Seminal plasma enhances and accelerates progesterone-induced decidualisation of human endometrial stromal cells.

In preparation for embryo implantation, endometrial stromal cells (ESC) undergo differentiation, termed decidualisation. Enhancing endometrial decidualisation may overcome reduced endometrial receptivity, a major limiting factor in natural and assisted reproduction. To determine whether seminal plasma (SP) influences decidualisation, primary human ESC were treated with progesterone (P4, 50 ng mL(-1)) in the presence or absence of dialysed SP (0.5%) for 24 h or for up to 27 days to investigate immediate early effects or the effects of prolonged exposure, respectively. Combined SP and P4 treatment induced ESC morphological differentiation. Relative to control, P4 alone, and SP alone combined treatment with SP and P4 for 27 days significantly upregulated mRNA levels of the decidua-specific markers prolactin (PRL) and insulin-like growth factor binding protein 1 (IGFBP1). Consistently, PRL protein secretion was significantly increased over the course of 27 days combined SP and P4 treatment relative to control, P4 alone and SP alone. Likewise, IGFBP1 secretion was significantly greater relative to control and P4 alone over the course of 27 days. Thus, SP enhances and accelerates P4-mediated decidualisation of human ESC and may enhance endometrial receptivity.

Prenatal diagnosis of intrauterine premature closure of the ductus arteriosus following maternal diclofenac application.

We report a case of prenatal diagnosis of premature closure of the ductus arteriosus following maternal diclofenac therapy at 35 weeks of gestation. Fetal echocardiography at 37 weeks of gestation revealed a dilated right ventricle with moderate tricuspid regurgitation, pulmonary insufficiency and complete closure of the ductus arteriosus. Immediate Cesarean section resulted in an excellent neonatal outcome. Whereas the effect of indomethacin on prenatal ductal constriction is well known, widely prescribed non-steroidal anti-inflammatory drugs such as diclofenac can have an equally deleterious effect and are best avoided in the third trimester of pregnancy.

Sex-specific antenatal reference growth charts for uncomplicated singleton pregnancies at 15-40 weeks of gestation.

OBJECTIVE: Female fetuses, on average, weigh less than male fetuses at all gestational ages. The purpose of this study was to compare female and male fetuses in terms of intrauterine ultrasound growth measurements and to develop gestational-age-related charts based on a computerized perinatal database. METHODS: This was a retrospective study of unselected women in the second and third trimesters of pregnancy, who had a normal scan at 10-14 weeks. Data analysis was performed using measurements obtained from a mixed-race population of 4234 women, who underwent 5198 ultrasound examinations. The scans were performed by four trained sonographers, according to a standardized protocol. Routine measurements included biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC) and femur length (FL). The main end-points were sex- and race-specific differences in fetal biometry, which were also used to estimate fetal weight. RESULTS: The base-line demographic characteristics and risk factors were comparable in female and male fetuses. Significant differences in fetal BPD, HC, AC and estimated fetal weight, but not FL, were seen between male and female fetuses. Centile charts for each of these variables were constructed for both male and female fetuses. CONCLUSIONS: This study suggests that small but consistent sex-related differences in prenatal BPD, HC and AC measurements are established by as early as 15 weeks of gestation. The use of sex-specific nomograms may improve the prenatal assessment of fetal growth as well as the diagnosis of structural abnormalities.

Late onset microcephaly: failure of prenatal diagnosis.

We present a case of recurrent primary developmental microcephaly of late onset, the prenatal diagnosis of which could not be achieved despite performing targeted serial ultrasound scans that revealed no obvious fetal abnormality. Serial scans for head measurements and detailed examination of the brain anatomy by both transabdominal and transvaginal sonography including color and power Doppler assessment revealed no obvious brain abnormality. Frontal lobe distance and thalamic frontal lobe distance at 36 weeks were on the 30th and 50th centiles, respectively. Growth velocity remained on the 50th centile up to 36 weeks; between 36 and 38 weeks measurements were between the 35th and 40th centiles. The infant was delivered by Cesarean section at 38 weeks on parental request. On examination after birth the head circumference was on the 9th centile, but the facies was that of a microcephalic child with a sloping forehead and neurologically he was severely abnormal. The adequacy of the normal reference ranges used is reviewed: the use of sex-specific growth charts at 38 weeks would have demonstrated the biparietal diameter and the head circumference to be on the 20th and 15th centiles, respectively, rather than just below the 40th centile. However, even sex-specific charts may not allow the recognition of a substantial number of affected fetuses.

Prenatal diagnosis of de novo mosaic deletion 13q associated with multiple abnormalities.

A case of prenatal diagnosis of de novo mosaic deletion of the long arm of chromosome 13 (del(13)(q13.3)) is presented. Routine scanning in a 27-year-old primigravida at 25 weeks' gestation showed fetal bilateral hydronephrosis. Detailed anomaly scanning in our tertiary referral center further demonstrated posterior meningoencephalocele, sloping forehead, microcephaly, syndactyly and hypoplastic thumbs. Both genetic amniocentesis and cordocentesis revealed a mosaic karyotype, 46,XY/46,XY,del(13)(q13.3). Sonographic findings were confirmed by postmortem autopsy and additional abnormalities such as agenesis of corpus callosum, hypoplastic cerebellum and macroglossia were diagnosed. Detailed sonography in this case thus revealed multiple malformations that prompted fetal karyotyping at 25 weeks' gestation.

Preliminary experience with steroidal ovarian suppression for prevention of severe ovarian hyperstimulation syndrome in IVF patients.

The purpose of the study was to evaluate the efficiency of administration of high dose progesterone in combination with oestradiol during the luteal phase for the prevention of ovarian hyperstimulation syndrome in a high-risk population of patients undergoing in vitro fertilization. An observational study was carried out involving 21 women (mean age 28.6 years) undergoing controlled ovarian stimulation for in vitro fertilization. The women were identified as at risk of ovarian hyperstimulation syndrome as they had suffered from the condition when hCG was used for luteal phase support in previous cycles. Steroidal suppression of the stimulated ovary on days 2, 6, 10 and 14 after embryo transfer was achieved by intramuscular injections of 500 mg hydroxyprogesterone caproate and 10 mg oestradiol valerate. The incidence of moderate and severe ovarian hyperstimulation syndrome under steroidal ovarian suppression, serum progesterone concentration and pregnancy rates were compared with those in cycles in which human chorionic gonadotrophin was used for luteal phase support. No cases of moderate or severe ovarian hyperstimulation syndrome occurred under steroidal ovarian suppression. Despite low progesterone concentrations (mean 10.7 nmol l(-1), range 2.6-24.5), indicating almost complete ovarian suppression, the pregnancy rate was not impaired. These preliminary results indicate that steroidal ovarian suppression during the luteal phase is a promising tool for reducing the incidence and severity of ovarian hyperstimulation syndrome in a high-risk population, without compromising the pregnancy rate.

Prenatal findings on ultrasound and X-ray in a case of overgrowth syndrome associated with increased nuchal translucency.

A case of prenatal diagnosis of an overgrowth syndrome at 30 weeks of gestation is reported. The diagnosis was suggested on the basis of increased fetal growth from 16 weeks onwards, advanced bone age, and characteristic facial features such as hypertelorism, broad forehead and small chin. The fetus presented at 12 weeks with a markedly increased nuchal translucency thickness and generalized skin edema, but normal karyotype. Serial ultrasound scans revealed brain abnormalities including mild unilateral ventriculomegaly and a cyst in the cavum septi pellucidi. The pregnancy was terminated at the parents' request at 32 weeks of gestation and postmortem examination confirmed the prenatal findings. This case demonstrates the possibility of prenatal diagnosis of early overgrowth syndromes and highlights the dilemma arising from the prenatal diagnosis of a non-lethal condition associated with an uncertain prognosis and poorly documented in utero.

Longitudinal changes in the ductus venosus, cerebral transverse sinus and cardiotocogram in fetal growth restriction.

OBJECTIVE: To evaluate the changes in flow velocity waveforms in the transverse cerebral sinus in growth-restricted fetuses and to correlate these changes with (1) flow velocity waveforms in the ductus venosus and (2) changes in computerized analysis of the fetal cardiotocogram. DESIGN: Fetuses between 22 and 37 weeks' gestation with an estimated fetal weight below the fifth centile were included in this prospective longitudinal study. Doppler measurements of the umbilical artery, descending aorta, middle cerebral artery, transverse cerebral sinus and ductus venosus were recorded. Fetal heart rate was analyzed by a computer system according to the Dawes-Redman criteria. RESULTS: We measured a significant correlation between pulsatility index in the cerebral transverse sinus and in the ductus venosus over the study period and at delivery. There was a negative correlation between these indices and short- and long-term variability of the fetal heart rate. There was a parallel increase in pulsatility in the ductus venosus and the transverse cerebral sinus. These changes were inversely correlated with fetal heart rate variability and preceded fetal distress. CONCLUSION: Cerebral venous blood flow in IUGR fetuses may be a useful additional investigation to discriminate between fetal adaptation and fetal decompensation in chronic hypoxemia.

Screening for fetal aneuploidies and fetal cardiac abnormalities by nuchal translucency thickness measurement at 10-14 weeks of gestation as part of routine antenatal care in an unselected population.

OBJECTIVES: To evaluate first trimester pregnancy screening for fetal aneuploidy and congenital heart defects by maternal age and nuchal translucency measurement and screening for fetal aneuploidies and congenital heart defects by ultrasound in an unselected population. DESIGN: A prospective study. SETTING: Fetal medicine unit, St George's Hospital, London. SAMPLE: 4523 consecutive viable fetuses at 10-14 weeks with a crown-rump length between 38 and 80 mm were scanned transabdominally (93%) or transvaginally (7%). METHODS: Screening was performed by calculating the background risk from maternal age, gestational age and obstetric history, which was then adjusted with the nuchal translucency measurement in relation to crown-rump length (adjusted risk). MAIN OUTCOME MEASURES: Measurements of crown-rump length and nuchal translucency thickness. An adjusted risk of > 1:270 was considered as a positive screening test. Pregnancy outcome was obtained through karyotyping, outcome questionnaires and examination of the newborn infants. RESULTS: Mean maternal age was 29-4 years and mean gestational age 12.2 weeks. Screening was positive in 230/4523 fetuses (5.1%), when the adjusted risk (mean 1:2649) was > 1:270. Fetal karyotype was abnormal in 23 (0.51%) cases, including twelve with trisomy 21, five trisomy 18, one trisomy 13, one trisomy 10, one monosomy X and two triploidies. For a false positive rate of 4.7%, the sensitivity of this test was 78% in detecting any fetal aneuploidy. Only one out of nine major congenital heart defects in this population was found within the 110 euploid fetuses with increased nuchal translucency thickness (> 2.5 mm). CONCLUSION: Screening for fetal aneuploidy by maternal age and nuchal translucency measurement can be effective in an unselected population. However, our results do not support its effectiveness in the detection of cardiac abnormalities.

Lung development in diamniotic twins discordant for complete urinary tract obstruction.

OBJECTIVES: To investigate the effect of anhydramnios on the lung development of 1 twin in the presence of a normal amniotic fluid volume in its diamniotic co-twin. METHODS: Three sets of diamniotic twins, discordant for complete urinary tract obstruction and anhydramnios, were followed prospectively with regular ultrasound scans and after delivery. RESULTS: All 3 twins with complete urinary tract obstruction and anhydramnios died within 2 days after birth, with confirmed severe pulmonary hypoplasia. In every case the twin with a normal amount of surrounding amniotic fluid had a normal postnatal outcome. CONCLUSIONS: The observation that a normal amniotic fluid volume in one sac does not protect the anhydramniotic twin from pulmonary hypoplasia has important implications for the aetiology of the condition and for the possibility of therapeutic septostomy. These results are discussed in relation to previous human and animal studies.

Feasibility of the second-trimester fetal ultrasound examination in an unselected population at 18, 20 or 22 weeks of pregnancy: a randomized trial.

OBJECTIVE: To date, there have been no studies on the optimal timing of second-trimester ultrasound screening for fetal abnormalities. The purpose of this study was to investigate whether, of three gestational ages (18, 20 and 22 weeks), any one was associated with a significant advantage in terms of identification of abnormalities or need for further ultrasound assessment. DESIGN: Prospective, randomized study of second-trimester unselected pregnant women, who had had an ultrasound examination with normal results at 10-14 weeks. SUBJECTS AND METHODS: A total of 1206 women were randomized into three mutually exclusive groups relating to their second-trimester appointment for a screening ultrasound examination for fetal abnormalities in the second trimester of pregnancy: Group 1 at 18-18 + 6 weeks, Group 2 at 20-20 + 6 weeks and Group 3 at 22-22 + 6 weeks. The anomaly scans were carried out according to a standardized protocol. The fetuses were examined for structural and developmental abnormalities. Uterine artery Doppler measurements, including waveform recordings, were performed in all cases. The main end-points were the need for rescanning of all or part of the fetal anatomy, fetal outcome, placental localization, and incidence of notches in the uterine artery waveform. RESULTS: The baseline demographic characteristics and risk factors in the three groups were similar and gestational age-related fetal measurements were comparable. There were significantly higher percentages of completed scans in Group 2 (90%) and Group 3 (88%) than in Group 1 (76%; p < 0.001), but no significant difference between those scanned at 20 and at 22 weeks. This was associated with a higher incidence of non-cephalic presentation in Group 1 (46%) than in the other two groups (36%, p < 0.001). Significant differences in completing the assessment of the thorax, heart, spine and skeleton were also observed. There was no significant difference in maternal body habitus, fetal movements or the occurrence of uterine fibroids between the study groups. The incidences of low-lying placenta and of abnormal uterine artery Doppler screening were also higher at 18 weeks than at 20 and 22 weeks (p < 0.001 for both variables), with no difference seen between Groups 2 and 3. The numbers of fetal anomalies detected in the three groups were three, two and two, respectively; these did not differ significantly between the groups. CONCLUSIONS: This study suggests that, in an unselected pregnant population, second-trimester ultrasound screening is easier to perform and less likely to require an additional scan at 20-22 weeks than at 18 weeks.

Prenatal diagnosis of fetal adrenal masses: differentiation between hemorrhage and solid tumor by color Doppler sonography.

We present four cases of fetal adrenal masses detected by routine prenatal ultrasound, of which three were adrenal hemorrhages and one was a fetal neuroblastoma. The differential diagnoses of fetal adrenal mass include adrenal hemorrhage, neuroblastoma, adrenal and cortical renal cysts, pulmonary sequestrations, duplication of the renoureteral system and Beckwith-Wiedemann syndrome. These can pose a diagnostic and therapeutic dilemma. A systematic comparison of the pre- and postnatal sonographic features including color Doppler imaging may help to differentiate adrenal hemorrhage from neuroblastoma prenatally.

The conservative management of first trimester miscarriages and the use of colour Doppler sonography for patient selection.

This study of patients with first trimester miscarriage evaluates whether conservative management is a feasible strategy and assesses the value of colour Doppler ultrasonography for patient selection. After confirmation of the diagnosis by transvaginal sonography all patients were offered the choice of immediate dilatation and curettage or conservative management. The presence of a gestational sac, the occurrence of spontaneous complete miscarriage within 28 days, detectable pulsatile blood flow within the placenta in the presumed region of the intervillous space and post-treatment complications were the main end-points. Out of a total of 108 women recruited, 23 (21.3%) elected to undergo immediate dilatation and curettage and 85 (78.7%) chose conservative management. The treatment groups were similar in age, gestational age, gestational sac diameter, serum concentrations of human chorionic gonadotrophin (HCG) and progesterone, and proportion of patients who had post-treatment complications (12-13%). Of patients in the conservative management group, 71 out of 85 (84%) had a spontaneous, complete abortion, while 37 out of 46 cases (80%) with detectable presumed intervillous pulsatile blood flow had a complete, spontaneous abortion within 1 week; this occurred in 23% of cases with no detectable flow. This suggests that conservative management is a successful approach for many patients with first trimester miscarriage; colour Doppler ultrasonography can be used to select the most suitable patients for this strategy, and thus reduce the need for hospital admission and surgery.

Trisomy 2 in an acardiac twin in a triplet in-vitro fertilization pregnancy.

A case is reported of twin reversed arterial perfusion (TRAP) sequence in a triamniotic dichorionic triplet pregnancy conceived by in-vitro fertilization which was diagnosed at 25 weeks of gestation by colour Doppler sonography. It highlights the risk of monochorionicity-associated morbidity in multiple pregnancies obtained by assisted conception and stresses the importance of chorionicity determination by early ultrasound examination. Cytogenetic analysis of skin from the acardius showed trisomy 2 in all cells, whereas the karyotype in the monochorionic triplet was normal. This is an example of heterokaryotypic monozygotism where the chromosomal abnormality must have occurred during the early cleavage divisions. Aneuploidy as a possible aetiological factor of TRAP sequence is discussed.

Subjective assessment of adnexal masses with the use of ultrasonography: an analysis of interobserver variability and experience.

OBJECTIVE: The aim of the study was to evaluate the subjective assessment of ultrasonographic images for discriminating between malignant and benign adnexal masses. STUDY DESIGN: The study was prospective. Initially, one ultrasonographer preoperatively assessed 300 consecutive patients with adnexal masses. Subsequently, the recorded transparent photographic prints were independently assessed by five investigators, with different qualifications and level of experience, who were also given a brief clinical history of the patients (i.e. the age, menstrual status, family history of ovarian cancer, previous pelvic surgery and the presenting symptoms). The diagnostic performance of the observers was compared with the histopathology classification of malignant or benign tumors. The end-points were accuracy, interobserver agreement and the possible effect of experience. RESULTS: The first ultrasonographer and the most experienced investigator both obtained an accuracy of 92%. There was very good agreement between these two investigators in the classification of the adnexal masses (Cohen's kappa 0.85). The less experienced observers obtained a significantly lower accuracy, which varied between 82% and 87%. Their interobserver agreement was moderate to good (Cohen's kappa 0.52 to 0.76). CONCLUSION: Experienced ultrasonographers using some clinical information and their subjective assessment of ultrasonographic images can differentiate malignant from benign masses in most cases. The accuracy and the level of interobserver agreement are both correlated with experience. About 10% of masses were extremely difficult to classify (only < 50% of assessors were correct).

Trisomy 10: first-trimester features on ultrasound, fetoscopy and postmortem of a case associated with increased nuchal translucency.

We report a case of the prenatal diagnosis of trisomy 10 in a fetus presenting with an increased nuchal translucency thickness (5 mm) on a routine first-trimester anomaly scan at 12 weeks' gestation. Multiple abnormalities were diagnosed by ultrasound and fetoscopy. Karyotyping on chorionic villus sampling led to the diagnosis of homogeneous trisomy 10 which was confirmed by in situ hybridization on fetal tissue samples. Postmortem examination confirmed major anatomical malformations, including facial cleft, arthrogryposis of the upper and lower limbs and bilateral diaphragmatic hernia, and also revealed hypoplastic lungs, right renal agenesis and a complex cardiac malformation. Trisomy 10 is an uncommon chromosomal abnormality that is likely to be associated with increased fetal nuchal translucency. This case also emphasizes the value of a detailed anomaly scan in high-risk patients in the first trimester of pregnancy.

Diagnosis of twin reversed arterial perfusion sequence in the first trimester by transvaginal color Doppler ultrasound.

A case of twin reversed arterial perfusion (TRAP) sequence was diagnosed at 12 weeks' gestation using transvaginal color Doppler ultrasound, which demonstrated the presence of retrograde perfusion in the umbilical artery of the abnormal twin. Ultrasound imaging showed a monochorionic-diamniotic twin pregnancy with an inappropriately grown second twin, the morphological evaluation of which revealed an abnormal cephalic pole with acrania, diffuse subcutaneous edema and the presence of cardiac activity in an abnormal heart with a single chamber.