Risk of hypertensive disorders in pregnancy following assisted reproductive technology: overview and meta-analysis.

The extent of the increased risk of pregnancy hypertensive disorders following assisted reproductive technology (ART) was investigated. PubMed and the Cochrane Collaboration Library were used as data sources to identify and select longitudinal cohorts comparing pregnancies following ART with spontaneously conceived pregnancies, between 1978 and June 2016. Risk ratios and 95% confidence intervals (CIs) of three outcomes, ie, gestational hypertension (GH), preeclampsia (PE), and their sum (PHD), were calculated. Stratification of results by gestation order (singletons and nonsingletons) was pursued, but a separate "all orders" mixed stratification was considered. Sixty-six longitudinal studies (7 038 029 pregnancies; 203 375 following any ART) were eligible. All outcomes independent of gestation order ("all orders") were increased following any invasive ART: GH (+79% [95% CI, 24%-157%]) and PE (+75% [95% CI, 50%-103%]) to a greater extent, with smaller increases in PHD (+54% [95% CI, 39%-70%]). The risk of PHD following ART steadily increased independent of gestation order.

Angiopoietin-2 primes infection-induced preterm delivery.

Current knowledge on the participation of angiopoietin-2 (Ang-2) in the inflammatory process and on the importance of bacterial endotoxins (LPS) in the induction of preterm delivery (PTD) led us to investigate the role of Ang-2/LPS interplay in the pathogenesis of PTD. At a first stage, Ang-2 was measured at the end of the first trimester of pregnancy in the serum of 50 women who delivered prematurely; of 88 women well-matched for age and parity who delivered full-term; and of 20 non-pregnant healthy women. Ang-2 was greater in pregnant than in non-pregnant women. The time until delivery was shorter among those with Ang-2 greater than 4 ng/ml (odds ratio for delivery until week 34; p: 0.040). To further investigate the role of Ang-2 for PTD, an experimental model of PTD induced by the intraperitoneal injection of LPS in mice was used. Ang-2 was administered intraperitoneally before LPS on day 14 of pregnancy. When Ang-2 was administered before the LPS diluent, all mice delivered full-term. However, administration of Ang-2 prior LPS accelerated further the time until delivery. Sacrifice experiments showed that the effect of Ang-2 was accompanied by decrease of the penetration of Evans Blue in the embryos and by increase of its penetration in maternal tissues. In parallel, the concentration of tumour necrosis factor-alpha in the maternal circulation, in fetal tissues and in the placentas was significantly decreased. Results indicate that Ang-2 accelerated the phenomena of PTD induced by LPS. This is related with deprivation of fetal perfusion.

Predictive value of increased nuchal translucency as a screening test for the detection of fetal chromosomal abnormalities.

OBJECTIVE: The study aimed to estimate the incidence of increased nuchal translucency in the first trimester ultrasound scan results (cut-off limit 2.5 mm) and to evaluate the predictive value of increased nuchal translucency as a screening test for the detection of fetal chromosomal abnormalities. METHODS: We used the ultrasound scan results of nuchal translucency evaluation and the results of chromosomal analysis of the invasive prenatal control performed as a result of increased nuchal translucency. RESULTS: We collected 2183 nuchal translucency ultrasound scans in which we detected 21 embryos with a pathologic value (0.96%). We collected the data of 168 cases of invasive prenatal control due to increased nuchal translucency from which 122 cases were found. A total of 122 cases of pregnant women undergone an invasive prenatal diagnostic method due to increased nuchal translucency, of which 11 fetuses were found with trisomy 21 (Down syndrome) (9%), 3 fetuses with trisomy 13 (Patau syndrome) (2.45%), 3 fetuses with monosomy 45XO (Turner syndrome) (2.45%) and 1 fetus with translocation (0.8%). CONCLUSIONS: The positive predictive value of the increased fetal nuchal translucency as a screening test for the detection of fetal chromosomal abnormalities based on the results of the chromosomal-genetic analysis of the invasive prenatal diagnostic procedures is 14.8%.

Cytokine concentrations during the first days of life.

OBJECTIVE: To evaluate the cytokine concentration patterns during the first 5 days of life by measuring serum concentrations of type-1 cytokines, like interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) and type-2 cytokines, like IL-4, as well as the receptors of IL-2 (sIL-2R) and IL-4 (sIL-4R) during the early neonatal period. SUBJECTS AND METHODS: Forty-two healthy term neonates were included in the study. Cytokine concentrations were measured in umbilical cord, in the 1st and 5th day after birth and compared with those in serum of 30 healthy adults. RESULTS: IL-2 concentrations presented a decrease trend from umbilical cord to 5th day, while sIL-2R showed a significant elevation from umbilical cord to 5th day after birth. IL-4 concentrations did not differ significantly among umbilical cord, the 1st and the 5th day, while the sIL-4R showed the highest values in the 1st day after birth. Both IL-4 and sIL-4R concentrations in neonatal samples were elevated compared to adults. IFN-gamma concentrations increased significantly from umbilical cord to 5th day of life. CONCLUSION: Our findings indicate a dysregulation among IL-2, IL-4 and IFN-gamma concentrations during the 1st day after birth, favoring a more precocious expression of IL-2 and IL-4 against IFN-gamma that seems to be ameliorated in the end of the 1st week of life.

Autoimmune hemolytic anemia caused by cold agglutinins in a young pregnant woman.

Autoimmune hemolytic anemia is a rare disorder. A 34-year old woman presented with thrombophlebitis after her first delivery, during puerperium. A high titer of cold agglutinins was found. Lymphomas, systemic lupus erythematosus, and tumors were excluded. She conceived again. Due to the anemia she had frequent blood transfusions and she delivered at 38 weeks of gestation.

Fetal pulse oximetry and wavelet analysis of the fetal heart rate in the evaluation of abnormal cardiotocography tracings.

AIM: Previous studies indicate that the addition of wavelet analysis of the fetal pulse oximetry tracings (FSPO2) and fetal heart rate (FHR) variability to cardiotocography (CTG), for intrapartum fetal monitoring, provides useful information on the fetal response to hypoxia. We applied the new procedure in non-reassuring CTG patterns, in which cesarean section was performed, and tested its accuracy in the diagnosis of the intrapartum fetal compromise. METHODS: At the 'Aretaieion' University Hospital labor ward, 318 women with term fetuses in the cephalic presentation entered the trial during labor. They all were monitored with external CTG and fetal pulse oximetry. In the cases that cesarean section was applied, because of abnormal CTG tracings, we applied a method based on the multiresolution wavelet analysis and a self-organized map neural network on the first and second stage of labor. The main outcome parameter was the rate of cord metabolic acidosis at birth (pH < 7.05). Secondary outcomes included Apgar scores at 5 min, fetal transmission to neonatal intensive care unit (NICU) and neonatal encephalopathy. RESULTS: Fifty out of 318 cases delivered operatively because of abnormal CTG patterns (rate 15.72%). In 30 cases, cord pH was >7.05, while in 11 Apgar scores at 5 min were <7, while none of those neonates were transferred to NICU. In the rest 20 cases cord pH was <7.05; in all of these cases Apgar scores at 5 min were <7, while four neonates were transferred to NICU. In one of them, neonatal encephalopathy was diagnosed. After the offline application of wavelet analysis and neural networks to the pulse oximetry and FHR variability readings of the 50 cases, statistics calculated that the system showed a sensitivity of 85% and a specificity of 93%, while false negative and false positive rates were 15% and 7%, respectively. CONCLUSION: Computerized FHR and FSPO2 monitoring shows an excellent efficacy and reliability in interpreting non-reassuring FHR recordings.

Immunological factors and their role in the genesis and development of endometriosis.

The article presents an overview of immunological factors and their role in the genesis and development of endometriosis, with emphasis on inflammatory cytokines and growth and adhesion factors. Although retrograde menstruation is a common phenomenon among women of reproductive age, not all women with retrograde menstruation suffer the disease. Development of endometriosis seems to be a complex process, facilitated by several factors, including quantity and quality of endometrial cells in peritoneal fluid (PF), increased inflammatory activity in PF, increased endometrial-peritoneal adhesion and angiogenesis, reduced immune surveillance and clearance of endometrial cells, and increased production of autoantibodies against endometrial cells. Potential biomarkers like cytokines and autoantibodies, upregulated during development of endometriosis, seem useful in the development of a non-surgical diagnostic tool. In this review work, the immune role in endometriosis is examined through the role of immunological factors in the genesis and development of the disease. Furthermore, it could be concluded that, although endometriosis can be treated using hormonal suppression, there is a need today for non-hormonal drugs, probably to modulate immune function, in order to confront the disease and alleviate pain or infertility without inhibition of ovulation.

Ultrasonographic evaluation of a uterine malignant melanoma presenting as a large pelvic mass.

The uterus is an extremely rare location for a primary or metastatic melanoma. We describe the ultrasonographic appearance of a malignant melanoma of the uterus presenting clinically as a large mass in a 78-year-old woman. Transabdominal sonography revealed a solid uterine mass measuring 13 x 11.5 x 8.5 cm with inhomogeneous echotexture and bright internal echoes. The tumor showed a diffuse spread inside the uterine corpus, and the endometrium was not demonstrated ultrasonographically.

Alterations in Doppler velocimetry indices of the umbilical artery during fetal hypoxia in labor, in relation to cardiotocography and fetal pulse oximetry findings.

AIM: The aim was to investigate fetal peripheral blood flow using external cardiotocography (CTG), Doppler velocimetry, and pulse oximetry (PO) in normal labor compared with those complicated by hypoxia. SUBJECTS: During labor, 35 term fetuses with oxygen saturation values (FSPO(2)) between 30 and 40%, and 25 term fetuses with FSPO(2) values < or =30% for a period of 20 s to 2 min were studied. Fetuses were assessed using simultaneous CTG, PO, and Doppler ultrasonography of the umbilical artery (UA). The pulsatility index (PI), resistance index (RI), and flow velocity integral (FVI) were recorded. Peripartum outcomes were compared with those of 30 fetuses with SPO(2) values >40%. All groups presented abnormal CTG patterns and were comparable with regard to maternal age and parity. SETTING: The Fetal Surveillance Unit of the 2nd Department of Obstetrics and Gynecology, "Aretaieion" Hospital, Athens University, Greece. RESULTS: Umbilical artery Doppler revealed an initial increase in the RI and the PI in the presence of decreased oxygen saturation. The differences observed in Doppler velocity and impedance indices correlated with PO values. Fetal outcomes correlated with UA Doppler findings. CONCLUSIONS: Alterations in UA Doppler velocimetry indices were observed during labor-induced fetal hypoxia. PO readings of <40% provoked an increase in the RI and PI. When PO readings remained <30% for >2 min, both the PI and the RI were further increased in a more prominent way. UA velocimetry indices correlated with perinatal outcome.

Gestational diabetes exhibits lack of carnitine deficiency despite relatively low carnitine levels and alterations in ketogenesis.

OBJECTIVE: Previous studies have underlined the importance of the carnitine shuttle system and its dysfunction both in normal pregnancy and in type 1 and 2 diabetes. The objective of this paper was to delineate more systematically the role of the carnitine shuttle system in normal pregnancy and in gestational diabetes. METHODS: A total of 119 women matched for age comprised three groups: 40 normal adult non-pregnant women (NNP), 46 normal pregnant women with uncomplicated pregnancy (NP) and 33 women with gestational diabetes (GDM). The latter group was further subdivided into those being managed either by diet alone (25 women, GDM-D) or by insulin (8 women,GDM-I). The following biochemical parameters were assayed: fasting plasma total, free and acyl-carnitine, FFA and beta-OH-butyrate, together with several essential anthropometric parameters. RESULTS: Women with GDM, in contrast to the control groups, displayed the biochemical features characteristic of insulin resistance: higher body weight, higher BMI, higher skinfold and higher HbAlc levels. No differences on any parameters were found between the two GDM subgroups. Both NP and GDM groups had low levels of total carnitine compared to NNP control group, but surprisingly, the GDM group did not exhibit any further decrease of carnitine levels, as would have been expected by the combination of pregnancy and diabetes. Both groups, despite these low carnitine levels, had no clinical symptoms of carnitine deficiency. Furthermore, the GDM group displayed higher levels of FFA and beta-hydroxybutyrate, which were statistically significant compared to the other two control groups. CONCLUSIONS: The data corroborate the negative effect of normal gestation on the carnitine shuttle system, while they document for the first time that GDM does not further affect the efficiency of the carnitine system. The mild effect of GDMon carnitine status could be explained by the concurrent increased gluconeogenesis, a process which does not affect directly carnitine metabolism.

Insulin levels, insulin resistance, and leptin levels are not associated with the development of ovarian hyperstimulation syndrome.

Insulin levels, insulin resistance, and leptin levels were evaluated in 47 women who developed ovarian hyperstimulation syndrome (OHSS) after participation in assisted reproduction technologies programs and in 47 matched controls who did not develop such a complication. Analysis of the results in relation to underlying polycystic ovarian syndrome and hyperinsulinemia revealed no association of insulin levels, insulin resistance, and leptin levels with the development of OHSS.

Thyroid hormone resistance and enlargement of the sella turcica during pregnancy.

CASE REPORT: A 26-year-old pregnant woman was admitted to our institution running her 30 weeks of gestation. The patient had a past history of total thyroidectomy cause of a thyroid papillary carcinoma and presented with increased supraphysiological TSH levels under 250 microg T4, while slightly hyperthyroid, from the clinical point of view. Partial resistance to thyroid replacement therapy or TSH-secreting tumour was evoked. Pituitary MRI revealed a pituitary enlargement without excluding a pituitary adenoma. To avoid further stress on pituitary a caesarean section was performed at 38 weeks of gestation. MRI 7 months later was normal, while the patient remained under high doses of T4 replacement therapy and TSH was found at the upper limits of normalcy, while T3, T4 and FTI were above normalcy. CONCLUSION: We conclude that, in the absence of thyroid gland, high TSH levels due to thyroid hormone resistance could be erroneously attributed to a pituitary TSH secreting tumour, when associated with a pregnancy-related pituitary enlargement.

Evaluation of fetal intrapartum hypoxia by middle cerebral and umbilical artery Doppler velocimetry with simultaneous cardiotocography and pulse oximetry.

OBJECTIVE: To investigate fetal circulation at different stages of hypoxia during labor, and to study blood flow alterations in the brain and peripheral tissues, through simultaneous use of three non-invasive techniques. MATERIALS AND METHODS: Ninety two pregnant women between 38 and 41 weeks of gestation, comparable for maternal age and parity, were simultaneously monitored with cardiotocography (CTG), continuous fetal pulse oximetry and Doppler ultrasonography during the first stage of labor. In 70 cases evaluation was successful, and useful data was obtained. Doppler waveforms were obtained before and during abnormal CTG patterns, of both the umbilical (UA) and middle cerebral artery (MCA) to measure the pulsatility index (PI), resistance index (RI), and flow velocity integral (FVI). The study population was divided in three groups, according to CTG and fetal pulse oximetry tracings: 20 term fetuses with normal CTG patterns and oxygen saturation (FSPO(2)) values >40%, 30 term fetuses with abnormal CTG patterns and FSPO(2) values between 30 and 40%, and 20 fetuses with abnormal CTG patterns and FSPO(2) values <30% for a time up to 2 min. These were studied and peripartum outcomes were compared. RESULTS: Redistribution of blood flow was noted at FSPO(2) values of 37%, in all groups. In the presence of reduced oxygen saturation (near to or below 30%), MCA Doppler showed significantly lower PI (1.06+/-0.33 vs.0.74+/-0.39, p=0.03) and RI (0.59+/-0.14 vs. 0.44+/-0.14, p=0.03), while that of the UA showed mildly higher resistance indices (0.98+/-0.14 vs. 1.28+/-0.50, p=0.01 and 0.57+/-0.12 vs. 0.79+/-0.24, p=0.004, respectively). When an oxygen saturation value of <30% was maintained for greater than 2 min, MCA Doppler indices reversed, likely indicating morbid fetal hypoxia. Differences in fetal outcomes between groups correlated with Doppler and pulse oximetry tracings. CONCLUSIONS: During active labor the fetus maintains oxygen supply to the brain by redistributing blood flow. In cases of hypoxia this is feasible for only 2 min. We note a strong correlation between fetal pulse oximetry, Doppler velocimetry of the MCA and UA, and fetal morbidity.

Intrapartum surveillance of IUGR fetuses with cardiotocography and fetal pulse oximetry.

OBJECTIVE: To investigate the efficacy and safety of intrapartum fetal pulse oximetry, as a predictor of metabolic acidosis at birth of fetuses with intrauterine growth retardation (IUGR). STUDY DESIGN: We studied 18 IUGR fetuses (group I) and a control group of 30 appropriate for gestational age (AGA) fetuses (group II) during labor. Both groups had abnormal fetal heart rate tracings and were monitored simultaneously throughout labor with cardiotocography and fetal pulse oximetry. Apgar scores, pH and base excess of fetal blood obtained from the umbilical artery after delivery were compared in both groups. SETTING: The Fetal Surveillance Unit of the 2nd Department of Obstetrics and Gynecology, Aretaieion Hospital, Medical School, Athens University. RESULTS: In IUGR fetuses, when their oxygen saturation value (FSPO2) was less than 34%, cord artery pH was 7.10 +/- 0.04, base excess -13 +/- -1 mmol/l and Apgar scores < or =5 at the 5th min, and when FSPO2 was over 35%, artery pH was 7.29 +/- 0.08, base excess -8 +/- -2 mmol/l and Apgar scores > or =7 at the 5th minute. In cases of drops of FSPO2)below 30% for more than 2 min, labor was completed operatively and cord pH was 7.00 +/- 0.04, base excess -15 +/- -2 mmol/l and Apgar scores < or =5 at the 5th minute. In AGA fetuses, when FSPO2 was over 30%, artery pH was over 7.20, base excess <-11 mmol/l and Apgar scores > or =9 at the 5th minute; in contrast, when FSPO2 was <30% for 2 min, a cesarean section was performed and cord pH was < or =7.02, base excess > or =-13 mmol/l and Apgar scores < or =4 at the 5th minute. CONCLUSIONS: In IUGR fetuses, FSPO2 values less than 34% represent an acidotic status, while values of > or =35% are well tolerated. Fetal pulse oximetry proved reliable, according to umbilical cord blood measurements and Apgar scores, reducing cesarean deliveries in cases of nonreassuring cardiotocographic patterns in IUGR fetuses.

Maternal serum leptin concentration during the second trimester of pregnancy: association with fetal chromosomal abnormalities.

Recent studies suggest that leptin, the product of the obese gene, is produced by the placenta during pregnancy. The present study addressed the question whether second trimester maternal serum leptin could be altered by fetal Down syndrome or Edwards syndrome. Maternal serum leptin concentrations were measured in 18 pregnancies complicated with Down syndrome, six pregnancies complicated with Edwards syndrome and 183 uncomplicated pregnancies during the second trimester of pregnancy. The present results demonstrate that leptin concentrations in uncomplicated pregnancies slightly decrease from the 16th week of pregnancy, reaching a minimum of 18.8 ng/ml around the 20th week, and then rapidly increase to 28.2 ng/ml by the 24th week. Leptin correlation with maternal body weight decreases from r=0.695 at 16-17 week of gestation to r=0.544 at >22 weeks of gestation. There was no significant difference between the mean MoMs of Down syndrome- (0.926) or Edwards syndrome- (0.960) affected pregnancies and normal pregnancies (1.002). A weak correlation (r=0.18, p<0.02) was observed between corrected leptin MoMs and human chorionic gonadotrophin (hCG) MoMs in normal pregnancies. It is assumed that around the 20th week of pregnancy placental leptin production is activated or at least is accelerated and it is added to the amount of leptin produced by maternal adipose tissue. Fetal Down syndrome or Edwards syndrome does not seem to alter maternal leptin concentration and therefore leptin cannot be used as a marker for these chromosomal abnormalities in the early second trimester of pregnancy.