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.

Design: Systematic review and meta-analysis of cohort studies.

Data sources: Medline and Embase.

Eligibility criteria: 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.

Analysis: 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.

Conclusion: 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.

Fig 1 PRISMA flowchart

Fig 2 Meta-analysis on overall pregnancy rates in treated versus untreated women. LLETZ=large loop excision of the transformation zone; LEEP=loop electrosurgical excisional procedure

Fig 3 Meta-analysis on pregnancy rates in women with an intention to conceive, and time to conception greater than 12 months in treated versus untreated women. CKC=cold knife conisation; LLETZ=large loop excision of the transformation zone; LEEP=loop electrosurgical excisional procedure

Fig 4 Forest plots from meta-analysis on rates for total miscarriage in treated versus untreated women. CKC=cold knife conisation; LLETZ=large loop excision of the transformation zone; LEEP=loop electrosurgical excisional procedure

Fig 5 Forest plots from the meta-analysis on rates for miscarriage in first and second trimesters in treated versus untreated women. CKC=cold knife conisation; LLETZ=large loop excision of the transformation zone; LEEP=loop electrosurgical excisional procedure