Abstract: Fifteen studies (2,223,592 participants - 25,008 treated and 2,198,584 untreated) that fulfilled the inclusion criteria for this review were identified from the literature search. The meta-analysis demonstrated that treatment for CIN did not adversely affect the chances of conception. The overall pregnancy rate was higher for treated (43%) versus untreated women (38%; RR 1.29, 95% CI 1.02 to 1.64; 4 studies, 38,050 participants, very low quality), although the inter-study heterogeneity was considerable (P < 0.01). The pregnancy rates in treated and untreated women with an intention to conceive (88% versus 95%, RR 0.93, 95% CI 0.80 to 1.08; 2 studies, 70 participants, very low quality) and the number of women requiring more than 12 months to conceive (14% versus 9%, RR 1.45, 95% CI 0.89 to 2.37; 3 studies, 1348 participants, very low quality) were no different. Although the total miscarriage rate (4.6% versus 2.8%, RR 1.04, 95% CI 0.90 to 1.21; 10 studies, 39,504 participants, low quality) and first trimester miscarriage rate (9.8% versus 8.4%, RR 1.16, 95% CI 0.80 to 1.69, 4 studies, 1103 participants, low quality) was similar for treated and untreated women, CIN treatment was associated with an increased risk of second trimester miscarriage, (1.6% versus 0.4%, RR 2.60, 95% CI 1.45 to 4.67; 8 studies, 2,182,268 participants, low quality). The number of ectopic pregnancies (1.6% versus 0.8%, RR 1.89, 95% CI 1.50 to 2.39; 6 studies, 38,193 participants, low quality) and terminations (12.2% versus 7.4%, RR 1.71, 95% CI 1.31 to 2.22; 7 studies, 38,208 participants, low quality) were also higher in treated women. The results should be interpreted with caution. The included studies were often small with heterogenous design. Most of these studies were retrospective and of low or very low quality (GRADE assessment) and were therefore prone to bias. Subgroup analyses for the individual treatment methods and comparison groups and analysis to stratify for the cone length was not possible. This meta-analysis suggests that treatment for CIN does not adversely affect fertility, although treatment was associated with an increased risk of miscarriage in the second trimester. These results should be interpreted with caution as the included studies were non-randomised and many were of low or very low quality and therefore at high risk of bias. Research should explore mechanisms that may explain the increase in mid-trimester miscarriage risk and stratify this impact of treatment by the length of the cone and the treatment method used.

Plain-language summary: We included all studies that assessed fertility and early pregnancy outcomes in women who had local treatment of CIN versus untreated women. We identified fifteen suitable studies.Fertility outcomesThe results suggest that local treatment of the cervix does not adversely affect the ability to conceive; in fact the overall pregnancy rate was higher for treated women when compared to untreated women (43% versus 38%). There was no difference in the pregnancy rates in women that intended to conceive (88% treated versus 95% untreated) or in the number of women requiring more than 12 months to conceive (15% treated versus 9% untreated). Early pregnancy outcomes  The rates of total (less than 24 weeks of gestation) and first trimester (less than 12 weeks of gestation) miscarriage were no different. However, women after treatment had a significantly higher second trimester miscarriage rate (between 12 and 24 weeks of gestation) compared to untreated controls (1.6% versus 0.4%). The rates of ectopic pregnancies and terminations of pregnancy were higher for treated versus untreated women. The results should be interpreted with caution as the included studies were small and of mixed design. Most of the studies were of low quality and retrospective (looking at information recorded previously). Investigation of the effect of different treatments techniques and of the size of the tissue removed (i.e. cone length) was not possible. The results suggest that treatment for CIN does not adversely affect the chances of a successful conception, although treatment is associated with an increased risk of miscarriage in the second trimester. These conclusions should be interpreted with caution as the quality of the included studies was low or very low. Future research should investigate the impact related to the extent of the treatment and the treatment method used.