D.J. Kaser

Embryonic Factors Associated with Recurrent Implantation Failure

Recurrent implantation failure (RIF) is a frustrating clinical scenario for the patient, physician, and embryology team alike. When seemingly “good-quality embryos” fail to implant in a normal uterus following multiple embryo transfers, there is often no immediate obvious reason. Despite considerable improvements in both clinical protocols and laboratory technologies over the last 30 years of assisted reproduction, the question remains as to how best to select the most developmentally competent embryo from a given cohort. The purpose of this chapter is not to provide a comprehensive review of the normal developmental kinetics or morphologic scoring systems of the human preimplantation embryo (reviewed by Matchinger and Racowsky (Reprod Biomed Online 26:210–21, 2013)). Rather, this chapter will (1) focus on embryonic factors associated with implantation in general and RIF specifically and (2) identify interventions in the IVF laboratory at the cleavage and blastocyst stages that may optimize pregnancy rates in this challenging patient population.

Crossing the germline: CRISPR-Cas9 and our responsibility as reproductive endocrinology and infertility physicians

Eighty years after this question was raised in an anonymously penned editorial in the New England Journal of Medicine, largely attributed to the giant Dr. John Rock, we may have an answer. The clustered regularly interspaced short palindromic repeat (CRISPR)-associated system (Cas) geneediting technology now has been applied to gametes and triploid and diploid human embryos. The ease, speed, and low cost of the system have been hailed by many scientists as a tremendous breakthrough. The possibility that this technology, in the not too distant future, could be applied clinically for primary prevention of disease indeed may appeal to doctors and patients alike. Serious concerns remain, however, regarding both the ethics of the technology and technical limitations including its efficiency and fidelity [2–4]. Authors from a prominent gene-editing laboratory stated in a recent manuscript, BSeparately from the debate of the merit and ethics of germline editing in humans, the feasibility of correcting genetic defects via CRISPR technology in human zygotes has not been really tested^ [4]. This view implies that ethics and technical advancement occur independent of one another; it seems vital, however, that the ethics of any disruptive technology be considered together with, if not before, the technical development itself. Unfortunately, history has shown that often technology is developed first, and then society reacts by accepting or rejecting it. Now, more than ever, our field is pressed with questions of where we are headed; should we, as infertility specialists, continue this line of investigation, and if so, under what circumstances is application of this technology clinically, morally, and socially acceptable? If we do not take the lead on this, which specialty will and to what end? A 2017 joint report by the National Academies of Sciences, Engineering, andMedicine entitled BHuman Genome Editing: Science, Ethics and Governance^ seeks to address these questions and others [5]. This 261-page PDF is available for free download online (https://www.nap.edu/catalog/24623/ human-genome-editing-science-ethics-and-governance). There are 22 co-authors on this report, including medical geneticists, stem cell and cancer biologists, pediatricians, internists, lawyers, and bioethicists. Surprisingly, not a single reproductive endocrinology and infertility (REI) physician, arguably the one most likely to counsel patients about this technology if it were ever applied clinically, was involved in drafting this document.

Characterization of reproductive endocrinology and infertility (REI) fellowship applicants: guiding our mentees toward success

BackgroundAdvanced subspecialty training in reproductive endocrinology and infertility (REI) entails a competitive application process with many data points considered. It is not known what components weigh more heavily for applicants. Thus, we sought to study the REI fellow applicant and compare 1) those who apply but do not receive an interview, 2) those who receive an interview but do not match, and 3) those who successfully match.MethodsThis retrospective cohort study was conducted at a single REI fellowship program from 2013 to 2017. Academic variables assessed included standardized test scores and total number of publications listed on their curriculum vitae. Logistic regression models were constructed to determine variables that were predictive of being offered an interview in our program and of matching in any program.ResultsThere were 270 applicants, of which 102 were offered interviews. Interviewed applicants had significantly higher mean USMLE 1 and CREOG scores, as well as total publications and total abstracts. There was no difference in Step 2 and Step 3 scores or in number of book chapters. Of those interviewed, USMLE scores remained predictive of matching in any program; however, publications and scientific abstracts were no longer predictive.ConclusionsThe decision to offer applicants interviews appears to be influenced by objective standardized test scores, as well as a threshold of academic productivity. These items are less predictive of matching once the interview process begins, indicating that other factors, such as performance during the interview day, may be more heavily weighted.