A Randomized Trial of Progesterone in Women with Bleeding in Early Pregnancy

BACKGROUND Bleeding in early pregnancy is strongly associated with pregnancy loss. Progesterone is essential for the maintenance of pregnancy. Several small trials have suggested that progesterone therapy may improve pregnancy outcomes in women who have bleeding in early pregnancy. METHODS We conducted a multicenter, randomized, double-blind, placebo-controlled trial to evaluate progesterone, as compared with placebo, in women with vaginal bleeding in early pregnancy. Women were randomly assigned to receive vaginal suppositories containing either 400 mg of progesterone or matching placebo twice daily, from the time at which they presented with bleeding through 16 weeks of gestation. The primary outcome was the birth of a live-born baby after at least 34 weeks of gestation. The primary analysis was performed in all participants for whom data on the primary outcome were available. A sensitivity analysis of the primary outcome that included all the participants was performed with the use of multiple imputation to account for missing data. RESULTS A total of 4153 women, recruited at 48 hospitals in the United Kingdom, were randomly assigned to receive progesterone (2079 women) or placebo (2074 women). The percentage of women with available data for the primary outcome was 97% (4038 of 4153 women). The incidence of live births after at least 34 weeks of gestation was 75% (1513 of 2025 women) in the progesterone group and 72% (1459 of 2013 women) in the placebo group (relative rate, 1.03; 95% confidence interval [CI], 1.00 to 1.07; P=0.08). The sensitivity analysis, in which missing primary outcome data were imputed, resulted in a similar finding (relative rate, 1.03; 95% CI, 1.00 to 1.07; P=0.08). The incidence of adverse events did not differ significantly between the groups. CONCLUSIONS Among women with bleeding in early pregnancy, progesterone therapy administered during the first trimester did not result in a significantly higher incidence of live births than placebo. (Funded by the United Kingdom National Institute for Health Research Health Technology Assessment program; PRISM Current Controlled Trials number, ISRCTN14163439. opens in new tab.

Correlation of Sagittal Skeletal malocclusion and Growth patterns between Digital and Conventional Dermatoglyphics

Background: The craniofacial morphology and its growth pattern are determined by the influence of various environmental factors depending on the genetic background. Due to the close association of MSX 1 and SMARCAD gene on the same chromosome, it can be hypothesized that malocclusion and fingerprint pattern are related. Furthermore, it is observed that the orofacial structures originate from the same embryonic tissue as the epidermal ridges, which are the ectoderm. Thus, the simultaneous development of the epidermal ridges and the orofacial structure during this time is deciphered and reflected in the fingerprint patterns. Aim: This study aimed to analyse, compare, and correlate the fingerprint patterns of individuals with different skeletal malocclusions and growth patterns using manual and digital methods. Materials and Methods: Patients (a random sample of 544) who were undergoing orthodontic treatment and were able to give informed consent were included in the study. Informed consent was obtained prior to the start of the procedure, with due regard to ethical issues and the confidentiality of fingerprint records. The anteroposterior jaw relation was determined from the patient's lateral cephalogram with evaluation of the parameters: SNA, ANB, SNB and growth patterns are determined using the mandibular plane angle according to Steiners analysis, the nature of the growth patterns, i.e., horizontal (HGP), Average (AGP) and vertical (VGP) growth pattern. Results: Individuals with loop patterns had a frequency of skeletal class I malocclusion, Whorl patterns with skeletal class II malocclusion, and Arch patterns with skeletal class III malocclusion. Consistent with the growth patterns, the whorl pattern was seen more prominently in the horizontal growth pattern, Arch pattern in the average growth pattern, and the loop pattern in the vertical growth pattern. Conclusion: Thus, the dermatoglyphics can be used as a screening tool for early prediction of skeletal malocclusion in a younger age group

Recombinant human granulocyte - colony stimulating factor in women with unexplained recurrent pregnancy losses: a randomised clinical trial

Study question: Does administration of recombinant human granulocyte colony stimulating factor in the first trimester improve pregnancy outcomes, among women with a history of unexplained recurrent pregnancy loss? Summary answer: Recombinant human granulocyte colony stimulating factor administered in the first trimester of pregnancy did not improve outcomes among women with a history of unexplained recurrent pregnancy loss.What is known already: The only previous randomised controlled study of granulocyte colony stimulating factor in recurrent miscarriage in sixty-eight women with unexplained primary recurrent miscarriage found a statistically significant reduction in miscarriage and improvement in live birth rates. A further four observational studies where G-CSF was used in a RM population was identified in literature, two of which confirmed statistically significant increase in clinical pregnancy and live birth rates. Study design, size, duration: A randomised, double-blind, placebo controlled clinical trial involving 150 women with a history of unexplained recurrent pregnancy loss was conducted at 21 sites with established recurrent miscarriage clinics in the United Kingdom between 23 June 2014 and 05 June 2016. The study was coordinated by University of Birmingham, UK. Participants/materials, setting, methods: 150 women with a history of unexplained recurrent pregnancy loss: 76 were randomised to recombinant human granulocyte – colony stimulating factor and 74 to placebo. Daily subcutaneous injections of recombinant human granulocyte – colony stimulating factor 130 mcg or identical appearing placebo from as early as three to five weeks of gestation for a maximum of 9 weeks. The trial used central randomisation with allocation concealment. The primary outcome was clinical pregnancy at 20 weeks of gestation, as demonstrated by an ultrasound scan. Secondary outcomes included miscarriages, livebirth, adverse events, stillbirth, neonatal birth weight, changes in clinical laboratory variables following study drug exposure, major congenital anomalies, preterm births and incidence of anti-drug antibody formation. Analysis was by intention to treat. Main results and the role of chance: A total of 340 participants were screened for eligibility of which 150 women were randomised. 76 women (median age, 32[IQR, 29-34] years; mean BMI, 26.3[SD, 4.2] and 74 women (median age, 31[IQR, 26-33] years; mean BMI, 25.8[SD, 4.2] were randomised to placebo. All women were followed-up to primary outcome, and beyond to live birth. The clinical pregnancy rate at 20 weeks, as well as the live birth rate, was 59.2% (45/76) in the rhG-CSF group, and 64.9% (48/74) in the placebo group, giving a relative risk of 0.9 (95% CI: 0.7 to 1.2; p=0.48). There was no evidence of a significant difference between the groups for any of the secondary outcomes. Adverse events (AEs) occurred in 52 (68.4%) participants in rhG-CSF group and 43 (58.1%) participants in the placebo group. Neonatal congenital anomalies were observed in 1/46 (2.1%) of babies in the rhG-CSF group versus 1/49 (2.0%) in the placebo group (RR of 0.9; 95% CI: 0.1to 13.4; p=0.93). Limitations, reasons for caution: This trial was conducted in women diagnosed with unexplained recurrent pregnancy loss and therefore no screening tests (commercially available) were performed for immune dysfunction related pregnancy failure/s. Wider implications of the findings: To our knowledge, this is the first multicentre study and largest randomised clinical trial to investigate the efficacy and safety of granulocyte human colony stimulating factor in women with recurrent miscarriages. Unlike the only available single centre RCT, our trial showed no significant increase in clinical pregnancy or live births with the use of rhG-CSF in the first trimester of pregnancy. Study funding/competing interest(s): Mark Joing, Paul Kwon, Jeff Tong and Darryl Carter were or are employees of Nora Therapeutics, Inc. Arri Coomarasamy received consulting fees from Nora Therapeutics through his employer, University of Birmingham. Ruth Bender Atik received consulting fees from Nora 97 Therapeutics which was paid to The Miscarriage Association, UK. No other potential conflict of interest relevant to this article was reported. Disclosure forms provided by the authors are available with full text of this article.<br/