Non-alcoholic fatty liver disease in polycystic ovarian syndrome in Indian women.

Non-alcoholic fatty liver disease (NAFLD) is a frequent occurrence in polycystic ovarian syndrome (PCOS). We studied the frequencies and characteristics of NAFLD in PCOS women. We compared various methods of detection of advanced fibrosis/cirrhosis. One hundred and forty women with PCOS and seventy controls, matched for age, were evaluated for the presence of NAFLD. Anthropometric variables, serum levels of aminotransferases, glucose, lipids and transient elastography were done. Thirty-six percent of the NAFLD patients had abnormal aminotransferases. In women presenting to an infertility clinic, NAFLD was higher in both obese and non-obese PCOS women, being present in 117 (83.6%) of PCOS cases and 32 (45.7%) of non-PCOS controls (p< .001). Fibroscan is helpful in evaluating for liver fibrosis in patients with NAFLD.Impact StatementWhat is already known on this subject? Polycystic ovarian syndrome (PCOS) has been associated with many long-term health complications including endometrial cancer, diabetes, hypertension and metabolic syndrome. The association of PCOS with NAFLD has been suggested. NAFLD is recognised as a leading cause of liver dysfunction which can progress to long-term sequel of cirrhosis.What do the results of this study add? In this study, asymptomatic women seeking treatment of infertility were screened for presence of NAFLD. The study shows a high prevalence of NAFLD in young Indian women. The prevalence was significantly higher in women with PCOS than non-PCOS women.What are the implications of these findings for clinical practice and/or further research? The findings of the study suggest that all infertile women, especially those with PCOS, should be screened for NAFLD. This will help in early identification and management of this condition and to avoid long-term consequences of liver dysfunction and cirrhosis. PCOS is an independent risk factor for the development of NAFLD in obese women. Liver ultrasound, serum levels of transaminases clinch the diagnosis. Short of liver biopsy, non-invasive tests like Fibroscan and NAFLD fibrosis score are useful to assess the stage of fibrosis.

Chemoradiation therapy induces in vivo changes in gene promoter methylation & gene transcript expression in patients with invasive cervical cancer.

BACKGROUND & OBJECTIVES: Invasive cervical cancer patients are primarily treated with chemoradiation therapy. The overall and disease-free survival in these patients is variable and depends on the tumoral response apart from the tumour stage. This study was undertaken to assess whether in vivo changes in gene promoter methylation and transcript expression in invasive cervical cancer were induced by chemoradiation. Hence, paired pre- and post-treatment biopsy samples were evaluated for in vivo changes in promoter methylation and transcript expression of 10 genes (ESR1, BRCA1, RASSF1A, MYOD1, MLH1, hTERT, MGMT, DAPK1, BAX and BCL2L1) in response to chemoradiation therapy. METHODS: In patients with locally advanced invasive cervical cancer, paired pre- and post-treatment biopsies after 10 Gy chemoradiation were obtained. DNA/RNA was extracted and gene promoter methylation status was evaluated by custom-synthesized methylation PCR arrays, and the corresponding gene transcript expression was determined by absolute quantification method using quantitative reverse transcription PCR. RESULTS: Changes in the gene promoter methylation as well as gene expression following chemoradiation therapy were observed. BAX promoter methylation showed a significant increase (P< 0.01) following treatment. There was a significant increase in the gene transcript expression of BRCA1 (P< 0.01), DAPK1 and ESR1 (P< 0.05), whereas MYOD1 and MLH1 gene transcript expression was significantly decreased (P< 0.05) following treatment. INTERPRETATION & CONCLUSIONS: The findings of our study show that chemoradiation therapy can induce epigenetic alterations as well as affect gene expression in tissues of invasive cervical cancer which may have implications in determining radiation response.

Effect of Placental Transfusion on Iron Stores in Moderately Preterm Neonates of 30-33 weeks Gestation.

OBJECTIVE: To assess the effect of placental transfusion by delayed cord clamping (DCC) of 60 s or cord milking (CM) on serum ferritin levels at hospital discharge and 3 mo of postmenstrual age (PMA) in preterm neonates of 30 to 33 wk gestation in comparison to early cord clamping (ECC) within 10 s. METHODS: This mixed longitudinal study was conducted in moderately preterm neonates of 30 to 33 wk gestation born in a level III unit in Northern India with the study sample nested within a randomized controlled trial on placental transfusion. Intervention was delayed cord clamping for 60 s or cord milking compared with early cord clamping (within 10 s). Primary outcome measure was serum ferritin levels at discharge. Secondary outcome measures were serum ferritin levels at 3 mo PMA, incidence of anemia, need for blood transfusion and incidence of iron deficiency by 3 mo PMA. RESULTS: Out of the 215 randomly chosen infants, serum ferritin levels were estimated at least at one time point (at discharge or at 3 mo PMA) in 197 neonates [placental transfusion - 107; early cord clamping - 90]. Amongst them, ferritin level was estimated at discharge in 141 neonates, at 3 mo PMA in 76 neonates and at both time points in 20 neonates. Median (IQR) serum ferritin (µg/L) at discharge was significantly higher in placental transfusion group in comparison to the ECC group [399 (309,600) (n = 79) vs. 254 (190,311) (n = 62); p < 0.001]. Median (IQR) ferritin level at 3 mo PMA was not different between the study groups [20 (14,57) (n = 39) vs. 24 (8,52) (n = 37); p = 0.2]. The incidence of anemia by 3 mo PMA was significantly lesser in the placental transfusion group. No difference was observed in anemia requiring blood transfusion and iron deficiency by 3 mo PMA between the groups. CONCLUSIONS: In 30 to 33 wk preterm neonates, placental transfusion resulted in significantly higher serum ferritin at discharge in comparison to early cord clamping. However, this benefit did not persist till 3 mo PMA.

Ovulation Induction Using Clomiphene Citrate Using Stair - Step Regimen versus Traditional Regimen in Polycystic Ovary Syndrome Women - A Randomized Control Trial.

OBJECTIVE: To determine the efficacy of the stair-step protocol (SSP) using clomiphene citrate (CC) in patients with polycystic ovary syndrome (PCOS) and compare it with traditional regimen. DESIGN: This was randomized control trial. SETTING: Infertility Clinic. PATIENTS: Sixty infertile PCOS women. INTERVENTIONS: Patients were randomized into the study (SSP - 30 patients) and control group (traditional protocol - 30 patients). In the SSP, patients were treated with CC 50 mg/day for 5 days and in nonresponsive patients, the dosage was increased to 100 mg/day for 5 days in the same cycle. Maximum dose of 150 mg was given until the dominant follicle was generated. In control group, the dose increment in nonovulatory cases was done in subsequent cycle. Ultrasonography follow-up was done to detect ovulation. MAIN OUTCOME MEASURES: Ovulation rate and duration of treatment. RESULTS: Ovulation (66.7% vs. 50% respectively) and pregnancy rates (26.7% vs. 15.7%) were similar between the stair step and the control group. The duration of treatment was significantly shorter in stair step compared to traditional protocol (17.23 vs. 53 days). CC 100 mg was the most effective dose for ovulation in either group. There were no significant differences in the systemic side effect. CONCLUSIONS: By using SSP, effective treatment is provided in significantly shorter time period without any detrimental effect on the ovulation and pregnancy rates.

Vitamin-D Deficiency Is Associated with Gallbladder Stasis Among Pregnant Women.

BACKGROUND: Pregnant women are at increased risk of gallbladder (GB) stasis, an important risk factor for gallstones (GS). In non-pregnant women, Vitamin-D deficiency (VDD) is associated with GB stasis, which improves on supplementation. Relationship of VDD with GB stasis among pregnant women is not known. METHODS: This is a prospective study in tertiary care centre. Consecutive healthy pregnant women (12-16 weeks gestation) were enrolled. Serum 25(OH) vitamin-D was estimated, and levels <20 ng ml(-1) were considered as VDD. Risk factors and clinical features of VDD were assessed. Gallbladder ejection fraction (GBEF) was assessed by ultrasound after a standard fatty meal, and <40 % was defined as stasis. Statistical analysis was performed to assess relationship of GB stasis and vitamin-D levels and identify factors associated with VDD. KEY RESULTS: Median serum vitamin-D in 304 women was 7.9 ng ml(-1) (IQR 5.7, 12). VDD afflicted 92 % of them. Women with VDD more often had GB stasis (20 % vs 0 %; p = 0.015) and had lower GBEF [53.7 ± 17 % vs 59 ± 10 %; p = 0.026] compared to those with normal vitamin-D. GBEF showed positive correlation with vitamin-D levels (r = 0.117; p = 0.042). Risk factors for low vitamin-D levels were urban residence (p = 0.001), lower sun-exposure time (p = 0.005), limited skin exposure (p < 0.001), higher BMI (p = 0.05) and higher socioeconomic status (p = 0.02). Vitamin-D deficiency was associated with low serum calcium (ρ = 0.457; p < 0.001). CONCLUSIONS: Vitamin D deficiency is highly prevalent among pregnant Indian women. It is associated with GB stasis and lower GBEF. The risk factors for VDD were reduced sun exposure, inadequate dietary intake and urban lifestyle.

Ultrasonography of the ovaries and its correlation with clinical and endocrine parameters in infertile women with PCOS.

OBJECTIVES AND METHODS: In 100 anovulatory infertile women with polycystic ovary syndrome attending the infertility clinic of this institute, transvaginal ultrasound findings of ovaries were correlated with both clinical and hormonal parameters using Chi-square test. RESULTS: All women in the study had oligomenorrhea or amenorrhea, 70% had hirsutism and more than half were obese. On transvaginal ultrasound, ovarian volume was more than 10 cm3 in all, 90% had more than 10 follicles in each ovary, 75% had stromal thickness more than 1 cm and more than half had increased stromal echogenicity. Seventy percent had high testosterone levels and 60% were detected to have insulin resistance. Ovarian volume correlated positively with body mass index, waist/hip ratio and menstrual cycle irregularity (p < 0.05). The correlation between ovarian size, LH/FSH ratio and hyperinsulinemia was highly significant (p < 0.005), but was low for serum androgens and also hirsutism. Number of follicles per ovary correlated positively with body mass index, menstrual irregularity (p < 0.01), insulin resistance as well as androgens (p < 0.005). Positive predictive value of ovarian follicle number was 100% for insulin resistance as well as D4 androstenedione. Increased stromal thickness also showed 70% positive prediction for clinical parameters, 66% for insulin resistance and 82% for serum D4 androstenedione. Contrary to the other ultrasound parameters of polycystic ovary, stromal echogenicity did not significantly correlate with any of the clinical or hormonal parameters except serum testosterone. CONCLUSION: Transvaginal ultrasonography of the ovaries confirms the clinical profile and also gives an insight to the hormonal milieu of the women with PCOS.

Herniation of gravid uterus: report of 2 cases and review of literature.

Anterior abdominal wall hernias are uncommon, and herniation of a gravid uterus into these hernias is even rarer. Although reducible initially, the herniation of pregnant uterus may be complicated by incarceration and subsequent strangulation within the hernial sac, late in the course of pregnancy. There is no consensus over the management of this rare condition. Each case should be individualized. If uncomplicated, a conservative approach until term followed by delivery and herniorrhaphy is a good option. Here, 2 cases of herniation of gravid uterus into the anterior abdominal wall are described along with a brief review of literature pertaining to its presentation, complications, and management.

Minimal stimulation protocol for use with intrauterine insemination in the treatment of infertility.

OBJECTIVE: To determine whether minimal stimulation with clomiphene and one injection of 150 IU of human menopausal gonadotrophin (hMG) provides pregnancy rates comparable with those in a conventional full hMG stimulation protocol for infertile patients undergoing intrauterine insemination (IUI). METHODS: A prospective study was carried out at the Infertility Clinic of a teaching institute and tertiary care referral center in Chandigarh, India. Two hundred couples with either unexplained infertility or ovulatory dysfunction cases who ovulated with clomiphene citrate (CC) but failed to conceive were offered ovarian stimulation with CC and hMG along with IUI for 420 cycles. Pregnancy rate, medication and monitoring cost were compared between minimal and conventional stimulation protocols. RESULTS: There was no difference in the couples of the two stimulation protocols regarding their age, duration and type of infertility as well as cause of infertility. Number of ampoules of hMG and monitoring costs were significantly higher in the full hMG stimulation cases whereas pregnancy rate was comparable in both protocols. CONCLUSION: Minimal stimulation appears to be an effective protocol in cases of unexplained infertility undergoing intrauterine insemination. Reduced cost and minimal monitoring is appealing to patients and the clinician.