Department of Obstetrics & Gynaecology
April 9, 2021
|8:40||Land Acknowledgment||Dr. Jennifer McCall|
|Opening Remarks||Dr. Graeme Smith|
Moderator: Dr. Maria Velez
|Room 1: Basic Science||Moderator: Dr. Samantha Benton|
|Room 2: Clinical Science I||Moderator: Dr. Olga Bougie|
|Room 3: Clinical Science II||Moderator: Dr. Maha Othman|
|11:00||Keynote Address||Dr. Maria B. Ospina|
|11:55||Closing Remarks||Dr. Maria Velez|
Main Room [Oral Presentations and Keynote]
Meeting ID: 989 9411 5414
Find your local number: https://queensu.zoom.us/u/acTUCSxSlm
Poster Session Room 1
Meeting ID: 967 1846 0816
Find your local number: https://queensu.zoom.us/u/addHsKkQcd
Poster Session Room 2
Meeting ID: 979 3281 3791
Find your local number: https://queensu.zoom.us/u/aWA4ukBbE
Poster Session Room 3
Meeting ID: 946 4022 5844
Find your local number: https://queensu.zoom.us/u/awjukPqBe
Full Program for Download [PDF]
Dr. Maria B. Ospina, MSc, PhD
Ehawawisit (With Child): A Mixed-Methods Evaluation of Maternal and Perinatal Health among the Métis in Alberta?
Dr. Maria Ospina is an assistant professor with the Department of Obstetrics & Gynecology, a clinical epidemiologist, and population health researcher. She is a Canada Research Chair in Life Course, Social Environments and Health and member of the Women and Children’s Health Research Institute. She has developed an innovative multidisciplinary translational research program to understand how the first 1,000 days of human life influence future health: DMETRE (Developmental Maternal and perinatal Epidemiology and Translational Research Evidence: Data, Birth, Babies + Beyond). DMETRE is based on a knowledge-to-action approach in which epidemiological methods are applied to produce maternal and perinatal epidemiological knowledge in relation to three main themes:
- Developmental Trajectories of Chronic Diseases
- Pathways of Inequalities in Maternal and Perinatal Health
- Synthesis of Maternal and Perinatal Research Evidence
Her work is supported by the Canadian Institutes of Health Research, PolicyWise for Children and Families, the Lung Association, the Alberta Health Services Strategic Clinical Network, and through the generosity of the Alberta Women’s Health Foundation through the Women and Children’s Health Research Institute.
AUTHORS: Jessica N Blom (R2),1 Maria P Velez,1,2 Chad McClintock,2 Jessica Pudwell,1 Susan Brogly,2,3 Olga Bougie.1
1Dept OBGYN, Queen’s University, Kingston Health Sciences Centre, Kingston, ON, Canada;
2ICES Queen’s, Kingston, ON, Canada;
3Dept Surgery, Queen’s University, Kingston, ON, Canada
INTRODUCTION: Although cardiovascular disease (CVD) remains the leading cause of premature death in women worldwide, screening, diagnosis and treatment strategies were developed based on the male CVD experience. Female specific risk factors for CVD must be identified to improve patient outcomes. Endometriosis affects up to 10% of the female population, and may increase one’s risk for CVD through chronic inflammation and early menopause. The OBJECTIVE of this study was to determine the association between a diagnosis of endometriosis and subsequent risk of CVD.
METHODS: We conducted a population-based cohort study using administrative health data from ICES in Ontario. The incidence of CVD and cardiovascular health outcomes was compared between women with endometriosis (exposed) and 2 age-matched women without endometriosis (unexposed) from 1993-2015 who were 18-50 years old upon enrollment. Women were considered to have endometriosis if they had a confirmed surgical diagnosis at any time (ICD9-617, ICD10-N80), or if they had 2 codes indicating a medical diagnosis (OHIP dx617). Exclusion criteria included CVD parameters at baseline. The primary outcome was composite hospitalizations due to CVD events. Secondary outcomes included composite CVD events of interest. Outcomes were based on previously validated composites. Cox-proportional hazards models were used to estimate hazard ratios (HR) by endometriosis status while adjusting for sociodemographic and prior health factors.
RESULTS: A total of 500,559 patients were enrolled in the study (166,853 exposed and 333,706 unexposed). Average age of enrollment was 36.4 years for both groups. Women with endometriosis had a higher incidence of hospitalization for CVD (197 cases / 100,000 person-years) as compared to unexposed (164 cases / 100,000 person-years) and a significantly reduced time to event (HR 1.16; 95% CI 1.11-1.20; p<0.001). Similarly, the incidence of secondary CVD events was higher in the exposed group (292 cases / 100,000 person-years) as compared to unexposed (224 cases / 100,000 person-years) and the time to event was reduced (HR 1.25; 95% CI 1.21-1.29; p<0.001).
CONCLUSION: This is the first population-based study to examine the association between endometriosis and CVD. Our results indicate that endometriosis may be a risk factor for the development of premature CVD. Further studies will need to be conducted to elucidate the potential mechanism, including the mediating role of surgical menopause.
AUTHORS: Hossai Furmli (PGY2), Jessica Pudwell, Rebecca Griffiths, Michael Green, Maria Velez.
Queen’s University Department of Family Medicine, Department of Obstetrics and Gynecology.
Objective: To compare differences in the proportion of infertility diagnoses, contraception use and therapeutic abortion among refugee, non-refugee and Canadian born women.
Study methods: A retrospective matched cohort design was employed using the IC/ES database to assess the outcomes of interest. A total of 59 259 refugee women and 382 108 non-refugee immigrant women were identified and matched to two Canadian born controls. Differences in each group was assessed using a standardized difference calculation. Conditional Poisson regression was then used to calculate the relative risk of each reproductive health outcome based on immigration exposure after controlling for age, income quintile, rurality, and year of arrival.
Results: Both refugee and non-refugee immigrant women had decreased rates of contraception counseling and increased rates of infertility diagnoses compared to their Canadian born matches. Refugee women had an increased relative risk of therapeutic abortion (1.82) as well as IUD usage (1.70) compared with their matches.
Conclusion: There is a need to have more advocacy and discussions around contraception use for immigrant women. Further studies are needed to identify specific gaps that can be addressed in education and access to care in relation to reproductive health for this population.
AUTHORS: Anique Le Roux (Meds 2022), Jennifer McCall (R3), Jessica Pudwell, Jamie Pyper, Olga Bougie.
Department of Obstetrics and Gynecology and Queen’s University School of Medicine
Objective: Endometriosis in adolescents is underrecognized and understudied, leading to delayed diagnosis and reduced quality of life. We aimed to appreciate the diagnostic and therapeutic journey of adolescents with endometriosis, including disease presentation, obstacles to diagnosis and management, and the impact of endometriosis on their life.
Study Methods: Women under twenty-eight years with severe dysmenorrhea were included. Participants were identified through a retrospective review of gynecology rosters at Kingston General hospital and invited to complete a questionnaire assembled from the World Endometriosis Research Foundation and the SF36 questionnaire. A mixed study design was utilized. Participants were further invited to complete a semi-structured phone interview. Questionnaire data was analyzed using descriptive statistics. Interviews were coded inductively using the constant comparative analysis method by two analyzers and inter-rater reliability was calculated. Thereafter, both sets of data were compared using a cross-sectional method. The study was approved by the Queen's University Health Sciences and Affiliated Teaching Hospitals Research Ethics Board (HSREB) (approval number #6029585).
Results: We reviewed 23 charts. 23 participants were invited to participate in the study, 8 declined or never responded, 10 participants completed the survey and 5 participated in the interview. Onset of pelvic pain was reported at a mean age of 13.9 years (SD 1.9). Of surveyed participants, 50% identified that they have an endometriosis diagnosis, diagnosed at a mean age of 19.2 years (SD 2.6). Mean dysmenorrhea pain score was 8.3 (SD 1.8) on a 10-point severity scale. 90% reported severe pain requiring bed rest and medication. When experiencing pelvic pain, 90% of participants reported dyspareunia. Initial presentation to health care was through an emergency department visit for the majority (16/23) of patients. Mean age of interview participants was 23.6 (SD 2.61). Thematic analysis of patient interviews revealed three major themes: (1) endometriosis broadly impacts all aspects of an individual’s life, (2) systemic unawareness and misunderstanding regarding endometriosis and women’s health, especially in adolescents, by both health care providers and the public create delays for diagnosis and therapy, and (3) and the journey with disease begins long before diagnosis and creates a culture of self-directed care.
Conclusions: Adolescents with endometriosis encounter multiple obstacles. From our analysis, patients with endometriosis present with symptoms at a young age and often self-manage before receiving a formal diagnosis. Quality of life is reduced in all aspects of a person’s life. There is a delay in diagnosis due to a knowledge translation gap with awareness and understanding regarding female reproductive health.
Funding: Queen’s University Department of Obstetrics and Gynecology
AUTHORS: *Noor Shakfa, Elizabeth Lightbody, Deyang Li, Juliette Wilson-Sanchez, Gwenaelle Conseil, Afrakoma Afriyie-Asante, Stephen Chenard, Ali Hamade, Madhuri Koti
*PhD Candidate, Department of Biomedical and Molecular Science
Background & Objective: Ovarian cancer is the most lethal gynaecologic malignancy, accounting for ~152,000 deaths globally each year. High-grade serous ovarian carcinoma (HGSC) is the most common subtype, with a 5-year survival rate of 45%. Although most patients show initial response to treatment, over 70% of cases will relapse due to developed chemotherapy resistance. Our work aims to counter the chemoresistance seen in HGSC patients via immune sensitization. Previous studies from our group have demonstrated the variable tumor immune microenvironment states that associate with platinum chemotherapy response. We further showed the significance of the interferon (IFN) induced chemokine CXCL10 as a key mediator of tumor infiltrating immune cell recruitment. Using the ID8-Trp53−/− murine model of HGSC, we demonstrated the potential of Stimulator of Interferon Genes (STING) pathway activation in enhancing response of HGSC tumors to carboplatin chemotherapy and sensitizing them to immune checkpoint blockade therapy through a heightened type 1 IFN response. CXCL10 production via IFN1 is also governed by genes that regulate cellular DNA damage repair pathways. Evolving evidence indicates a role of BRCA1 and PTEN genes in mediating cellular IFN1 responses. Losses in the function of these genes is widely prevalent in a large proportion of HGSC tumors, where tumors with BRCA1 mutations (~25% of HGSC cases) have higher CD8+ T cell infiltration in contrast to those with loss of PTEN (~10% of cases). We hypothesized that HGSC tumors with loss of PTEN expression can be rendered susceptible to immune mediated killing via activating the STING pathway.
Study Methods: TIME of tumors generated from ID8 Trp53-/-; Brca1-/- cells and those from ID8 Trp53-/-; Pten-/- cells were characterized. The response of these distinct cells (in vitro), and tumors (in vivo) to combination carboplatin and STING agonist therapy was determined. Local and systemic immune responses post-treatment were measured using our immune profiling protocols.
Results: Tumors generated from ID8-Trp53−/−; Brca1−/− cells and those from ID8-Trp53−/−; Pten−/− cells in C57BL6 mice showed significant immunologic differences through local and systemic immune profiling. The addition of STING agonist treatment significantly increased chemosensitivity and improved overall response in mice implanted with ID8-Trp53−/−; Pten−/− cells compared to those treated with carboplatin alone, altering immune responses.
Conclusion: This study is foundational to inform rational combinations of STING pathway activating therapies in HGSC, augmenting responses to existing chemotherapy regimens and prolonging survival rates in patients.
Funding Sources: Canadian Institutes of Cancer Research & Ontario Ministry of Research and Innovation Early Researcher Award.
AUTHORS: Aline Atallah (MSc), Takafumi Ushida, Nicole Protopapas, Shannyn Macdonald-Goodfellow, Charles Graham and Tiziana Cotechini
Objectives: Children born to women who experience pre-eclampsia are at increased risk of developing cardiovascular (CV) and metabolic disease in adult life, while daughters experience an increased risk of developing pregnancy complications themselves. Though aberrant maternal inflammation contributes to the pathophysiology of pregnancy complications, its generational impact on the development and persistence of risk factors for CV and metabolic disease and pregnancy outcomes in offspring remains unclear. Using a rat model of inflammation-induced pregnancy complications, we examined whether aberrant inflammation in pregnancy leads to the development of known CV and metabolic disease risk factors in offspring, and whether female offspring develop pregnancy complications during their reproductive life.
Methods: Pregnant Wistar rats (F0 generation) were administered low-dose lipopolysaccharide (LPS; 10-40ug/kg) or saline on gestational days 13.5-16.5 and allowed to deliver F1 offspring. Cardiovascular and metabolic parameters were evaluated in F1 offspring at 24-weeks of age using glucose tolerance test and cardiac growth-related gene expression. To evaluate the generational effect of pregnancy complications, F1 females were mated to non-experimental male rats. F1 dams were sacrificed on gestational day 17.5 and fetal weights of the F2 generation were assessed. Placentas from the F2 generation were processed for immunohistochemistry to assess the expression of the glucose transporter, GLUT1.
Results: F1 offspring born to LPS-treated dams exhibited increased cardiac growth-related gene expression and abnormal glucose metabolism compared with F1 offspring born to saline-treated dams. Weights of F2 fetuses from LPS-treated grandmothers were significantly reduced compared with weights of F2 fetuses from saline-treated control grandmothers. Compared with controls, F2 fetuses from LPS-treated grandmothers displayed reduced GLUT1 immunoreactivity in the labyrinth zone of the placenta.
Conclusion: Abnormal maternal inflammation may contribute to increased risk of CV and metabolic disease in affected offspring. Moreover, our data provide evidence of a generation impact of pregnancy complications in subsequent generations, which may be mediated by impaired glucose transport to the neonate. Management of inflammation during pregnancy may be an important strategy to prevent pregnancy complications and their transgenerational effects.
Funding source: CIHR
AUTHORS: Jean-François Paré (Research Associate), Kira King, Graeme N. Smith, and Charles H. Graham
Department of Biomedical and Molecular Sciences and Obstetrics and Gynaecology, Queen’s University
Aberrant inflammation has an important role in the pathophysiology of pregnancy complications and could contribute to the subsequent increased risk of metabolic diseases in the mother. We are investigating the role of trained immunity, a.k.a. innate-immune memory, in the hyper-inflammatory status of patients with pregnancy complications, more specifically the contribution of monocytes. We purified classical monocytes from third-trimester maternal blood and at six months post-delivery from patients with normal pregnancy, preeclampsia (PE), or intra-uterine growth restriction (IUGR). To evaluate the acquisition of trained immunity in these cells, we quantified their release of pro-inflammatory cytokines following exposure to a heterologous stimulus, lipopolysaccharide (LPS). We also investigated the epigenetic changes associated with pregnancy complications by quantifying chromatin accessibility at promoter regions of pro-inflammatory genes. We found that, in patients with pregnancy complications, the release of pro-inflammatory cytokines from classical monocytes was dampened when compared with monocytes from patients with normal pregnancy. We also found that chromatin accessibility at pro-inflammatory genes was reduced in pregnancy complications cases, as demonstrated by lower tri-methylation at lysine 4 residue of histone 3 (H3K4me3) at these genomic sites. Moreover, classical monocytes from some mothers who had pregnancy complications remained hypo-responsive six months after delivery. These results indicate that classical monocytes from patients with pregnancy complications may have acquired a tolerance phenotype due to prior hyper-activation, and/or that other subsets of leukocytes (e.g. non-classical monocytes, natural killer (NK) cells) could mediate the inflammation associated with pregnancy complications. Further tests with various stimuli and other leukocytes subsets will help us elucidate the complexity aberrant inflammation associated with pregnancy complications.
Funding source: CIHR