Obstetrics and Gynaecology - Research Publications
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ItemDifferential Gene Expression in Menstrual Endometrium From Women With Self-Reported Heavy Menstrual Bleeding(SAGE PUBLICATIONS INC, 2017-01)Heavy menstrual bleeding (HMB) is a significant social and public health issue for menstruating women. Development of targeted treatments has been limited by poor understanding of local mechanisms underlying HMB. We aimed to determine how gene expression differs in menstrual phase endometrium from women with HMB. Menstrual phase endometrial biopsies were collected from women with (n = 7) and without (n = 10) HMB (regular menstrual cycles, no known pelvic pathology), as well as women with uterine fibroids (n = 7, n = 4 had HMB). Biopsies were analyzed using Illumina Sentrix Human HT12 arrays and data analyzed using "Remove Unwanted Variation-inverse". Ingenuity Pathway Analysis and the Database for Annotation, Visualization and Integrated Discovery v6.7 were used to identify gene pathways, functional gene clusters, and upstream regulators specific to the clinical groupings. Individual genes of interest were examined using quantitative polymerase chain reaction. In total, 829 genes were differentially expressed in one or more comparisons. Significant canonical pathways and gene clusters enriched in controls relative to both HMB and fibroid groups suggest the mechanisms responsible for HMB include modifications of the endometrial inflammatory or infection response. In contrast, differentially expressed genes in women with fibroids suggest modifications of hemoglobin, antigen processing, and the major histocompatibility complex (class II, beta chain) activity. In conclusion, HMB associated with fibroids may be regulated by different endometrial mechanisms from HMB in women without fibroids and from normal menstrual bleeding. These novel data provide numerous testable hypotheses that will advance our understanding of the mechanisms responsible for HMB.
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ItemNo Preview AvailableMaternal factors and the risk of birth defects after IVF and ICSI: a whole of population cohort study(WILEY, 2017-09)OBJECTIVE: To assess the contribution of maternal factors to major birth defects after in vitro fertilisation (IVF), intracytoplasmic sperm injection (ICSI), and natural conception. DESIGN: Retrospective cohort study in South Australia for the period January 1986 to December 2002. SETTING: A whole of population study. POPULATION: A census of all IVF and ICSI linked to registries for births, pregnancy terminations, and birth defects (diagnosed before a child's fifth birthday). METHODS: Odds ratios (ORs) for birth defects were calculated among IVF, ICSI, and natural conceptions for maternal age, parity, pre-pregnancy BMI, smoking, pre-existing diseases, and conditions in pregnancy, with adjustment for confounding factors. MAIN OUTCOME MEASURES: Birth defects classified by International Classification of Diseases (ninth revision) and British Paediatric Association (ICD9-BPA) codes. RESULTS: There were 2211 IVF, 1399 ICSI, and 301 060 naturally conceived births. The unadjusted prevalence of any birth defect was 7.1, 9.9, and 5.7% in the IVF, ICSI, and natural conception groups, respectively. As expected, the risk of birth defects increased with maternal age among the natural conceptions. In contrast, for IVF and ICSI combined, relative to natural conceptions, births to women aged ≤29 years had a higher risk (adjusted odds ratio, aOR 1.42; 95% confidence interval, 95% CI 1.04-1.94), births to women aged 35-39 years had no difference in risk (aOR 1.01; 95% CI 0.74-1.37), and births to women aged ≥40 years had a lower risk of defects (aOR 0.45; 95% CI 0.22-0.92). Defects were also elevated for nulliparity, anaemia, and urinary tract infection in births after ICSI, but not after IVF. CONCLUSIONS: The usual age-birth defect relationship is reversed in births after IVF and ICSI, and the associations for other maternal factors and defects vary between IVF and ICSI. TWEETABLE ABSTRACT: Risk of birth defects in women over 40 years is lower after infertility treatment than for natural conceptions.
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ItemManaging menopausal symptoms after breast cancer - A multidisciplinary approach(ELSEVIER IRELAND LTD, 2017-11)More than 6 million women worldwide are living with a past diagnosis of breast cancer. Most survive their illness, and management of the long-term consequences of treatment has become a priority in cancer care. Menopausal symptoms affect most breast cancer survivors and may significantly impair quality of life. We describe a multidisciplinary model to evaluate and manage these women using a patient-focused approach. The 'Multidisciplinary Menopause After Cancer Clinic' includes gynecologists, endocrinologists, GPs, a psychologist and a clinical nurse specialist. Benefits of this model include improved coordination of patient care, education, communication and evidence-based decision making.
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ItemAge at Menarche and Age at First Sexual Intercourse: A Prospective Cohort Study(AMER ACAD PEDIATRICS, 2013-12)OBJECTIVE: Younger age at menarche (AAM) may put girls at risk for earlier first sexual intercourse (FSI). Young age at FSI has far-reaching negative outcomes. We describe the longitudinal relationship between AAM and FSI in a large prospective birth cohort. METHODS: AAM was collected from 554 girls from the Western Australia (Raine) Pregnancy Cohort Study, prospectively from age 10 or retrospectively at age 14. Age at FSI was collected at ages 17 and 20. Cox regression models describe likelihood of FSI by age and years since menarche for younger (<12 years) and older (≥14 years) AAM relative to average AAM (12-13 years). RESULTS: Girls with younger AAM and average AAM were equally likely to have FSI by age 16 (adjusted hazard ratio [aHR]: 0.90 [95% confidence interval (CI): 0.60-1.35]). FSI by age 16 was less likely among girls with older AAM than those with average AAM (aHR: 0.35 [95% CI: 0.17-0.72]). Girls with younger AAM had a longer median interval between menarche and FSI than girls with average AAM (5.0 years [interquartile range: 4.4-8.5 years] vs 3.7 years [interquartile range: 2.4-5.3 years]). Those with younger AAM were less likely to report FSI within 4 years of menarche than those with average AAM (0-2 years aHR: 0.04 [95% CI: 0.01-0.31]; 2-4 years aHR: 0.36 [95% CI: 0.23-0.55]). By age 20, 429 girls (77.4%) reported FSI. CONCLUSIONS: Younger AAM was not a risk factor for younger age at FSI in this cohort.
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ItemNo Preview AvailableVasomotor Symptoms, Sexual Function, and Quality of Life After Breast Cancer: The Impact of Chemotherapy.(SAGE PUBLICATIONS INC, 2015-03)
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ItemFixed or Rotating Night Shift Work Undertaken by Women: Implications for Fertility and Miscarriage(THIEME MEDICAL PUBL INC, 2016-03)This review summarizes the evidence concerning effects of night shift work on women's reproductive health, specifically difficulty in conceiving and miscarriage. We distinguish between fixed night shift and rotating night shift, as the population subgroups exposed, the social and biological mechanisms, and the magnitude of effects are likely to differ; of note, women working fixed night shift are known to have high tolerance for this schedule. We identified two relevant systematic reviews with meta-analyses and five additional studies. Night shift work may give rise to menstrual cycle disturbances, but effect sizes are imprecise. Endometriosis may be elevated in night shift workers, but evidence is only preliminary. Adequate data are lacking to assess associations between night shift work and infertility or time to pregnancy. The weight of evidence begins to point to working at night, whether in fixed or rotating shifts, as a risk factor for miscarriage. There are many methodological problems with this literature, with substantial variation in the definitions of night shift and schedule types making comparisons between studies difficult and pooling across studies questionable. Nevertheless, there appears to be grounds for caution and counselling where women have concerns about night shift work and their reproductive health.
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ItemMechanisms of HIV Transmission in Depo-Provera Users: The Likely Role of Hypoestrogenism(LIPPINCOTT WILLIAMS & WILKINS, 2016-01-01)Almost half of new HIV infections worldwide occur in women, and vaginal intercourse is the most common mode of transmission. Accumulating evidence suggests that depot medroxyprogesterone acetate may increase HIV transmission, but little is known about the underlying mechanisms. We propose that hypoestrogenism in depot medroxyprogesterone acetate may contribute to increased HIV transmission. We present supportive evidence and propose potential interventions to prevent or treat vaginal hypoestrogenism using vaginal estrogens.
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ItemNature and severity of menopausal symptoms and their impact on quality of life and sexual function in cancer survivors compared with women without a cancer history(LIPPINCOTT WILLIAMS & WILKINS, 2014-03)OBJECTIVE: After cancer treatment, troublesome menopausal symptoms are common but poorly understood. Using standardized instruments, we measured differences in symptom nature, severity, impact on quality of life, and sexual function between cancer survivors and noncancer participants. METHODS: The Menopause Symptoms After Cancer Clinic operates within the general menopause service in a large women's hospital, providing menopause advice and management to women with menopausal symptoms and a cancer history. Menopausal symptoms were recorded using the Greene Climacteric Scale, past-week symptoms were recorded using the Functional Assessment of Cancer Therapy breast cancer subscale and endocrine symptom subscale, and sexual symptoms were recorded using Fallowfield's Sexual Activity Questionnaire. RESULTS: Cancer survivors (n = 934) and noncancer participants (n = 155) did not significantly differ by age at menopause (46 y) or age at first clinic visit (51 y). Cancer survivors were more likely than noncancer participants to be severely troubled by vasomotor symptoms (hot flushes and night sweats; odds ratio, 1.71; 95% CI, 1.06-2.74) and reported more frequent (6.0 vs 3.1 in 24 h; P < 0.001) and more severe (P = 0.008) hot flushes. In contrast, cancer survivors were significantly less troubled by psychological and somatic symptoms and reported better quality of life than noncancer participants. Groups did not differ significantly in physical or functional well-being, gynecologic symptom severity, or sexual function. CONCLUSIONS: Cancer survivors are more troubled by vasomotor symptoms than noncancer participants, but noncancer participants report greater psychological symptoms. Sexual function does not differ. An improved understanding of the nature and impact of menopause on cancer survivors can be used to direct management protocols.
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ItemNo Preview AvailableHow does adjuvant chemotherapy affect menopausal symptoms, sexual function, and quality of life after breast cancer?(LIPPINCOTT WILLIAMS & WILKINS, 2016-09)OBJECTIVE: The aim of the study was to determine the association between adjuvant chemotherapy for breast cancer and menopausal symptoms, sexual function, and quality of life. METHODS: Participants attended a menopause clinic with a dedicated service for cancer survivors at a large tertiary women's hospital. Information about breast cancer treatments including adjuvant chemotherapy was collected from medical records. Menopausal symptoms were recorded with the Greene Climacteric Scale and Functional Assessment of Cancer Therapy, Breast Cancer, and Endocrine Symptom Subscales. Sexual symptoms were recorded using Fallowfield's Sexual Activity Questionnaire. Quality of life was measured with Functional Assessment of Cancer Therapy scales. RESULTS: The severity of vasomotor, psychological, or sexual symptoms (apart from pain) did not differ between those who had received adjuvant chemotherapy (n = 339) and other breast cancer survivors (n = 465). After adjustment for current age, time since menopause, and current use of antiestrogen endocrine therapy, the risk of "severe pain" with sexual intercourse was twice as common after chemotherapy (31.6% vs 20.0%, odds ratio [OR] 2.18, 95% CI 1.25-3.79). Those treated with chemotherapy were more likely to report "severe problems" with physical well-being (OR 1.92, 95% CI 1.12-3.28) and lower breast cancer-specific quality of life (OR 1.89 95% CI 1.13-3.18), but did not differ in other quality of life measures. CONCLUSIONS: In this large study of breast cancer patients presenting to a specialty menopause clinic, previous chemotherapy was not associated with current vasomotor or psychological symptoms. Severe pain with intercourse was significantly more common in those treated with adjuvant chemotherapy.