Increased risk of preterm delivery and pre-eclampsia in women with polycystic ovary syndrome and hyperandrogenaemia.

OBJECTIVE: To study the risk of adverse pregnancy outcomes in women with polycystic ovary syndrome (PCOS), and to examine the role of hyperandrogenaemia. DESIGN: Cohort study. SETTING: Singleton pregnancies in women with PCOS identified at a private fertility clinic during 1997-2010 and a background population including all singleton deliveries at Hvidovre Hospital, Denmark, in 2005. POPULATION: A cohort of 459 women with PCOS and a background population of 5409 women. METHODS: Obstetric outcomes were extracted from national Danish registries and odds ratios (ORs) were calculated by multiple logistic regression analysis, adjusting for age, parity, and body mass index. MAIN OUTCOME MEASURES: Risk of pre-eclampsia, preterm delivery, and small for gestational age offspring in the entire PCOS population and in a subsample with hyperandrogenaemia. RESULTS: Women with PCOS had an increased risk of preterm delivery <37 weeks of gestation (OR 2.28; 95% confidence interval, 95% CI, 1.51-3.45; P < 0.0001). The elevated risk was confined to hyperandrogenic women with PCOS: preterm delivery before 37 weeks of gestation (OR 2.78; 95% CI 1.62-4.77; P < 0.0001), and was not seen in normoandrogenic women with PCOS (OR 1.35; 95% CI 0.54-3.39; P = 0.52). The overall risk of pre-eclampsia was not elevated (OR 1.69; 95% CI 0.99-2.88; P = 0.05) compared with the background population, but was significantly increased in the hyperandrogenic subsample (OR 2.41; 95% CI 1.26-4.58; P < 0.001). The risk of small for gestational age offspring was similar in all groups. CONCLUSION: Women with PCOS had an increased risk of preterm delivery compared with the background population. The increased risk was confined to hyperandrogenic women with PCOS who had a two-fold increased risk of preterm delivery and pre-eclampsia.

Interruption of early pregnancy with mifepristone in combination with gemeprost.

BACKGROUND: Mifepristone in combination with prostaglandin has been used since 1988 for induction of early abortion. The aim of the present investigation was to assess the tolerance and efficacy of 600 mg. mifepristone orally followed by gemeprost 1 mg. vaginally either 24 hours (group one) or 48 hours (group two) later. METHODS: Sixty-four healthy women applying for abortion within the first 8 weeks of pregnancy were randomly allocated to one of the two treatment groups. Intrauterine pregnancy and gestational age were verified by ultrasonography. Symptoms after administration of mifepristone and gemeprost were recorded, and the patients observed at the hospital for at least three hours after prostaglandin-insertion. Blood samples for blood group, hemoglobin, beta-chorion-gonadotrophin, aspartate-aminotransferase and creatinine were drawn. RESULTS: Outcome was established by gynecological examination, the level of beta-hCG and ultrasonography, at visits one, two and if necessary three to four weeks later. Surgical curettage was performed in case of incomplete abortion, of which there were four in the 24-hour interval group and five in the 48-hour interval group with a success rate (complete abortion) of 55 out of 64 patients (86%). CONCLUSIONS: There was no difference in efficacy or side effects whether the prostaglandin was administered 24 or 48 hours after mifepristone intake, which suggests that the treatment period can be reduced from the conventional 48 hours.

A Danish national cohort of 730 infants born after intracytoplasmic sperm injection (ICSI) 1994-1997.

This national cohort study included all clinical pregnancies obtained after intracytoplasmic sperm injection (ICSI) registered in Denmark between January 1994 and July 1997 at five public and eight private fertility clinics. Laboratory and clinical data were obtained from the fertility clinics. The couples answered a questionnaire regarding the pregnancy and the health of the child (response rate 94%). Data validation was carried out through discharge charts. The mean age of the women was 32.1 years. In 84.2% of couples, male factor was the main reason for performing ICSI, and in 4.8% epididymal spermatozoa were used. The mean number of embryos replaced was 2.3 (range 1-3) and in 95% of cases fresh embryos were transferred. Only 183 women (28.5%) underwent prenatal diagnosis, resulting in 209 karyotypes with seven (3.3%) chromosome aberrations. Six major chromosomal abnormalities (2.9%) and one inherited structural chromosome aberration (0.5%) were found, but no sex chromosome aberrations. The frequency of multiple birth, Caesarean section rate, gestational age, preterm birth, and birth weight were comparable with previous studies. The perinatal mortality rate was 13.7 per 1000 children born with a gestational age of 24 weeks or more. In 2.2% (n = 16) of the liveborn infants, and in 2.7% (n = 20) of all infants, major birth defects were reported by the parents. Minor birth defects were found in nine liveborn infants (1.2%). In conclusion, the results of this study on outcome of ICSI pregnancies are in line with earlier reports, except that no sex chromosome abnormalities were found.

A new method for the purification of human motile spermatozoa applying density-gradient centrifugation: polysucrose media compared to Percoll media.

PURPOSE: A newly developed method for the isolation of human motile spermatozoa using density-gradient centrifugation was compared with the traditionally used Percoll technique. METHOD: Sperm samples were divided into two equal aliquots, which were purified with either the traditionally performed Percoll technique or a new alternative based on polysucrose/Optiprep media. For each sample the isolation was performed during the same run of the centrifuge. RESULTS: The average recovery of progressively motile spermatozoa with the polysucrose/Optiprep method was significantly higher (48 +/- 7%) than with the Percoll method (38 +/- 6%) (n = 18). The average percentage of motile spermatozoa and the motility score were similar in the purified preparations. CONCLUSIONS: The new polysucrose/Optiprep-based density-gradient centrifugation technique for the isolation of motile human spermatozoa is as good as the traditionally used Percoll method and may replace it in connection with assisted reproduction techniques.

A sporadic case of delayed implantation after in-vitro fertilization in the human?

A possible case of delayed implantation after in-vitro fertilization (IVF) is described. The patient was sterilized in 1981, and made fertile again by tubal anastomosis in 1988. In 1990 and 1992 the patient had two right-sided tubal pregnancies, the first was treated with prostaglandin instillation, the second with salpingectomy. In connection with the salpingectomy in 1992, the left tube was observed to be constricted in the middle part and with phimosis of the ostium. In 1994 three IVF embryos were transferred, but 15 days after the transfer, serum human chorionic gonadotrophin (HCG) was negative (< 10 IU/ml). Seven weeks after the embryo transfer, menstruation was still missing, and the serum HCG was now positive (329 IU/ml). Subsequent ultrasound scans were compatible with an intrauterine pregnancy, progressing normally, but 5 weeks delayed compared with the oocyte aspiration. The pregnancy was successfully carried to term. Such a long delay in detection of HCG, in association with a normal pregnancy, has not been described in the literature before.

Nucleotide sequence within Tn3926 confirms this as a Tn21-like transposable element and provides evidence for the origin of the mer operon carried by plasmid pKLH2.

The DNA sequence of the resolvase gene, resolution sites, and the region between the transposition functions and the end of the mercury resistance operon of the bacterial transposon, Tn3926, is presented. The sequence of Tn3926 upstream of the resolution sites is homologous to that bordering the 11.2-kb insert of Tn21, supporting the idea that this insert transposed into a progenitor of Tn3926. This region of Tn3926 also shows 97.0% identity to the mercury-resistant determinant of the plasmid, pKLH2, suggesting that this plasmid once harbored a close relative of Tn3926. It is proposed that the mercury resistance operon of Tn3926 will have a structure very similar to that found on pKLH2.

Differential in vitro inhibition of feline enteric coronavirus and feline infectious peritonitis virus by actinomycin D.

The growth of feline enteric coronavirus strain 79-1683 in whole feline embryo cells was inhibited by the presence of 1 microgram/ml of actinomycin D in the culture fluid. No virus-specific mRNAs could be detected in such cultures and yields of infectious virus were depressed by > 99%. By contrast, the antigenically related feline infectious peritonitis virus strain 79-1146 was unaffected by the presence of actinomycin D, indicating a fundamental difference between the two feline coronavirus strains in their requirements for host-encoded function(s).

Effects of lidocaine aerosol on postoperative pain and wound tenderness following minor gynaecological laparotomy.

Twenty-four female patients undergoing sterilization through a minor lower laparotomy received, in a double-blind, randomized study, either lidocaine spray 200 mg or placebo in the surgical wound. Postoperative pain intensity was evaluated on a verbal and a visual analogue scale and wound tenderness with an algometer. During mobilisation from the supine to the sitting position, VAS-score was lower (P less than 0.05) in the lidocaine group 2 h postoperatively, but not 4, 6 and 8 h postoperatively (P greater than 0.05). No significant differences were found in VAS-scores at rest or during cough, or in verbal scale ratings during rest, cough or mobilisation, and postoperative consumption of morphine was similar in the two groups. Pressure pain thresholds were higher (P less than 0.05) 2 h postoperatively in the lidocaine group, but not 4, 6 and 8 h postoperatively. In conclusion, topically applied lidocaine aerosol in the surgical wound leads to very short and clinically insignificant relief of postoperative pain.

The Tn21 subgroup of bacterial transposable elements.

The Tn3 family of transposable elements is probably the most successful group of mobile DNA elements in bacteria: there are many different but related members and they are widely distributed in gram-negative and gram-positive bacteria. The Tn21 subgroup of the Tn3 family contains closely related elements that provide most of the currently known variation in Tn3-like elements in gram-negative bacteria and that are largely responsible for the problem of multiple resistance to antibiotics in these organisms. This paper reviews the structure, the mechanism of transposition, the mode of acquisition of accessory genes, and the evolution of these elements.

Temperature sensitivity of transposition of class II transposons.

It has been reported that transposition of Tn3 is temperature-sensitive. The effect of temperature on the transposition of other class II bacterial transposable elements is reported here: Tn21, Tn501, Tn1721, Tn2501 and Tn3926 all also display temperature-sensitivity of transposition. The temperature at which the highest transposition frequency was observed varied between room temperature and 30 degrees C.

Prediction of ovulation.

The purpose of this investigation was to evaluate all available ovulatory diagnostics with respect to sensitivity, specificity, diagnostic specificity (predictive value of a positive test, PVP) and diagnostic sensitivity (predictive value of a negative test, PVN). Twenty-one ovulatory women with more than 3 years of infertility problems were included in the study. PVP and PVN were highest for detection of urinary luteinizing hormone (LH) peak at ovulation (PVP = 90%, PVN = 95%) and for serum-estradiol peak 1 day before ovulation (PVP = 83%, PVN = 97%). The predictive values were lower for all other tests. The PVP (54%) and PVN (90%) were rather low for detection of ovulation with vaginal electric impedance. However, all ovulations were predicted when urinary LH peak and vaginal impedance were combined. Two women were stimulated with human chorionic gonadotropin to investigate a possible connection between the LH peak and the preovulatory vaginal electric impedance. No close connection between them could be demonstrated. Basal body temperature should not be used for the prediction of ovulation (PVP = 25%). We suggest that ovulation should primarily be predicted from the identification of the urinary LH peak and that other methods be supplementary.

"Stat" measurements of L-lactate in whole blood and cerebrospinal fluid assessed.

A first-generation semi-automatic amperometric lactate analyzer (Yellow Springs Instrument Co.) was assessed for urgent ("stat"), rapid laboratory measurements in whole blood and cerebrospinal fluid. For whole blood, measured lactate concentration and hematocrit were linearly correlated. An improved equation is presented for estimating the concentration of lactate in plasma from measurements in whole blood. The 95% reference range for the concentration of lactate in paired samples of capillary and venous whole blood from 40 healthy laboratory adults was found to be 0.4-1.5 mmol/L and 0.3-1.5 mmol/L, respectively. The 95% ranges for lactate in whole blood from 24 uncomplicated vaginal deliveries at term were established for cord venous blood, 1.2-5.0 mmol/L; cord arterial blood, 1.6-5.5 mmol/L; and maternal venous blood, 1.7-6.6 mmol/L. The 95% paired ranges were established for 20 lumbar-anaesthetized urological patients without neurological disorders after induction of anaesthesia for venous whole blood and cerebrospinal fluid (venous blood, 0.5-1.3 mmol/L; cerebrospinal fluid, 1.1-2.4 mmol/L).

Effects of variation of inverted-repeat sequences on reactions mediated by the transposase of Tn21.

The frequencies of one-ended transposition and normal transposition of derivatives of Tn21 that contain mutant inverted-repeat sequences (IRs) have been measured. In general, there was a linear relationship between the log of the frequency of one-ended transposition of a mutant IR and the log of the frequency of normal transposition of an element flanked by a wild-type IR at one end and by the mutant IR at the other. This implied that one-ended and normal transposition share the rate-limiting step that determines the frequency of transposition and that both IRs are involved in the rate-limiting step in normal transposition. Surprisingly, it was found that only the outer 18 base pairs of the IR of Tn21 engaged accurately in both one-ended and normal transposition, at about 1% of the frequency of the wild-type IR.

Factors that affect transposition mediated by the Tn21 transposase.

The frequencies of one-ended transposition mediated by the Tn21 transposase acting on plasmids containing 38-bp inverted repeat sequences (IRs) of both Tn21 and of Tn501/Tn1721 and Tn2501 were measured. The enzyme acted on all these IRs, but more efficiently on the homologous sequences. These differences were magnified when the enzyme acted on plasmids containing two copies of the IRs, inverted with respect to each other. The Tn21 enzyme did not recognize the IR of Tn3. The Tn501 transposase did not mediate measurable one-ended transposition of any of the plasmids used, including those containing an IR of Tn501.

Analysis of the variable endpoints generated by one-ended transposition of Tn21.

One-ended transposition of Tn21 generates recombinants usually containing a whole copy of the donor replicon plus a short duplication of it (S. Mötsch, R. Schmitt, P. Avila, F. de la Crue, E. Ward, and J. Grinsted, Nucleic Acids Res. 13:3335-3342, 1985). This work shows that recombinants containing less than a whole copy of the donor replicon (hereafter called short recombinants) could also be detected when plasmid donors which contained two selectable genetic markers were used. Short recombinants were produced at the same frequency from TnpR+ donor molecules as from TnpR- donor molecules in a RecA- background. Therefore, they were not resolution products of larger recombinants. This result invalidates a previous hypothesis to explain one-ended transposition, that is, that one-ended transposition arises from the use of secondary ends by the transposition apparatus. On the other hand, it suggests that one-ended transposition of Tn21 occurs via a simple insertion mechanism.

Gas-chromatographic measurement of carboxyhemoglobin in blood from mothers and newborns.

HbCO in blood sampled from 20 mothers and newborns immediately after birth was measured with a new, simple gas-chromatographic method for CO. The mean ratio of HbCO to total hemoglobin for 13 non-smoking mothers did not differ significantly from that for their infants (mean 0.38%, SD 0.26% vs 0.38%, SD 0.13%), but the HbCO ratio varied more in the mothers than in the infants (P less than 0.05). The infants of seven cigarette-smoking mothers, tobacco-abstinent for 7 h during labor, had higher HbCO ratios than their mothers (mean 1.88% vs 1.28%, P less than 0.05). The results are in harmony with the concept of equal affinities of fetal and adult hemoglobin for CO and a long time for passage of CO across the placenta.