Faculty Bibliography

Objective: Current data suggests that use of oral antibiotics and corticosteroids (AC) prior to embryo transfer (ET) does not improve ET outcomes. We hypothesized that patients with a history of chronic endometritis (CE) may be an exception to this finding. The objective was to investigate the utility of AC prior to single thawed euploid embryo transfer (STEET) in patients with CE.
Design(s): Retrospective cohort study.
Material(s) and Method(s): Patients who underwent STEET at an academic medical center from 1/2000 to 4/2019 were identified. Cycles prior to 1/2018 received 100 mg doxycycline bid and methylprednisolone 16 mg daily (Pre) prior to ET, and cycles performed after this date did not (Post). Cycles were evaluated for performance of endometrial biopsy (EMB) for CE, with CE defined as presence of plasma cell marker CD-138 (not by hematoxylin and eosin stain alone). Patients positive for CE were treated with 2-3 weeks antibiotics prior to ET cycle start. Outcomes were recorded as not pregnant (NP), biochemical pregnancy (BP), ectopic (E), or intrauterine pregnancy (IUP). Rates of IUP were compared to NP+E and BP. Chi-squared test was used for analysis (p<0.05).
Result(s): 2774 STEET cycles were included. There were 1870 Pre and 904 Post. 462 cycles had an EMB for CE performed. Of these, 238 were positive for CE and 224 were negative. Rates of IUP versus NP, BP, and E combined were not significantly different between all Pre (n=1247, 67%) and all Post (n=628, 68%) with X²(2, N=2765) =2.24 P>.05. Similarly, rates of IUP were not significantly different in patients who had not had an EMB (Untested), or in patients who were tested for CE and found to be negative. In patients with a history of CE there was a small but significant increase in IUP in Post (n=61, 54%) compared to Pre (n=46, 37%) X²(2, N=238) =9.31 P<0.05.
Conclusion(s): Overall, treatment with AC was not associated with higher IUP rates. The use of AC did not improve outcomes in patients with a history of CE, and unexpectedly resulted in lower IUP rates. [Figure presented]
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Introduction: Clinical pregnancy represents success outcome in a PGT-a in cycle. It can be defined as the presence of sacs with fetal heart beats at 7-8 weeks. Main purpose of PGT-a study is to identify euploid embryos in order to be replaced to patient endometrium. Nevertheless, PGT-a cycles differs in relation with attributes related to patients as well cycle information. The main goal of the present study is to design an predictive model capable to give a probability of clinical pregnancy before embryo transfer takes place.
Material(s) and Method(s): Dataset used included 1190 cycles that belong at New York University Fertility Center between 2012 and 2015. Patient id was encrypted with an alphanumeric code. The classifier implement was a Multilayer Perceptron. Feature engineering and standardization was carried out in the original variables. Algorithm was implemented using Python programing language.Model parameters was searched using grid search methodology. Classification performance was evaluated via 5-fold cross validation and area under the curve (AUC) Results: Variables used as a predictor were: maternal age, biopsy specimen method, reason for referral and quantity of euploid and aneuploid embryos generated in the cycle. In order to evaluate normality distribution among the dependent variables selected D'Agostino's K2 test was performed as a goodness-of-fit measure. Results variables showed a non gaussian distribution (p>0.05). Lack of normality was due to presence of outliers. To mitigate it effects we employed a technique called feature engineering applying mathematical function to the original variables. In order to include categorical variables, it were coded using numerical encoding. Model implemented achieves an Area Under the Curve (AUC) of 80%. In other words, the sensitivity-specificity tradeoff in the classifier was of 80%. It is important to note that threshold selected was 0.5. It means that cases with an output after classification with values higher than the cut-off were classified as Pregnant. On the other hand cases with output lower than 0.5 were assigned as non pregnant. Furthermore, Sensitivity (True Positive / True Positive + False Negative) and Specificity (True Negative / True Negative + False Positive) were 82% and 69% respectively.
Conclusion(s): We are aware about the presence of an intrinsic bias closely related to the Fertility Center where the PGT-a cycles was performed. In order to overcome that we are developing a new algorithm capable to solve current limitation being capable to be adapted for a specific center. A scoring tool based on artificial intelligence can be helpful in selecting those patients with high probability to achieve clinical pregnancy during PGT-a cycle. Artificial neural networks is a robust estimator that allowed us to overcome multicollinearity between the original variables. Overall performance of the model was high (80%) giving strong evidence that the cycles can be accurately classified.
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PURPOSE/OBJECTIVE:To assess the experiences of two large fertility clinics in which embryos with positive results following preimplantation genetic testing for monogenic disorders (PGT-M) were transferred upon patient request, in order to explore the nature of the conditions for which these requests have been made and review ethical considerations. METHODS:Retrospective review of previous embryo transfers at the NYU Langone Fertility Center and ORM Fertility was performed. Embryo transfers prior to May 2019 in which embryo biopsy and PGT-M occurred were reviewed, and transferred embryos that were positive for a monogenic disorder (excluding autosomal recessive carriers) were identified. RESULTS:Seventeen patients were identified who elected to transfer 23 embryos that tested positive for nine different monogenic disorders. Most of the embryos transferred were positive for disorders that are autosomal dominant (15/23), are adult-onset (14/23), are associated with reduced penetrance (16/23), and have available management to lessen symptom severity (22/23). Transfer of positive embryos most commonly occurred for hereditary cancer susceptibility syndromes (9/23 embryos), particularly hereditary breast and ovarian cancer syndrome. CONCLUSIONS:When unaffected embryos are not produced following in vitro fertilization with PGT-M, some patients request to transfer embryos with positive test results. The majority of transfers were for embryos positive for adult-onset, reduced penetrance diseases. As these requests will likely increase over time, it is essential to consider the practical and ethical implications.

STUDY QUESTION/OBJECTIVE:What factors are associated with decision regret and anxiety following preimplantation genetic testing for aneuploidy (PGT-A)? SUMMARY ANSWER/UNASSIGNED:The majority of patients viewed PGT-A favourably regardless of their outcome; although patients with negative outcomes expressed greater decision regret and anxiety. WHAT IS KNOWN ALREADY/UNASSIGNED:PGT-A is increasingly utilized in in vitro fertilization (IVF) cycles to aid in embryo selection. Despite the increasing use of PGT-A technology, little is known about patients' experiences and the possible unintended consequences of decision regret and anxiety related to PGT-A outcome. STUDY DESIGN, SIZE, DURATION/UNASSIGNED:Anonymous surveys were distributed to 395 patients who underwent their first cycle of autologous PGT-A between January 2014 and March 2015. PARTICIPANTS/MATERIALS, SETTING, METHODS/UNASSIGNED:There were 69 respondents who underwent PGT-A at a university-affiliated fertility centre, completed the survey and met inclusion criteria. Respondents completed three validated questionnaires including the Brehaut Decision Regret (DR) Scale, short-form State-Trait Anxiety Inventory (STAI-6) and a health literacy scale. The surveys also assessed demographics, fertility history, IVF and frozen embryo transfer cycle data. MAIN RESULTS AND THE ROLE OF CHANCE/UNASSIGNED:The majority of respondents were Caucasian, >35 years of age and educated beyond an undergraduate degree. The majority utilized PGT-A on their first IVF cycle, most commonly to 'maximize the efficiency of IVF' or reduce per-transfer miscarriage risk. The overall median DR score was low, but 39% of respondents expressed some degree of regret. Multiple regression confirmed a relationship between embryo ploidy and decision regret, with a lower number of euploid embryos associated with a greater degree of regret. Patients who conceived following euploid transfer reported less regret than those who miscarried or failed to conceive (P < 0.005). Decision regret was inversely associated with number of living children but not associated with age, education, race, insurance coverage, religion, marital status or indication for IVF/PGT-A. Anxiety was greater following a negative pregnancy test or miscarriage compared to successful conception (P < 0.0001). Anxiety was negatively associated with age, time since oocyte retrieval and number of living children, and a relationship was observed between anxiety and religious affiliation. Overall, decision regret was low, and 94% of all respondents reported satisfaction with their decision to pursue PGT-A; however, patients with a negative outcome were more likely to express decision regret and anxiety. LIMITATIONS, REASON FOR CAUTION/UNASSIGNED:This survey was performed at a single centre with a relatively homogenous population, and the findings may not be generalizable. Reasons for caution include the possibility of response bias and unmeasured differences among those who did and did not respond to the survey, as well as the possibility of recall bias given the retrospective nature of the survey. Few studies have examined patient perceptions of PGT-A, and our findings should be interpreted with caution. WIDER IMPLICATIONS OF THE FINDINGS/UNASSIGNED:Overall decision regret was low following PGT-A, and the vast majority deemed the information gained valuable for reproductive planning regardless of outcome. However, more than one-third of the respondents expressed some degree of regret. Respondents with no euploid embryos were more likely to express regret, and those with a negative outcome following euploid embryo transfer expressed both higher regret and anxiety. These data identify unanticipated consequences of PGT-A and suggest opportunities for additional counselling and support surrounding IVF with PGT-A. STUDY FUNDING/COMPETING INTEREST(S)/UNASSIGNED:No external funding was obtained for this study. D.H.M. reports personal fees, honorarium, and travel expenses from Ferring Pharmaceuticals, personal fees and travel expenses from Granata Bio, and personal fees from Biogenetics Corporation, The Sperm and Embryo Bank of New York, and ReproART: Georgian American Center for Reproductive Medicine. All conflicts are outside the submitted work.

OBJECTIVE:To assess patient decisions regarding mosaic embryos and their impact on clinical outcomes. DESIGN/METHODS:Review of patients who had genetic counseling regarding mosaic embryos. SETTING/METHODS:Academic department. PATIENT(S)/METHODS:Ninety-eight patients who had mosaic embryos but no euploid embryos. INTERVENTION(S)/METHODS:Genetic counseling to discuss mosaic-embryo transfer (MET) after preimplantation genetic testing for aneuploidy. MAIN OUTCOME MEASURE(S)/METHODS:Patient decisions regarding MET. Outcomes for patients who pursued MET were compared with those for patients who pursued additional in vitro fertilization or intrauterine insemination cycles. Decisions regarding prenatal testing after MET were assessed. RESULT(S)/RESULTS:Initially, 29.6% of patients pursued MET and 41.8% attempted a new treatment cycle. Only 6.1% of patients discarded their mosaic embryos without further treatment. Of the remaining patients, 2.0% transported their mosaic embryos to a different facility and 20.5% had not taken further action while their embryos remain stored. Patients who pursued additional cycles were more likely to have an ongoing pregnancy compared with those who pursued MET (51.2% vs. 27.6%; P<.05); however, there was no statistically significant difference in the percentage of patients who had at least one biochemical pregnancy or spontaneous abortion. Ultimately, 32.7% of patients underwent MET, and 54.5% of pregnant patients pursued amniocentesis. CONCLUSION(S)/CONCLUSIONS:MET is desired by a substantial proportion of patients who do not have euploid embryos. Patients who opt for additional treatment cycles have a greater chance of achieving an ongoing pregnancy compared with those who pursue MET; however, future studies are needed to compare the cost-effectiveness for both options.

Two of the many milestone developments in the field of assisted reproduction have been oocyte donation and preimplantation genetic testing for aneuploidy (PGT-A). Because it has been demonstrated that even young women produce a meaningful proportion of aneuploid embryos, screening out such abnormalities could potentially increase the efficacy of donor egg (DE) cycles. In this retrospective cohort study, we investigated the effect of PGT-A on DE cycle outcomes, including implantation rate (IR), spontaneous abortion rate (SABR), and ongoing pregnancy/live birth rate. We used fresh and frozen donor cycles not using PGT-A as comparison groups; all cases involved single embryo transfer. Data analysis revealed that PGT-A did not improve pregnancy outcome metrics in DE cycles, although there was a trend toward decreasing the SABR. There was a significant increase in IR with fresh cycles outperforming all frozen cycles. Overall, these results suggest that the benefits of performing PGT-A on embryos derived from young DEs may be limited and that there is an effect of the freezing process on pregnancy outcomes. These findings may provide useful insights into the science and practice of PGT-A across all of its applications.