S.A. Neal

Hematologic Disease in Implantation Failure

Successful embryo implantation involves a number of events that occur at the microvascular level. Hematologic pathology, specifically inherited and acquired thrombophilias, has been proposed as a potential etiology for implantation failure. This idea has largely evolved from the robust body of literature surrounding thrombophilias and recurrent pregnancy loss. The impact of thrombophilias on recurrent implantation failure is less clear, although it is thought to have a similar underlying mechanism, namely, that microthrombosis causes disturbed blood flow to the endometrium and, in the case of recurrent implantation failure, impairs the initial vascularization process that is necessary for successful implantation to occur. In this chapter, the available literature regarding the potential role of thrombophilias in implantation failure and the evidence for possible therapeutic options will be reviewed.

Diminished ovarian reserve and poor response to stimulation in patients <38 years old: a quantitative but not qualitative reduction in performance

STUDY QUESTION Do infertile women aged <38 years with quantitative evidence of diminished ovarian reserve and/or poor response to stimulation also exhibit poor oocyte quality as measured by blastulation rates, aneuploidy rates, and live birth rates? SUMMARY ANSWER Young women with evidence of accelerated follicular depletion, either by precycle ovarian reserve testing or postcycle evidence of low oocyte yield, exhibit equivalent blastulation rates, aneuploidy rates and live birth rates per euploid embryo transfer as age-matched controls with normal precycle and postcycle parameters. WHAT IS KNOWN ALREADY Previous studies are conflicted as to whether women with evidence of diminished ovarian reserve and/or poor ovarian response are also at increased risk of exhibiting evidence of poor oocyte quality. Most prior studies have failed to adequately control for the confounding effect of female age on typical markers of oocyte quality in poor responders. The rate of follicular depletion occurs at around 38 years on average; thus, evidence of quantitative depletion before this would indicate a premature diminution of ovarian reserve and allow evaluation of whether markers of oocyte quality are tied to quantitative markers. STUDY DESIGN, SIZE, DURATION This was a retrospective cohort study at a single center between 2012 and 2016. This time frame was specifically chosen as all embryos were cultured to the blastocyst stage at this center during the study period (no cleavage stage transfers were performed). Two comparisons were made: precycle assessment of ovarian reserve (based on anti-mullerian hormone (AMH) level) and postcycle oocyte yield results. For each comparison, patients in <10th percentile were compared to patients in the interquartile range (IQR) with respect to blastulation rate, aneuploidy rate and live birth rate. A mixed effects model was created to control for female age (in the <38 year old range) and correlation among oocytes from a given cohort. PARTICIPANTS/MATERIALS, SETTING, METHODS For the precycle blastulation analysis, only patients with AMH data available were included (345 patients with AMH in the <10th percentile versus 1758 patients with AMH in the 25th to 75th percentile (IQR)). To compare aneuploidy rates, the subset of these patients who pursued preimplantation genetic testing for aneuploidy (PGT-A) was then analyzed (124 patients in the <10th percentile versus 782 patients in the IQR). For the postcycle blastulation analysis, all patients who proceeded to retrieval (whether or not they also had AMH data available) were included (535 patients with oocyte yield in the <10th percentile versus 2675 patients in the IQR). To compare aneuploidy rates, the subset of these patients who pursued PGT-A was then analyzed (156 patients in the <10th percentile versus 1100 patients in the IQR). MAIN RESULTS AND THE ROLE OF CHANCE The adjusted odds of a given fertilized oocyte developing to a blastocyst, being aneuploid or leading to a live birth after euploid transfer were no different if the oocyte was retrieved from a cycle with ovarian reserve parameters or oocyte yield in the <10th percentile compared to an oocyte retrieved in a cycle with those parameters in the 25-75th percentile. An AMH level in the <10th percentile did more commonly result in cycle cancellation prior to retrieval and after retrieval prior to transfer due to global arrest of embryos. LIMITATIONS, REASONS FOR CAUTION The timing of retrieval in patients with fewer oocytes may be more optimal given the greater ability to discern the overall maturity of the cohort, thus enhancing performance per retrieved oocyte. Analyses included only first cycles. Subsequent adjustment of protocol due to prior performance may mean that some patients in the <10th percentile for oocyte yield are actually better prognosis patients than their first cycle indicates. Data on whether or not patients were on oral contraceptives at time that AMH level drawn was not available. Other unknown biases are also likely to be present given retrospective nature of the study. WIDER IMPLICATIONS OF THE FINDINGS While young women with evidence of quantitative depletion of ovarian reserve have lower live birth rates per stimulation cycle, this not attributable to poor oocyte quality because the blastulation rate per fertilized oocyte and live birth rate per embryo transfer are equivalent to that in women with normal quantitative markers of ovarian reserve. Thus, the pathophysiology mediating a premature quantitative decline in ovarian reserve appears different than that which mediates markers of oocyte quality, such as aneuploidy. Young poor responders may use this information to help guide embryo accumulation strategies when considering their family building plans. STUDY FUNDING/COMPETING INTEREST(S) None. TRIAL REGISTRATION NUMBER N/A.

The impact of contemporary preimplantation genetic screening and diagnosis on the detection of aneuploidy and inherited genetic diseases

Pre‐implantation genetic screening and diagnosis represent important tools for embryo selection in patients undergoing in vitro fertilization. Methods have evolved in recent years and it can be challenging to remain up to date on the current technology. This review article seeks to provide an overview of pre‐implantation genetic screening and diagnosis methods, the associated clinical outcomes, and the limitations of this technology.

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.