A Multicenter, Randomized, Open-Label Trial Comparing the Efficacy and Safety of Monoclonal Anti-Rh (D) Immunoglobulin with Polyclonal Anti-Rh (D) Immunoglobulin for the Prevention of Maternal Rh-Isoimmunization.

OBJECTIVES: To compare the efficacy and safety of monoclonal anti-Rhesus (anti-D) immunoglobulin (IgG) with polyclonal anti-D IgG in the prevention of maternal Rh-isoimmunization. METHODS: This was a randomized, multicenter, open-label, comparative clinical trial conducted in the obstetric in-patient departments of nine tertiary care hospitals in India. 206 Rhesus (D)-negative women, not sensitized to Rh antigen, and delivering Rh positive babies, received postpartum intramuscular administration of monoclonal or polyclonal anti-D IgG. The main outcome measures were the proportion of subjects protected from Rh-isoimmunization, identified by a negative indirect Coombs test (ICT) result, at day 180 after anti-D IgG administration, and incidence of adverse events. RESULTS: 105 subjects were randomized to the monoclonal group and 101 to the polyclonal group. 94 from the monoclonal group had a negative ICT result and none had a positive ICT result at day 180, whereas 87 from the polyclonal group had a negative ICT result and one had a positive ICT result; the rest (11 and 13 subjects respectively) were lost to follow-up. A total of 5 adverse events were reported (3 in the monoclonal group and 2 in the polyclonal group); only one of these was serious. All the adverse events were judged to be unrelated to the interventional drug. None of the subjects in the monoclonal group developed immunogenic reaction to the monoclonal anti-D. CONCLUSION: The efficacy and safety of the monoclonal preparation of anti-D was comparable to the polyclonal preparation of anti-D when used in the prevention of maternal Rh-isoimmunization.Trial registration Clinical Trial Registration Number: CTRI/2015/09/006172.

A Multicenter, Randomized, Equivalence Trial of a New Recombinant Human Chorionic Gonadotropin Preparation versus Ovitrelle® for Ovulation in Women Undergoing Intrauterine Insemination Following Ovarian Stimulation.

CONTEXT: A new indigenous recombinant human chorionic gonadotropin (r-hCG) has been developed in India with a comparable pharmacological profile to that of Ovitrelle® (Merck Serono). AIMS: This study aims to compare the efficacy and safety of the new r-hCG with that of Ovitrelle for induction of ovulation in women undergoing intrauterine insemination (IUI). SETTINGS AND DESIGN: Randomized (2:1), multicenter, open-label, equivalence clinical trial conducted in India. SUBJECTS AND METHODS: A total of 217 women, aged 20-37 years, undergoing IUI were administered the new r-hCG (test) 250 mcg or Ovitrelle 250 mcg (comparator) after ovarian stimulation with gonadotropins. The ovulation rate was compared as the primary outcome. In addition, pregnancy rates, incidence of adverse events (AEs), and development of immunogenicity were assessed. Statistical Analysis Used: The ovulation and pregnancy rates were compared using Chi-squared test with statistical significance at P < 0.05. RESULTS: With 144 women in the test group and 73 in the comparator group, the ovulation rate (85.4% vs. 78.1%; P = 0.17) and pregnancy rate (serum ß hCG test) (11.8% vs. 12.3%; P = 0.91) were similar in both groups. A total of 15 AEs were reported (11 in the test r-hCG group and 4 in the comparator group) in 11 women; none of these were serious, and all were judged to be unrelated to the study drug. No subject developed immunogenic reaction to the test drug. CONCLUSIONS: The new preparation of r-hCG was equivalent to the conventional preparation of r-HCG in the induction of ovulation in patients undergoing IUI.

A Multicenter Phase IV Study to Investigate the Immunogenicity of Recombinant Human Follicle-Stimulating Hormone and Its Impact on Clinical Outcomes in Females Undergoing Controlled Ovarian Stimulation.

CONTEXT: Therapeutic proteins can cause immune responses, which may have clinical implications. AIMS: The aim of the study was to assess the immunogenicity of recombinant human follicle-stimulating hormone (r-hFSH), when used for controlled ovarian stimulation (COS). SETTINGS AND DESIGN: Prospective, multicenter study conducted at reproductive medicine clinics in India and Vietnam. MATERIALS AND METHODS: A total of 285 women, aged 20-40 years, undergoing 354 COS cycles for either intrauterine insemination (IUI) or in vitro fertilization (IVF) were studied. The primary outcome measure was the incidence of development of anti-drug antibodies (ADA) and their neutralization potential. Other outcome measures were follicle development, dose and duration of r-hFSH, positive serum pregnancy test, clinical pregnancy, cycle cancellation, and adverse events (AEs). STATISTICAL ANALYSIS USED: A sample size of 250 was planned. Descriptive statistics are presented. RESULTS: Four patients tested positive for ADA after r-hFSH administration at different time points; all of them tested negative, subsequently. None were found to have neutralization potential. The mean dose and duration of r-hFSH were 816 IU and 8.1 days in IUI and 2183 IU and 9.5 days in IVF, respectively. The serum and clinical pregnancy rates were 12.4% and 11.6% in IUI and 32.7% and 29.9% in IVF cycles, respectively. Seven AEs were reported, including two cases of ovarian hyperstimulation syndrome; two AEs were judged to be serious. CONCLUSIONS: The tested r-hFSH has very low immunogenic potential and did not lead to the development of neutralizing antibodies. The overall efficacy and safety of the drug were in-line with existing literature data, and no specific clinical impact of immunogenicity could be identified.

Retrospective study of risk factors and maternal and fetal outcome in patients with abruptio placentae.

INTRODUCTION: Abruptio placentae (AP) which is a major cause of maternal morbidity and perinatal mortality globally is of serious concern in the developing world. We retrospectively analyzed the AP cases and evaluated its impact on fetal and maternal outcomes. MATERIALS AND METHODS: The present study was undertaken from September 2007-August 2009 at a tertiary care center attached to medical college; patients of AP were selected from all cases with minimum of 28 weeks of gestation, presenting with antepartum hemorrhage. Patients underwent complete obstetrical investigations and were managed according to maternal and fetal condition. RESULTS: 4.4% incidence rate of AP was documented accounting for 318 cases during the study period. Most of cases were unbooked, with an average age of 34.5 years (range, 18-44) and nearly two-third of the patients were from lower socioeconomic class. Anemia was observed in 96% of patients, with 3.5 and 68% incidence of maternal and fetal mortality, respectively. CONCLUSION: We observed a higher than expected frequency of AP and neonatal mortality in our study population, which is of major concern. We envisage need for mass information regarding the importance of antenatal maternal care and improvement in nutritional status, which may reduce the frequency of maternal and fetal morbidity and mortality associated with AP.