Obstetric Outcomes after Conservative Treatment of

Intraepithelial and Early Invasive Cervical Lesions

นำเสนอโดย พ.ญ. ลินลดา วิจักขณ์อุรุโรจน์
อาจารย์ที่ปรึกษา ศ.น.พ. จตุพล ศรีสมบูรณ์

Introduction

            Cervical intraepithelial neoplasia(CIN) often arises in an area of metaplasia in transformation zone at squamocolumnar junction(SCJ). CIN is most likely to begin during menarche or after pregnancy when metaplasia is most active. Thus, the treatment of CIN and early invasive cervical lesion should be effective and have minimal adverse effect on fertility and pregnancy outcomes.

Treatment

            Normally, there are 2 categories of treatment :

  1. 1.Excision

–      Cold knife conization (CKC)

–      Loop electrosurgical excision procedure (LEEP) or large loop excision of the transformation zone(LLETZ)

–      Laser conization

  1. 2.Ablation

–      Cryotherapy

–      Laser ablation

–      Cold coaglulation

–      Diathermy

Management of CIN,CIS,AIS during pregnancy

–      All pregnancies with abnormal cytologies should be examined with colposcopy.

–      If colposcopic findings are satisfactory and nomicroinvasive or invasive carcinoma is detected ,no need to perform serial colposcopy during pregnancy, but if microinvasive lesions could not be excluded, serial colposcopy q 12 wks is recommended.

–      Expectant management for CIN is acceptable during pregnancy. Definite treatment should be initiated in post-partum period.

What if the women become pregnant after these procedures.

Basically, cervical surgery involves removal or destruction of both cervical gland and stroma. Many studies have been issued on conservative treatment and reproductive and obstetric outcomes. Mechanisms on reproductive effect have been postulated as followed:

–      Removal of cervical glands alters cervical mucus that is necessary for normal sperm migration and viability which may impair fertility.

–      Destruction of cervical collagen matrix => decreased cervical strength => increased risk of preterm labour

–      Both destruction of cervical gland and stroma, along with shortening of the cervix and decreased cervical mucus function make bacteria easier to migrate and access to uterine cavity resulting in increasing risk of ascending infection.

–      Scarring after surgery cause cervical stenosis leading to difficult cervical dilatation during labour causing amniotic membrane vulnerable to rupture => preterm premature ruptured of membrane (preterm PROM).

After literature reviewon the obstetric outcomes after conservative treatment for CIN,

the conclusions are:

Conservative treatment affects reproductive and obstetric outcomes as followed :

  1. 1.Infertility

–      All treatment of CIN & AIS do not impair fertility.

–      No effect of time interval on pregnancy(OR 0.98, 95%CI (0.96-1.00)2

  1. 2.Second trimester loss

–      Higher risk of delivery at GA less than 24 wk in patient with prior conization , but data are limited due to most of birth registry do not collect this type of data and second trimester loss are rare.

  1. 3.Preterm PROM

–      Excisional methods : increase risk

(pooled RR 3.4,95% CI (1.63-1.88))3

( LEEP : pooled RR 2.69, 95%CI ( 1.62-4.46)4

(Laser conization : pooled RR 2.18 ,95% CI(0.77-6.16)4

–      Laser ablation : not increase (pooled RR 1.23,95%CI(0.56-2.70))4

–      Cryotherapy : insufficient data

  1. 4.Preterm labour and LBW

–      Excisional method increase risk esp. if LEEP depth > 10 mm or repeated LEEP

(LEEP : pooled OR 1.85,95%CI(1.59-2.15))3

(CKC : RR 3.41,95%CI(2.38-4.88))3

( Laserconization : RR 3.58,95%CI(1.93-6.61))3

–      Severity of CIN : not increase risk of preterm delivery

  1. 5.Route of delivery : no association

 

Fetal Surveillance

  1. 1.Second trimester transvaginal ultrasound for cervical length : Recommended to perform in post-conization or deep LEEP or LEEP >1 times: at GA 16-32 wk q 2 wk
  2. 2.Fetal fibronectin : if indicated after GA 22 wk
  3. 3.Prophylactic cervical cerclage

– Controversial

– Not recommended in patients who previously undergo cold knife conization

  1. 4.Progesterone supplement to prevent preterm birth

-No evidence

 

 

A recent retrospective study on loop electrosurgical excision procedure(LEEP) and risk for preterm delivery in Finland from 1997 to 2009.Case group women consisted of 20,011 women who underwent LEEP during the study period and their subsequent singleton deliveries in 1998-2009. Control population included women with no LEEP (n=430,975).The study showed statistically significant findings as followed :

– Women with LEEP had higher rate for preterm delivery when compared to pregnant

   women without prior LEEP history (OR 1.61,95%CI (1.47-1.75),NNH 38.5)

– LEEP for no- CIN lesion increased the risk twice (OR 2.04, 95%CI :1.46-1.85)

– LEEP for cancerous lesion have a higher risk        (OR 2.55,95%CI:1.68-3.87)

– Repeat LEEP increased the risk 3 folds                  (OR 2.8, 95%CI :2.28-3.44)

– LBW also increased in LEEP group                       (OR 1.50, 95%CI:1.30-1.37)

       Other non-significant findings were :

– Severity of CIN did not increase preterm delivery

– Time interval since LEEP has no effect on preterm birth

– SGA and perinatal mortality did not increase after LEEP

– After adjusted for maternal age, socioeconomic status,maritalstatus,urbanism,history of

   previous preterm birth did not change the results

 

Strength and weakness of this study :

• Strength

– Large population

– No reporting,recall and participation bias

– Adjusting the results for several important factor that were associated with preterm

delivery

• Weakness

– The study did not determine the cone size because of no available information

– LEEP group had higher rate of smoking during pregnancy, though the study did not adjust

the results for smoking status because of inaccuracy data. But they claimed that

socioeconomic status are associated with smoking status, then the result might have been

in the same way.

– Comparison between LEEP women and normal population may be a selection bias because

normal population seemed to have lower risk for preterm birth than LEEP women.

 

References

 

  1. Jonathan S. Berek.Berek&Novak’s Gynecology. Fifteenth edition.Philadelphia:Wolters Kluwer business;2012
  2. Heinonen A, Gissler M, Riska A, Paavonen J, Tapper AM, Jakobsson M. Loop electrosurgical excision procedure and the risk for preterm delivery. ObstetGynecol 2013;121(5):1063-8.
  3. Bruinsma FJ, Quinn MA.The risk of preterm birth following treatment for precancerous changes in the cervix: a systematic review and meta-analysis.BJOG2011;118(9):1031-41.
  4. Kyrgiou M, Koliopoulos G, Martin-Hirsch P, Arbyn M, Prendiville W, Paraskevaidis E. Obstetric outcomes after conservative treatment for intraepithelial or early invasive cervical lesions: systematic review and meta-analysis.Lancet 2006;367(9509):489-98.
  5. Mi-Young Shin, Eun-Sung Seo, Suk-Joo Choi, Soo-Young Oh, Byoung-Gie Kim, Duk-SooBae,et al. The role of prophylactic cerclage in preventing preterm delivery after electrosurgical conization. J GynecolOncol 2010;21; 230-6.
  6. Crane JM, Delaney T, Hutchens D. Transvaginal ultrasonography in the prediction of preterm birth after treatment of CIN. ObstetGynaecol 2006;107(1);34-44.
  7. ASCCP. Consensus guideline on treatment and colposcopy during pregnancy.2006;215-8 

 

Heinonen A, Gissler M, Riska A, Paavonen J, Tapper AM, Jakobsson M. Loop electrosurgical excision procedure and the risk for preterm delivery. Obstet Gynecol. 2013;121(5):1063-8.

 

Abstract

 

OBJECTIVE: To estimate whether the severity of cervical intraepithelial neoplasia (CIN) and the loop electrosurgical excision procedure (LEEP) increase the risk for preterm delivery, and to evaluate the role of repeat LEEP and time interval since LEEP.

 

METHODS:This was a retrospective register-based study from Finland from 1997 to 2009. We linked Hospital Discharge Register and Finnish Medical Birth Register data. Case group women consisted of 20,011 women who underwent LEEP during the study period and their subsequent singleton deliveries in 1998-2009. Control population included women from the Medical Birth Register with no LEEP (n=430,975). The main outcome measure was preterm delivery before 37 weeks of gestation.

 

RESULTS: The risk for preterm delivery increased after LEEP. Women with previous LEEP had 547 (7.2%) preterm deliveries, whereas the control population had 30,151 (4.6%) preterm deliveries (odds ratio [OR] 1.61, confidence interval [CI] 1.47-1.75, number needed to harm 38.5). The overall preterm delivery rate in the study period was 4.6% for singleton deliveries. Repeat LEEP was associated with an almost threefold risk for preterm delivery (OR 2.80, CI 2.28-3.44). The severity of CIN did not increase the risk for preterm delivery. However, with LEEP for carcinoma in situ or microinvasive cancer, the risk for preterm delivery was higher (OR 2.55, CI 1.68-3.87). The increased risk also was associated with non-CIN lesions (OR 2.04, CI 1.46-2.87). Similarly, the risk was increased after diagnostic LEEP (OR 1.39, 95% CI 1.16-1.67). Time interval since LEEP was not associated with preterm delivery. Adjusting for maternal age, parity, socioeconomic or marital status, urbanism, and previous preterm deliveries did not change the results.

 

CONCLUSION: The risk for preterm delivery was increased after LEEP regardless of the histopathologic diagnosis. The risk was highest after repeat LEEP, which should be avoided, especially among women of reproductive age.

 

LEVEL OF EVIDENCE: II.

 

                                                                                   Presenter: Dr. LinladaVijakururote M.D.

                                                                                   Advisor : Prof. JatupolSrisomboon, M.D.

 

 

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