Elsevier

The Lancet

Volume 367, Issue 9509, 11–17 February 2006, Pages 489-498
The Lancet

Articles
Obstetric outcomes after conservative treatment for intraepithelial or early invasive cervical lesions: systematic review and meta-analysis

https://doi.org/10.1016/S0140-6736(06)68181-6Get rights and content

Summary

Background

Conservative methods to treat cervical intraepithelial neoplasia and microinvasive cervical cancer are commonly used in young women because of the advent of effective screening programmes. In a meta-analysis, we investigated the effect of these procedures on subsequent fertility and pregnancy outcomes.

Methods

We searched for studies in MEDLINE and EMBASE and classified them by the conservative method used and the outcome measure studied regarding both fertility and pregnancy. Pooled relative risks and 95% CIs were calculated with a random-effects model and interstudy heterogeneity was assessed with Cochrane's Q test.

Findings

We identified 27 studies. Cold knife conisation was significantly associated with preterm delivery (<37 weeks; relative risk 2·59, 95% CI 1·80–3·72, 100/704 [14%] vs 1494/27 674 [5%]), low birthweight (<2500 g; 2·53, 1·19–5·36, 32/261 [12%] vs 905/13 229 [7%]), and caesarean section (3·17, 1·07–9·40, 31/350 [9%] vs 22/670 [3%]). Large loop excision of the transformation zone (LLETZ) was also significantly associated with preterm delivery (1·70, 1·24–2·35, 156/1402 [11%] vs 120/1739 [7%]), low birthweight (1·82, 1·09–3·06, 77/996 [8%] vs 49/1192 [4%]), and premature rupture of the membranes (2·69, 1·62–4·46, 48/905 [5%] vs 22/1038 [2%]). Similar but marginally non-significant adverse effects were recorded for laser conisation (preterm delivery 1·71, 0·93–3·14). We did not detect significantly increased risks for obstetric outcomes after laser ablation. Although severe outcomes such as admission to a neonatal intensive care unit or perinatal mortality showed adverse trends, these changes were not significant.

Interpretation

All the excisional procedures to treat cervical intraepithelial neoplasia present similar pregnancy-related morbidity without apparent neonatal morbidity. Caution in the treatment of young women with mild cervical abnormalities should be recommended. Clinicians now have the evidence base to counsel women appropriately.

Introduction

The introduction of systematic call and recall screening programmes during the past 20 years has produced a profound decrease in the incidence of invasive cervical cancer. This trend has happened because of the treatment of pre-invasive lesions1 detected by the screening programmes. These interventions are undertaken on asymptomatic women previously unaware of any potential or real disease. These women who are treated for cervical intraepithelial neoplasia are of reproductive age, with a mean age of about 30 years, although the disorder can take place in much younger women.2, 3 That treatment should be effective is paramount, but it should also have minimum adverse effects on future fertility and pregnancy outcomes.

Cold knife conisation, laser ablation, laser conisation, and large loop excision of the transformation zone (LLETZ; also known as LEEP, or loop electrosurgical excisional procedure)4, 5 are all conservative methods of treatment used to remove or destroy the transformation zone containing abnormal cells and preserve cervical function at the same time.

Characteristics of these treatments are well described and established in published work.6 LLETZ, laser excision, and laser ablation are usually done under local anaesthesia in an outpatient setting, whereas cold knife cone biopsy needs general anaesthesia and hospital care. Theoretically, the excisional techniques (cold knife conisation, laser conisation, LLETZ) are better than the destructive techniques (laser ablation), because they allow a comprehensive histological investigation of the extirpated tissue and entire transformation zone with precise assessment of excision margins. Ablative techniques destroy the epithelium of the transformation zone and preclude histological investigation; therefore, accurate pre-treatment biopsy samples are needed at a separate initial visit. LLETZ is by far the most popular procedure,4 by combining all the advantages of the excisional techniques mentioned above, together with a relatively short duration, low cost, good compliance, simplicity, and an easier learning curve.

The best available evidence suggests that these methods present similarly low morbidity and are equally successful at eradicating intraepithelial lesions6, 7 and preventing invasive cervical cancer.8, 9, 10 However, the existing data for future fertility and pregnancy outcomes are conflicting.

Observational studies have indicated that these treatments could have adverse effects on fertility and pregnancy outcomes, although their conclusions are usually equivocal, perhaps due to the weakness associated with small sample sizes. We have not found any published randomised controlled trials comparing pregnancy outcome between treated and untreated women in published work. Because of the premalignant nature of the condition treated, a randomised trial might not ever be undertaken. Thus, the best available level of evidence on this subject may be provided by a systematic review and meta-analysis of the controlled observational studies, which we present here.

Section snippets

Types of studies, interventions, and inclusion and exclusion criteria

We included all the studies that compared obstetric outcomes in pregnant women with or without a previous conservative intervention on the cervix. The considered intervention was treatment of cervical intraepithelial neoplasia or stage I A1 cervical cancer by conservative methods (ablative [laser ablation] or excisional [cold knife conisation, LLETZ, laser conisation]). Studies without an untreated control group11, 12, 13, 14, 15, 16, 17, 18 were excluded. Studies including different treatment

Results

We identified 27 studies that fulfilled the inclusion criteria,25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51 all of which studied retrospective cohorts. Ten studies reported the effects of LLETZ,25, 26, 27, 28, 29, 30, 31, 32, 33, 34 seven of laser conisation,30, 35, 36, 37, 38, 39, 40 four of laser ablation,30, 40, 41 and ten of cold knife conisation.42, 43, 44, 45, 46, 47, 48, 49, 50, 51 Table 1 summarises the characteristics of

Discussion

With respect to pregnancy outcomes, our meta-analysis has revealed that cold knife conisation is associated with an increased risk of preterm delivery, low birthweight, and caesarean section rate. Likewise, the risk of preterm delivery, low birthweight, and pPROM increased significantly after LLETZ. However, our analysis of laser conisation marginally failed to detect a significant difference regarding preterm delivery, and none of the other outcomes was affected significantly. Furthermore, we

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