Maternal and neonatal vitamin-D status in twin versus singleton pregnancies.

AIM: There is a paucity of information on vitamin D status of women with twin pregnancy and their newborns. This case-control study compared maternal and neonatal vitamin-D status in twin versus singleton pregnancies. METHODS: Subjects included 50 women with twin pregnancy delivering at >28 weeks and 50 gestational-age-matched women with singleton pregnancy delivering during the same period. Maternal and neonatal serum 25-hydroxy vitamin D [25(OH)D] was compared between the two groups using the independent Student's t-test on log values. Serum albumin-adjusted calcium, inorganic phosphate, and intact parathormone levels were also compared. RESULTS: Maternal vitamin-D deficiency (VDD; serum 25(OH)D < 30 nmol/L) was present in 90% of twin and 88% of singleton pregnancies. The prevalence of neonatal VDD was 89% in twin and 74% in singleton pregnancies (P = 0.03). Maternal serum 25(OH)D was lower in the twin group as compared to the singleton group (14.3 ± 10.47 vs 18.5 ± 12.36 nmol/L; P = 0.02). Mean serum calcium, intact parathormone, and inorganic phosphate were comparable between the women in the two groups. Maternal and neonatal 25(OH)D showed positive correlation in the two groups (P < 0.001). Mean cord blood 25(OH)D was significantly lower in the twins than in singleton newborns (14.8 ± 12.63 vs 22.6 ± 16.68 nmol/L; P = 0.002). The difference persisted even after adjustment for birthweights and maternal serum 25(OH)D. Mean serum calcium was significantly lower in the twins. CONCLUSION: Twin newborns and their mothers have higher VDD as compared to singleton newborns and their mothers in the VDD population.

Low grade endometrial stromal sarcoma: a case report.

Endometrial stromal sarcoma (ESS) is a rare malignant tumor of the endometrium, occurring in the age group of 40-50 years. We report a case of low-grade ESS in a 39-year-old woman, presenting as rapid enlargement of a uterine fibroid polyp associated with irregular and excessive vaginal bleeding. Polypectomy followed by pan hysterectomy was performed. Histopathological examination and immunohistochemistry confirmed LGESS. As the tumor is rarely encountered, management protocols are still questionable. In our case, we tried a different post-surgical protocol and the patient is being closely followed up. Although rare, ESS should be considered in the differential diagnosis of all women who present with a rapid enlargement of a uterine leiomyoma.

Physical state & copy number of high risk human papillomavirus type 16 DNA in progression of cervical cancer.

BACKGROUND & OBJECTIVES: High-risk human papilloma virus (HR-HPV) infection and its integration in host genome is a key event in malignant transformation of cervical cells. HPV16 being a dominant HR-HPV type, we undertook this study to analyze if viral load and physical state of the virus correlated with each other in the absence of other confounding variables and examined their potential as predictors of progressive cervical lesions. METHODS: Both, viral load and integration status of HPV16 were determined by real time URR PCR and estimation of E2:E6 ratio in a total of 130 PGMY-RLB -confirmed, monotypic HPV16-infected cervical DNA samples from biopsies of cytology-confirmed low grade (LSIL, 30) and high grade (HSIL, 30), and invasive carcinoma, (squamous cell carcinoma SCC, 70) cases. RESULTS: Investigation of DNA samples revealed a gradual increase in HPV16 viral load over several magnitudes and increased frequency of integration from LSIL to HSIL and HSIL to invasive cancer in relation to the severity of lesions in monotypic HPV16-infected cervical tissues. In a substantial number of precancer (11/60) and cancer cases (29/70), HPV16 was detected in concomitant mixed form. The concomitant form of HPV16 genome carried significantly higher viral load. INTERPRETATION & CONCLUSIONS: Overall, viral load and integration increased with disease severity and could be useful biomarkers in disease progression, at least, in HPV16-infected cervical pre-cancer and cancer lesions.

Vaginal misoprostol versus vaginal estradiol in overcoming unsatisfactory colposcopy.

BACKGROUND: Unsatisfactory colposcopy, an inability to visualize the entire transformation zone, is found in about 10-20% of the patients undergoing the procedure. These patients usually require conization for a comprehensive evaluation of the cervix. Our study aims to compare the efficacy and safety of vaginal misoprostol versus vaginal estradiol in overcoming unsatisfactory colposcopy. METHODS: We studied 48 women with unsatisfactory colposcopy. They were randomized into two groups: group I (n = 24) received 200 µg misoprostol vaginally and colposcopy was repeated after 6 h, while the subjects in group II (n = 24) were prescribed a 7-day course of 50 µg estradiol for vaginal insertion followed by a repeat colposcopy. The efficacy and safety of these two drugs were compared. RESULTS: Repeat colposcopy was satisfactory in 70.8% of the women given vaginal misoprostol compared to 82.6% of the women who used vaginal estradiol. The difference was not statistically significant. The adverse effects were reported more often by the women in the misoprostol group (41.6%) as compared to those in estradiol group (13%) (p = 0.04). CONCLUSION: Both estradiol and misoprostol were comparable in overcoming unsatisfactory colposcopy. However, a higher incidence of adverse effects was noted with misoprostol as compared to estradiol.

Facility-based review of 296 maternal deaths at a tertiary centre in India: could they be prevented?

AIMS: The aim of this study was to identify causes of maternal mortality at the facility and to assess the standard of care, deficiencies in health services and preventability of these deaths using facility-based maternal death reviews. MATERIAL AND METHODS: This was a prospective study at a tertiary care hospital that included all women who died during pregnancy or within 42 days of being pregnant during 2005-2010. RESULTS: A review of 296 maternal deaths revealed that 59% of these occurred in medical wards. Indirect maternal deaths (54%) outnumbered the direct deaths (46%). Main causes were hepatitis (18%), hemorrhage (10%) and puerperal sepsis (10%). Only 5% of the women had received antenatal care at the facility. One-third (34%) were referred from other centers. The majority (74%) were critically sick at admission. Most of the women (62%) died postpartum. Substandard care and deficient health services were identified in 8% and 20% of the cases, respectively. Sixteen (5%) maternal deaths were deemed preventable and another 36 (12%) possibly preventable. Since most of the preventable deaths (12/16) were due to hemorrhage, measures to control postpartum hemorrhage were promoted at the facility. Findings of the maternal death reviews were regularly conveyed to the State Health Department for prioritization and resource allocation to prevent maternal mortality. CONCLUSION: More maternal deaths occurred in the medical than in the obstetrics wards at the facility. The leading causes were hepatitis, hemorrhage and puerperal sepsis. Most of the deaths were non-preventable as the women were critically sick at admission; however, substandard care and health service deficiency were contributory in some of the cases.

HPV typing and its relation with apoptosis in cervical carcinoma from Indian population.

Definite progress in understanding the etiology of cervical cancer has been achieved, and some types of human papillomavirus have been established as the central cause of cervical cancer worldwide. This study investigates the human papillomavirus infection and its correlation with apoptosis and clinicopathologic characteristics in squamous cell carcinoma of uterine cervix. Human papillomavirus typing was done by type-specific primers for high-risk human papillomavirus using standard polymerase chain reaction method. Programmed cell death (apoptosis) was determined by terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling assay. Human papillomavirus infection in tissue biopsy of cervical carcinoma was detected in 131 of 135 (97%) cases. Among the positive cases of human papillomavirus, 123 (94%) cases were human papillomavirus type 16, and five (4%) cases were human papillomavirus type 18. Out of 135 cervical carcinoma cases, 81 (60%) cases showed presence of apoptosis. The phenomenon of apoptosis was seen slightly higher in squamous cell carcinoma than in adenocarcinoma (40% in squamous cell carcinoma and 33% in adenocarcinoma). The human papillomavirus infection in cervical cancer might not play any role in the occurrence of apoptosis.

Obstetric and gynecological outcome in a patient with traumatic pelvic fracture and perineal injuries.

A 19-year-old woman presented with pelvic trauma following a road accident. She was hemodynamically stable. Examination revealed perineal injuries and type C pelvic fracture, which was stabilized with an external fixator. The broken ends of the pubic bone were brought together by an orthopedic wire. The detached vaginal wall and torn anal sphincter were surgically repaired after making a diverting colostomy. The postoperative period was uneventful. Colostomy was reversed after 3 months. Postoperatively the patient developed a cystocele, dyspareunia and vaginal pain. She conceived spontaneously and was planned for an elective cesarean at 37 weeks gestation; however, she presented in labor at 36 weeks and had a normal vaginal delivery. Pelvic fractures may be associated with genitourinary and anal sphincter injuries, which require management by a multidisciplinary team. On recovery the patient may develop prolapse, dyspareunia and persistent local pain. Spontaneous conception and normal vaginal delivery are nevertheless possible.

Idiopathic primary ovarian insufficiency: a study of serial hormonal profiles to assess ovarian follicular activity.

BACKGROUND: Ovarian follicular activity in serial hormone profiles has been reported in up to 86% of patients with primary ovarian insufficiency (POI). In most of these studies, patients had a short duration of amenorrhea or irregular menstrual cycles which could influence the occurrence of spontaneous follicular activity. The aim was to study the incidence of follicular activity in serial hormonal profiles of women with spontaneous POI and amenorrhea of 1 year duration. METHODS: This observational study involved 20 patients with spontaneous POI, amenorrhea of >1 year duration and normal karyotype. Serum measurements of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), progesterone, free T3, free T4, thyroid-stimulating hormone and anti-thyroperoxidase antibodies, taken in the absence of estrogen replacement, were followed by weekly measurements of serum E2, FSH, LH and progesterone for 1 month then monthly measurements for 2 months. Increases in serum E2 >184 pmol/l and serum progesterone >10 nmol/l were taken as evidence of follicular activity and ovulation, respectively. RESULTS: A rise in serum E2 >184 pmol/l was noted in 2/18 subjects [11.1%; 95% confidence interval (CI): 1.4-34.7%]. Though the corresponding serum FSH levels showed a decline, the values remained >40 IU/l. None of the subjects had serum progesterone levels >10 nmol/l, return of menses or pregnancy. CONCLUSION: Endogenous ovarian follicular function is intermittently present in only 11.1% of Asian Indian women with POI. However, the 95% CI (1.4-34.7%) was large due to a small sample size.

Contralateral ovarian pregnancy after single tubal recanalisation.

Ovarian pregnancy accounts for less than 3% of all ectopic pregnancies. A 30-year-old who had undergone right tubal reanastomosis seven months prior presented with pain abdomen and spotting. Her last menstrual period was 30 days prior. Examination revealed stable vitals, tenderness and shifting dullness per abdomen, fullness in the pouch of Douglas, a tender left adnexal mass and normal size uterus. Urine pregnancy test was positive. Culdocentesis revealed blood. A heteroechoic 3 × 3.2 × 3.1 cm left adnexal mass and free fluid were detected on ultrasound. There was no intrauterine gestational sac. On laparotomy 800 mL of hemoperitoneum was present. There was no evidence of tubal pregnancy. Left ovary had a 3 × 5 cm hemorrhagic mass. Partial ovariectomy was done and histopathology revealed ovarian pregnancy. This is the first reported case of an ovarian pregnancy occurring after tubal recanalisation. After successful tubal recanalisation procedure, altered motility of the reconstructed tube may cause expulsion of fertilized ovum into the peritoneal cavity and contralateral ovarian implantation.

Fetal scalp stimulation test: an adjunct to intermittent auscultation in non-reassuring fetal status during labor.

AIMS: To evaluate fetal scalp stimulation test (FSST) as an adjunct to intermittent auscultation in diagnosis of intrapartum fetal acidosis and associate result of FSST with cord blood pH and immediate neonatal outcome. MATERIAL & METHODS: This study was conducted at a tertiary hospital in India. Digital FSST was performed in seven hundred and fifty women in labor with singleton gestation ≥37 weeks, cephalic presentation and fetal heart abnormalities and/or thick meconium stained amniotic fluid. Intermittent auscultation was used for fetal monitoring during labor. The outcome measure was cord blood pH < 7.20 and neonatal morbidity. RESULTS: The non-reactive FSST is associated with lower umbilical cord blood pH, lower Apgar scores and higher asphyxia related neonatal morbidity (P-value < 0.001). The non-reactive FSST had 41% sensitivity and 84% specificity to detect pH < 7.20. The positive predictive value of FSST for fetal acidosis is 44% and negative predictive value is 83%. The likelihood ratio for acidosis with noncreative FSST is 2.57. CONCLUSIONS: Non-reactive FSST is associated with adverse neonatal outcomes. The positive and negative predictive values of FSST to diagnose fetal cord blood pH < 7.20 during labor are 44% & 83%, respectively.

Can visual inspection with acetic acid under magnification substitute colposcopy in detecting cervical intraepithelial neoplasia in low-resource settings?

PURPOSE: To compare the sensitivity, specificity, positive and negative predictive values and accuracy of visual inspection with acetic acid under magnification (VIAM) and colposcopy for detecting cervical intraepithelial neoplasia (CIN) to determine if VIAM can substitute colposcopy in identifying the biopsy site in screen-positive cases. METHODS: A prospective cross-sectional study was carried out on 408 symptomatic multiparous women in the reproductive age group (15-49 years) at a tertiary care teaching hospital. VIAM and colposcopy were used to screen for cervical precancerous lesions. Screen-positive women underwent guided biopsy and endocervical curettage. The site of biopsy was recorded as VIAM guided or colposcopy guided. Histopathology was taken as the gold standard. RESULTS: The mean age was 32.3 ± 6.8 years (range 15-49), whilst the mean parity was 2.9 ± 1.2 (range 1-9). A total of 113 women screened positive. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of VIAM and colposcopy were 95, 78, 19, 99 and 79%, and 86, 79, 18, 99 and 79%, respectively for high-grade lesions. CONCLUSIONS: VIAM can be a useful alternative to colposcopy when the latter is not available, as it has better sensitivity and equivalent specificity for detecting high-grade CIN.

Aberrant expression and constitutive activation of STAT3 in cervical carcinogenesis: implications in high-risk human papillomavirus infection.

BACKGROUND: Recent observations indicate potential role of transcription factor STAT3 in cervical cancer development but its role specifically with respect to HPV infection is not known. Present study has been designed to investigate expression and activation of STAT3 in cervical precancer and cancer in relation to HPV infection during cervical carcinogenesis. Established cervical cancer cell lines and prospectively-collected cervical precancer and cancer tissues were analyzed for the HPV positivity and evaluated for STAT3 expression and its phosphorylation by immunoblotting and immunohistochemistry whereas STAT3-specific DNA binding activity was examined by gel-shift assays. RESULTS: Analysis of 120 tissues from cervical precancer and cancer lesions or from normal cervix revealed differentially high levels of constitutively active STAT3 in cervical precancer and cancer lesions, whereas it was absent in normal controls. Similarly, a high level of constitutively active STAT3 expression was observed in HPV-positive cervical cancer cell lines when compared to that of HPV-negative cells. Expression and activity of STAT3 were found to change as a function of severity of cervical lesions from precancer to cancer. Expression of active pSTAT3 was specifically high in cervical precancer and cancer lesions found positive for HPV16. Interestingly, site-specific accumulation of STAT3 was observed in basal and suprabasal layers of HPV16-positive early precancer lesions which is indicative of possible involvement of STAT3 in establishment of HPV infection. In HPV16-positive cases, STAT3 expression and activity were distinctively higher in poorly-differentiated lesions with advanced histopathological grades. CONCLUSION: We demonstrate that in the presence of HPV16, STAT3 is aberrantly-expressed and constitutively-activated in cervical cancer which increases as the lesion progresses thus indicating its potential role in progression of HPV16-mediated cervical carcinogenesis.

A SRY-HMG box frame shift mutation inherited from a mosaic father with a mild form of testicular dysgenesis syndrome in Turner syndrome patient.

BACKGROUND: Sex determining factor (SRY) located on the short arm of the Y chromosome, plays an important role in initiating male sex determination, resulting in development of testicular tissue. Presence of the SRY gene in females results in XY sex reversal and increased risk of gonadal germ cell tumours if the karyotype also includes the so-called GonadoBlastoma on the Y chromosome (GBY) region. The majority of mutations within the SRY gene are de novo affecting only a single individual in the family. The mutations within the high-mobility group (HMG) region have the potential to affect its DNA binding activity. CASE PRESENTATION: We performed G- and R-banding cytogenetic analysis of the patient and her family members including her father. We also performed molecular genetic analysis of SRY gene. Cytogenetic analysis in the patient (Turner Syndrome) revealed the mosaic karyotype as 45, X/46, XY (79%/21% respectively) while her father (milder features with testicular dysgenesis syndrome) has a normal male karyotype (46, XY). Using molecular approach, we screened the patient and her father for mutations in the SRY gene. Both patient and her father showed the same deletion of cytosine within HMG box resulting in frame shift mutation (L94fsX180), the father in a mosaic pattern. Histological examination of the gonads from the patient revealed the presence of gonadoblastoma formation, while the father presented with oligoasthenozoospermia and a testicular seminoma. The frameshift mutation at this codon is novel, and may result in a mutated SRY protein. CONCLUSION: Our results suggest that lack of a second sex chromosome in majority cells of the patient may have triggered the short stature and primary infertility, and the mutated SRY protein may be associated with the development of gonadoblastoma. It is of importance to note that mosaic patients without a SRY mutation also have a risk for malignant germ cell tumors.

Comparison of Papanicolaou test with visual detection tests in screening for cervical cancer and developing the optimal strategy for low resource settings.

OBJECTIVES: To compare the sensitivity, specificity, positive and negative predictive values, and accuracy of Papanicolaou test with visual inspection with acetic acid (VIA)/VIA using magnification devices (VIAM) and develop the best strategy for screening in low resource settings. MATERIALS AND METHODS: This is a prospective cross-sectional study on 408 symptomatic multiparous women in the reproductive age group, sequentially using the Papanicolaou test, the VIA, and the VIAM for screening. Women with a positive screening test underwent guided biopsy and endocervical curettage. The site of biopsy was recorded. Histopathological findings were taken as the "gold" standard in comparing the methods. RESULTS: The mean (SD) age was 32.3 (6.8) years (range, 15-49 years), whereas the mean (SD) parity was 2.9 (1.2) (range, 1-9). Abnormal cytological findings were detected in 2.9% patients, whereas the remaining smears were negative for any intraepithelial lesion or malignancy. A total of 113 cases were screened positive by one/all methods. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the Papanicolaou test, the VIA, and the VIAM were 24, 98, 42, 96, and 94%; 95, 78, 19, 99, and 79%; and 95, 78, 19, 99, and 79%, respectively, for high-grade lesions. CONCLUSIONS: The Papanicolaou test had low sensitivity but high specificity, whereas visual detection methods had a high sensitivity in addition to being cheaper. Alternative methods of screening such as VIA/VIAM can be a valuable alternative to the Papanicolaou test for cervical cancer screening in low resource settings. Visual inspection using magnification devices may be of benefit over VIA in doubtful cases.

Evaluation of intravaginal misoprostol for medical management of pregnancies less than 20 weeks of gestation with absent cardiac activity.

AIM: To assess the efficacy and side-effects of misoprostol (800 microg used intravaginally) for terminating non-viable pregnancies up to 20 weeks of gestation. METHODS: Sixty five patients with non-viable pregnancies up to 20 weeks of gestation were given 800 microg misoprostol intravaginally on day 1. A second dose of 800 microg was repeated after 24 h if complete abortion was not attained with one dose. Primary outcome measure was success (defined as complete abortion in 48 h without surgical intervention). Duration and amount of blood loss, fall in hemoglobin, and other side-effects (pain, vomiting, diarrhea, fever and chills) were studied as secondary outcome measures. RESULTS: 73.8% of our patients had a gestational age

Genetic variant of CCND1: association with HPV-mediated cervical cancer in Indian population.

The potential association of single nucleotide polymorphisms (SNPs) (G870A and G1722C) of CCND1 with susceptibility to cervical cancer was investigated. The study included 200 cervical cancer cases along with an equal number of healthy controls. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis and direct sequencing were employed for genotyping. We found that women carrying the 870AA genotype have a 2.49-fold increased risk for the development of cervical cancer (odds ratio (OR) 2.49; 95% confidence interval (CI) 1.51-4.09; p = 0.0004) compared with GG+GA genotypes. For the 1722 locus, the frequency of the polymorphic 'C' allele was strongly associated with a reduced risk of cervical cancer (p = 0.019; OR 0.71; 95% CI 0.54-0.94). Our data suggest that CCND1 G870A polymorphism could act as a risk factor for the development of cervical cancer. And G1722C polymorphism may play a protective role against the development of human papillomavirus-associated cervical cancer among Indian women.

Calcium supplementation for the prevention of pre-eclampsia.

OBJECTIVE: To study the effect of calcium supplementation during pregnancy on blood pressure and maternal and neonatal outcomes. METHOD: A total of 524 healthy primigravidas with a blood pressure less than 140/90 mm Hg were randomly assigned between the 12th and 25th weeks to receive 2 g of elemental calcium or placebo and were followed-up until delivery. RESULTS: The incidence of pre-eclampsia was significantly less in the calcium than in the placebo group (4.0% vs 12.0%; odds ratio [OR], 0.31; 95% confidence interval [CI], 0.15-0.63); the mean systolic and diastolic blood pressures at study completion were different in the calcium and placebo group (P=0.007 and P=0.02). The risk for preterm delivery was less in the calcium (7.0%) than in the placebo (12.7%) group (OR, 0.51; 95% CI, 0.28-0.93). The mean baseline calcium intake was 313.83+/-203.25 mg/day (range, 85.71-910.71 mg/day), which is lower than the recommended dietary intake of 1000 mg, and the 24-hour urinary calcium excretion was 130.82+/-67.44 mg/dL (range, 40.5-387 mg/dL). CONCLUSION: Calcium supplementation appears to reduce the occurrence of pre-eclampsia and preterm delivery in primigravidas who have a daily dietary calcium intake less than the recommended dietary allowances.

Calcium in midpregnancy.

OBJECTIVE: To establish reference value for serum calcium concentration and urinary calcium excretion during mid pregnancy and to find out variation of calcium intake in pregnant women. MATERIALS AND METHODS: This was a cross sectional study conducted in antenatal clinic of department of Obstetrics and Gynaecology. A total of 543 pregnant women with pregnancy period of second trimester were enrolled for the study. Eligible healthy, vegetarian primigravid women provided serum and 24 h urinary samples for determination of serum calcium and urinary calcium excretion. Dietary intake calculated by 3-day recall method. Variation of calcium intake according to various demographic characteristics was noted. RESULTS: Statistical analysis done with SPSS software. The mean total serum calcium and 24 h urinary calcium and dietary intake of calcium were 8.1+/-1.5 mg/dl (5.1-11.9), 129.56+/-67.08 mg (40.5-400) and 324.37+/-199.47 mg/day (85.71-910.71) respectively. The 95th percentiles for serum calcium were 10.56 mg/dl and urinary calcium excretion was 280.70 mg/24 h. Educational level, monthly income and height were positive correlated with calcium intake. CONCLUSION: This preliminary study defines the first standard value for calcium status in pregnant second trimester females of northern India. Calcium intake in pregnant females is affected by various demographic characteristics. There is need to change dietary pattern by improving education and socio-economic level.