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      The Potential Role for Host Genetic Profiling in Screening for Chlamydia-Associated Tubal Factor Infertility (TFI)—New Perspectives

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          Abstract

          Host immunogenetic factors can affect late complications of urogenital infections with Chlamydia trachomatis. These findings are creating new avenues for updating existing risk prediction models for C. trachomatis-associated tubal factor infertility (TFI). Research into host factors and its utilization may therefore have future implications for diagnosing C. trachomatis-induced infertility. We outline the epidemiological situation regarding C. trachomatis and TFI in high-income countries. Thereupon, we review the main characteristics of the population undergoing fertility work-up and identify screening and diagnostic strategies for TFI currently in place. The Netherlands is an exemplary model for the state of the art in high-income countries. Within the framework of existing clinical approaches, we propose a scenario for the translation of relevant genome-based information into triage of infertile women, with the objective of implementing genetic profiling in the routine investigation of TFI. Furthermore, we describe the state of the art in relevant gene- and single nucleotide polymorphism (SNP) based clinical prediction models and place our perspectives in the context of these applications. We conclude that the introduction of a genetic test of proven validity into the assessment of TFI should help reduce patient burden from invasive and costly examinations by achieving a more precise risk stratification.

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          Most cited references51

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          Female subfertility.

          With an average monthly fecundity rate of only 20%, human beings are not fertile mammals. 10-15% of couples have difficulties conceiving, or conceiving the number of children they want, and seek specialist fertility care at least once during their reproductive lifetime. Dependent on the two main factors that determine subfertility, duration of childlessness and age of the woman, three questions need to be addressed before treatment is offered. Is it time to start the routine fertility investigation?--ie, has sufficient exposure to the chance of conception taken place? Are cost-effective, safe, and reliable treatments available for the disorder diagnosed? And, should the couple be referred straightaway for assisted reproduction?
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            Chlamydia Trachomatis Infection-Associated Risk of Cervical Cancer

            Abstract As whether Chlamydia trachomatis infection increases the risk of cervical cancer is controversial in the literature, we performed a meta-analysis. Based on a comprehensive search of publications in the Medline, Cochrane, and EMBASE databases, we identified and extracted data from all relevant articles examining C. trachomatis infection and the risk of cervical cancer. The quality of each included study was assessed according to the 9-star Newcastle–Ottawa scale. The strength of association between the C. trachomatis and risk of cervical cancer was estimated by odds ratio (OR) and 95% confidence intervals (CIs). This review was registered at PROSPERO with registration No. CRD42014015672. A total of 22 studies with 4291 cervical cancer cases and 7628 controls were identified. Overall, C. trachomatis was significantly linked to increased cervical cancer risk in prospective studies (OR = 2.21, 95% CI: 1.88–2.61, P < 0.001), as well as in retrospective studies (OR = 2.19, 95% CI: 1.74–2.74, P < 0.001). Additionally, with a multivariate logistic regression analysis adjusted for HPV and age, C. trachomatis infection was identified as an independent predictor of cervical cancer in 11 studies (OR = 1.76, 95% CI: 1.03–3.01, P = 0.04). Coinfection of human papilloma virus and C. trachomatis has a higher risk of cervical cancer (OR = 4.03, 95% CI: 3.15–5.16, P < 0.001). A subgroup analysis based on histological type indicated an elevated risk for both squamous cell carcinoma (OR = 2.21, 95% CI: 2.00–2.45, P < 0.001), and adenocarcinoma (OR = 1.61, 95% CI: 1.21–2.15, P = 0.001), in associated with C. trachomatis. Subgroup analysis by where C. trachomatis infection was detected showed a significantly higher risk of cervical cancer associated with C. trachomatis infection detected in serum (OR = 2.20, 95% CI: 2.01–2.42, P < 0.001), cervical tissue blocks (OR = 2.88, 95% CI: 1.21–6.83, P = 0.02), and cervical secretion (OR = 2.71, 95% CI: 1.41–5.20, P = 0.003), especially in serum with no obvious heterogeneity. In conclusion, our novel data demonstrate that individuals infected with C. trachomatis have a higher risk of cervical cancer. Therefore, it is necessary to expand C. trachomatis infection screening and treat women with C. trachomatis promptly, particularly those with human papilloma virus infections. This approach will not only protect against pelvic inflammatory disease and infertility, but may also prevent cervical cancer.
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              Effectiveness of yearly, register based screening for chlamydia in the Netherlands: controlled trial with randomised stepped wedge implementation

              Objective To evaluate the effectiveness of register based, yearly chlamydia screening. Design Controlled trial with randomised stepped wedge implementation in three blocks. Setting Three regions of the Netherlands: Amsterdam, Rotterdam, and South Limburg. Participants 317 304 women and men aged 16-29 years listed on municipal registers at start of trial. Intervention From March 2008 to February 2011, the Chlamydia Screening Implementation programme offered yearly chlamydia screening tests. Postal invitations asked people to use an internet site to request a kit for self collection of samples, which would then be sent to regional laboratories for testing. Treatment and partner notification were done by the general practitioner or at a sexually transmitted infection clinic. Main outcome measures Primary outcomes were the percentage of chlamydia tests positive (positivity), percentage of invitees returning a specimen (uptake), and estimated chlamydia prevalence. Secondary outcomes were positivity according to sex, age, region, and sociodemographic factors; adherence to screening invitations; and incidence of self reported pelvic inflammatory disease. Results The participation rate was 16.1% (43 358/269 273) after the first invitation, 10.8% after the second, and 9.5% after the third, compared with 13.0% (6223/48 031) in the control block invited at the end of round two of the intervention. Chlamydia positivity in the intervention blocks at the first invitation was the same as in the control block (4.3%) and 0.2% lower at the third invitation (odds ratio 0.96 (95% confidence interval 0.83 to 1.10)). No substantial decreases in positivity were seen after three screening rounds in any region or sociodemographic group. Among the people who participated three times (2.8% of all invitees), positivity fell from 5.9% to 2.9% (odds ratio 0.49 (0.47 to 0.50)). Conclusions There was no statistical evidence of an impact on chlamydia positivity rates or estimated population prevalence from the Chlamydia Screening Implementation programme after three years at the participation levels obtained. The current evidence does not support a national roll out of this register based chlamydia screening programme. Trial registration NTR 3071 (Netherlands Trial Register, www.trialregister.nl).
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                Author and article information

                Journal
                Genes (Basel)
                Genes (Basel)
                genes
                Genes
                MDPI
                2073-4425
                28 May 2019
                June 2019
                : 10
                : 6
                : 410
                Affiliations
                [1 ]Institute of Public Health Genomics, Department of Genetics and Cell Biology, Research Institute GROW, Faculty of Health, Medicine & Life Sciences, University of Maastricht, 6211 LK Maastricht, The Netherlands; jelena.malogajski@ 123456liu.edu (J.M.); ibrankovic80@ 123456gmail.com (I.B.); j.land@ 123456maastrichtuniversity.nl (J.A.L.); j.land@ 123456maastrichtuniversity.nl (P.P.M.T.); samorretravel@ 123456yahoo.co.uk (S.A.M.)
                [2 ]Department of Public Health, School of Health Professions, Long Island University–Brooklyn, Brooklyn, New York, NY 11201, USA
                [3 ]Department of Molecular Biology, Max Planck Institute for Infection Biology, 10117 Berlin, Germany
                [4 ]Laboratory of Immunogenetics, Department of Medical Microbiology and Infection Control, VU University Medical Center, 1081 HV Amsterdam, The Netherlands
                Author notes
                [* ]Correspondence: e.ambrosino@ 123456maastrichtuniversity.nl ; Tel: +31-43-3884081
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0001-6975-8213
                Article
                genes-10-00410
                10.3390/genes10060410
                6627277
                31142036
                b724426d-3b49-46a8-9fa1-de54bbcc8805
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 26 April 2019
                : 24 May 2019
                Categories
                Perspective

                chlamydia trachomatis,tubal factor infertility (tfi),screening,diagnostic test,host genetic markers

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