Safety and effectiveness of intravenous iron sucrose versus standard oral iron therapy in pregnant women with moderate-to-severe anaemia in India: a multicentre, open-label, phase 3, randomised, controlled trial.

BACKGROUND: Intravenous iron sucrose is a promising therapy for increasing haemoglobin concentration; however, its effect on clinical outcomes in pregnancy is not yet established. We aimed to assess the safety and clinical effectiveness of intravenous iron sucrose (intervention) versus standard oral iron (control) therapy in the treatment of women with moderate-to-severe iron deficiency anaemia in pregnancy. METHODS: We did a multicentre, open-label, phase 3, randomised, controlled trial at four government medical colleges in India. Pregnant women, aged 18 years or older, at 20-28 weeks of gestation with a haemoglobin concentration of 5-8 g/dL, or at 29-32 weeks of gestation with a haemoglobin concentration of 5-9 g/dL, were randomly assigned (1:1) to receive intravenous iron sucrose (dose was calculated using a formula based on bodyweight and haemoglobin deficit) or standard oral iron therapy (100 mg elemental iron twice daily). Logistic regression was used to compare the primary maternal composite outcome consisting of potentially life-threatening conditions during peripartum and postpartum periods (postpartum haemorrhage, the need for blood transfusion during and after delivery, puerperal sepsis, shock, prolonged hospital stay [>3 days following vaginal delivery and >7 days after lower segment caesarean section], and intensive care unit admission or referral to higher centres) adjusted for site and severity of anaemia. The primary outcome was analysed in a modified intention-to-treat population, which excluded participants who refused to participate after randomisation, those who were lost to follow-up, and those whose outcome data were missing. Safety was assessed in both modified intention-to-treat and as-treated populations. The data safety monitoring board recommended stopping the trial after the first interim analysis because of futility (conditional power 1·14% under the null effects, 3·0% under the continued effects, and 44·83% under hypothesised effects). This trial is registered with the Clinical Trial Registry of India, CTRI/2012/05/002626. FINDINGS: Between Jan 31, 2014, and July 31, 2017, 2018 women were enrolled, and 999 were randomly assigned to the intravenous iron sucrose group and 1019 to the standard therapy group. The primary maternal composite outcome was reported in 89 (9%) of 958 patients in the intravenous iron sucrose group and in 95 (10%) of 976 patients in the standard therapy group (adjusted odds ratio 0·95, 95% CI 0·70-1·29). 16 (2%) of 958 women in the intravenous iron sucrose group and 13 (1%) of 976 women in the standard therapy group had serious maternal adverse events. Serious fetal and neonatal adverse events were reported by 39 (4%) of 961 women in the intravenous iron sucrose group and 45 (5%) of 982 women in the standard therapy group. At 6 weeks post-randomisation, minor side-effects were reported by 117 (16%) of 737 women in the intravenous iron sucrose group versus 155 (21%) of 721 women in the standard therapy group. None of the serious adverse events was found to be related to the trial procedures or the interventions as per the causality assessment made by the trial investigators, ethics committees, and regulatory body. INTERPRETATION: The study was stopped due to futility. There is insufficient evidence to show the effectiveness of intravenous iron sucrose in reducing clinical outcomes compared with standard oral iron therapy in pregnant women with moderate-to-severe anaemia. FUNDING: WHO, India.

Pan endoscopic approach "hysterolaparoscopy" as an initial procedure in selected infertile women.

INTRODUCTION: Tuboperitoneal pathology is responsible for 40-50% cases of infertility. Hysterosalpingography (HSG) & laparoscopy are the two classic methods available for evaluation of tubal pathology and are complementary to each other. Though pelvic sonography and HSG are good enough to exclude gross intrauterine pathology, but subtle changes in the form of small polyps, adhesions and seedling fibroid are better picked up on magnification with hysteroscopy. Combined hysterolaparoscopy may obviate need for HSG, as complete evaluation and treatment is possible in the same sitting. AIM: To assess the utility of Hysterolaparoscopy as one step procedure and compare it with HSG, in the subset of ovulatory infertile women with normal pelvic sonography / seminogram /hormonal assays. MATERIALS AND METHOD: In this analytical prospective study, 193 infertile women aged 19 to 42 years underwent HSG and Hysterolaparoscopy over a period of six months. They were confirmed to have ovulatory cycles and normal seminogram. Patient with active genital infection were excluded. Findings were categorized as normal/abnormal and therapeutic intervention done, if required. Statistical evaluation was carried out using Chi- square test. RESULT: On comparing HSG and Hysteroscopy, uterine findings matched in 66.3% patients. HSG failed to detect uterine pathology in 32.12% patients (62/193) with a sensitivity of 21.3% and specificity of 97.45%. Ninety three percent of intrauterine adhesions/polyps were missed on HSG. Hysteroscopic intervention was required in 23.83% cases, adhesiolysis being the commonest. On comparing tubal patency on HSG and laparoscopy, the sensitivity of HSG in detecting bilateral tubal block was 80.6% and specificity of 81.5%. With regard to unilateral tubal block, sensitivity was 34.6% and specificity 89.8%. The agreement between the two was 74%. Pathology such as adhesions, fimbrial agglutination and endometriosis were dealt surgically in 65.8% patients. As per HSG, 112/193 women had both tubes patent and 177 revealed normal uterine cavity. When these 112 women (58.03%) with normal HSG report were further subjected to hysterolaparoscopy, only 35/193 (18.13%) of them actually had normal tubes and uterus; rest 77 women (39.89%) were benefited by one step procedure of hysterolaparoscopic evaluation and intervention and further treatment done. CONCLUSION: Hysterolaparoscopy (Pan Endoscopic) approach is better than HSG and should be encouraged as first and final procedure in selected infertile women.