In vitro and in vivo identification of clinically approved drugs that modify ACE2 expression.

The COVID-19 pandemic caused by SARS-CoV-2 has is a global health challenge. Angiotensin-converting enzyme 2 (ACE2) is the host receptor for SARS-CoV-2 entry. Recent studies have suggested that patients with hypertension and diabetes treated with ACE inhibitors (ACEIs) or angiotensin receptor blockers have a higher risk of COVID-19 infection as these drugs could upregulate ACE2, motivating the study of ACE2 modulation by drugs in current clinical use. Here, we mined published datasets to determine the effects of hundreds of clinically approved drugs on ACE2 expression. We find that ACEIs are enriched for ACE2-upregulating drugs, while antineoplastic agents are enriched for ACE2-downregulating drugs. Vorinostat and isotretinoin are the top ACE2 up/downregulators, respectively, in cell lines. Dexamethasone, a corticosteroid used in treating severe acute respiratory syndrome and COVID-19, significantly upregulates ACE2 both in vitro and in vivo. Further top ACE2 regulators in vivo or in primary cells include erlotinib and bleomycin in the lung and vancomycin, cisplatin, and probenecid in the kidney. Our study provides leads for future work studying ACE2 expression modulators.

Fractional-Pixel CO2 Laser Treatment in Patients With Urodynamic Stress Urinary Incontinence: 1-Year Follow-Up.

BACKGROUND AND OBJECTIVES: Vaginal pixelated low power and long pulses (LPLP) CO2 laser has been suggested as an optional treatment for stress urinary incontinence (SUI) with many studies reporting short-term improvements. The objective of this study was to assess the 1-year subjective and objective efficacy of vaginal CO2 laser in women with urodynamic SUI. STUDY DESIGN/MATERIALS AND METHODS: This was a prospective multicenter study. Patients with confirmed urodynamic SUI graded as mild or moderate were included. We used three sessions of fractional pixelated CO2 laser for vaginal application and followed up the patients at 6 and 12 months. We used the following measures at follow-up: 1-hour pad test (ICS protocol), questionnaires including Pelvic Floor Distress Inventory 20 (PFDI-20), Pelvic Floor Impact Questionnaire (PFIQ), Patient Global Impression of Improvement (PGI-I), and a 3-day urinary diary. The urodynamic assessment was repeated at 6 months. RESULTS: Fifty-two patients with SUI had three laser treatments, of whom 48 completed a 6-month follow-up and 42 patients completed 12-month follow-up. No serious adverse events were recorded during the study period. A significant reduction on the 1-hour pad test was found from baseline (6.3 ± 1.6 g) to the 12-month follow-up (3.7 ± 1.4 g, P < 0.05) was found. PGI-I showed 75.0%, 61.9%, and 64.3% improvements at 3, 6, and 12 months, respectively. PFDI improved significantly and consistently from baseline until 12 months (37.2 ± 3.89 to 16.1 ± 3.7, P < 0.05). Similarly, PFIQ showed significant improvements from the first treatment up to 12 months. Urodynamic assessment at 6 months showed that 41.4% of patients had no stress incontinence. CONCLUSION: The vaginal CO2 laser was found to be effective for mild-to-moderate SUI over a follow-up period of 1 year, according to a variety of objective and subjective parameters. The wide range of parameters enables optimal patient consultation and subsequent treatment. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Assessment of a double freezing approach in the management of surplus embryos in IVF.

RESEARCH QUESTION: What pregnancy rates are achieved after transfer of cryopreserved double slow-frozen embryos in IVF cycles? Patients in whom surplus thawed cleaved embryos (day 2 or 3) were grown to the blastocyst stage, re-frozen and then re-thawed for transfer (double freezing) were included. DESIGN: Data were collected on all patients who had undergone the above procedure at the IVF unit of Assuta Ramat Hachayal Hospital, Tel Aviv, during a 7-year period. For each patient in the study group, the two-consecutive, matched-by-age patients treated with frozen-thawed single blastocyst transfer were selected to form a 2:1 ratio control group. All embryos were frozen using the slow freeze protocol. RESULTS: A total of 54 patients had 70 embryos that were re-frozen at the blastocyst stage. Twenty-eight of these blastocysts were thawed and 27 underwent transfer to 25 patients. A single embryo was transferred to 23 patients and two embryos were transferred to two patients. The survival rate of the second thawing was 96.4% (27/28). Clinical pregnancy rate was 16% (4/25) and implantation rate was 14.8% (4/27). In the study group, pregnancies were achieved in 22 out of the 25 patients using IVF treatment, indicating good receptivity of the uterus. In the control group, the implantation/pregnancy rates were significantly higher (44.2% [23/52]; P < 0.01). CONCLUSION: The transfer of twice slow-frozen and thawed embryos does not seem to be a beneficial approach in the planned management of cryopreserved surplus embryos owing to the low pregnancy rate achieved after transfer of the re-frozen blastocyst embryos.

The Impact of Sperm and Egg Donation on the Risk of Pregnancy Complications.

OBJECTIVE: The aim of this study was to evaluate obstetric outcomes in relation to the extent of donor sperm exposure with and without egg donation. MATERIALS AND METHODS: This is a retrospective cohort study in a single tertiary care center. All women with a singleton pregnancy who conceived following sperm donation (SD) were included. Obstetrics and neonatal outcomes for pregnancies following single SD were compared with pregnancies following repeat SD from the same donor. In a secondary analysis, we compared pregnancy outcomes among three modes of assisted reproductive technology (intrauterine insemination [IUI-SD], in vitro fertilization [IVF-SD], and IVF sperm + egg donation [IVF-SD + ED]). RESULTS: A total of 706 pregnant women met the inclusion criteria, 243 (34.4%) following the first SD and 463 (65.6%) following repeat donations. Compared with repeat SDs, single donation was not associated with higher rates of preterm delivery (12.8 vs. 12.7%, respectively, p = 0.99), preeclampsia (7.0 vs. 6.9%, p = 0.999), and intrauterine growth restriction (4.1 vs. 3.9%, p = 0.88). Pregnancies following IVF-SD + ED had increased risk for preeclampsia (adjusted odds ratio [AOR], 3.1; 95% confidence interval [CI], 1.5-6.6), preterm labor (AOR, 2.4; 95% CI, 1.1-5.4), and cesarean section (AOR, 2.1; 95% CI, 1.0-4.3) compared with IUI-SD and IVF-SD. CONCLUSION: The extent of donor sperm exposure did not correlate with obstetrics complications, but double gamete donation was associated with increased risk for preeclampsia, preterm labor, and cesarean section.

Sonographic large fetal head circumference and risk of cesarean delivery.

BACKGROUND: Persistently high rates of cesarean deliveries are cause for concern for physicians, patients, and health systems. Prelabor assessment might be refined by identifying factors that help predict an individual patient's risk of cesarean delivery. Such factors may contribute to patient safety and satisfaction as well as health system planning and resource allocation. In an earlier study, neonatal head circumference was shown to be more strongly associated with delivery mode and other outcome measures than neonatal birthweight. OBJECTIVE: In the present study we aimed to evaluate the association of sonographically measured fetal head circumference measured within 1 week of delivery with delivery mode. STUDY DESIGN: This was a multicenter electronic medical record-based study of birth outcomes of primiparous women with term (37-42 weeks) singleton fetuses presenting for ultrasound with fetal biometry within 1 week of delivery. Fetal head circumference and estimated fetal weight were correlated with maternal background, obstetric, and neonatal outcome parameters. Elective cesarean deliveries were excluded. Multinomial regression analysis provided adjusted odds ratios for instrumental delivery and unplanned cesarean delivery when the fetal head circumference was ≥35 cm or estimated fetal weight ≥3900 g, while controlling for possible confounders. RESULTS: In all, 11,500 cases were collected; 906 elective cesarean deliveries were excluded. A fetal head circumference ≥35 cm increased the risk for unplanned cesarean delivery: 174 fetuses with fetal head circumference ≥35 cm (32%) were delivered by cesarean, vs 1712 (17%) when fetal head circumference <35 cm (odds ratio, 2.49; 95% confidence interval, 2.04-3.03). A fetal head circumference ≥35 cm increased the risk of instrumental delivery (odds ratio, 1.48; 95% confidence interval, 1.16-1.88), while estimated fetal weight ≥3900 g tended to reduce it (nonsignificant). Multinomial regression analysis showed that fetal head circumference ≥35 cm increased the risk of unplanned cesarean delivery by an adjusted odds ratio of 1.75 (95% confidence interval, 1.4-2.18) controlling for gestational age, fetal gender, and epidural anesthesia. The rate of prolonged second stage of labor was significantly increased when either the fetal head circumference was ≥35 cm or the estimated fetal weight ≥3900 g, from 22.7% in the total cohort to 31.0%. A fetal head circumference ≥35 cm was associated with a higher rate of 5-minute Apgar score ≤7: 9 (1.7%) vs 63 (0.6%) of infants with fetal head circumference <35 cm (P = .01). The rate among fetuses with an estimated fetal weight ≥3900 g was not significantly increased. The rate of admission to the neonatal intensive care unit did not differ among the groups. CONCLUSION: Sonographic fetal head circumference ≥35 cm, measured within 1 week of delivery, is an independent risk factor for unplanned cesarean delivery but not instrumental delivery. Both fetal head circumference ≥35 cm and estimated fetal weight ≥3900 g significantly increased the risk of a prolonged second stage of labor. Fetal head circumference measurement in the last days before delivery may be an important adjunct to estimated fetal weight in labor management.

Does antenatal steroids treatment prior to elective cesarean section at 34-37 weeks of gestation reduce neonatal morbidity? Evidence from a case control study.

OBJECTIVE: To determine whether antenatal corticosteroids administration prior to an elective cesarean section (ECS) at 34-37 weeks gestation is associated with improved neonatal outcome. MATERIALS AND METHODS: A case control study of women with singleton pregnancies who underwent ECS between 34 and 37 weeks of gestation including two groups: (1) study group in which patients were treated with betamethasone prior to ECS (n = 58) and (2) control group matched for gestational age at delivery in which patients did not receive betamethasone (n = 107). Neonatal measures including respiratory distress syndrome (RDS), transient tachypnea of the newborn (TTN), oxygen requirement, admission to the special care unit, hypoglycemia, hyperbilirubinemia and length of hospitalization were determined in both groups. Composite respiratory morbidity was defined as the presence of either RDS, TTN, mechanical ventilation or oxygen requirement. RESULTS: There was no significant difference in the rate of composite respiratory morbidity nor its components between patients with and without betamethasone treatment (25.9 vs. 25.2%, respectively, p = 0.9). CONCLUSION: Antenatal treatment with corticosteroids prior to ECS at 34-37 weeks of gestation did not result in significant reduction in neonatal respiratory morbidity in our cohort of patients.

In-office Hysteroscopic Extraction of Intrauterine Devices in Pregnant Patients Who Underwent Prior Ultrasound-guided Extraction Failure.

STUDY OBJECTIVE: To determine an effective method of intrauterine device (IUD) retrieval from pregnant women who had previous unsuccessful ultrasound-guided IUD extraction failure. DESIGN: A retrospective cohort study (Canadian task force classification II-1). SETTING: A gynecology department of an outpatient clinic. PATIENTS: Pregnant patients in their first trimester with IUD in situ who underwent prior unsuccessful ultrasound-guided IUD extraction. INTERVENTIONS: Hysteroscopic IUD extraction guided by transabdominal ultrasound. MEASUREMENTS AND MAIN RESULTS: Between 2011 and 2014, 7 of 8 pregnant patients who had undergone previous failed attempts at IUD retrieval via ultrasound guidance underwent successful removal via ultrasound-guided hysteroscopy performed without anesthesia. The sole patient with extraction failure was in her 12th week of pregnancy, and the procedure was concluded to avoid risk to the fetus. Minimal vaginal bleeding was experienced by 2 patients after the procedure. Seven of 8 patients delivered at term without any obstetric complications. One patient had a miscarriage in her 8th week of pregnancy, 2 weeks after successful IUD removal. CONCLUSION: A novel, easy outpatient hysteroscopic technique without anesthesia is presented in case of failure of previous ultrasound-guided IUD removal in early pregnancy. Results are encouraging in this difficult context.

The Yield of Abdominal Ultrasound in the Evaluation of Elevated Liver Enzymes during the Second and the Third Trimester of Pregnancy.

AIMS: To determine the clinical yield of abdominal ultrasound in the evaluation of elevated liver enzymes (ELEs) in the second and the third trimester of pregnancy. METHODS: A retrospective cohort study including all pregnant women admitted to a single tertiary care center was conducted between April 2011 and January 2015 with ELE. Inclusion criteria included gestational age above 24 weeks and ELEs, abdominal ultrasound report, and live fetus. Exclusion criteria included known maternal liver disease, structural or chromosomal fetal anomalies, and positive serology for viral hepatitis. All patients underwent abdominal ultrasound. A significant finding of this study led to a change in treatment. RESULTS: One hundred and twenty patients (41.8%) met inclusion criteria: 93 (77.5%) had a normal scan and 27 (22.5%) had abnormal findings. Significant ultrasound findings were found only in 2 (1.6%) patients: gallstones in the common bile duct and suspected autoimmune hepatitis. There were no significant differences between patients with and without ultrasound findings in the rate of cholestasis of pregnancy, preeclampsia, chronic hypertension, and gestation diabetes. CONCLUSION: Abdominal ultrasound examination in this population has a low clinical yield. The decision to perform an abdominal ultrasound must be individualized based on the obstetric history, clinical findings, and the level of liver enzymes.

Pre-implantation genetic diagnosis-should we use ICSI for all?

OBJECTIVE: Intracytoplasmic sperm injection (ICSI) is commonly used during pre-implantation genetic diagnosis (PGD) in vitro fertilization (IVF), aiming to eliminate the risk of contamination from extraneous sperm DNA. Recently, ICSI "overuse" in non-male infertility has been doubted, since it does not offer an advantage over IVF. Prompted by the aforementioned observations, we sought to assess the accuracy of IVF vs ICSI in PGD cases, as might be reflected by a difference in the prevalence of discarded embryos as a consequent of parental contamination. METHODS: Cohort-historical study of all consecutive patients admitted to the IVF-PGD program in a large tertiary center. The percentages of complete, incomplete diagnosis, PCR failure, abnormal embryos, and the contamination rate with paternal DNA in the IVF-only and the ICSI-only groups. We reviewed the computerized files of all consecutive women admitted to our IVF for a PGD-PCR cycle. Patients were divided accordingly into three groups: an IVF group-where all the oocytes underwent IVF only, an ICSI group-where all oocytes underwent ICSI, and a mixed group-where sibling oocytes underwent both IVF and ICSI. The laboratory data and the genetic diagnostic results were collected and compared between the different insemination groups. RESULTS: Nine-hundred and twenty-seven patients underwent IVF-PGD cycles in our program, 315 in the IVF group, 565 in the ICSI group, and 47 in the mixed group. No differences were observed in fertilization rates, the percentage of embryos available for biopsy, and the percentages of complete, incomplete diagnosis, PCR failure, or abnormal embryos, between the IVF-only and the ICSI-only groups and between the IVF and the ICSI of sibling oocytes in the mixed group. Moreover, contamination with paternal DNA, through contamination with sperm cells, was negligible. Not one single case of misdiagnosis was encountered during the study period. CONCLUSION: It might be therefore concluded that IVF should be the preferred insemination methods in PGD cycles, and ICSI should be indicated only in cases of male-factor infertility.

Trial of labour after caesarean (TOLAC) is associated with increased risk for instrumental delivery.

We compared the rates of instrumental delivery in a cohort of nulliparous women at term (n = 19,416), to primiparous women who attempted labour after prior caesarean (TOLAC) (n = 1747). The rate of instrumental deliveries was higher in the TOLAC group compared to nulliparous gravidas (17.3 vs. 15% respectively, p = 0.001). The difference was more prominent for women who eventually had successful vaginal delivery (TOLAC: 23.9% vs. CONTROLS: 17.1%, p < 0.0001 respectively). Based on our results, previous caesarean whether urgent or elective was associated with an increased risk of instrumental delivery in the subsequent pregnancy.

In Vitro Fertilization Outcomes After Placement of Essure Microinserts in Patients With Hydrosalpinges Who Previously Failed In Vitro Fertilization Treatment: A Multicenter Study.

STUDY OBJECTIVE: To investigate whether hysteroscopic proximal tubal occlusion with Essure microinserts (Conceptus Inc.; Bayer, AG, North Rhine-Westphalia, Germany) can improve pregnancy rates in patients with hydrosalpinges who had failed in vitro fertilization (IVF) treatment. DESIGN: A prospective cohort study. SETTING: University-affiliated tertiary centers. PATIENTS: Twenty-four consecutive women with hydrosalpinges who had failed IVF treatment were included. INTERVENTIONS: Hysteroscopic placement of Essure microinserts for hydrosalpinx blockage followed by IVF treatment. MEASUREMENTS AND MAIN RESULTS: Ongoing pregnancy and live birth rates were recorded. Of the 24 patients undergoing a total of 42 IVF cycles after Essure insertion, 18 (75% of patients and 42.8% of IVF cycle attempts) conceived and 16 delivered live births (66.6% of patients and 38.1% of IVF cycle attempts). CONCLUSION: Hysteroscopic proximal occlusion of hydrosalpinges with Essure microinserts is a valuable alternative to laparoscopic salpingectomy, resulting in reasonable pregnancy rates.

Pregnancy and Birth Outcomes Among Primiparae at Very Advanced Maternal Age: At What Price?

OBJECTIVES: In light of the potential physical and emotional costs to both woman and child, this study was conducted to assess pregnancy complications and birth outcomes in primiparae at very advanced maternal age (VAMA, aged ≥45) compared to younger primiparae. METHODS: Retrospective cohort study comparing 222 VAMA primiparae and a reference group of 222 primiparae aged 30-35, delivering at Sheba Medical Center from 2008 through 2013. RESULTS: VAMA primiparae were more likely than younger primiparae to be single, to have chronic health conditions, and higher rates of gestational diabetes mellitus (GDM), gestational-hypertension (GHTN) and preeclampsia-eclampsia. VAMA primiparae conceived mostly by oocyte donation. They were more likely to be hospitalized during pregnancy, to deliver preterm and by cesarean birth. Infants of VAMA primiparae were at greater risk for low birthweight and Neonatal Intensive Care Unit admission. There were no differences in outcomes between VAMA primiparae with or without preexisting chronic conditions, or between those aged 45-49 and ≥50. In multivariable analysis VAMA was an independent risk factor for GDM, GHTN and preeclamsia-eclampsia, with adjusted odds ratio of 2.38 (95 % CI 1.32, 4.29), 5.80 (95 % CI 2.66, 12.64) and 2.45 (95 % CI 1.03, 5.85); respectively. The effect of age disappeared in multiple pregnancies. CONCLUSIONS: Primiparity at VAMA holds a significant risk for adverse pregnancy and birth outcomes. The absence of chronic medical conditions or the use of a young oocyte donor does not improve these outcomes. Multiple pregnancies hold additional risk and may diminish the effect of age. Primiparity at an earlier age should be encouraged.

The effect of mode of conception on obstetrical outcomes differs by body mass index.

This study compared the odds of adverse obstetrical outcomes of pregnancies in women who conceived from IVF (n = 464) versus spontaneous conception (n = 1171) after stratification into three body mass index (BMI) groups: normal weight (18.5-24.9 kg/m(2)), overweight (25.0-29.9 kg/m(2)) and obese (>30 kg/m(2)). With increasing BMI, incidences of complications between IVF and spontaneously conceived groups narrowed. Among women with normal BMI, IVF pregnancies were associated with increased odds of placental ischaemic disorders (11.3% versus 7.0%, adjusted odds ratio [aOR] = 2.24; 95% confidence interval [CI] = 1.25-4.04) and low birthweight <2500 g (10.6% versus 8.0%, aOR = 2.08; 95% CI = 1.12-3.88). Among overweight women, only low birthweight (<2500 g) was significantly increased (15.6% versus 6.2%, aOR = 4.33; 95%, CI = 1.61-11.63). For obese women, there were no differences between IVF and spontaneously conceived pregnancies for either placental ischaemic disorders (12.5 versus 20.2%, OR = 0.43, 95% CI = 0.17-1.1) or low birthweight (10.0% versus 11.0%, aOR = 0.7, 95% CI = 0.24-2.08). Overall, the odds of adverse obstetrical outcomes were not significantly greater in IVF singleton pregnancies compared with those conceived spontaneously as BMI increased.

Mode of delivery of twin gestation with very low birthweight: is vaginal delivery safe?

OBJECTIVE: The purpose of this study was to determine whether planned vaginal delivery is associated with increased risk of perinatal death and morbidity in twin pregnancies that are complicated by a very low birthweight of the second twin. STUDY DESIGN: We conducted a retrospective cohort study of twin pregnancies in which the second twin's birthweight was ≤1500 g. One hundred ninety-three twin gestations met the study criteria; patients were classified into 2 groups according to the planned mode of delivery: (1) cesarean delivery (n = 142) and (2) vaginal delivery (n = 51). In the vaginal delivery group, 21 pairs were in cephalic-cephalic presentation at the time of delivery; 28 pairs were cephalic-noncephalic, and 2 pairs were noncephalic-noncephalic. Composite adverse neonatal outcome was defined as the presence of neonatal death, respiratory distress syndrome, sepsis, necrotizing enterocolitis, or intraventricular hemorrhage grade 3-4. RESULTS: Trial of vaginal delivery was successful for both twins in 90.5% of cephalic-cephalic twins and 96.4% in cephalic-noncephalic twins. The rate of intraventricular hemorrhage was significantly higher in the vaginal delivery group (29.4% vs 8.5%, respectively; P = .013; adjusted odds ratio [OR], 3.65; 95% confidence interval [CI], 1.32-10.1). The increased risk of intraventricular hemorrhage in the vaginal delivery groups was evident in both twin A (17.6% vs 7.0%; P = .029) and twin B (15.7% vs 4.9%; P = .014); however, these differences were not significant after adjustment for possible confounders (twin A: adjusted OR, 1.79; 95% CI, 0.58-5.55; twin B: adjusted OR, 2.13; 95% CI, 0.63-7.25). In addition, subgroup analysis revealed that both cephalic-cephalic and cephalic-noncephalic twins who were delivered vaginally had increased risk for intraventricular hemorrhage. There were no significant differences between the cesarean and vaginal delivery groups in the rates of Apgar score <7 at 5 minutes, arterial cord pH <7.1, composite adverse neonatal outcome, and neonatal mortality rate. However, the rate of respiratory distress syndrome was significantly lower in the vaginal delivery group (66.7% vs 69%; P = .042; OR, 0.34; 95% CI, 0.12-0.96). CONCLUSION: Vaginal delivery of very low birthweight twins is associated with an increased risk of intraventricular hemorrhage, regardless of presentation. Because of the small sample size and the retrospective cohort design, large prospective randomized studies are needed.

A novel sonographic scoring system for antenatal risk assessment of obstetric complications in suspected morbidly adherent placenta.

OBJECTIVES: The purpose of this study was to evaluate a novel sonographic scoring system for risk assessment of complications in patients suspected of having morbidly adherent placenta. METHODS: This retrospective study evaluated the association between maternal complications and a grayscale sonographic scoring system for adherent placenta before surgery. Criteria for adherent placenta included uteroplacental and uterobladder demarcation lines and the presence of lacunae. Placentas were classified into 4 stages: stage 0, normal placentation; stage 1, low probability of adherence; stage 2, moderate possibility of adherence; and stage 3, high suspicion of adherence. Placental adherence as assessed by a surgical team, estimated blood loss, and postoperative hospitalization days were determined for each group, as well as the rates of the need for packed blood cells, cryoprecipitate units, and hysterectomy. RESULTS: One hundred nine women were included in the study. Twenty-six (23.8%) women were given a score of stage 0, 22 (20.2%) stage 1, 28 (25.7%) stage 2, and 33 (30.3%) stage 3. Linear regression analysis demonstrated that the sonographic staging was the only variable significantly associated with the number of packed cells or cryoprecipitate units transfused (P< .001) and a clinical diagnosis of adherent placenta (P< .001). In addition, both sonographic staging and a history of cesarean delivery were significantly associated with hysterectomy (P = .01; P = .03, respectively), treatment with any blood products (P< .001; P= .01), and the duration of postoperative hospitalization (P< .001; P = .006). CONCLUSIONS: A scoring system based on simple grayscale parameters may be effective for antenatal risk assessment of maternal complications in cases of suspected morbidly adherent placenta.

Disparity in post-treatment maternal circulating magnesium sulfate levels between twin and singleton gestation: Is this the missing link between plurality and adverse outcome?

OBJECTIVE: Magnesium sulfate (MgSO4) administered to women at risk for preterm delivery decreases the risk of cerebral palsy in their children. However, the neuroprotective effect of MgSO4 has not been shown in twin gestations. Thus, the aim of this study was to determine the maternal serum levels of magnesium in twin vs. singleton pregnancies following intravenous treatment of MgSO4. METHODS: Case control study including two groups of pregnant women who received intravenous MgSO4: (1) twin gestations (n=83) and (2) singleton pregnancies (n=83). Maternal serum magnesium levels 6 and 24 h after initiation of treatment were determined in both groups. RESULTS: Maternal serum levels of magnesium were significantly lower among patients with twin gestations compared to those with singleton ones 6 h after initiation of treatment (4.6 vs. 4.8 mg/dL, P=0.003). In addition, the rate of pregnant women who obtained therapeutic levels 6 h after initiation of treatment was significantly lower in twin gestations than in singleton ones (36% vs. 58%, P=0.008). Multiple regression analysis revealed that twin gestations were independently and significantly associated with low maternal serum magnesium levels. CONCLUSIONS: Maternal serum concentrations of magnesium are lower in twin pregnancies than in singleton ones following MgSO4 treatment, which might explain the decreased neuroprotective effect of MgSO4 reported in twin pregnancies.

Advanced cervical dilatation and spontaneous preterm labor: a comparison between twin and singleton gestations.

OBJECTIVE: To determine the admission to delivery interval and the rate of immediate delivery in twin versus singleton gestation complicated by spontaneous preterm labor (SPTL). METHODS: A retrospective cohort study of pregnant women presenting with advanced cervical dilatation of 3-5 cm and frequent uterine contractions at 24-34 weeks of gestation was performed. The rate of progression to delivery within 12 h and 24 h, as well as rates of prolonged latency, were compared between twins and singletons gestations. RESULTS: Sixty-nine women were included, of which 25 carried twins and 44 singletons. The overall rate of spontaneous delivery within 12 h and 24 h was 47.8% and 59.4%, respectively, and similar between twins and singletons. Nevertheless, prolonged latency of 10 days or more after presentation was more frequent among twins compared with singletons [10/25 (40%) vs. 7/44 (15.9%), respectively; P=0.026]. Moreover, women carrying twins presenting with advanced cervical dilatation had a better chance of completing a full 2-dose antenatal betamethasone course compared with singletons [19/25 (76%) of twins compared with 21/44 (47.7%) of singletons, odds ratio 3.5, 95% confidence interval 1.16-10.34; P=0.022]. CONCLUSION: Up to 60% of women presenting with advanced cervical dilatation prior to 34 weeks' gestation give birth within 24 h. Nevertheless, women carrying twins have a better chance of completing a betamethasone course and having prolonged latency compared with singletons.

Omentin, an adipokine with insulin-sensitizing properties, is negatively associated with insulin resistance in normal gestation.

OBJECTIVE: Omentin, a newly identified adipokine, enhances insulin mediated glucose uptake in human adipocytes, thus, inducing systemic insulin-sensitizing effect. The aims of this study were to determine whether circulating maternal omentin levels are associated with insulin resistance indices and to assess which compartment, maternal, fetal, or placental, is the source of omentin in maternal circulation. METHODS: Fasting serum glucose, insulin, and omentin were determined in 25 healthy pregnant women at the third trimester, before and 3 days after elective cesarean section. Cord blood omentin was measured in the 25 term neonates. Homeostasis model assessment (HOMA) was used to evaluate insulin sensitivity before and after delivery. RESULTS: Antepartum maternal omentin levels were negatively correlated with insulin levels (r=-0.41, P=0.04) and positively correlated with insulin sensitivity (HOMA%S; r=0.4, P=0.04). Postpartum omentin levels were negatively correlated with maternal body mass index (r=-0.44, P=0.02). Median maternal omentin levels was comparable before and after delivery (57.2, inter-quartile range: 38.2-76.2 ng/mL vs. 53.4, 39.8-69.4 ng/mL, respectively, P=0.25) and highly correlated (r=0.83, P<0.001). Antepartum maternal and neonatal omentin levels did not differ significantly (fetal: 62.2, 44.3-74.2 ng/mL, P=0.77) and did not correlate (P=0.6). CONCLUSIONS: Circulating maternal omentin levels are correlated with insulin resistance indices, suggesting that this adipokine may play a role in metabolic adaptations of normal gestation. The strong correlation between anteparum and postpartum maternal omentin levels, as well as the lack of association between maternal and neonatal omentin levels, suggest that placental or fetal compartments are unlikely as the main source of circulating maternal omentin.

Circulating angiogenic factors in monochorionic twin pregnancies complicated by twin-to-twin transfusion syndrome and selective intrauterine growth restriction.

OBJECTIVE: To determine maternal plasma levels of soluble vascular endothelial growth factor receptor-1 (sVEGFR-1), placental growth factor (PLGF), and soluble endoglin (sEng) in monochorionic diamniotic (MC/DA) twin pregnancies complicated by twin-to-twin transfusion syndrome (TTTS) or selective intrauterine growth restriction (sIUGR). STUDY DESIGN: A longitudinal cohort study of pregnant women with MC/DA twins who were classified into 3 groups: (1) uncomplicated MC/DA twins (n = 22), (2) TTTS (n = 23), and (3) sIUGR (n = 15). Maternal plasma samples were obtained between 13-20 and 21-28 weeks of gestation and cord blood samples were collected at delivery. Maternal plasma concentrations of sVEGFR-1, PLGF, and sEng, as well as cord blood levels of sVEGFR-1 were measured by enzyme-linked immunoassay. RESULTS: Maternal plasma levels of sVEGFR-1 and sEng were significantly higher in patients with TTTS at the early and late second trimester compared with normal monochorionic pregnancies (P < .01). In contrast, in the sIUGR group, sVEGFR-1 and sEng levels were significantly higher only at the late second trimester (P < .05). PLGF levels were significantly lower at the early and late second trimester in both TTTS and sIUGR compared with controls (P < .01). Plasma concentrations of sVEGFR-1 were significantly higher among TTTS pregnancies compared with sIUGR at the late second trimester (P = .027). Cord blood levels of sVEGFR-1 were significantly higher in the smaller intrauterine growth restricted twin compared with the normal cotwin. CONCLUSION: Monochorionic pregnancies complicated by TTTS and sIUGR are characterized by decreased angiogenic activity. The disparity in severity of the antiangiogenic state between TTTS and sIUGR suggests that these 2 conditions may represent a continuum.

Peripartum thromboprophylaxis for homozygous and heterozygous FVL mutation carriers yields similar pregnancy outcome.

BACKGROUND: Homozygous carriers of factor V Leiden (FVL) have an up to 80-fold increased risk of venous thrombosis, but the risk of obstetric complications in FVL homozygosity is unclear. OBJECTIVES: To compare obstetric and thromboembolic complications among factor V Leiden (FVL) homozygous and heterozygous carriers treated with prophylactic dose anticoagulation during pregnancy. METHODS: In this retrospective case-control study we performed a chart review for the years 2004-2010 of homozygous and heterozygous FVL carriers who were treated with low molecular weight heparin (LMWH) at a dose of 0.6 mg/kg/day during pregnancy. Adverse outcomes included thromboembolic and obstetric complications. A composite adverse obstetric outcome was defined as the presence of at least one of the following: late intrauterine fetal demise, severe intrauterine growth restriction (< 5th percentile), preeclampsia, and placental abruption. Pregnancy outcomes of homozygous and heterozygous FVL carriers were compared. RESULTS: We compared the pregnancies of 13 homozygous FVL women with those of 82 heterozygous FVL carriers. Thromboembolic events occurred only in heterozygous FVL controls. Gestational age and birth weight were similar. The composite adverse obstetric outcome rate was higher for homozygous compared with heterozygous FVL carriers (23.1% vs. 11%, respectively), although not statistically significant. A trend for prematurity among homozygous FVL patients was evident, with 2/13 women (15.3%) in the homozygous FVL group giving birth before 34 weeks gestation, compared with only 2/82 (2.3%) in the heterozygous group. CONCLUSIONS: Pregnancy outcome was similar for homozygous and heterozygous FVL carriers on LMWH thromboprophylaxis. The overall likelihood of thromboembolic complications was low. Thromboprophylaxis may decrease the risk for placental and thromboembolic complications in homozygous FVL patients to a similar level as in heterozygotes.