Royal Women's Hospital Research Articles

Microinvasive Adenocarcinoma of the Cervix

Departments of Pathology and Gynecology, The Royal Women's Hospital, Melbourne, Australia. Obstet Gynecol 1997;89: 88-93.

Artificial insemination and in-vitro fertilization using donor spermatozoa: a report on 15 years of experience

Donor insemination (DI) using cryopreserved semen commenced at The Royal Women's Hospital in 1976. Over the next 15 years we performed 5953 treatment cycles to achieve 816 pregnancies (13.7% per cycle) and 706 live births. In-vitro fertilization (IVF) using donor spermatozoa commenced in 1986. Over the next 5 years we performed 303 treatment cycles for 185 couples. Including subsequent transfer of cryopreserved embryos, a total of 33% of couples achieved a successful pregnancy by IVF. Statistical analysis indicated that, for DI pregnancies, the most important semen variable was the percentage post-thaw motility, whilst for normal fertilization in IVF it was the pre-freeze motility. These results may be explained by the compensatory effects of post-thaw processing of spermatozoa for IVF, but not for DI in our clinic.

Career Paths of Obstetricians and Gynaecologists Trained at The Royal Women's Hospital, Melbourne

This study documents the contribution made to women's health by the 177 obstetricians and gynaecologists trained at The Royal Women's Hospital in the 35-year period 1960-1994. Whilst there were no female graduates during the first 15 years of the study period, female trainees now outnumber male trainees. Royal Women's Hospital-trained specialists are less likely to practise in Victorian provincial cities than graduates who have trained elsewhere. During the study period there has been a notable increase in the proportion of graduates entering subspecialist practice with a consequent decrease in the proportion providing obstetrics care.

Changes over time in attitudes to treatment and survival rates for extremely preterm infants (23-27 weeks' gestational age).

We determined the changes over time in attitude to treatment of very preterm infants (23-27 weeks of gestational age) born at the Royal Women's Hospital, Melbourne, and their survival rate. The subjects were consecutive livebirths at 23-27 weeks' gestational age born from 1983-1994, inclusive. The main outcomes measured were the proportions of livebirths treated intensively and survival rates to hospital discharge, both excluding lethal abnormalities. Over the 12 years of the study there were 788 livebirths free of lethal abnormalities born at 23-27 week's gestational age. Overall 669 (85%) were treated intensively; the proportions treated intensively rose significantly over time from 74% in 1983-1985 to 91% in 1992-1994, and with increasing gestational age, from 19% at 23 weeks to 100% at 27 weeks. Overall 439 (56%) survived their primary hospitalization; the survival rate rose significantly over time, from 43% in 1983-1985 to 70% in 1992-1994, and with increasing gestational age, from 3% at 23 weeks to 78% at 27 weeks. In 1992-1994, the survival rates were 11% at 23 weeks, 53% at 24 weeks, 70% at 25 weeks, 81% at 26 weeks, and 87% at 27 weeks. For infants treated intensively, the survival rate rose significantly from 53% in 1983-1985 to 76% in 1992-1994. The largest increases in survival have occurred in the 1990s, and at 24 and 25 weeks' gestational age. The proportions of very preterm infants treated intensively and their survival rates have increased over time, and have always been higher with increasing gestational age.

Failed homebirths: reasons for transfer to hospital and maternal/neonatal outcome.

A review of patients who had been transferred to the Royal Women's Hospital, Brisbane after a failed homebirth was undertaken over a period of 5 1/2 years. There were 27 patients identified. The most common reason for transfer was failed progress in labour, although 4 patients were transferred after delivery. Despite the resistance of these patients to medical intervention, the study found that 63% of patients required assistance at delivery, by vacuum extraction, forceps or Caesarean section. The morbidity suffered by the babies was significant (8 were admitted to special and intensive care nursery) but long-term sequelae cannot be determined because of early discharge against medical advice and refusal to be followed-up in some instances.

Women's evaluations of their experience with fetal intrapartum oxygen saturation monitoring and participation in a research project

Objective: to evaluate women's perceptions of their participation in a research project in labour and their experience with fetal oxygen saturation monitoring. Design: survey using a questionnaire of women's ratings of ten aspects of their experience with the project. Setting: Royal Women's Hospital, Brisbane, Australia. Participants: women who had participated in clinical observational studies of fetal intrapartum oxygen saturation monitoring. Findings: 78 questionnaires were distributed and 77 returned. Overall, women evaluated their participation in this research project favourably, in terms of both their involvement in the research study and the use of fetal oxygen saturation monitoring. Several women commented that they appreciated the additional support they received from the research midwife. Key conclusions: responses indicated that the women surveyed appreciated the opportunity to participate in research, were not averse to this new technology, and benefited from the perceived additional human contact and support they received. The high response rate to the questionnaire indicates that childbearing women are willing to be included in assessing the appropriateness of new birth technologies that may affect the well-being of women and babies in the future.

Book Reviews

Book reviewed in this article:Dewhurst's Textbook of Obstetrics and Gynaecology for Postgraduates fifth edition., Author: Charles R Whitfield.Progress in Obstetrics and Gynaecology Volume II. Author: John Studd.The ABC of Antenatal Care. Author: Geoffrey Chamberlain.Cancer of the Cervix. Author: Hugh M Shingleton & James W Orr Jr.Comprehensive Cancer Cytopathology of the Cervix Uteri. Author: Yi‐Jing Shu and Etienne Gloor.Community‐Based Distribution of Contraceptives. Author: World Health Organization Geneva 1995.Active and Pregnant‐A Guide to Exercise in the Childbearing Year. Author: Vicfit andThe Royal Women's Hospital. Pelvic Floor Re‐Education‐Principles and Practice. Author: Bernard Schussler, Jo Laycock, Peggy A. Norton Stuart L. Stanton.Osteoporosis. Author: Robert Marcus.Manual of Practical Gynaecological Oncology. Author: Basil Bloch, Katrien Debaeck and, Robbert Soeters.Automated Cervical Cancer Screening. Author. Heinz K Grohs and OA Nasseem Husain.Androgenic Disorders. Author: Geoffrey P Redmond.Manual of Diagnostic Ultrasound. Author: P.E.S. Palmer.Transvaginal Sonography in Infertility. Author: Bill Yee, Gregory F, Rosen and Denise L. Cassidenti.Transvaginal Colour Doppler. Author: T.H. Bourne, E. Jauniaux and D. Jurkovic.Clinical Applications of Doppler Ultrasound. Author: Kenneth J.W. Taylor, Peter N. Bums and Peter NT. Wells.

Growth and Physical Outcome of Children Conceived by In Vitro Fertilization

To determine the growth and physical outcome at 2 years of age for children born after assisted reproductive techniques in the state of Victoria. Using a case-matched control study between January 1991 and July 1993, 314 children (196 singletons, 47 sets of twins, 8 sets of triplets) conceived after in vitro fertilization (IVF) and related techniques at the Monash IVF and Royal Women's Hospital Reproductive Biology Unit and 150 control children (113 singletons, 17 sets of twins, 1 set of triplets) randomly selected from the general population using the Victorian Perinatal Data Collection Unit records were enrolled to be examined for minor dysmorphic and major organ abnormalities. Singleton and twin cases were matched for plurality and gestation and date of birth. Triplets were not matched. IVF status was not a significant independent factor for physical outcomes, including malformation rates, nor for days of hospitalization postdischarge and operations. There was no significant interaction between IVF status and mean percentiles for weight and head circumference. The IVF group had a greater mean length percentile. Twins in both groups had significantly poorer physical outcomes than singletons on some measures. This study did not demonstrate an independent IVF effect on the growth and physical outcome of children at 2 years of age when matched for plurality and gestation. The poor outcomes where noted were related to the effects of multiple births. These findings must be viewed in context of the response rates and therefore representativeness of the data. The need for longitudinal studies is demonstrated.

Assisted ventilation and survival of extremely low birthweight infants

To determine the incremental consumption of ventilator resources associated with the improving survival rate of extremely low birthweight (ELBW birthweight 500-999g) infants, from the time assisted ventilation was introduced. Cohort study of ELBW infants born in one tertiary perinatal centre (The Royal Women's Hospital, Melbourne). All ELBW infants born from 1971 to 1993 were included in the study. In hospital survival rates and patient-days of assisted ventilation were the main outcome measures. Discrete eras of relatively stable survival rate and consumption of ventilator resources were identified. These comprised the years 1971-74, 1977-83, 1985-90, and 1992-93. Cost-effectiveness ratios (the incremental consumption of ventilator resources per additional survivor) were calculated between adjacent eras by dividing the increment in the consumption of ventilator resources by the increment in the survival rate. The survival rates rose progressively between eras (6.2, 33.9, 49.1, 68.8%, respectively, as did the consumption of ventilator resources (0.1, 6.6, 16.2, 24.7 patient-days of assisted ventilation per livebirth, respectively). The cost-effectiveness ratio deteriorated initially, increasing from 23.2 to 63.5 additional patient-days of assisted ventilation per additional survivor, but then improved, falling to 43.1 additional patient-days of assisted ventilation per additional survivor in the last era. These changes were even more marked for those of birthweight 750-999g (20.0, 63.2 to 35.9 additional patient-days of assisted ventilation per additional survivor, respectively). In contrast, the cost-effectiveness ratio was initially worse for those of birthweight 500-749 g, being three-fold higher than for the larger infants, and only improved substantially in the last era (59.8, 58.3 to 44.1 additional patient-days of assisted ventilation per additional survivor, respectively). The initial deterioration in cost-effectiveness ratios between successive eras probably reflected the increased availability of resources for assisted ventilation, without any other major advances in perinatal care. The improvement in cost-effectiveness in the last era reflected, in part, the increased use of antenatal steroid therapy and the introduction of exogenous surfactant to neonatal intensive care.

Patient profiles and tumour characteristics in 259 breast cancers detected on first round screening in an open access breast screening clinic

<h2>Abstract</h2> In this analysis, data in relation to 259 breast malignancies detected on first round screening at the Royal Women's Hospital Breast Screening Clinic (RWHBSC), Brisbane, in the first 6 years of its function, is reviewed. A reduction in recall rate was noted when two-view mammography was adopted as the method of screening over single-view mammography plus physical examination, which was practised for the first 2 years of the Clinic's operation. The parameters of clinic performance, including a recall rate of 9.1%, an open surgical biopsy rate of 1.5%, a benign to malignancy biopsy ratio of 1.1:1, a cancer detection rate of 7.1 cancers per 1000 women screened, and a cancer detection rate for tumours < 10 mm of 1.6 cancers per 1000 women screened, reflect favourably on the standard of conduct of the Clinic. The results of this review indicate that early detection of breast cancer by mammography screening can be successfully achieved, provided strict quality assurance guidelines are followed.

Passive smoking and respiratory function in very low birthweight children.

To determine if an adverse relationship exists between passive smoking and respiratory function in very low birthweight (VLBW) children at 11 years of age. The Royal Women's Hospital, Melbourne. 154 consecutive surviving children of less than 1501 g birthweight born during the 18 months from 1 October 1980. Respiratory function of 120 of the 154 children (77.9%) at 11 years of age was measured. Exposure to passive smoking was established by history; no children were known to be actively smoking. The relationships between various respiratory function variables and the estimated number of cigarettes smoked by household members per day were analysed by linear regression. Most respiratory function variables reflecting airflow were significantly diminished with increasing exposure to passive smoking. In addition, variables indicative of air-trapping rose significantly with increasing exposure to passive smoking. Passive smoking is associated with adverse respiratory function in surviving VLBW children 11 years of age. Continued exposure to passive smoking, or active smoking, beyond 11 years may lead to further deterioration in respiratory function in these children.

Operative laparoscopic management of adnexal cysts: initial experience at the Royal Women's Hospital 1991-1994.

The introduction of operative laparoscopic surgery for benign adnexal cysts had led to shorter postoperative hospitalization (mean stay of 2.0 days) in association with a low rate of major complications (1.6%). A planned laparoscopic approach was successful in 95.2% (179/188) of patients. The majority of women were premenopausal (93.6%) and the most common procedure performed was an ovarian cystectomy (73.5% of cysts). Three ovarian cysts that were thought to be benign by preoperative and intraoperative assessment were subsequently found to be ovarian tumours of low malignant potential after histological examination. Operative laparoscopy has become the preferred mode of treatment for benign adnexal cysts at the Royal Women's Hospital. It confers a wide range of benefits to patients, reduces health-care costs and appears to be a safe and effective treatment modality.

Episiotomy at the Royal Women's Hospital, Brisbane: a comparison of practices in 1986 and 1992

Objective: to determine whether the incidence of perineal outcomes, including episiotomy, at the Royal Women's Hospital (RWH) Brisbane reflected trends reported in the literature. Design: retrospective record review. Setting: RWH Brisbane. Participants: 953 women who delivered vaginally at the RWH in 1986 and 1992. Measurements and findings: there was a decline in the episiotomy rate from 65% in 1986 to 36% in 1992. This was accompanied by an increase in the incidence of intact perinea and spontaneous perineal tears. There was no difference in the incidence of spontaneous third degree tears. The decline in the incidence of episiotomy was found when other factors, such as parity, were considered, with the exception of operative vaginal delivery, where no difference in the use of episiotomy was found. There was no significant increase in the number of babies with an Apgar score of <7 at one minute of age, despite a significant reduction in the use of episiotomy when delivering these babies (55% in 1986 and 19% in 1992; P<0.001). The second stage was significantly longer in 1992 ( P<0.01). Key conclusions: the findings reflect the decline in the incidence of episiotomy reported in the literature. This decline in rate was accompanied by an increase in the length of second stage and in the incidence of both intact perinea and perineal tears. Lowering the incidence of episiotomy did not result in a rise in the rate of babies with an Apgar score of <7 at one minute.

HLA-G deletion polymorphism and pre-eclampsia/eclampsia.

To investigate a HLA-G deletion polymorphism in pre-eclamptic pedigrees and the general population. A population association study of HLA-G genotypes from pre-eclamptic/eclamptic patients and control groups. Analyses undertaken in the School of Biological Sciences, Macquarie University. Patients were from Royal Women's Hospital, Melbourne, and controls were from Westmead Hospital and Macquarie University, Sydney. One hundred and ninety-six individuals, consisting of 29 pre-eclamptic/eclamptic (PE/E) patients, 13 individuals born of a PE/E pregnancy, 46 blood relatives of PE/E patients, 21 husbands of PE/E patients, 25 women normotensive in first pregnancy, 15 husbands of women normotensive in first pregnancy and 47 staff and students of Macquarie University. Genotypic and gene frequencies were not significantly different in the seven groups examined. There is no detectable relationship between susceptibility to pre-eclampsia or being born of a pre-eclamptic pregnancy and HLA-G genotype.

Do childbirth classes influence decision making about labor and postpartum issues?

This study investigated the role of childbirth education for women attending the Royal Women's Hospital Family Birth Center, Melbourne, Australia, in relation to making decisions about breastfeeding, pain medication, and length of hospital stay. Fifty-nine primiparous women completed a questionnaire after delivery about the influence of childbirth education classes on their decisions during pregnancy, birth, and the postnatal period. The results indicated that although the women enjoyed childbirth education classes, the information they received had minimal effect on their decision to breastfeed and the appropriateness of a 24-hour stay. Information gained about the use of pain medication in labor was clearly helpful when women made decisions about pain relief. Educational strategies have failed to address the tendency of nulliparous women to postpone making decisions about the postnatal period such as early discharge, and further investigation on this aspect of a childbirth education program is suggested.

The Amniotic Fluid Embolism Syndrome: 10 Years' Experience at a Major Teaching Hospital

A review of the syndrome of amniotic fluid embolism (AFE) was carried out over a 10 year period, 1984-1993, at the Royal Women's Hospital, Brisbane. There were 9 patients with AFE, of whom 2 died--this gave an incidence of fatal AFE of 3.37 per 100,000 pregnancies at the hospital, in comparison with an incidence of 1.03 per 100,000 pregnancies over a 27-year period in Australia. The study revealed no identifiable risk factors in the characteristics of the patient or her baby, labour and delivery. Three of the patients did not undergo labour and in 4 of the 6 who did, the duration was less than 12 hours. The AFE syndrome could present before, during or after delivery; the common features were shock and respiratory distress, with coagulopathy occurring in 5 patients. Current views of predisposing factors, pathogenesis, diagnosis and management are discussed.

Retinopathy of prematurity in infants weighing 1000‐1499 g at birth

To review the incidence and severity of retinopathy of prematurity (ROP) in infants with birthweights 1000-1249 g and 1250-1499 g, to establish whether the upper weight limit for routine ophthalmological examination might safely be lowered. Prospective cohort study of infants born between 1 January 1977 and 31 December 1992 cared for in the neonatal nurseries at the Royal Women's Hospital, Melbourne. Data were retrieved on 1373 infants who survived their initial hospitalization. They comprised 657 with birthweights 1000-1249 g (group 1) and 716 with birthweights 1250-1499 g (group 2). There were 76 outborn infants in group 1 and 97 in group 2; the remaining infants were all born at the Royal Women's Hospital. Ocular examinations commenced at 2 weeks of age, when possible, and at 2-weekly intervals after that. In group 1, ROP was detected in 14.6% (96/657) and severe ROP (bilateral stage 3-5) in 5.0% (33/657). Five (0.8%) children required surgical intervention (reaching threshold disease); following surgery, one was legally blind, one had severely impaired vision, and the other three had near-normal vision. Another child was blind; he was born at 28 weeks gestational age with a birthweight of 1170 g, and was transferred to a Level II hospital at 9 weeks chronological age with no detectable retinopathy. He returned 1 year later totally blind with detached retinae (grade 5 ROP). The prevalence of bilateral blindness in this group was 0.3% (2/657). In group 2, ROP was detected in 6.4% (46/716) and severe ROP in 0.8% (6/716). No children required surgery; three were found to be myopic at follow-up but the corrected visual acuity was normal. No children in group 2 were blind. No significant difference was found between the rates of ROP in inborn and outborn infants. In neonatal units with similar rates of ROP and visual outcome, routine ophthalmological examination in the neonatal nursery of infants weighing more than 1249 g at birth is probably unnecessary.

Tumour necrosis factor alpha during human pregnancy and labour: maternal plasma and amniotic fluid concentrations and release from intrauterine tissues.

The aims of this study were: to quantify immunoreactive tumour necrosis factor alpha (TNF-alpha) concentrations in maternal plasma and amniotic fluid obtained from women during pregnancy and labour, both at term and preterm; and to establish the effects of bacterial endotoxin and cytokines on the in vitro release of TNF-alpha from intrauterine tissues. Maternal plasma TNF-alpha concentrations did not change during pregnancy (457.2 +/- 102.9 ng/l, mean +/- SEM, N = 52) or at the time of labour (543.5 +/- 138.6 ng/l, N = 43). In contrast, amniotic fluid TNF-alpha concentrations increased significantly (p < 0.05) during pregnancy (early pregnancy, EP, 93.0 +/- 24.8 ng/l, N = 7; preterm not-in-labour, PNIL, 186.8 +/- 42.9 ng/l, N = 16; term not-in-labour. TNIL, 499.7 +/- 150.9 ng/l, N = 13) and in association with preterm labour (preterm in-labour, PIL, 958.7 +/- 575.6 ng/l, N = 5 vs PNIL, 186.8 +/- 42.9 ng/l, N = 16). Choriodecidual and placental explants (N = 3) maintained in in vitro culture released TNF-alpha. Furthermore, the release of TNF-alpha was increased significantly (p < 0.05) by bacterial endotoxin (lipopolysaccharide, 10 ng/l-10 mg/l) but was not affected by the following cytokines at the indicated doses: interleukin-1 alpha (0.28 nmol/l), interleukin-6 (12.5 nmol/l), granulocyte colony-stimulating factor (2.5 nmol/l), granulocyte-macrophage colony-stimulating factor (35 nmol/l), macrophage colony-stimulating factor (1.2 nmol/l), leukaemia inhibitory factor (0.45 nmol/l) and transforming growth factor-beta (0.4 nmol/l).(ABSTRACT TRUNCATED AT 250 WORDS)

Vaginal Agenesis and the Embryology of Vaginal Epithelium

EDITORIAL COMMENT: We have accepted this paper for publication because we hope that readers will enjoy the discussion about the embryology of the vagina. Although the hymen has stratified squamous epithelium on both superior and inferior surfaces there are reported cases (A) of a transverse vaginal septum above the level of the hymen where the superior surface was covered by columnar epithelium and the inferior surface by squamous epithelium (figure A, 1 and 2). One interpretation of this finding is that the columnar epithelium was derived from Mullerian duct tissue and thus, that the squamous epithelium of the vagina arises by replacing Mullerian duct tissue. There is controversy regarding whether this second epithelium arises from endoderm of the urogenital sinus, mesoderm of the Wolffian ducts or ectoderm of the cloacal membrane (B). Recently a case of double uterus with 1 side having a blind vagina was seen in the University Department at the Mercy Hospital for Women. With this article in mind biopsies were taken from the vaginal walls in the side that had the haematocolpos. The biopsies showed columnar epithelium similar to endocervical epithelium. The editorial committee referred this article for opinion from anatomists and embryologists at the University of Melbourne, Department of Anatomy and Cell Biology and their comments are included as an addendum to this paper. Some of the arguments presented are not easy to follow and the editor considers that a convincing case is yet to be made to reverse the traditional teaching on the embryology of the vagina. Stewart AD. Cryptomenorrhoea due to a transverse vaginal septum. Aust N Z J Obstet Gynaecol 1968; 8: 45–48. Deppisch LM. Transverse vaginal septum. Histologic and embryologic considerations. Obstet Gynecol 1972; 193–198. Summary: A review has been made of 29 cases of vaginal agenesis treated by the Sheares technique of vaginoplasty at the Royal Women's Hospital, Melbourne since 1976. Spontaneous epithelialization of the neovagina is rapid providing the newly created space is kept patent by regular dilatation. The process is usually complete by the 10th to 12th postoperative week. A review of the embryology of vaginal epithelium suggests that it is entirely of urogenital sinus origin. In cases of vaginal reconstruction where no grafting technique is employed it seems likely that epithelial rests are responsible for the rapid epithelialization that occurs.

Review of the Management of Ectopic Pregnancy in a Major Teaching Hospital: Laparoscopic Surgical Treatment and Persistent Ectopic Pregnancy

Summary: Two hundred and three cases of ectopic pregnancy were examined to determine the current management trends at the Royal Women's Hospital during a period where laparoscopic and conservative therapies were being increasingly used. Only 25% of patients were managed by the previous method of laparotomy and salpingectomy. Ten (8.8%) of 114 cases treated by laparoscopic procedures had persistent trophoblast activity and 8 of these required further surgical or medical treatment. Seven (14.9%) of 47 cases treated by laparoscopic salpingostomy resulted in persistent ectopic pregnancy (PEP). The postoperative beta HCG profiles of 41 patients were examined to identify differences between the ‘persistent ectopic’ and ‘resolved ectopic’ groups. Postoperative serum beta HCG monitoring should be performed at day 4 and day 7 to enable the early detection of treatment failure. The risk of developing a PEP after laparoscopic salpingostomy was significantly increased (p &lt;0.01) if the preoperative serum beta HCG was greater than 3,000 IU/L. A laparoscopic salpingectomy should be performed in cases where the preoperative beta HCG is above 3,000 IU/L and the contralateral tube appears normal.