Telomere length heterogeneity in placenta revealed with high-resolution telomere length analysis.

INTRODUCTION: Telomeres, are composed of tandem repeat sequences located at the ends of chromosomes and are required to maintain genomic stability. Telomeres can become shorter due to cell division and specific lifestyle factors. Critically shortened telomeres are linked to cellular dysfunction, senescence and aging. A number of studies have used low resolution techniques to assess telomere length in the placenta. In this study, we applied Single Telomere Length Analysis (STELA) which provides high-resolution chromosome specific telomere length profiles to ask whether we could obtain more detailed information on the length of individual telomeres in the placenta. METHODS: Term placentas (37-42 weeks) were collected from women delivering at University Hospital of Wales or Royal Gwent Hospital within 2 h of delivery. Multiple telomere-length distributions were determined using STELA. Intraplacental variation of telomere length was analysed (N = 5). Telomere length distributions were compared between labouring (N = 10) and non-labouring (N = 11) participants. Finally, telomere length was compared between female (N = 17) and male (N = 20) placenta. RESULTS: There were no significant influences of sampling site, mode of delivery or foetal sex on the telomere-length distributions obtained. The mean telomere length was 7.7 kb ranging from 5.0 kb to 11.7 kb across all samples (N = 42) and longer compared with other human tissues at birth. STELA also revealed considerable telomere length heterogeneity within samples. CONCLUSIONS: We have shown that STELA can be used to study telomere length homeostasis in the placenta regardless of sampling site, mode of delivery and foetal sex. Moreover, as each amplicon is derived from a single telomeric molecule, from a single cell, STELA can reveal the full detail of telomere-length distributions, including telomeres within the length ranges observed in senescent cells. STELA thus provides a new tool to interrogate the relationship between telomere length and pregnancy complications linked to placental dysfunction.

Placental expression of imprinted genes varies with sampling site and mode of delivery.

UNLABELLED: Imprinted genes, which are monoallelically expressed by virtue of an epigenetic process initiated in the germline, are known to play key roles in regulating fetal growth and placental development. Numerous studies are investigating the expression of these imprinted genes in the human placenta in relation to common complications of pregnancy such as fetal growth restriction and preeclampsia. This study aimed to determine whether placental sampling protocols or other factors such as fetal sex, gestational age and mode of delivery may influence the expression of imprinted genes predicted to regulate placental signalling. METHODS: Term placentas were collected from Caucasian women delivering at University Hospital of Wales or Royal Gwent Hospital within two hours of delivery. Expression of the imprinted genes PHLDA2, CDKN1C, PEG3 and PEG10 was assayed by quantitative real time PCR. Intraplacental gene expression was analysed (N = 5). Placental gene expression was compared between male (N = 11) and female (N = 11) infants, early term (N = 8) and late term (N = 10) deliveries and between labouring (N = 13) and non-labouring (N = 21) participants. RESULTS: The paternally expressed imprinted genes PEG3 and PEG10 were resilient to differences in sampling site, fetal sex, term gestational age and mode of delivery. The maternally expressed imprinted gene CDKN1C was elevated over 2-fold (p < 0.001) in placenta from labouring deliveries compared with elective caesarean sections. In addition, the maternally expressed imprinted gene PHLDA2 was elevated by 1.8 fold (p = 0.01) in samples taken at the distal edge of the placenta compared to the cord insertion site. CONCLUSION: These findings support the reinterpretation of existing data sets on these genes in relation to complications of pregnancy and further reinforce the importance of optimising and unifying placental collection protocols for future studies.

Medical terminations of pregnancy: a viable source of tissue for cell replacement therapy for neurodegenerative disorders.

"Proof-of-principle" that cell replacement therapy works for neurodegeneration has been reported, but only using donor cells collected from fetal brain tissue obtained from surgical terminations of pregnancy. Surgical terminations of pregnancy represent an increasingly limited supply of donor cells due to the tendency towards performing medical termination in much of Europe. This imposes a severe constraint on further experimental and clinical cell transplantation research. Therefore, we explore here the feasibility of using medical termination tissue as a donor source. Products of conception were retrieved from surgical terminations over the last 7 years and from medical terminations over the last 2.5 years. The number of collections that yielded fetal tissue, viable brain tissue, and identifiable brain regions (ganglionic eminence, ventral mesencephalon, and neocortex) were recorded. We studied cell viability, cell physiological properties, and differentiation potential both in vitro and following transplantation into the central nervous system of rodent models of neurodegenerative disease. Within equivalent periods, we were able to collect substantially greater numbers of fetal remains from medical than from surgical terminations of pregnancy, and the medical terminations yielded a much higher proportion of identifiable and dissectible brain tissue. Furthermore, we demonstrate that harvested cells retain the capacity to differentiate into neurons with characteristics appropriate to the region from which they are dissected. We show that, contrary to widespread assumption, medical termination of pregnancy-derived fetal brain cells represent a feasible and more readily available source of human fetal tissue for experimental cell transplantation with the potential for use in future clinical trials in human neurodegenerative disease.

The use of Kielland's forceps and obstetricians' anxiety trait.

There is very limited literature available on the use of Kielland's forceps in the management of deep transverse arrest, and currently no studies looking at the correlation between obstetricians' personality traits and Kielland's forceps use. This study, therefore, aims to explore this relationship. All practicing consultant obstetricians in Wales received a postal invitation, including a psychometric questionnaire. The results showed that 32.7% currently use Kielland's compared with 36.7% who have never used Kielland's forceps. The remainder (30.6%) have used Kielland's in the past, but have since abandoned their use. Anxiety levels were actually lowest in those consultants who have never used Kielland's and highest in those who have abandoned their use. This could reflect the fact that Kielland's users tend to be the more senior consultants, who have perhaps become discouraged by recent changes in practice.

The effects of the attending obstetrician's anxiety trait and the corresponding obstetric intervention rates.

Anecdotally, it has been suggested that obstetricians of similar training and experience have different intervention rates on the labour ward. This phenomenon has not been studied in depth. The aim of this study was to record the intra-partum intervention rates for third on-call registrars and correlate this with the anxiety traits of the corresponding registrars. An analysis of births occurring during out-of-hours in the main delivery unit of a large teaching hospital during the period September 2005-September 2006 was carried out. The rate of interventions per cumulative number of deliveries that occurred specific to each doctor on-call was calculated. Anxiety traits were calculated with a validated questionnaire. There is a significant difference in the caesarean section rates between registrars of similar experience. There is also a strong correlation between the registrar's anxiety trait level and the registrar's emergency caesarean section rates (Pearsons correlate 0.722, p<0.01).

Rectovaginal endometriosis -- a frequently missed diagnosis.

To assess the proportion of women found to have rectovaginal endometriosis who underwent a previous laparoscopy with negative findings, a 5-year retrospective observational study was carried out at the University Hospital of Wales, Cardiff UK, from 2001 to 2005. A total of 61 cases with potential symptoms of rectovaginal endometriosis who underwent laparoscopy were identified. Rectovaginal endometriosis was identified in 16 of these cases. Previous laparoscopy was carried out in 33 of these 61 cases. In the group of women found to have rectovaginal endometriosis, 14 cases of rectovaginal endometriosis were not identified by pre-referral laparoscopy. This study supports the anecdotal idea that rectovaginal endometriosis is an often missed diagnosis at the time of laparoscopy. Diagnostic laparoscopy by generalist gynaecologists frequently fails to diagnose rectovaginal endometriosis. The routine use of rectal probes at laparoscopy is recommended to increase diagnostic accuracy.

Predicting the presence of rectovaginal endometriosis from the clinical history: a retrospective observational study.

Rectovaginal endometriosis is a severe variant of endometriosis. Common presenting symptoms for endometriosis include dysmenorrhoea, pelvic pain and dyspareunia. It is now recognised that there are other less traditional symptoms of endometriosis that are also relatively common. The aim of this study is to assess the relative strength of each of the potential symptoms of rectovaginal endometriosis and compare these with the laparoscopic and histological findings. In this retrospective, observational study the overall prevalence of rectovaginal endometriosis in the group was 31.4%. The presence of dyschesia gave a likelihood ratio of 1.27 (95% CI: 0.56 - 2.89) with a predictive prevalence of rectovaginal endometriosis of 37%. Apareunia and nausea or abdominal bloating were particularly strong markers for rectovaginal disease with a predictive prevalence of 87% and 89%, respectively. The classical symptoms often attributed to irritable bowel syndrome are also common in women with rectovaginal disease.

A prospective observational study of the safety and acceptability of vaginal hysterectomy performed in a 24-hour day case surgery setting.

OBJECTIVE: To assess the safety and acceptability of vaginal hysterectomy with and without simultaneous oophorectomy in a 24-hour day case surgery setting for women with nonprolapse indications for surgery. DESIGN: Prospective observational study. SETTING: A busy teaching hospital and tertiary referral centre for Obstetrics and Gynaecology. POPULATION: Seventy-one women from one consultant's practice underwent a vaginal hysterectomy with a planned discharge within 24 hours after the procedure. All women had a body mass index less than 40 and a suitable home environment for routine day case surgery, other than that the women were from an unselected population. METHOD: Prospective observational study. MAIN OUTCOME MEASURES: The duration of the operation and mean blood loss were recorded. Any intraoperative complications were noted. In addition, the proportion of women discharged home within 24 hours of the operation was recorded together with any readmissions to hospital. Returns to theatres and any postoperative complications were also recorded. Postoperative pain scores were assessed 6 and 24 hours after procedure in selected women. RESULTS: Seventy-one vaginal hysterectomies were performed as 24-hour day case procedures. The intraoperative complication rate was 1.4%. Sixty-five women were discharged home within 24 hours (91.5%). The readmission rate within this group was 6.2%. The duration of the procedure, mean blood loss, return to theatre rate and incidence of febrile illness were comparable with rates recorded in inpatient studies. CONCLUSIONS: Vaginal hysterectomy performed as a 24-hour day case procedure appears to be as safe as traditional inpatient management, with a high rate of early discharge and a low rate of readmission. This may have additional advantages for the woman and healthcare provider alike.

Self-administration of vaginal misoprostol after mifepristone for termination of pregnancy: patient acceptability.

This was a questionnaire survey involving women who self-administered vaginal misoprostol in the hospital setting following oral mifepristone for medical termination of pregnancy. The sample number was 89 with a median gestational age of 9 weeks; median dose of misoprostol used was 1600 mug and median induction abortion interval was 5.3 h. The success rate was 100% with the majority finding it easy to self-administer vaginal misoprostol and two-thirds did not mind doing this. Only one-third experienced adverse effects of the medication and 83% were satisfied with the procedure. Only one-third was willing to try it at home in future if necessary. Self-administration of vaginal misoprostol for termination of pregnancy in the hospital is safe and effective. Although women were comfortable in self administering the pessaries in the hospital, they do not appear to be keen to do it at home without any supervision. However, as this is the first study in the UK involving women expressing their views regarding this issue, added research in this area is required.

Self-administration of misoprostol for termination of pregnancy: safety and efficacy.

We conducted a retrospective study to determine the efficacy and safety of self-administration of vaginal misoprostol (following oral mifeprestone) for medical termination of pregnancy. This study revealed that self-administration was accepted by the majority of the patients (90%) and the success rate (98.4%) and duration of hospital stay was not altered significantly compared to our previous year's data, where women were administered vaginal misoprostol by the staff. Based on this study's results, we are of the opinion that this regimen not only demedicalises the problem but also decreases the workload for the medical staff.

Laparoscopic management of benign ovarian disease.

There was little controversy in the management of ovarian cysts until 15 years ago when operative endoscopy gained popularity. Before this time, laparotomy was the standard form of treatment for pelvic masses. Simple cysts were treated laproscopically by aspiration and solid or large tumors with any malignant potential by laparotomy. Constantly improving technology and instrumentation has allowed more and more operations to be performed laparoscopically. The gynecological oncologist has been wary of adopting this form of surgery for potential gynecological malignancies because of the safety and efficacy issues. Pelvic pathology, particularly ovarian tumors, pose a difficult problem. Apart from difficulty in screening, it is also difficult to confirm the nature of an ovarian pathology using the currently available investigative modalities. If the nature of an ovarian cyst can be ascertained beyond doubt, then the treatment can be simple, laparoscopy for benign and laparotomy for malignant. Having said that, more enthusiastic operative laparoscopists are using this approach to treat gynecological malignancies. We discuss the role of laparoscopy in the management of ovarian cysts.

Training in endoscopic surgery in gynaecology.

Over the last decade there has been an explosion of endoscopic surgical procedures that is now having profound effects on training in gynaecology. As trainees adopt these new procedures, they should obtain formal training supplemented by appropriate senior supervision which has been shown to reduce the risk of iatrogenic endoscopic complications.