Preimplantation genetic testing for aneuploidy in patients with low embryo numbers: benefit or harm?

PURPOSE: We sought to explore the utility of preimplantation genetic testing for aneuploidy (PGT-A) in a poor prognosis group of women with few embryos available for transfer. METHODS: This was a retrospective matched cohort study examining records for first or second-cycle IVF patients with 1 to 3 blastocysts. The study group comprised 130 patients who underwent PGT-A on all embryos. The control group included 130 patients matched by age, BMI, and blastocyst number and quality who did not undergo PGT-A during the same time period. RESULTS: The live birth rate (LBR) per embryo transfer (ET) were similar in the PGT-A and control groups, and the spontaneous abortion (SAB) rate was the same (23%). However, we found a significantly higher LBR per oocyte retrieval in the control group vs the PGT-A group (43% vs 20%, respectively) likely due to the many no-euploid cycles in the PGT-A group. In a subgroup analysis for age, the similar LBR per ET persisted in women < 38. However, in older women, there was a trend to a higher LBR per ET in the PGT-A group (43%) vs the control group (22%) but a higher LBR per oocyte retrieval in the control group (31%) vs the PGT-A group (13%). CONCLUSIONS: Overall, we observed a significant increase in LBR per oocyte retrieval in women in the control group compared to women undergoing PGT-A, and no difference in SAB rate. Our data suggests that PGT-A has no benefit in a subpopulation of women with few embryos and may cause harm.

Knowledge and attitudes regarding elective oocyte cryopreservation in undergraduate and medical students.

BACKGROUND: To assess knowledge and attitudes regarding elective oocyte cryopreservation among female undergraduate students (UG) and medical students (MS) in Eastern Virginia. METHODS: An anonymous cross-sectional study surveying female UG at a local university and MS at our academic medical center in May of 2017. The survey contained questions on demographic information, interest in fertility preservation, and knowledge about age related changes in fertility. RESULTS: There were 74 of 102 female UG and 95 of 117 female MS who responded, for a response rate of 73 and 81% respectively. UG were significantly younger than MS (21.4 vs 26.8, p < 0.001). Further, UG generally planned on conceiving at a younger age than MS (age 26-30 vs 31-35), and favored younger ages to consider oocyte cryopreservation (age 26-30 vs 31-35). Only a minority of both UG and MS were willing to undergo egg freezing at the current price of approximately $10,000 (15% vs 26% respectively, p = 0.044). Moreover, 73% of students overall responded that they would be more likely to freeze oocytes if their employer paid. Notably, both UG and MS underestimated age of fertility decline. CONCLUSION: Both UG and MS revealed a need for education on age-related changes in fertility. Most UG and MS would not undergo elective oocyte cryopreservation at the present cost but would consider it at a lower cost.

The role of microRNAs in human embryo implantation: a review.

MicroRNAs (miRNAs) are emerging as important in human embryo implantation, and we present here a review of the literature from a clinical perspective. Implantation involves complex interactions between the blastocyst and endometrium. miRNAs have been shown to be differentially expressed in implanted compared with non-implanted blastocysts and euploid compared with aneuploid blastocysts. Further, miRNAs are differentially expressed in proliferative compared with decidualized endometrium, and in receptive compared with pre-receptive endometrium. miRNAs are also differentially expressed in endometrium of women who failed implantation, and in endometrium of women with recurrent implantation failure. Due to the complexity of miRNA signaling, studies have suffered from inconsistency in reproducibility of results. However, miRNAs show potential as biomarkers in the pursuit of more reliable prediction of embryo implantation.

The Toxicology of Methadone-Related Death in Infants Under 1 Year: Three Case Series and Review of the Literature.

Methadone-related fatalities occur rarely in infants under 1 year, with five confirmed cases in the literature. The interpretation of pediatric postmortem toxicology relies on adult data; however, infants have crucial physiological differences that may impact interpretation of results. Retrospective case review included scene investigation, interviews, autopsy, and NIH/CDC Sudden Unexplained Infant Death Investigation Reporting Form. Methadone levels were confirmed by liquid chromatography/tandem mass spectrometry (LC-MS/MS). The fatal blood methadone levels in this case series ranged from 69 to 700 ng/mL. This review of the literature adds toxicological findings of three methadone-related infant fatalities and reviews the current literature on methadone-related death in infants under 1 year. With opioid use on the rise in today's society, forensic experts should have a high index of suspicion for the possibility of intentional or unintentional poisoning in infants.

Unnatural pregnancy deaths in Las Vegas: A descriptive study.

This study reports descriptive data assessing the prevalence of various risk factors and associations among pregnancy-related death by unnatural causes (PRUD), namely suicide, homicide and accidental causes in the city of Las Vegas. In 7215 women referred for autopsy, results showed PRUD 0.1% (n = 37) was more common in the Caucasian race 45.9% (n = 17), and ages 20-30 years 43.2% (n = 16). We also identified high prevalence of mental illness 51.3% (n = 19) and low prenatal care 37.8% (n = 14), particularly in our suicide cohort 100.0% (n = 13), and 15.3% (n = 2) respectively. Our study demonstrates the first investigation to identify the relationship between mental illness, particularly mood and substance disorders with pregnancy-related unnatural death.

Pelvic Examination at the 6-Week Postpartum Visit After Cesarean Birth.

INTRODUCTION: The objective of this study was to assess the utility of the pelvic examination at the 6-week postpartum visit after cesarean birth. METHODS: Data were collected from retrospective chart review in an obstetric resident clinic in Detroit, Michigan. Women included were those who had a cesarean birth between January 2012 and June 2014. RESULTS: Of 388 women who had a cesarean birth, 211 (54.4%) presented for the 6-week postpartum visit and underwent pelvic examination. Of these women, 185 (87.7%) were asymptomatic, and 26 (12.3%) reported vaginal discharge. No other concerns were elicited. Of those with symptoms, 4 (15%) had no finding, 13 (50%) had bacterial vaginosis (BV) alone, 2 (8%) had BV and Candida sp, 2 (8%) had BV and Trichomonas vaginalis, 2 (8%) had T vaginalis alone, and 3 (11%) had Chlamydia trachomatis. One woman with C trachomatis had tested positive during pregnancy and possibly had treatment failure. Of the 185 asymptomatic women, 91 (49%) were deemed to have vaginal discharge on examination and underwent testing for Neisseria gonorrhoeae and C trachomatis; results were negative in all cases. DISCUSSION: In this population, it appears unnecessary to perform routine pelvic examination on asymptomatic women at the 6-week postpartum visit after cesarean birth. When vaginal discharge was noted during pelvic examination of asymptomatic women, no pathology was identified.

Differentially expressed genes in adipocytokine signaling pathway of adipose tissue in pregnancy.

OBJECTIVE: To profile the differential gene expression of the KEGG Adipocytokine Signaling pathway in omental compared to subcutaneous tissue in normal pregnancy. STUDY DESIGN: Subjects included 14 nonobese, normal glucose tolerant, healthy pregnant women. Matched omental and subcutaneous tissue were obtained at elective cesarean delivery. Gene expression was evaluated using microarray and validated by RT-PCR. Differential gene expression was defined as ≥1.5 fold increase at p < 0.05. RESULTS: Six genes were significantly downregulated with two upregulated genes in omental tissue. Downregulation of Adiponectin and Insulin Receptor substrate, key genes mediating insulin sensitivity, were observed with borderline upregulation of GLUT-1. There were downregulations of CD36 and acyl-CoA Synthetase Long-chain Family Member 1which are genes involved in fatty acid uptake and activation. There was a novel expression of Carnitine palmitoyltransferase 1C. CONCLUSION: Differential gene expression of Adipocytokine Signaling Pathway in omental relative to subcutaneous adipose tissue in normal pregnancy suggests a pattern of insulin resistance, hyperlipidemia, and inflammation.

Role of the sulfonium center in determining the ligand specificity of human s-adenosylmethionine decarboxylase.

S-Adenosylmethionine decarboxylase (AdoMetDC) is a key enzyme in the polyamine biosynthetic pathway. Inhibition of this pathway and subsequent depletion of polyamine levels is a viable strategy for cancer chemotherapy and for the treatment of parasitic diseases. Substrate analogue inhibitors display an absolute requirement for a positive charge at the position equivalent to the sulfonium of S-adenosylmethionine. We investigated the ligand specificity of AdoMetDC through crystallography, quantum chemical calculations, and stopped-flow experiments. We determined crystal structures of the enzyme cocrystallized with 5'-deoxy-5'-dimethylthioadenosine and 5'-deoxy-5'-(N-dimethyl)amino-8-methyladenosine. The crystal structures revealed a favorable cation-pi interaction between the ligand and the aromatic side chains of Phe7 and Phe223. The estimated stabilization from this interaction is 4.5 kcal/mol as determined by quantum chemical calculations. Stopped-flow kinetic experiments showed that the rate of the substrate binding to the enzyme greatly depends on Phe7 and Phe223, thus supporting the importance of the cation-pi interaction.