Multiple embryo manipulations in PGT-A cycles may result in inferior clinical outcomes.

RESEARCH QUESTION: Do embryos that undergo a thaw, biopsy and re-vitrification (TBR) for pre-implantation genetic testing for aneuploidy (PGT-A) have different ploidy and transfer outcomes compared with fresh biopsied embryos? DESIGN: Retrospective cohort study of all embryos that underwent the following procedures: fresh biopsy for PGT-A (fresh biopsy); embryos that were warmed, biopsied for PGT-A and re-vitrified (single biopsy TBR); embryos with a no signal result after initial biopsy that were subsequently warmed, biopsied and re-vitrified (double biopsy TBR). The patients who underwent transfers of those embryos at a single academic institution between March 2013 and December 2021 were also studied. RESULTS: About 30% of embryos planned for TBR underwent attrition. Euploidy rates were similar after biopsy: fresh biopsy (42.7%); single biopsy TBR (47.5%) (adjusted RR: 0.99, 0.88 to 1.12); and double biopsy TBR 50.3% (adjusted RR: 0.99, 0.80 to 1.21). Ongoing pregnancy over 8 weeks was not statistically significant (double biopsy TBR: 6/19 [31.6%] versus fresh biopsy: 650/1062 [61.2%]) (adjusted RR 0.52, 95% CI 0.26 to 1.03). The miscarriage rate increased (double biopsy TBR: 4/19 [21.1%] versus fresh biopsy: 66/1062 [6.2%])(RR 3.39, 95% CI 1.38 to 8.31). Live birth rate was also lower per transfer for the double biopsy TBR group (double biopsy TBR [18.75%] versus fresh biopsy [53.75%]) (RR 0.35, 95% CI 0.12 to 0.98), though not after adjustment (adjusted RR 0.37, 95% CI 0.13 to 1.09). These differences were not seen when single biopsy TBR embryos were transferred. CONCLUSIONS: Embryos that undergo TBR have an equivalent euploidy rate to fresh biopsied embryos. Despite that, double biopsy TBR embryos may have impaired transfer outcomes.

Deep technology for the optimization of cryostorage.

Cryopreservation, for many reasons, has assumed a central role in IVF treatment cycles, which has resulted in rapidly expanding cryopreserved oocyte and embryo inventory of IVF clinics. We aspire to consider how and with what resources and tools "deep" technology can offer solutions to these cryobiology programs. "Deep tech" has been applied as a global term to encompass the most advanced application of big data analysis for the most informed construction of algorithms and most sophisticated instrument design, utilizing, when appropriate and possible, models of automation and robotics to realize all opportunities for highest efficacy, efficiency, and consistency in a process.

Meeting the challenge of unclaimed cryopreserved embryos.

With the rise of efficient and highly effective embryo cryopreservation techniques, the modern in vitro fertilization laboratory has unintentionally become a long-term storage facility for embryos and gametes. One challenge posed by long-term storage is the issue of unclaimed, effectively abandoned, cryopreserved embryos whose owners cannot be identified or are unable to provide a dispositional decision. Given the nuanced nature of dealing with human tissue, no straightforward solutions for managing this novel scenario have prevailed. In this article, we discuss the problem faced by physicians, clinics, and patients alike when faced with unclaimed cryopreserved embryos. We also review strategies for proactive prevention and resolution of conflicts that may arise when making dispositional decisions.

Impact of daylight savings time on spontaneous pregnancy loss in in vitro fertilization patients.

Transition into daylight savings time (DST) has studied negative impacts on health, but little is known regarding impact on fertility. This retrospective cohort study evaluates DST impact on pregnancy and pregnancy loss rates in 1,654 autologous in vitro fertilization cycles (2009 to 2012). Study groups were identified based on the relationship of DST to embryo transfer. Pregnancy rates were similar in Spring and Fall (41.4%, 42.2%). Pregnancy loss rates were also comparable between Spring and Fall (15.5%, 17.1%), but rates of loss were significantly higher in Spring when DST occurred after embryo transfer (24.3%). Loss was marked in patients with a history of prior spontaneous pregnancy loss (60.5%).

'By the work, one knows the workman': the practice and profession of the embryologist and its translation to quality in the embryology laboratory.

The embryologist presides over the fulfillment of a patient's treatment in the laboratory for IVF through use of assisted reproduction techniques, and is in a unique position to impart quality to the process. Although the technical skill of the embryologist is critical, the embryologist's contribution to quality is equally conveyed through a knowledge of reproductive biology, keen observation and judgment, astute decision-making, the 'grit' to work under pressure and time constraints, and a sense of mission in the provision and continual development of a safe and effective laboratory. The embryologist also ensures that the laboratory complies with the regulations of federal, state, local and institutional authorities and the recommendations and guidelines of professional associations. In these roles, the embryologist assumes unique responsibilities counterbalanced by the unique rewards of assisting patients in having a family. This article aspires to illuminate this singular profession for those who may be contemplating a career in embryology and act as a resource for those who seek insight into this amalgam of basic science, technical proficiency, and managerial skill and acumen that characterize the practice of clinical embryology and the myriad of ways that practitioners contribute to the quality of assisted reproduction techniques and patient care.

Comprehensive evaluation of contemporary assisted reproduction technology laboratory operations to determine staffing levels that promote patient safety and quality care.

OBJECTIVE: To consider how staffing requirements have changed with evolving and increasingly more complex assisted reproduction technology (ART) laboratory practice. DESIGN: Analysis by four laboratory directors from three different ART programs of the level of complexity and time requirements for contemporary ART laboratory activities to determine adequate staffing levels. SETTING: University-based and private ART programs. PATIENT(S): None. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Human resource requirements for ART procedures. RESULT(S): Both complexity and time required for completion of a contemporary ART cycle have increased significantly compared with the same requirements for the "traditional cycle" of the past. The latter required roughly 9 personnel hours, but a contemporary cycle can require up to 20 hours for completion. Consistent with this increase, a quantitative analysis shows that the number of embryologists required for safe and efficient operation of the ART laboratory has also increased. This number depends on not only the volume but also the types of procedures performed: the higher the number of complex procedures, the more personnel required. An interactive Personnel Calculator is introduced that can help determine staffing needs. CONCLUSION(S): The increased complexity of the contemporary ART laboratory requires a new look at the allocation of human resources. Our work provides laboratory directors with a practical, individualized tool to determine their staffing requirements with a view to increasing the safety and efficiency of operations. The work could serve as the basis for revision of the 2008 American Society for Reproductive Medicine (ASRM) staffing guidelines.

Reprogramming within hours following nuclear transfer into mouse but not human zygotes.

Fertilized mouse zygotes can reprogram somatic cells to a pluripotent state. Human zygotes might therefore be useful for producing patient-derived pluripotent stem cells. However, logistical, legal and social considerations have limited the availability of human eggs for research. Here we show that a significant number of normal fertilized eggs (zygotes) can be obtained for reprogramming studies. Using these zygotes, we found that when the zygotic genome was replaced with that of a somatic cell, development progressed normally throughout the cleavage stages, but then arrested before the morula stage. This arrest was associated with a failure to activate transcription in the transferred somatic genome. In contrast to human zygotes, mouse zygotes reprogrammed the somatic cell genome to a pluripotent state within hours after transfer. Our results suggest that there may be a previously unappreciated barrier to successful human nuclear transfer, and that future studies could focus on the requirements for genome activation.

Receiver operating characteristic (ROC) analysis of day 5 morphology grading and metabolomic Viability Score on predicting implantation outcome.

PURPOSE: Assessment of embryo viability is a key component of in vitro fertilization (IVF) and currently relies largely on embryo morphology and cleavage rate. In this study, we used receiver operating characteristic (ROC) analysis to compare the Viability Score (generated by metabolomic profiling of spent embryo culture media using near infrared (NIR) spectroscopy) to morphologic grading for predicting pregnancy in women undergoing single embryo transfer (SET) on day 5. METHODS: A total of 198 spent embryo culture media samples were collected in four IVF centers located in the USA, Europe and Australia. First, 137 samples (training set) were analyzed by NIR to develop an algorithm that generates a Viability Score predictive of pregnancy for each sample. Next, 61 samples (validation set) were analyzed by observers blinded to embryo morphology and IVF outcome, using the Day 5 algorithm generated with the training set. Pregnancy was defined as fetal cardiac activity (FCA) at 12 weeks of gestation. RESULTS: The Area Under the Curve (AUC) was greater for the metabolomic Viability Score compared to Morphology [Training set: 0.75 versus 0.55, p = 0.0011; Validation set: 0.68 versus 0.50, P = 0.021], and for a Composite score (obtained using a model combining Viability Score with morphologic grading), compared to morphology alone [0.74 versus 0.50, p = 0.004]. CONCLUSIONS: Our findings suggest that Viability Score alone or in combination with morphologic grading has the potential to be a better classifier for pregnancy outcome than morphology alone in women undergoing SET on day 5.

The role of assisted reproductive technology in the management of recurrent pregnancy loss.

PURPOSE OF REVIEW: Description of genetic screening of preimplantation embryos as a means of reducing miscarriages in patients with recurrent pregnancy loss. RECENT FINDINGS: That the promise of preimplantation genetic screening (PGS) for ameliorating recurrent pregnancy loss has been fulfilled is controversial. An array of comparative studies has suggested a positive effect of PGS on implantation rate, but these have been balanced by studies showing no effect or a negative effect, highlighting the need for more rigorously designed studies and randomized controlled trials. Emerging technologies may provide more information from the embryo biopsies even as the mosaicism of the embryo and its implications for interpreting PGS data are recognized. SUMMARY: Through the screening of embryos for abnormality in chromosome number or structure and selecting only normal embryos for transfer, PGS was envisioned and applied as a therapeutic tool for improving implantation and live birth rates from in-vitro fertilization and providing a means of attenuating pregnancy loss in recurrent pregnancy loss patients. An array of reports on the effects of PGS on embryo implantation and live birth rates has been made since its introduction, showing, variously, increases, decreases or no changes in these parameters. Various factors may influence the efficacy of PGS, including the patient population to which it is applied, technical aspects such as embryo biopsy, the genetic analysis and embryo culture environment, the current limitation of the genetic analysis (a subset of, rather than all, the 24 chromosomes) and the mosaicism of the embryo and blastocyst. Collectively, these contribute to the challenge of optimizing PGS and understanding how the screening result reflects the ultimate genetic constitution of the conceptus. Emerging cytogenetic and molecular technologies such as comparative genomic hybridization and microarray analysis may provide a broader appraisal of the embryo for a more comprehensive evaluation of developmental potential and prognosis for live birth.