OBJECTIVE

To investigate maternal serum unconjugated oestriol (uE3) and human chorionic gonadotrophin (hCG) levels in pregnant women with insulin-dependent diabetes mellitus and to consider the implications of the results for antenatal screening for Down's syndrome.

METHODS

Descriptive study using stored antenatal serum samples.

METHODS

Stored serum samples collected from women receiving routine antenatal care in Oxford.

METHODS

126 singleton pregnancies in 92 women with insulin-dependent diabetes mellitus and for each pregnancy, two pregnancies without diabetes matched for gestational age and duration of storage of the serum sample. None of the pregnancies was associated with fetal neural tube defect or Down's syndrome.

METHODS

Maternal serum uE3 and hCG levels at 15-22 weeks gestation. Alpha-fetoprotein (AFP) levels were also measured for comparison.

RESULTS

The median uE3 level in the diabetic pregnancies was 0.92 multiples of the median (MoM) for pregnancies without diabetes at the same gestational age (P less than 0.05); and the hCG level was 0.95 MoM (P = 0.48). The median AFP level was also reduced to 0.77 MoM (P less than 0.001).

CONCLUSIONS

The reduction in uE3 and AFP levels in insulin-dependent diabetic pregnancies is sufficiently great to be taken into account in maternal serum screening programmes for Down's syndrome. Dividing the uE3 and AFP levels in such pregnancies by the corresponding median for insulin-dependent diabetic pregnancies will yield a similar false-positive rate in pregnancies with and without insulin-dependent diabetes mellitus.

Serum oestriol, oestrone and 17 beta-oestradiol concentrations during oral oestriol succinate treatment were investigated in ovariectomized women. Either a single dose of 8 mg or two doses of 4 mg were given daily. With the second divided dosage the serum oestriol levels remained uniform. The oestriol concentrations were clearly higher than in the beginning or in the middle of the normal menstrual cycle in the fertile woman. With both treatment schemes the ratio E3/(E2 + E1) was clearly higher than before treatment and during the normal menstrual cycle. Oestriol succinate treatment lowered the ratio E1/(E2 + E3), which was rather similar to the one during normal menstrual cycle.

Serum oestrone, oestradiol and oestriol concentrations were investigated during oral treatment with oestradiol valerate and oestriol succinate in ovariectomized women. The dosages used were 1 mg oestradiol valerate in the morning and 2 mg oestriol succinate in the evening of the first day and 2 mg oestradiol valerate in the morning of the second day of treatment. The other group of patients received the same therapy in reverse order. The variation in the serum oestrone and oestradiol concentrations with a daily dose of 1 or 2 mg of oestradiol valerate were considerable. 2 mg oestriol succinate caused a fairly small elevation of serum oestriol concentration. In both treatment groups the quotient E3/(E2 + E1) was similar to that found at the 6-7th day and in the middle of the normal menstrual cycle, the quotient E1/(E2 + E3) was somewhat higher than during normal cycle.

An automated enzymatic assay which measures combined concentrations of urinary oestrone and oestradiol within 15 minutes of hydrolysis has been developed using placental 17 beta oestradiol dehydrogenase. This assay is comparable to radioimmunoassay in its precision and sensitivity and is quicker, more convenient, and more economical. The 17 beta oestradiol dehydrogenase assay was used to monitor ovarian response in infertile women being treated through stimulated ovarian cycles or in vitro fertilisation programmes. Because the assay did not respond to oestriol it was less reliable than total urinary oestrogens in monitoring ovarian responses, particularly during treatment with drugs which enhanced oestriol excretion. In natural ovulatory cycles rising 17 beta oestradiol dehydrogenase values preceded peak luteotropin concentrations by up to 18 hours and improved detection of ovulation. The 17 beta oestradiol dehydrogenase assay processes large numbers of urine samples quickly and economically and enables accurate monitoring of oocyte maturity and ovulation.

The aim of this prospective study was to compare triple test screening (alpha-fetoprotein, beta-chorionic gonadotrophin and unconjugated oestriol) with amniocentesis in the detection of fetuses with Down's syndrome in women of 35 years of age or more. Between 1992 and 1996, maternal serum markers were evaluated in 1406 women who had amniocentesis for prenatal diagnosis of chromosomal abnormalities related to a maternal age of 35 or more years. Sixteen fetuses with Down's syndrome were identified in the whole group by amniocentesis and karyotyping. The group with negative triple test screening consisted of 919 pregnancies and included two fetuses with trisomy-21 (false negatives). With triple test screening in the age group over 35, there was a detection rate of 87.5% for cut-off points ranging from 1:200 up to 1:350, with corresponding false positive rates ranging between 23% and 34%. In our population, if we had practiced the policy of offering amniocentesis only to women screening positive for the ages of 35 and 36 and to all pregnant women of 37 or more, we would have carried out 30% less amniocenteses. In this group of 1406 women, 33 abnormal karyotypes were detected with amniocentesis (16 Down's syndrome included) and equal number of elective abortions were carried out. Nevertheless, 19 healthy fetuses and neonates were lost after amniocentesis. Considering the high detection rates that can be achieved with triple test screening, the existing procedure related risk of amniocentesis (0.5-1.0%), and the facts that conception in women over 35 years of age is usually more difficult and the background loss usually higher than in younger women, we believe that in the future women over 35 should be offered a choice between non-invasive and invasive procedures after being thoroughly informed.

Changes in the excretion of immunoreactive oestrogens and biologically active LH were assessed from measurements on small samples of urine collected from a capuchin, a tamarin, a spider monkey and a squirrel monkey. The hormone profiles were used to time matings of the capuchin and spider monkey; conception and pregnancy ensued. Detailed analysis of one urine sample from each female by using partition chromatography and reverse-phase high-pressure liquid chromatography showed that oestrone was more abundant than oestradiol-17 beta and oestriol combined, but the relative contribution of individual oestrogens to the total oestrogen complement differed. In the sample from the capuchin, an immunoreactive oestrogen slightly less polar than oestradiol appeared to be the most abundant urinary oestrogen.

Oestradiol-17beta and oestriol both sequentially stimulate the synthesis of heterogeneous nuclear RNA and rRNA in vivo. However, the stimulation by oestradiol-17beta, particularly of rRNA synthesis, is very much greater than that elicited by oestriol.

In this work, the potential of a hollow-fibre liquid-phase microextraction (LPME)-based method has been studied and validated for the extraction of a group of nine oestrogenic compounds four of them being natural (oestriol, 17β-oestradiol, 17α-oestradiol and oestrone), four being synthetic (17α-ethynyloestradiol, diethylstilbestrol, dienestrol and hexestrol) and one metabolite (2-hydroxyoestradiol) in different dairy products (whole and skimmed natural yogurt, a probiotic yogurt-type drink and cheese). The methodology includes a prior protein precipitation with acidified acetonitrile for all samples and an additional defatting step with n-hexane for cheese, the matrix with the highest fat content. Later separation, determination and quantification were done by high-performance liquid chromatography coupled to a diode array detector and a fluorescence detector set in series. Calibration, sensitivity, precision and accuracy of the method were carried out in the selected matrices, providing good linearity, LODs in the low μg/kg or μg/L range, good precision and appropriate accuracy.

The efficacy of a dialysate of calf blood in the treatment of chronic placental insufficiency is assessed using the urinary oestriol elimination as parameter. Compared with a control group, those cases receiving 2 times 250 ml protein-free dialysate of calf blood (Solcoseryl) in saline solution over 9 days showed a significant increase in the daily quantity of urinary oestriol elimination already from the second day of treatment onwards. Other conventional procedures in the medical treatment of placental insufficiency are discussed. Some of these are known to have secondary effects or must be regarded as invasive.

81 women were included in a prospective randomised 12-year personal study. The "pathological cervical factor" was confirmed by periovulatory daily examination of the quality of the cervical mucus, using a new modified scheme of cervical score by examining the oestrogenic activity in the vaginal smear and results of sperm-penetration tests after Sims- Huhner , partly also by periovulatory determination of the concentration of luteinising hormone in the serum. The presence of ovulatory cycles could also be determined by regular registration of the cycle length, measurement of the basal body temperature and partly by premenstrual endometrium biopsies; these determinations were of course effected during cycles without therapy. All 81 cases with abnormal preovulatory production of cervical mucus were treated in a total of 234 cycles by intravaginal application of oestriol tablets 1 to maximal 3 mg daily for 1 or more subsequent cycles. On the basis of these criteria, the quality of cervical mucus and postcoital tests improved with a satisfying intravaginal resorption of the oestriol tablets; no side effects were seen. After this therapy, very good results were obtained with intravaginally administered oestriol tablets in 59.3% of the patients with a pregnancy rate of 27.2%; 24.7% of the cases only showed a moderate improvement of the mucus; 16.0% did not respond to oestriol treatment and, therefore, had to be considered as therapeutic failures. The present study again confirms the results of other investigators on the local effectiveness of intravaginal application of oestriol tablets.(ABSTRACT TRUNCATED AT 250 WORDS)

The finding that climacteric symptoms are caused mainly by a decline of the oestrogen level and that their development can practically always be prevented by long-term local or general oestrogen treatment was a great asset to the treatment of this problem. Oestriol, a less effective natural oestrogen, has a favourable effect on urogenital tissues without stimulating the endometrium [2]. The objective of the present investigation was to analyze ultrasonographic parameters of the lower urinary tract in women after the menopause with the stress or mixed type of urinary incontinence before and after two-month local oestriol treatment (Ovestin). The trial comprised 40 women with confirmed stress (GSI) or the mixed type of urinary incontinence. The group with GSI comprised 124 patients and the group suffering from the mixed type of incontinence comprised 26 women. The type of incontinence was assessed by urogynaecological examination. This was followed by transperineal and introital ultrasound examination of patients in a supine position by means of an Acuson 128 XP10 apparatus using a convex probe with a frequency of 5 MHz and a vaginal probe with a frequency of 7.0 MHz. Assessment of the position and mobility of the urethrovesical junction was implemented by the transperineal route using a convex probe and filling the bladder with 300 ml. After urination followed assessment of the urethral sphincter by the introital route in a vertical plane whereby the authors followed the anterior and posterior surface of the rhabdosphincter, and in a horizontal plane its left and right surface (10). The authors assessed also in both planes the maximal thickness of the sphincter. In the vertical plane and in a proximal position in relation to the urethra they evaluated the vascular supply qunatitatively (minimal-1 to very abundant-4) and also the arterial flow-the pulsatile index PI was investigated as well as the resistance index RI. In the vertical plane 1 cm from the urethrovesical junction the authors assessed the thickness of the urethral mucosa; at the same level they evaluated the thickness of the urinary bladder wall; the anterior wall, the vertex and the area of the trigone. They assessed also the thickness of pelvic floor muscles. The assessments were made before and after two-month intravaginal oestriol administration (Ovestin crm)-two weeks 0.5 mg/day and then 0.5 mg twice a week. After treatment no statistically significant differences in thickness and areas of the urethral sphincter were found nor in the thickness of the pelvic floor muscles before and after oestriol administration. Statistically significant differences were recorded in the mobility of the urethrovesical junction and there was a significant increase in the thickness of the urethral mucosa and a more abundant vascularization was recorded during the quantitative evaluation and evaluation of PI. In women with the mixed type of incontinence after oestrogen treatment a decline in the thickness of the urinary bladder was found. Ultrasound examination of the lower urinary tract before and after oestriol treatment (Ovestin crm) is a useful supplement of common examination methods and it confirms its favourable therapeutic effect when administered by the intravaginal route.

OBJECTIVE

To evaluate if levels of pregnancy-associated plasma protein-A (PAPP-A), free β-hCG and nuchal translucency (NT) used in first trimester aneuploidy screening and α-fetoprotein (AFP), unconjugated oestriol (UE3) and free β-hCG in the second trimester are altered in pregnancies with human immunodeficiency virus (HIV) infection.

METHODS

Median MoM values of biochemical markers and δ-NT in 92 women with HIV infection in the first trimester were compared with those from 912 HIV-seronegative controls. In the second trimester, biochemical marker levels were compared in 52 women with HIV infection and 378 HIV-seronegative controls.

RESULTS

First trimester free β-hCG median MoM levels in HIV-infected pregnancies were not different to controls (0.978 vs. 0.981, p = 1.000), as were PAPP-A levels (1.190 vs. 1.102, p = 0.099) and δ-NT (0.1374 vs. 0.0445, p = 0.0631). Second trimester levels of free β-hCG were not significantly different (1.0575 vs. 0.9619, p = 0.1827), as was AFP (0.9734 vs. 0.9350, p = 0.6576), although UE3 was significantly lower (0.970 vs. 1.110, p = 0.0005).

CONCLUSIONS

In the first trimester, marker levels are not affected by the presence of HIV infection, and risks for aneuploidy are likely to be accurate in this group. Further studies are required to evaluate if UE3 levels continue to be low in HIV-infected women since this may have an impact on screening in the second trimester.

Skinfold thickness was measured in 130 post-menopausal women treated with long-term hormone therapy. One group of 50 women took oestradiol valerate 2 mg/day for 3 wk out of 7, a second group comprising 19 women received oestriol succinate 2 mg/day and the remaining group of 61 women used oestradiol valerate 2 mg/day combined sequentially with norgestrel 0.5 mg/day. The duration of treatment in these groups was 6.3 +/- 0.4, 6.4 +/- 0.4 and 3.3 +/- 0.3 yr, respectively. The control group was made up of a further 89 post-menopausal women. The skinfold thickness in all the treated groups was significantly greater than that in the controls.

The paper presents the current status of knowledge about pathology of preterm delivery with presentation of biochemical markers diagnostically useful in prediction of this pathology. Infectious cause of preterm delivery and usefulness of infection diagnostic markers in it's prediction are discussed. Diagnostic potential of immunological inflammatory markers such as IL-6, TNF-alfa and fibronectin and oestriol are emphasised in the context of recently published data. The present status of knowledge doesn't allow for pointing of the most sensitive and specific single predictor of preterm delivery. The most promising are multi-marker investigations performed in pregnancy with risk factors.

The levels of the maternal serum markers alpha-fetoprotein (AFP), human chorionic gonadotrophin (hCG), and unconjugated oestriol (uE3) in 35 pregnant women with early second-trimester oligohydramnios differed from those in a reference population of 1699 singleton pregnancies. Maternal serum AFP levels above the 95th centile of the population distribution were observed in 80 per cent (16/20) of oligohydramnios cases with a normal fetus and in only 20 per cent (3/15) of the cases with a fetus displaying urogenital tract malformations. Elevated levels of hCG (above the 95th centile) and decreased levels of uE3 (below the fifth centile) were encountered in 26 per cent (9/35) and 17 per cent (6/35) of the women, irrespective of the fetal condition. The abnormal profile of the serum markers in early second-trimester oligohydramnios resulted in 57 per cent (20 out of 35) of screen-positive cases for either fetal Down's syndrome or neural tube defects, compared with 8.4 per cent (143 out of 1699) in the reference population.

Anomalies occur with greater frequency in twin gestations than in singleton pregnancies. Anencephaly is not an uncommon defect, but because of its multifactorial inheritance pattern, twins are usually discordant for this anomaly. We present a case of monoamniotic twins concordant for anencephaly. Monoamniotic anencephalic twins were diagnosed at 15 weeks' gestation. Normal interval growth occurred until intrauterine demise of both fetuses at 28 weeks. Maternal serum obtained at 16.5 weeks demonstrated low unconjugated oestriol (uE3) levels and elevated values of alpha-fetoprotein, although this result was lower than expected. Human chorionic gonadotropin (hCG) levels were significantly elevated. Monoamniotic twins concordant for anencephaly occur with extreme rarity. To our knowledge, maternal serum uE3 and hCG levels in fetuses concordant for neural tube defects have not been previously reported.

A study of 533 women with very low urinary oestriol excretion during the third trimester of pregnancy showed an incidence of major fetal malformations among their infants of 7-1% and a perinatal mortality rate of 14-6%. Thirteen of the malformations were cases of anencephaly, and 26 of the 78 perinatal deaths were due to or associated with major fetal malformations. The incidence of these complications was higher when maternal oestriol excretion was lower. Routine screening by urinary oestriol assay, with fetal radiography when values below 20-8 mumol/24 hours (6 mg/24 h) are detected is the most reliable method of detecting anencephaly before birth.

Unconjugated oestriol (uE3) and human chorionic gonadotropin (hCG) levels were determined in second-trimester maternal serum (MS) samples from 21 pregnancies associated with fetal anencephaly and 15 pregnancies associated with fetal open spina bifida. Each measurement was expressed as a multiple of the median (MoM) for unaffected pregnancies for each completed week of gestation. In pregnancies associated with anencephaly, the median value for MSuE3 was very low (0.17 MoM, range less than 0.12-0.33 MoM), suggesting a functional defect in the fetal adrenal prior to 20 weeks' gestation; the median value for MShCG was also low (0.73 MoM), although not to the same extent as for MSuE3. A biological explanation for the hCG result is not apparent. In pregnancies associated with open spina bifida, the MSuE3 and MShCG values were unremarkable, consistent with a lack of involvement of these open fetal defects in the synthesis and secretion of uE3 and hCG.