Comparative study on complications and difficulties in laparoscopy in female genital tuberculosis cases versus non-tuberculosis cases.

BACKGROUND AND OBJECTIVE: Female genital tuberculosis (FGTB) is an important type of extrapulmonary tuberculosis (TB) associated with morbidity especially infertility in developing countries. Laparoscopy may be difficult and hazardous in FGTB. The aim of the study was to observe the difficulties and complications of laparoscopy in FGTB cases. MATERIALS AND METHODS: It was a prospective study over 12 years' period on 412 cases of diagnostic laparoscopy performed on FGTB cases with infertility. All patients underwent history taking and clinical examination and endometrial sampling for acid-fast bacilli (AFB) microscopy, culture, polymerase chain reaction (PCR), gene Xpert (last 212 cases) and histopathological evidence of epithelioid granuloma. Another 412 cases of diagnostic laparoscopy in the absence of FGTB performed during same time were taken as controls from the pool of non-TB cases. Various difficulties and complications were noted in both groups and statistical analysis was done. RESULTS: Mean age, parity, body mass index and duration of infertility were 26.8 versus 25.4 years, 0.32 versus 0.28, 23.15 versus 25.28 Kg/m 2 and 4.15 versus 5.12 years, respectively. Primary and secondary infertility was seen in 78.6% and 20.38% of cases in the study group and 74.75% and 25.24% in the control group, respectively. Endometrial biopsy showed AFB microscopy in 5.3%, culture in 6.3%, epithelioid granuloma in 15.77% and on peritoneal biopsy granuloma in 6.55%, positive PCR in 368 (89.32%) and positive gene Xpert in 38 out of 212 (17.92%, out of last 212 cases). Definite findings of FGTB were seen in 171 (41.50%) cases. Probable findings of FGTB were seen in 241 (58.49%) cases. Various complications were difficulty in the creation of pneumoperitoneum or insertion of trocar and cannula in 16.74% and 13.10% of cases as compared to 1.94% and 1.69% in the control group. Excessive bleeding was seen in 5.09% versus 0.97% cases, respectively. Various injuries observed were bowel injury in 1.69% versus 0.24% cases (small bowel in 1.21% vs. 0.24%, large bowel in 0.48% vs. 0.1%), while bladder injury was seen in 0.97% versus 0.24% cases, subacute intestinal obstruction was seen in 5.8% versus 0.72% cases respectively while flare up of TB was seen in 5.09% versus 0% in cases and controls, respectively. Wound infection was seen in 8.48% versus 1.25% cases, respectively. INTERPRETATION AND CONCLUSION: FGTB is associated with increased complications and difficulties as compared to laparoscopy in other cases.

Laparoscopic Management of Disseminated Peritoneal Leiomyomatosis.

STUDY OBJECTIVE: To show laparoscopic management of disseminated peritoneal leiomyomatosis (DPL). DESIGN: Stepwise demonstration of the technique with narrated video footage. SETTING: DPL is characterized by dissemination and proliferation of peritoneal and subperitoneal lesions primarily originating from smooth muscle cells [1]. Generally considered benign, cases of malignant transformation to leiomyosarcoma have been reported [2,3]. Iatrogenic DPL occurs because of unconfined morcellation resulting in small fragments of myoma that may implant on any organ and start deriving blood supply from it or may be pulled into port site while withdrawing laparoscopic cannulas [4]. It is estimated that the overall incidence of DPL after laparoscopic uncontained morcellation was 0.12% to 0.95% [5]. Mainstay of treatment is surgical resection of myomas and regular follow-up with imaging. A 28-year-old unmarried girl presented with complain of lump abdomen increasing in size for 1 year. She also complained of a 15 kg weight loss in the last 1 year; 4 years ago, patient had undergone laparoscopic myomectomy with unconfined morcellation for a 10 × 8 cm cervical myoma. Presently her menses were regular with a 28-day cycle and 3 to 4 days' average flow. Magnetic resonance imaging showed multiple nodular lesions of varying sizes in relation to small bowel, colon, uterus, and anterior abdominal wall  suggestive of DPL. Bilateral ovaries were normal. Tumor markers were as follows: CA 125 23.2 (<35) U/mL Carcinoembryonic antigen 1.67 (<8) ng/mL CA 19-9 47 (<37) U/mL Lactate dehydrogenase 809 (180-360) IU/L Alpha-fetoprotein 2.03 (<10) ng/mL Beta human chorionic gonadotropin 1.2(<2) mIU/mL Tru-cut biopsy was done elsewhere to rule out peritoneal carcinomatosis in view of raised CA 19-9 and lactate dehydrogenase, history of weight loss, and imaging showing multiple abdominal masses. Histopathological examination showed leiomyomatosis and immunohistochemistry for smooth muscle actin, desmin, and vimentin were positive. INTERVENTIONS: On laparoscopy the abdominal cavity was found studded with multiple leiomyomas of varying sizes deriving blood supply from ilium, transverse, descending and sigmoid colon, rectum, left tube, left ovary, pouch of Douglas, bilateral uterosacrals, uterovesical fold, and anterior abdominal wall. Large blood vessels were seen traversing between the descending and sigmoid colon and the myomas. Principles of surgery were as follows: 1. Complete removal of myomas 2. Cauterization of blood vessels feeding the parasitic myomas to minimize blood loss 3. Disscetion abutting the myoma to prevent injury to adjacent viscera. A total of 26 myomas were removed. All the myomas were retrieved by morcellation in a bag. Histopathology confirmed the diagnosis of diffuse peritoneal leiomyomatosis. Follow-up ultrasound at 6 months showed no recurrence of leiomyomatosis. CONCLUSION: Proper mapping of lesions and surgery for complete removal of all masses is the mainstay of treatment. Contained morcellation in bag should be the norm to prevent iatrogenic DPL. Regular follow-up with imaging is required to rule out recurrence.

Laparoscopic Management of Partial Molar Caesarean Scar Ectopic Pregnancy.

STUDY OBJECTIVE: To demonstrate laparoscopic management of a molar scar ectopic pregnancy. DESIGN: Stepwise demonstration of the technique with narrated video footage. SETTING: Cesarean scar ectopic pregnancy and molar pregnancy are 2 separate extremely rare pathologies with an incidence range from 1/1800 to 1/2500 of all pregnancies for the former [1,2]. The concurrence of both cesarean scar ectopic and molar pregnancy is furthermore exceptionally rare, and there are only 8 reported cases of cesarean scar molar pregnancy in literature till date [3]. There is a high risk of uterine rupture, uncontrolled hemorrhage, hysterectomy, and significant maternal morbidity owing to thin myometrium and fibrous scar after cesarean section [4,5]. Knowledge and awareness about this clinical condition aid in early diagnosis and reduced morbidity. Here, we present a rare case of cesarean scar ectopic pregnancy that was operated for failed medical management and diagnosed to be molar scar ectopic pregnancy intraoperatively. INTERVENTIONS: Total laparoscopic approach to molar scar ectopic pregnancy excision involved the following steps, strategies to minimize blood loss, and complete enucleation of tissue: (1) Hysteroscopy to localize the scar ectopic and its type and size (2) Bladder dissection to expose scar (3) Intramyometrial injection of vasopressin (4) Use of harmonic scalpel to delineate the gestational sac (5) Complete evacuation of products of conception (6) Excision of scar tissue (7) Uterine repair in 2 layers CONCLUSION: There are only 8 reported cases of cesarean scar molar pregnancy in literature till date, and all patients had at least 2 previous uterine curettages with abnormally increased ß-hCG levels. The clinical manifestations were varied, the most common symptom being vaginal bleeding for a period >1 month, including our case [3]. Considering the limitations of ultrasound, magnetic resonance imaging, and serum hCG levels in the differential diagnosis of molar cesarean scar pregnancy from normal cesarean scar pregnancy, postoperative specimen should be sent for histologic examination [6]. As seen in our case, the possibility of molar pregnancy at cesarean scar ectopic site should be kept in mind in cases with rising ß-hCG levels despite continuous medical interventions, which was being medically managed for 3 months. Our case is the first to be successfully managed with laparoscopic surgery as the previously reported cases were managed with suction evacuation, chemotherapy, laparotomy, or hysterectomy [3].

Correction: The World Health Organization Fetal Growth Charts: A Multinational Longitudinal Study of Ultrasound Biometric Measurements and Estimated Fetal Weight.

[This corrects the article DOI: 10.1371/journal.pmed.1002220.].

Sequential analysis of heart rate variability, blood pressure variability and baroreflex sensitivity in healthy pregnancy.

OBJECTIVE: The aim of this study was to demonstrate the temporal profile of changes in heart rate variability (HRV), blood pressure variability (BPV), and cardiac baroreflex sensitivity (BRS) during the course of a healthy pregnancy. MATERIALS AND METHODS: This was a longitudinal study during which autonomic variability parameters (HRV, BPV, BRS) were assessed in 66 pregnant women at 11-13, 20-22 and 30-32 weeks of gestation. A lead II electrocardiogram tracing and beat-to-beat blood pressure were recorded with the subject breathing spontaneously in the supine position. Changes in the parameters were analyzed using repeated measures analysis of variance. RESULTS: Overall HRV (SDNN; standard deviation of all NN intervals) was found to decrease significantly over the course of pregnancy (p < 0.05). Similarly, indices which represent the parasympathetic component of these variables (SDSD [standard deviation of differences between adjacent NN intervals]; pNN50 [NN50 count {number of pairs of adjacent NN intervals differing by more than 50 ms} divided by the total number of all NN intervals]; high-frequency [HF] power) were also found to decrease significantly from the first to third trimester of pregnancy (p < 0.05). Low-frequency (LF) power increased over the course of pregnancy (p < 0.05). The LF/HF ratio increased significantly from first to third trimester of pregnancy (median: 0.66 [first trimester] vs.1.02 [second] vs. 0.91 [third]; p < 0.05) Overall BPV increased during the course of pregnancy, with a significant rise in the HF component of BPV and a significant fall in the LF component of BPV with advancing gestation (p < 0.05). BRS decreased over the course of pregnancy (median: 16.31, interquartile range [IQR] 11.04-23.13 [first trimester] vs. 11.42, IQR 8.54-19.52 [second] vs. 8.84, IQR 7.15-12.45 [third] ms/mmHg; p < 0.05). CONCLUSION: Pregnancy is associated with decreased vagal and increased sympathetic modulation of cardiac autonomic tone with advancing gestation, together with increased BPV. The reduction in cardiac BRS may play a role in increasing BPV and decreasing HRV over the course of pregnancy.

Cytokine and growth factor profile in endometriosis: a multiplex analysis of peritoneal fluid to assess diagnostic utility.

We aimed to assay cytokines and growth factors in peritoneal fluid samples from women with and without endometriosis to understand the inflammatory milieu, and assess their potential diagnostic utility. This cross-sectional study conducted at a tertiary care hospital included 54 women, aged 20-45 years, with regular menstrual history and undergoing diagnostic/therapeutic laparoscopy for infertility and/or pain. Peritoneal fluid samples were collected after insertion of trocar & laparoscope but prior to other surgical intervention. A multiplex immunoassay of 27 cytokines and growth factors was performed. The concentration of FGF2 and CSF3 were significantly lower in women with endometriosis than without endometriosis (p = .043 and .003, respectively). The levels of CCL2 and IL1RN were significantly higher in moderate-severe than in minimal-mild endometriosis (p = .038 and .043, respectively). Phase-specific comparison revealed that in proliferative phase, the levels of CSF2 and CSF3 were lower in women with endometriosis than without the disease (p = .047 and .013, respectively). The ROC curve analysis provided a cutoff value 0.78 and 0.76 for FGF2 and CSF3, respectively. Cytokines and growth factors such as FGF2, CSF3, CSF2, CCL2 and IL1RN seem to contribute to the pathogenesis of endometriosis and may have a potential utility for the diagnosis of endometriosis.

Pregnancy with Klippel-Trenaunay syndrome.

Klippel-Trenaunay syndrome (KTS) is a rare congenital disorder characterized by the presence of vascular naevi, varicose veins and soft tissue or bone hypertrophy affecting one or more extremities. Due to the rarity of the syndrome, there is limited literature regarding the current practice in the management of pregnancy complicated with KTS. Successful management of pregnancy with KTS is a challenge for clinicians as pregnancy exacerbates the already increased risk of thrombosis and haemorrhage associated with this syndrome. We report a patient with KTS with previous poor obstetric history managed with favourable maternal and foetal outcomes.

Comparison of ferric Carboxymaltose and iron sucrose complex for treatment of iron deficiency anemia in pregnancy- randomised controlled trial.

BACKGROUND: To evaluate the efficacy and safety of intravenous Ferric Carboxymaltose. (FCM) in comparison with intravenous Iron sucrose complex (ISC) for treatment of iron deficiency anemia in pregnancy. METHODS: A randomized clinical trial was conducted from (January 2016-August 2017). at a tertiary hospital. Pregnant women diagnosed with moderate to severe iron deficiency anaemia were screened for the study. One hundred patients were randomized to receive either intravenous FCM or ISC. Primary outcome was rise in hemoglobin (Hb) from baseline after 12 weeks. Secondary outcomes were change in RBC indices, serum iron studies, improvement in fatigue scores, number of visits and perinatal outcome. RESULTS: Mean rise in Hb at 12 weeks was significantly higher in FCM group (29 g/L vs 22 g/L; p value < 0.01). FCM was associated with greater improvement in fatigue scores. Number of visits were significantly less in FCM group. No serious adverse events were noted in either group. CONCLUSION: Treatment with FCM resulted in rapid replenishment of iron stores in pregnant women with significantly higher Hb rise over a 12 week period. The convenient dosing with lesser number of total doses to complete the treatment will lead to better compliance in community setting. CLINICAL TRIAL REGISTRATION ( WWW.CTRI.NIC.IN ): CTRI/2015/09/006224. Registered on 21/07/2017 (Trial registered retrospectively).

Comparison of metformin plus myoinositol vs metformin alone in PCOS women undergoing ovulation induction cycles: randomized controlled trial.

The present study was planned to evaluate the benefit of synergetic effect of Metformin plus Myo-inositol versus Metformin alone in infertile polycystic ovarian syndrome (PCOS) women undergoing ovulation induction. One hundred and twenty infertile PCOS women were randomized: Group I (n = 60) received Metformin (500 mg) plus Myoinositol(600 mg) three times a day; Group II received Metformin 500 mg three times a day. Subjects were advised to try for spontaneous conception. Those who did not conceive after 3 months, were given three cycles of ovulation induction + intrauterine insemination. Hormonal and biochemical profile parameters were done at baseline and after 3 months of therapy. Primary outcome measure was live birth rate. Secondary outcomes were improvement in menstrual cycle, hormonal and biochemical parameters, spontaneous conception, abortions, multiple pregnancy, and ovarian hyperstimulation syndrome. Baseline demographic, hormonal and biochemical parameters were comparable in two groups. There was a significant improvement in menstrual cycles (cycle length and bleeding days) in Group I as compared to Group II. The improvement in biochemical and hormonal parameters were comparable in the two groups after 3 months. Live birth rate was significantly higher in the Group I as compared to Group II [55% (33/60); 26.67% (16/60); p = .002]. The study concluded significantly higher live birth rate in women receiving the combination as compared to metformin alone.

Fertility awareness and knowledge among Indian women attending an infertility clinic: a cross-sectional study.

BACKGROUND: To evaluate fertility knowledge and awareness among infertile women attending an Indian assisted fertility clinic and their understanding of the menstrual cycle, how age affects fertility and need for assisted fertility treatment. METHODS: A cross sectional study was conducted including 205 women seeking fertility treatment at an assisted reproductive unit between March 2017 to August 2017. Patients were interviewed with the help of structured questionnaire by a fertility counsellor. The previous studies were reviewed and a questionnaire was made according to our patient profile and sociodemographic characteristics. Knowledge and awareness was stratified according to socioeconomic status (SES). RESULTS: Most women (59%) were aged between 20 to 30 years indicating concern about their fertility and need for evaluation. More than half (63%) women were from the middle socio-economic strata. Knowledge about fertility and reproduction was low: 85% were not aware of the ovulatory period in the menstrual cycle, only 8% considered age more than 35 years as the most significant risk factor for infertility and most were unaware of when to seek treatment for infertility after trying for pregnancy. Less than half of women understood the need for assisted fertility treatment and donor oocytes in advanced age. CONCLUSIONS: Most Indian women across different SES are unaware of the effect of age on fertility. Targeted educational interventions are needed to improve knowledge regarding ideal age of fertility, factors affecting fertility potential and fertility options available for sub-fertile couples. Fertility counselling and information should be provided to young people at every contact with health care professionals.

Tuberculosis of the cervix: An uncommon cause of vaginal discharge in a post-menopausal woman.

Discharge per vaginum is a common symptom of a variety of gynaecological diseases. Among post-menopausal women, atrophic vaginitis, cervicitis and cervical carcinoma are common causes of this symptom. We present a 64-year-old woman who had foul-smelling discharge per vaginum for the past 1 year. Per speculum examination revealed an unhealthy-looking cervix and white discharge. On bi-manual examination, the cervix was flush with the vagina. There was no obvious growth felt, the exact uterine size could not be ascertained and the finger was stained with thick discharge. A biopsy of the cervix showed epithelioid cell granulomas and a diagnosis of tuberculosis was made. The patient responded to antitubercular therapy. Tuberculosis of the cervix may be a rare cause of foul- smelling discharge per vaginum in post-menopausal women but there should be a high index of suspicion of this condition, especially in areas where tuberculosis is common. We report this post-menopausal woman owing to the rarity of tuberculosis of the cervix mimicking a gynaecological malignancy.

The World Health Organization Fetal Growth Charts: A Multinational Longitudinal Study of Ultrasound Biometric Measurements and Estimated Fetal Weight.

BACKGROUND: Perinatal mortality and morbidity continue to be major global health challenges strongly associated with prematurity and reduced fetal growth, an issue of further interest given the mounting evidence that fetal growth in general is linked to degrees of risk of common noncommunicable diseases in adulthood. Against this background, WHO made it a high priority to provide the present fetal growth charts for estimated fetal weight (EFW) and common ultrasound biometric measurements intended for worldwide use. METHODS AND FINDINGS: We conducted a multinational prospective observational longitudinal study of fetal growth in low-risk singleton pregnancies of women of high or middle socioeconomic status and without known environmental constraints on fetal growth. Centers in ten countries (Argentina, Brazil, Democratic Republic of the Congo, Denmark, Egypt, France, Germany, India, Norway, and Thailand) recruited participants who had reliable information on last menstrual period and gestational age confirmed by crown-rump length measured at 8-13 wk of gestation. Participants had anthropometric and nutritional assessments and seven scheduled ultrasound examinations during pregnancy. Fifty-two participants withdrew consent, and 1,387 participated in the study. At study entry, median maternal age was 28 y (interquartile range [IQR] 25-31), median height was 162 cm (IQR 157-168), median weight was 61 kg (IQR 55-68), 58% of the women were nulliparous, and median daily caloric intake was 1,840 cal (IQR 1,487-2,222). The median pregnancy duration was 39 wk (IQR 38-40) although there were significant differences between countries, the largest difference being 12 d (95% CI 8-16). The median birthweight was 3,300 g (IQR 2,980-3,615). There were differences in birthweight between countries, e.g., India had significantly smaller neonates than the other countries, even after adjusting for gestational age. Thirty-one women had a miscarriage, and three fetuses had intrauterine death. The 8,203 sets of ultrasound measurements were scrutinized for outliers and leverage points, and those measurements taken at 14 to 40 wk were selected for analysis. A total of 7,924 sets of ultrasound measurements were analyzed by quantile regression to establish longitudinal reference intervals for fetal head circumference, biparietal diameter, humerus length, abdominal circumference, femur length and its ratio with head circumference and with biparietal diameter, and EFW. There was asymmetric distribution of growth of EFW: a slightly wider distribution among the lower percentiles during early weeks shifted to a notably expanded distribution of the higher percentiles in late pregnancy. Male fetuses were larger than female fetuses as measured by EFW, but the disparity was smaller in the lower quantiles of the distribution (3.5%) and larger in the upper quantiles (4.5%). Maternal age and maternal height were associated with a positive effect on EFW, particularly in the lower tail of the distribution, of the order of 2% to 3% for each additional 10 y of age of the mother and 1% to 2% for each additional 10 cm of height. Maternal weight was associated with a small positive effect on EFW, especially in the higher tail of the distribution, of the order of 1.0% to 1.5% for each additional 10 kg of bodyweight of the mother. Parous women had heavier fetuses than nulliparous women, with the disparity being greater in the lower quantiles of the distribution, of the order of 1% to 1.5%, and diminishing in the upper quantiles. There were also significant differences in growth of EFW between countries. In spite of the multinational nature of the study, sample size is a limiting factor for generalization of the charts. CONCLUSIONS: This study provides WHO fetal growth charts for EFW and common ultrasound biometric measurements, and shows variation between different parts of the world.

Correction: The World Health Organization Fetal Growth Charts: A Multinational Longitudinal Study of Ultrasound Biometric Measurements and Estimated Fetal Weight.

[This corrects the article DOI: 10.1371/journal.pmed.1002220.].

The temporal trend of vascular function in women with gestational diabetes.

The objective of the study was to assess the temporal changes in vascular function during pregnancy in healthy women and in those with gestational diabetes mellitus (GDM). Assessment of vascular function was done at three time points, 11-13+6 weeks+days, 20-22+6 weeks+days and 30-32+6 weeks+days, by flow-mediated dilatation (FMD), augmentation index (AIx) and carotid-radial pulse wave velocity (crPWV) in women ( n=100) with singleton pregnancies. Out of the 100 women, 20 developed GDM, who were compared with 20 healthy, age-matched pregnant women in a nested case-control design. Women with GDM had lower FMD% in the third compared to the first trimester (6.77 (4.36-9.96) vs 9.76 (6.66-16.61)%; p = 0.026); however, FMD% was similar on inter-group comparison between GDM and healthy pregnancies. AIx was significantly higher in GDM than healthy pregnancies at both first (15.35 ± 10.57 vs 6.45 ± 9.81%; p<0.05) and second trimesters (15.00 ± 8.44 vs 2.50 ± 9.01%; p<0.05). A higher AIx in early pregnancy differentiates women with GDM from those with healthy pregnancies.

Pregnancy after endometrial scratching in infertile couples undergoing ovulation induction and intrauterine insemination cycles-a randomized controlled trial.

PURPOSE: To study the effect of endometrial scratching in infertile couples undergoing ovulation induction and intrauterine insemination (IUI) cycles. METHODS: A prospective randomized controlled trial was conducted in the Department of Obstetrics and Gynaecology, AIIMS, New Delhi, India. One hundred forty-four women with primary/secondary infertility were recruited. Couples were either unexplained or male factor infertility. Subjects were randomized into intervention (scratching) and control group. All patients received ovulation induction with clomiphene citrate (day 2-6) 50 mg/day +75 IU HMG on days 6 and 7. In addition, endometrial scratching was done on day 8 of ovulation induction cycle in intervention group. All couples were planned for three cycles of ovulation induction and IUI over 6 months. After each failed cycle, couple was advised to try for natural conception for one cycle. Those who conceived were excluded from further analysis. Primary outcome was clinical pregnancy rate. Secondary outcome measures included conception rate, ongoing pregnancy, abortion and ectopic rate. RESULTS: Baseline characteristics were comparable in both groups. Clinical pregnancy rate was significantly higher in intervention group (31.9%; 23/72) as compared to control group (16.7%; 12/72) (p value 0.030). On per cycle analysis, first IUI cycle had significantly high pregnancy rate (18.1%; 13/72) as compared to control group (5.6%; 4/72). Three patients in intervention group and one in control group conceived in wash out cycle. Ongoing pregnancy rate was significantly higher in scratching group (30.0%; 21/70) as compared to control group (15.7%; 11/70) (p value0.044). CONCLUSIONS: Endometrial scratching can be used as a low cost-effective tool to improve clinical pregnancy and ongoing pregnancy rate in IUI cycles. Further large number studies are required to document its role in improving live birth rate. TRIAL REGISTRATION NUMBER: CTRI/2015/12/006419.

A Comparison of the Strength of Association of Reid Colposcopic Index and Swede Score With Cervical Histology.

OBJECTIVE: Colposcopic scoring systems provide an objective diagnosis and select patients who require treatment. A new scoring system, Swede score, has added lesion size as a parameter. This study aimed to compare the strength of association of Reid colposcopic index versus Swede score and assess their utility in low-resource settings. METHODS: In this prospective study, 150 women aged 30 to 59 years with abnormal screening result were enrolled. All women underwent colposcopy; the findings were scored by both Reid colposcopic index and Swede score, biopsy taken from all abnormal areas. Performances of both the scores were calculated. RESULTS: A total of 33 (22%) CIN 2+ lesions were detected. Reid colposcopic index at a cutoff of 5 had sensitivity, specificity, positive predictive value, and negative predictive value for detecting CIN2+ lesions of 96.97%, 95.35%, 88.89%, and 98.8%, respectively. Using Swede score at a cutoff of 8, sensitivity, specificity, positive predictive value, and negative predictive value were 42.42%, 100%, 100%, and 81.9%, and with a cutoff of 5, these were 100%, 88.37%, 76.74%, and 100%, respectively. The correlation coefficient (R) was 0.919. By Spearman rank correlation coefficient, the strength of correlation between Swede score and RCI was 0.937 (p < .001). CONCLUSIONS: Swede score can be used flexibly depending on the setting. The lower threshold (5) with high sensitivity can be used for screening, whereas the higher threshold (8) with high specificity can be used for screen-and-treat selection to decrease the overtreatment rate. Thus, it is a more attractive option for cancer prevention programs in low-resource settings.

Immunogenicity and HPV infection after one, two, and three doses of quadrivalent HPV vaccine in girls in India: a multicentre prospective cohort study.

BACKGROUND: An increase in worldwide HPV vaccination could be facilitated if fewer than three doses of vaccine are as effective as three doses. We originally aimed to compare the immunogenicity and frequency of persistent infection and cervical precancerous lesions caused by vaccine-targeted HPV after vaccination with two doses of quadrivalent vaccine on days 1 and 180 or later, with three doses on days 1, 60, and 180 or later, in a cluster-randomised trial. Suspension of the recruitment and vaccination due to events unrelated to our study meant that some enrolled girls could not be vaccinated and some vaccinated girls received fewer than the planned number of vaccinations by default. As a result, we re-analysed our data as an observational cohort study. METHODS: Our study was designed to be done in nine locations (188 clusters) in India. Participants were unmarried girls aged 10-18 years vaccinated in four cohorts: girls who received three doses of vaccine on days 1, 60, and 180 or later, two doses on days 1 and 180 or later, two doses on days 1 and 60 by default, and one dose by default. The primary outcomes were immunogenicity in terms of L1 genotype-specific binding antibody titres, neutralising antibody titres, and antibody avidity after vaccination for the vaccine-targeted HPV types 16, 18, 6, and 11 and incident and persistent infections with these HPVs. Analysis was per actual number of vaccine doses received. This study is registered with ISRCTN, number ISRCTN98283094; and with ClinicalTrials.gov, number NCT00923702. FINDINGS: Vaccination of eligible girls was initiated on Sept 1, 2009, and continued until April 8, 2010. Of 21 258 eligible girls identified at 188 clusters, 17 729 girls were recruited from 178 clusters before suspension. 4348 (25%) girls received three doses, 4979 (28%) received two doses on days 1 and 180 or later, 3452 (19%) received two doses at days 1 and 60, and 4950 (28%) received one dose. Immune response in the two-dose HPV vaccine group was non-inferior to the three-dose group (median fluorescence intensity ratio for HPV 16 1·12 [95% CI 1·02-1·23] and for HPV 18 1·04 [0·92-1·19]) at 7 months, but was inferior in the two-dose default (0·33 [0·29-0·38] for HPV 16 and 0·51 [0·43-0·59] for HPV 18) and one-dose default (0·09 [0·08-0·11] for HPV 16 and 0·12 [0·10-0·14] for HPV 18) groups at 18 months. The geometric mean avidity indices after fewer than three doses by design or default were non-inferior to those after three doses of vaccine. Fewer than three doses by design and default induced detectable concentrations of neutralising antibodies to all four vaccine-targeted HPV types, but at much lower concentration after one dose. Cervical samples from 2649 participants were tested and the frequency of incident HPV 16, 18, 6, and 11 infections was similar irrespective of the number of vaccine doses received. The testing of at least two samples from 838 participants showed that there was no persistent HPV 16 or 18 infections in any study group at a median follow-up of 4·7 years (IQR 4·2-5·1). INTERPRETATION: Despite the limitations imposed by the suspension of the HPV vaccination, our findings lend support to the WHO recommendation of two doses, at least 6 months apart, for routine vaccination of young girls. The short-term protection afforded by one dose of HPV vaccine against persistent infection with HPV 16, 18, 6, and 11 is similar to that afforded by two or three doses of vaccine and merits further assessment. FUNDING: Bill & Melinda Gates Foundation.

Efficacy of ormeloxifene versus oral contraceptive in the management of abnormal uterine bleeding due to uterine leiomyoma.

AIM: To compare ormeloxifene with combined oral contraceptive (COC) in abnormal uterine bleeding (AUB) due to leiomyoma (AUB-L). METHODS: Fifty women with AUB-L were randomized after informed consent and institute ethics clearance. Group I (n = 25) was given ormeloxifene (a SERM i.e. selective estrogen receptor modulator) 60 mg twice per week and group II (n = 25) was given COC (ethinyl estradiol 30 µg with desogestrel 150 µg) on days 1-21 for 6 months. Menstrual blood loss was assessed on pictorial blood loss assessment chart (PBAC) score and leiomyoma volume was assessed on ultrasound. Fibroids were classified according to FIGO-PALM-COEIN classification for AUB where leiomyomas were further sub-classified as types 0 to 8 according to their location. Follow up was done at 1, 3, 6 and 9 months. RESULTS: Mean PBAC score reduced by 81% with ormeloxifene (group I) compared with 43.8% for COC (group II). After 6 months, 18 patients (72%) in group I had PBAC score in the non-menorrhagic range (<100) compared with only two (8%) in group II. In group I, PBAC score in FIGO-PALM-COEIN leiomyoma types 2, 3, 4, 5, 6 reduced by 90.2%, 82.5%, 93.3%, 56.4% and 100%, respectively and 14 (56%) developed amenorrhea; compared with reduction of 64%, 27.5%, 25.9% in types 4, 5 and 6, respectively in group II. Dysmenorrhea visual analog scale score decreased in both groups. Mean leiomyoma volume increased in both groups: by 25.7% with ormeloxifene versus 16.9% with COC; only grade 2 leiomyoma in group I reduced by 44%. One patient in group II with grade 2 leiomyoma discontinued treatment at 3 months. Seven patients (28%) developed ovarian cyst in group I with no other major adverse effect in either group. CONCLUSION: Ormeloxifene with its convenient twice-weekly dosage schedule was effective in treating AUB-L, with 72% of patients responding to 6-month treatment compared with 8% with COC, even though leiomyoma volume increased insignificantly with both ormeloxifene and COCs.

Assessment and comparison of pregnancy outcome among anaemic and non anaemic primigravida mothers.

BACKGROUND: Primigravidas (PGs) are high-risk women and anemia in pregnancy is one of the commonest causes of maternal morbidity and mortality. OBJECTIVES: The study was conducted to assess impact of anemia on course and outcome of pregnancy in anemic (Hemoglobin 8-10.9 gm%) and nonanemic PGs. METHODS: This prospective longitudinal study was conducted in All India Institute of Medical Sciences, New Delhi. PGs 20-30 years age, gestation age 16-18 weeks, hemoglobin >8 gm%, live singleton pregnancy, and no other medical illness were recruited after informed consent. The women were Grouped 1 and 2 if hemoglobin was ≥11 gm% and 8-10.9 gm%, respectively. Complete hemogram done at enrollment, 28-30 weeks of pregnancy and 6 weeks postdelivery. Obstetric outcome and presence of anemia postdelivery were compared between groups using Chi-square test and Fisher's exact test. RESULTS: A total of 377 PGs were enrolled and obstetric outcomes studied in 179 (Group 1) and 149 (Group 2) excluding women who did not complete study. There was no statistically significant difference in baseline characteristics, antenatal complications, gestational age, mode of delivery, and neonatal outcome. At 28-30 weeks of gestation, in spite of iron supplementation higher percentage (64.4%) (P < 0.05) of anemic patients remained anemic. At 6 weeks postdelivery, 15.6% and 24.2% were anemic in Group 1 and 2, respectively (P > 0.05). The adverse postpartum events (7.6%) were seen more in anemic compared to nonanemic pregnant women (P < 0.05). CONCLUSIONS: Cautious approach required in postpartum period of anemic women though antenatal period is similar as nonanemic pregnant women.