Predictive value of volume of cervical tissue removed during LLETZ on subsequent preterm delivery: a cohort study

doi:10.1016/j.ejogrb.2014.06.011

European Journal of Obstetrics & Gynecology and Reproductive Biology

Volume 180, September 2014, Pages 51-55

https://doi.org/10.1016/j.ejogrb.2014.06.011 Get rights and content

Abstract

Objective

To evaluate the impact of volume of tissue removed during large loop excision of transformation zone on subsequent preterm birth rates.

Study design

A retrospective cohort study was carried out in a single, large tertiary referral unit in UK. A total of 556 women who delivered between January 2008 and December 2011 following a previous large loop excision of transformation zone procedure or punch biopsy were identified from the maternity and colposcopy databases. Demographic data, gestational age at delivery, birthweight, neonatal outcome and dimensions of excised cervical specimen were collected. Pregnancy outcomes for women who had a previous loop excision were compared to a matched control group who had undergone punch biopsies only.

Results

There was a significant increase in preterm birth rate in the large loop excision group compared to the control group (9.0% vs. 3.6%, respectively, RR 2.5, 95% CI 1.224–5.107). Women who had undergone at least one previous loop excision had more than a threefold increased risk of spontaneous preterm birth compared with their matched controls. However, no relationship between volume or depth of cervical tissue excised and subsequent gestation at delivery could be demonstrated.

Conclusions

Whilst LLETZ is associated with an increased rate of preterm birth, the volume of tissue removed does not appear to influence the subsequent gestational age at delivery. This should reassure clinicians who should continue to perform LLETZ with adequate tissue margins to ensure complete resection of disease.

Introduction

Colposcopy services have been transformed in recent years in response to advances in HPV screening and vaccination. Increased public acceptance of screening following high profile media cases means that increasing numbers of women attend for screening and are recommended LLETZ procedures to treat CIN. The majority of affected women are of reproductive age and, therefore, the impact of treatment on future pregnancy outcomes must be considered. Concerns have been raised about an increased risk of preterm delivery, particularly when more than one LLETZ is performed. The published data, however, have failed to reach a unified conclusion [1], [2], [3], [4], [10], [12], [13].

Recently attention has focussed on the impact of depth of tissue excised on subsequent preterm delivery risk, again with conflicting results [3], [5], [6], [7]. Defining an appropriate control group for comparison in such studies has frequently proven to be difficult. Many consider cases following treatment of CIN by LLETZ to those of the untreated obstetric population as a whole without considering known influencing factors. CIN and preterm labour share many associated risk factors, such as smoking. Studies evaluating the impact of LLETZ on preterm birth rates, therefore, must take this into account.

The impact of LLETZ on cervical function is unlikely to be purely due to a reduction in length as demonstrated by the conflicting evidence in the literature discussing the predictive value of cervical length on the risk of preterm delivery [8], [9]. The volume (or physical dimensions) of tissue removed at the time of LLETZ is commonly reported to clinicians. If this proved to be a useful predictor of pregnancy outcome, the quality of counselling given to women regarding the impact of their colposcopy treatment on future pregnancy risk would be significantly improved.

A study was, therefore, designed to evaluate the impact of prior LLETZ on the risk of subsequent preterm birth in singleton pregnancies compared to a control group matched for known risk factors for preterm birth and CIN. Secondary analysis was performed to investigate the predictive value of volume of tissue and depth of tissue removed during treatment on the risk of preterm birth.

Section snippets

Materials and methods

A retrospective cohort study was carried out in a large tertiary referral unit in the North East of England delivering over 7000 women annually. Women who had a previous LLETZ procedure performed between 2000 and 2010 and subsequently delivered a singleton pregnancy of at least 20 weeks gestation between January 2008 and December 2011 were identified from the pathology and maternity databases. Only those women for whom the index pregnancy was the first pregnancy occurring after the LLETZ

Results

A total of 278 women were identified from the maternity and pathology databases having undergone at least one prior LLETZ procedure and had delivered a singleton pregnancy during the specified time interval. A corresponding control group of 278 women who had had previous punch biopsies only were selected from the same databases, matching as a cohort for age, parity and smoking status (Table 1). A total of 30 (10.8%) women underwent two or more LLETZ procedures. The characteristics of this

Comment

This study demonstrates a significant increase in the preterm birth rate for women delivering singleton pregnancies following a previous LLETZ procedure, compared to a matched cohort. This effect was seen in deliveries pre-37 weeks and at the more significant level of pre-34 weeks gestation and included those that had undergone only one prior LLETZ as well as those who had experienced two or more procedures. This was associated with a lower mean birth weight and an increase in neonatal

Conclusion

Our study demonstrates an increased risk of preterm delivery and PPROM following LLETZ treatment compared with a matched control group. We did not, however, elucidate a relationship between the volume of cervical tissue excised and the subsequent gestational age at delivery. This further emphasises that reduction in cervical length is unlikely to be the sole contributing factor to the risk of preterm birth, rather complex interactions between the cervix, infectious agents and pro-inflammatory

Conflict of interest

The authors have no conflicts of interest to disclose.

Contribution to authorship

SK designed the study, contributed to data collection, performed the analyses and drafted the manuscript. EG contributed to data collection and revision of the manuscript. EM contributed to revision of the manuscript. MS contributed to study design, discussion of analysis and revision of the manuscript. All authors contributed to the final manuscript.

Details of ethic approval

Approval for the study was obtained from the North East-Northern and Yorkshire research ethics committee. The Research Ethics Committee reference number is 12/NE/0252, dated 7th August 2012.

Funding

No financial support.

Acknowledgements

Special thanks to Jilly Goodfellow, nurse colposcopist, for her help with colposcopy data collection and James Summerton, IT manager, for his assistance in performing searches within the maternity database.

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BJOG

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Terminology for cone dimensions after local conservative treatment for cervical intraepithelial neoplasia and early invasive cervical cancer: 2022 consensus recommendations from ESGO, EFC, IFCPC, and ESP
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The volumetric fluid displacement technique is likely to represent the most accurate measurement (the gold standard), whereby the difference in fluid level before and after the immersion of a cone is recorded (Archimedes' principle; appendix p 6).15,17,36–42 When this technique is not feasible, researchers have used various formulas to calculate the volume of a cone from its dimensions.16,32,43–54 As the shape of cones can vary, researchers have used different cone shapes to determine volume, such as a cone, a semi-ellipsoid, an ellipsoid, a parallelepiped, and a truncated cone (frustum; appendix pp 2–3, 7–8).
Local cervical treatment for squamous intraepithelial lesion (SIL) or cervical intraepithelial neoplasia (CIN) removes or ablates a cone-shaped or dome-shaped part of the cervix that contains abnormal cells. This Series paper introduces the 2022 terminology for cone dimensions after local conservative treatment for SIL, CIN, or early invasive cervical cancer. The terminology was prepared by the Nomenclature Committee of the European Society of Gynaecologic Oncology, the European Federation for Colposcopy, the International Federation of Cervical Pathology and Colposcopy, and the European Society of Pathology. Cone length should be tailored to the type of transformation zone. Treatment of SIL or CIN is associated with an increased risk of preterm birth, which escalates with increasing cone length. There is a lack of agreement regarding terms used to report excised specimen dimensions both intraoperatively and in the pathology laboratory. Consensus is needed to make studies addressing effectiveness and safety of SIL or CIN treatment comparable, and to facilitate their use to improve accuracy of antenatal surveillance and management. This Series paper summarises the current terminology through a review of existing literature, describes new terminology as agreed by a group of experts from international societies in the field of cervical cancer prevention and treatment, and recommends use of the new terminology that will facilitate communication between clinicians and foster more specific treatment guidelines that balance obstetrical harm against therapeutic effectiveness.
A retrospective analysis on 1901 women with high grade cervical intraepithelial neoplasia by colposcopic biopsy
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Thus, an unbefitting management for HSIL may result from an inaccurate diagnosis by colposcopic biopsy. When colposcopic biopsy is over-diagnosis, women may undergo unnecessary cervical conization, which has been reported to be associated with potential complications, including some harmful perinatal outcomes in future pregnancies such as elevated risk of premature delivery [8–11]. On the other hand, an under-diagnosis by colposcopic biopsy can miss invasive cervical cancer.
Clinically, an unbefitting management for high grade squamous intraepithelial lesion (HSIL) may result from an inaccurate diagnosis by colposcopy bioposy.The study aimed to assess the diagnostic accuracy by colposcopic biopsy and evaluate the associated factors in diagnosing HSIL.
Clinical data of 1901 women who were primarily diagnosed as HSIL by colposcopic biopsy and then underwent definitive surgery within six-month interval in Women’s Hospital, School of Medicine, Zhejiang University during 2009–2015, were retrospectively collected. The diagnostic accuracy of HSIL by colposcopic biopsy was assessed and the correlations between diagnostic accuracy and clinic-pathological variables were calculated by univariate and multivariate analysis using the pathological diagnosis by definitive surgery as a reference standard.
The accordance rate of HSIL diagnosis between colposcopic biopsy and definitive surgery was 80.6%, with an under-diagnosis rate of 5.8% and an over-diagnosis rate of 13.6%. Cytology ≤ low grade squamous intraepithelial lesion(LSIL) (OR:1.599;95%CI:1.185–2.160), colposcopy ≤ LSIL (OR:2.083;95%CI:1.537–2.824), endocervical curettage (ECC) ≤ LSIL(OR:2.813;95%CI:2.051–3.857), and lesion without gland involved (OR:1.751;95%CI:1.299–2.361) were independent risk factors for over-diagnosis of HSIL. Women with ≥ 3 risk factors had a 5.078-flod higher risk for over-diagnosis of HSIL compared to those with ≤ 1 risk factor. Irregular vaginal bleeding (OR:2.570,95%CI:1.668–3.960), colposcopy = HSIL (OR:1.699,95%CI:1.022-2.824), ECC = HSIL (OR:2.666, 95%CI:1.728–4.113), and multiple biopsies (OR:1.818, 95%CI:1.153–2.868) were independent risk factors for under-diagnosis of HSIL. Women with ≥3 risk factors had a 5.710-flod higher risk for under-diagnosis of HSIL compared to those with ≤1 risk factor.
The diagnostic accuracy of HSIL by colposcopic biopsy is about 80% and associated with some factors including symptom, cytology result, colposcopy diagnosis, and biopsy number. These variables may be predictors for over-diagnosis or under-diagnosis of HSIL by colposcopic biopsy.
Pregnancy outcome after cervical conisation: A 2nd retrospective cohort study in the Leuven University Hospital
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However, only eight pregnancies occurred after multiple conisations. This is partly in concordance with British findings [11]. Kitson et al. found an increased risk of preterm birth in women with a history of one or more conisations, but could not correlate this with the volume nor the depth of the cone.
To evaluate whether the dimensions of the cones removed during large loop excision of the transformation zone have decreased over time. Secondly, whether these changes were associated with a lower risk of obstetrical harms on a subsequent pregnancy.
A retrospective matched cohort study was performed in a tertiary referral unit in Belgium. A total of 97 women were identified from a database of women who underwent excisional treatment for cervical precancer between January 1st, 2004 and December 31st, 2012, and delivered before December 31st, 2014. The control group consisted of 120 non-treated women who had no history of cervical intra-epithelial neoplasia. Data on smoking status; gestational age at delivery; number of conisations; time interval between treatment and pregnancy; dimensions of the cone; severity of the lesion; and the extra resection of endocervical tissue were collected. These data were compared with those from a previous similar study at the University Hospital of Leuven in 2009, which database we enriched with information on the cone dimensions. Main outcome variables were gestational age at delivery, birthweight and neonatal condition at birth.
Only a significant lower birthweight could be found in the treated group compared to the control group (3364 g [95% CI 3094–3290] versus 3364 g [95% CI 3253–3475], P = 0.023). The current study showed no increase in preterm birth rate after conisation and no relationship between volume or depth of the cone and preterm birth could be found. Over the period 1999–2014, a significant decrease in all dimensions was observed: on average −0.3 mm, −0.3 mm, −0.4 mm and −132 mm³ per year, for the depth, anteroposterior and transverse diameter and the volume, respectively.
Our two successive studies showed a significant trend towards smaller cones which was accompanied by a decrease in preterm birth after excisional treatment. The clinician could limit the size of the cone to avoid obstetrical harms, but needs to be aware of the oncological safety as well.
Operator Sex and Experience Do Not Influence Conization Outcomes in Terms of Cone Volume, Depth or Resection Margins
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Association between loop electrosurgical excision procedure and adverse pregnancy outcomes: a meta-analysis
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View all citing articles on Scopus

View full text

Predictive value of volume of cervical tissue removed during LLETZ on subsequent preterm delivery: a cohort study

Abstract

Objective

Study design

Results

Conclusions

Introduction

Section snippets

Materials and methods

Results

Comment

Conclusion

Conflict of interest

Contribution to authorship

Details of ethic approval

Funding

Acknowledgements

The Lancet

Eur J Obstet Gynecol Reprod Biol

Loop electrosurgical excision procedure and risk of preterm birth

Obstet Gynecol

Pregnancy outcome after loop electrosurgical excision procedure of the management of cervical intraepithelial neoplasia

Arch Gynecol Obstet

Perinatal mortality and other severe adverse pregnancy outcomes associated with treatment of cervical intraepithelial neoplasis: meta-analysis

BMJ

Depth of cervical cone removed by loop electrosurgical excision procedure and subsequent risk of preterm birth

Obstet Gynecol

Treatment for cervical intraepithelial neoplasia and risk of preterm delivery

JAMA

The effect of loop electrosurgical excision on future pregnancy outcome

Obstet Gynecol

Transvaginal ultrasonography in the prediction of preterm birth after treatment for cervical intraepithelial neoplasia

Obstet Gynecol

Cervical length screening in patients who have undergone loop electrosurgical excision procedure

J Reprod Med

The volume perspective: a comparison of two excisional treatments for cervical intraepithelial neoplasia (laser versus LLETZ)

BJOG