Practice guidelines for management of ovarian cancer in Korea: a Korean Society of Gynecologic Oncology Consensus Statement / 부인종양

Since after 2006 when the first edition of practice guidelines for gynecologic oncologic cancer treatment was released, the Korean Society of Gynecologic Oncology (KSGO) has published the following editions on a regular basis to suggest the best possible standard care considering updated scientific evidence as well as medical environment including insurance coverage. The Guidelines Revision Committee was summoned to revise the second edition of KSGO practice guidelines, which was published in July 2010, and develop the third edition. The current guidelines cover strategies for diagnosis and treatment of primary and recurrent ovarian cancer. In this edition, we introduced an advanced format based on evidence-based medicine, collecting up-to-date data mainly from MEDLINE, EMBASE, and Cochrane Library CENTRAL, and conducting a meta-analysis with systematic review. Eight key questions were raised by the committee members. For every key question, recommendations were developed by the consensus meetings and provided with evidence level and strength of the recommendation.

Is the ovarian preservation safe in young women with stages IB–IIA villoglandular adenocarcinoma of the uterine cervix? / 부인종양

OBJECTIVE: Because villoglandular adenocarcinoma (VGA) of the uterine cervix has favorable features and outcomes, patients receive less radical surgery and young women preserve their ovaries. We aimed to evaluate the clinicopathological features and outcomes of VGA and to see if the ovarian preservation is safe in young women with VGA. METHODS: We retrospectively reviewed medical records and identified patients with VGA, who had been treated and followed from January 2004 to December 2015. RESULTS: This study consisted of 17 patients with VGA, including 9 premenopausal women. International Federation of Gynecology and Obstetrics (FIGO) stage IB1 disease was found in 12 patients (70.6%), IA1 in 2, IA2 in 1, IB2 in 1, and IIA1 in 1. Of the 12 women diagnosed with stage IB1 disease, a young woman received only conization and she has not showed a recurrence. During a median follow-up of 58 months (range: 12–116), 4 patients, who had undergone radical surgery for stage IB1 disease, had a recurrence and one of them died due to disease progression. Among patients with stages IB–IIA disease, 2 premenopausal women did not receive simultaneous oophorectomy or chemoradiation therapy. Both of them had a recurrent tumor at adnexa. CONCLUSION: This study revealed favorable features and outcomes of VGA. However, the appropriate treatment for young women with early-stage VGA must be cautiously selected. Ovarian preservation might not be safe when young women with stages IB–IIA VGA undergo surgical procedures.

Fertility-preserving treatment in complex atypical hyperplasia and early endometrial cancer in young women with oral progestin: Is it effective?

OBJECTIVE: The aim of this study is to assess the effectiveness of oral progestin treatment in women diagnosed with complex atypical hyperplasia (CAH) or grade 1 endometrial cancer (G1EC), who desire to preserve their fertility, as alternative treatment to a hysterectomy. METHODS: We reviewed the medical records of women younger than 45 years old that had been diagnosed with CAH or G1EC, who expressed a desire to preserve their fertility using alternative treatment at our institution. Women without evidence of myometrial invasion on pelvic magnetic resonance imaging scans were included. The study period was between 2004 and 2014. Endometrial biopsies were taken at follow-up appointments. RESULTS: We identified 31 young women with CAH or G1EC. The median age was 33 years old (range, 20 to 41), and the median period of time undertaking the treatment was 5 months (range, 1 to 12). Twenty-three patients (74.2%) achieved complete remission (CR; median time to CR was 3 months; range, 1 to 22), 16 patients (88.9%) with CAH and 7 (53.8%) with G1EC achieved CR. 6 patients (26.1%) who had achieved CR, had recurrence of the disease (median time from CR to recurrence was 12.5 months; range, 4 to 18). Eight patients (25.8%) finally underwent a hysterectomy. CONCLUSION: Oral progestin therapy is an alternative treatment for women with CAH or G1EC who desire fertility preservation. However, more prospective studies are needed for standard progestin regimen. Also, there still remains a risk of disease progression and recurrence. Therefore, close follow-up is important during treatment and after CR. In addition, a hysterectomy is recommended as a definitive treatment after completion of childbearing.

A case of advanced-stage endometrial stromal sarcoma of the ovary arising from endometriosis

Endometrial stromal sarcoma (ESS) is a rare malignancy. Development of extrauterine ESS form endometriosis is particularly rare. The majority of extrauterine ESS occurs in areas with preexisting endometriosis. The most common site is the ovary. We experienced a case of ESS of the ovary that arose from endometriosis with multiple disseminated lesions. This disease was managed by total abdominal hysterectomy, bilateral salpingo-oophorectomy, both pelvic lymph nodes dissection, omentectomy, and appendectomy followed by postoperative high-dose progesterone therapy. Here, we report this case with literature review.

A human papillomavirus (HPV)-16 or HPV-18 genotype is a reliable predictor of residual disease in a subsequent hysterectomy following a loop electrosurgical excision procedure for cervical intraepithelial neoplasia 3 / 부인종양

OBJECTIVE: This study was conducted using the human papillomavirus (HPV) DNA chip test (HDC), in order to determine whether the HPV genotype is a predictor of residual disease in a subsequent hysterectomy following a loop electrosurgical excision procedure (LEEP) for cervical intraepithelial neoplasia (CIN) 3. METHODS: Between January 2002 and February 2015, a total of 189 patients who underwent a hysterectomy within 6 months of LEEP caused by CIN 3 were included in this study. We analyzed their epidemiological data, pathological parameters, high-risk HPV (HR-HPV) load as measured by the hybrid capture II assay, and HR-HPV genotype as measured by the HDC. A logistic regression model was used to analyze the relationship between covariates and the probability of residual disease in subsequent hysterectomy specimens. RESULTS: Of the 189 patients, 92 (48.7%) had residual disease in the hysterectomy specimen, CIN 2 in seven patients, CIN 3 in 79 patients, IA1 cancer in five patients, and IA2 cancer in one patient. Using multivariate analysis, the results were as follows: cone margin positivity (odds ratio [OR], 2.43; 95% CI, 1.18 to 5.29; p or =220 relative light unit (OR, 2.98; 95% CI, 1.38 to 6.43; p<0.01), positive endocervical cytology (OR, 8.97; 95% CI, 3.81 to 21.13; p<0.001), and HPV-16 or HPV-18 positivity (OR, 9.07; 95% CI, 3.86 to 21.30; p<0.001). CONCLUSION: The HPV-16 or HPV-18 genotype is a reliable predictive factor of residual disease in a subsequent hysterectomy following a LEEP for CIN 3.

Development and Validation of the Korean Version of Hand-Foot Skin Reaction and Quality of Life Questionnaire (HF-QoL-K)

Given the growing number of cancer patients and the resulting increase in the administration of chemotherapeutic agents, convenient and effective methods for measuring the symptoms and quality of life associated with the hand-foot syndrome (HFS) are needed. Therefore, the aim of this study was to develop and validate the Korean version of the hand-foot skin reaction and quality of life questionnaire (HF-QoL-K), comprising a 20-item symptom domain and an 18-item daily activity domain. After we developed the HF-QoL-K, 209 Korean patients with gynecologic cancer who were undergoing chemotherapeutic agents relating the HFS were asked to fill in the questionnaire. The content validity, internal consistency reliability, and test-retest reliability were evaluated. The internal validity index, Cronbach’s alpha coefficient, and intra-class correlation coefficient of the HF-QoL-K were 0.90, 0.958, and 0.825 (95% confidence interval [CI], 0.774–0.865), respectively. The scatter plot (Pearson correlation coefficient, 0.826) and the Bland-Altman plot for test-retest reliability were also acceptable. The HF-QoL-K instrument is a valid and reliable questionnaire for the measurement of the symptoms and quality of life in Korean cancer patients suffering HFS.

The prognostic value of squamous cell carcinoma antigen for predicting tumor recurrence in cervical squamous cell carcinoma patients

OBJECTIVE: The aim of this study was to evaluate the prognostic value of squamous cell carcinoma antigen (SCC-Ag) and the optimal cut-off value for predicting recurrence in cervical squamous cell carcinoma patients with complete remission after primary treatment. METHODS: We reviewed the records of 783 cervical squamous cell cancer patients who underwent primary therapy and showed complete remission at our institution between January 2000 and April 2014. A receiver operating characteristic curve was used to determine the optimal SCC-Ag threshold to predict recurrence. Cox regression model for disease free survival was used to assess differences in outcome. RESULTS: The median follow-up period was 41.2 months, and 154 patients (19.7%) had recurrent disease. The median pretreatment and posttreatment SCC-Ag level was 2.6 ng/mL (range, 0.1 to 532.0 ng/mL) and 0.7 ng/mL (range, 0.0 to 46.8 ng/mL), respectively. Both pretreatment and posttreatment SCC-Ag levels were higher in the recurrence group (P=0.017 and P=0.039). Optimal cut-off value of pretreatment and posttreatment SCC-Ag for predicting recurrence was 1.86 ng/mL (area under the curve, 0.663; P=0.000), and 0.9 ng/mL (area under the curve, 0.581; P=0.002), respectively. In the multivariate Cox regression model, pretreatment SCC-Ag >1.86 ng/mL (odds ratio, 2.11; 95% confidence interval, 1.38 to 3.22; P=0.001) and posttreatment SCC-Ag >0.9 ng/mL (odds ratio, 1.64; 95% confidence interval, 1.18 to 2.28; P=0.003) were significantly associated with poor disease free survival. CONCLUSION: Patients with pretreatment SCC-Ag >1.86 ng/mL or posttreatment SCC-Ag >0.9 ng/mL should be considered at high risk for cancer recurrence after complete remission, and therefore, closer surveillance is needed.

Erratum: Author Correction

The author list should be corrected.

Serous borderline tumor of the fallopian tube

Serous borderline tumors of the ovary are fairly common, making up between 4% and 14% of ovarian epithelial tumors. While to our knowledge serous borderline tumor of the fallopian tube occurs rarely with only ten previously reported cases in literature. We report the case of the serous borderline tumor of the fallopian tumor in a 25-year-old woman and review the literature.

Pre-Treatment Diffusion-Weighted MR Imaging for Predicting Tumor Recurrence in Uterine Cervical Cancer Treated with Concurrent Chemoradiation: Value of Histogram Analysis of Apparent Diffusion Coefficients

OBJECTIVE: To evaluate the value of apparent diffusion coefficient (ADC) histogram analysis for predicting tumor recurrence in patients with uterine cervical cancer treated with chemoradiation therapy (CRT). MATERIALS AND METHODS: Our institutional review board approved this retrospective study and waived informed consent from each patient. Forty-two patients (mean age, 56 +/- 14 years) with biopsy-proven uterine cervical squamous cell carcinoma who underwent both pre-treatment pelvic magnetic resonance imaging with a 3.0 T magnetic resonance scanner and concurrent CRT were included. All patients were followed-up for more than 6 months (mean, 36.4 +/- 11.9 months; range 9.0-52.8 months) after completion of CRT. Baseline ADC parameters (mean ADC, 25th percentile, 50th percentile, and 75th percentile ADC values) of tumors were calculated and compared between the recurrence and no recurrence groups. RESULTS: In the recurrence group, the mean ADC and 75th percentile ADC values of tumors were significantly higher than those of the no recurrence group (p = 0.043 and p = 0.008, respectively). In multivariate analysis, the 75th percentile ADC value of tumors was a significant predictor for tumor recurrence (p = 0.009; hazard ratio, 1.319). When the cut-off value of the 75th percentile ADC (0.936 x 10-3 mm2/sec) was used, the overall recurrence free survival rate above the cut-off value was significantly lower than that below the cut-off value (51.9% vs. 91.7%, p = 0.003, log-rank test). CONCLUSION: Pre-CRT ADC histogram analysis may serve as a biomarker for predicting tumor recurrence in patients with uterine cervical cancer treated with CRT.

Prognostic value of serum CA-125 in patients with advanced epithelial ovarian cancer followed by complete remission after adjuvant chemotherapy

OBJECTIVE: The aim of this study was to evaluate the prognostic value of serum CA-125 in advanced epithelial ovarian cancer with complete remission after primary adjuvant chemotherapy. METHODS: We reviewed the records of 120 patients with advanced epithelial ovarian cancer who underwent primary surgery followed by adjuvant therapy at our institution between January 1998 and December 2005. RESULTS: The median progression free survival was 21.6 months and 12.5 months in patients with nadir CA-125 levels 35 U/mL, respectively, after first cycle of adjuvant chemotherapy. CONCLUSION: Serum CA-125 level after the first cycle of adjuvant chemotherapy is a strong independent prognostic factor for advanced epithelial ovarian cancer with complete response.

Expression of peroxiredoxin I regulated by gonadotropins in the rat ovary / 대한생식의학회지

OBJECTIVE: Peroxiredoxins (Prxs) play an important role in regulating cellular differentiation and proliferation in several types of mammalian cells. This report examined the expression of Prx isotype I in the rat ovary after hormone treatment. METHODS: Immature rats were injected with 10 IU of pregnant mare's serum gonadotropin (PMSG) to induce the growth of multiple preovulatory follicles and 10 IU of human chorionic gonadotropin (hCG) to induce ovulation. Immature rats were also treated with diethylstilbestrol (DES), an estrogen analogue, to induce the growth of multiple immature follicles. Northern blot analysis was performed to detect gene expression. Cell-type specific localization of Prx I mRNA were detected by in situ hybridization analysis. RESULTS: During follicle development, ovarian Prx I gene expression was detected in 3-day-old rats and had increased in 21-day-old rats. The levels of Prx I mRNA slightly declined one to two days following treatment with DES. A gradual increase in Prx I gene expression was observed in ovaries obtained from PMSG-treated immature rats. Furthermore, hCG treatment of PMSG-primed rats resulted in a gradual stimulation of Prx I mRNA levels by 24 hours (2.1-fold increase) following treatment, which remained high until 72 hours following treatment. In situ hybridization analysis revealed the expression of the Prx I gene in the granulosa cells of PMSG-primed ovaries and in the corpora lutea of ovaries stimulated with hCG for 72 hours. CONCLUSION: These results demonstrate the gonadotropin and granulosa cell-specific stimulation of Prx I gene expression, suggesting its role as a local regulator of follicle development.

Complications Following Outside-in and Inside-out Transobturator-Tape Procedures with Concomitant Gynecologic Operations / 전남의대학술지

This study was undertaken to compare the complications of outside-in transobturator tape procedures (TOT) and inside-out transobturator tape procedures (TVT-O) with concomitant gynecologic surgery for the treatment of female stress urinary incontinence (SUI). A retrospective review of 206 consecutive patients who underwent either TOT or TVT-O with concomitant gynecologic operations between March 2008 and February 2011 was conducted. The incidence of perioperative complications was compared. For statistical analysis, chi-squared tests were used. There were no reports of intraoperative complications such as vaginal injury or bladder perforation. Postoperative complications were noted in 23 procedures (11.2%). These included 6 cases of urinary retention (2.9%), 2 cases of vulva hematoma (1.0%), 7 cases of urinary tract infection (3.4%), 4 cases of de novo urgency (2.9%), and 4 cases of vaginal erosion (2.9%). There were no significant differences in complication rates between the two groups. Our results suggest that inside-out and outside-in procedures are simple and safe techniques that may have a low rate of complications when used with a concomitant gynecologic operation.

Complications Following Outside-in and Inside-out Transobturator-Tape Procedures with Concomitant Gynecologic Operations / 전남의대학술지

This study was undertaken to compare the complications of outside-in transobturator tape procedures (TOT) and inside-out transobturator tape procedures (TVT-O) with concomitant gynecologic surgery for the treatment of female stress urinary incontinence (SUI). A retrospective review of 206 consecutive patients who underwent either TOT or TVT-O with concomitant gynecologic operations between March 2008 and February 2011 was conducted. The incidence of perioperative complications was compared. For statistical analysis, chi-squared tests were used. There were no reports of intraoperative complications such as vaginal injury or bladder perforation. Postoperative complications were noted in 23 procedures (11.2%). These included 6 cases of urinary retention (2.9%), 2 cases of vulva hematoma (1.0%), 7 cases of urinary tract infection (3.4%), 4 cases of de novo urgency (2.9%), and 4 cases of vaginal erosion (2.9%). There were no significant differences in complication rates between the two groups. Our results suggest that inside-out and outside-in procedures are simple and safe techniques that may have a low rate of complications when used with a concomitant gynecologic operation.

Evaluation of length, volume and gray-scale histogram of the cervix as predictors of successful induction / 대한산부인과학회지

OBJECTIVE: The aim of this study was to evaluate whether the Bishop score, length, volume and gray-scale histogram of the cervix has a predictive value of assessing the rate of success in trial of induction. METHODS: Forty-one nulliparous patients with its Bishop score six or less were enrolled for this prospective study. All were on prostaglandin E2 (PGE2, Propess(R); Controlled Therapeutics Ltd) pessary. Three-dimensional transvaginal ultrasound scans of the cervix were performed on the ACCUVIX XQ (Medison) to measure length, volume, and gray-scale histogram. Bishop score was determined by digital examination. The successful induction was defined as the ability to achieve the active phase of labor corresponding to a cervical dilatation of > or =4 cm within 12 hours of removing the PGE2 pessary. The receiver operating characteristics (ROC) curves were also used to estimate an optimal cutoff point for the Bishop score, length, volume, and gray-scale histogram of the cervix. Logistic regression analysis was used for statistical analyses. RESULTS: The overall successful rate of labor induction was 73.2% (30/41). Multiple logistic regression analyses demonstrated that the value of anterior lip histogram was significantly associated with the successful labor induction. ROC curve for anterior lip histogram value in predicting success of induction indicated a significant relationship with successful induction. The best cutoff value was 69.4. CONCLUSION: The value of anterior lip histogram associates significantly with the prediction of successful induction in nulliparous women. But, Bishop score and other sonographic measurement of cervical length, volume, and posterior lip histogram have no predictive values for successful induction.

A case of giant fibroepithelial polyp of the vulva / 대한산부인과학회지

Fibroepithelial polyps are benign soft tissue tumors that occur in a wide variety of sites, including the lower female genital tract. They exhibit a wide range of morphologic appearances and can be misinterpreted as malignant. A 16-year-old woman presented with a 28x27 cm polypoid lesion localized on the right labium. The labial lesion was resected and recurred 6 years following the initial treatment. The histologic findings of the initial and recurrent lesions were consistent with fibroepithelial polyps. We present a case of a fibroepithelial polyp that is larger than any previously described lesion and recurred lesion with a brief review of the literature.

Lipid peroxidation and total antioxidant ability in venous plasma and amniotic fluid of pregnant women with preterm premature rupture of membranes / 대한산부인과학회지

OBJECTIVE: To evaluate their roles in the pathophysiology of preterm premature rupture of membranes (PPROM), we checked interleukin (IL)-6, lipid peroxide, oxygen-radical absorbance capacity (ORAC) and antioxidant vitamin in the venous plasma and amniotic fluid of women with PPROM. METHODS: Venous plasma and amniotic fluid was taken from 20 normal pregnant women and 20 PPROM pregnancy women. IL-6 levels was determined by enzyme-linked immunosorbent assay. Lipid peroxide levels were measured by thiobarbituric acid reaction. The ORAC levels and the antioxidant levels were measured by Cao's method and by high performance liquid chromatography. RESULTS: The IL-6 levels in the venous plasma and amniotic fluid of PPROM pregnancy women were significantly higher than normal pregancy (P<0.01, P<0.01). The lipid peroxide levels in the venous plasma and amniotic fluid of PPROM pregnancy women were significantly higher than normal pregancy (P<0.01, P<0.01). The ORAC values in the venous plasma and amniotic fluid of PPROM pregnancy women were significantly higher than normal pregancy (P<0.01, P<0.01). The ORAC values/lipid peroxide levels in the venous plasma and amniotic fluid of PPROM pregnancy women were significantly higher than normal pregancy (P<0.01, P<0.01). The ascorbic acid levels in the venous plasma and amniotic fluid of PPROM pregnancy women were significantly higher than normal pregancy (P<0.05, P<0.01). CONCLUSION: This result suggest that the increased inflammatory bioactivity, increased lipid peroxidation and decreased antioxidant activity may be involved in the pathophysiology of PPROM. Low levels of ascorbic acid appears to be an important determinant of PPROM.

Changes in lipid peroxidation and protein oxidation by antibiotic therapy in the maternal venous plasma of preterm premature rupture of membranes / 대한산부인과학회지

OBJECTIVE: To investigate and compare the amount of the lipid peroxidation and the protein carbonyls formation in maternal venous plasma of preterm premature rupture of membranes (PPROM) during antibiotics administration. METHODS: PPROM were selected between 25 and 32 weeks of gestation. Eighteen patients (group 1) were treated with amoxicillin and erythromycin for 7 day period, 18 patients (group 2) were treated with 3rd generation cephalosporin (cefodizime, cefditoren) and erythromycin for the same period. Maternal blood were obtained from the two groups before and after the antibiotics administration, day 3 and day 7. Lipid peroxidation levels and protein carbonyl contents were measured by thiobarbituric acid reaction and 2,4-dinitrophenyl hydrazine method. Other 18 women with normal pregnancy between 25 and 32 weeks of gestation of venous blood were checked same things in vitro. Interleukin (IL) -6 was measured by enzyme-linked immunosorbent assay. RESULTS: 1. The lipid peroxidation levels and protein carbonyls formation in the maternal venous plasma of PPROM was significantly higher than that of normal pregnancy (lipid peroxidation levels; 4.77+/-.36 vs 7.11+/-.41 nmol/mg protein, P<001, protein carbonyls formation; 3.55+/-.22 vs 5.69+/-.30 nmol/mg protein, P<001). 2. There were no significant differences in the lipid peroxidation levels and protein carbonyls formation of the maternal venous plasma with PPROM mixed and incubated by amoxicillin, cefodizime, cefditoren, and erythromycin (in vitro). 3. There were no significant differences in the lipid peroxidation levels and protein carbonyls formation of the venous plasma of group 1 between before and after antibiotics administration, day 3 and day 7. 4. There were no significant differences in the lipid peroxide levels of the venous plasma of group 2 between before and after antibiotics administration, day 3 and day 7. 5. The protein carbonyls formation in the venous plasma of group 2 was significantly decreased at day 3 and day 7 after antibiotics administration than that of before (6.04+/-.44 and 5.53+/-.37 vs. 7.04+/-.51 nmol/mg protein, P<005). 6. The levels of IL-6 in the venous plasma of group 2 was significantly decreased at day 7 after antibiotics administration than that of before (7.50+/-.35 vs. 3.13+/-.37 pg/mL, P<005). CONCLUSION: In the maternal venous plasma of PPROM, the lipid peroxidation levels and protein carbonyls formation were increased. The formation of protein carbonyls and IL-6 in the maternal blood of PPROM was decreased by combined treatment of 3rd generation cephalosporin and erythromycin. The results suggest that reactive oxygen species formation by inflammatory reaction is suppressed by the 3rd generation cephalosporins and erythromycin combined treatment.

Vaginal evisceration after radical hysterectomy and adjuvant radiation / 부인종양

Vaginal evisceration is a rare complication after a hysterectomy, especially a radical hysterectomy. Up to now, there have only been three cases of transvaginal evisceration after radical hysterectomy reported in the English literature. We report one case of transvaginal evisceration occurring after radical hysterectomy and adjuvant radiotherapy for stage IIA cervical cancer, with a brief review of the literature.

Effect of vitamin C and E on the lipid peroxide, antioxidant ability, and antioxidant vitamin levels in maternal and umbilical venous plasma / 대한산부인과학회지

OBJECTIVE: This controlled trial investigated the effect of supplementation with vitamins C and E on the lipid peroxide, antioxidant ability, and antioxidant vitamin levels in full term maternal and umbilical venous plasma. METHODS: Forty pregnant women were randomized in this study. They were nulliparous or multiparous women with history of preeclampsia or preterm premature rupture of membranes (PPROM). Twenty women were given vitamin C (1,000 mg/day) and vitamin E (400 IU/day) from 15~20 gestational weeks to delivery. The others were not given, as a control group. Maternal venous blood was obtained before vitamin supplementation and just before delivery. Umbilical venous blood was obtained after delivery. Lipid peroxide level and oxygen-radical absorbance capacity (ORAC) were measured by thiobarbituric acid reaction and Cao's method, respectively. Ascorbic acid, uric acid, beta-carotene, retinol, alpha-tocopherol, and gamma-tocopherol were measured by high performance liquid chromatography. Results: Supplementation with vitamins C and E was associated with decrease in lipid peroxide levels and increase in ORAC values and alpha-tocopherol levels in maternal venous plasma. And it was also associated with decrease in lipid peroxide levels and increase in ORAC values and alpha-tocopherol levels in umbilical venous plasma. CONCLUSION: Supplementation with vitamins C and E may be beneficial in the prevention of oxidant-antioxidant imbalance origin diseases such as preeclampsia, PPROM. And it also may affect antioxidant ability of the fetus.