, but not in intrauterine growth restriction placentas. Human telomerase reverse-transcriptase was significantly higher in the controls compared with the other groups. CONCLUSION: Telomeres are shorter in placentas from preeclampsia and intrauterine growth restriction pregnancies. Increased telomere aggregate formation in preeclampsia but not in intrauterine growth restriction pregnancies, implies different placental stress-related mechanisms in preeclampsia with or without intrauterine growth restriction.

Nulliparity, fertility treatments and twins: a time for rethinking.

OBJECTIVE: To evaluate the risk that nulliparity poses to the outcome of twin pregnancies, an issue that gained importance due to the rise of twin gestations following assisted reproduction interventions. DESIGN: A prospective cohort study. SETTING AND PATIENT(S): Between January 1, 2004, and January 7, 2008, we prospectively enrolled all pregnancies achieved by assisted reproduction techniques and including ovulation induction, which successfully completed the first trimester. Pregnancies achieved by egg donation were excluded. MAIN OUTCOME MEASURE(S): Second trimester abortion and severe prematurity (delivery before 32 weeks) rates and the number of live births. RESULT(S): Two-hundred-forty-three twin pregnancies were available for evaluation. Second trimester miscarriage rate was 9.3% in nulliparas and 2.4% in multiparas (P=0.061). Severe prematurity rate was 15.1% in nulliparas compared with 2.5% in multiparas (P=0.003). Better outcome of multiparas was also demonstrated by the calculated chance of taking home at least one baby: 97.6% for multiparas compared with 89.2% in nulliparas (P=0.024). CONCLUSION(S): Nulliparity is a risk factor for a poor outcome in twin pregnancies achieved by fertility treatments and is associated with an increased risk for severe prematurity and possibly late abortions. This information should be relayed to the patients undergoing fertility treatments and is a consideration regarding the number of fetuses in relation to parity.

Who should be offered fetal echocardiography? One center's experience with 3965 cases.

BACKGROUND: Although the comprehensive evaluation of the fetal heart includes echocardiography by an experienced pediatric cardiologist, economic constraints sometimes dictate the need to select patients. OBJECTIVES: To analyze the usefulness of fetal echocardiography in the detection of congenital heart disease according to the referral indication. METHODS: This retrospective survey relates to all 3965 FE studies performed in our center from January 2000 to December 2004. The diagnosed cardiac anomalies were classified as significant and non-significant malformations. All FE studies were done by a single operator (A.L.) at Meir Medical Center, a referral center for a population of about 400,000. The 3965 FE studies were performed for the following indications: abnormal obstetric ultrasound scans, maternal and family history of cardiac malformations, medication use during the pregnancy, and maternal request. The relative risk of detecting CHD was calculated according to the various referral indications. RESULTS: Overall, 228 (5.8%) cases of CHD were found. The most common indication for referral was suspicion of CHD during a four-chamber view scan in a basic system survey or during a level II ultrasound survey. No correlation was found between maternal age and gestational age at the time of scanning and the likelihood of finding CHD. CONCLUSIONS: Our data suggest that a suspicious level II ultrasound orthe presence of polyhydramnios is an important indication for FE in the detection of significant CHD.

Maternal serum triple marker levels in immigrants to Israel from Ethiopia.

OBJECTIVES: To determine if Ethiopian immigrants have similar triple marker levels as the general Israeli population. MATERIAL AND METHODS: Second-trimester maternal serum results on 346 Ethiopians were obtained from records of 36,309 women. Two series were constructed for comparison among patients screened between 2000 and 2001 ('old group') and 2005 and 2007 ('new group'). RESULTS: The median and 95% confidence intervals (CI) were: alpha-fetoprotein (AFP) 1.080 multiples of median (MoM) (95% CI 1.03-1.13); human chorionic gonadotrophin (hCG) 0.895 MoM (95% CI 0.82-0.97), and unconjugated estriol (uE(3)) 1.050 MoM (95% CI 1.00-1.10). The differences between the AFP and hCG medians for the old and new series were not statistically significant (p = 0.06 and 0.20) whilst the uE(3) difference was significant (p = 0.04). There was a general tendency for the levels to be closer to 1 MoM over time. CONCLUSIONS: Triple marker serum levels of AFP and hCG among Ethiopian patients may need to be slightly corrected, particularly for hCG.

Telomere aggregates in trisomy 21 amniocytes.

Trisomy 21 is the most common chromosomal abnormality among persons with intellectual disability, with a live birth rate of 1 in 800-1,000. As such, this abnormality may serve as a model for human disorders that result from supernumerary copies of a genomic region. Down syndrome carries an increased risk of developing acute leukemia and other malignancies. Telomeres of tumor cells nuclei tend to form aggregates (TA). This study evaluated TA formation in amniocytes from trisomy 21 pregnancies, compared with amniocytes from normal euploid pregnancies. A commercially available peptide nucleic acid telomere kit was used to evaluate TA formation, using two-dimensional fluorescence microscopy. Significantly higher frequencies of TA were found in trisomy 21 amniocytes than in amniocytes from normal pregnancies. The TAs found in trisomy 21 amniocytes apparently represent an additional parameter that reflects the high genetic instability of this syndrome and its recognized predisposition to develop leukemia and other malignancies.

Telomere aggregate formation in placenta specimens of pregnancies complicated with pre-eclampsia.

Telomeres are specific repetitive DNA sequences that cap and stabilize the ends of chromosomes. Functional telomeres are essential for the normal segregation and maintenance of chromosomes during mitotic and meiotic division. Pre-eclampsia, a pregnancy-specific syndrome of increased blood pressure accompanied by proteinuria, is often associated with growth deficiency in the fetus. Oxidative stress is a major component in the pathophysiology of pre-eclampsia. In contrast to the nonoverlapping nature of telomeres in normal nuclei, telomeres of tumor nuclei tend to form aggregates (TAs) in various numbers and sizes. The formation of TAs represents a stress-related process and is independent of telomere length and telomerase activity. The aim of this study was to evaluate TA formation in paraffin-embedded placentas from pregnancies complicated with pre-eclampsia (study group), compared with placentas from normal pregnancies (control group). There were significantly more TAs in the study group (mean, 8.00 TAs per case) than in the control group (mean, 2.36 TAs per case) (P < 0.01). Pre-eclampsia-related stress may accelerate apoptosis and cell death and lead to placental dysfunction. TAs formation, which has been linked to stress and tumorgenesis is increased in placentas of pre-eclamptic patients.

Telomere capture in hepatitis C infection.

Broken chromosomes can acquire new telomeres by "telomere capture" (TC), and it has become possible to investigate the terminus in cytogenetically visible telomere rearrangements. The TC phenomenon was observed in malignant conditions. We evaluated the TC rate in hepatitis C virus (HCV) patients compared to non-Hodgkin's lymphoma patients, as well as relative to a control group. For this purpose, we used two Cytocell probes, 15qter and 13qter. Higher TC rates were found in the three study groups relative to the control group. Our results showed that HCV patients have some of the components that can initiate the cascade of events leading to malignancies.

Adverse outcome of pregnancies with extremely high levels of maternal serum human chorionic gonadotropin.

BACKGROUND: The associated risk of elevated levels of maternal serum human chorionic gonadotropin (MShCG) with pregnancy complications was reported in many studies. However, the outcome of pregnancies with extremely high levels of MShCG was never independently studied. METHODS: We report on 6 out of 45,990 studied patients with extremely high levels of MShCG (>15 multiples of the medians) analyzed during the second trimester. RESULTS: Although our patient population was composed of more Jewish than Arab pregnant women, all those patients were Arabs. Overall, the prognosis of those pregnancies was poor. In 1 case, an antepartum fetal death occurred, 2 had premature deliveries (one of the newborns had severe failure to thrive), and 2 delivered small for gestational age babies. In 5 of these 6 cases, no specific diagnosis was established. One case was complete hydatidiform mole with a coexisting normal fetus. CONCLUSIONS: We recommend that these patients undergo counseling in which the predicted outcome will be described. In addition, a follow-up of high-risk pregnancy should be implemented: sonographic evaluation should be performed, initially to rule out a molar gestation. The patients should then be followed for growth restriction and they should be monitored to rule out other pregnancy complications such as premature labor and antepartum fetal death. Finally, the overrepresentation of Arabs among our affected patients raises the question of a possible genetic tendency for increased MShCG levels especially in the extreme level group.