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Objectives Approximately 1% of term deliveries are complicated by retained products of conception. Untreated, this condition may cause bleeding, infection and intrauterine adhesions. This study assessed whether performing routine bedside uterine ultrasound immediately after manual removal of the placenta reduced the occurrence of undiagnosed, retained products of conception and its associated complications. Study design A retrospective study was conducted using the records of patients who delivered and underwent manual removal of placenta at a single obstetrics center over a 6-year period. The outcomes of patients who were assessed using immediate bedside ultrasound were compared to a similar group who were treated based on clinical evaluation alone. All patients underwent ultrasound examination prior to discharge. Outcome variables included the rate of additional interventions (medical or surgical), abnormal pre-discharge uterine ultrasound findings, postpartum hemorrhage rate, puerperal fever and length of hospital stay. Results A total of 399 charts were reviewed. Immediate post-procedural ultrasound was performed in 235 patients. The remaining 164 women did not undergo immediate post-procedural ultrasound. All patients underwent an ultrasound examination prior to discharge. Among the patients who had an immediate post-procedural ultrasound, 12 (5.1%) received immediate re-intervention (2 methergine, 6 curettage and 4 manual uterine revision) vs. no intervention in the second group ( p No statistically significant difference was found between the group of patients who had immediate post-procedural ultrasound and those who did not, in the rates of postpartum hemorrhage (3.1% vs. 0.7%, p = 0.13), abnormal ultrasound findings prior to discharge (14.9% vs. 14.8%, p = 0.96) or additional late intervention (7.2% vs. 7.9%, p = 0.79), respectively. Conclusions Our findings suggest that immediate, bedside uterine ultrasound examination after manual removal of placenta might not change patient outcomes. Furthermore, it might increase unnecessary interventions. Further studies are needed to prospectively assess the benefit of routine uterine ultrasound examination after manual removal of placenta.

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.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.The percentage of trophoblasts with SAHF was higher in IUGR compared to control samples, (25±13.4% vs. 1.6±1.6%, P0.0001), hTERT mRNA was decreased (0.5±0.2 vs. 0.9±0.1, P0.0001) and telomere capture was increased (13.2±9.7% vs.1.3±2.5%, P0.001).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.

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.

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.

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.

In this study we evaluated the aneuploidy rate of cells from patients considered to have a premalignant condition (monoclonal gammopathy or MGUS) and patients with multiple myeloma, as well as healthy controls. By applying a fluorescence situ hybridization technique, we estimated the random aneuploidy rate of alpha-satellite (centromeres) probes from chromosomes 9 and 18. The monosomy and total aneuploidy rates were higher in the two study groups compared to the control group. The monosomy rate was significantly higher in the MGUS group compared to the group with chromosome 18 alpha-satellite probes, a finding that was reported before in preneoplastic conditions. Our results support the cancer aneuploidy theory that carcinogenesis is initiated by a random aneuploidy, which is induced either spontaneously or by a carcinogen. The resulting karyotype instability sets a chain reaction of aneuploidization, which generates even more abnormal and eventually cancer-specific combinations and rearrangements of chromosomes.

Ataxia telangiectasia (AT) is a pleiotropic and rare (1:40,000 to 1:100,000) recessive disease. Laboratory investigations have failed to detect any consistent anomaly in cells from AT heterozygotes. To estimate random aneuploidy, we applied a fluorescence in situ hybridization technique with alpha-satellite probes for chromosomes 8 and 9 and replication pattern for RB-1, HER-2/neu, and the imprinted SNRPN loci on primary AT carrier fibroblasts. Higher random aneuploidy was not found in the carrier fibroblasts compared to control amniocytic cells. The asynchrony pattern was higher in the AT carrier cells with the RB-1 locus (P=0.057) and significantly higher with the HER-2/neu locus (P < 0.001) compared to control cells. As for the imprinted locus SNRPN, there was a significantly lower asynchrony rate in the AT carriers (P < 10(-5)) compared to the control group. Molecular cytogenetic parameters of random aneuploidy and replication pattern may reflect predisposition for the development of cancer. It is possible that in some AT carriers the genetic instability phenomena associated with the abnormal replication pattern may represent their potential for developing malignancies.

The most common treatment of chronic lymphocytic leukemia (CLL) is the alkylating agent chlorambucil (CLB), with or without prednisone. In the present study, our aim was to evaluate whether treatment with CLB for more than one year induced genetic changes manifested by comparative genomic hybridization (CGH) as new chromosomal aberrations. We also studied whether CLB affected the pattern of replication by using fluorescence in situ hybridization (FISH). We found a similar rate of asynchronous pattern of replication in both treated and untreated patients with CLL. Most of the aberrations found with CGH were previously reported in CLL. More prognostically unfavorable aberrations and more cases with genetic changes were found in the treated group. The changes found were not typical of the secondary genetic aberrations associated with alkylating agents. Thus, we conclude that treatment of CLL with CLB for at least a year does not affect the parameters analyzed in this study. Longer studies are needed to further explore the effects of alkylating agents on normal and malignant cells.

We applied a comparative genomic hybridization (CGH) technique to paraffin-embedded tissue samples taken from fibroadenomas, benign breast tumors, to detect possible numerical and unbalanced genetic changes. We compared the results to those from previous cytogenetic studies of fibroadenomas. In concurrence with previous cytogenetic studies of fibroadenomas, we detected genetic aberrations in chromosomes 4–6, 8–13, 16, 18, 19, 20, and 22. In addition, with the CGH technique we were able to find two new aberrations, 15q+ and 16p−. Because these aberrations have also been reported to be present in breast cancer, the importance of this finding is yet to be determined.

To evaluate possible genomic instability and possible random aneuploidy, we applied comparative genomic hybridization and fluorescence in situ techniques, and evaluated telomerase activity in 16 cases of Ewing sarcoma (EWS) and compared the results to 7 controls. Common secondary aberrations (gains of chromosomes 8 and 12) were found in the study group. There was a direct correlation between the detection of random aneuploidy and development of tumor relapse (P = 0.0047). Other detectable abnormal parameters (secondary) and high telomerase activity were also more common among the cases with relapse but did not reach a statistical significance (probably because of the small sample size). In EWS, the detection of random aneuploidy seems to be a sensitive parameter in the prediction of tumor relapse.

The replication status of malignant cells is usually asynchronous. However, to date the pattern of replication has not been studied in myeloproliferative disorders nor has the effect of chemotherapy been systematically evaluated. Therefore, we used fluorescence in situ hybridization to interphase nuclei in PHA-stimulated peripheral blood lymphocytes to examine replication timing of three alleles associated with the malignant process. The study group comprised hydroxyurea treated and untreated patients with essential thrombocytosis (ET) or polycythemia vera (PV). A significantly higher rate of the asynchronous pattern of replication in both treated and untreated patients was found as compared to healthy controls. The highest rate of asynchronous replication was observed in untreated patients. Also, the frequency of the two doublets pattern was significantly higher in the untreated group compared to the treated patients and to the control groups. In conclusion, patients with PV and ET have a higher rate of asynchronous pattern of replication. A possible correlation between disease activity and the pattern of replication is suggested. The effect of hydroxyurea on the pattern of replication is variable.

Polycythemia vera (PV) and essential thrombocytosis (ET) are clonal chronic myeloproliferative disorders originating from a multipotent stem cell. Bone marrow examinations reveal chromosomal abnormalities in 15-43% of PV patients and 5% of ET patients, but no specific recurring abnormality has been found to date. We aimed to find cytogenetic aberrations in PV and ET by comparative genomic hybridization (CGH), a relatively new molecular cytogenetic technique. In this study, CGH analysis was performed on peripheral blood leukocytes of 12 PV patients and 8 ET patients. One patient (8.3%) with PV had an abnormal karyotype with a deletion in 7q11.2 and one patient with ET (12.5%) had a gain in 18p. Peripheral blood analysis by CGH revealed a low frequency of cytogenetic abnormalities in PV and ET patients. However, using CGH we were able to detect two cytogenetic aberrations that were not reported previously in these disorders.

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.

Recently, a working-model of a stepwise malignant transformation in the molecular pathogenesis of multiple myeloma (MM) was proposed, involving the tumor suppressor gene TP53 and retinoblastoma gene (RB1) as prominent components of cell cycle control. To further define the role of TP53 and RB1 in disease progression, we retrospectively analyzed by fluorescence in situ hybridization (FISH) cytological material from 16 patients who underwent sequential bone marrow biopsies during the course of their disease. For TP53, no deletions were detected at presentation or during follow-up. It is possible that the patients reported here represent a subset with relatively long survival, and therefore did not demonstrate the TP53 deletions that had been reported in patients with a very poor prognosis. For RB1, monoallelic deletion was demonstrated in nine patients. In each case, the deletion appeared already in the first biopsy analyzed. The presence of a deletion did not affect the rate of tumor progression or the length of follow-up, and thus prognosis. Monoallelic deletions of RB1 appear to be a frequent and early event in the pathogenesis of MM, without obvious relevance for disease progression.

In this study we evaluated the replication pattern and cell-cycle dynamics of cells from patients considered to have a premalignant condition (monoclonal gammopathy, or MGUS) and patients with multiple myeloma (MM), as well as healthy controls. We applied the fluorescence in situ hybridization (FISH) technique with the TP53, RB-1 and 21q22 loci on the patient's cells. Asynchrony was determined by the presence of one single and one set of double dots in the same cell. The rate of asynchronic replication was significantly higher in the cells from MM patients, with intermediate value in the cells from MGUS, while the lowest rate was in cells from controls. We suggest that these results may reflect the changes in gene replication and cell-cycle progression that occur in premalignant and malignant cells.

Chromosomal aberrations can be detected in 50% of patients with chronic lymphocytic leukemia (CLL). A role for tumor suppressor genes in the genesis of lymphoid tumors has been reported. In B-CLL, p53 gene mutations were found in 10-15% of the patients. We used fluorescence in situ hybridization (FISH) to detect p53 deletion in B-CLL. We also correlated the cytogenetic findings with the clinical course. In situ hybridization to interphase nuclei showed monallelic p53 deletion in 6 of 23 patients (26%). The percentage of cells with one p53 signal ranged from 12 to 100. A statistically significant correlation between p53 deletion and progression of CLL was demonstrated. We conclude that FISH is a sensitive and reliable method to detect deletion of specific genes (i.e., p53) in CLL. The finding of p53 deletion is associated with disease progression.

Essential thrombocytosis (ET) is a clonal, chronic myeloproliferative disorder (MPD) originating from a multipotent stem cell. To date no specific cytogenetic marker has been found in ET. It was recently reported that chromosomal aberrations have been detected by fluorescence in situ hybridization (FISH) in patients with normal karyotypes or nonanalyzable metaphases. Therefore, we evaluated whether trisomies 8 and 9, which are commonly found in MPDs, can be detected in ET by FISH and compared the results with chromosome analysis. Peripheral blood mononuclear cells of patients with essential thrombocytosis were studied by classical chromosome banding and by FISH. We used biotin labeled α satellite of chromsome 8 and biotin labeled β satellite of chromosome 9 as probes for the FISH studies. FISH detected 5 patients with trisomy 8 and 5 with trisomy 9 of the 18 patients evaluated. No trisomy was found by cytogenetic studies. The trisomies were detected by FISH in only a minority of the cells. No correlation was found between the presence of a trisomy and clinical characteristics. FISH is a sensitive method for the detection of trisomes 8 and 9 in patients with ET. The common finding of these chromosomal aberrations in MPD suggests that genes associated with myeloid proliferation are located on these chromosomes. Standardization of interphase cytogenetics is needed before this technique can be accepted for routine use in the clinic.

The malignant plasma cells of multiple myeloma (MM) have a low proliferative activity and therefore cytogenetic studies of the disease have been severely limited. We evaluated the role of fluorescence in situ hybridization (FISH) in the detection of numerical chromosomal abnormalities in early stages of myeloma and the applicability of the method to stored archival slides. Old air-dried bone marrow smears from 15 myeloma patients obtained at presentation were probed with α satellite DNA sequences to chromosomes 3 and 7. Numerical chromosome aberrations were found in eight (53%) of the patients, including six (of 12) with trisomy 7, and two (of eight) with trisomy 3. This study demonstrates that FISH is a sensitive method for the detection of numerical aberrations in myeloma and for the study of old slides for retrospective analysis.

Five cases of supernumerary marker chromosomes were identified in prenatal diagnosis as derived from chromosomes 18, X, and Y. One unexpected finding was in a case where the PCR was positive for the SRY gene while fluorescence in situ hybridization was positive for two X centromeres. In another case with an X derived supernumerary marker the newborn was phenotypically normal. Two women with fetal mar(18) and mar(Xp) decided to terminate the pregnancy. The fifth pregnancy had a karyotype of 46,XX,-15,+der(15)t(Y:15)(q11,23;p13). A phenotypically normal girl was born at term.

Objective To provide an up-to-date review of studies that have examined the relative role of endometrial development in in vitro fertilization (IVF) and embryo transfer (ET) treatment in relation to the treatment outcome. Data Identification The most important published studies and personal communications related to this topic have been identified through a computerized bibliographical search (MEDLINE). Study Selection Studies that have evaluated the endometrial maturation in IVF and ET treatment with respect to different treatment protocols of ovarian stimulation. Clinical trials exploring the efficacy of various combinations of hormonal supplementation that aim to improve the endometrial environment and treatment outcome. Publications and personal communications reporting a variety of treatment protocols and drugs utilized for the creation of artificial endometrial cycles in IVF treatment employing donated eggs. Results Ovarian stimulation frequently adversely affects the process of endometrial maturation. Various kinds of hormonal supplementation, used in clomiphene citrate- and/or human menopausal gonadotropin (hMG)-stimulated cycles have not improved treatment outcome. Human chorionic gonadotropin or natural progesterone (P) supplementation administered after controlled ovarian stimulation with gonadotropin-releasing hormone and hMG effectively corrected the luteal phase defect and resulted in an improved conception rate. The endometrium of agonadal women is highly conducive to hormonal manipulation. All estrogen preparations used effectively promoted endometrial growth and proliferation. Natural P is superior to synthetic progestins for induction of receptive secretory endometrium. Conclusion The development of adequately receptive endometrium is a major factor determining the outcome of IVF and ET treatment.

We describe the use of the fluorescence in situ hybridization (FISH) technique to detect residual Philadelphia chromosome-positive (Ph+) cells in a patient with blastic phase chronic myelogenous leukemia (CML) after aggressive cytoreductive treatment. The analysis was made in interphase nuclei because of the very small number of recognizable metaphases in leukemic patients. FISH was a reliable tool for the detection of chromosome translocations in interphase nuclei as compared with conventional cytogenetic and polymerase chain reaction (PCR) techniques.

The study investigates the effect of sperm preincubation with FF on the fertilization rate in an IVF program. The oocytes inseminated with FF pretreated semen showed a significantly higher rate of fertilization. The percentage of cleavage and polypronuclear occurrence did not differ from the controls.

608 Senescence in genotoxic amniocytes and stressed trophoblasts Tal Biron-Shental, Moshe Fejgin, Yehudit Sharon, Dvora Kidron, Aliza Amiel Meir Medical Center, Sackler School of Medicine, Tel Aviv University, Obstetrics and Gynecology, Kfar Saba, Israel, Meir Medical Center, Tel Aviv University, Genetic Institute, Kfar Saba, Israel, Bar Ilan University, Faculty of Life Science, Ramat Gan, Israel, Meir Medical Center, Sackler School of Medicine, Tel Aviv University, Pathology, Kfar Saba, Israel OBJECTIVE: Cellular senescence is a state of metabolic and cell cycle arrest evoked by exogenous or endogenous stressors, especially genotoxic stress. Some cases of senescence are characterized by formation of senescence-associated heterochromatin foci (SAHF). Short, dysfunctional telomeres lead to senescence. We have previously reported short telomeres in aneuploidy, intrauterine hypoxia (which causes intrauterine fetal growth restriction [IUGR]), and in uncontrolled gestational diabetes mellitus. We studied senescence in amniocytes and placentas from aneuploidic fetuses, in trophoblasts from IUGR fetuses, and from diabetic placentas, by assessing SAHF. STUDY DESIGN: Using DAPI staining, we counted the percentage of cells with increased nuclear fragmentation (SAHF). We assessed SAHF expression in trophoblasts from placental biopsies (n 7) and in amniocytes (n 10) from known trisomy-21 fetuses and compared the results to control placentas (n 6) and to amniocytes (n 10) from fetuses with a known normal karyotype. We also assessed the presence of SAHF in trophoblasts from pregnancies complicated by IUGR (n 12) and from pregnancies complicated by uncontrolled diabetes mellitus [DM] (n 10) and compared them to gestational-agematched controls from uncomplicated pregnancies (n 12). RESULTS: A significantly higher rate of cells with SAHF was found in trisomy-21 placentas and amniocytes, as well as in IUGR and in trophoblasts from pregnancies with uncontrolled diabetes compared to the control samples (Figure). CONCLUSION: Increased SAHF formation in amniocytes and in trophoblasts that were previously found to express shorter telomeres emphasizes the correlation between short telomeres and senescence. These findings may be linked to other genetic instability parameters previously described in trisomy-21 and help explain intrauterine programming in pregnancies with IUGR and uncontrolled diabetes mellitus. 609 Insulin growth factor 1 (IGF-1) therapy restored IUGR induced alteration in pancreatic tissues Khaled Omar, Tarek Alsaied, Ahmed Lababidi, Helen Jones, Swathi Balaji, Sundeeb Keswani, Timothy Crombleholme, Mounira Habli Cincinnati Childrens Hospital medical center, Center for molecular fetal therapy, Cincinnati, OH, Cincinnati Childrens Hospital medical center, Pediatrics, Cincinnati, OH, Colorado Childrens Hospital medical center, Pediatric surgery, Aurora, CO OBJECTIVE: We demonstrated that intraplacental gene therapy with adenoviral insulin growth factor (Ad-hIGF1) corrects impaired birthweight and glucose regulatory response in a mouse model of placental insufficiency. Evidence from diabetic patients and Murine IUGR offspring demonstrates decreased area and mass of islets and beta cells. We hypothesized that one of the mechanisms of AdhIGf1 induced attenuation in IUGR related adult onset diabetes is by restoring pancreatic mass, beta and alpha cell ratio. STUDY DESIGN: Laparotomy was performed on pregnant C57BL/6J mice at gestational day 18 and pups were divided into 3 groups (n 3). Control: Sham operated; IUGR: by ligation of a branch of mesenteric uterine artery; IGF1-Treated: intra placental injection of Ad hIGF1 after ligation. Pups were delivered on day 20, cross-fostered to CD1 mice. At 32 weeks, Pancreas of the off springs were weighed, and histologically processed and whole mounted. After every 20 section, a 5 um consecutive primary and reference sections were obtained for the entire pancreas. Immunohistochemistry staining was performed for Beta (anti-insulin) and Alpha (anti-glucagon) cells, and area was quantified (design-based stereology). Data were analysed using ANOVA. RESULTS: Male IUGR demonstrated 22% significant reduction in pancreatic mass (230.6 5.8 vs 296 5.7 vs 290 10 mg, p 0.01), 84 % reduction in Islets/Pancreas percentage area (2.5 1.1% vs 14.8 2.6% vs 16 3.7%, p 0.02), 80% in Beta cell/Alpha cell percentage area and 12% in Beta cell/ Islets percentage area (Table) as compared to SHAM, which was restored to normal with IGF1 treatment. Total area of pancreas, Islets, beta and alpha cells did not show any significant differences among 3 groups. CONCLUSION: Intra-placental gene transfer of Ad-hIGF1 restored IUGR-induced alterations in pancreatic mass, beta and alpha cell ratio. These changes may represent a potential mechanism of fetal reprogramming by which (AdhIGF1) may attenuate fetal predisposition to adult onset Diabetes. Algorithm for stepwise, contingent Down syndrome screening www.AJOG.org Academic Issues, Antepartum Fetal, Clinical Ob, Fetus, Genetics, Hypertension, Med-Surg-Diseases, Operative Ob, U/S Poster Session IV

pregnancies complicated with intrauterine growth restriction Tal Biron-Shental, Yudith Sharon, Dvora Kidron, Moshe D. Fejgin, Aliza Amiel Meir Medical Center, Tel Aviv University, Obstetrics and Gynecology, Kfar Saba, Israel, Meir Medical Center, Genetic Institute, Kfar Saba, Israel, Meir Medical Center, Tel Aviv University, Pathology, Kfar Saba, Israel, Meir Medical Center, Faculty of Life Sciences, Bar Ilan University, Genetic Institute, Kfar Saba, Israel OBJECTIVE: Telomeres are nucleoprotein structures sited at the termini of the chromosomes that protect them from end to end fusion and degradation. Intrauterine Growth Restriction (IUGR) correlates with placental telomere shortening and with senescence. Senescence is associated with changes in the nuclear chromatin known as senescence-associated heterochromatin foci (SAHFs). Shortened and therefore unstable chromosomes can be stabilized by transfer of telomeres from other chromosomes. This process is termed telomere capture. Our aim was to assess mechanisms of telomere shortening in placentas from pregnancies complicated with IUGR. STUDY DESIGN: Placental biopsies derived from 13 pregnancies complicated with IUGR and from 12 gestational-age matched uncomplicated pregnancies. Clinical and histopathological characteristics were collected to ensure IUGR was secondary to placental insufficiency. We estimated the percentage of trophoblasts with SAHFs and the expression of the telomere capture mechanism using Dapi staining and FISH technique. RESULTS: Significantly increased expression of SAHFs (p 0.013) and significantly increased appearance of the telomere capture mechanism (p 0.023) were observed in placental biopsies from pregnancies complicated with IUGR compared to the control samples. (table). CONCLUSION: These results support and explain the observations of telomere shortening in IUGR placentas. We suggest that these findings may play a role in the pathophysiology of IUGR, perhaps by promoting senescence in trophoblasts of IUGR placentas.

and improving insulin sensitivity. We sought to assess whether the addition of metformin to insulin treated pregnant women would improve glucose control and lower insulin requirements. STUDY DESIGN: This retrospective study included pregnant women with diabetes requiring 100 units of insulin to achieve euglycemia. Unbalanced glucose levels mandating further treatment ( 100 daily units of insulin) were divided into 2 groups: Group A treated with increasing doses of insulin solely. Group B addition of metformin 850mg bid along with insulin. The groups were compared for parameters of glucose control (number of daily hyperglycemia levels, time needed to achieve optimal control, maternal satisfaction on a scale from 1 to 5 and perinatal outcome (birthweight, macrosomia, shoulder dystocia, neonatal hypoglycemia). RESULTS: 64 pregnant women meeting the inclusion crtieria were included. Metformin was added to the insulin treatment in 24 women (group B) while the other 40 were administered with increasing doses of insulin to achieve euglycemia (group A). The two groups were similar with regards to maternal age, body mass index, uterine scar and percentage of pre-gestational diabetes. Mean daily insulin requirements were significantly higher in group A (1352.3 vs 1053.6 units, p 0.05). Optimal glycemic control was achieved earlier with the combined treatment (8.31.2 days vs 10.11.2 days, p 0.05) and was better tolerated by the parturients (satisfaction score of 4.3 vs 3.6, p 0.05). Obstetrical performance was similar between the two groups with similar birthweights (3485212gr vs 3387138gr), NICU admission rates, neonatal hypoglycemia and macrosomia. CONCLUSION: The addition of metformin to pregnant women with diabetes requiring large amounts of insulin resulted in more rapid glucose control and higher maternal satisfaction and should be considered in these cases.

Laparoscopic surgery is currently the preferred diagnostic and treatment modality for ectopic pregnancy (EP). Cornual pregnancy, a rare and dangerous form of EP, is usually treated by cornual resection or hysterectomy. We report the first case to be treated by laparoscopic surgery. A 27 year old, gravida 3 para 2, was diagnosed with a nine week right cornual pregnancy. Laparoscopy revealed a 3 x 4 cm bulge into the right cornual area. Both fallopian tubes were otherwise normal. The uterus was fixed by a grasping forceps and the right tube and ovarian ligament were coagulated to reduce the blood supply. The gestational area was entered via a 1 cm incision using unipolar scissors and electrocoagulation. The pregnancy contents were suctioned; cavity margins and placental bed were coagulated until hemostasis was secured. The uterus contracted. The posterior leaf of the broad ligament was flapped over the incision site and attached by coagulation points. Postoperative course was uneventful. A hysterosalpingogram performed 4 months post surgery revealed a normal uterine cavity and blocked right tube.