title: Fertility and early pregnancy outcomes after treatment for cervical intraepithelial neoplasia: systematic review and meta-analysis.
abstract: OBJECTIVE
  To determine the impact of cervical excision for cervical intraepithelial neoplasia on fertility and early pregnancy outcomes.
  
  
  METHODS
  Systematic review and meta-analysis of cohort studies.
  
  
  METHODS
  Medline and Embase.
  
  
  METHODS
  Studies assessing fertility and early pregnancy outcomes in women with a history of treatment for cervical intraepithelial neoplasia versus untreated women. We classified the included studies according to treatment type and fertility or early pregnancy endpoint.
  
  
  METHODS
  Pooled relative risks and 95% confidence intervals using a random effect model, and interstudy heterogeneity with I(2) statistics.
  
  
  RESULTS
  15 studies fulfilled the inclusion criteria and were included. The meta-analysis did not provide any evidence that treatment for cervical intraepithelial neoplasia adversely affected the chances of conception. The overall pregnancy rate was higher for treated women than for untreated women (four studies; 43% v 38%, pooled relative risk 1.29, 95% confidence interval 1.02 to 1.64), although the heterogeneity between studies was high (P<0.0001). Pregnancy rates did not differ between women with an intention to conceive (two studies; 88% v 95%, 0.93, 0.80 to 1.08) and the number requiring more than 12 months to conceive (three studies, 15% v 9%, 1.45, 0.89 to 2.37). Although the rates for total miscarriages (10 studies; 4.6% v 2.8%, 1.04, 0.90 to 1.21) and miscarriage in the first trimester (four studies; 9.8% v 8.4%, 1.16, 0.80 to 1.69) was similar for treated and untreated women, cervical treatment was associated with a significantly increased risk of miscarriage in the second trimester. The rate was higher for treated women than for untreated women (eight studies; 1.6% v 0.4%, 16,558 women; 2.60, 1.45 to 4.67). The number of ectopic pregnancies (1.6% v 0.8%; 1.89, 1.50 to 2.39) and terminations (12.2% v 7.4%; 1.71, 1.31 to 2.22) was also higher for treated women.
  
  
  CONCLUSIONS
  There is no evidence suggesting that treatment for cervical intraepithelial neoplasia adversely affects fertility, although treatment was associated with a significantly increased risk of miscarriages in the second trimester. Research should explore mechanisms that may explain this increase in risk and stratify the impact that treatment may have on fertility and early pregnancy outcomes by the size of excision and treatment method used.
authors.affiliation: Institute of Reproductive and Developmental Biology, Department of Surgery & Cancer, Faculty of Medicine, Imperial College, London W12 0NN, UK m.kyrgiou@imperial.ac.uk.
authors.forename: Maria
authors.initials: M
authors.lastname: Kyrgiou
authors.affiliation: Institute of Reproductive and Developmental Biology, Department of Surgery & Cancer, Faculty of Medicine, Imperial College, London W12 0NN, UK.
authors.forename: Anita
authors.initials: A
authors.lastname: Mitra
authors.affiliation: Unit of Cancer Epidemiology, Scientific Institute of Public Health, Brussels, Brussels.
authors.forename: Marc
authors.initials: M
authors.lastname: Arbyn
authors.affiliation: Create Infertility Clinic, London, UK Department of Obstetrics and Gynaecology, University Hospital of Ioannina, Greece.
authors.forename: Sofia Melina
authors.initials: SM
authors.lastname: Stasinou
authors.affiliation: Department of Gynaecologic Oncology, Lancashire Teaching Hospitals, Preston, UK Department of Biophotonics, Lancaster University, Lancaster, UK.
authors.forename: Pierre
authors.initials: P
authors.lastname: Martin-Hirsch
authors.affiliation: Institute of Reproductive and Developmental Biology, Department of Surgery & Cancer, Faculty of Medicine, Imperial College, London W12 0NN, UK.
authors.forename: Phillip
authors.initials: P
authors.lastname: Bennett
authors.affiliation: Department of Obstetrics and Gynaecology, University Hospital of Ioannina, Greece.
authors.forename: Evangelos
authors.initials: E
authors.lastname: Paraskevaidis
mesh_terms: D002584:Cervix Uteri / Q000601:surgery*; D019092:Conization / Q000379:methods; D005260:Female; D005298:Fertility; D006801:Humans; D015233:Models, Statistical; D011183:Postoperative Complications; D011247:Pregnancy; D011248:Pregnancy Complications / Q000209:etiology*; D011256:Pregnancy Outcome; D018873:Pregnancy Rate; D002583:Uterine Cervical Neoplasms / Q000601:surgery*; D002578:Uterine Cervical Dysplasia / Q000601:surgery*