Obstetrics and Gynaecology - Research Publications

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    Ethical issues associated with prenatal screening using non-invasive prenatal testing for sex chromosome aneuploidy
    Johnston, M ; Warton, C ; Pertile, MD ; Taylor-Sands, M ; Delatycki, MB ; Hui, L ; Savulescu, J ; Mills, C (WILEY, 2022-08-27)
    Prenatal screening for sex chromosome aneuploidies (SCAs) is increasingly available through expanded non-invasive prenatal testing (NIPT). NIPT for SCAs raises complex ethical issues for clinical providers, prospective parents and future children. This paper discusses the ethical issues that arise around NIPT for SCAs and current guidelines and protocols for management. The first section outlines current practice and the limitations of NIPT for SCAs. It then outlines key guidelines before discussing the ethical issues raised by this use of NIPT. We conclude that while screening for SCAs should be made available for people seeking to use NIPT, its implementation requires careful consideration of what, when and how information is provided to users.
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    Medical termination of pregnancy for fetal anomaly at or beyond 20 weeks' gestation-What are the maternal risks?
    Stewart, B ; Kane, SC ; Unterscheider, J (WILEY, 2022-10-02)
    OBJECTIVE: To evaluate the common and severe maternal morbidities associated with medical termination of pregnancy (MTOP) for fetal anomaly ≥20 weeks' gestation. METHODS: A 10-year retrospective cohort study (January 2010-December 2019) analyzing 407 consecutive singleton pregnancies MTOP for fetal anomaly ≥20 weeks' gestation, at a quaternary maternity centre in Australia (Royal Women's Hospital, Melbourne). RESULTS: The cohort comprised of 191 primiparous and 216 multiparous women, of whom 75 (34.7%) had at least one prior Cesarean; 13 women had a low-lying placenta or placenta praevia. The average gestation was 23 weeks (interquartile range 22-26 weeks). A spontaneous unassisted vaginal delivery was achieved by the majority (n = 403, 99.0%). The most common maternal morbidities were transferred to the theater for manual removal of retained placental tissue (n = 65, 16.0%) and postpartum haemorrhage (PPH) (n = 45, 11.1%). Severe maternal morbidity occurred in six cases (1.3%) and included amniotic fluid embolism, cardiac arrest, major obstetric haemorrhage, uterine rupture and intensive care unit admission. There were no maternal deaths. CONCLUSIONS: The most common complications of MTOP for fetal anomaly ≥20 weeks' gestation were manual removal of placenta and PPH. Severe maternal morbidity affected 1 in 81 women.
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    Molecular and clinical predictors of improvement in progression-free survival with maintenance PARP inhibitor therapy in women with platinum-sensitive, recurrent ovarian cancer: A meta-analysis
    Lee, CK ; Friedlander, ML ; Tjokrowidjaja, A ; Ledermann, JA ; Coleman, RL ; Mirza, MR ; Matulonis, UA ; Pujade-Lauraine, E ; Bloomfield, R ; Goble, S ; Wang, P ; Glasspool, RM ; Scott, CL (WILEY, 2021-07-15)
    BACKGROUND: The authors performed a meta-analysis to better quantify the benefit of maintenance poly(ADP-ribose) polymerase inhibitor (PARPi) therapy to inform practice in platinum-sensitive, recurrent, high-grade ovarian cancer for patient subsets with the following characteristics: germline BRCA mutation (gBRCAm), somatic BRCA mutation (sBRCAm), wild-type BRCA but homologous recombinant-deficient (HRD), homologous recombinant-proficient (HRP), and baseline clinical prognostic characteristics. METHODS: Randomized trials comparing a PARPi versus placebo as maintenance treatment were identified from electronic databases. Treatment estimates of progression-free survival were pooled across trials using the inverse variance weighted method. RESULTS: Four trials included 972 patients who received a PARPi (olaparib, 31%; niraparib, 35%; or rucaparib, 34%) and 530 patients who received placebo. For patients who had germline BRCA1 mutation (gBRCAm1) (N = 471), the hazard ratio (HR) was 0.29 (95% CI, 0.23-0.37); for those who had germline BRCA2 mutation (gBRCAm2) (N = 236), the HR was 0.26 (95% CI, 0.17-0.39); and, for those who had sBRCAm (N = 123), the HR was 0.22 (95% CI, 0.12-0.41). The treatment effect was similar between the gBRCAm and sBRCAm subsets (P = .48). In patients who had wild-type BRCA HRD tumors (excluding sBRCAm; N = 309), the HR was 0.41 (95% CI, 0.31-0.56); and, in those who had wild-type BRCA HRP tumors (N = 346), the HR was 0.64 (95% CI, 0.49-0.83). The relative treatment effect was greater for the BRCAm versus HRD (P = .03), BRCAm versus HRP (P < .00001), and HRD versus HRP (P < .00001) subsets. There was no difference in benefit based on age, response after recent chemotherapy, and prior bevacizumab. CONCLUSIONS: In platinum-sensitive, recurrent, high-grade ovarian cancer, maintenance PARPi improves progression-free survival for all patient subsets. PARPi therapy has a similar magnitude of benefit for sBRCAm and gBRCAm. Although patients with BRCAm derive the greatest benefit, the absence of a BRCAm or HRD could not be used to exclude patients from maintenance PARPi therapy.
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    Determining a threshold measurement of endometrial thickness for asymptomatic postmenopausal women: A tertiary centre case series
    Stewart, A ; Gill, G ; Readman, E ; Grover, SR ; Mooney, SS (WILEY, 2022-08-21)
    BACKGROUND: An incidental finding of a thickened endometrium on ultrasound in the postmenopausal patient without bleeding is a common presentation to gynaecological services; however there is limited evidence to guide clinical practice as to when hysteroscopic evaluation and endometrial sampling is required. AIMS: To determine the endometrial thickness at which endometrial sampling is indicated in asymptomatic postmenopausal women referred with thickened endometrium on ultrasound. MATERIALS AND METHODS: A single-centre retrospective case series of postmenopausal women without bleeding undergoing hysteroscopy was conducted. Logistic regression was used to examine the association between a range of variables and pre-malignant or malignant pathology and endometrial thickness. The optimal endometrial thickness threshold was identified to maximise model sensitivity. RESULTS: A total of 404 postmenopausal women were included in this study, having undergone a hysteroscopy at the study site between 1 July 2008 and 30 June 2018. The mean (SD) age of patients at presentation was 65 (9.09) years and the mean body mass index was 29.86 kg/m2 (6.52). Of these women, nine (2.2%) were diagnosed with endometrial carcinoma and seven (1.7%) had endometrial hyperplasia with atypia. The most common histopathological finding was of a benign endometrial polyp (153: 37.9%). When including hyperplasia with or without atypia in histopathology of interest, a cut-off of ≥9 mm provides the greatest sensitivity (83.3%) and specificity (63.8%) for a diagnosis of pre-malignant or malignant pathology (classification accuracy of 64.8%; area under the receiver operating characteristic: 0.7358, 95% CI: 0.6439, 0.8278) in this cohort. CONCLUSIONS: Using an endometrial thickness of ≥9 mm can be used as a cut-off for endometrial sampling in postmenopausal women without bleeding.
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    Risk factors for pre-eclampsia: Received wisdom versus reality
    Kane, SC ; Costa, FDS (WILEY, 2022-11-22)
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    Virtual clinics in gynaecology - Can we shorten the wait? A randomised controlled trial implementing a novel care pathway for postmenopausal bleeding
    Mooney, SS ; Gill, GK ; Readman, E (WILEY, 2022-10)
    BACKGROUND: Postmenopausal bleeding (PMB), a common symptom of endometrial cancer, necessitates prompt clinical and sonographic assessment, often followed by hysteroscopy. Unfortunately, due to traditional gynaecology outpatient clinic paradigms, unnecessary patient-clinician encounters are common and may lead to delays in diagnosis. AIM: The aim was to assess a novel clinic model for the management of women with PMB based on virtual assessment and routine use of the outpatient hysteroscopy clinic. METHODS: An unblinded pragmatic randomised controlled trial was performed, comparing a 'virtual clinic' to routine outpatient clinical care. The primary outcome for assessment was time, measured as the interval (days) between referral triage and discharge for definitive management or to the general practitioner. Demographical and clinical data were collected. After discharge from the system, patients completed a satisfaction and feedback questionnaire. Log-rank tests were used to compare the equality of time-to-event functions across randomised groups. RESULTS: There were 96 participants, 46 in the intervention arm and 50 controls. The total time spent in the gynaecology system differed between groups (Χ2 (1) = 6.94, P = 0.008), with a median total time of 55 days (95% confidence interval (CI): 37-66 days) for the intervention group compared to a median of 84 days (95% CI: 54-101 days) for the control group. The number of in-person gynaecology encounters differed between those randomised to intervention (P < 0.001). Overall, 96% of respondents indicated a positive score for overall satisfaction. CONCLUSIONS: The proposed clinic model resulted in a significant reduction in the time between referral and discharge, without compromising patient satisfaction.
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    The 5-minute Apgar score and childhood school outcomes
    Selvaratnam, RJ ; Wallace, EM ; Davis, PG ; Rolnik, DL ; Fahey, M ; Davey, M-A (WILEY, 2022-10)
    AIM: To examine the association between Apgar score at 5 min and childhood developmental and educational outcome. METHODS: A population-based data linkage study of births ≥37 weeks' gestation linked to developmental outcomes at preparatory school and educational outcomes at school grades 3, 5 and 7 in Victoria, Australia. Multivariable logistic regressions and generalised estimating equations were used. RESULTS: There were 167,126 singleton infants with developmental results and 392,933 singleton infants with at least one educational result. There was an inverse relationship between Apgar score at 5 min and poor developmental and educational outcomes, with the worst outcomes among Apgar scores of 0-3. Apgar scores of 7, 8 and 9 were all associated with poorer developmental outcomes (aOR = 1.31, 95% CI: 1.12-1.54; aOR = 1.17, 95% CI: 1.05-1.29; aOR = 1.08, 95% CI: 1.02-1.13 respectively), while Apgar scores of 7 and 8 were associated with poorer educational outcomes at grades 3, 5, and 7. With progression through grades 3, 5, and 7, the extent of the difference in educational outcomes diminished (e.g. for Apgar scores of 0-3: aOR = 3.33, 95% CI: 1.85-6.00 in grade 3 and aOR = 1.49, 95% CI: 0.75-2.96 in grade 7). CONCLUSION: Apgar scores below 10 at 5 min are associated with poorer developmental and educational outcomes in school.
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    Medical management of secondary postpartum haemorrhage: A prospective cohort study
    Fox, R ; Anderson, J ; Young, N ; Davis, L ; Cvejic, E ; Mooney, SS (WILEY, 2022-06-14)
    BACKGROUND: Secondary postpartum haemorrhage (PPH) complicates ~1% of pregnancies and can cause serious maternal morbidity. However, evidence guiding optimal management is scarce and often based on case series and expert opinion. AIMS: To measure the success of primary medical therapy in managing secondary PPH and to identify factors associated with need for surgical management. MATERIALS AND METHODS: Postpartum patients presenting to a tertiary women's hospital emergency department between July 2020 and October 2021 with secondary PPH were recruited. Data from the acute presentation were prospectively collected. Antenatal and intrapartum data were collected from medical record review. The primary outcome was the success of medical management for secondary PPH, defined by the implementation of medical or expectant measures without subsequent need for surgical intervention. RESULTS: One-hundred and twenty patients underwent primary medical management for secondary PPH. Ninety-eight (82%) were managed successfully with medical management and 22 (18%) required surgery. Medical management involved misoprostol (n = 33; 27.5%), antibiotics (n = 108; 90%), and less commonly other uterotonics (n = 6; 5%). Factors associated with lower rates of successful medical management included: antecedent manual removal of placenta (MROP) (odds ratio (OR) 0.2, P = 0.047), primary PPH ≥500 mL (OR 0.39, P = 0.048) or ≥1 L (OR 0.24, P = 0.009), >200 mL blood loss at presentation (OR 0.17, P = 0.015), increasing time post-delivery (OR 0.84, P = 0.044), retained products of conception (RPOC) on ultrasound (OR 0.024, P = 0.001) and vaginal birth (OR 0.27, P = 0.027). CONCLUSION: Medical management was highly successful. Vaginal birth, MROP, primary PPH, RPOC on ultrasound and increasing time post-delivery were associated with increased need for surgical management.
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    Respiratory outcomes in preterm babies: Is bronchopulmonary dysplasia important?
    Barrington, KJ ; Church, PT ; Luu, TM ; Davis, PG (WILEY, 2022-09)