Cervical intraepithelial neoplasia: Reproductive effects of treatment
- Maija Jakobsson, MD, PhD
Maija Jakobsson, MD, PhD
- Helsinki University Hospital
- Errol R Norwitz, MD, PhD, MBA
Errol R Norwitz, MD, PhD, MBA
- Professor and Chair
- Department of Obstetrics and Gynecology
- Tufts Medical Center and Tufts University School of Medicine
- Section Editors
- Barbara Goff, MD
Barbara Goff, MD
- Section Editor — Gynecologic Oncology
- Professor of Gynecologic Oncology
- University of Washington
- Susan M Ramin, MD
Susan M Ramin, MD
- Section Editor — Obstetrics
- Professor of Obstetrics and Gynecology
- Baylor College of Medicine
Cervical intraepithelial neoplasia (CIN) is a precursor to cervical cancer that is managed with either surveillance (cervical cytology and colposcopy) or treatment. Treatments for CIN include ablative or excisional cervical procedures. These treatments are often performed in reproductive-age women and may impact future fertility and pregnancy outcome. Awareness of reproductive risks associated with CIN treatment allows clinicians and patients to choose the optimal treatment method and to address subsequent reproductive issues.
CIN is also referred to as cervical dysplasia or cervical squamous intraepithelial lesions (CSIL). (See "Cervical intraepithelial neoplasia: Terminology, incidence, pathogenesis, and prevention", section on 'Terminology'.)
Reproductive effects of CIN treatment are reviewed here. General principles of CIN management and techniques for CIN treatment are discussed separately. (See "Cervical intraepithelial neoplasia: Management of low-grade and high-grade lesions" and "Cervical intraepithelial neoplasia: Procedures for cervical conization" and "Cervical intraepithelial neoplasia: Ablative therapies".)
EXCISION VERSUS ABLATION
There are two main categories of cervical intraepithelial neoplasia (CIN) treatment, excision and ablation. In excisional procedures (also referred to as conization; procedures include cold knife conization, loop electrosurgical excision procedure [LEEP], and laser conization), a segment of the cervix is removed and examined histologically. In ablative procedures (techniques include cryotherapy, laser, cold coagulation, diathermy), the tissue is destroyed, but remains in place; no histologic confirmation of the diagnosis is performed.
LEEP and cold knife conization are the most commonly used excisional methods; cryotherapy is the most commonly used ablative therapy. Laser conization and ablation are used less frequently, since they require expensive and bulky equipment. Diathermy and cold coagulation ablation are rarely used.
- Svare JA, Andersen LF, Langhoff-Roos J, et al. The relationship between prior cervical conization, cervical microbial colonization and preterm premature rupture of the membranes. Eur J Obstet Gynecol Reprod Biol 1992; 47:41.
- Masamoto H, Nagai Y, Inamine M, et al. Outcome of pregnancy after laser conization: implications for infection as a causal link with preterm birth. J Obstet Gynaecol Res 2008; 34:838.
- Hassan S, Romero R, Hendler I, et al. A sonographic short cervix as the only clinical manifestation of intra-amniotic infection. J Perinat Med 2006; 34:13.
- Svare J, Andersen LF, Langhoff-Roos J, et al. Uro-genital microbial colonization and threatening preterm delivery. Acta Obstet Gynecol Scand 1994; 73:460.
- Kyrgiou M, Koliopoulos G, Martin-Hirsch P, et al. Obstetric outcomes after conservative treatment for intraepithelial or early invasive cervical lesions: systematic review and meta-analysis. Lancet 2006; 367:489.
- Jakobsson M, Gissler M, Tiitinen A, et al. Treatment for cervical intraepithelial neoplasia and subsequent IVF deliveries. Hum Reprod 2008; 23:2252.
- Cruickshank ME, Flannelly G, Campbell DM, Kitchener HC. Fertility and pregnancy outcome following large loop excision of the cervical transformation zone. Br J Obstet Gynaecol 1995; 102:467.
- Baldauf JJ, Dreyfus M, Wertz JP, et al. [Consequences and treatment of cervical stenoses after laser conization or loop electrosurgical excision]. J Gynecol Obstet Biol Reprod (Paris) 1997; 26:64.
- Kyrgiou M, Mitra A, Arbyn M, et al. Fertility and early pregnancy outcomes after treatment for cervical intraepithelial neoplasia: systematic review and meta-analysis. BMJ 2014; 349:g6192.
- Sjøborg KD, Vistad I, Myhr SS, et al. Pregnancy outcome after cervical cone excision: a case-control study. Acta Obstet Gynecol Scand 2007; 86:423.
- Albrechtsen S, Rasmussen S, Thoresen S, et al. Pregnancy outcome in women before and after cervical conisation: population based cohort study. BMJ 2008; 337:a1343.
- Castanon A, Brocklehurst P, Evans H, et al. Risk of preterm birth after treatment for cervical intraepithelial neoplasia among women attending colposcopy in England: retrospective-prospective cohort study. BMJ 2012; 345:e5174.
- Arbyn M, Kyrgiou M, Simoens C, et al. Perinatal mortality and other severe adverse pregnancy outcomes associated with treatment of cervical intraepithelial neoplasia: meta-analysis. BMJ 2008; 337:a1284.
- Noehr B, Jensen A, Frederiksen K, et al. Loop electrosurgical excision of the cervix and subsequent risk for spontaneous preterm delivery: a population-based study of singleton deliveries during a 9-year period. Am J Obstet Gynecol 2009; 201:33.e1.
- Werner CL, Lo JY, Heffernan T, et al. Loop electrosurgical excision procedure and risk of preterm birth. Obstet Gynecol 2010; 115:605.
- Jakobsson M, Gissler M, Paavonen J, Tapper AM. Loop electrosurgical excision procedure and the risk for preterm birth. Obstet Gynecol 2009; 114:504.
- Bruinsma F, Lumley J, Tan J, Quinn M. Precancerous changes in the cervix and risk of subsequent preterm birth. BJOG 2007; 114:70.
- Noehr B, Jensen A, Frederiksen K, et al. Depth of cervical cone removed by loop electrosurgical excision procedure and subsequent risk of spontaneous preterm delivery. Obstet Gynecol 2009; 114:1232.
- Shanbhag S, Clark H, Timmaraju V, et al. Pregnancy outcome after treatment for cervical intraepithelial neoplasia. Obstet Gynecol 2009; 114:727.
- Ortoft G, Henriksen T, Hansen E, Petersen L. After conisation of the cervix, the perinatal mortality as a result of preterm delivery increases in subsequent pregnancy. BJOG 2010; 117:258.
- Hillier SL, Nugent RP, Eschenbach DA, et al. Association between bacterial vaginosis and preterm delivery of a low-birth-weight infant. The Vaginal Infections and Prematurity Study Group. N Engl J Med 1995; 333:1737.
- Viikki M, Pukkala E, Nieminen P, Hakama M. Gynaecological infections as risk determinants of subsequent cervical neoplasia. Acta Oncol 2000; 39:71.
- Kekki M, Kurki T, Pelkonen J, et al. Vaginal clindamycin in preventing preterm birth and peripartal infections in asymptomatic women with bacterial vaginosis: a randomized, controlled trial. Obstet Gynecol 2001; 97:643.
- Sadler L, Saftlas A, Wang W, et al. Treatment for cervical intraepithelial neoplasia and risk of preterm delivery. JAMA 2004; 291:2100.
- Quenby S. Obstetric management of women after treatment for CIN. BJOG 2010; 117:243.
- Castanon A, Landy R, Brocklehurst P, et al. Risk of preterm delivery with increasing depth of excision for cervical intraepithelial neoplasia in England: nested case-control study. BMJ 2014; 349:g6223.
- Kyrgiou M, Valasoulis G, Stasinou SM, et al. Proportion of cervical excision for cervical intraepithelial neoplasia as a predictor of pregnancy outcomes. Int J Gynaecol Obstet 2015; 128:141.
- Samson SL, Bentley JR, Fahey TJ, et al. The effect of loop electrosurgical excision procedure on future pregnancy outcome. Obstet Gynecol 2005; 105:325.
- Founta C, Arbyn M, Valasoulis G, et al. Proportion of excision and cervical healing after large loop excision of the transformation zone for cervical intraepithelial neoplasia. BJOG 2010; 117:1468.
- Himes KP, Simhan HN. Time from cervical conization to pregnancy and preterm birth. Obstet Gynecol 2007; 109:314.
- Jakobsson M, Gissler M, Sainio S, et al. Preterm delivery after surgical treatment for cervical intraepithelial neoplasia. Obstet Gynecol 2007; 109:309.
- Conner SN, Cahill AG, Tuuli MG, et al. Interval from loop electrosurgical excision procedure to pregnancy and pregnancy outcomes. Obstet Gynecol 2013; 122:1154.
- Noehr B, Jensen A, Frederiksen K, et al. Loop electrosurgical excision of the cervix and risk for spontaneous preterm delivery in twin pregnancies. Obstet Gynecol 2009; 114:511.
- Berghella V, Pereira L, Gariepy A, Simonazzi G. Prior cone biopsy: prediction of preterm birth by cervical ultrasound. Am J Obstet Gynecol 2004; 191:1393.
- Crane JM, Delaney T, Hutchens D. Transvaginal ultrasonography in the prediction of preterm birth after treatment for cervical intraepithelial neoplasia. Obstet Gynecol 2006; 107:37.
- Miller ES, Grobman WA. The association between cervical excisional procedures, midtrimester cervical length, and preterm birth. Am J Obstet Gynecol 2014; 211:242.e1.
- Zeisler H, Joura EA, Bancher-Todesca D, et al. Prophylactic cerclage in pregnancy. Effect in women with a history of conization. J Reprod Med 1997; 42:390.
- Frey HA, Stout MJ, Odibo AO, et al. Risk of cesarean delivery after loop electrosurgical excision procedure. Obstet Gynecol 2013; 121:39.
- EXCISION VERSUS ABLATION
- MECHANISMS OF REPRODUCTIVE EFFECTS
- CERVICAL STENOSIS
- SECOND TRIMESTER PREGNANCY LOSS
- PRETERM PREMATURE RUPTURE OF MEMBRANES
- PRETERM DELIVERY AND PERINATAL MORTALITY
- Risks of individual treatment methods
- Modifying factors
- - Depth of excision
- - Number of procedures
- - Short interval from treatment to pregnancy
- - Multiple gestation
- PERFORMANCE OF PROCEDURES DURING PREGNANCY
- OBSTETRIC MANAGEMENT IN SUBSEQUENT PREGNANCIES
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS