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Prospective management of stage IA(1) cervical adenocarcinoma by conization alone to preserve fertility: a preliminary report.

OBJECTIVE: Microinvasive cervical adenocarcinoma has an excellent prognosis and emerging data support the hypothesis that it should be treated in the same way as its squamous counterpart. We report our preliminary experience prospectively treating stage IA(1) cervical adenocarcinoma by conization alone in women who strongly desired to preserve their fertility. METHODS: Since May 1998, all patients with stage IA(1) cervical adenocarcinoma who expressed a strong desire to preserve fertility have been offered cold knife conization (CKC) and careful surveillance without hysterectomy. Women with lesions identifiable only microscopically, up to 3 mm invasive depth, up to 7 mm tumor width, and a conization specimen including the entire lesion with negative margins were eligible for conservative management. Postconization surveillance consisted of a Pap smear and endocervical curettage every 4 months. Medical records were reviewed for clinical data, follow-up, and disease status. RESULTS: Five women ages 26-33 elected CKC and surveillance. Four were nulliparous and one primiparous. Four tumors were endocervical cell type; one was adenosquamous. Three were grade 1, one was grade 2, and one grade 3. None had lymph-vascular space invasion. None of the patients has developed recurrent disease after 6-20 months of follow-up. CONCLUSIONS: Our preliminary data suggest that patients with FIGO stage IA(1) cervical adenocarcinoma who strongly desire to preserve their fertility may be treated by conization alone if they are fully informed of the unknown risks for disease recurrence and are carefully followed. A multicenter trial is the next logical step to test the efficacy of this approach.

Adenocarcinoma↗

Persistence of human papillomavirus infection after therapeutic conization for CIN 3: is it an alarm for disease recurrence?

OBJECTIVE: The aims of this study were (1) to examine whether HPV DNA is persistently detected in the cervix after therapeutic conization for CIN 3 and (2) to explore whether a patient with persistence of HPV infection is at risk of developing recurrent disease. METHODS: Of 74 patients referred with CIN 3, 58 who were tested for HPV DNA in the pretreatment cervical lesions were enrolled in the study. After standard therapeutic conization, patients were followed prospectively at the outpatient clinic. Our follow-up protocol was to follow patients without therapeutic intervention as long as they developed no recurrence or recurrence of CIN 1 or 2, while patients who experienced recurrence of CIN 3 were recommended for reconization or hysterectomy. The polymerase chain reaction for detecting HPV DNA was performed using fresh cell samples from the cervix. RESULTS: In 56 of 58 patients (96.6%), HPV DNAs were detected in their primary cervical lesions prior to conization. With regard to the distribution of HPV types, HPV type 16 family (types 16, 31, and 35) was identified in 28 cases (50.0%), type 18 family (types 18, 33 and 58) in 15 (26.8%), and type X in 18 (32.1%). Up to August 1999, all of the 58 patients have been followed with a mean follow-up period of 31.8 months (range: 12 to 73 months). After treatment, HPV DNA was persistently detected in 11 (19.6%) but negative in 45 (80.4%) of 56 HPV DNA-positive patients. HPV DNA was not detected in both HPV DNA-negative patients. Five of 11 persistently HPV DNA-positive patients (45.5%) developed CIN recurrence, while none of 45 persistently HPV DNA-negative patients did. Thus, there was a significant difference between the recurrence rates of these two groups (P < 0.0001). Both patients who were initially HPV DNA-negative developed no recurrence. Accordingly, the overall recurrence following conservative treatment for CIN 3 was 5 of 58 patients (8.6%). CONCLUSIONS: Patients with persistent HPV infection after conization for CIN 3 should be especially closely followed because they are at increased risk of developing disease recurrence.

Adult↗

Endocervical curettage at conization to predict residual cervical adenocarcinoma in situ.

OBJECTIVE: To determine if performing an endocervical curettage (ECC) at the time of conization is a useful diagnostic tool for predicting residual cervical adenocarcinoma in situ (AIS) among women who might wish to preserve their fertility. METHODS: All patients diagnosed with AIS from 1995 to 2000 at four institutions were identified. Data were retrospectively extracted from clinical records. Women included in the statistical analysis were (1) younger than 40 years, (2) had an ECC performed at the time of the initial cone biopsy, (3) had a clearly demarcated surgical margin pathologically, and (4) underwent a second surgical procedure. RESULTS: Twenty-nine (24%) of 123 AIS patients met criteria for inclusion. The median age was 33 years (range, 17 to 39) and 13 (46%) were nulliparous. Initial surgery was a cold-knife conization (n = 17) or loop electrosurgical excision procedure (n = 12). Twelve (41%) ECCs and 15 (52%) cone margins were histologically positive. Sixteen patients underwent a repeat conization; 13 underwent hysterectomy. Thirteen (45%) patients had residual AIS at the time of their second surgical procedure. ECC had a superior positive predictive value (100% vs 47%; P < 0.01) and negative predictive value (94% vs 57%; P = 0.01) compared to cone margin in predicting residual AIS. None of the women undergoing fertility-sparing surgery developed recurrent AIS or adenocarcinoma. CONCLUSION: ECC performed at the time of conization may be a useful tool for predicting residual AIS in women considering fertility preservation.

Adenocarcinoma↗

Usefulness of human papillomavirus testing in the follow-up of patients with high-grade cervical intraepithelial neoplasia after conization.

OBJECTIVE: We aimed to define the adjunctive role of human papillomavirus (HPV) DNA testing in the follow-up of high-grade cervical intraepithelial neoplasia (CIN) after conization. STUDY DESIGN: We analyzed a consecutive series of 2,154 patients who received conization. Patients who had cone diagnosis of cervical cancer or CIN 1, a hysterectomy within 12 weeks after conization, and no follow-up data were excluded. The remaining 765 patients (monitored by Pap smears, colposcopy with or without high-risk HPV DNA testing) were analyzed. RESULTS: Of the 765 patients, 279 had CIN at cone margin or endocervix (group A) while 486 were both margin- and endocervix-free (group B). The 3-year cumulative rate of residual/recurrent high-grade CIN was 10.3% (95% CI, 6.9-13.7). HPV follow-up status (P=.015), margin status (P=.001), and follow-up cervical cytology (P<.0001) were significant predictors for residual/recurrent high-grade CIN by multivariate analysis. Four high-grade CINs and 1 microinvasive carcinoma of group A were detected initially by HPV testing, while 48.3% (199/410) of those without recurrent/persistent high-grade CIN still had persistent HPV infection. CONCLUSION: HPV DNA testing is useful in the follow-up and understanding of the natural history after conization for high-grade CIN.

Adenocarcinoma↗

Residual and recurrent lesions after conization for cervical intraepithelial neoplasia grade 3.

OBJECTIVES: To evaluate the importance of regular and long-term follow-up of patients who had conization for cervical intraepithelial neoplasia grade 3 (CIN 3); and to assess the risk of residual/recurrent lesions of the cervix uteri. METHODS: Retrospective analysis of 934 patients with CIN 3 who underwent conization over the period 1 January 1985-31 December 1997. The analysis included 38 (4.1%) patients who had involved resection margins and 896 (95.9%) patients who had free resection margins. RESULTS: Twenty-three out of 934 (2.5%) patients had another operation (reconization in 17 and hysterectomy in six) whereas one patient had a biopsy. Residual or recurrent lesion after conization was found in 23 patients out of 934 (2.5%). Three patients had invasive cervical cancer (0.3%), 19 had CIN 3 (2.0%) and one patient had CIN 1 (0.1%). One of the 24 patients (4.2%) was diagnosed with no lesion after repeated operation. Eleven patients out of 38 (28.9%) with involved resection margins during the first conization had residual/recurrent disease, compared with eight out of 896 patients (0.9%) who had free resection margins. CONCLUSION: Another operation is recommended only in cases when, on the basis of cytological, colposcopical and histological findings, the gynecologist suspect the residual/recurrent lesions.

Cervix Uteri↗

Cervical intraepithelial neoplasia III: long-term follow-up after cold-knife conization with involved margins.

OBJECTIVE: To evaluate the long-term outcome of patients with severe cervical intraepithelial neoplasia (CIN) III or squamous carcinoma in situ after cold-knife conization with involved margins. METHODS: A total of 390 patients (median age 39 years, range 20-69) with positive margins after cold-knife conization for CIN III were followed expectantly for a mean of 19 (range 6-30) years. Follow-up consisted of colposcopy, cytology, histology, and pelvic examination. RESULTS: Overall, 306 (78%) patients remained free of CIN III, and 84 (22%) had persisting or recurrent CIN III (n = 78) or developed invasive carcinoma (n = 6). Fifty-three patients had persisting CIN III (diagnosed within 1 year of conization), 25 developed recurrent CIN III after a median of 3 (range 2-28) years, five developed microinvasive carcinomas (at 3, 6, 7, 12, and 23 years), and one developed a stage IB carcinoma at 8 years. Persisting or recurrent disease was more common in patients in whom both the endocervical and the ectocervical cone margins were involved than in those in whom only the ectocervical or the endocervical margin was positive (52% versus 17% and 21%, respectively, P <.001). CONCLUSION: Expectant management is reasonable for patients with CIN III and positive margins after cold-knife conization. However, these patients require careful follow-up, particularly during the first year.

Adult↗

Risk of cervical stenosis after large loop excision or laser conization.

OBJECTIVE: To assess the frequency of cervical stenosis in patients treated by laser conization or the loop electrosurgical excision procedure and to determine the preoperative and therapeutic factors associated with its occurrence. METHODS: Two hundred fifty-five women treated by laser conization and 277 treated by loop electrosurgical excision procedure were followed regularly by postoperative colposcopy for mean periods of 38 and 16 months, respectively. Stenosis was defined as cervical narrowing that prevented insertion of a 2.5-mm Hegar dilator. RESULTS: Thirty-eight cases of cervical stenosis, of which seven were complete, were diagnosed up to 28 months after treatment. The risk of postoperative cervical stenosis was higher for patients over 50 years of age (relative risk [RR] 3.07, 95% confidence interval [95% CI] 1.30, 7.26; P = .031), for those with a totally endocervical lesion (RR 3.79, 95% CI 1.88, 7.62; P = .001), for those with an excision 20 mm high or greater (RR 2.96, 95% CI 1.63, 5.38; P = .005), and for those with laser conization (RR 2.35, 95% CI 1.24, 4.46; P = .009). Parity, menopause, previous treatment for cervical intraepithelial neoplasia, satisfactory colposcopy, size of the lesion, its histologic diagnosis, and the extent of excision did not increase the risk for cervical stenosis. Excision was not as high with loop electrosurgical excision as with laser conization (14.3 +/- 5.0 mm versus 20.2 +/- 6.0 mm). The height of excision (RR 1.95, 95% CI 1.02, 3.76; P = .04) and a totally endocervical lesion (RR 5.07, 95% CI 1.96, 14.44; P = .001) were the only independent factors associated with postoperative stenosis identified by a multivariate analysis using logistic regression. CONCLUSION: The height of excision and a totally endocervical lesion were the main factors associated with cervical stenosis. The decreased risk associated with the loop electrosurgical excision procedure seems to be due to a shorter endocervical excision.

Adolescent↗

Stage Ia1 cervical squamous cell carcinoma: conservative management after laser conization with positive margins.

OBJECTIVE: Cone margin status has been reported to be the most important predictor of recurrent disease in patients with cervical intraepithelial neoplasia (CIN) undergoing cervical conization. Our purpose was to evaluate the conservative management of selected patients with microinvasive (FIGO stage Ia1) squamous cell carcinoma who have been treated by cervical conization with positive margins. METHODS: Twenty-seven patients underwent KTP laser conization and vaporization for stage Ia1 squamous cell carcinoma followed by careful observation. Involved margins were diagnosed if CIN III or more was present at the ectocervical or endocervical margin and 7 patients formed the basis of the present study. Follow-up consisted of cytology, histology, and pelvic examination. Disease recurrence was defined as a histology diagnosis of CIN III or more on colposcopically directed biopsy or endocervical curettage. RESULTS: The endocervical margins were involved by carcinoma in situ in seven (26%) patients. No ectocervical margin involvement was detected. No lymph-vascular space involvement (LVSI) and confluent invasion were seen. All seven patients were free of recurrent disease during median follow-up of 4.0 (range 2.3-7.6) years. CONCLUSION: These results suggest that laser conization and vaporization may be a reasonable treatment option in patients with microinvasive (FIGO Stage Ia1) squamous cell carcinoma despite positive cone margins without invasive disease when LVSI is not demonstrated.

Adult↗

Prediction of persistence or recurrence after conization for cervical intraepithelial neoplasia III.

OBJECTIVE: To estimate the predictive factors for persistent/recurrent disease before and after conization for cervical intraepithelial neoplasia III. METHODS: Patients who received conization due to histologic diagnosis of cervical intraepithelial neoplasia III from 1998 to 2000 and who had at least one cytologic/histologic follow-up within one year of conization (n = 449) were enrolled in our study. All available demographic and pathologic parameters were analyzed. RESULTS: We performed multivariable logistic regression analysis to identify predictive factors for cervical intraepithelial neoplasia III persistence/recurrence. Age (greater than 50 years) was the only preoperative predictor and had an odds ratio equaling 3.070 (95% confidence interval [CI] 1.421-6.630, P = .004). Post-cone endocervical curettage was found to be the most statistically significant factor for predicting persistent disease (odds ratio 7.940, 95% CI 3.428-18.390, P < .001). Positive endocervical curettage was associated with 65.5% (36/55) of persistent disease, whereas negative endocervical curettage was associated with only 7.6% (26/342). Positive endocervical resection margins and multiple-quadrant disease also had predictive values with odds ratios equaling 2.972 (95% CI 1.401-6.281, P = .004) and 2.180 (95% CI 1.014-4.689, P = .046), respectively. The positive predictive values for age (> 50 years), positive endocervical curettage, positive endocervical resection margin, and multiple quadrant disease were 31.7%, 65.5%, 40.0%, and 21.9%, respectively. CONCLUSION: We found that age is the only preoperative predictive factor. Pathologic parameters, including endocervical curettage, endocervical resection margins, and multiple-quadrant disease are the only postoperative predictive factors for cervical intraepithelial neoplasia persistence or recurrence found in our study. These factors should be considered in patient management before and after therapeutic conization for cervical intraepithelial neoplasia III. LEVEL OF EVIDENCE: II-3.

Adult↗

Is laser conization adequate for therapeutic excision of adenocarcinoma in situ of the uterine cervix?

AIMS: To determine the safety of uterine-preserving operations for adenocarcinoma in situ of the cervix. METHODS: Fifteen cases of adenocarcinoma in situ (AIS) were diagnosed using neodymium:yttrium aluminum garnet (Nd:YAG) laser conization. The accuracy of preconization histology or cytology was evaluated in 15 AIS cases. In these AIS cases, we investigated how far the tumor was located from the squamocolumnar junction (SCJ) and the endocervix. Fourteen cases of the 15 AIS-affected patients were treated using laser conization alone. These patients were closely followed up. RESULTS: Precise agreement between preconization diagnosis and conization histology was seen in 46.7% (7/15) of the AIS cases. In 14 of the 15 cases of AIS (93.3%), the tumor was adjacent to the transitional zone, within 3 mm of the SCJ, and in the other case (6.7%), the tumor was between 0 and 5 mm away from the SCJ. In all subjects, cone height was 8-18 mm (mean 13.1 mm). None of the 15 patients showed any recurrence of AIS during follow up ranging from 15 to 75 months (43.1 months on average). CONCLUSIONS: Women with AIS who want to preserve their fecundity might be treated with laser conization alone.

Adenocarcinoma↗

Conization by harmonic scalpel for cervical intraepithelial neoplasia: a clinicopathological study.

The Harmonic Scalpel((R)) (HS) is a new surgical tool that cuts and coagulates by converting electrical energy into ultrasonic mechanical vibrations. The purpose of our study was to compare HS conization and the loop electrosurgical excision procedure (LEEP) for cervical intraepithelial neoplasia (CIN) with respect to both clinical and pathological features. Fifty-one consecutive women conservatively treated (29 with LEEP and 22 with HS conization) for CIN III were retrospectively reviewed. The background of the patients was similar. Operative time, intra- and postoperative blood loss were not significantly different. With HS conization all specimens were removed in one piece, but with LEEP the median number of specimens obtained per patient was 3.3 (p<0.0001) with a maximum of 5. The depth of thermal artifacts at the endocervical margin was significantly less with HS conization (0.20 mm) than with LEEP (0.30 mm; p = 0.0006). This new method produced an ideal-shaped specimen without increasing complications and thermal artifacts compared with LEEP.

Adult↗

Early cervical neoplasia confirmed by conization: diagnostic accuracy of cytology, colposcopy and punch biopsy.

OBJECTIVE: To investigate the accuracy rates of cytology, colposcopy and punch biopsy in early cervical neoplasia confirmed by conization. STUDY DESIGN: During the 10 years from 1984 to 1993, cold knife conization was performed on 151 patients with early cervical neoplasia proven by punch biopsy at our department. The accuracy rates of cytology, colposcopy and punch biopsy were investigated. RESULTS: The accuracy rates of cytology, colposcopy and punch biopsy were 52% (78 of 151), 66% (100 of 151) and 66% (100 of 151), respectively. CONCLUSION: These results suggest that a composite diagnosis with cytology, colposcopy and punch biopsy is necessary for a correct evaluation. Early cervical neoplasms are frequently seen in young women, and conservative procedures, such as conization, cryosurgery and laser vaporization, are the treatments of choice in order to preserve reproductive function. We recommend conization as the best conservative procedure, with preservation of reproductive function.

Biopsy↗

[Pregnancy and delivery outcomes in women with previous cervical conization].

OBJECTIVE: The purpose of this study was to assess the effect of cervical conization on subsequent pregnancy and delivery outcomes. METHOD/STUDY DESIGN: We used a retrospective design that included the records of all women who had conization of the cervix in our department between March 1st 1993 and September 1st 2001. Loop electrosurgical excision procedure (LEEP) was performed in every woman. From the totality of records we selected the ones who subsequently got pregnant (20 patients) and determined the pregnancy and delivery events. RESULTS: 113 women in the reproductive years underwent cervical conization during this period; 45 (39.8%) were lost to follow up, 48 (42.5%) didn't get pregnant and 20 (11.7%) women achieved 21 pregnancies. Among these 21 pregnancies there were 2 (9.5%) spontaneous abortions, 2 (9.5%) voluntary terminations of pregnancies, 1 (4.8%) elective termination of pregnancy, 1 (4.8%) ectopic pregnancy, 1 (4.8%) pregnancy evolving in the first trimester at the time of the study and 14 (66.7%) term deliveries. This last group was studied with more detail. Half of the women were nulliparous and half were multiparous. There were 2 cases of threatened preterm labour, 2 gestation diabetes, 1 pregnancy induced hypertension, 1 intrauterine growth restriction, 1 macrosomic foetus, 1 premature rupture of membranes and in three cases the labour was induced. The mean time between conization and delivery was 35.75 months. All deliveries occurred between 37 and 40 weeks of gestation; 11 (78.6%) women delivered vaginally and 3 (21.4%) had caesarean section. Only one newborn weighted less than 2500 g. The mean duration of labour (active phase of the first stage and 2nd stage) was 130.92 minutes (95 minutes for multiparous and 157.5 minutes for nulliparous women). CONCLUSION: Despite the small number of cases, pregnant patients who previously underwent LEEP don't seem to be at increased risk of adverse pregnancy outcome, preterm delivery, caesarean delivery or low birth weight. There was, however, a tendency to short duration of labour.

Adult↗

[Consequences and treatment of cervical stenoses after laser conization or loop electrosurgical excision].

OBJECTIVE: To assess the frequency and the consequences of cervical stenosis in patients treated by laser conization or loop electrosurgical excision procedure (LEEP) and to analyse the results of cervical enlargement plastic surgery or neostomia. METHODS: Two hundred and fifty-five women treated by laser conization and 277 by LEEP were regularly followed by postoperative colposcopy, for a mean period of 38 and 16 months, respectively. Stenosis was defined as cervical narrowing which could not admit a 2.5 mm-diameter Hegar's dilator. RESULTS: Stenosis complicated 10.2% of the laser conizations and 4.3% of the LEEP. Thus, 38 cases of cervical stenosis of which 7 were complete were diagnosed 2 to 40 months after treatment. Among the 34 non-menopaused women who developed a stenosis, 5 had a secondary amenorrhea, 6 a severe dysmenorrhea and one an infertility related to oligoamucorrhea. In the patients with stenosis, endocervical cell retrieval was possible in 21 (55%) cases and in none the squamocolumnar junction was visible at colposcopy. Seven patients underwent an enlargement plastic surgery of the cervical canal for incomplete stenosis and two a neostomia for complete stenosis. Cervical restenosis has been observed in 7 of 9 cases in a mean delay of 12 months (3 to 48 months). Nevertheless, the endocervical cell retrieval remained possible in 8 of 9 cases and after a mean follow-up of 26 months no menstrual troubles recurred. CONCLUSION: LEEP provides fewer cervical stenosis than laser conization. The enlargement plastic surgery allows to correct durably the menstrual troubles in spite of the very frequent restenosis.

Adult↗

Clinicopathologic variables predictive of residual dysplasia after cervical conization.

OBJECTIVE: To evaluate the clinicopathologic variables that are important for predicting residual dysplasia after cervical conization or the loop electroexcisional procedure. STUDY DESIGN: A retrospective review of 80 cases was performed on patients with squamous dysplasia in the conization specimen, endocervical curettage (ECC) performed immediately after resection, margin status reported by the pathologist and adequate postprocedure follow-up. RESULTS: Twelve patients had residual dysplasia. No case progressed to invasive carcinoma. A multivariate analysis was performed with presence or absence of residual dysplasia as the dependent variable and patient age, type of procedure (cold knife conization or loop excision), grade of dysplasia, margin status and ECC status as independent variables. Margin status was the strongest predictor of residual disease, followed by ECC status. Patient age had a minimal association with persistence. Of the 12 patients with residual dysplasia, 11 had a positive margin, and 8 had a positive ECC. Only 38% of patients with a positive margin had residual disease, but 67% with a positive margin and ECC had residual dysplasia. CONCLUSION: Margin status and ECC are useful in predicting residual dysplasia after conization.

Adolescent↗

Evaluating cervical neoplasia. LEEP as an alternative to cold knife conization.

OBJECTIVE: To determine how the loop electrosurgical excision procedure (LEEP) compares to cold knife conization in providing an adequate diagnostic specimen. STUDY DESIGN: Between 1991 and 1995, 95 patients underwent either diagnostic LEEP or cold knife conization at Allegheny University Hospitals. The indications for the procedure were a cytologic/histologic discrepancy, unsatisfactory colposcopic evaluation, positive endocervical curettage or exclusion of invasion. RESULTS: Severe thermal artifact rendered the LEEP specimens uninterpretable in 4.4% of cases. A median number of two passes were required for LEEP excision of the transformation zone. The number of passes correlated with the amount of thermal artifact detected (P = .034). Regarding recurrence patterns, normal follow-up cervical cytology was similar for both groups: 96.7% in the LEEP group vs. 100% in the cold knife conization group. CONCLUSION: We conclude that LEEP is an acceptable diagnostic alternative to traditional cold knife conization. Thermal artifact remains a disadvantage that can be minimized by limiting the number of passes required to obtain a complete specimen.

Adolescent↗

Conization as only treatment of carcinoma in situ of the uterine cervix.

Knife conization was performed in 2,099 cases with abnormal vaginal smears. The frequency of complications was low. Carcinoma in situ was diagnosed in 1,500 cases and follow-up showed that conization was curative in 87%. The curative rate was depending on whether the resection margins were free of pathologic epithelium or not. If smears were repeatedly negative the first year after conization a new diagnosis of cancer was made in 0.4%. It was not possible to decide whether these lesions were residual changes or true recurrences. Treatment of carcinoma in situ by conization has so far reduced the frequency of invasive cervical cancer by 60%.

Adolescent↗

The relationship between prior cervical conization, cervical microbial colonization and preterm premature rupture of the membranes.

The occurrence of prior cervical conization and the cervical microbial colonization was investigated in 38 women with idiopathic preterm labor, 35 women with preterm premature rupture of the membranes (PPROM) and 75 normal pregnant women at 26-34 weeks of gestation. Data were analyzed by Fisher's exact test (two-tailed). The frequency of prior cervical conization was significantly higher in PPROM patients compared to normal pregnant women (P < 0.001) and to patients in preterm labor (P < 0.01). Lactobacilli occurred with a lower frequency in patients with PPROM compared to patients in preterm labor (P < 0.05) and control patients (P = 0.0543)-and with a lower frequency in patients with prior cervical conization (P < 0.05). All other microorganisms occurred with the same frequencies in all groups. The absence of lactobacilli may indicate changes in the cervical flora, which could increase the risk of PPROM. Prior cervical conization may impair the antimicrobial defense-mechanisms in the cervix, which could facilitate ascending microbial colonization. This may lead to a release of prostaglandins and proteolytic enzymes and subsequently preterm labor and rupture of the membranes.

Adult↗