The Relevance of the Second Cesarean Delivery in the Reduction of Institutional Cesarean Delivery Rates.

OBJECTIVE: The cesarean delivery rate has increased worldwide. The aim of our study was to assess the events associated with the second cesarean deliveries in our institution. SUBJECTS AND METHODS: All cesarean deliveries at the Maternity Hospital, Kuwait, from January 1 to December 31, 2013, were identified. A comparative study was undertaken on patients having their first and second cesarean deliveries. The social and clinical characteristics of these patients were extracted from our records and the antenatal, intrapartum, and postpartum course of the pregnancies and their outcomes documented. RESULTS: During the study period, 10,586 deliveries were recorded, including 3,676 cesarean deliveries, i.e., a cesarean delivery rate of 34.7%. 840 of these patients were undergoing their first cesarean delivery (group A) and 607 patients were undergoing their second (group B); 484 patients from group A and 341 patients from group B with complete records were analyzed. Mean age (30.89 ± 4.93 vs. 29.94 ± 5.56 years, p = 0.008), parity (1.49 ± 1.22 vs. 0.98 ± 1.60, p < 0.0001), gestational age at delivery (38.12 ± 2.61 vs. 37.66 ± 3.11 weeks, p = 0.02), and fetal birth weight (3,211.60 ± 691.51 vs. 2,829.73 ± 863.26 g, p < 0.001) were significantly higher in group B than in group A. 53.2% of the patients in group B requested repeat cesarean delivery, their second cesarean. The rate of maternal morbidity was low. CONCLUSIONS: The incidence of repeat cesarean delivery in group B is high, and its reduction should contribute to a lowering of the overall cesarean delivery rate.

Epithelioid trophoblastic tumor: report of two cases in postmenopausal women with literature review and emphasis on cytological findings.

BACKGROUND: Epithelioid trophoblastic tumor (ETT) is a rare gestational trophoblastic neoplasm of intermediate trophoblasts. It was first described by Shih and Kurman [Am J Surg Pathol 1998;22:1393-1403] who outlined its clinicopathologic characteristics in 14 cases, establishing it as a distinct entity of gestational trophoblastic tumors. It represents 1.39% of all gestational trophoblastic diseases. Most cases are reported in reproductive-age women following a prior gestation with a time interval between 2 weeks and 30 years. ETT is extremely rare in postmenopausal women. It is commonly misdiagnosed as a squamous cell carcinoma (SCC), poorly differentiated carcinoma or another gestational trophoblastic tumor. Limited data is available regarding its cytological features on Pap smears. CASES: We report 2 cases of uterine ETT occurring in postmenopausal women. In both cases, an initial diagnosis of an SCC and a poorly differentiated carcinoma was rendered. We highlight the features of ETT helpful in differentiating it from other mimickers with emphasis on rarely reported cytological features of this neoplasm. CONCLUSION: ETT is a rare tumor with characteristic cytological features, but is commonly confused with SCC. A high index of suspicion is needed to make the correct diagnosis or to raise the consideration of ETT, especially in cases with an increased ß-human chorionic gonadotropin.

Phylogenetic analysis of partial L1 gene of 10 human papillomavirus types isolated most commonly from women with normal and abnormal cervical cytology in Kuwait.

This study was undertaken to evaluate the presence of human papillomavirus (HPV) variants in cervical samples. L1 genetic variable region was studied in 10 HPV types: HPV 11, 16, 18, 33, 53, 54, 56, 61, 66 and 81. A total of 116 isolates were examined, including 47 HPVs isolated from women with normal cytology and 69 with abnormal cytology of different grades. HPV sequences were detected using MY09/MY11 consensus primers. Fifty silent and 65 missense mutations were detected. Two missense mutations were detected in HPV18, 3 in HPV56 and 17 in HPV61. The number of missense mutations per isolate ranged from 1 to 3, except in HPV54 and HPV61, where 7 and 11 missense mutations were found, respectively. Most of the isolates (52.3 %) with missense mutations were isolated from women with abnormal cervical samples. Low-grade squamous intraepithelial lesion cytology diagnosis dominated all cervical abnormalities. This study is the first on the identification of molecular variants in the Middle East and suggests the circulation of new HPV subtypes and variants in Kuwait, which needs to be confirmed by further analysis of the complete HPV genome.

Immunocytochemical detection of raf kinase inhibitor protein and human papillomavirus profiling of normal and abnormal cervical ThinPrep samples.

OBJECTIVES: This study investigates the potential value of Raf kinase inhibitor protein (RKIP) as a marker of normal squamous cells in ThinPrep slides. RKIP was evaluated for its ability to distinguish between normal and abnormal cervical samples in the context of human papillomavirus (HPV) infections. STUDY DESIGN: A total of 316 ThinPrep samples were taken from women with normal and abnormal cervices. ThinPrep slides were Papanicolaou stained and reported. Residual samples were used for RKIP immunostaining and HPV PCR-based sequencing. RESULTS: RKIP expression was seen in both nuclei and cytoplasm in 83.7% of samples. RKIP expression was highest (84.6%) in samples with a diagnosis of high-grade squamous intraepithelial lesion (HSIL) or worse; expression was lower in low-grade squamous intraepithelial lesions (73%) and was lowest in samples with normal cytology (p = 0.0023). A total of 74% of HPV-infected ThinPrep samples were immunopositive, and 67% of samples that did not harbor HPV were also immunopositive (p = 0.414). Sensitivity and specificity of RKIP were 84.6 and 34.6%, respectively, for the detection of samples with HSIL or worse. CONCLUSIONS: This study showed that RKIP expression may be of some value as a marker for abnormal cervical cells. Combined RKIP expression and HPV testing could improve the identification of samples with abnormal cytology.

Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study.

BACKGROUND: Knowledge about the distribution of human papillomavirus (HPV) genotypes in invasive cervical cancer is crucial to guide the introduction of prophylactic vaccines. We aimed to provide novel and comprehensive data about the worldwide genotype distribution in patients with invasive cervical cancer. METHODS: Paraffin-embedded samples of histologically confirmed cases of invasive cervical cancer were collected from 38 countries in Europe, North America, central South America, Africa, Asia, and Oceania. Inclusion criteria were a pathological confirmation of a primary invasive cervical cancer of epithelial origin in the tissue sample selected for analysis of HPV DNA, and information about the year of diagnosis. HPV detection was done by use of PCR with SPF-10 broad-spectrum primers followed by DNA enzyme immunoassay and genotyping with a reverse hybridisation line probe assay. Sequence analysis was done to characterise HPV-positive samples with unknown HPV types. Data analyses included algorithms of multiple infections to estimate type-specific relative contributions. FINDINGS: 22,661 paraffin-embedded samples were obtained from 14,249 women. 10,575 cases of invasive cervical cancer were included in the study, and 8977 (85%) of these were positive for HPV DNA. The most common HPV types were 16, 18, 31, 33, 35, 45, 52, and 58 with a combined worldwide relative contribution of 8196 of 8977 (91%, 95% CI 90-92). HPV types 16 and 18 were detected in 6357 of 8977 of cases (71%, 70-72) of invasive cervical cancer. HPV types 16, 18, and 45 were detected in 443 of 470 cases (94%, 92-96) of cervical adenocarcinomas. Unknown HPV types that were identified with sequence analysis were 26, 30, 61, 67, 69, 82, and 91 in 103 (1%) of 8977 cases of invasive cervical cancer. Women with invasive cervical cancers related to HPV types 16, 18, or 45 presented at a younger mean age than did those with other HPV types (50·0 years [49·6-50·4], 48·2 years [47·3-49·2], 46·8 years [46·6-48·1], and 55·5 years [54·9-56·1], respectively). INTERPRETATION: To our knowledge, this study is the largest assessment of HPV genotypes to date. HPV types 16, 18, 31, 33, 35, 45, 52, and 58 should be given priority when the cross-protective effects of current vaccines are assessed, and for formulation of recommendations for the use of second-generation polyvalent HPV vaccines. Our results also suggest that type-specific high-risk HPV-DNA-based screening tests and protocols should focus on HPV types 16, 18, and 45.

Venous Thromboembolism Risk and Adequacy of Prophylaxis in High Risk Pregnancy in the Arabian Gulf.

OBJECTIVES: To estimate the prevalence of venous thromboembolism (VTE) risk factors in pregnancy and the proportion of pregnancies at risk of VTE that received the recommended prophylaxis according to the American College of Chest Physicians (ACCP) 2012 published guidelines in antenatal clinics in the Arabian Gulf. METHODS: The evaluation of venous thromboembolism (EVE)-Risk project was a non-interventional, cross-sectional, multi-centre, multi-national study of all eligible pregnant women (≥17 years) screened during antenatal clinics from 7 centres in the Arabian Gulf countries (United Arab Emirates, Kuwait, Bahrain, Qatar and Oman). Pregnant women were recruited during a 3-month period between September and December 2012. RESULTS: Of 4,131 screened pregnant women, 32% (n=1,337) had ≥1 risk factors for VTE. Common VTE risk factors included obesity (76%), multiparity (33%), recurrent miscarriages (9.1%), varicose veins (6.9%), thrombophilia (2.6%), immobilization (2.0%), sickle cell disease (2.8%) and previous VTE (1.6%). Only 8.3% (n=111) of the high risk patients were on the recommended VTE prophylaxis. Enoxaparin was used in 80% (n=89) of the cases followed by tinzaparin (4%; n=4). Antiplatelet agents were prescribed in 11% (n=149) of pregnant women. Of those on anticoagulants (n=111), 59% (n=66) were also co-prescribed antiplatelet agents. Side effects (mainly local bruising at the injection site) were reported in 12% (n=13) of the cases. CONCLUSION: A large proportion of pregnant women in the Arabian Gulf countries have ≥1 VTE risk factor with even a smaller fraction on prophylaxis. VTE risk assessment must be adopted to identify those at risk who would need VTE prophylaxis.

Consecutive successful pregnancies subsequent to intravenous immunoglobulin therapy in a patient with recurrent spontaneous miscarriage.

BACKGROUND: Recurrent spontaneous miscarriage (RSM) has a multifactorial etiology, mainly due to karyotype abnormalities including balanced translocation, anatomical uterine disorders, and immunological factors, although in 50%-60% the etiology is unexplained. The treatment of RSM remains challenging, and the role of intravenous immunoglobulin (IVIG) in RSM is controversial. CASE REPORT: Mrs HM, 37 years old, obstetric summary: P0+1+13+1, a known case of hypothyroidism/polycystic ovary syndrome, married to an unrelated 47-year-old man, presented to our RSM clinic in early January 2014 for investigation and treatment. She has had multiple failed in vitro fertilization trials and 13 first-trimester missed miscarriages terminating at 6-7 weeks, all without IVIG therapy. Her tenth pregnancy was spontaneous, managed in London, UK, with multiple supportive therapy and courses of IVIG starting from the third to the 30th week of pregnancy. The pregnancy ended at 36 weeks of gestation with a cesarean section and a live girl baby was delivered. Mrs HM had balanced translocation, 46XX t (7:11) (p10:q10). Preimplantation genetic diagnosis/intracytoplasmic sperm injection/in vitro fertilization was performed with embryo transfer on May 29, 2014, and resulted in a successful pregnancy. She was commenced immediately on metformin, luteal support, and IVIG therapy, started at 6 weeks of gestation and at monthly intervals until 30 weeks of gestation, and also received additional therapy. The pregnancy was monitored with ultrasound, progressed uneventfully until admission at 35 weeks of gestation, with mildly elevated liver enzymes and suspected fetal growth restriction. She was managed conservatively, and in the light of nonreassuring fetal status, a live female infant weighing 2.29 kg was delivered by emergency cesarean section on January 14, 2015, with an Apgar score of 8 and 9 and mild respiratory distress, and was admitted to the Special Care Baby Unit for intensive therapy. The mother and baby made satisfactory progress and were discharged on January 24, 2015. CONCLUSION: Two consecutive successful pregnancies in Mrs HM with multiple causes of RSM treated with other medications and IVIG strongly suggest that IVIG has a positive role in RSM.

Molecular characterization of a population-based series of endometrial stromal sarcomas in Kuwait.

Endometrial stromal sarcomas (ESSs) frequently harbor genetic fusions, including JAZF1-SUZ12 and equivalent fusions in low-grade ESS (LGESS) and YWHAE-NUTM2 in high-grade ESS (HGESS). This study aims to classify a population-based series of ESSs in Kuwait based on the 2014 World Health Organization classification system and to assess the diagnostic use of interferon-induced transmembrane protein 1 (IFITM1) immunomarker for ESSs. Twenty ESSs including 19 LGESSs and 1 HGESS treated during the period between 2002 and 2013 were identified, and the cases were reviewed and characterized using fluorescence in situ hybridization and immunohistochemical studies. Thirteen (81.3%) of 16 LGESSs with interpretable results showed JAZF1 and/or PHF1 genetic rearrangements by fluorescence in situ hybridization, and the only HGESS in the series showed YWHAE genetic rearrangement. All LGESSs with interpretable results showed positive immunostaining for CD10 compared with 11 (61%) of 18 that showed positive immunostaining for IFITM1; 4 of 7 IFITM1-negative LGESSs showed JAZF1 and/or PHF1 rearrangements. A series of uterine leiomyomas, leiomyosarcomas, adenosarcomas, and carcinosarcomas were included for comparison, and positive IFITM1 staining was found in 1 of 10 leiomyomas, 3 of 13 leiomyosarcomas, 3 of 4 adenosarcomas, and 3 of 8 carcinosarcomas, compared to 0 of 10 leiomyomas, 9 of 13 leiomyosarcomas, 3 of 4 adenosarcomas, and 5 of 8 carcinosarcomas that were positive for CD10. Our results demonstrated characteristic genetic rearrangements in a high percentage of LGESSs in this Middle Eastern population, and IFITM1 antibody appears to be less sensitive than CD10 for LGESS.

Viral load of human papillomavirus in women with normal and abnormal cervical cytology in Kuwait.

INTRODUCTION: Human papillomaviruses (HPV) are the most commonly known sexually transmitted agents. Almost all cases of cervical cancer are caused by persistent infection. This study was conducted to ascertain whether there is a difference in HPV load in cervical samples with normal and abnormal cervical cytology reports in Kuwait. METHODOLOGY: HPV-positive abnormal ThinPrep samples (n = 206) and normal ThinPrep samples (n = 120) were taken from women attending gynecology clinics. Real-time PCR was used to measure the viral load for all HPV genotypes. RESULTS: The median normalized viral load in samples with normal and abnormal cytology reports was 0.86 × 10-7 and 4.66 × 10-7, respectively (p = 0.001). Median normalized viral load of high-risk (HR), intermediate-risk (IR) and low-risk (LR) HPV was 4.04 × 10-7, 0.71 × 10-7 and 2.38 × 10-7, respectively, (p = 0.002). CONCLUSIONS: The findings suggest that, in the absence of a proper screening programme in Kuwait, quantification of HPV viral load could be considered as a surrogate virology test to identify women with abnormal cytology. Further population-based prospective studies are needed to include more women with high-grade and invasive carcinoma reports.

Trace elements and cell-mediated immunity in gestational and pre-gestational diabetes mellitus at third trimester of pregnancy.

THE AIM OF THE STUDY: To evaluate the correlations between Zn2+, Cu2+, Mg2+, Se2+ and Cr3+ and alteration in T cell subsets during diabetic and normal pregnancy. METHODS: The study involved 63 women with gestational diabetes mellitus (GD) and 16 pregnant women with Type 2 diabetes and 48 healthy, non-pregnant women were included as controls. Ten ml of whole venous blood from each participant was analyzed for electrolytes by atomic absorption; total antioxidant activity, individual enzymatic antioxidants by spectrophotometry; and lymphocyte sub-populations by flow cytometry. RESULTS: There were significant changes in lymphocyte sub-populations: Naïve T cells were decreased and memory T-cells and activated T cells (CD4+HLA-DR+, CD4+CD29+) were increased in diabetes in pregnancy. Zn2+ and Cr3+ deficiency were observed in Type 2 diabetics with an increase in Cu2+ in all pregnant cohorts. In healthy pregnant subjects, CD4+-HLA-DR+ was increased in direct proportion to serum Mg2+ (p<0.05) and Se2+ (p<0.01). In insulin-treated GD patients, CD4+CD29+ cells were increased proportionally to serum Zn2+ (p<0.05) while in diet controlled GD cohort CD45RO+/ CD45RA+ T cells correlated directly with serum Mg (p<0.05) and Zn2+ (p<0.01) while it correlated inversely with serum Cu2+ (p<0.01). CONCLUSIONS: The results of the present study show a correlation between trace element deficiency and increased lipid peroxidation in diabetes in pregnancy and lymphocyte activation. Dietary manipulation may, therefore, point to improvement in existing approaches to management of diabetes mellitus in pregnancy.

Uterine rupture and subsequent pregnancy outcome--how safe is it? A 25-year study.

OBJECTIVES: (a) To review the cases of ruptured uterus over the last 25 years and analyze the causative factors with a view to its prevention (b) To analyze subsequent pregnancy outcome with a view to its safety. METHOD: The case notes were reviewed for all patients with ruptured uterus over a period of 25 years from January 1982 to January 2007. Relevant dates relating to the characteristics of labor, delivery, maternal, perinatal, and subsequent pregnancy outcomes were assessed. RESULTS: The incidence of ruptured uteri was calculated to be 0.03%. Total deliveries included in the study were 152,426. There were 46 cases of ruptured uteri and 44 were available for study. Twenty-two (52%) ruptured uteri occurred in patients with previous caesarean scars, of which 10 occurred in women with previous four or more caesarean sections. In 12 cases (27%), uterine rupture occurred due to oxytocin; PGE2 and oxytocin were used in 3 of these 12 cases. Two (4.5%) ruptures occurred due to non-removal of cervical cerclage during labor. Two (4.5%) primigravidae ruptured their uterus following road traffic accident, resulting in maternal and fetal deaths. Malpresentation in labor resulted in eight (18%) ruptures. Rupture occurred at the fundus in 10 cases and in the lower segment in the remaining 34. Fetal heart abnormalities were observed in all cases in which the uterus ruptured during labor. Abdominal hysterectomy was performed in 20 cases (45%) of which 13 were subtotal and 7 (10%) were total. Of the remaining 24 (55%) patients, 10 had suture repair and in addition 14 patients underwent hypogastric artery ligation. Later, 22/24 (92%) women became pregnant. Twenty (91%) were delivered by planned caesarean section. There were no maternal or fetal complications. The remaining two women had previous classical scar, undetected malpresentation, and sparse antenatal care. Their uteri ruptured spontaneously at 32 and 35 weeks at home. They died intra-operatively due to intractable hemorrhage along with their fetus. CONCLUSION: In the previous caesarean section, the indiscriminate use of oxytocin and malpresentation are the risk factors for uterine rupture. Child birth after uterine rupture is not to be recommended routinely. Most women with a previous uterine rupture with meticulous tertiary level antenatal care had a favorable outcome in subsequent pregnancies.