Faculty Bibliography

OBJECTIVE: The ongoing COVID-19 pandemic has disrupted the normal methods of communication used by physicians and patients, as well as the standard protocols and procedures by which medical clinics operate. Pandemic related stresses may have also influenced patient's fertility goals and/or their ovarian response.We questioned whether these changes resulted in any unanticipated effects in the treatments and outcomes of ART patients. DESIGN: Retrospective cohort. MATERIALS AND METHODS: Patients who underwent GnRH-antagonist IVF cycles from January 2020 through June 2020 at NYU Fertility Center, a period in New York City over which the COVID-19 pandemic escalated and life in the city drastically changed as a result of new social distancing measures, were separated by month of treatment and compared with patients from the corresponding month in the prior year (January 2019 through June 2019). Patient age, AMH, days gonadotropin, #oocytes retrieved, #oocytes matured, #fertilized, #blastocysts, and #euploid embryos were compared using Student's T-test.
RESULT(S): 1881 patients were compared over the parallel six-month periods. Clinic visits were markedly decreased over the months of March and April of 2020, when the pandemic was at its peak in NYC and treatments were suspended as per the ASRM pandemic guidelines. There were no differences in age, AMH, #oocytes retrieved, #mature oocytes, or #fertilized between the two years. In April of 2020 there were significantly more blastocysts per patient, as compared to April of 2019, however, in May and June of 2020 there were significantly fewer euploid embryos per patient, as compared to May and June of 2019 (see table).
CONCLUSION(S): In the months following the end of the COVID-19 treatment suspension, there were no apparent differences in patient characteristics or the quantitative responses to stimulation. However, there was a significant qualitative difference as expressed in the number of euploid embryos. It remains unclear if or how the pandemic is related to this difference

OBJECTIVE:To study the effect of frozen embryo transfer (FET) preparation protocol on incidence of subchorionic hematoma (SCH) and serum hormone levels. DESIGN/METHODS:Retrospective cohort study. SETTING/METHODS:University-affiliated fertility center. PATIENT(S)/METHODS:Patients who underwent FET at the New York University Langone Fertility Center. INTERVENTION(S)/METHODS:None. MAIN OUTCOME MEASURE(S)/METHODS:The primary outcome was incidence of SCH by protocol in FET cycles. RESULT(S)/RESULTS:There were 1,273 FET cycles that met criteria for inclusion. The frequency of SCH was lower in natural compared with programmed cycles (P<.05; relative risk = 0.4 [0.27-0.78]; odds ratio = 0.4 [0.23-0.75]). Serum estrogen level was higher in programmed compared with natural cycles on day of progesterone initiation (P<.001) and cycle day 28 (P<.001). However, serum estrogen levels at the same time points were not associated with formation of SCH in programmed or natural cycles. CONCLUSION(S)/CONCLUSIONS:This is the first study to evaluate the formation of SCHs by FET protocol type. Our results highlight that high serum estradiol levels do not independently lead to an increase in rate of SCH. Further research must be done to understand other clinical, or perhaps molecular, differences between natural and programmed FET cycle preparations that can be better associated with SCH formation.

PURPOSE/OBJECTIVE:To examine fertility-related social media accounts and influencers on two social media platforms. METHODS:The search function of Twitter (TW) and Instagram (IG) was used to generate a list of accounts with the terms: fertility, infertility, ttc, egg freezing, ivf, endometriosis, and reproductive. Accounts not in English, in private, with no posts in > 1 year, or with content unrelated to search terms were excluded. Accounts were assessed for author type; REI board certification (REI-BC); influencer (INF) status (> 10 K followers on IG; verified check mark on TW); account demographics; and content in last 5 posts. Statistical analysis included unpaired t tests, a classification and regression tree (CART) analysis, and stepwise multiple logistic regression. RESULTS:Seven hundred ten accounts were identified and 537 (278 TW, 259 IG) were included. Account types included societies, clinics, physicians, patients, groups, and "other." Instagram content (1290 posts reviewed) was primarily personal stories (31.7%) or inspiration/support (23.7%). Twitter content (1390 posts reviewed) was mostly promotion (28.2%) and research/education (20.2%). Thirty-nine accounts (12.5%) were influencers. Fertility influencers were most often awareness/support accounts (59.8% TW, 25.0% IG), patients (12.8% TW, 25% IG), or other (17.9% TW, 21.0% IG). Only 7.7% TW and 7.1% IG INFs were board-certified REI physicians. The best predictor for classification as an influencer was high activity (> 50 posts/month TW, > 10 posts/month IG). CONCLUSION/CONCLUSIONS:As patients increasingly utilize social media to obtain and engage with health information, it is critical to understand the fertility-related SM landscape. This understanding may help to successfully enhance relationships with patients and ensure dissemination of accurate information.

PURPOSE/OBJECTIVE:To assess the accuracy and reliability of comprehensive chromosome screening by next-generation sequencing (NGS) of human trophectoderm (TE) biopsy specimens. METHODS:The reliability and accuracy of diagnoses made by preimplantation genetic testing for aneuploidy (PGT-A) from TE biopsy were tested. Repeat biopsies of TE and inner cell mass (ICM) samples were obtained from thawed blastocysts previously tested by NGS. To test for the reliability of the NGS assay, biopsy samples were compared with the original PGT-A results. Prior NGS testing classified the TE samples as euploid, aneuploid, or aneuploid-mosaic. The resulting re-biopsied samples underwent SurePlex whole genome amplification followed by NGS via the MiSeq platform, with copy number value (CNV) determined using BlueFuse Multi Software. The primary outcome measure was reliability, defined as concordance between initial TE result and the repeat biopsies. Accuracy was determined by concordance between the TE and ICM samples, and compared between three chromosome types (disomic, aneuploid, and mosaic). RESULTS:Re-biopsies were performed on 32 embryos with prior PGT-A showing euploidy (10 embryos), aneuploidy of one or two chromosomes (4 embryos), or aneuploid-mosaic with one aneuploid chromosome and one mosaic chromosome (18 embryos). One hundred twenty-nine biopsy samples completed NGS (90 TE and 39 ICM biopsies) and 105 biopsy results were included in the analysis. TE biopsies provide a highly accurate test of the future fetus, with the ICM disomic concordance rate of 97.6%. Clinical concordance rates indicate that TE biopsies provide a reliable test when the result is euploid (99.5%) or aneuploid (97.3%), but less reliable when the result is mosaic (35.2%). CONCLUSION/CONCLUSIONS:TE biopsies predict euploidy or aneuploidy in the ICM with a high degree of accuracy. PGT-A with NGS of TE biopsies is shown to be highly reliable, with clinically relevant concordance rates for aneuploidy and euploidy over 95%. TE biopsies indicating mosaicism were less reliable (35.2%), presumably because mitotic non-disjunction events are not uniformly distributed throughout the blastocyst. However, classification of TE biopsy of PGT-A with NGS results as either aneuploid or euploid provides a highly reliable test.

OBJECTIVE:To investigate the use of preimplantation genetic testing for aneuploidy (PGT-A) among patients pursuing embryo banking (EB) for medically indicated fertility preservation (FP). DESIGN/METHODS:Retrospective cohort. SETTING/METHODS:University-affiliated fertility center. PATIENTS/METHODS:All patients who underwent in vitro fertilization with or without PGT-A for medically indicated FP between January 2014 and April 2018. INTERVENTIONS/METHODS:None MAIN OUTCOME MEASURES: EB cycle characteristics, subsequent cycle pursuit/outcomes, and frozen embryo transfer (FET) outcomes. RESULTS:A total of 58 medical EB cycles were compared; 34 cycles used PGT-A. Of the EB patients with breast cancer, 67% used PGT-A; other indications were evenly divided between PGT-A (FP/PGT-A) and no PGT-A (FP). PGT-A use increased over the study period. Groups were similar in age, days of stimulation, and days from initial FP consultation to treatment initiation. Number of oocytes (14.5 [2-63] FP vs. 17.5 [1-64] FP/PGT-A), 2PN zygotes (7 [1-38] FP vs. 9 [0-36] FP/PGT-A), and blastocysts (5.5 [0-22] FP vs. 5 [0-18] FP/PGT-A) cryopreserved were similar between groups. Equal numbers cryopreserved both oocytes and embryos (5 vs. 3). Five FP/PGT-A patients underwent a second EB cycle. Among FP/PGT-A patients, an average of 6.7 ± 5 blastocysts underwent PGT-A, with 3.5 ± 3 (48.2%) euploid embryos cryopreserved for future FET compared to an average of 7.2 ± 7 untested embryos in the FP group. CONCLUSION/CONCLUSIONS:PGT-A in medical EB cycles increased over time and did not limit the use of other FP methods such as oocyte cryopreservation. In some cases, poor PGT-A results informed patients to pursue a second EB cycle. When counseling patients, the prognostic benefits of PGT-A must be weighed against the financial costs and potential for "terminal" fertility diagnosis.

We investigated clinical error rates with single thawed euploid embryo transfer (STEET) diagnosed by next generation sequencing (NGS) and array comparative genomic hybridization (aCGH). A total of 1,997 STEET cycles after IVF with preimplantation genetic testing for aneuploidy (PGT-A) from 2010 to 2017 were identified; 1,151 STEET cycles utilized NGS, and 846 STEET cycles utilized aCGH. Any abortions, spontaneous or elective, in which products of conception (POCs) were collected were reviewed. Discrepancies between chorionic villus sampling, amniocentesis, or live birth results and PGT-A diagnosis were also included. Primary outcomes were clinical error rate per: ET, pregnancy with gestational sac, live birth, and spontaneous abortion with POCs available for analysis. Secondary outcomes included implantation rate (IR), spontaneous abortion rate (SABR), and ongoing pregnancy/live birth rate (OPR/LBR). The clinical error rates in the NGS cohort were: 0.7% per embryo, 1% per pregnancy with gestational sac, and 0.1% rate per OP/LB. The error rate per SAB with POCs was 13.3%. The IR was 69.1%, the OPR/LBR was 61.6%, and the spontaneous abortion rate was 10.2%. The clinical error rates in the aCGH cohort were: 1.3% per embryo, 2% per pregnancy with gestational sac, and 0.4% rate per OP/LB. The error rate per SAB with POCs was 23.3%. The IR was 63.8%, the OPR/LBR was 54.6%, and the SAB rate was 12.4%. Our findings demonstrate that, although NGS and aCGH are sensitive platforms for PGT-A, errors still occur. Appropriate patient counseling and routine prenatal screening are recommended for all patients undergoing IVF/PGT-A.

Study question: Is the clinical outcome of mosaic embryos influenced by chromosomal constitution? Summary answer: Reproductive potential of mosaic embryos is affected by the complexity of and the number of aneuploidy cells present in trophectoderm (TE) biopsy. What is known already: Chromosomal mosaic embryos are characterized by the presence of chromosomally different cell lines within the same embryo. While the transfer of these embryos is now offered as an option for women who undergo in vitro fertilization (IVF), several concerns remain. For instance, the limited data on pregnancy outcome and the possibility that intra-biopsy mosaicism in the TE is a poor predictor of the ploidy status of the ICM. Therefore, some argue that mosaicism should be not reported until a clear classification of such embryos in relation with their reproductive potential has been defined. Study design, size, duration: We collected the clinical outcomes of 822 mosaic embryos transferred in women underwent IVF between May 2016-May 2019. All embryos were cultured to blastocyst stage; trophectoderm (TE) biopsy was performed on Day-5 of development or Day6/7 for slow growing embryos. The clinical outcome obtained after transfer of mosaic embryos with different chromosomal constitution was compared with each other and with that obtained from a control group of 3781 euploid blastocysts. Participants/materials, setting, methods: Preimplantation genetic testing (PGT) was performed using high resolution next generation sequencing (NGS) methodology. TE biopsies were classified as mosaic if they had 20%-80% abnormal cells. For statistical analysis mosaic embryos were divided in groups based on mosaic levels and chromosomal constitution detected in TE: single mosaic aneuploidy (monosomy/trisomy; SM), double mosaic chromosomes (monosomy/trisomy or combination, DM), complex mosaic aneuploidy (>2 different aneuploidies; CM) and mosaic segmental aneuploidy (single and double deletion/insertion >5Mb, MS). Main results and the role of chance: The embryos were plotted in 10% increments, representing a progressive increase in the proportion of aneuploid cells in the TE, and linear regression showed a statistically significant decline in rates of implantation and ongoing pregnancy/birth (regression function with respective slopes -0.42 and -0.55, P=0.0381 and 0.0099). Regarding chromosomal constitution, MS had the best outcomes, followed by the group with one affected chromosome, followed by the group with two affected chromosomes, followed by the complex group (implantation P<0.0001, ongoing pregnancy/birth P<0.0001). MS showed a significantly poorer clinical outcomes compared to the euploid control group (implantation 51.3% vs 61.1%, P=0.0004; ongoing pregnancy/birth 42.6% vs 52.7%, P=0.0003). Limitations, reasons for caution: Additional clinical data must be obtained to evaluate the contribution of each different chromosome before this approach can be evaluated as an additional tool to choose mosaic embryos for transfer. Wider implications of the findings: The study provides the largest dataset of transferred mosaic embryo outcomes reported to date. This compiled analysis conclusively shows that embryos with different pattern of chromosomal mosaicism have a distinct set of clinical outcomes. This findings should be considered for genetic counseling