New aspects of injectable contraception.

Despite the availability of efficacious and safe contraceptive agents, not all women's contraceptive needs are being met. An injectable contraceptive method offers convenience and encourages compliance, both very important aspects for women seeking ideal contraception. Depot medroxyprogesterone acetate (DMPA) is a long-acting injectable, and is highly effective; one injection provides 3 months of contraception. Drawbacks of DMPA include irregular bleeding and a slow return to fertility. A new monthly injectable contraceptive agent is medroxyprogesterone acetate/estradiol cypionate suspension (Lunelle). It provides menstrual regulation and a rapid return to fertility. The estrogen ensures a withdrawal bleed monthly; however, women with contraindications to estrogen-containing contraception are not candidates for Lunelle.

Fetal 'space-suit' hydrops in the first trimester: differentiating risk for chromosome abnormalities by delineating characteristics of nuchal translucency.

Detecting first trimester fetuses with pan-body hydrops, giving the appearance of a 'space-suit,' is associated with a marked increased risk for chromosome abnormalities. In 30 consecutive fetuses prospectively characterized by space-suit hydrops, detected at or before 13.9 weeks' gestation, 26 (86.7%) were characterized by chromosome abnormalities. However, as opposed to the preponderance of autosome abnormalities among first-trimester fetuses with prominent nuchal translucencies, 15 of the 26 fetuses (57.7%) with abnormal complements were characterized by sex chromosome aneuploidies. Genetic counselling and consideration of invasive prenatal testing is warranted when space-suit hydrops is detected in the first trimester.

Preliminary comparison of papanicolaou smear and speculoscopy for assessing cervical cancer precursor lesions in pregnant adolescents.

BACKGROUND: The objective of this study was to assess the efficacy of speculoscopy in screening pregnant adolescents for abnormal cervical pathology. METHODS: This was a prospective comparative study of the Papanicolaou smear and speculoscopy in pregnant adolescents (< 17 years of age at the time of examination) presenting for their initial obstetric visits. This study was conducted at private offices of a general obstetrics and gynecology academic practice. Interventions included Papanicolaou smears and speculoscopic examinations; patients with a positive result for either intervention were offered colposcopy. Main outcome measures were Papanicolaou smear and speculoscopy outcomes and results of colposcopy and cervical biopsies. RESULTS: Thirty consecutive pregnant adolescents were included in the study. Papanicolaou smears and speculoscopic examinations were well tolerated by all adolescents. Twenty-one adolescents had negative Papanicolaou smears and speculoscopic examinations, and one woman had a positive Papanicolaou smear and a negative speculoscopic examination. Four adolescents had positive speculoscopic examinations and negative Papanicolaou smears; of these cases, significant pathology was found in one case. Four adolescents had positive Papanicolaou smears and speculoscopic examinations, with significant pathology in two of these adolescents. CONCLUSION: This preliminary study shows speculoscopy to be well tolerated, not causing cervical trauma, and as effective as the Papanicolaou smear for detecting cervical pathology in pregnant adolescents.

Primed in situ labeling for rapid prenatal diagnosis.

OBJECTIVE: Our purpose was to assess the feasibility of primed in situ labeling for analysis of prenatal diagnostic specimens. STUDY DESIGN: Prenatal diagnostic specimens were chosen at random for analysis without knowledge of clinical indication. Primed in situ labeling with primers for chromosomes 18, 21, X, and Y was performed separate from conventional cytogenetic analyses. All clinical management considerations were based solely on conventional cytogenetic analyses. RESULTS: Forty-one samples were analyzed by primed in situ labeling: 35 direct preparations of chorionic villi and 6 uncultured amniotic fluid samples. In all cases analysis confirmed the particular chromosome number determined by conventional cytogenetic analysis. CONCLUSIONS: Although conventional metaphase studies remain the standard for prenatal cytogenetic analyses, the preliminary feasibility study finds primed in situ labeling to be a rapid and reliable adjunctive diagnostic technique applicable for prenatal diagnosis in certain clinical situations. Further study is needed to assess the efficacy of primed in situ labeling in comparison to fluorescent in situ hybridization and conventional cytogenetic analyses for prenatal diagnoses.

Renal hemodialysis and maternal serum triple analyte screening.

The obstetrical management of women with renal disease is complicated and associated with increased fetal and maternal morbidity. However, maternal serum screening is an integral part of obstetrical care and should be offered to all women. We found that maternal serum levels of a-fetoprotein and human chorionic gonadotropin did not significantly change as a result of hemodialysis, whereas levels of unconjugated estriol were markedly decreased following hemodialysis. Maternal serum screening should be limited to alpha-fetoprotein analysis in women undergoing hemodialysis until the effects of hemodialysis on all serum analytes are better delineated.

Frequency of nucleated red blood cells in maternal blood during the different gestational ages.

We wished to determine the time of pregnancy at which optimal numbers of nucleated red blood cells (NRBC) are present in maternal blood. Because 30% of the NRBC in maternal blood are fetal, there are implications for prenatal screening and diagnosis. Samples of whole blood were collected from each of 225 women at various times during pregnancy. The samples were processed by charge flow separation (CFS), the NRBC enumerated, and the numbers compared on a week-to-week basis. To quantify the relationship between week of pregnancy and actual and log-transformed numbers of NRBC recovered, Pearson product moment and Spearman correlation coefficient were estimated for each of four CFS instruments and for the four instruments combined. When the data were analyzed, we found no relationship between stage of pregnancy and numbers of NRBC recovered. Even after logarithmic transformation, variability among the women, estimated by standard deviation, was large and relatively stable across the different stages of pregnancy. The number of NRBC recoverable by CFS appears to be constant between 7 and 25 weeks.

A survey of attitudes about maternal serum screening for fetal chromosome abnormalities in women 35 years of age and older.

We asked two groups of women their opinion on prenatal diagnosis and maternal serum screening (MSS): group 1 comprised women who had undergone a prenatal diagnostic procedure (amniocentesis or chorionic villus sampling) for advanced maternal age (>/=35 years) and group 2 women who had undergone MSS and were 30-34 years old. Women in group 1 were found significantly less likely to choose MSS over prenatal diagnosis than were women in group 2. The sensitivity of MSS and the age-related risk of chromosome abnormalities influenced opinions on whether to choose MSS or prenatal diagnosis. In both groups, the majority stated that they would accept MSS over prenatal diagnosis, if their obstetrician recommended it.

Discordant direct and culture results following chorionic villus sampling and the diagnosis of a third cell line in the fetus.

We report a case of discordant non-mosaic karyotypes following chorionic villus sampling (CVS). A 45,XX,der(21;21)(q10;q10) karyotype was found on direct preparation of cytotrophoblasts and 46,XX was found on long-term culture of mesenchymal core cells. Analysis of amniotic fluid cells and fetal tissue revealed a third karyotype: 46,XX,+21,der(21;21)(q10;q10). Had only culture analysis been performed, follow-up studies might not have been undertaken. This case demonstrates the importance of direct CVS preparation in helping to identify fetal abnormalities, and the need for follow-up of discordant CVS results.

Cartilage-hair hypoplasia syndrome: implications for prenatal diagnosis.

Cartilage-hair hypoplasia (CHH) is a rare autosomal recessive skeletal dysplasia characterized by short stature, sparse hair, and a variable degree of immunodeficiency. We describe here the prenatal diagnosis of CHH in a woman who was previously delivered of a similarly affected infant. In addition, we review the prenatal diagnostic implications of the localization, by linkage analysis, of the gene responsible for many cases of CHH.

A jumping Robertsonian translocation: a molecular and cytogenetic study.

We report a patient with mosaicism for two different Robertsonian translocations, both involving chromosome 21. She carries an unbalanced cell line with an i(21q) and a balanced cell line with a rob(21q22q). She is phenotypically normal but has two children who inherited the i(21q) and have Down syndrome. We demonstrate that both abnormal chromosomes are dicentric and that the proband's 21/21 rearrangement is an isochromosome formed from a maternally derived chromosome 21. We propose a model in which the i(21q) is the progenitor rearrangement in the proband, which subsequently participated in a nonreciprocal rearrangement characteristic of a jumping translocation. In addition, we review other cases of constitutional mosaicism involving jumping translocations.

Fetal cells in maternal blood: recovery by charge flow separation.

Fetal blood cells can be recovered from the maternal circulation by charge flow separation (CFS), a method that obviates the risks associated with amniocentesis and chorionic villus sampling. By CFS, we processed blood samples from 13 women carrying male fetuses, 2 carrying fetuses with trisomy 21, and 1 who had delivered a stillborn infant with trisomy 18. On average more than 2000 fetal nucleated red blood cells were recovered per 20-ml sample of maternal blood. Recovery of fetal cells was confirmed by fluorescence in situ hybridization with probes for chromosomes Y, 18 and 21. After culturing of CFS-processed cells, amplification by the polymerase chain reaction revealed Y-chromosomal DNA in clones from four of six women bearing male fetuses, but not in clones from three women bearing female fetuses.

Maternal serum analyte levels after first-trimester multifetal pregnancy reduction.

OBJECTIVE: Our purpose was to assess the effect of multifetal pregnancy reduction on maternal serum levels of analytes used for screening low-risk women for fetal chromosome abnormalities and neural tube defects. STUDY DESIGN: Peripheral blood samples were obtained between 15.09 and 20.9 weeks' gestation from 10 consecutive women who had undergone first-trimester multifetal pregnancy reduction. The samples were assayed for levels of alpha-fetoprotein, human chorionic gonadotropin, and unconjugated estriol. Analyte concentrations were interpreted within our maternal serum screening program. RESULTS: Levels of alpha-fetoprotein were significantly elevated in all samples. In each pregnancy levels of human chorionic gonadotropin and unconjugated estriol were consistent with the number of continuing gestations. CONCLUSIONS: First-trimester multifetal reduction does not alter second-trimester levels of human chorionic gonadotropin and unconjugated estriol. Further study is needed to determine whether these analytes could be used to screen pregnancies for fetal chromosome abnormalities after first-trimester multifetal reduction.

Risk of fetal mosaicism when placental mosaicism is diagnosed by chorionic villus sampling.

OBJECTIVE: Our purpose was to determine the risk of fetal mosaicism when placental mosaicism is found on chorionic villus sampling. STUDY DESIGN: We present a case of mosaic trisomy 22 detected on chorionic villus sampling and subsequently found in the fetus. A review of comprehensive chorionic villus sampling studies with emphasis on follow-up for fetal mosaicism was conducted. RESULTS: Among 13 studies reviewed, 469 cases of placental mosaicism are presented; fetal mosaicism was found in 50 (10.7%). Factors associated with fetal mosaicism are (1) mosaicism on mesenchymal core culture and (2) type of chromosome abnormality involved--specifically, marker chromosomes (26.7%) and common autosomal trisomies (19.0%). Amniocentesis predicted fetal genotype in 93% to 100% of cases of placental mosaicism, depending on the cell type in which mosaicism was diagnosed. CONCLUSIONS: Although mosaicism is usually confined to the placenta, the fetus is involved in about 10% cases. Patients should be counseled about this risk and the accuracy of follow-up amniocentesis.

Transplacental needle passage in early amniocentesis and pregnancy loss.

OBJECTIVE: To determine whether transplacental needle passage affects the frequency of pregnancy loss in early amniocentesis. METHODS: We reviewed 380 consecutive cases of amniocentesis performed before 14.9 weeks' gestation because of advanced maternal age (at least 35 years old). Procedure and pregnancy outcome data were obtained from reviews of patients' charts and telephone contact with patients or referring physicians. RESULTS: Transplacental needle passage occurred in 147 cases (38.7%). Pregnancy loss rates were similar in the transplacental and nontransplacental groups. Only the frequency of bloody taps was significantly increased among women undergoing early transplacental amniocentesis. CONCLUSION: Transplacental needle passage in cases of amniocentesis performed before 14.9 weeks' gestation does not appear to increase the risk of pregnancy loss. Therefore, deferring early amniocentesis to a later time at which nontransplacental amniocentesis may be performed should be reserved only for cases complicated by placental vessels, placental vascular lacuna ("placental lakes"), or subchorionic hematomas that should not be traversed by a needle.

Cystic fibrosis mutations among African Americans in the southeastern United States.

Since the cloning of the cystic fibrosis (CF) gene and the identification of delta F508, the most common CF mutation, screening the general population for CF has been vigorously debated. Adding to the controversy is the question of whether screening should be offered to African Americans, whose incidence of CF (1/17,000) is much lower than that of whites (1/2500). We tested for five common mutations (delta F508, G551D, G542X, R553X, and N1303K) in order to determine the frequency of common mutations in African Americans with CF from the southeastern United States. delta F508 was found on 50% of CF chromosomes; 46% of CF mutations were undetermined mutations. Our data indicate that at the current detection rate, the sensitivity of CF screening in African Americans would be appreciably lower than that of whites, and thus their inclusion in screening programs probably would not be warranted.