Single or double needle insertion in twin's amniocentesis: Does the technique influence the risk of complications?

OBJECTIVE: To compare complication rates following amniocentesis in twin gestations, according to sampling technique and number of needle insertions. STUDY DESIGN: A retrospective cohort study of all women with twin gestations who underwent amniocentesis and delivered in a single university affiliated medical center during 2002-2016. Amniocentesis was performed either through one uterine entry with passage through the inter-twin membrane or through two different entries to the two amniotic sacs. Pregnancy outcome of women that underwent single needle insertion amniocentesis, was compared to this of double needle insertion. Primary outcome was neonatal complications within 4 weeks after amniocentesis (late abortion, chorioamnionitis, preterm premature rupture of membranes, or hospitalization due to related symptoms). Secondary outcomes were gestational week at delivery and labor characteristics. RESULTS: The study group comprised 212 women. Of them, 73 (34.4%) underwent a single uterine insertion and 139 (65.6%) two separate needle insertions. Baseline characteristics did not differ between the groups. The amniocentesis complication rate was 13.7% in the single insertion group and 16.5% in the double insertion group (p = 0.587). Multivariate analysis found that a single insertion method had no statistically significant influence on complication rate, after making adjustments for potential confounders (OR = 1.085, 95% CI 0.4-2.9; p = 0.871). Other labor characteristics were similar between the groups. CONCLUSION: Needle insertion technique in twin gestation amniocentesis was not associated with procedure related complications.

Preoperative sleep quality predicts postoperative pain after planned caesarean delivery.

BACKGROUND: Severe post-caesarean pain remains an important issue associated with persistent pain and postpartum depression. Women's sleep quality prior to caesarean delivery and its influence on postoperative pain and analgesic intake have not been evaluated yet. METHODS: Women undergoing caesarean delivery with spinal anaesthesia (bupivacaine 12 mg, fentanyl 20 µg, morphine 100 µg) were evaluated preoperatively for sleep quality using the Pittsburgh Sleep Quality Index (PSQI) questionnaire (PSQI 0-5 indicating good sleep quality, PSQI 6-21 poor sleep quality). Peak and average postoperative pain scores at rest, movement and uterine cramping were evaluated during 24 h using a verbal numerical pain score (VNPS; 0 indicating no pain and 100 indicating worst pain imaginable), and analgesic intake was recorded. Primary outcome was peak pain upon movement during the first 24 h. RESULTS: Seventy-eight of 245 women reported good sleep quality (31.2%; average PSQI 3.5 ± 1.2) and 167 poor sleep quality (68.2%; average PSQI 16.0 ± 3.4; p < 0.001). Women with poor sleep quality had significantly higher peak pain scores upon movement (46.7 ± 28.8 vs. 36.2 ± 25.6, respectively; p = 0.006). With multivariable logistic regression analysis, poor sleep quality significantly increased the risk for severe peak pain upon movement (VNPS ≥70; OR 2.64; 95% CI 1.2-6.0; p = 0.02). DISCUSSION: A significant proportion of women scheduled for caesarean delivery were identified preoperatively as having poor sleep quality, which was associated with more severe pain and increased analgesic intake after delivery. The PSQI score may therefore be a useful tool to predict increased risk for acute post-caesarean pain and higher analgesic requirements, and help tailor anaesthetic management. SIGNIFICANCE: Multiple studies have evaluated predictors for severe acute pain after caesarean delivery that may be performed in a clinical setting, however, sleep quality prior to delivery has not been included in predictive models for post-caesarean pain. The PSQI questionnaire, a simple test to administer preoperatively, identified that up to 70% of women report poor sleep quality before delivery, and poor sleep quality was associated with increased post-caesarean pain scores and analgesic intake, indicating that PSQI could help identify preoperatively women at risk for severe pain after caesarean delivery.

Optimizing the process of fertility preservation in pediatric female cancer patients - a multidisciplinary program.

BACKGROUND: Current evidence indicates sub-optimal incidence of fertility preservation (FP) in eligible patients. We present herein our designated multidisciplinary program for FP in pediatric and adolescent population and present our data on FP in female patients. METHODS: Pediatric patients (age 0-18) who were candidate for highly gonadotoxic treatments were referred to FP program for a multidisciplinary discussion and gonadal risk-assessment followed by either oocyte cryopreservation or ovarian cryopreservation (OCP) for female patients, and sperm banking for male patients. The OCP protocol consists of aspiration of oocytes from small antral follicles and in-vitro maturation followed by cryopreservation, as well as ovarian tissue cryopreservation. RESULTS: The establishment of a designated FP program resulted in a significant increase in referral and subsequent FP procedures of all eligible patients. Sixty-two female patients were referred for FP discussion during a period of 36 months; 41 underwent OCP; 11 underwent oocyte cryopreservation and six were declined due to parental decision. The median age was 13.2y (range 18 months-18y). Thirty-two (51.6 %) were chemotherapy-naïve. Seventeen patients (27 %) had sarcoma, 16 patients (26 %) had acute leukemia. The mean number of mature oocytes that were eventually vitrified was significantly higher in chemotherapy-naïve patients compared with chemotherapy-exposed patients (mean 12 oocytes (1-42) versus 2 (0-7)). CONCLUSION: Multidisciplinary programs that encompass experts of all relevant fields, skilled laboratory resources and a facilitated path appear to maximize the yield. We observed a considerable higher referral rates following launching a designated program and earlier OCP in chemo-naïve patients that culminated in a better fertility preservation procedure.

Cryopreservation of in vitro matured oocytes in addition to ovarian tissue freezing for fertility preservation in paediatric female cancer patients before and after cancer therapy.

STUDY QUESTION: Is a protocol that combines in vitro maturation of germinal vesicle-stage oocytes and their vitrification with freezing of cortical ovarian tissue feasible for use in fertility preservation for both chemotherapy-naive paediatric patients as well as patients after initiation of cancer therapy? SUMMARY ANSWER: Follicle-containing ovarian tissue as well as oocytes that can undergo maturation in vitro can be obtained from paediatric patients (including prepubertal girls) both before and after cancer therapy. WHAT IS KNOWN ALREADY: Anticancer therapy reduces the number of follicles/oocytes but this effect is less severe in young patients, particularly the paediatric age group. Autotransplantation of ovarian tissue has yielded to date 60 live births, including one from tissue that was cryostored in adolescence. However, it is assumed that autografting cryopreserved-thawed ovarian cortical tissue poses a risk of reseeding the malignancy. Immature oocytes can be collected from very young girls without hormonal stimulation and then matured in vitro and vitrified. We have previously shown that there is no difference in the number of ovarian cortical follicles between paediatric patients before and after chemotherapy. STUDY DESIGN, SIZE, DURATION: A prospective study was conducted in a cohort of 42 paediatric females with cancer (before and after therapy initiation) who underwent fertility preservation procedures in 2007-2014 at a single tertiary medical centre. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study group included girls and adolescent females with cancer: 22 before and 20 after chemotherapy. Following partial or complete oophorectomy, immature oocytes were either aspirated manually ex vivo from visible small antral follicles or filtered from spent media. Oocytes were incubated in oocyte maturation medium, and those that matured at 24 or 48 h were vitrified. Ovarian cortical tissue was cut and prepared for slow-gradual cryopreservation. Anti-Mullerian hormone (AMH) levels were measured in serum before and after oophorectomy. MAIN RESULTS AND ROLE OF CHANCE: Ovarian tissue was successfully collected from 78.7% of the 42 patients. Oocytes were obtained from 20 patients before chemotherapy and 13 after chemotherapy. The youngest patients from whom oocytes were retrieved were aged 2 years (two atretic follicles) and 3 years. Of the 395 oocytes collected, ∼30% were atretic (29.6% in the pre-chemotherapy group, 37% in the post-chemotherapy group). One hundred twenty-one oocytes (31%) were matured in vitro and vitrified: 67.8% from patients before chemotherapy, the rest after chemotherapy. Mature oocytes suitable for vitrification were obtained from 16/20 patients before chemotherapy and from 12/13 patients after chemotherapy (maturation rate, 32 and 26.4%, respectively). There were significant correlations of the number of vitrified oocytes with patient age (more matured oocytes with older age) (P = 0.001) and with pre-oophorectomy AMH levels (P = 0.038 pre-chemotherapy group, P = 0.029 post-chemotherapy group). Oocytes suitable for vitrification were obtained both by manual aspiration of antral follicles (45%) and from rinse solutions after dissection. There were significantly more matured oocytes in the pre-chemotherapy group from aspiration than in the post-chemotherapy group after both aspiration (P < 0.033) and retrieval from rinsing fluids (P < 0.044). The number of pre-antral follicles per histological section did not differ in the pre- versus post-chemotherapy. AMH levels dropped by approximately 50% after ovarian removal in both groups, with a significant correlation between pre- and post-oophorectomy levels (P = 0.002 pre-chemotherapy group, P = 0.001 post-chemotherapy group). LIMITATIONS, REASONS FOR CAUTION: There were no patients between 5 years and 10 years old in the post-chemotherapy group, which might have affected some results and correlations. Oocytes from patients soon after chemotherapy might be damaged, and caution is advised when using them for fertility-restoration purposes. The viability, development capability and fertilization potential of oocytes from paediatric patients, especially prepubertal and after chemotherapy, are unknown, in particular oocytes recovered from the media after the tissue dissection step. WIDER IMPLICATIONS OF THE FINDINGS: Although more oocytes were collected and matured from chemotherapy-naïve paediatric patients, ovarian tissue and immature oocytes were also retrieved from young girls in whom cancer therapy has already been initiated. Our centre has established a protocol for potential maximal fertility preservation in paediatric female patients with cancer. Vitrified-in vitro-matured oocytes may serve as an important gamete source in paediatric female patients with cancer because the risk of reseeding the disease is avoided. Further studies are needed on the fertility-restoring potential of oocytes from paediatric and prepubertal patients, especially after exposure to chemotherapy. STUDY FUNDING/COMPETING INTERESTS: The study was conducted as part of the routine procedures for fertility preservation at our IVF unit. No funding outside of the IVF laboratory was received. Funding for the AMH measurements was obtained by a research grant from the Israel Science Foundation (to B.-A.I., ISF 13-1873). None of the authors have competing interests. TRIAL REGISTRATION NUMBER: N/A.

Robotic blue-dye sentinel lymph node detection for endometrial cancer - Factors predicting successful mapping.

OBJECTIVE: Sentinel lymph node (SLN) mapping has emerged as a viable option for the treatment of patients with endometrial cancer. We report our initial experience with SLN mapping algorithm, and examine the factors predicting successful SLN mapping. METHODS: We analyzed all data recorded in our institute on robotic blue-dye SLN detection mapping from the time it was first introduced to our department in January 2012-December 2014. Data included patient demographics, SLN allocation, operating room times, and pathology results. RESULTS: During the study period, 74 patients had robotic assisted surgery for endometrial cancer with attempted SLN mapping. SLN was found overall in 46 patients (62.1%). At first, SLN was detected in only 50% of cases, but after performing 30 cases, detection rates rose to 84.6% (OR = 3.34, CI 1.28-8.71; p = 0.003). Univariate analysis showed a higher detection rate with methylene blue than patent blue dye, 74.3% vs. 52.3% (OR = 2.744, 95% CI 1.026-7.344; p = 0.042). In multivariate analysis, high body mass index (BMI) was associated with failed mapping (OR = 0.899; 95% CI 0.808-1.00), as was the presence of lymph-vascular space invasion (LVSI) (OR = 0.126; 95% CI 0.24-0.658) and few cases per surgeon (OR = 1.083, 95% CI 1.032-1.118). Factors related to uterine pathology itself, including tumor histology, grade, method of diagnosis, the presence of an endometrial polyp, and lower uterine segment involvement were not found to be associated with successful mapping. CONCLUSIONS: Surgeon experience, BMI and LVSI may affect the success rate of SLN mapping for endometrial cancer. These factors should be investigated further in future studies.

Antibodies to islet cell autoantigens, rotaviruses and/or enteroviruses in cord blood and healthy mothers in relation to the 2010-2011 winter viral seasons in Israel: a pilot study.

AIMS: To determine whether antivirus and/or islet cell antibodies can be detected in healthy pregnant mothers without diabetes and/or their offspring at birth in two winter viral seasons. METHODS: Maternal and cord blood sera from 107 healthy pregnant women were tested for islet cell autoantibodies using radioligand binding assays and for anti-rotavirus and anti-CoxB3 antibody using an enzyme-linked immunosorbent assay. RESULTS: Glutamic acid decarboxylase (GAD)65 autoantibodies and rotavirus antibodies, present in both maternal and cord blood sera, correlated with an odds ratio of 6.89 (95% CI: 1.01-46.78). For five, 22 and 17 pregnancies, antibodies to GAD65, rotavirus and CoxB3, respectively, were detected in cord blood only and not in the corresponding maternal serum. In 10 pregnancies, rotavirus antibody titres in the cord blood exceeded those in the corresponding maternal serum by 2.5-5-fold. Increased antibody titres after the 20(th) week of gestation suggested CoxB3 infection in one of the 20 pregnancies and rotavirus in another. CONCLUSION: The concurrent presence of GAD65 antibodies in cord blood and their mothers may indicate autoimmune damage to islet cells during gestation, possibly caused by cross-placental transmission of viral infections and/or antivirus antibodies. Cord blood antibody titres that exceed those of the corresponding maternal sample by >2.5-fold, or antibody-positive cord blood samples with antibody-negative maternal samples, may imply an active in utero immune response by the fetus.

The placental factor in early- and late-onset normotensive fetal growth restriction.

OBJECTIVE: Our objective was to investigate the placental component in early- and late-onset fetal growth restriction (FGR) compared to placentas from neonates appropriate for gestational age (AGA). STUDY DESIGN: Placentas from normotensive women who gave birth at 24-42 weeks to neonates with a birth-weight below the 10th percentile (FGR group), or to healthy AGA neonates (AGA group), were analyzed. Placental lesions were classified to lesions related to maternal underperfusion, lesions consistent with fetal thrombo-occlusive disease and inflammatory lesions. Findings were compared between patients who delivered ≤ 34 weeks (early-onset FGR) or >34 weeks (late-onset FGR) and controls with AGA neonates. RESULTS: The early-onset FGR group (n = 24) had a higher rate of placental vascular lesions related to maternal underperfusion than the late-FGR group (n = 334) (41.7% vs. 8.7%, P < 0.001) and more villous lesions related to maternal underperfusion than the preterm AGA group (n = 68) (70.8% vs. 5.9%, P < 0.001). The late-onset FGR group had more placental villous lesions related to maternal underperfusion (57% vs. 19% P < 0.001) and more lesions consistent with fetal thrombo-occlusive disease (26.3% vs. 8.5%, P < 0.001) than the term AGA group (n = 153). CONCLUSION: Early- and late-onset FGR have different placental pathology compared with AGA controls, suggesting that a combination of fetal and maternal vascular compromise is more dominant in the late-onset FGR, rather than more severe maternal vascular compromise in early-onset FGR.

Does use of a sex-specific model improve the accuracy of sonographic weight estimation?

OBJECTIVE: To determine whether the use of a sex-specific sonographic model improves the accuracy of fetal weight estimation. METHODS: New regression models (sex-independent and sex-specific) were developed, based on 1708 sonographic weight estimations performed within 3 days prior to delivery. The accuracy of these models was compared to that of several published models including two of the original Hadlock models (which incorporate the biometric indices abdominal circumference (AC), biparietal diameter (BPD), femur diaphysis length (FL) and head circumference (HC) as follows: AC-FL-BPD and AC-FL-HC, designated here as Hadlock I and Hadlock II, respectively), modified versions of the Hadlock I and II models for which coefficients were adjusted to our local cohort, sex-specific versions of the Hadlock I and II models and Schild's model (a previously published sex-specific model). RESULTS: The unadjusted models of Hadlock and Schild were associated with the highest systematic error (1.6-4.9%; P < 0.001) which was significantly higher for females (2.3-4.9%) compared to males (1.6-2.0%; P < 0.001). Adjustment of model coefficients to the local population decreased the systematic error (-1.4% to 1.5%) and resulted in a systematic error that was of similar magnitude (P = 0.3) but opposite in direction for male and female fetuses. The sex-specific models (adjusted or newly developed) were associated with the lowest systematic error (-0.4 to 0.5%) and were the only models for which the systematic error was similar for male and female fetuses. There were no differences in the systematic error between adjusted sex-specific versions of the Hadlock I and II models and the newly developed sex-specific models (0.0% to 0.4% vs. - 0.4% to 0.5%; P = 0.4). The random error was similar for all models and, for most of the models, was unrelated to fetal sex. CONCLUSIONS: The use of sex-specific models appears to improve the accuracy of fetal weight estimation, principally because the optimal set of model coefficients differs for male and female fetuses. The improved accuracy is mainly the result of a decrease in systematic error, as the random error was not affected by the use of such sex-specific models.

Association of non-reassuring fetal heart rate and fetal acidosis with placental histopathology.

OBJECTIVE: To investigate the association between different placental lesions and non-reassuring fetal heart rate (NRFHR) pattern and fetal acidosis in labor. STUDY DESIGN: Placentas from 213 women who underwent cesarean section because of NRFHR with or without fetal acidosis (pH < 7.2) were classified by histopathologic findings: consistent with maternal circulation abnormalities i.e., namely, marginal or retroplacental hemorrhage (M0), maternal underperfusion, vascular (M1) or villous changes (M2), and those consistent with fetal thrombo-occlusive disease due to vascular (F1) or villous (F2) changes. Lesions were also analyzed by maternal (MIR) or fetal (FIR) origin of inflammatory responses. RESULTS: Cord blood pH was normal in 169 neonates (7.29 ± 0.04; control group) and <7.2 in 44 (7.10 ± 0.07; study group). The study group had higher rates of histologic chorioamnionitis; MIR was detected in 34.1% compared to17.8% of controls (p = 0.018), and FIR, in 18.2% compared to 6.5% (p = 0.016). Neonates in the study group had lower Apgar scores and longer hospitalization. CONCLUSIONS: Placental MIR and FIR are associated with cord blood acidosis in neonates delivered by cesarean section for NRFHR tracings in labor.

Accuracy of sonographic weight estimation as a function of fetal sex.

OBJECTIVES: To determine whether the accuracy of sonographic fetal weight estimation is related to fetal sex. METHODS: The accuracy of sonographic fetal weight estimation was compared between male and female fetuses using 3672 sonographic weight estimations performed within 3 days prior to delivery. Fetal weight was estimated using eight regression models that are based on different combinations of the following biometric parameters: abdominal circumference (AC), femur diaphysis length (FL), biparietal diameter (BPD) and head circumference (HC). RESULTS: In seven out of the eight models tested, the presence of a male fetus was associated with a significantly lower systematic error compared with a female fetus (-0.2 to 2.1% vs. 1.3 to 6%, P<0.001). On multivariate analysis, fetal sex was independently associated with sonographic accuracy so that the likelihood of a weight estimation within 10% of birth weight was 30% higher for male fetuses compared with female fetuses. The biometric parameters that contributed most to these sex-related differences were FL and AC, while models that included HC were associated with the lowest differences in the systematic error between male fetuses and female fetuses. For most models, the random error and correlation between estimated weight and birth weight were not affected by fetal sex (8.1-12.8% vs. 8.2-13.6%, and 0.856-0.944 vs. 0.842-0.944, respectively). CONCLUSION: Sonographic estimation of fetal weight is more accurate for male fetuses than for female fetuses. The use of sex-specific models may improve the accuracy of fetal weight estimation for female fetuses.

Accuracy of sonographic fetal weight estimation: a matter of presentation.

OBJECTIVES: To assess the accuracy of sonographic weight estimation for fetuses in breech presentation, and to determine whether certain sonographic models perform better than others in cases of breech presentation. METHODS: This was a retrospective cohort study of all sonographic weight estimations of fetuses in breech presentation performed within 3 days prior to delivery (n = 165). The accuracy of weight estimation was evaluated using eight sonographic models and was compared with a control group of fetuses in vertex presentation matched to the study group by birth weight and fetal gender (n = 165). RESULTS: After exclusion of a model based on femur diaphysis length alone, which was found to be highly inaccurate, the systematic error for fetuses in breech presentation was smaller than that observed for fetuses in vertex presentation (mean of all models - 0.14% vs. 2.0%, P = 0.01). The random error was higher in cases of breech presentation (9.4-13.2% vs. 7.5-8.9%, P < 0.05), and was lower for models that are based on three to four biometric indices (9.4-9.5%) compared with models that incorporate one to two biometric indices (10.8-13.6%, P < 0.05). Overall, the higher random error outweighed the decrease in the systematic error, as reflected by the lower fraction of weight estimations within 10% of birth weight among fetuses in breech presentation. Models based on three to four biometric indices were more accurate in detecting the weight thresholds beyond which a trial of vaginal delivery is usually not recommended. CONCLUSION: Sonographic weight estimation appears to be less accurate for fetuses in breech presentation, principally because of a larger random error. The use of sonographic models that are based on three to four biometric indices, training aimed at improving measurement in breech fetuses and the development of sonographic models derived from fetuses in breech presentation, may improve the accuracy of weight estimation in these cases.

Prediction of fetal macrosomia: effect of sonographic fetal weight-estimation model and threshold used.

OBJECTIVE: To compare the accuracy of 21 sonographic fetal weight-estimation models and abdominal circumference (AC) as a single measure for the prediction of fetal macrosomia (> 4000 g) using either fixed or optimal model-specific thresholds. METHODS: A total of 4765 sonographic weight estimations performed within 3 days prior to delivery were analyzed. The predictive accuracy of 21 published sonographic fetal weight-estimation models was calculated using three different thresholds: a fixed threshold of 4000 g; a model-specific threshold obtained from the inflexion point of the receiver-operating characteristics (ROC) curve; and a model-specific threshold associated with the highest overall accuracy. Cluster analysis was used to determine whether a certain combination of fetal biometric indices is associated with a higher predictive accuracy than others. RESULTS: For a fixed threshold of > 4000 g, there was considerable variation among the models in sensitivity (range, 13.6-98.5%) and specificity (range, 63.6-99.8%) for fetal macrosomia. Use of the threshold derived from the inflexion point of the ROC curve decreased the intermodel variation to a minimum (sensitivity, 84.4-91.4%; and specificity, 79.5-86.3%). Even when this optimal model-specific threshold was applied, models based on three to four biometric indices were more accurate than were models based on only two biometric indices or on AC as a single measure (P=0.03). CONCLUSIONS: Sonographic fetal weight-estimation models based on three to four biometric indices appear to be more accurate than are models based on two indices or on AC as a single measure, for the diagnosis of macrosomia. In these cases, the use of an optimal, model-specific threshold is associated with a higher degree of accuracy than is the uniform use of a fixed threshold of an estimated weight of > 4000 g.

Sonographic estimation of fetal head circumference: how accurate are we?

OBJECTIVES: To assess the accuracy of sonographic estimation of fetal head circumference (HC). METHODS: We compared sonographic estimations of fetal HC with actual measurements performed immediately after delivery using 3008 sonographic examinations performed within 3 days prior to delivery. The following measures of accuracy were calculated: correlation with actual HC, systematic error, random error, simple error, mean absolute percentage error and fraction of estimates within 5% of actual HC. Multivariate logistic regression analysis was used to identify factors affecting the accuracy of sonographic HC estimation. RESULTS: There was a high correlation between sonographic and postnatal measurements of HC (r = 0.845, P < 0.001). Overall, sonographic HC measurements consistently underestimated actual HC measured postnatally (mean simple error, - 13.6 mm; 95% CI, - 13.2 to - 13.9), and the difference increased with gestational age. A high cephalic index (> 0.81) (odds ratio (OR), 0.3; 95% CI, 0.2-0.4), HC > 90(th) centile (OR, 0.5; 95% CI, 0.3-0.6), delivery by vacuum extraction (OR, 0.6; 95% CI, 0.4-0.8), gestational week (OR, 0.7; 95% CI, 0.6-0.9) and male fetal gender (OR, 0.8; 95% CI, 0.6-0.9) were associated with decreased sonographic accuracy. At term, breech presentation at the time of sonographic examination was associated with a higher sonographic accuracy compared with vertex presentation (-12.0; 95% CI, - 10.5 to - 13.5 vs. - 13.9 mm; 95% CI, - 13.6 to - 14.3; P = 0.02). The random error was relatively constant, and was unaffected by any of the obstetric factors studied. CONCLUSION: Sonographic estimation of HC is associated with significant underestimation compared with the actual postnatal HC. This measurement error may have important clinical implications and should be taken into account in the interpretation of sonographically measured HC.

Effect of vaginal progesterone, administered to prevent preterm birth, on impedance to blood flow in fetal and uterine circulation.

OBJECTIVE: To evaluate the effect on the maternal and fetal circulation of progesterone administered to prevent preterm birth. METHODS: We used an observational cohort study design. The study group included 44 women at 18-32 weeks' gestation who presented with an episode of preterm labor, with or without history of delivery before 34 weeks' gestation, or an incidental finding of short cervix (≤ 25 mm). Doppler flow assessment of the umbilical artery, fetal middle cerebral artery and uterine arteries was performed before and 24 h after vaginal administration of progesterone. RESULTS: Seventeen (38.6%) women gave birth before term, but only nine (20.4%) did so before 34 weeks' gestation. Following progesterone treatment, there was a statistically significant decrease in the pulsatility index of the fetal middle cerebral artery (mean reduction, 18.2%; mean change in pulsatility index, 0.44 (95% CI, 0.25-0.63), P < 0.001), with no changes in the other vessels. Comparison of the women who gave birth before with those who delivered at term yielded no significant differences in Doppler flow parameters in any vessel examined, either before or after progesterone treatment. CONCLUSION: Treatment with vaginal progesterone is associated with a lower pulsatility index in the fetal middle cerebral artery, suggesting a vasodilatory effect on the fetal circulation.

Primary atherothrombotic occlusive vascular events in premenopausal women with history of adverse pregnancy outcome.

OBJECTIVE: To determine if adverse pregnancy outcomes are associated with atherothrombotic occlusive vascular disease (AOVD) in premenopausal women. DESIGN: Retrospective matched case-control study. SETTING: Tertiary, university-affiliated medical center. POPULATION: Women aged less than 50 years treated for an AOVD (primary cerebrovascular, myocardial, or peripheral arterial ischemic event) from 1995 to 2004. METHOD: The files were reviewed for classical risk factors for AOVD and complications of pregnancy (abortions, pregnancy-induced hypertension, preeclampsia, gestational diabetes, intrauterine growth restriction (IUGR), fetal loss and preterm delivery). Findings were compared with healthy women matched for age and body mass index. MAIN OUTCOME MEASURES: Past pregnancy complications in premenopausal women with AOVD. RESULTS: Of the 101 women with AOVD, 53 had a myocardial ischemic event, 33 a cerebrovascular event, and 15 a peripheral ischemic arterial event. On multivariate analysis, IUGR (OR 8.41, 95% CI 2.36-29.9, p=0.001) and more than one pregnancy complication (OR 13.7, 95% CI 1.56-120, p=0.02) were found to be independent significant variables associated with AOVD. CONCLUSION: IUGR and composite pregnancy complications are independent significant variables associated with AOVD in premenopausal period. Pregnancy outcome might serve as a means to identify patients who may require increased medical surveillance and preventive measures for later vascular disease.

Prostaglandin E2 induction of labor for isolated oligohydramnios in women with unfavorable cervix at term.

OBJECTIVE: To evaluate the maternal and neonatal outcomes of pregnancies complicated with isolated oligohydramnios at term, managed by induction of labor. METHODS: We conducted a retrospective case-control study. 138 women with uncomplicated oligohydramnios at term [amniotic fluid index (AFI) < or =5 cm] and a low Bishop score (< or =6) underwent induction of labor with prostaglandin E2. These women were compared to 67 women who underwent induction of labor at 42 weeks' gestation and 276 women at low-risk pregnancy and spontaneous onset of labor, matched for parity and race. RESULTS: Cesarean section (CS) rate was similar in the study and the post-date group (17.4 and 17.9%, respectively), but significantly higher than the spontaneous labor group (5.8%, OR 3.42, 95% CI 1.75-6.68). No differences were found with other outcomes. CONCLUSION: Pregnancies with isolated oligohydramnios at term apparently are not at higher risk of perinatal complications, but induction of labor is associated with increased rate of CS.

In vitro maturation of human primordial ovarian follicles: clinical significance, progress in mammals, and methods for growth evaluation.

As cancer treatment improves, more young women of reproductive age are surviving, but they suffer from infertility as a consequence of the radiation and chemotherapy. Human ovarian tissue containing immature primordial follicles has been successfully cryopreserved. The ultimate aim of this technique is to induce ovarian function by re-plantation of ovarian tissue or, further into the future, by in vitro maturation (IVM) of the oocytes derived from the cryopreserved-thawed ovarian tissue, followed by routine in vitro fertilization. IVM of primordial follicles from young cancer survivors would avoid the risk of cancer re-transmission by the ovarian grafts. The present review discusses the current achievements in IVM of female germ cells and primordial ovarian follicles and the attempts to improve their development by adding various factors to the culture medium. The established methods for the evaluation of survival and growth in culture are also discussed: follicular counts, immunocytochemical methods, transmission electron microscopy, fluorescent viability markers and endocrine assays. Although the development of IVM systems is still in its infancy, researchers need to pursue their approach step-by-step, especially with regard to factors that might be involved in the activation of the ovarian follicles or female germ cells. The final measure of success will be the ability of the in vitro matured oocytes to fertilize and produce healthy offsprings. The availability of such treatment will probably lead to its demand not only by cancer patients but by other women as well.

The pharmacologic approach to the prevention of preeclampsia: from antiplatelet, antithrombosis and antioxidant therapy to anticonvulsants.

Preeclampsia has been suggested to be a two-stage disorder of an alteration in placental perfusion (stage 1) leading to generalized vascular endothelial damage (stage 2). Because the mechanism linking the two stages remains unclear, effective primary prevention is still impossible. However, advances made in our understanding of the pathophysiology of preeclampsia have paved the way for secondary and tertiary prevention approaches. Platelets are known to be activated in early pregnancy. They also play a pivotal role in the process of inflammation, as demonstrated by the finding that CD40 ligand is shed from activated platelets to directly initiate inflammation of the vessel wall. According to the Cochrane Library Update summarizing data from over 30,000 women, secondary prevention with antiplatelet drugs is associated with a 19% decrease in the risk of preeclampsia. Additional randomized controlled trials are needed to establish the association between preeclampsia and thrombophilia. The effect of the antithrombotic agent heparin on pregnancy outcome in preeclampsia and its potential preventive action in high-risk patients need to be elucidated. One of the several hypotheses of the pathogenesis of preeclampsia focuses on the oxidative stress caused by the imbalance in prooxidant and antioxidant forces. Preliminary findings on vitamin E and vitamin C supplementation in preeclamptic women are encouraging, and suggest a rationale for larger clinical trials. Although there is currently no explanation for the positive effect of magnesium sulfate on eclamptic seizures, studies have provided enough evidence to encourage its worldwide use as the primary anticonvulsant of choice in the tertiary prevention of maternal and perinatal death in severe preeclampsia/eclampsia. In conclusion, secondary and tertiary prevention of preeclampsia is possible when targeted at reducing maternal and neonatal morbidity and mortality.

Presence of NGF and its receptors in ovaries from human fetuses and adults.

The ability to mature human primordial follicles in vitro would assist fertility restoration. However, the signals initiating growth of primordial follicles are unknown. Growth factors such as nerve growth factor (NGF) may play a role in this process. To investigate the expression of NGF and its receptors, p75 and TrkA, in early developing follicles (mostly primordial, primary and secondary follicles), ten ovarian samples from adolescents/adults aged 13-39 and 33 ovaries from human fetuses aged 19-33 gestational weeks (GW) were obtained and immediately fixed or frozen. The fixed samples were prepared for a study of immunocytochemical staining of NGF and its two receptors. Total RNA was extracted from the frozen ovarian samples, and the expression of NGF, TrkA and p75 was investigated by RT-PCR. Products were resolved by 1% agarose gel electrophoresis and image analysis. Immunocytochemical staining revealed the expression of NGF in granulosa cells (GC) and oocytes; TrkA was mainly in oocytes and in GC in minority of the samples; and p75 was in some of the stroma cells from fetuses aged less than 22 GW. Transcripts of NGF and TrkA were identified by RT-PCR in all samples, while those for p75 were detected only in ovarian samples from fetuses aged less than 22 GW. To elucidate if NGF is indeed involved in growth initiation of human primordial follicles, it should be added to their culture medium. The immunocytochemical detection of p75 in some of the stroma cells and transcripts in ovarian samples of fetuses less than 22 GW may suggest its role in follicular assembly.