Demetrios Kassanos

First trimester prediction of small- and large-for-gestation neonates by an integrated model incorporating ultrasound parameters, biochemical indices and maternal characteristics.

Objective. To identify maternal/pregnancy characteristics, first trimester ultrasound parameters and biochemical indices which are significant independent predictors of small‐for‐gestational age (SGA) and large‐for‐gestational age (LGA) neonates. Design. Retrospective cross‐sectional study. Setting. Two fetal Medicine Units. Population. 4 702 singleton pregnancies presenting for screening for chromosomal abnormalities by nuchal translucency and maternal serum biochemistry at 11–14 weeks. Methods. Reference ranges for birthweight applied to our population were constructed by the Royston and Wright method. Multiple logistic regression was applied to develop first trimester prediction models for SGA and LGA. Main outcome measures. Birth of SGA or LGA neonate. Results. Maternal height, parity, smoking, assisted conception, delta crown–rump length, delta nuchal translucency, free beta human chorionic gonadotrophin and pregnancy‐associated plasma protein‐A were significant independent predictors of SGA. Maternal weight and height, smoking, delta crown–rump length and delta nuchal translucency were significant independent predictors of LGA. Models for SGA (AUC=0.7296, CI: 0.69–0.76, p<0.0001) and LGA (AUC=0.6901, CI: 0.65–0.72, p<0.0001) were derived, applicable to routine obstetric population at low risk for these conditions. For 20% screen positive rate the modeling achieves sensitivities of about 55% for SGA and 48% for LGA neonates. Conclusion. Prediction for birthweight deviations is feasible using data available at the routine 11–14 weeks’ examination. Delta CRL and delta nuchal translucency were significant independent predictors for both SGA and LGA.

Culture of seminal fluid in infertile men and relationship to semen evaluation.

Bacterial flora of the seminal fluid and its influence on semen quality, was examined in 225 asymptomatic unselected men. Each semen sample was cultured aerobically, anaerobically, for genital mycoplasmas, and for Chlamydia trachomatis. Semen analysis was made according to standard methods recommended by the W.H.O. All 225 semen samples had microbial isolates. All isolates had colony counts of 102 colony forming units (cfu/ml). Thirty‐three cases had > 102 cfu/ml, 85 cases had > 103 cfu/ml and 78 cases > 105 cfu/ml. The most common organisms isolated were Ureaplasma urealyticum in 86 samples and C. trachomatis in 26 samples. The most frequent abnormal parameters were viability (117 of 212, 52%), motility (85 of 212, 40%) and number of sperm cells (74 of 225, 32.8%). No significant correlation was found between abnormal semen parameters and presence of U. urealyticum, and C. trachomatis. We concluded that asymptomatic bacteriospermia (infection) in the semen did not significantly affect the count, motility or morphologic features of the specimen.

Hormonal and ultrasound characteristics of menstrual function during chronic hemodialysis and after successful renal transplantation

The cycles of 11 renal transplant recipients (RTR), at least 24 months after stabilization of graft function and four hemodialyzed (HD) patients, menstruating regularly, were evaluated by concurrent and systematic determinations throughout the cycle of LH, FSH, estradiol, progesterone, testosterone, prolactin and SHBG and in the case of RTR also by ultrasound follow‐up. Biphasic estradiol secretion, midcycle LH and FSH surge, duration of luteal phase, midluteal progesterone values and in the case of RTR, ultrasonic parameters were consistent with: (1) normal ovulatory cycles in five RTR; (2) ovulatory cycles with luteal phase deficiency in five RTR and two HD patients; (3) anovulatory cycles in one RTR and two HD patients. Thus, in HD patients only abnormal cycles of central etiology were found, while in RTR, luteal phase deficiency was a very common syndrome, in equal percentage with normal ovulatory cycles.

Congenital adrenal hyperplasia because of 21-hydroxylase deficiency. A genetic disorder of interest to obstetricians and gynecologists.

Congenital adrenal hyperplasia (CAH) due to deficiency of the enzyme 21-hydroxylase (21-OH), is distinguished in its classical and nonclassical form and is one of the most common autosomal recessive inherited diseases in humans. The classical form appears between 1:5000 and 1:15000 among the live neonates of North America and Europe, whereas the nonclassical form occurs in approximately 0.2% of the general white populations. Three alleles are associated with the 21-OH locus and can be combined in various ways to individuals who are either unaffected, heterozygote carriers, or affected with the classical or nonclassical disease. Variable signs and symptoms of hyperandrogenism are common to both types of the disorder. In women with CAH, hyperandrogenism may be present, extending from virilization of external genitalia and salt-wasting in classical (C)-CAH cases, to menstrual irregularity, obesity, short stature, infertility or subfertility and skin disorders such as hirsutism, in nonclassical (NC)-CAH cases. These clinical characteristics of NC-CAH cases do not differ unmarkedly from those shown in patients with polycystic ovary syndrome, idiopathic hirsutism, or hyperinsulinemia. The significant advances in molecular biology and gene analysis over the past 2 decades have led to the development of novel sensitive methods of DNA analysis and study, including polymerase chain reaction and Southern blot analysis. Thus it has been revealed that the 21-OH gene (CYP21A2) and its nonfunctional pseudogene (CYP21A1P) are located on chromosome 6 (6p21.3), sharing a high homology of about 98%. Inactivating mutations occur as complete gene deletions, large gene conversions and pseudogene-derived mutations. Target Audience: Obstetricians & Gynecologists, Family Physicians Leaning Objectives: After completion of this article, the reader should be able to recall the epidemiology of carrier status for 21-hydroxylase deficiency, identify phenotypic characteristics for classic and non-classic congenital adrenal hyperplasia, and describe the consequences of 21-hydroxylase block with respect to production of other hormones and enzymes.

An update to 21-hydroxylase deficient congenital adrenal hyperplasia

Congenital adrenal hyperplasia (CAH) due to deficiency of the enzyme 21-hydroxylase (21-OH) is distinguished in classical (C-CAH) and non-classical form (NC-CAH), and it is also one of the most common autosomal recessive inherited disorders in humans. The prevalence of C-CAH is between 1:10,000 and 1:15,000 among the live neonates of North America and Europe while the NC-CAH occurs in approximately 0.2% of the general white population. The highest incidence of CAH (1:282 and 1:2141, respectively) has been evaluated in Yupik Eskimos in Alaska and in the populations of the island La Reunion (France), while the lower was detected in New Zealand newborns (0.3%). Nowadays, it has been established that except for the adrenal cortex in CAH cases, the adrenal medulla was also affected. In human 21-OH deficient adrenal gland it has been discovered that not only the chromaffin cells formed extensive neurites, expanding between adrenocortical cells, but also that the adrenal androgens promote outgrowth, whereas glucocorticoids preserve neuroendocrine cells. It seems that normal cortisol secretion by the adrenal cortex is necessary for adrenomedullary organogenesis. The synthesis of 21-OH is controlled by the active CYP21A2 gene located at a distance of 30 kb from a highly homologous pseudogene designated CYP21A1P.

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%.

Addition of prednisolone and heparin in patients with failed IVF/ICSI cycles: a preliminary report of a clinical trial

Abstract Through a non-randomized clinical trial, we examined the theoretical benefit of the coadministration of low molecular weight heparin (LMWH) and prednisolone on pregnancy outcomes in women with previously failed IVF/ICSI cycles. Fifteen women constituted the study group, and were compared with 19 women receiving LMWH alone and another 18 women with no drugs. Our finding that the combination of the two drugs produced positive differences in terms of embryo quality, pregnancy and live birth rates points to the necessity for adequately powered randomized trials.

Cardiotocography alone versus cardiotocography plus Doppler evaluation of the fetal middle cerebral and umbilical artery for intrapartum fetal monitoring: a Greek prospective controlled trial

Objective: The present study was designed to assess the utility of Doppler velocimetry in the setting of non-reassuring cardiotocography tracings. Methods: Two hundred fifty six women with term singleton pregnancies were enrolled in a controlled trial. Patients received either routine cardiotocograpic (CTG) monitoring, or CTG with the addition of Doppler velocimetry in cases of non-reassuring CTG tracings. The results were analyzed according to protocol. Results: In the CTG+Doppler group, there was a trend toward lower risk of neonatal metabolic acidosis than in the CTG group, although the incidence was rare. The CTG+Doppler group had significantly lower rates of cesarean section for fetal distress, and improved neonatal outcomes. Conclusions: We conclude that intrapartum fetal Doppler velocimetry, when combined with CTG, increases the clinicians’ ability to accurately identify fetal hypoxia, and decreases the rate of Cesarean section.

Mucin-like carcinoma-associated antigen (MCA) during normal pregnancy

OBJECTIVE To assess the usefulness of Mucin-like carcinoma-associated antigen (MCA) in monitoring pregnant patients with breast cancer. STUDY DESIGN Maternal serum (MS) and amniotic fluid (AF) antigen values were measured by an enzyme immunoassay in 30 pregnant women during the second trimester, in 28 during the third and in 26 at parturition. Sera only from 26 women in the first trimester and from 26 healthy, non-pregnant women (controls) were also analyzed. RESULTS Maternal serum MCA concentrations increased significantly with gestational age (p<0.0001). The frequency of elevated serum values was 5% in the first, 35% in the second and 100% in the third trimester and at parturition. Antigen values in AF were markedly higher than those in MS (p<0.0001) and increased also significantly with advancing gestation (p<0.0001). A strong correlation was observed between MS and AF antigen values (r=0.77, p<0.0001). Maternal serum values at parturition were dependent on the mode of delivery, being higher in the cases who delivered vaginally, compared to those delivered by elective caesarean section (p<0.006). CONCLUSION Our data suggest that pregnancy affects significantly maternal serum MCA. Consequently, MCA seems to be a non-reliable marker in monitoring pregnant patients.

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.