Bedside estimation of Down syndrome risk from second-trimester ultrasound prenasal thickness.

OBJECTIVES: To construct tables for 'bedside' estimation of Down syndrome risk based on maternal age and ultrasound prenasal thickness (PT) measurements. METHODS: Likelihood ratios were calculated using a log Gaussian model of the PT distribution in multiples of the gestational age-specific median (MoM). The model parameters were derived from 80 Down syndrome and 850 unaffected pregnancies scanned at 14-27 weeks; these data had been published previously, in three series, except for 18 Down syndrome and 119 affected pregnancies. The means were estimated as the median, and the SDs as the 10(th)-90(th) range divided by 2.563. RESULTS: A log Gaussian model fitted well the distribution of PT values in Down syndrome and unaffected pregnancies with medians of 1.31 MoM and 1.01 MoM, and log(10) SDs of 0.075 and 0.082, respectively. CONCLUSIONS: The tables provide a simple 'bedside' estimation of Down syndrome risk without the need for computerized software or complicated calculations. More prospective data on PT in combination with other first- and second-trimester screening markers are needed.

Correlation between nuchal translucency and nuchal skin-fold measurements in Down syndrome and unaffected fetuses.

OBJECTIVE: To assess whether there is a correlation between nuchal translucency (NT) and nuchal skin-fold (NF) measurements, in Down syndrome and in normal pregnancies. METHODS: Nineteen Down syndrome and 224 normal fetuses underwent ultrasound sequential examinations at 11-13 weeks and 14-28 weeks' gestation. NT was measured at the earlier examination and NF at the later one. Both markers were expressed in multiples of the normal gestation-specific median (MoM). The affected cases had been referred to us for termination of pregnancy; NT had been measured locally and NF was measured at our center prior to the procedure. All unaffected pregnancies were scanned routinely at our center. RESULTS: There was no statistically significant correlation between NT and NF, in either the Down syndrome (r = 0.076, P = 0.76) or the unaffected (r = - 0.021, P = 0.76) pregnancies. The median NF value in Down syndrome fetuses was 1.538 MoM, compared with 0.990 in unaffected fetuses (P < 0.0001). Gaussian modeling with parameters from a published meta-analysis, updated to include the current series, predicted a 91% detection rate of Down syndrome for a 5% false-positive rate when NF replaced second-trimester biochemistry in a sequential contingent screening strategy. CONCLUSION: While this study cannot exclude a small correlation between NT and NF, and the Down syndrome karyotype was known at the time of the NF scan, the markers can be considered as independent determinants of Down syndrome risk. Modeling suggests that sequential contingent screening incorporating NF is an effective screening strategy, although this needs to be confirmed in a prospective study.

Placental isoferritin levels during first trimester of normal and complete molar gestations.

Serum placental isoferritin levels (PLF) levels were measured in 33 patients admitted for routine scanning of a first trimester normal singleton pregnancy and six patients who were hospitalized for uterine evacuation of a complete molar gestation. Venous blood was obtained upon admission and before curettage, when necessary. Serum was separated into glass tubes, immediately frozen and stored at -20 degrees C until analysed. The mean serum PLF levels were 18.1 (+/- 14) U/ml and 5.5 (+/- 2) U/ml for normal and molar gestations, respectively, with a significant difference between the two groups (P = 0.001). Sixty-seven per cent of normal pregnancies had serum PLF levels > or = 10 U/ml, whereas none of the molar gestation group reached this threshold level. Furthermore, the molar gestation group's low serum PLF levels remained unchanged throughout the entire follow-up period and until their beta-human chorionic gonadotrophin levels were undetectable. Unlike normal pregnancies, the molar trophoblast does not seem to secrete or synthesize PLF, suggesting that the complete molar placenta has different protein-producing capabilities when compared with those found in normal pregnancies. Further studies, including serum PLF among other categories of gestational trophoblastic neoplasms, are recommended before this data can be integrated into routine clinical work.

Amniotic fluid volume, total phospholipids concentratio, and L/S ratio in term pregnancies.

Amniotic fluid volume, lecithin/sphringomyelin ratio, total phospholipid concentration and total phospholipid per sac were investigated in 53 term pregnancies. A definite influence of amniotic fluid volume on the phospholipid concentration was noted, while no influence on the L/S ratio was observed. Amniotic fluid volume showed a tendency to decrease after the 40th week of gestation. The total quantity of phospholipids per sac showed no significant variation between the 36th and 42nd week of gestation.

Dexamethasone for prevention of respiratory distress syndrome: multiple perinatal factors.

Antepartum dexamethasone administration was associated with a significant lowering of the incidence of respiratory distress syndrome (RDS) and with marked reduction of early neonatal mortality in premature infants. Dexamethasone had its greatest effect in infants delivered between 28 and 32 weeks' gestation (P < .001), and the difference was still significant up to 34 weeks' gestation (P < .05). Although the effect of dexamethasone was more marked in patients with intact membranes, it was also effective in those with prolonged rupture of the membranes. Membrane condition before delivery was unrelated to the incidence of RDS. The effectiveness of dexamethasone was analyzed with respect to the condition of the infant at delivery, the mode of delivery, and multiple births. As compared to the controls, dexamethasone was most effective in singletons, infants delivered vaginally, and those with high Apgar scores. The effect of dexamethasone was not significant in twins, breech deliveries, cesarean section deliveries, or infants with low Apgar scores. The effects of dexamethasone appear to be modified by intrauterine asphyxia. Dexamethasone therapy cannot be substituted for optimal delivery conditions of the premature.

Triplet and quadruplet pregnancies and management.

The rate of multiple pregnancies with more than 2 fetuses has significantly increased since the introduction of ovulation induction agents. From 1970 through 1978, there were 19 triplets and 6 quadruplets in the authors' department, incidences of 1:696 and 1:5370, respectively. Eighteen (72%) of the 25 multiple pregnancies followed treatment with ovulation induction agents and 7 were spontaneous. The diagnosis of more than 2 fetuses was made earlier in the induced than in the uninduced pregnancies. Management, initiated upon diagnosis, included bed rest, high-protein diet, beta-mimetic agents, progestins, dexamethasone late in the second trimester, and selective cerclage. The mean gestational age was 34 weeks in the triplets and 35 weeks in the quadruplets. Forty-four percent of the deliveries were by cesarean section and the remainder were by vaginal delivery. The mean weight of the neonates was 1807 g in the triplets and 1950 g in the quadruplets. The mean overall Apgar score was 8.16, and the perinatal mortality was 185 per 1000, corrected (more than 28 weeks) to 137 per 1000. The main neonatal complications resulted from prematurity, and maternal complications noted were postpartum hemorrhage necessitating hysterectomy in 2 patients. The preferable mode of delivery cannot be stated dogmatically. Fetal outcome was similar in vaginal and cesarean deliveries among the various gestational age groups.

Mifepristone (RU486) alone or in combination with a prostaglandin analogue for termination of early pregnancy: a review.

The availability of a medical mode of termination of early pregnancy by the administration of RU486, an antiprogesterone alone, or in combination with one of the PG analogues significantly reduces the maternal morbidity and mortality associated with the classical surgical abortion. RU486 given alone in early pregnancy induces complete abortion in 60% to 85% of cases, and when combined with prostaglandin analogues, gemeprost or sulprostone, reaches a success rate of 95% to 99%. RU486 may also be of potential value in the medical treatment of ectopic pregnancy. Its use as a postcoital contraception is suggested, but further research is required to determine whether RU486 can be used on a once-a-month basis for contraception.

PIP: This review of trials of RU-486 with prostaglandin for termination of early pregnancy begins with a summary of experimental and conventional early abortion techniques, introduces RU-486 with explanations of its mechanism of action, pharmacology, effects on adrenocortical receptors, the hypothalamic axis, and endometrium and ends with a discussion of its use in ectopic pregnancy and post-coital contraception. RU-486 acts by stabilizing the progesterone receptor so it cannot signal its DNA site to effect hormone action. Its peak plasma level is achieved in 2 hours, with a half life of 20 hours. RU-486 has anti-glucocorticoid effects at high doses. It also inhibits gonadotropin secretion in a dose-dependent manner, blocking ovulation. The main use of RU=-486 is in early pregnancy termination, a procedure termed contragestion, a consequence of its anti-progesterone action on the endometrium. Given alone, it is effective only 60-73% of pregnant women. Supplemented with an injection of Sulprostone, or a vaginal suppository of Gemeprost, both prostaglandin analogs, RU-486 typically will induce abortion in 96% of women up to 7 weeks pregnant. The abortion interval depends of prostaglandin dose. About 1% of women fail to abort, about 2% are incomplete, and 1% require treatment for hemorrhage, in a French trial of 2115 women. RU-486 has been used to manage ectopic pregnancy in preliminary studies. It is also being investigated as a postcoital agent, and appears to be effective from midcycle through the premenstrual phase, a wider window than current medical methods.

Reproductive outcome after laparoscopic local methotrexate injection for tubal pregnancy.

OBJECTIVE: To evaluate reproductive outcome after laparoscopic local methotrexate (MTX) injection for tubal pregnancy. DESIGN: Follow-up was performed after 77 women were treated with local MTX injection between January 1, 1987 and December 31, 1990. SETTING: Department of Obstetrics and Gynecology in a university medical center. MAIN OUTCOME MEASURES: Concise patient details about tubal patency in hysterosalpingography, pelvic findings at laparoscopy or laparotomy performed after the treatment, and the intrauterine and extrauterine pregnancy rates (PRs) are given. RESULTS: Intrauterine PR of 67% and extrauterine PR of 13% were achieved. CONCLUSION: Local MTX injection does not modify tubal or pelvic anatomy and does not impair subsequent reproductive performance.

Results of in vitro fertilization and embryo transfer by combined long-acting gonadotropin-releasing hormone analog D-Trp-6-luteinizing hormone-releasing hormone and gonadotropins.

To avoid cancellation of in vitro fertilization (IVF) because of early luteinization, pituitary suppression by gonadotropin-releasing hormone (GnRH) was carried out in 111 cycles. D-Trp-6-luteinizing hormone-releasing hormone (LH-RH) microcapsules were administered intramuscularly at menstruation and menotropin (hMG) stimulation was started 19 days (mean) later. In 3 cycles (2.7%), only early luteinization occurred. The mean number of oocytes per cycle was 6.7, with a fertilization and cleavage rate of 50 and 95%, respectively. A mean of 3.4 embryos were transferred per cycle. The 111 cycles resulted in 34 clinical pregnancies, 41% per cycle with embryo transfer. The early abortion, multiple pregnancy, and ovarian hyperstimulation rates were 24, 18, and 11%, respectively. It is concluded that D-Trp-6-LH-RH/hMG cycles are associated with a very low occurrence of early luteinization, high number of oocytes and embryos, and a substantial incidence of ovarian hyperstimulation syndrome.

The effect of chronic gonadotropin-releasing hormone analog (D-Trp-6) treatment on elevated and normal serum prolactin levels.

A long-acting GnRHa (D-Trp-6 microcapsules) proved capable of lowering serum PRL levels in a young hyperprolactinemic patient treated for a large myomatous uterus. No similar inhibitory effect was found in normoprolactinemia. Chronic GnRHa therapy may constitute an alternative to the existing forms of treatment for hyperprolactinemia and pituitary adenomas.

Ovarian hyperstimulation syndrome following D-Trp-6 luteinizing hormone-releasing hormone microcapsules and menotropin for in vitro fertilization.

In 143 cycles of in vitro fertilization the ovarian hyperstimulation syndrome (OHSS) occurred in 12 (8.4%) cycles. Six were in the moderate form and 6 severe. Ovarian stimulation by menotropins was preceded by induction of hypopituitary hypogonadism using D-Trp6-LH-RH microcapsules. The OHSS cycles are characterized by improved ovarian response expressed by the increased serum levels of estradiol, number of follicles, oocytes, embryos and pregnancy rate as compared to cycles with no OHSS. All patients recovered uneventfully. The follicular puncture did not have the suggested protective effect against OHSS. It is suggested that the substantial incidence of OHSS is probably related to the excessive ovarian stimulation not interrupted by early luteinization which is practically abolished by this protocol. The role of the given luteal hCG doses in the genesis of OHSS is questioned.

The role of tubal pathology and other parameters in ectopic pregnancies occurring in in vitro fertilization and embryo transfer.

Contradictory findings were reported concerning the role of tubal disease in the genesis of ectopic pregnancy in in vitro fertilization and embryo transfer (IVF-ET). We report on six ectopics that occurred in 141 IVF-ET pregnancies (4.3%). All of the six cases were among 84 patients with tubal disease, and none occurred in the remaining 57 patients with other etiological factors. No correlation was found in other parameters including: ovulation induction, number of embryos transferred, and luteal support. A comparison between the ectopics and six matched controls demonstrated similar estradiol levels, but beta-hCG levels on day 15 to 17 after ET were lower. Homolateral salpingectomy was performed in all six cases, but a contralateral resection was carried out in three of them. More comprehensive studies are needed to clarify whether tubal pathology really increases the risk for ectopic gestation in IVF-ET.

Sterilization at the time of cesarean section: tubal ligation or hysterectomy?

The operative, postoperative and subsequent course of 86 patients who underwent cesarean hysterectomy (C.H.) during the years 1970-1979 are compared to an equal number of cesarean sections with tubal ligation (C.S.L.). Both groups are similar regarding age, gravidity, parity, number of living children and indications for abdominal delivery. Operative and postpartum complications of both groups were all minor, although significantly (p less than 0.05) more frequent in the C.S.L. group. More patients of the C.H. group required blood transfusions than the C.S.L. group (p less than 0.01). The mean period of hospitalization was similar in both groups. Two pregnancies occurred after tubal sterilization, a failure rate of 1:43. During the follow-up period, 49 surgical gynecological procedures were performed in the C.S.L. group compared to 1 in the C.H. group. Ten patients of the C.S.L. group subsequently underwent abdominal hysterectomy. Hysterectomy is the procedure of choice for permanent sterilization and prevention of many subsequent gynecological problems. Consideration must be given to coexisting gynecological conditions while considering sterilization at elective C.S. and C.H. should be offered to those patients.

PIP: The operative, postoperative, and subsequent course of 89 patients who underwent cesarean hysterectomy (CH) during the period 1970-79 are compared to an equal number of cesarean sections with tubal ligation (CSL). Both groups are similar with regard to age, parity, gravidity, number of living children, and indications for abdominal delivery. Operative and postpartum complications of both groups were all minor, although significantly (p0.05) more frequent in the CSL group. More patients in the CH group required blood transfusions than the CSL group (p0.01). The mean period of hospitalization was similar in both groups. 2 pregnancies occurred after tubal sterilization, a failure rate of 1:43. During the follow-up period, 49 surgical gynecological procedures were performed in the CSL group compared to 1 in the CH group. 10 patients in the CSL group subsequently underwent abdominal hysterectomy. Hysterectomy is the procedure of choice for permanent sterilization and prevention of many subsequent gynecological problems. Consideration must be given to coexisting gynecological conditions while considering sterilization at elective CSL and CH should be offered to those patients.

Clear ovarian cyst aspiration guided by vaginal ultrasonography.

Thirty patients with clear ovarian cysts underwent aspiration guided by vaginal ultrasound. In 23 cases a complete aspiration was accomplished. In 4 only partial aspiration was possible, and in the remaining 3 failed aspiration led to surgery. Histological findings correspond to retroperitoneal lipoma and mucinous cystadenoma (2 cases). Malignant cells were not detected in the fluid of any of the 27 aspirates. Eight of the ten patients presenting with abdominal pain experienced a relief following aspiration. Recurrence of the cyst occurred in 12 cases (40%) with significantly smaller dimensions (P less than 0.01). Vaginal ultrasound aspiration of clear cyst is easy and safe and can be considered as an outpatient procedure.

Sonographic assessment of cervical changes during pregnancy and delivery: current concepts.

Correct detection of premature contractions and incompetent uterine cervix is still a challenging obstetrical problem since these factors remain a major cause of perinatal loss. Ultrasonography offers additional important data for the prediction of these pathologies which have common sonographic patterns; shortening of the cervical length, funneling of the membranes and dilatation of the endocervical canal. The first section of this review highlights sonography of normal cervical anatomy, while the second section focuses on recent advances in sonographic detection of premature contractions and incompetent cervix. It is believed that due to its accuracy and reproducibility, this noninvasive technique should become more integrated into this aspect of antenatal care.

Flow analysis in the pulmonary trunc in fetuses with tetralogy of Fallot by colour Doppler flow mapping; two case reports.

Prenatal diagnosis of tetralogy of Fallot by two-dimensional echocardiography, which is based on demonstration of a ventricular septal defect and a large overriding aorta, is difficult. In the majority of cases the main pulmonary artery is small. In utero, there is no pathologically increased degree of the physiological right-ventricular hypertrophy. Colour Doppler flow mapping of reverse flow from the descending aorta via the ductus arteriosus into the main pulmonary artery is easily demonstrated, and provides an indirect sign of severe right-ventricular outlet obstruction. The technique also differentiates between pulmonary stenosis and atresia; the stenotic jet, even small, is identified by demonstration of high velocities and turbulences in the main pulmonary artery.

Thickness of basal cell epithelioma measured preoperatively by ultrasonography.

A new approach to the diagnosis and measurement of the thickness of basal cell epithelioma (BCE) by ultrasonography is described. The advantages and efficacy of the new technique are presented.

Enhancement of cytotoxic agent accumulation by Doppler flow sonication of human ovarian cancer cells.

The intracellular accumulation of adriamycin (ADR) by Doppler flow sonication was investigated in a human ovarian carcinoma line. Cytofluorometry was performed on cells treated by ADR (0.5, 1 and 2 micrograms/mL) alone, or in conjunction with Doppler flow sonication for 5, 10, and 15 minutes. Increased intracellular accumulation of ADR was observed in cells treated at each of these test intervals. Statistically significant increases in high permeability, due to Doppler sonication, were around 1.5 fold at each of the test intervals, with a maximum observed at 10 minutes of treatment. Examination of ADR dose effect showed that the most vigorous to Doppler sonication occurred at 1 micrograms/mL ADR. Although statistically non-significant, a trend towards the most prominent egect of 91.6% cell validity was noticed after 15 minutes of treatment. Our findings demonstrate that an improvement of ADR penetration into malignant cells can be obtained in this bioultrasound model. Wowever, caution is advised when extrapolating in vitro experimental results to in vivo phenomena.

[Trisomy 18 anomalies on sonography and calculated risk of chromosomal abnormalities during first trimester].

Trisomy 18 is a chromosomal disorder giving multiple anomalies. Its frequency depends on maternal age. We report a 28-year-old woman in her first pregnancy, who underwent first trimester scanning for screening. Due to increased nuchal translucency and exomphalos, chorionic villous sampling was performed. Cytogenetic diagnosis was trisomy 18 and termination of pregnancy was carried out immediately.

[Screening for Down's syndrome at week 10-14 by measuring fetal nuchal translucency thickness].

Increased fetal muchal translucency (NT) thickness at 10-14 weeks of gestation may indicate underlying fetal chromosomal abnormalities, anatomical anomalies and genetic syndromes. Between January 1997 and May 1998, 1400 women 10-14 weeks pregnant underwent sonographic screening for detection of Down's syndrome (DS). Follow-up was complete in 1208 (86%). Maternal age ranged from 17-44 years (mean 18.0). 87% were found by screening to have a higher risk (1:380) for DS diagnosed at birth. All these fetuses were karyotyped and 8 had chromosomal abnormalities. 2 fetuses with normal NT were diagnosed later as having DS, 1 by the mid-gestation triple test and 1 by amniocentesis because of advanced maternal age. Thus sonographic screening identified 8 out of 10 fetuses found to have chromosomal abnormalities at birth. Neonates not karyotyped before birth had no traits at birth that justified chromosomal analysis. Results of this study suggest that NT measurement, combined with maternal age, is an effective 1st trimester screening method for DS in an unselected obstetric population.