Biomedical subjects
Allan Templeton
Publications and source records attributed to Allan Templeton.
Parallel observation of four methods for screening women under 25 years of age for genital infection with Chlamydia trachomatis.
OBJECTIVES: To compare four methods of screening women for Chlamydia trachomatis in an obstetrics and gynaecology department. STUDY DESIGN: A total of 303 healthy women under 25 years were recruited from antenatal, induced abortion, and family planning clinics. Each underwent parallel testing of endocervical specimens by enzyme immunoassay (EIA) and ligase chain reaction (LCR), vulval swabs by LCR, and urine by LCR. Outcome measures included sensitivity, specificity, acceptability of each method, and the influence of pregnancy. RESULTS: Overall prevalence (95% CI) was 9.9% (6.8-14%). All methods had a high rate of detection (75-100%), not affected by pregnancy. Urine was most acceptable, followed by vulval swabbing. CONCLUSIONS: Opportunistic screening of women under 25 years attending obstetric and gynaecology affiliated clinics found high rates of C. trachomatis infection. Both urine and vulval swab methods were highly sensitive, acceptable, and not affected by pregnancy status. Due to pragmatic issues surrounding the urine method, screening by vulval swabs deserves wider recognition.
Medical abortion at 64 to 91 days of gestation: a review of 483 consecutive cases.
OBJECTIVE: The purpose of this study was to assess the uptake and outcome of medical abortion in the late first trimester of pregnancy. STUDY DESIGN: We conducted a review of the cases of 483 consecutive women in a university hospital who underwent medical abortion at 64 to 91 days of gestation and who used mifepristone that was followed 36 to 48 hours later by repeated doses of misoprostol. RESULTS: A total of 891 abortions were carried out at 64 to 91 days of gestation from October 2000 to April 2002; of these, 483 cases (54.2%) were undertaken medically. Complete abortion occurred in 458 cases (94.8%). Efficacy decreased with advancing gestational age. Surgical evacuation was carried out in 1 woman (0.9%) at 9 to 10 weeks of gestation, in 8 women (5.3%) at 10 to 11 weeks of gestation, in 7 women (6.2%) at 11 to 12 weeks of gestation, and in 9 women (7.9%) at 12 to 13 weeks of gestation. Indications for surgery included ongoing pregnancy in 8 cases (1.7%), missed abortion in 3 cases (0.6%), incomplete abortion in 13 cases (2.7%), and emergency curettage for bleeding in 1 case (0.2%). The mean number of misoprostol doses used was 2.3; of those women who had a complete abortion, 152 women (32.6%) aborted within 4 hours of receiving the misoprostol. The mean induction to abortion interval was 5.5 hours; most cases (452; 93.6%) were treated as day cases. CONCLUSION: Medical abortion between 64 and 91 days of gestation is effective and has a high uptake. Consideration should be given to extending the availability and choice of medical abortion to women in this gestational group.
Ooplasmic transfer--proceed with care.
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In-vitro fertilisation and risk of multiple pregnancy.
There is concern about the medical, social, and economic consequences of multiple pregnancy after in-vitro fertilisation (IVF). The most effective way to limit the risk of such a pregnancy is to replace only one or two embryos simultaneously. This strategy, however, is thought to reduce pregnancy rates. We analysed the rates of multiple pregnancies and live-births in all clinics in the UK in relation to their elective two-embryo transfer (ETT) policies. Our results suggest that replacement of two embryos eliminates the chance of triplets without affecting overall success rates.
A comparison of two dosage regimens of oral misoprostol for labor induction at term.
METHODS: 251 women with indications for labor induction at term were randomised to receive either 50 or 100 microgs of oral misoprostol, repeated every 4 h to a maximum of 5 doses. Parous women in the higher dose group received 50 microgs as their first dose, subsequent doses being 100 microgs. Women who failed to respond to the 5 doses of misoprostol had the option of having vaginal PGE2 gel. The primary outcome measure was the induction to delivery interval in those who delivered vaginally. Patient satisfaction was assessed by postnatal questionnaire. RESULTS: The induction to vaginal delivery interval, although shorter in the 100 microgs group was not statistically significant (26.8 versus 33.7 h, mean difference 6.9 h, 95% CI 0.4-13). There were, however, more failed inductions with misoprostol in the 50 microgs group (12.7% Vs 4.8%, RR 2.6, 95% CI 1.07-6.5). There were no differences in the modes of delivery, number of caesarean sections for fetal distress or in the neonatal outcomes in the two groups. Most patients, 83% and 92% in the 50 and 100 microgs, respectively, were satisfied with their inductions, and 64% of patients would prefer to have the inducing agent given orally if they were to have another induction. CONCLUSION: Oral misoprostol is effective in inducing labor and seems acceptable to patients. Both the 50 and 100 microgs dose regimens have a reasonable safety profile, but in view of the higher incidence of failed inductions with the 50 microgs dosage, the 100 microgs dose regimen may be the preferred dose regimen.
Factors affecting the outcome of early medical abortion: a review of 4132 consecutive cases.
OBJECTIVE: To assess the outcome of a regimen of a reduced dose of mifepristone followed by one or two doses of vaginal misoprostol as a non-surgical method for termination of pregnancy. DESIGN: Prospective observational study. SETTING: Aberdeen Royal Infirmary, Aberdeen, Scotland. POPULATION: Women seeking abortion under the 1967 Abortion Act. METHODS: Factors influencing the outcome in a consecutive series of 4132 women undergoing early medical abortion in one Scottish teaching hospital since 1994. MAIN OUTCOME MEASURES: Complete abortion rates following one or two doses of misoprostol. The effect of age, gestation, previous pregnancy and previous termination on complete abortion rates following the medical regimen. RESULTS: Of the 4132 women, 95 (2.3%) aborted within 48 hours of mifepristone and a further 3942 (95.4%) achieved complete abortion following administration of one or two doses of misoprostol. Thus, the overall complete abortion rate was 97.7% (4037/4131). A total of 94 (2.3%) women required surgical intervention of whom 13 (0.3%) had a continuing pregnancy. Following change of the regimen to include the possibility of two doses of misoprostol the continuing pregnancy rates were significantly reduced (OR = 5.88) and gestation ceased to have an effect on overall efficacy. Women who had a previous abortion were more likely to have a failed medical abortion (OR = 2.09), while women with no previous termination, but a previous live birth were more likely to have a failed abortion (OR = 2.03). CONCLUSION: Mifepristone in combination with one to two doses of vaginal misoprostol is an effective regimen for early medical abortion. The option of administering two doses of misoprostol significantly reduced the ongoing pregnancy rates and abolished the effect of gestation on overall efficacy. Previous termination was the strongest predictor of failed medical abortion.
Surgical abortion.
This review of surgically-induced abortion focuses on conventional first trimester suction evacuation. Manual vacuum aspiration at early gestations and dilatation and evacuation at more advanced gestation are also considered. The place of surgical abortion in contemporary abortion practice is reviewed alongside developments in medical abortion. There is still debate about the best method for later abortions. Patient choice and pre-procedure assessment are considered fundamental to practice. The importance of antibiotic prophylaxis or infection screening is highlighted. The value of ultrasound emerges. The need for cervical priming is considered along with choice of suitable pharmacological agents. Current practice and the procedure of surgical abortion is outlined. Complications and strategies to minimize risk are detailed. The overview concludes with consideration of the impact on future reproductive health.
Sublingual misoprostol for the induction of labor at term.
OBJECTIVE: To evaluate the efficacy, safety, and patient acceptability of sublingual misoprostol compared with an equivalent dose administered orally for labor induction at term. STUDY DESIGN: One hundred women with medical or obstetric indications for induction of labor after 37 weeks of gestation and unfavorable cervices were randomized to receive 50 microg of misoprostol either orally or sublingually. The dose was repeated every 4 hours to a maximum of 5 doses if indicated. Previous cesarean delivery was a criteria for exclusion. Our primary outcome measure was the number of patients who went on to have a vaginal delivery within 24 hours of the induction. The need for oxytocin, mode of delivery, number of cesarean deliveries for fetal distress, uterine hyperstimulation rates, and neonatal outcomes were secondary outcome measures. Patient acceptability was assessed by questionnaires completed after delivery. RESULTS: Significantly more patients were delivered of infants within 24 hours (73.8% versus 45.7%; relative risk, 1.6; 95% confidence interval, 1.1 to 2.4) and the induction to delivery intervals were significantly shorter (20 hours versus 28.3 hours; mean difference, 8.3 hours; 95% confidence interval, 1.2 to 15.4) in the sublingual group compared with the oral group. There was 1 case of uterine hyperstimulation in the sublingual group. There were no significant differences in the mode of delivery, interventions for fetal distress, or neonatal outcomes in the 2 groups. The satisfaction rates were 82.5% and 85.7% in the oral and sublingual groups respectively, and 9.5% of patients thought that the sublingual tablets did not dissolve completely. CONCLUSION: There has been no previous report in the literature of misoprostol given sublingually for labor induction. Sublingual misoprostol seems to have better efficacy than oral misoprostol, seems to be acceptable to patients, and is an option to be considered to induce labor at term.
New challenges for gamete donation programmes: changes in guidelines are needed.
In the UK, the Human Fertilisation and Embryology Act 1990 prevents children born as a result of donor-assisted conception from gaining access to identifying information about their genetic origins. There is growing concern that current screening protocols regarding gamete donation are ill-suited, especially in relation to genetic disease. There are no guidelines addressing the issues of confidentiality that might arise if a disease emerges after insemination and establishment of pregnancy. Donors may become aware that they are at risk of a familial condition after they have donated gametes or recipients of donated gametes may become aware of a genetic illness in the resulting child. At present, there is no agreed method for allowing this information to be given to the donor or other recipients of gametes from that person. We suggest that these issues should be raised with donors, and appropriate counselling and predictive tests offered to them. Changes in regulations regarding gamete donation should be considered that accommodate recent and possible future developments in genetics. Furthermore, consideration should be given to the storage of samples of DNA from donors for the future provision of genetic information.
A randomized comparison of medical abortion and surgical vacuum aspiration at 10-13 weeks gestation.
BACKGROUND: Since 1991, mifepristone in combination with a prostaglandin analogue has been licensed for termination of pregnancy in the UK at up to 9 weeks amenorrhoea, and since 1995, beyond 13 weeks. Surgical methods are used almost exclusively at 10-13 weeks amenorrhoea. METHODS: A patient-centred, partially randomized, controlled trial was carried out. Those who expressed a strong preference for either medical (n = 15) or surgical (n = 62) abortion were allocated to that method. The remainder agreed to be randomized. The medical method (n = 188) was mifepristone 200 mg followed by misoprostol up to 3 doses, and surgery (n = 180) was by vacuum aspiration under general anaesthesia. Outcome measures included efficacy rates, medical complications within 8 weeks of the procedure, patient preferences and acceptability. RESULTS: Among women who underwent medical abortion, 5.4% required a second procedure compared with 2.1% who had surgery, although this difference was not statistically significant. Side effects experienced were higher in women who underwent medical abortion compared with those who underwent surgery. There were no significant differences in the rates of major complications up to 8 weeks. Prior to termination, 80% of women had a preference for a method, with 72% preferring medical and 28% preferring surgical abortion. Following abortion, 70% of those who underwent medical termination and 79% who underwent surgery would opt for the same method in the future. CONCLUSION: Medical abortion is safe and effective at 10-13 weeks gestation and should be considered an option for those women who wish to avoid surgery and anaesthesia.
The accuracy and efficacy of screening tests for Chlamydia trachomatis: a systematic review.
Screening women for lower genital tract infection with Chlamydia trachomatis is important in the prevention of pelvic inflammatory disease, ectopic pregnancy and infertility. This systematic review aims to state clearly which of the available diagnostic tests for the detection of C. trachomatis would be most effective in terms of clinical effectiveness. The review included all studies published from 1990 onward that evaluated diagnostic tests in asymptomatic, young, sexually active populations. Medline and Embase were searched electronically and key journals were hand-searched. Further studies were identified through the Internet and contact with experts in the field. All studies were reviewed by two reviewers and were scored by Irwig's assessment criteria. Additional quality assessment criteria included a documented sexual history and recording of previous chlamydial infection. The reviews were subjected to meta-analysis and meta-regression. The 30 studies that were included examined three types of DNA-based test--ligase chain reaction (LCR), PCR and gene probe--as well as enzyme immuno-assay (EIA). The results showed that while specificities were high, sensitivities varied widely across the tests and were also dependent on the specimen tested. Pooled sensitivities for LCR, PCR, gene probe and EIA on urine were 96.5%, 85.6%, 92% and 38%, respectively, while on cervical swabs the corresponding sensitivities of PCR, gene probe and EIA were 88.6%, 84% and 65%. Meta-analysis demonstrated that DNA amplification techniques performed best for both urine and swabs in low prevalence populations. We conclude that nucleic acid amplification tests used on non-invasive samples such as urine are more effective at detecting asymptomatic chlamydial infection than conventional tests, but there are few data to relate a positive result with clinical outcome.
Medical management of early fetal demise using sublingual misoprostol.
The aim of this study was to determine the efficacy of mifepristone in combination with sublingual misoprostol for the medical management of early fetal demise. Fifty-six consecutive women were studied prospectively. The mean (SD) gestation at diagnosis was 9.6 weeks (1.84). Four women had complete miscarriage with mifepristone alone. The overall success rate was 83.9% and the median induction-miscarriage interval was 8.19 hours (range 0.83 to 37.50 hours). Of those women who had a successful outcome, 91.5% were satisfied with the regimen. Sublingual misoprostol in combination with mifepristone is an effective and safe alternative to vaginal or oral misoprostol in the management of early fetal demise.
Medical management of late intrauterine death using a combination of mifepristone and misoprostol.
OBJECTIVE: To assess the efficacy and safety of mifepristone in combination with misoprostol in the management of late fetal death. DESIGN: Observational study. SETTING: Aberdeen Maternity Hospital, Aberdeen. METHODS: A consecutive series of 96 women with intrauterine death after 24 weeks of gestation were studied. Each woman received a single dose of 200 mg mifepristone orally, following which a 24-48 hour interval was recommended before administration of misoprostol. For gestations of 24-34 weeks, 200 microg of intravaginal misoprostol was administered, followed by four oral doses of 200 microg at three hourly intervals. Gestations over 34 weeks were given a similar regimen but a reduced dose of 100 microg misoprostol. RESULTS: The average induction to delivery interval was 8.5 hours. Ninety-five women (98.9%) were delivered within 72 hours of administration of first dose of misoprostol, with 66.7%, 87.5%, 92.7% and 95.8% women delivering within 12, 24, 36 and 48 hours, respectively. No significant correlation was found between mean induction to delivery interval and maternal age, parity, Bishop's score, birthweight and mifepristone/ misoprostol interval. The induction to delivery interval was shorter with increasing gestation (P = 0.04). Mild side effects were noted in eight (8.3%) women. Three (3.1%) women had treatment for presumed or proven pelvic sepsis. No cases of uterine tachysystole, haemorrhage or coagulopathy were recorded. CONCLUSION: The combination of mifepristone and misoprostol for induction of labour following late fetal death is an effective and safe regimen. The induction to delivery interval with this regimen appears shorter than studies using mifepristone or misoprostol.
A randomised study comparing a low dose of mifepristone and the Yuzpe regimen for emergency contraception.
OBJECTIVE: To compare 100 mg mifepristone with the standard Yuzpe regimen for emergency contraception. DESIGN: Randomised controlled trial. SETTING: Family Planning Clinic, Aberdeen. SAMPLE: One thousand women seeking emergency contraception within 72 hours after an episode of unprotected sexual intercourse. METHODS: Women were randomised to receive either 100 mg (half tablet) of mifepristone as a single dose or the Yuzpe regimen (two tablets each with 50 microg ethinyloestradiol and 0.25 mg levonorgestrel, to be repeated 12 hours later). OUTCOME MEASURES: Crude pregnancy rates, proportion of pregnancies prevented, side effects and patient acceptability. RESULTS: The crude pregnancy rates (95% CI) for the Yuzpe regimen and mifepristone were 3.6% (2.3-5.7) and 0.6% (0.2-1.8), respectively, with a significant difference between the two groups (RR 6.04; 95% CI 1.75-20.75). Mifepristone prevented 92% of pregnancies and the Yuzpe regimen preventing 56%. An increasing coitus to treatment interval was associated with contraceptive failure in the Yuzpe group (P = 0.03) with no association seen with mifepristone. Following administration of mifepristone 24.5% and 13.1% given the Yuzpe regimen had a delayed period (RR 2.14; 95% CI 1.46-3.15). Overall, mifepristone was better tolerated than the Yuzpe regimen with significantly fewer side effects. More women were satisfied (P < 0.0001) with mifepristone as an emergency contraceptive and would recommend it to a friend (P = 0.02). CONCLUSION: Mifepristone administered in a 100 mg dose is a highly effective post-coital contraceptive with high patient acceptability and fewer side effects compared with the standard Yuzpe regimen. Delay in the onset of menstruation did not decrease patient acceptability.
Sublingual compared with oral misoprostol in term labour induction: a randomised controlled trial.
OBJECTIVE: To compare the efficacy and patient acceptability of 50 microg of sublingual misoprostol with 100 microg of oral misoprostol in the induction of labour at term. DESIGN: Non-blinded randomised comparative trial. SETTING: Tertiary level UK Hospital. SAMPLE: Two hundred and fifty women at term with indications for labour induction. METHODS: Fifty micrograms of sublingual misoprostol or 100 microg of oral misoprostol was administered every four hours after random allocation, to a maximum of five doses. MAIN OUTCOME MEASURES: Number of patients delivering vaginally within 24 hours of the induction, mode of delivery, neonatal outcomes and patient acceptability. RESULTS: There was no significant difference in the number of women delivering vaginally within 24 hours of the induction in the sublingual group as compared with the oral group (62.8% vs 59%, RR 1.1, 95% CI 0.6-2.1), or in the mean induction to delivery time (21.8 vs 24.1 h, mean difference 2.3 h 95% CI -2.2 to +6.7). There was no difference in the uterine hyperstimulation rates (1.6% in both groups), operative delivery rates or neonatal outcomes. In the sublingual group, 92.6% found the induction acceptable with 15.8% finding the tablets with an unpleasant taste, while in the oral group it was 96.9% and 4%, respectively. More patients in the oral group thought that they would consider the same method of induction again as compared with the sublingual group (58.6% vs 40%, RR 1.4, 95% CI 1.04-1.9). CONCLUSION: Fifty micrograms of sublingual misoprostol every four hours has the same efficacy and safety profile as compared with 100 microg orally, but the oral route might be preferred by women.
Peritoneal environment, cytokines and angiogenesis in the pathophysiology of endometriosis.
Endometriosis, defined by the presence of viable endometrial tissue outside the uterine cavity, is a common condition affecting 2-3% of women of reproductive age. Today, a composite theory of retrograde menstruation with implantation of endometrial fragments in conjunction with peritoneal factors to stimulate cell growth is the most widely accepted explanation. There is substantial evidence that immunological factors and angiogenesis play a decisive role in the pathogenesis of endometriosis. In women with endometriosis, there appears to be an alteration in the function of peritoneal macrophages, natural killer cells and lymphocytes. Furthermore, growth factors and inflammatory mediators in the peritoneal fluid, produced mainly by peritoneal macrophages, are altered in endometriosis, indicating a role for these immune cells and mediators in the pathogenesis of this disease.