Research Articles (Obstetrics and Gynaecology)

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    Exploring options for the secondary prevention of cervical cancer in South Africa
    (Stellenbosch University, 2024-12) Adams, Robyn Anne; Botha, Matthys Hendrik; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. Obstetrics and Gynaecology.
    ENGLISH ABSTRACT: Cervical cancer stands as a significant global health challenge, impacting millions of women annually. While primary prevention measures like human papilloma virus (HPV) vaccination show promise, the role of secondary prevention, including screening programmes and early detection methods, is paramount. This thesis aims to assess and elucidate the multifaceted nature of secondary prevention strategies for cervical cancer. In Chapter 2, the evolution and current state of cervical cytology in South Africa is discussed, highlighting its successes and systemic challenges. The chapter emphasises the need for robust infrastructure, efficient follow-up systems, and the lessons learned from cytology that can inform the implementation of HPV DNA screening. In Chapter 3, the study findings suggest that visual inspection methods perform better in women living with HIV (WLWH) compared to HIV-negative women. This implies the justification for utilizing visual inspection methods in cervical cancer screening for WLWH. However, it is noted that these methods exhibit satisfactory sensitivity only under rigorous quality assurance measures, which might pose challenges in non-academic settings, potentially leading to over-treatment due to reduced specificity. Chapter 4 explores cervical cancer control guidelines in the Southern African Development Community (SADC) region, highlighting the reliance on visual inspection as a screening method, despite the World Health Organization (WHO) prioritizing HPV deoxyribose nucleic acid (DNA) testing in its guideline of 2021. HPV DNA testing offers high sensitivity and a negative predictive value approaching 100%, reducing the need for frequent follow-up visits and additional tests, thus enhancing cost-effectiveness. However, HPV DNA testing alone may not provide clinically relevant information without a triage test to identify women with clinically significant disease. A pragmatic advantage of HPV testing is its compatibility with triage tests like host-cell DNA methylation assessment, streamlining the diagnostic process and reducing discomfort for individuals undergoing screening. In South Africa, HPV testing is increasingly available, with reflex cytology recommended as the triage test, though molecular biomarkers like DNA methylation show promise for further risk stratification. However, more evidence is needed, particularly in low- and middle-income countries (LMICs), to support their inclusion in screening programmes. Chapter 5 discusses the potential of DNA methylation assays as triage tools, citing studies showing high sensitivity for cervical cancer detection. However, conclusive evidence is lacking, especially in LMICs, necessitating further research and adaptation of methylation assays for cost-effective use. Longitudinal studies focusing on women living with HIV are particularly crucial due to limited existing research. Chapter 6 outlines a study protocol comparing thermal ablation (TA) to large loop excision of the transformation zone (LLETZ) in treating cervical precancer, acknowledging South Africa's human immunodeficiency virus (HIV) burden and high-risk HPV prevalence. Understanding TA's efficacy including treatment failure rates is vital for adopting accessible treatments, considering the context of resource constraints. In summary, secondary prevention of cervical cancer involves a diverse array of strategies, from screening methods to treatment modalities. While HPV DNA testing represents a significant advancement, challenges remain in implementation, especially in LMICs. Further research, particularly on triage methods and treatment efficacy, is essential for improving outcomes, especially in populations disproportionately affected by cervical cancer.
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    HIV prevalence in patients with cervical carcinoma : a cohort study at a secondary hospital in South Africa
    (Wolter Kluwer Health, 2021) Mohosho, Mokoena Martins
    The Human Immunodeficiency Virus (HIV) seropositive prevalence among women with cervical cancer varies in different parts of the world and even within a country. This study aimed to document the prevalence of HIV infection in women with newly diagnosed cervical cancer at a secondary hospital in South Africa. This study is a retrospective review of records of 89 women who were newly diagnosed with cervical cancer between 01 June 2010 and 31 May 2013 at Pelonomi Hospital, Mangaung, South Africa. Data such as age, parity, gravidity, marital status, occupation, HIV status, CD4 count, on anti-retroviral treatment, clinical stage of disease were retrieved from the case files, the Meditech-patient record and Disa laboratory system. Data analysis was done using the SAS statistical package. HIV-seropositive prevalence was 52.4%, with the highest prevalence (91.3%) in the age group 40 years and younger. In HIV-positive women, the mean CD4 cell count was 280 cell/mm3 and 43% of them were not on anti-retroviral treatment. The majority (86%) of all patients presented with late stage disease (International Federation of Gynecology and Obstetrics Stage III and IV) when newly diagnosed with cervical cancer. This study highlights high HIV-seropositive prevalence; severe immunosuppression and late presentation of the disease in women newly diagnosed with cervical cancer. Cervical cancer screening programs need to be fully reinforced into existing HIV health care services to allow for ideal prevention and early detection of the disease. Anti-retroviral treatment needs to be prioritized for HIV-positive women.
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    PROVE—Pre-Eclampsia Obstetric Adverse Events: Establishment of a Biobank and Database for Pre-Eclampsia
    (MDPI, 2021-04) Bergman, Lina; Bergman, Karl; Langenegger, Eduard; Moodley, Ashley; Griffith-Richards, Stephanie; Wikström, Johan; Hall, David; Joubert, Lloyd; Herbst, Philip; Schell, Sonja; Van Veen, Teelkien; Belfort, Michael; Tong, Stephen Y. C.; Walker, Susan; Hastie, Roxanne; Cluver, Catherine
    Pre-eclampsia is a leading cause of maternal and perinatal morbidity and mortality. The burden of disease lies mainly in low-middle income countries. The aim of this project is to establish a pre-eclampsia biobank in South Africa to facilitate research in the field of pre-eclampsia with a focus on phenotyping severe disease.The approach of our biobank is to collect biological specimens, detailed clinical data, tests, and biophysical examinations, including magnetic resonance imaging (MRI) of the brain, MRI of the heart, transcranial Doppler, echocardiography, and cognitive function tests.Women diagnosed with pre-eclampsia and normotensive controls are enrolled in the biobank at admission to Tygerberg University Hospital (Cape Town, South Africa). Biological samples and clinical data are collected at inclusion/delivery and during the hospital stay. Special investigations as per above are performed in a subset of women. After two months, women are followed up by telephonic interviews. This project aims to establish a biobank and database for severe organ complications of pre-eclampsia in a low-middle income country where the incidence of pre-eclampsia with organ complications is high. The study integrates different methods to investigate pre-eclampsia, focusing on improved understanding of pathophysiology, prediction of organ complications, and potentially future drug evaluation and discovery.
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    Effects of Prenatal Exposure to Alcohol and Smoking on Fetal Heart Rate and Movement Regulation
    (Frontiers Media, 2021-07) Lucchini, Maristella; Shuffrey, Lauren C.; Nugent, J. David; Pini, Nicoló; Sania, Ayesha; Shair, Margaret; Brink, Lucy; Du Plessis, Carlie; Odendaal, Hein J.; Nelson, Morgan E.; Friedrich, Christa; Angal, Jyoti; Elliott, Amy J.; Groenewald, Coen A.; Burd, Larry T.; Myers, Michael M.; Fifer, William P.
    egative associations of prenatal tobacco and alcohol exposure (PTE and PAE) on birth outcomes and childhood development have been well documented, but less is known about underlying mechanisms. A possible pathway for the adverse fetal outcomes associated with PTE and PAE is the alteration of fetal autonomic nervous system development. This study assessed PTE and PAE effects on measures of fetal autonomic regulation, as quantified by heart rate (HR), heart rate variability (SD-HR), movement, and HR-movement coupling in a population of fetuses at ≥ 34 weeks gestational age. Participants are a subset of the Safe Passage Study, a prospective cohort study that enrolled pregnant women from clinical sites in Cape Town, South Africa, and the Northern Plains region, United States. PAE was defined by six levels: no alcohol, low quit early, high quit early, low continuous, moderate continuous, and high continuous; while PTE by 4 levels: no smoking, quit early, low continuous, and moderate/high continuous. Linear regression analyses of autonomic measures were employed controlling for fetal sex, gestational age at assessment, site, maternal education, household crowding, and depression. Analyses were also stratified by sleep state (1F and 2F) and site (South Africa, N = 4025, Northern Plains, N = 2466). The final sample included 6491 maternal-fetal-dyad assessed in the third trimester [35.21 ± 1.26 (mean ± SD) weeks gestation]. PTE was associated with a decrease in mean HR in state 2F, in a dose dependent fashion, only for fetuses of mothers who continued smoking after the first trimester. In state 1F, there was a significant increase in mean HR in fetuses whose mother quit during the first trimester. This effect was driven by the Norther Plains cohort. PTE was also associated with a significant reduction in fetal movement in the most highly exposed group. In South Africa a significant increase in mean HR both for the high quit early and the high continuous group was observed. In conclusion, this investigation addresses a critical knowledge gap regarding the relationship between PTE and PAE and fetal autonomic regulation. We believe these results can contribute to elucidating mechanisms underlying risk for adverse outcomes.
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    Diagnosis and treatment of vulvo-perineal endometriosis: a systematic review
    (Frontiers Media S.A, 2021-05) Maillard, Charlotte; Alami, Zineb Cherif; Squifflet, Jean-Luc; Luyckx, Mathieu; Jadoul, Pascale; Thomas, Viju; Wyns, Christine
    Objective: To describe the available knowledge on vulvo-perineal endometriosis including its diagnosis, clinical management and recurrence rate. Methods: We followed the PRISMA guidelines for Systematic Reviews and our study was prospectively registered with PROSPERO (CRD42020202441). The terms “Endometriosis” and “Perineum” or “Vulva” were used as keywords. Cochrane Library, Medline/Pubmed, Embase and Clinicaltrials.gov were searched. Papers in English, Spanish, Portuguese, French or Italian from inception to July 30, 2020 were considered. Reference lists of included articles and other literature source such as Google Scholar were also manually scrutinized in order to identify other relevant studies. Two independent reviewers screened potentially eligible studies according to inclusion criteria. Results: Out of 539 reports, 90 studies were eligible including a total of 283 patients. Their mean age was 32.7 ± 7.6 years. Two hundred sixty-three (95.3%) presenting with vulvo-perineal endometriosis have undergone either episiotomy, perineal trauma or vaginal injury or surgery. Only 13 patients (4.7%) developed vulvo-vaginal endometriosis spontaneously i.e., without any apparent condition favoring it. The reasons that motivated the patients to take medical advice were vulvo-perineal cyclical pain increasing during menstruations (98.2% of the patients, n = 278). Out of the 281 patients for whom a clinical examination was described, 274 patients (97.5%) showed a vulvo-perineal nodule, mass or swelling while six presented with bluish cutaneous lesions (2.1%) and 1 with bilateral polyps of the labia minora (0.4%). All but one patients underwent surgical excision of their lesions but only 88 patients (28.1%) received additional hormonal therapy. The recurrence rate was 10.2% (29 patients) considering a median follow-up period of 10 months (based on 61 studies). Conclusion: In conclusion, vulvo-perineal endometriosis is a rare entity with approximately 300 cases reported in the literature since 1923. With the available knowledge shown in this systematic review, we encourage all practitioners to think about perineal endometriosis in case of perineal cyclical pain with or without previous perineal damage. Diagnosis should be done with clinical exam, perineal ultrasound and pelvic MRI when available. In case of anal sphincter involvement, perianal ultrasound should be performed. Surgical excision of the lesion should be realized in order to remove the lesion and to confirm the diagnosis histologically. Hormonal treatment could be proposed to attempt to decrease the size of a large lesion before surgery or to avoid recurrence of the lesion. As evidence-based approach to the diagnosis, treatment and recurrence rate of affected patients remains a challenge given its low prevalence, the variations in management found in the articles included and the limited quality of available studies, we suggest that a prospective database on vulvo-perineal endometriosis should be generated to increase knowledge but also awareness among healthcare professionals and optimize patients' care. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42020202441.