Stratified rates of cesarean sections and spontaneous vaginal deliveries. Data from five labor wards in Denmark--1996.

BACKGROUND: A fundamental point when auditing labor management is to ensure present and stratified process data. METHOD: Stratification of deliveries into ten mutually exclusive groups enabled comparisons of rates of cesarean sections and rates of spontaneous vaginal deliveries between labor wards. RESULTS: Data from five labor wards in Denmark in 1996 were included in the study comprising a total of 11,287 women. The overall cesarean section rates were between 13.2 and 15.2% which was not a significant difference, whereas cesarean section rates in several of the ten groups and the rates of spontaneous vaginal delivery in group 1 and 3 were significantly different between the labor wards. DISCUSSION: The method presented here is simple and can be used as an integrated part of the daily work and quality assurance. We advocate that stratification of the delivering women into ten groups should take place in every labor ward with focus on both the cesarean section rate and the rate of spontaneous vaginal delivery. Stratification provides data for periodical evaluation of the outcome within a department and for comparison between departments with different populations and policy.

Loop diathermy or laser excisional conization for cervical intraepithelial neoplasia.

BACKGROUND: Cervical intraepithelial neoplasia (CIN) can be managed by ablative or excisional procedures. We have compared the excision time, effectiveness, and safety of loop diathermy (loop) against laser conization. METHODS: In a prospective study in two hospital departments 222 women were randomized to loop or laser conization. Data were collected by questionnaires after operation and at two follow-up examinations. RESULTS: At department A (122 women), two physicians performed 27% of the loop and 35% of the laser excisions; at department B (100 women), the corresponding figures were 69% and 59%. Loop was quicker than laser conization in both departments (median 3-4 min versus 10-20 min), while laser conization was more time consuming in department A (median A/B = 20/10 min). Peroperative bleeding dominated during the laser procedure in both departments and complicated the loop procedure more frequently in department A. Postoperative bleeding occurred with equal frequency in the four groups (41.8%, 52.7%, 59.2%, 64.7%). At both departments, bleeding for more than two weeks was reported twice as often after laser conization (A:13.8%, B:24.2%), when compared to loop excision (A:7.1%, B:13.7%). Residual CIN was found in all of three re-conizations and in one of eight hysterectomy specimens. CONCLUSIONS: Loop was quicker than laser excision, per- and postoperative bleeding diminished, and the success rates were comparable. Physicians mastered Loop excision after a few attempts. However, the results improved, when performed by a restricted number of physicians. Histological incomplete excision indicates close colposcopic and cytologic follow-up to identify residual CIN.

[An outpatient unit for early pregnancy. Establishment and effects on the pattern of hospital admissions]. / Ambulatorium for tidlig graviditet. Etablering og indflydelse på indlaeggelsesmønster.

The aim of the study was to evaluate the effect of an assessment of complications in early pregnancy in an "early pregnancy unit" opened in May 1993. The purpose of the "early pregnancy unit" was to avoid routine admission of women with pain/bleeding in early pregnancy. All general practitioners were informed of the possibility of referring patients to examination and ultrasonography in the "early pregnancy unit" during daytime, instead of acute admission to the ward. Data was compiled from the hospital admission and the emergency unit register for the years 1992-1996. These showed that admissions for early pregnancy complications decreased from 714 (1992) to 315 (1996) accounting for 41% (1992) and 16% (1996) of total admissions to the department, and 23% (1992) and 10% (1996) of the numbers of deliveries, respectively. Women referred between 00:00 hours and 7 a.m. accounted for 23% (1992) and 9% of admissions of total admissions or of deliveries (1996). It is concluded that initiation of the early pregnancy assessment unit resulted in a reduction in the number of admissions. The hospital staff experienced a reduced workload during the night.

Accuracy of cytogenetic findings on chorionic villus sampling (CVS)--diagnostic consequences of CVS mosaicism and non-mosaic discrepancy in centres contributing to EUCROMIC 1986-1992.

Of 62,865 karyotyped chorionic villus (CV) samples that were reported to EUCROMIC 1986-1992, 98.5 per cent showed either a normal karyotype (true negative result; 94.8 per cent of the total) or a non-mosaic chromosomal aberration (true positive non-mosaic result; 3.7 per cent). True fetal mosaicism was diagnosed in about 0.15 per cent of the 62,865 CV samples, while confined placental mosaicism (CPM) occurred in 1.0 per cent. False-positive non-mosaic aberrations were observed in 0.15 per cent and false-negative CVS (chorionic villus sampling) results in only 0.03 per cent. The remaining 0.15 per cent of the CVS results were unclassifiable. These figures determined a sensitivity of CVS for prenatal detection of chromosome aberrations of 98.9-99.6 per cent (95 per cent confidence intervals), a specificity of 98.5-98.8 per cent, a positive predictive value of 72.6-78.3 per cent, and a negative predictive value of 99.95-99.98 per cent. False-positive non-mosaic aberrations that could not from the outset be suspected of being confined to the placenta were very rare (0.07 per cent of CV samples). They most often involved non-mosaic monosomy X and trisomy 18 encountered after direct preparation alone. False-negative CVS results were extremely rare (0.03 per cent) and occurred, with only one exception, after direct preparation alone. Thirteen of the 19 false-negative CVS diagnoses were from pregnancies at a particularly high risk for fetal chromosomal aberration. Seventy-five per cent of the pregnancies with CVS mosaicism or non-mosaic discrepancy and known outcome continued to livebirth. When CVS mosaicism was encountered, the definitive prenatal cytogenetic diagnosis was most often obtained through subsequent amniocentesis. However, the use of amniocentesis and the frequency of pregnancy termination depended on the type of chromosomal aberration involved. We conclude that CVS is an accurate method for prenatal chromosome analysis. In pregnancies at high risk for fetal chromosomal abnormality, we recommend, however, not relying solely on a normal karyotype obtained after direct preparation alone.

European collaborative research on mosaicism in CVS (EUCROMIC)--fetal and extrafetal cell lineages in 192 gestations with CVS mosaicism involving single autosomal trisomy.

Cytogenetic information on cells from cytotrophoblast, villus mesenchyme, and one or more fetal tissues was available for 192 gestations with mosaicism or non-mosaic fetoplacental discrepancy involving a single autosomal trisomy in the chorionic villus sample (CVS), registered in a collaborative study (EUCROMIC) during the period 1986-1994. In order to identify predictors of confined placental mosaicism (CPM), generalized mosaicism and/or uniparental disomy (UPD), distribution of the mosaic and nonmosaic aneuploid cell lines in the different fetal and extrafetal cell lineages were analyzed. Data were related to existing hypotheses on mechanisms leading to fetoplacental discrepancies and early extraembryonic cell differentiation. Trisomy 21 mosaicism was the one most frequently confirmed in the fetus. Non-mosaic trisomy 13, 18, and 21 in the villus mesenchyme indicated the presence of a trisomic cell line in the fetus proper. Non-mosaic trisomy 2, 7, and 16 in villus mesenchyme was always found with concomitant mosaic or non-mosaic trisomy in the cytotrophoblast, but was never recovered in the fetus. Mosaic trisomy 3, 7, and 20 was predominantly restricted to the cytotrophoblast, mosaic trisomy 2 to the villus mesenchyme. Trisomies 15 and 16 were most often found in both cytotrophoblast and villus mesenchyme and not in fetal cells. This supports the hypothesis that mosaicism/discrepancy for trisomies 15 and 16 results more often than for the other trisomies from trisomic zygote rescue, enhancing their risk for UPD. We recommend, due to the risk of fetal trisomy, amniocentesis in all gestations involving mosaic autosomal trisomy in villus mesenchyme. In gestations with mosaic or non-mosaic autosomal trisomy in both cytotrophoblast and villus mesenchyme we recommend, in order to exclude fetal trisomy and/or UPD, depending on the chromosome involved, further examination by amniocentesis, ultrasound and/or test for UPD. We also recommend, due to a small but not negligible risk of false negative and false positive diagnoses, not to solely use direct preparation.

Pre- and postoperative therapy with GnRH agonist for endometrial resection. A prospective, randomized study.

BACKGROUND: To assess the value of endometrial preparation, with preoperative and pre- and postoperative GnRH agonist therapy in transcervical endometrial resection. METHODS: Sixty women with menorrhagia were randomly divided between three groups: A: no preoperative preparation, B: goserelin 3.6 mg given as a subcutaneous implant 4-6 weeks preoperatively, and C: the same regimen as B, and repeated on the day of endometrial resection. At follow-up visits 1, 3, 6 and 12 months after operations the patients were interviewed for duration, amount and pains of menstrual periods. RESULTS: The duration of surgery for the pretreated group (32.8 +/- 5.1 min) and the group treated postoperatively (30.9 +/- 8.9 min) were significantly shorter than that in the control group (46.4 +/- 11.5 min) (p < 0.01). The weight of endomyometrial strips was about 3 times lower for group B and C as compared to group A (p < 0.01). Three months following the procedure twenty five percent of patients in group A were amenorrheic or showed scanty bleeding as compared to 58% and 85% in group B and C (p < 0.05 and p < 0.01), respectively. At 12 months follow-up these rates were 35%, 58% and 67% respectively (A versus B: NS, A versus C: p < 0.05) and 24%, 65% and 75% after excluding larger submucosal fibroids (A versus B: p < 0.025, A versus C: p < 0.005). No statistical difference was demonstrated between group B and C. Sixty-nine percent of pretreated patients (group B + C) versus 35% of women in group A reported improved or relieved menstrual cramps (p < 0.05). CONCLUSIONS: GnRH pretreatment facilitates endometrial resection and increases the rate of amenorrhea and scanty bleeding postoperatively. Whether supplementary postoperative therapy with GnRH agonist enhances the success rate further is uncertain.

Prenatal diagnosis in Denmark.

Prenatal diagnosis (PND) in Denmark is covered by 5 genetic departments. More than 10% of all pregnancies are monitored by amniocentesis (AC) or chorionic villus sampling (CVS). Prenatal cytogenetic analyses are recorded in the Danish Central Cytogenetic Register (DCCR), which provides information on individual cases for genetic counselling and allows the Health Authorities to monitor prenatal diagnosis (PND). About 40% of trisomy 21 is diagnosed prenatally. The present procedures are AC, CVS, chordocentesis, and ultrasound scan. The methods include a wide range of cytogenetic, molecular, and biochemical analyses. Fluorescent in situ hybridisation, comparative genomic hybridisation, and fetal cells in maternal blood are currently investigated. PND is a public health service; the expenses are covered by the counties. The National Board of Health provides guidelines for indications for PND, while termination of pregnancy because of abnormal findings after the 12th week is evaluated on an individual basis. The current legislation prevents pre-implantation diagnosis. This year, clinical genetics was registered as a speciality in Denmark.

Function of the corpus luteum, the endometrium and the trophoblast after treatment of tubal pregnancy by prostaglandin F2 alpha.

The activity of the corpus luteum, the endometrium and the trophoblast was studied after local medical treatment of 31 women with tubal pregnancy. We measured the serum concentration of progesterone, the secretory endometrial protein placental protein 14 (PP14), and human chorionic gonadotrophin (HCG) before and after treatment by injection of prostaglandin F2 alpha into the site of the gestation and into the corpus luteum. There was no significant difference in the pre-treatment serum progesterone and serum PP14 concentrations of 26 women who were treated successfully and of five women, who were operated on after failure of the treatment. After the prostaglandin treatment the serum progesterone and PP14 concentrations decreased simultaneously with the serum HCG concentration or remained at a low, constant concentration. We conclude that measurement of serum progesterone and PP14 cannot be used for selection of patients for treatment by prostaglandin F2 alpha or for monitoring the effect of the treatment. The injection of prostaglandin into the ovary has either no effect on the activity of the corpus luteum or induces only a partial luteolysis.

Genetic analysis of repeated, biparental, diploid, hydatidiform moles.

A woman presented with five consecutive pregnancies displaying molar morphology. In the fifth pregnancy, a non-malformed, liveborn infant was delivered. Genetic analyses (RFLP analysis, cytogenetics, flow cytometry) were performed in pregnancies II-V. It was demonstrated that these pregnancies originated in separate conceptions, all conceptuses were diploid, and all had maternally as well as paternally derived genetic markers. By cytogenetic analysis, aberrant heteromorphisms were noted; no other abnormalities were observed in chromosome structure or in DNA sequence. Many different causes for the abnormal development can be envisaged, environmental as well as genetic. To conform to current ideas of molar pathogenesis, it is suggested that the present conceptuses might have arisen from imbalances in imprinted genomic regions. This could be a consequence of uniparental disomy in critical regions generated by somatic crossing over. Alternatively, it could be caused by a malfunction in the generation or maintenance of imprinting.

The secretory endometrial protein, placental protein 14, in women with ectopic gestation.

OBJECTIVE: To determine the serum level of the secretory endometrial protein, placental protein 14 (PP14) and progesterone (P) in women with ectopic gestation. DESIGN: Blood samples were collected prospectively and preoperatively. Reference range was determined from a prospective population of 98 women with uncomplicated pregnancies and normal outcome. SETTING: The women were admitted to a university hospital. PATIENTS: Fifty-nine women with laparoscopically verified ectopic pregnancy entered the study. INTERVENTION: At the time of diagnosis PP14 and P were measured. MAIN OUTCOME MEASURE: After observing the low serum levels of PP14 and P, a correlation analysis was made and compared with the findings in normally pregnant women. RESULTS: A significant positive correlation was found between the level of PP14 and P (P less than 0.00002), not found in normal intrauterine pregnancies. CONCLUSIONS: These findings suggest that the regulation of the PP14 production involves either a control mechanism from the ovary or is mediated by paracrine secretion.

Treatment of tubal pregnancy by local injection of prostaglandin: selection of patients and evaluation of subsequent tubal patency.

Thirty women who had a small unruptured tubal pregnancy were treated by laparoscopically guided injection of prostaglandin F2 alpha into the oviduct and into the corpus luteum. They had no side effects. The serum human chorionic gonadotropin (S-HCG) concentration decreased in 25 women to less than 20 IU/l in a median time of 8 days (range 1-45). Five women were operated on because of increasing S-HCG concentration. The median diameter of the oviduct at the site of the gestation, the tubal localisation and the gestational age was similar in the women treated by prostaglandin and those, who were operated on after failure of the procedure. Four of the 6 women, with S-HCG concentrations of more than 2000 IU/l, needed subsequent operative treatment, compared to only one of 24 with a lower concentration. The median duration of the hospital stay after treatment was 2 days for the group of women with a S-HCG concentration of less than 2000 IU/l. Hysterosalpingography 3 months after treatment showed patency on the side of the pregnancy in 12 of 14 women. Prostaglandin injection seems to be an appealing option for the treatment of selected ectopic pregnancies.

Clinical management and diagnostic possibilities in hydatidiform mole with coexistent fetus.

The goal of the current review is to present the figures essential for counseling, when hydatidiform mole and normal fetus occur together. Previous reviews of prognosis and risks when mole and fetus are observed together did not adjust for differences in genetic constitution and thus varying risks for gynecologic and obstetric complications. A literature search from 1903 to 1989 revealed 113 reports of pregnancies with mole and fetus in which there appeared to be no major malformations or cytogenetic abnormalities; 87 of those were intended to continue. This group provides the most appropriate risk figures, when mole and karyotypically normal child are detected by first or second trimester prenatal diagnosis. Fifty-two pregnancies (59.8 per cent) proceeded to the 28th week without spontaneous abortion or interruption of pregnancy. None of the children delivered before week 28 survived. Of the pregnancies continuing beyond this time 69.2 per cent of the children survived, 7.7 per cent were live-born with unknown long-term outcome, 17.3 per cent died neonatally, and 5.8 per cent succumbed before delivery. Persistent trophoblastic disease was reported in 19.2 per cent of pregnancies interrupted at diagnosis, as well as in 9.1 per cent of those intended to continue. Due to advances in prenatal diagnosis, clinicians will be confronted with counseling in pregnancies with mole and fetus more often than expected from the literature. Chorionic villus biopsy or amniocentesis can disclose those triploid gestations without possibility of a surviving child. First trimester ultrasound demonstration of a partially cystic placenta and abnormal high se-hCG values should initiate prenatal diagnosis for evaluation of the fetal karyotype, before deciding whether to abort or continue the pregnancy.

Hydatidiform mole and fetus with normal karyotype: support of a separate entity.

Repetitive hydatidiform mole was observed in four pregnancies. The pregnancies presented with heavy bleeding and vomiting, but the post-evacuation courses were uncomplicated, with rapid regression of serum hCG levels. Cytogenetic investigations, analyses of restriction fragment length polymorphisms, and flow cytometry in three pregnancies were consistent with diploid, biparental conception as the origin of fetal tissue and molar and nonmolar villi. In one pregnancy, the analyses of cytogenetic markers suggested the coexistence of two different cell lines of dizygotic, biparental origin, whereas DNA analysis was consistent with a single conception. With incomplete genetic information, a hydatidiform mole with coexistent normal fetus is generally considered to result from dizygous twinning comprising an androgenetic complete mole and a normal conception. In the present gestations, the results based on several techniques applied on numerous samples from different tissues render this possibility unlikely. Some of the contradictions between histologic and cytogenetic classifications of hydatidiform mole may be explained by diploid, biparental partial mole, which seems to constitute a separate subgroup within hydatidiform mole. Following chorionic villus sampling or amniocentesis, continued pregnancy may be considered, depending on prenatal diagnosis including genetic marker analysis.

Partial hydatidiform mole with subsequent trophoblastic tumor; a case report.

A case of partial hydatidiform mole revealed by genetic marker analysis one maternal and two paternal chromosome complements. Levels of serum human chorionic gonadotropin were persistently elevated during follow-up. Avillous curettage specimens prior to chemotherapy were morphologically suspicious for gestational choriocarcinoma. It is still uncertain whether the risk for gestational choriocarcinoma preceded by partial mole exceeds the risk related to non-molar abortions. Careful follow-up with serial serum human chorionic gonadotropin levels is required to detect persistent disease.

The vanishing twin: morphologic and cytogenetic evaluation of an ultrasonographic phenomenon.

Twin pregnancy was observed by ultrasonographic examination in the 6th week of gestation. After singleton term delivery a thickening of the membranes opposite to the main placenta showed degenerated chorionic villi embedded between one layer of amnion and chorion; no fetal parts were observed. Villus cells from both placentas were mainly diploid; 2 of 30 were tetraploid. However, 19 of 30 cells from membranes overlying the satellite placenta were tetraploid. Marker analysis was consistent with duplication of a normal conception diploid chromosome complement as the mechanism for tetraploidy. Postconceptional nondisjunction leading to tetraploidy in one twin conceptus may explain demise in early pregnancy. Tetraploidy observed by chorionic villus biopsy must be confirmed by amniocentesis before interruption of the pregnancy is considered.

The European collaborative study on mosaicism in chorionic villus sampling: data from 1986 to 1987.

Data on a total of 11,855 diagnostic chorionic villus samples obtained in the years 1986 and 1987 were compiled from a questionnaire filled in by 36 European cytogenetic centres. Mosaicism was reported in 141 cases. The cytogenetic findings were followed by induced abortion in 24 cases. Spontaneous abortion was observed in nine mosaic pregnancies, a rate not significantly different from that observed for CVS in total. Mosaicism was found in 1.2 per cent of analyses by direct analysis/short-term culture, in contrast to the 0.6 per cent found after long-term culture. Evidence for fetal non-mosaicism was found in 99 of the 141 cases. The finding of mosaicism in first-trimester CVS should always elicit further analyses, preferably after amniocentesis, to substantiate the suspected fetal chromosome aberration.

Local prostaglandin treatment of ectopic pregnancy.

Eleven women with small unruptured tubal pregnancies were treated by laparoscopically guided injection of prostaglandin F2 alpha in the oviduct and in the ovary which contained the corpus luteum. They had no side effects of the treatment and were discharged from hospital 1-3 days later. In 10 women the serum concentration of human chorionic gonadotrophin (HCG) decreased to less than 20 IU/l in a median time of 7.5 days, the range being 1-46 days. One woman required an operation 6 days after the treatment as her serum HCG level was stationary and she continued to have abdominal pain. Hysterosalpingography 3 months after the treatment showed patency of the oviduct on the side of the pregnancy in seven of the eight women who have been examined. We conclude that the injection of prostaglandin F2 alpha seems to promote the resolution of selected tubal pregnancies.

Genetically different cell subpopulations in hydatidiform moles. A study of three cases by RFLP, flow cytometric, cytogenetic, HLA, and morphologic analyses.

Most investigators find a good correlation between the morphologic and cytogenetic classification of hydatidiform moles (HM), but exceptions have been noted. We have examined three cases of HM, using chromosome marker analysis on cultured cells, human leukocyte antigen typing on cultured and uncultured tissue, and restriction fragment length polymorphism (RFLP) analysis and flow cytometry on uncultured cells. In one morphologically partial mole, only one cell population (triploid) was found and data obtained by the above-mentioned techniques were concordant. The other two moles, which were classified morphologically as complete, consisted of several cell subpopulations differing in DNA content. In both cases only one cell population was disclosed by cytogenetic investigation. In one case, the cytogenetic analysis indicated that the cultured cells were near triploid with paternal chromosomes exclusively, whereas RFLP analysis showed that maternal X chromosomal alleles were present in the mole. The present findings demonstrate that some HMs contain cellular subpopulations with differing DNA content. One explanation for discordance between cytogenetic and morphologic classification may thus be the detection of only one cell subpopulation when karyotyping.

Hydatidiform mole and HLA. III. HLA-antigen expression related to genomic origin.

In 52 conceptuses with known genomic origin, HLA determination was performed on whole villi and/or stromal cell cultures. In 26 androgenetic, diploid conceptuses, one or two paternal HLA-A,B haplotypes were found; twenty-four triploid conceptuses with two paternal and one maternal chromosome sets showed either one maternal and one paternal haplotype or one/two paternal HLA-A,B haplotypes. Consequently, androgenesis could not be demonstrated by lack of maternal antigens alone. Concomitant expression of three HLA haplotypes was not seen. HLA-A2 was passed on to the conceptus, both in the genetic subgroups and in the entire series, more frequently than expected.