Aris Antsaklis

Comparison of intrapartum electronic fetal heart rate monitoring versus intermittent auscultation in detecting fetal acidemia at birth

OBJECTIVEnOur purpose was to compare continuous intrapartum electronic fetal heart rate monitoring with intermittent auscultation for detecting fetal acidemia at birth.nnnSTUDY DESIGNnData from a previously published randomized trial of electronic fetal heart rate monitoring versus intermittent auscultation were analyzed to identify any differences between the two methods in detecting fetal acidemia at birth. Fetal acidemia at birth was defined as the presence of cord blood arterial pH < 7.15.nnnRESULTSnA total of 1419 patients with umbilical cord blood acid-base measurements were identified, 739 in the electronic FHR monitoring group and 680 in the auscultation group. Electronic FHR monitoring had significantly better sensitivity (97% vs 34%, p < 0.001), lower specificity (84% vs 91%, p < 0.001), higher positive predictive value (37% vs 22%, p < 0.05), and higher negative predictive value (99.5% vs 95%, p < 0.001) in detecting fetal acidemia at birth. In addition, electronic FHR monitoring was significantly better in detecting all types of acidemia: metabolic (95.5% vs 26.5%, p < 0.001), mixed (95% vs 37.5%, p < 0.001), and respiratory (100% vs 41.5%, p < 0.001).nnnCONCLUSIONnThese data suggest that electronic FHR monitoring is superior to intermittent auscultation in detecting fetal acidemia at birth.

REVIEW ARTICLE: Fetomaternal Immunotolerance

Implantation of mammalian conceptus in uterine cavity is the result of evolutionary adaptation, through high level of physiological procedures to ensure its success. However the majority of pregnancy losses occur before or during implantation. It is expected that exploring and defining the molecular and physiological road map during the crucial time of implantation will enable us to decode and effectively treat fertility defects. Immunological, hormonal and molecular factors participate in the feto‐maternal cross talk during implantation and designate the effectiveness of the process. The atypical expression of major histocompatibility complex and other protein‐antigens, such as Fas/FasL and petformin in human trophoblast, the modified function of cellular constituents of the feto‐maternal interface, as well as the specific role of some hormones and cytokines, represent substantive parameters of feto‐maternal immunotolerance during implantation.

Pharmacogenetics in Ovarian Stimulation—Current Concepts

Ovarian response to follicle‐stimulating hormone (FSH) action differs considerably among women; this has prompted researchers to determine which factors modify this response. The challenge is to identify the genes that affect the response to FSH stimulation by the application of pharmacogenetics to assisted reproduction techniques (ARTs). Recently, new insights have been gained in the investigation of the variability in the gene that encodes the FSH receptor (FSHR) gene or genes of the estrogen pathway. Several polymorphisms of the FSHR gene have been discovered, but Ser680Asn and Thr307Ala are the two most studied. The Ser680Asn polymorphism of the FSHR gene has been found to influence the ovarian response to FSH stimulation in women undergoing in vitro fertilization (IVF), and in women with the genotype Ser/Ser, the FSHR appears to be more resistant to FSH action. The clinical implications of this finding are highly important; the ultimate goal is to apply genetic markers as routine diagnostic tests before ovarian stimulation to predict ovarian response, determine the required FSH dose, and avoid the possible complications related to FSH stimulation.

Breast tuberculosis: Diagnosis, management and treatment

INTRODUCTIONnMammary (breast) tuberculosis is a rare manifestation of extra-pulmonary localization of the disease which accounts for less than 0.1% of breast conditions in developed countries, but reaches 3-4% in regions where the disease presents with high incidence (India, Africa). It appears mostly in women of reproductive age, multiparous, lactating. It has been scarcely reported to infect male patients, mainly before puberty, as well as women of older age. The most common presentation is that of a tumor in the middle or upper-outer quadrant of the breast, with multifocal involvement being rarely documented. The differential diagnosis includes breast cancer and abscess formation.nnnPRESENTATION OF CASEnWe report a case of breast tuberculosis that was treated in the Breast Unit of our hospital. Differential diagnosis, imaging methods, operative diagnostic approach and surgical treatment, histological verification of the disease and further therapeutic management are described.nnnDISCUSSIONnHigh risk population is identified, primary and secondary disease is described and clinical presentations are analyzed. Evaluation of diagnostic workup and limitations are reported.nnnCONCLUSIONnIn accordance with the present worldwide revival of the disease, mainly because of massive numbers of migrating population, this subject is reviewed, reminding us of a rather uncommon clinical entity.

Early hCG addition to rFSH for ovarian stimulation in IVF provides better results and the cDNA copies of the hCG receptor may be an indicator of successful stimulation

A simple, safe and cost-effective treatment protocol in ovarian stimulation is of great importance in IVF practice, especially in the case of previous unsuccessful attempts. hCG has been used as a substitute of LH because of the degree of homology between the two hormones. The main aim of this prospective randomized study was to determine, for the first time, whether low dose hCG added to rFSH for ovarian stimulation could produce better results compared to the addition of rLH in women entering IVF-ET, especially in those women that had previous IVF failures. An additional aim was to find an indicator that would allow us to follow-up ovarian stimulation and, possibly, modify it in order to achieve a better IVF outcome; and that indicator may be the cDNA copies of the LH/hCG receptor. Group A patients (n = 58) were administered hCG and Group B rLH (n = 56) in addition to rFSH in the first days of ovarian stimulation. The number of follicles and oocytes and, most importantly, implantation and pregnancy rates were shown to be statistically significantly higher in the hCG group. This study has also determined, for the first time to our best knowledge, m-RNA for LH/hCG receptors in the lymphocytes of peripheral blood 40 h before ovum pick-up. cDNA levels of the hCG receptor after ovarian stimulation were significantly higher among women receiving hCG compared to those receiving LH. In addition, higher levels were encountered among women with pregnancy compared to those without, although this was not statistically significant due to the small number of pregnancies. It seems that hCG permits a highly effective and more stable occupancy of rLH/hCG receptors and gives more follicles and more oocytes. The determination of cDNA copies could be, in the future, a marker during ovulation induction protocols and of course a predictor for the outcome of ART in the special subgroup of patients with previous failures.

hCG priming effect in controlled ovarian stimulation through a long protocol.

BackgroundRecently, it has been demonstrated that, in patients down-regulated by GnRH analogues (GnRHa), a short-term pre-treatment with recombinant LH (rLH), prior to recombinant FSH (rFSH) administration, increases the number of small antral follicle prior to FSH stimulation and the yield of normally fertilized embryos. However, no data exist in the literature regarding the potential beneficial effect of hCG priming in controlled ovarian hyperstimulation (COH) through a long GnRH-a protocol, which binds the same receptor (LH/hCGR), though it is a much more potent compared to LH. The primary aims of this study were to assess the effect of short-term pre-rFSH administration of hCG in women entering an ICSI treatment cycle on follicular development, quality of oocytes and early embryo development. The secondary endpoints were to record the effects on endometrial quality and pregnancy rate.MethodsPatients with a history of at least one previous unsuccessful ICSI cycle were randomly assigned into two groups to receive treatment with either a long protocol with rFSH (control group) or a long protocol with rFSH and pre-treatment with hCG (hCG group). In particular, in the latter group, a fixed 7 days course of 200 IU/day hCG was administered as soon as pituitary desensitization was confirmed.ResultsThe mean number of oocytes retrieved was not significantly different between the two treatment groups, although the percentage of mature oocytes tended to be higher but not significantly different in hCG-treated patients. The percentage of patients with more than one grade 3 embryos was higher in the pre-treatment group, which also showed a higher pregnancy rate.ConclusionAll the above clinical observations, in conjunction with previous data, suggest a point towards a beneficial hCG priming effect in controlled ovarian hyperstimulation through a long GnRH-a down-regulation protocol, particularly in patients with previous ART failures.

Corticotropin-releasing-hormone levels in pregnancy-induced hypertension

UNLABELLEDnHigh levels of corticotropin-releasing hormone (CRH) circulate in the plasma of pregnant women especially during the third trimester and even higher levels have been reported in abnormal pregnancies of various etiologies. One of these etiologies is pregnancy-induced hypertension (PIH).nnnOBJECTIVEnTo measure CRH blood levels with a sensitive method in a large number of pregnant women with PIH, starting from very early stages of gestation, and to compare them with those in normal controls.nnnSTUDY DESIGNnVenous blood was withdrawn from, (a) 10 healthy women aged 20-35 years, (b) 62 pregnant women with PIH (109 samples), mean age 29.1 years and (c) 75 healthy pregnant women (81 samples), mean age 28.5 years, used as matched controls. In pregnant women, blood collection started at the 10th week of gestation. In 14 women from group b and in 22 from group c blood was withdrawn during labor as well. CRH was assayed by RIA.nnnRESULTSnLevels in non-pregnant women were between 19.0-40.6 pg/ml (28.37 +/- 2.53 pg/ml, mean +/- S.E.M.). In both groups of pregnant women there was a progressive increase in plasma CRH levels becoming quite sharp towards the end of gestation. Between 10 and 20 weeks, CRH (mean +/- S.E.M.) in PIH group was 69.3 +/- 3.2 pg/ml versus 41.6 +/- 2.4 pg/ml in matched controls, at 21-25 weeks 168.0 +/- 12.8 pg/ml versus 58.5 +/- 3.8 pg/ml, at 32-35 weeks 1378.5 +/- 61.4 pg/ml versus 298.3 +/- 16.9 pg/ml and at 38 weeks 2800.0 +/- 114.1 pg/ml versus 825.0 +/- 59.8 pg/ml. At term, CRH levels were 3784.0 +/- 197.3 pg/ml in PIH, versus 1386.0 +/- 101.8 pg/ml in normal pregnancy. Statistically, at every stage of gestation, CRH levels were highly significantly different in the PIH group (P < 0.0005). One hour postpartum there was a c. 60% decrease in plasma CRH levels in both b and c groups. In three women with pre-eclampsia who underwent premature labor due to a dead fetus around the 30th week, very high levels were noticed in sequential blood samples for 4-5 weeks prior to labor.nnnCONCLUSIONSn(a) CRH levels in women with PIH are significantly higher compared to healthy pregnant women at any stage of gestation starting from week 10; (b) very high levels during pregnancy might be predictive of premature labor or fetal loss; and (c) CRH measurement might prove to be a helpful diagnostic tool in women with pregnancy-induced hypertension.

Effect of Vacuum Extraction on Umbilical Cord Blood Acid-Base Measurements

The objective of this study was to determine whether vacuum extraction is associated with umbilical cord blood acid-base changes when used electively or in the presence of suspected fetal distress. Data from 1,428 patients from a previously published randomized trial of intrapartum electronic fetal heart rate monitoring versus intermittent auscultation were analyzed to identify differences in umbilical cord blood acid-base measurements associated with the elective use of vacuum extraction (patients with duration of second stage of labor 60 min or less) and also in the presence of suspected fetal distress during the second stage of labor. When used electively, vacuum extraction was associated with lower pH (in both umbilical cord artery and vein), lower venous base excess, and higher venous carbon dioxide tension (PCO2), as compared to normal spontaneous vaginal delivery. After correcting for duration of second stage of labor, elective vacuum delivery was significantly associated only with a decrease in cord venous pH and increase in venous PCO2. However, these cord blood acid-base changes were not accompanied by any differences in perinatal morbidity and mortality or in the number of neonates born with acidemia (cord arterial pH < 7.15 or < 7.10). In cases of suspected fetal distress, the use of vacuum extraction was not associated with any detectable cord blood acid-base changes as compared to normal spontaneous vaginal delivery. These data support the continued use of vacuum extraction, especially in cases of suspected fetal distress during the second stage of labor.

Proteomic analysis of pubocervical fascia in women with and without pelvic organ prolapse and urodynamic stress incontinence

Introduction and hypothesisThis pilot study compares protein expression patterns in the pubocervical fascia of women with pelvic organ prolapse (POP) and stress urinary incontinence (SUI) and asymptomatic women with normal pelvic support.MethodsSamples of pubocervical fascia were collected from four women with POP and SUI and from three asymptomatic (control) women. These were analyzed using two-dimensional electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.ResultsThe expression levels of transgelin, smooth muscle gamma-actin, myosin light polypeptide 6, and alpha-1 antitrypsin precursor were more than twofold higher in patients than in controls. An additional five proteins were overexpressed (more than twofold) in patients, while three proteins were detected only in the patients.ConclusionThis pilot study is the first study to estimate changes in protein expression in the pubocervical fascia of human patients with POP. These changes could be related to the pathophysiology of POP.

The effect on the fetal pituitary-adrenal axis of dexamethasone administration early in the second trimester of pregnancy

Objective.u2003To evaluate the effect of a single dose of dexamethasone to pregnant women at early second trimester on the fetal pituitary-adrenal axis. Methods.u2003Thirty-eight women between 13 and 15 weeks gestation were included in the study. Blood was taken from the mothers and their fetuses for the evaluation of plasma ACTH, cortisol, and free cortisol levels before and after treatment with a single dose of 1u2009mg of dexamethasone orally at 11 p.m. the night before the termination of pregnancy. Results.u2003The mean plasma ACTH was significantly lower following dexamethasone administration (8.5u2009±u20095.1 vs. 18.4u2009±u200910.9 pg/ml). Similarly, plasma cortisol was significantly lower after dexamethasone treatment (208.3u2009±u2009168.7 vs. 772.7u2009±u2009206.1u2009nmol/l), as well as plasma free cortisol levels (2.6u2009±u20090.0 vs. 6.1u2009±u20096.1u2009nmol/l). Mean plasma ACTH levels were not significantly different in the fetuses after dexamethasone treatment (33.6u2009±u200922.7 vs. 42.5u2009±u200921.9 pg/ml). Moreover, mean fetal plasma cortisol was not different before and after treatment (108.2u2009±u200927.2 vs. 94.3u2009±u200947.2u2009nmol/l), as well as the mean free cortisol levels (7.7u2009±u20095.2 vs. 7.0u2009±u20094.3u2009nmol/l). Conclusions.u2003A single dose of 1u2009mg of dexamethasone to the mother early in the second trimester of pregnancy does not result in a significant suppression of the fetal pituitary axis.