The implantation of fertilized ova and the formation of the placenta are crucial steps in reproduction. This review summarizes current information about these steps, including some of the molecular mechanisms that mediate them and how they may go awry, with consequent loss of the pregnancy.
implantation fertilized ovum molecular mechanisms, early pregnancy survival placenta formation, Norwitz implantation review embryo attachment, placental development early pregnancy loss mechanisms, molecular biology embryo implantation uterine receptivity, early pregnancy failure implantation defects, trophoblast invasion placentation review, reproductive biology implantation process New England Journal, endometrial receptivity embryo implantation signaling
PMID 11794174 11794174 DOI 10.1056/NEJMra000763 10.1056/NEJMra000763
Cite this article
Norwitz, E. R., Schust, D. J., & Fisher, S. J. (2001). Implantation and the survival of early pregnancy. The New England journal of medicine, 345(19), 1400-1408. https://doi.org/10.1056/NEJMra000763
Norwitz ER, Schust DJ, Fisher SJ. Implantation and the survival of early pregnancy. N Engl J Med. 2001;345(19):1400-1408. doi:10.1056/NEJMra000763
Norwitz, Errol R., et al. "Implantation and the survival of early pregnancy." The New England journal of medicine, vol. 345, no. 19, 2001, pp. 1400-1408.
Lincoff AM et al., 2023·The New England journal of medicine
The cardiovascular safety of testosterone-replacement therapy in middle-aged and older men with hypogonadism has not been determined. In a multicenter, randomized, double-blind, placebo-controlled, noninferiority trial, we enrolled 5246 men 45 to 80 years of age who had preexisting or a high risk of cardiovascular disease and who reported symptoms of hypogonadism and had two fasting testosterone levels of less than 300 ng per deciliter. Patients were randomly assigned to receive daily transdermal 1.62% testosterone gel (dose adjusted to maintain testosterone levels between 350 and 750 ng per deciliter) or placebo gel. The primary cardiovascular safety end point was the first occurrence of any component of a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, assessed in a time-to-event analysis. A secondary cardiovascular end point was the first occurrence of any component of the composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization, assessed in a time-to-event analysis. Noninferiority required an upper limit of less than 1.5 for the 95% confidence interval of the hazard ratio among patients receiving at least one dose of testosterone or placebo. The mean (±SD) duration of treatment was 21.7±14.1 months, and the mean follow-up was 33.0±12.1 months. A primary cardiovascular end-point event occurred in 182 patients (7.0%) in the testosterone group and in 190 patients (7.3%) in the placebo group (hazard ratio, 0.96; 95% confidence interval, 0.78 to 1.17; P<0.001 for noninferiority). Similar findings were observed in sensitivity analyses in which data on events were censored at various times after discontinuation of testosterone or placebo. The incidence of secondary end-point events or of each of the events of the composite primary cardiovascular end point appeared to be similar in the two groups. A higher incidence of atrial fibrillation, of acute kidney injury, and of pulmonary embolism was observed in the testosterone group. In men with hypogonadism and preexisting or a high risk of cardiovascular disease, testosterone-replacement therapy was noninferior to placebo with respect to the incidence of major adverse cardiac events. (Funded by AbbVie and others; TRAVERSE ClinicalTrials.gov number, NCT03518034.).