{"paper_id":"023f389f-6848-47ef-bf32-ece62e999297","body_text":"Effect of Trophectoderm Biopsy for PGT-A on Live Birth Rate per Embryo in Good Prognosis Patients | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Effect of Trophectoderm Biopsy for PGT-A on Live Birth Rate per Embryo in Good Prognosis Patients Michael S Awadalla, Ravi Agarwal, Jacqueline R Ho, Lynda K McGinnis, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1359116/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 5 You are reading this latest preprint version Abstract Purpose: To determine if blastocyst trophectoderm biopsy for PGT-A is associated with an increased rate of live birth per embryo in good prognosis IVF patients at a single center. Methods: We performed a retrospective cohort study of good prognosis embryo transfer cycles at a single center from 1/1/2017 through 12/31/2019. We evaluated the rate of live birh per embryo with and without PGT-A for transfer of embryos in two groups of good prognosis patients: embryos from donor oocytes and embryos from autologous oocytes with maternal age less than 35 years at oocyte retrieval. 2-sided Fisher’s exact tests were used for comparisons between groups. Results: After transfer of embryos created from donor oocytes the live birth rate per euploid embryo was 70.6% (24/34) compared to 34.3% (35/102) for untested embryos for a rate difference of 36.3% (95% CI 18.4-54.1%, p < 0.01). After transfer of embros created from autologous oocytes with maternal age less than 35 years at oocyte retrieval the live birth rate per euploid embryo was 70.0% (49/70) compared to 52.5% (53/101) for untested embryos for a rate difference of 17.5% (95% CI 3.0-32.0%, p = 0.03). Conclusion: In good prognosis patients at our center the live birth rate per euploid blastocyst was higher than for untested blastocysts. in vitro fertilization trophectoderm biopsy preimplantation genetic testing euploid embryo Figures Figure 1 Figure 2 Figure 3 Introduction Theoretically PGT-A has the potential to benefit patients of all ages. Although the main benefit is to increase the live birth rate per embryo transferred, additional benefits include decreased rate of spontaneous abortion and genetically abnormal pregnancy [ 1 – 3 ]. At our center the euploidy rate ranges from 76% at a maternal age of 26 years old (at oocyte retrieval) to 24% at a maternal age of 43 years old [ 4 ]. Clearly there is more potential benefit of PGT-A at older ages. However, there is still an expected benefit of PGT-A for younger patients. So is PGT-A beneficial in good prognosis patients such as those using donor oocytes or autologous oocytes with a maternal age less than 35 years old? Current published literature shows conflicting results. Several studies have shown no benefit. A large retrospective paired cohort study of donor oocyte-recipient cycles found no difference in live birth comparing paired outcomes after PGT-A vs no PGT-A when evaluating outcomes of the first or all embryo transfers from 6 frozen donor oocytes [ 5 ]. A 2017 SART CORS database study found a reduced odds of live birth per cycle with PGT in donor-oocyte recipient cycles from 2005 to 2013 [ 6 ]. One study did not show an increased rate of ongoing pregnancy in a retrospective analysis of donor oocyte single embryo transfers with PGT-A compared to without PGT-A from 2011 to 2016 [ 7 ]. A retrospective single center study did not show any difference in live birth rate for single blastocyst transfers in women less than or equal to 37 years old when comparing transfer of PGT-A tested embryos to untested embryos [ 8 ]. On the other hand, some studies have shown increased ongoing pregnancy rates after PGT-A compared to morphological selection only. A 2012 prospective randomized study by Yang et al. in patients under 35 years old found an ongoing pregnancy rate after fresh blastocyst single embryo transfer of 69% using selection with PGT-A by aCGH compared to 42% with selection by morphology alone [ 9 ]. A recent large multicenter randomized clinical trial found no difference in ongoing pregnancy rate between selection by PGT-A or morphology overall but did find a 14% increase in ongoing pregnancy rate with PGT-A in a post hoc analysis of women aged 35–40 years old [ 10 ]. There are two main reasons we would not want to use PGT-A: misclassification of viable embryos as aneuploid and damage to the embryo from the biopsy [ 11 ]. A recent large nonelection study found 0 out of 102 single aneuploid embryos progressed to live birth [ 1 ]. This indicates that at some centers misclassification is likely very low. Embryo damage from the biopsy technique could theoretically result in loss of implantations or adverse obstetrical outcomes. Currently data seems to suggest that loss of implantations from the biopsy may be high at some centers and negligible at others. This may account for different outcomes reported from studies performed at different centers. We have found that loss of implantations from embryo biopsy likely decreases with increasing embryologist experience with embryo biopsy over the first few years of performing the technique [ 12 ]. Although there does not seem to be any clinically significant adverse obstetrical outcomes after embryo biopsy [ 13 ], one study found embryo biopsy for PGT to be associated with a small increase in preterm birth with an adjusted odds ratio of 1.20 [ 14 ]. The objective of this study was to determine if the live birth rate per embryo at our center is higher for embryos selected by PGT-A than for untested embryos in good prognosis patients. Materials And Methods Study Design and Patient Population This retrospective cohort study included 232 embryo transfers of 307 embryos from 2017 through 2019 at a single center (Fig. 1 ). We only analyzed our most recent data from 2017 and beyond because our clinic has seen increasing rates of fetal heartbeat per euploid embryo from 2015 when our clinic began performing embryo biopsy through 2017 [ 12 ]. Since this increased performance is attributed to a possible increase in proficiency of embryo biopsy, we aimed to analyze our most recent data as this represents our current state of practice. We performed two comparisons of live birth rate per embryo for embryos from donor oocytes and embryos from autologous oocytes with maternal age less than 35 years old at the time of oocyte retrieval. For each of the two comparisons the cohorts were divided by embryo biopsy for PGT-A versus no PGT-A testing (Table 1 ). In this per embryo analysis the numerator is the total number of live births and the denominator is the total numbers of embryos transferred. The average age of oocyte donors at our center is 28 years old [ 4 ]. Embryo transfers were excluded if a morula was transferred, embryo was biopsied on day 5 and transferred on day 6, PGT-A result showed low DNA, an embryo was given a D grade for trophectoderm (TE) or inner cell mass (ICM), an embryo was rebiopsied, concurrent transfer of a PGT tested and untested embryo, embryo frozen at an outside clinic, embryo thawed on day 3 and grown to the blastocyst stage, or use of a donor embryo. There were no mosaic embryo transfers. The mean maternal age was 44 years for those using donor oocytes and 32 years for those using autologous oocytes. The mean overall BMI was 24 kg/m 2 (Table 1 ). This study was approved by the University of Southern California IRB (HS-21-00206). Table 1 Baseline demographic and clinical characteristics per transfer All Donor Oocytes Autologous < 35 years No PGT-A n = 140 PGT-A n = 92 No PGT-A n = 72 PGT-A n = 31 No PGT-A n = 68 PGT-A n = 61 Maternal age at retrieval (years) 32.0 (2.6) 32.2 (2.4) Maternal age at transfer (years) 38.4 (7.6) 36.3 (6.5) 44.3 (5.8) 43.8 (5.6) 32.2 (2.7) 32.5 (2.3) BMI (kg/m 2 ) a 24.6 (4.4) 24.1 (6.3) 23.3 (2.5) 22.8 (6.9) 25.8 (5.3) 24.7 (5.9) Endometrial thickness (mm) 9.2 (1.6) 9.5 (1.8) 9.0 (1.5) 9.4 (1.9) 9.5 (1.5) 9.5 (1.7) Number of embryos transferred 1.45 1.13 1.42 1.10 1.49 1.15 Frozen oocyte 18 (13%) 2 (2%) 17 (24%) 2 (6%) 1 (1%) 0 Frozen embryo 83 (59%) 92 (100%) 35 (49%) 31 (100%) 48 (71%) 61 (100%) Gestational Carrier 9 (6%) 11 (12%) 6 (8%) 7 (23%) 3 (4%) 4 (7%) Race / ethnicity White 70 (50%) 53 (58%) 32 (44%) 22 (71%) 38 (56%) 31 (51%) Asian 29 (21%) 25 (27%) 18 (25%) 5 (16%) 11 (16%) 20 (33%) Hispanic 26 (19%) 7 (8%) 14 (19%) 3 (10%) 12 (18%) 4 (7%) African American 9 (6%) 1 (1%) 4 (6%) 1 (3%) 5 (7%) 0 Multiple 6 (4%) 5 (5%) 4 (6%) 0 2 (3%) 5 (8%) Unknown 0 1 (1%) 0 0 0 1 (2%) PGT Indication Aneuploidy screening 73 (79%) 26 (84%) 47 (77%) Advanced age 3 (3%) 2 (6%) 1 (2%) PGT-M/SR 3 (3%) 0 3 (5%) Sex determination 3 (3%) 0 3 (5%) Desired SET 8 (9%) 3 (10%) 5 (8%) Recurrent IVF Failure 1 (1%) 0 1 (2%) HLA determination 1 (1%) 0 1 (2%) Data are given as mean, mean (SD) or n (%). PGT = preimplantation genetic testing, M = monogenic/single gene defect, SR = structural rearrangements, RPL = recurrent pregnancy loss, SET = single embryo transfer, IVF = in vitro fertilization, HLA = human leukocyte antigen. a BMI available for 91% of cycles. IVF Protocols Our IVF protocols have been described previously [ 13 , 15 ]. Briefly, gonadotropin-releasing hormone (GnRH) antagonist, GnRH agonist suppression, and GnRH flare suppression stimulation protocols were used. A modified version of the Gardner and Schoolcraft blastocyst grading system[ 16 ] was used where occasionally a letter grade of D is assigned for very poor quality ICM or TE. Blastocyst biopsy and vitrification was performed once an embryo had a blastocoel greater than half of the volume of the embryo (expansion stage 2 or greater). When embryo biopsy was not performed embryos were vitrified once they reached expansion stage 1 (blastocoel less than half the volume of the embryo) or greater. Embryo culture was carried out until day 7 at which time embryos were transferred, cryopreserved, or discarded. Blastocyst biopsy was performed using a Lykos laser (Hamilton Thorne, Beverly, MA, USA) to separate the biopsy cells from the embryo. 90% of embryo biopsies were performed by the laboratory director and 10% were performed by a senior embryologist. PGT-A was performed using next generation sequencing (Progenesis, La Jolla, CA, USA). 95% of frozen embryo transfers at our center were performed in programmed cycles using 50mg of IM progesterone in ethyl oleate daily and 200mg of micronized progesterone vaginally twice a day. Blastocyst transfer was performed on day 6 of progesterone, approximately 108 hours after the start of progesterone exposure. Statistical Analysis Fisher’s exact test was used to compare rates of live birth per embryo (Stata version 16.1, StataCorp, College Station, TX, USA). This study had 80% power to detect a 17% absolute difference in live birth rate per embryo between the PGT-A and non PGT-A groups for all data combined at a 2-sided alpha level of 0.05. For embryos from donor oocytes there was 80% power to detect a 28% difference at this same significance level. For embryos from autologous oocytes there was 80% power to detect a 22% difference at this same significance level. There were no clinically significant differences in baseline demographics or clinical characteristics that were expected to have a large impact on live birth rates (Table 1 ). Embryo quality based on morphology and day of embryo blastulation was slightly worse in the PGT-A cohort for embryos from donor oocytes (Table 2 ). Worse morphology is an expected association with PGT-A since PGT-A deselects for embryo morphology. For this reason, statistical comparison without adjusting for embryo morphology was performed as this most closely corresponds to clinical decision making. Table 2 Distribution of embryo morphology and day of biopsy All n = 307 Donor Oocytes n = 136 Autologous < 35 years n = 171 No PGT-A n = 203 PGT-A n = 104 No PGT-A n = 102 PGT-A n = 34 No PGT-A n = 101 PGT-A n = 70 Day 5 Good (AA/AB/BA) 49 (24%) 22 (21%) 23 (23%) 6 (18%) 26 (26%) 16 (23%) Day 5 Fair (BB/CB/AC/CA) 96 (47%) 36 (35%) 51 (50%) 9 (26%) 45 (45%) 27 (39%) Day 5 Poor (BC/CC) 40 (20%) 15 (14%) 24 (24%) 7 (21%) 16 (16%) 8 (11%) Day 6 Good (AA/AB/BA) 0 1 (1%) 0 0 0 1 (1%) Day 6 Fair (BB/CB/AC/CA) 9 (4%) 8 (8%) 1 (1%) 6 (18%) 8 (8%) 2 (3%) Day 6 Poor (BC/CC) 9 (4%) 18 (17%) 3 (3%) 6 (18%) 6 (6%) 12 (17%) Day 7 Good (AA/AB/BA) 0 0 0 0 0 0 Day 7 Fair (BB/CB/AC/CA) 0 0 0 0 0 0 Day 7 Poor (BC/CC) 0 4 (4%) 0 0 0 4 (6%) Data are given as n (%). P < 0.01 for comparison of distributions between PGT-A and no PGT-A for all and donor oocyte comparisons. P = 0.18 for comparison of distributions for autologous embryos (Chi-square test, day 6 and day 7 embryos analyzed together as one group). Results After transfer of embryos created from donor oocytes the live birth rate per euploid embryo was 70.6% (24/34) compared to 34.3% (35/102) for untested embryos for a rate difference of 36.3% (95% CI 18.4–54.1%, p < 0.01). For untested embryos created from donor oocytes the live birth rate was 30.4% (7/23) when vitrified oocytes were used and 35.4% (28/79) when fresh oocytes were used. After transfer of embryos created from autologous oocytes with maternal age less than 35 years at oocyte retrieval the live birth rate per euploid embryo was 70.0% (49/70) compared to 52.5% (53/101) for untested embryos for a rate difference of 17.5% (95% CI 3.0–32.0%, p = 0.03). Overall analysis with data from both groups combined showed the live birth rate per euploid embryo was 70.2% (73/104) compared to 43.3% (88/203) for untested embryos for a rate difference of 26.8% (95% CI 15.7–38.0%, p < 0.01) as shown in Fig. 2 . Discussion There are multiple factors that need to be considered when analyzing euploid embryo transfer data and determining when PGT-A is clinically beneficial. One consideration is if PGT-A correctly identifies which embryos will progress to live birth. Although most PGT-A platforms have not performed clinical validation studies, clinical data from one center suggests that aneuploid embryos rarely progress to live birth [ 1 ]. Another consideration is if embryo biopsy causes a loss of implantations or live births. One group of investigators found that biopsy protocols can affect live birth rates [ 17 ]. It is likely that different biopsy protocols and embryologist experience contribute to variable rates of loss of implantations between clinics. At present, loss of implantations from embryo biopsy seems to be clinically insignificant at some centers and significant at others. This makes it challenging to interpret data from multicenter studies [ 10 ]. Centers with significant loss of implantations from embryo biopsy may be less likely to publish their data than other centers where the PGT-A data looks more favorable. If there is some loss of implantations with embryo biopsy then we would anticipate a smaller than expected increase in ongoing pregnancy for embryos that are euploid by PGT-A testing. In good prognosis patients with high euploid rates, the benefit of selecting euploid embryos may be negated by loss of implantations from the biopsy procedure. However, if there is minimal loss of implantations from the biopsy procedure, we would anticipate increased ongoing pregnancy and live birth rates from euploid embryos at all ages. Looking at our overall analysis we found a 43% live birth rate for untested embryos. With PGT-A and no loss of implantations from the biopsy procedure we would expect this live birth rate to increase proportionally to the euploidy rate. Based on age, approximately 70% of the untested embryos in this study are expected to be euploid [ 4 ]. We expect a live birth rate of 0.43/0.70 or 61% for PGT-A tested embryos. Indeed 61% falls within our 95% CI for live birth rate per embryo for PGT-A tested embryos (Fig. 2 ). Embryo mosaicism factors somewhat into the equation but since less than 2% of embryos are reported as mosaic by our testing platform this has minimal impact on calculating the expected increase in live birth rate with PGT-A [ 4 ]. Based on this data, PGT-A is a cost-effective approach for our patients. Going from a 40% to a 60% live birth rate per embryo would decrease the average number of single embryo transfers needed to achieve a live birth from 2.5 to 1.7 transfers as shown in Fig. 3 . At a cost of $ 4,000 per embryo transfer that would be a $ 3,200 savings on average per live birth. The current cost for embryo biopsy and PGT-A is approximately equal to the cost of one frozen embryo transfer cycle. Many good prognosis patients have more than 1 live birth per retrieval and they would have greater cost savings. Based on the current costs of embryo biopsy and PGT-A, the procedure seems approximately cost neutral at worst and cost effective at best for patients who have enough embryos for more than 1 live birth. Cost effectiveness studies based on data more than 5 or 10 years old or data from multiple centers may not be applicable to current practice at centers proficient in embryo biopsy and PGT-A [ 18 ]. There are some other considerations when deciding if PGT-A is a good option for a specific patient. Insurance may not cover PGT-A in younger patients due to lack of published literature supporting PGT-A use at younger ages. This may change with more clinical experience and more data being published each year. Although live birth rate per embryo is currently the main clinical consideration, euploid embryo transfer is also associated with decreased rates of spontaneous abortion and genetically abnormal pregnancy [ 1 – 3 ]. Limitations Couples at our center who purchase 6 vitrified donor oocytes for a frozen oocyte embryo transfer cycle typically transfer 1 embryo fresh without PGT-A and cryopreserve any additional embryos. On the other hand, couples using fresh donor oocytes are more likely have PGT-A testing performed since there are often excess embryos expected and this testing helps select embryos for transfer. With fresh donor oocyte cycles, typically there are 10–20 oocytes retrieved which in general is expected to result in higher quality embryos than cycles starting with only 6 frozen donor oocytes. There may be some uncorrected confounding between PGT-A and use of fresh oocytes. Despite this, transfer of embryos from donor oocytes using PGT-A actually had worse morphology than embryos from donor oocytes not using PGT-A due to the deselection of morphology that occurs with PGT-A testing and culture of embryos to expansion stage 2 before embryo biopsy (Table 2 ). Regardless, prospective studies are needed from centers proficient in embryo biopsy and PGT-A to verify our retrospective data. In this analysis we included use of embryos from fresh and frozen oocytes, fresh and frozen embryo transfer, transfers to gestational carriers, and single and double embryo transfers. Inclusion of these diverse types of transfers makes the data broadly applicable. However, this analysis is less controlled than ideal. Limiting the analysis to single frozen embryo transfers of embryos created from fresh oocytes would add more control but based on our dataset the numbers would have been too small to have sufficient statistical power. In the analysis in Fig. 2 the numerator is the total number of live births and the denominator is the total numbers of embryos transferred. We are essentially assuming that each embryo in a double embryo transfer implants independently of the other. This assumption is reasonable since most major endometrial factors are detected with modern ultrasound monitoring and uterine cavity imaging. We routinely performed saline infusion sonograms on all patients prior to embryo transfer. At least one study supports this conventional thinking that embryos implant independently of other embryos transferred concurrently [ 19 ]. Conclusion PGT-A of embryos from good prognosis patients likely increases the live birth rate per embryo transferred if loss of embryo implantations from the biopsy is low. This data supports the use of PGT-A in good prognosis patients at centers with data to support proficiency in this technique. Declarations Acknowledgements: None. Author Contributions MS Awadalla: protocol/project development, data collection, data analysis, manuscript writing/editing. R Agarwal: protocol/project development, data collection, manuscript writing/editing. JR Ho: manuscript writing/editing. LK McGinnis: manuscript writing/editing. A Ahmady: manuscript writing/editing. Funding The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. Competing Interests The authors have no relevant financial or non-financial interests to disclose. Ethics approval This study was approved by the University of Southern California IRB (HS-21-00206). Consent to participate Not applicable. Consent for publication Not applicable. References Tiegs AW, Tao X, Zhan Y et al (2021) A multicenter, prospective, blinded, nonselection study evaluating the predictive value of an aneuploid diagnosis using a targeted next-generation sequencing-based preimplantation genetic testing for aneuploidy assay and impact of biopsy. Fertil Steril 115:627–637. https://doi.org/10.1016/j.fertnstert.2020.07.052 Murugappan G, Ohno MS, Lathi RB (2015) Cost-effectiveness analysis of preimplantation genetic screening and in vitro fertilization versus expectant management in patients with unexplained recurrent pregnancy loss. Fertil Steril 103:1215–1220. https://doi.org/10.1016/j.fertnstert.2015.02.012 Sacchi L, Albani E, Cesana A et al (2019) Preimplantation Genetic Testing for Aneuploidy Improves Clinical, Gestational, and Neonatal Outcomes in Advanced Maternal Age Patients Without Compromising Cumulative Live-Birth Rate. J Assist Reprod Genet 36:2493–2504. https://doi.org/10.1007/S10815-019-01609-4 McDaniel KE, Awadalla MS, McGinnis LK, Ahmady A (2020) Transfer the Best and Biopsy the Rest? Blastocyst Euploidy Rates Vary Based on Morphology and Day of Biopsy. Arch Gynecol Obs 303:249–258. https://doi.org/10.1016/j.fertnstert.2020.02.061 Doyle N, Gainty M, Eubanks A et al (2020) Donor oocyte recipients do not benefit from preimplantation genetic testing for aneuploidy to improve pregnancy outcomes. Hum Reprod 35:2548–2555. https://doi.org/10.1093/humrep/deaa219 Barad DH, Darmon SK, Kushnir VA et al (2017) Impact of preimplantation genetic screening on donor oocyte-recipient cycles in the United States. Am J Obstet 217:576. https://doi.org/10.1016/j.ajog.2017.07.023 Masbou AK, Friedenthal JB, McCulloh DH et al (2019) A Comparison of Pregnancy Outcomes in Patients Undergoing Donor Egg Single Embryo Transfers With and Without Preimplantation Genetic Testing. Reprod Sci 26:1661–1665. https://doi.org/10.1177/1933719118820474 Kang H-JJ, Melnick AP, Stewart JD et al (2016) Preimplantation genetic screening: who benefits? Fertil Steril 106:597–602. https://doi.org/10.1016/j.fertnstert.2016.04.027 Yang Z, Liu J, Collins GS et al (2012) Selection of single blastocysts for fresh transfer via standard morphology assessment alone and with array CGH for good prognosis IVF patients: results from a randomized pilot study. Mol Cytogenet 5:24. https://doi.org/10.1186/1755-8166-5-24 Munné S, Kaplan B, Frattarelli JL et al (2019) Preimplantation genetic testing for aneuploidy versus morphology as selection criteria for single frozen-thawed embryo transfer in good-prognosis patients: a multicenter randomized clinical trial. Fertil Steril 112:1071–1079. https://doi.org/10.1016/j.fertnstert.2019.07.1346 Paulson RJ (2017) Preimplantation genetic screening: what is the clinical efficiency? Fertil Steril 108:228–230. https://doi.org/10.1016/j.fertnstert.2017.06.023 Awadalla MS, Ingles SA, Ahmady A (2021) Design and validation of a model for quality control monitoring of dichotomous in vitro fertilization outcomes. Fertil Steril 116:453–461. https://doi.org/10.1016/j.fertnstert.2021.02.002 Awadalla MS, Park KE, Latack KR et al (2021) Influence of Trophectoderm Biopsy Prior to Frozen Blastocyst Transfer on Obstetrical Outcomes. Reprod Sci 28:3459–3465. https://doi.org/10.1007/S43032-021-00552-Z Li M, Kort J, Baker VL (2021) Embryo biopsy and perinatal outcomes of singleton pregnancies: an analysis of 16,246 frozen embryo transfer cycles reported in the Society for Assisted Reproductive Technology Clinical Outcomes Reporting System. Am J Obstet Gynecol 224:500. e1-500.e18. https://doi.org/10.1016/J.AJOG.2020.10.043 Awadalla MS, Vestal NL, McGinnis LK et al (2021) Effect of age and morphology on sustained implantation rate after euploid blastocyst transfer. Reprod Biomed Online 43:395–403. https://doi.org/10.1016/j.rbmo.2021.06.008 Gardner DK, Schoolcraft WB (1999) In vitro culture of human blastocysts. In: Jansen R, Mortimer D, eds. Towards Reproductive Certainty: Fertility and Genetics beyond. 378–388 Rubino P, Tapia L, Ruiz de Assin Alonso R et al (2020) Trophectoderm biopsy protocols can affect clinical outcomes: time to focus on the blastocyst biopsy technique. Fertil Steril 113:981–989. https://doi.org/10.1016/j.fertnstert.2019.12.034 Facadio Antero M, Singh B, Pradhan A et al (2021) Cost-effectiveness of preimplantation genetic testing for aneuploidy for fresh donor oocyte cycles. F&S Rep 2:36–42. https://doi.org/10.1016/J.XFRE.2020.11.005 Hill MJ, Eubanks AE, Csokmay JM et al (2020) Is transferring a lower-quality embryo with a good-quality blastocyst detrimental to the likelihood of live birth? Fertil Steril 114:338–345. https://doi.org/10.1016/j.fertnstert.2020.03.027 Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 04 Mar, 2022 Reviewers invited by journal 04 Mar, 2022 Editor invited by journal 28 Feb, 2022 Editor assigned by journal 14 Feb, 2022 First submitted to journal 14 Feb, 2022 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {\"props\":{\"pageProps\":{\"initialData\":{\"identity\":\"rs-1359116\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":false,\"archivedVersions\":[],\"articleType\":\"Research Article\",\"associatedPublications\":[],\"authors\":[{\"id\":88236562,\"identity\":\"c270a210-c99f-46e1-9806-007feca0a085\",\"order_by\":0,\"name\":\"Michael S Awadalla\",\"email\":\"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABCklEQVRIiWNgGAWjYNACNgYZPgbmAwcYG+SAPMbGAwlEaOFhY2BLAGoxBnIYGw4kENQD1sJjwADRwsBwgAGPFt3+w88kfpTZ8bCxn/l4uHKHgZz5/OaGAw9/HGbgb+/GqtHsRpqZZM+5ZB42ntwNB8+eMTCWOQZ22GEGiTNnN2DXAkS8bcxAhwG1NLb9SZzBBtViIJGLXcv5499u/m2r52Hjf/MAqMWgnrCWAzlmt3nbDvOwSeQwgLQkSBDUciOn/LfMueNALc8MQFoMZ7AlArWkpfPg9Mv545sN35RVy/HzJz/+CNQiL8F8/OHDHzbWcvztvVi14ATNPCQpB4E6knWMglEwCkbBsAUA/T9pa+qHxBsAAAAASUVORK5CYII=\",\"orcid\":\"https://orcid.org/0000-0001-8910-7434\",\"institution\":\"University of Southern California\",\"correspondingAuthor\":true,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Michael\",\"middleName\":\"S\",\"lastName\":\"Awadalla\",\"suffix\":\"\"},{\"id\":88236563,\"identity\":\"623ba710-cb19-4c93-9293-8dd25e3b9795\",\"order_by\":1,\"name\":\"Ravi Agarwal\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Ravi\",\"middleName\":\"\",\"lastName\":\"Agarwal\",\"suffix\":\"\"},{\"id\":88236564,\"identity\":\"fcfde0d0-48ac-49dd-9f71-9dd0f0570b2a\",\"order_by\":2,\"name\":\"Jacqueline R Ho\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Jacqueline\",\"middleName\":\"R\",\"lastName\":\"Ho\",\"suffix\":\"\"},{\"id\":88236565,\"identity\":\"c153556a-5b78-478e-a02e-26e5bc146cb8\",\"order_by\":3,\"name\":\"Lynda K McGinnis\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Lynda\",\"middleName\":\"K\",\"lastName\":\"McGinnis\",\"suffix\":\"\"},{\"id\":88236566,\"identity\":\"e3e64840-6aa4-4c11-83cb-286340d38b6a\",\"order_by\":4,\"name\":\"Ali Ahmady\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Ali\",\"middleName\":\"\",\"lastName\":\"Ahmady\",\"suffix\":\"\"}],\"badges\":[],\"createdAt\":\"2022-02-14 16:46:51\",\"currentVersionCode\":1,\"declarations\":\"\",\"doi\":\"10.21203/rs.3.rs-1359116/v1\",\"doiUrl\":\"https://doi.org/10.21203/rs.3.rs-1359116/v1\",\"draftVersion\":[],\"editorialEvents\":[],\"editorialNote\":\"\",\"failedWorkflow\":false,\"files\":[{\"id\":18937394,\"identity\":\"abeff530-94c1-44a2-a501-231fbc1909f4\",\"added_by\":\"auto\",\"created_at\":\"2022-03-07 16:40:37\",\"extension\":\"png\",\"order_by\":1,\"title\":\"Figure 1\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":505461,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eFlow diagram with inclusion and exclusion criteria\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"OnlineFig1.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-1359116/v1/3a53f1c79ad9094d02a4eeff.png\"},{\"id\":18937395,\"identity\":\"3783e3b2-3807-49ba-bf02-d36907db319a\",\"added_by\":\"auto\",\"created_at\":\"2022-03-07 16:40:37\",\"extension\":\"png\",\"order_by\":2,\"title\":\"Figure 2\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":443435,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eLive birth rate per embryo with 95% CIs\\u003c/p\\u003e\\u003cp\\u003eP \\u0026lt; 0.01 for comparison of live birth rate per embryo for embryos from donor oocytes. P = 0.03 for embryos from autologous oocytes. P \\u0026lt; 0.01 for overall analysis with data from both groups combined.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"OnlineFig2.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-1359116/v1/9b829603030c800bbb68972f.png\"},{\"id\":18937962,\"identity\":\"6c370d2b-1ea6-4999-b012-ffac7616c9ce\",\"added_by\":\"auto\",\"created_at\":\"2022-03-07 16:43:37\",\"extension\":\"png\",\"order_by\":3,\"title\":\"Figure 3\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":460473,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eAverage number of single embryo transfers needed to achieve one live birth based on live birth rate per embryo\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"OnlineFig3.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-1359116/v1/f3fe93ee54a69b1847431396.png\"},{\"id\":18937963,\"identity\":\"edde64e4-ebb3-472b-b84d-9e0556c4ecf4\",\"added_by\":\"auto\",\"created_at\":\"2022-03-07 16:43:40\",\"extension\":\"pdf\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":273017,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"manuscript.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-1359116/v1/3ac827ea-5c06-4746-8dca-baf70c85a8d8.pdf\"}],\"financialInterests\":\"\",\"formattedTitle\":\"Effect of Trophectoderm Biopsy for PGT-A on Live Birth Rate per Embryo in Good Prognosis Patients\",\"fulltext\":[{\"header\":\"Introduction\",\"content\":\"\\u003cp\\u003eTheoretically PGT-A has the potential to benefit patients of all ages. Although the main benefit is to increase the live birth rate per embryo transferred, additional benefits include decreased rate of spontaneous abortion and genetically abnormal pregnancy [\\u003cspan additionalcitationids=\\\"CR2\\\" citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e]. At our center the euploidy rate ranges from 76% at a maternal age of 26 years old (at oocyte retrieval) to 24% at a maternal age of 43 years old [\\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e]. Clearly there is more potential benefit of PGT-A at older ages. However, there is still an expected benefit of PGT-A for younger patients. So is PGT-A beneficial in good prognosis patients such as those using donor oocytes or autologous oocytes with a maternal age less than 35 years old? Current published literature shows conflicting results.\\u003c/p\\u003e \\u003cp\\u003eSeveral studies have shown no benefit. A large retrospective paired cohort study of donor oocyte-recipient cycles found no difference in live birth comparing paired outcomes after PGT-A vs no PGT-A when evaluating outcomes of the first or all embryo transfers from 6 frozen donor oocytes [\\u003cspan citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e]. A 2017 SART CORS database study found a reduced odds of live birth per cycle with PGT in donor-oocyte recipient cycles from 2005 to 2013 [\\u003cspan citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e]. One study did not show an increased rate of ongoing pregnancy in a retrospective analysis of donor oocyte single embryo transfers with PGT-A compared to without PGT-A from 2011 to 2016 [\\u003cspan citationid=\\\"CR7\\\" class=\\\"CitationRef\\\"\\u003e7\\u003c/span\\u003e]. A retrospective single center study did not show any difference in live birth rate for single blastocyst transfers in women less than or equal to 37 years old when comparing transfer of PGT-A tested embryos to untested embryos [\\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e].\\u003c/p\\u003e \\u003cp\\u003eOn the other hand, some studies have shown increased ongoing pregnancy rates after PGT-A compared to morphological selection only. A 2012 prospective randomized study by Yang et al. in patients under 35 years old found an ongoing pregnancy rate after fresh blastocyst single embryo transfer of 69% using selection with PGT-A by aCGH compared to 42% with selection by morphology alone [\\u003cspan citationid=\\\"CR9\\\" class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e]. A recent large multicenter randomized clinical trial found no difference in ongoing pregnancy rate between selection by PGT-A or morphology overall but did find a 14% increase in ongoing pregnancy rate with PGT-A in a post hoc analysis of women aged 35\\u0026ndash;40 years old [\\u003cspan citationid=\\\"CR10\\\" class=\\\"CitationRef\\\"\\u003e10\\u003c/span\\u003e].\\u003c/p\\u003e \\u003cp\\u003eThere are two main reasons we would not want to use PGT-A: misclassification of viable embryos as aneuploid and damage to the embryo from the biopsy [\\u003cspan citationid=\\\"CR11\\\" class=\\\"CitationRef\\\"\\u003e11\\u003c/span\\u003e]. A recent large nonelection study found 0 out of 102 single aneuploid embryos progressed to live birth [\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e]. This indicates that at some centers misclassification is likely very low. Embryo damage from the biopsy technique could theoretically result in loss of implantations or adverse obstetrical outcomes. Currently data seems to suggest that loss of implantations from the biopsy may be high at some centers and negligible at others. This may account for different outcomes reported from studies performed at different centers. We have found that loss of implantations from embryo biopsy likely decreases with increasing embryologist experience with embryo biopsy over the first few years of performing the technique [\\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e]. Although there does not seem to be any clinically significant adverse obstetrical outcomes after embryo biopsy [\\u003cspan citationid=\\\"CR13\\\" class=\\\"CitationRef\\\"\\u003e13\\u003c/span\\u003e], one study found embryo biopsy for PGT to be associated with a small increase in preterm birth with an adjusted odds ratio of 1.20 [\\u003cspan citationid=\\\"CR14\\\" class=\\\"CitationRef\\\"\\u003e14\\u003c/span\\u003e].\\u003c/p\\u003e \\u003cp\\u003eThe objective of this study was to determine if the live birth rate per embryo at our center is higher for embryos selected by PGT-A than for untested embryos in good prognosis patients.\\u003c/p\\u003e\"},{\"header\":\"Materials And Methods\",\"content\":\"\\u003cdiv id=\\\"Sec3\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eStudy Design and Patient Population\\u003c/h2\\u003e \\u003cp\\u003eThis retrospective cohort study included 232 embryo transfers of 307 embryos from 2017 through 2019 at a single center (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e). We only analyzed our most recent data from 2017 and beyond because our clinic has seen increasing rates of fetal heartbeat per euploid embryo from 2015 when our clinic began performing embryo biopsy through 2017 [\\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e]. Since this increased performance is attributed to a possible increase in proficiency of embryo biopsy, we aimed to analyze our most recent data as this represents our current state of practice.\\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e \\u003cp\\u003eWe performed two comparisons of live birth rate per embryo for embryos from donor oocytes and embryos from autologous oocytes with maternal age less than 35 years old at the time of oocyte retrieval. For each of the two comparisons the cohorts were divided by embryo biopsy for PGT-A versus no PGT-A testing (Table\\u0026nbsp;\\u003cspan refid=\\\"Tab1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e). In this per embryo analysis the numerator is the total number of live births and the denominator is the total numbers of embryos transferred. The average age of oocyte donors at our center is 28 years old [\\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e]. Embryo transfers were excluded if a morula was transferred, embryo was biopsied on day 5 and transferred on day 6, PGT-A result showed low DNA, an embryo was given a D grade for trophectoderm (TE) or inner cell mass (ICM), an embryo was rebiopsied, concurrent transfer of a PGT tested and untested embryo, embryo frozen at an outside clinic, embryo thawed on day 3 and grown to the blastocyst stage, or use of a donor embryo. There were no mosaic embryo transfers. The mean maternal age was 44 years for those using donor oocytes and 32 years for those using autologous oocytes. The mean overall BMI was 24 kg/m\\u003csup\\u003e2\\u003c/sup\\u003e (Table\\u0026nbsp;\\u003cspan refid=\\\"Tab1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e). This study was approved by the University of Southern California IRB (HS-21-00206).\\u003c/p\\u003e \\u003cp\\u003e \\u003cdiv class=\\\"gridtable\\\"\\u003e\\u003ctable float=\\\"Yes\\\" id=\\\"Tab1\\\" border=\\\"1\\\"\\u003e \\u003ccaption language=\\\"En\\\"\\u003e \\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 1\\u003c/div\\u003e \\u003cdiv class=\\\"CaptionContent\\\"\\u003e \\u003cp\\u003eBaseline demographic and clinical characteristics per transfer\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/caption\\u003e \\u003ccolgroup cols=\\\"7\\\"\\u003e \\u003cthead\\u003e \\u003ctr\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e \\u003cth align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c3\\\" namest=\\\"c2\\\"\\u003e \\u003cp\\u003eAll\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c5\\\" namest=\\\"c4\\\"\\u003e \\u003cp\\u003eDonor Oocytes\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c7\\\" namest=\\\"c6\\\"\\u003e \\u003cp\\u003eAutologous\\u0026thinsp;\\u0026lt;\\u0026thinsp;35 years\\u003c/p\\u003e \\u003c/th\\u003e \\u003c/tr\\u003e \\u003c/thead\\u003e \\u003ctbody\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eNo PGT-A\\u003c/p\\u003e \\u003cp\\u003en\\u0026thinsp;=\\u0026thinsp;140\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003ePGT-A\\u003c/p\\u003e \\u003cp\\u003en\\u0026thinsp;=\\u0026thinsp;92\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003eNo PGT-A\\u003c/p\\u003e \\u003cp\\u003en\\u0026thinsp;=\\u0026thinsp;72\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003ePGT-A\\u003c/p\\u003e \\u003cp\\u003en\\u0026thinsp;=\\u0026thinsp;31\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003eNo PGT-A\\u003c/p\\u003e \\u003cp\\u003en\\u0026thinsp;=\\u0026thinsp;68\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003ePGT-A\\u003c/p\\u003e \\u003cp\\u003en\\u0026thinsp;=\\u0026thinsp;61\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eMaternal age at retrieval (years)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e32.0 (2.6)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e32.2 (2.4)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eMaternal age at transfer (years)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e38.4 (7.6)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e36.3 (6.5)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e44.3 (5.8)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e43.8 (5.6)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e32.2 (2.7)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e32.5 (2.3)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eBMI (kg/m\\u003csup\\u003e2\\u003c/sup\\u003e)\\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e24.6 (4.4)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e24.1 (6.3)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e23.3 (2.5)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e22.8 (6.9)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e25.8 (5.3)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e24.7 (5.9)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eEndometrial thickness (mm)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e9.2 (1.6)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e9.5 (1.8)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e9.0 (1.5)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e9.4 (1.9)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e9.5 (1.5)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e9.5 (1.7)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eNumber of embryos transferred\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e1.45\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e1.13\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e1.42\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e1.10\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e1.49\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e1.15\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eFrozen oocyte\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e18 (13%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e2 (2%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e17 (24%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e2 (6%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e1 (1%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e0\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eFrozen embryo\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e83 (59%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e92 (100%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e35 (49%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e31 (100%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e48 (71%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e61 (100%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eGestational Carrier\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e9 (6%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e11 (12%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e6 (8%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e7 (23%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e3 (4%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e4 (7%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colspan=\\\"7\\\" nameend=\\\"c7\\\" namest=\\\"c1\\\"\\u003e \\u003cp\\u003eRace / ethnicity\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eWhite\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e70 (50%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e53 (58%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e32 (44%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e22 (71%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e38 (56%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e31 (51%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eAsian\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e29 (21%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e25 (27%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e18 (25%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e5 (16%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e11 (16%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e20 (33%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eHispanic\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e26 (19%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e7 (8%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e14 (19%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e3 (10%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e12 (18%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e4 (7%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eAfrican American\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e9 (6%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e1 (1%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e4 (6%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e1 (3%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e5 (7%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e0\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eMultiple\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e6 (4%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e5 (5%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e4 (6%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e2 (3%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e5 (8%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eUnknown\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e0\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e1 (1%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e0\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e1 (2%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colspan=\\\"7\\\" nameend=\\\"c7\\\" namest=\\\"c1\\\"\\u003e \\u003cp\\u003ePGT Indication\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eAneuploidy screening\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e73 (79%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e26 (84%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e47 (77%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eAdvanced age\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e3 (3%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e2 (6%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e1 (2%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003ePGT-M/SR\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e3 (3%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e3 (5%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eSex determination\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e3 (3%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e3 (5%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eDesired SET\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e8 (9%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e3 (10%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e5 (8%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eRecurrent IVF Failure\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e1 (1%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e1 (2%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eHLA determination\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e1 (1%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e1 (2%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003c/tbody\\u003e \\u003c/colgroup\\u003e \\u003ctfoot\\u003e \\u003ctr\\u003e\\u003ctd colspan=\\\"7\\\"\\u003eData are given as mean, mean (SD) or n (%). PGT\\u0026thinsp;=\\u0026thinsp;preimplantation genetic testing, M\\u0026thinsp;=\\u0026thinsp;monogenic/single gene defect, SR\\u0026thinsp;=\\u0026thinsp;structural rearrangements, RPL\\u0026thinsp;=\\u0026thinsp;recurrent pregnancy loss, SET\\u0026thinsp;=\\u0026thinsp;single embryo transfer, IVF\\u0026thinsp;=\\u0026thinsp;in vitro fertilization, HLA\\u0026thinsp;=\\u0026thinsp;human leukocyte antigen. \\u003csup\\u003ea\\u003c/sup\\u003eBMI available for 91% of cycles.\\u003c/td\\u003e\\u003c/tr\\u003e \\u003c/tfoot\\u003e \\u003c/table\\u003e\\u003c/div\\u003e \\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec4\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eIVF Protocols\\u003c/h2\\u003e \\u003cp\\u003eOur IVF protocols have been described previously [\\u003cspan citationid=\\\"CR13\\\" class=\\\"CitationRef\\\"\\u003e13\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR15\\\" class=\\\"CitationRef\\\"\\u003e15\\u003c/span\\u003e]. Briefly, gonadotropin-releasing hormone (GnRH) antagonist, GnRH agonist suppression, and GnRH flare suppression stimulation protocols were used. A modified version of the Gardner and Schoolcraft blastocyst grading system[\\u003cspan citationid=\\\"CR16\\\" class=\\\"CitationRef\\\"\\u003e16\\u003c/span\\u003e] was used where occasionally a letter grade of D is assigned for very poor quality ICM or TE. Blastocyst biopsy and vitrification was performed once an embryo had a blastocoel greater than half of the volume of the embryo (expansion stage 2 or greater). When embryo biopsy was not performed embryos were vitrified once they reached expansion stage 1 (blastocoel less than half the volume of the embryo) or greater. Embryo culture was carried out until day 7 at which time embryos were transferred, cryopreserved, or discarded.\\u003c/p\\u003e \\u003cp\\u003eBlastocyst biopsy was performed using a Lykos laser (Hamilton Thorne, Beverly, MA, USA) to separate the biopsy cells from the embryo. 90% of embryo biopsies were performed by the laboratory director and 10% were performed by a senior embryologist. PGT-A was performed using next generation sequencing (Progenesis, La Jolla, CA, USA). 95% of frozen embryo transfers at our center were performed in programmed cycles using 50mg of IM progesterone in ethyl oleate daily and 200mg of micronized progesterone vaginally twice a day. Blastocyst transfer was performed on day 6 of progesterone, approximately 108 hours after the start of progesterone exposure.\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec5\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eStatistical Analysis\\u003c/h2\\u003e \\u003cp\\u003eFisher\\u0026rsquo;s exact test was used to compare rates of live birth per embryo (Stata version 16.1, StataCorp, College Station, TX, USA). This study had 80% power to detect a 17% absolute difference in live birth rate per embryo between the PGT-A and non PGT-A groups for all data combined at a 2-sided alpha level of 0.05. For embryos from donor oocytes there was 80% power to detect a 28% difference at this same significance level. For embryos from autologous oocytes there was 80% power to detect a 22% difference at this same significance level. There were no clinically significant differences in baseline demographics or clinical characteristics that were expected to have a large impact on live birth rates (Table\\u0026nbsp;\\u003cspan refid=\\\"Tab1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e). Embryo quality based on morphology and day of embryo blastulation was slightly worse in the PGT-A cohort for embryos from donor oocytes (Table\\u0026nbsp;\\u003cspan refid=\\\"Tab2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e). Worse morphology is an expected association with PGT-A since PGT-A deselects for embryo morphology. For this reason, statistical comparison without adjusting for embryo morphology was performed as this most closely corresponds to clinical decision making.\\u003c/p\\u003e \\u003cp\\u003e \\u003cdiv class=\\\"gridtable\\\"\\u003e\\u003ctable float=\\\"Yes\\\" id=\\\"Tab2\\\" border=\\\"1\\\"\\u003e \\u003ccaption language=\\\"En\\\"\\u003e \\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 2\\u003c/div\\u003e \\u003cdiv class=\\\"CaptionContent\\\"\\u003e \\u003cp\\u003eDistribution of embryo morphology and day of biopsy\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/caption\\u003e \\u003ccolgroup cols=\\\"7\\\"\\u003e \\u003cthead\\u003e \\u003ctr\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e \\u003cth align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c3\\\" namest=\\\"c2\\\"\\u003e \\u003cp\\u003eAll\\u003c/p\\u003e \\u003cp\\u003en\\u0026thinsp;=\\u0026thinsp;307\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c5\\\" namest=\\\"c4\\\"\\u003e \\u003cp\\u003eDonor Oocytes\\u003c/p\\u003e \\u003cp\\u003en\\u0026thinsp;=\\u0026thinsp;136\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c7\\\" namest=\\\"c6\\\"\\u003e \\u003cp\\u003eAutologous\\u0026thinsp;\\u0026lt;\\u0026thinsp;35 years\\u003c/p\\u003e \\u003cp\\u003en\\u0026thinsp;=\\u0026thinsp;171\\u003c/p\\u003e \\u003c/th\\u003e \\u003c/tr\\u003e \\u003c/thead\\u003e \\u003ctbody\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eNo PGT-A\\u003c/p\\u003e \\u003cp\\u003en\\u0026thinsp;=\\u0026thinsp;203\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003ePGT-A\\u003c/p\\u003e \\u003cp\\u003en\\u0026thinsp;=\\u0026thinsp;104\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003eNo PGT-A\\u003c/p\\u003e \\u003cp\\u003en\\u0026thinsp;=\\u0026thinsp;102\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003ePGT-A\\u003c/p\\u003e \\u003cp\\u003en\\u0026thinsp;=\\u0026thinsp;34\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003eNo PGT-A\\u003c/p\\u003e \\u003cp\\u003en\\u0026thinsp;=\\u0026thinsp;101\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003ePGT-A\\u003c/p\\u003e \\u003cp\\u003en\\u0026thinsp;=\\u0026thinsp;70\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eDay 5 Good (AA/AB/BA)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e49 (24%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e22 (21%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e23 (23%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e6 (18%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e26 (26%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e16 (23%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eDay 5 Fair (BB/CB/AC/CA)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e96 (47%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e36 (35%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e51 (50%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e9 (26%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e45 (45%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e27 (39%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eDay 5 Poor (BC/CC)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e40 (20%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e15 (14%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e24 (24%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e7 (21%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e16 (16%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e8 (11%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eDay 6 Good (AA/AB/BA)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e0\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e1 (1%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e0\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e1 (1%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eDay 6 Fair (BB/CB/AC/CA)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e9 (4%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e8 (8%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e1 (1%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e6 (18%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e8 (8%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e2 (3%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eDay 6 Poor (BC/CC)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e9 (4%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e18 (17%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e3 (3%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e6 (18%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e6 (6%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e12 (17%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eDay 7 Good (AA/AB/BA)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e0\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e0\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e0\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e0\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eDay 7 Fair (BB/CB/AC/CA)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e0\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e0\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e0\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e0\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eDay 7 Poor (BC/CC)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e0\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e4 (4%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e \\u003cp\\u003e0\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e \\u003cp\\u003e4 (6%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003c/tbody\\u003e \\u003c/colgroup\\u003e \\u003ctfoot\\u003e \\u003ctr\\u003e\\u003ctd colspan=\\\"7\\\"\\u003eData are given as n (%). P\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.01 for comparison of distributions between PGT-A and no PGT-A for all and donor oocyte comparisons. P\\u0026thinsp;=\\u0026thinsp;0.18 for comparison of distributions for autologous embryos (Chi-square test, day 6 and day 7 embryos analyzed together as one group).\\u003c/td\\u003e\\u003c/tr\\u003e \\u003c/tfoot\\u003e \\u003c/table\\u003e\\u003c/div\\u003e \\u003c/p\\u003e \\u003c/div\\u003e\"},{\"header\":\"Results\",\"content\":\"\\u003cp\\u003eAfter transfer of embryos created from donor oocytes the live birth rate per euploid embryo was 70.6% (24/34) compared to 34.3% (35/102) for untested embryos for a rate difference of 36.3% (95% CI 18.4\\u0026ndash;54.1%, p\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.01). For untested embryos created from donor oocytes the live birth rate was 30.4% (7/23) when vitrified oocytes were used and 35.4% (28/79) when fresh oocytes were used.\\u003c/p\\u003e \\u003cp\\u003eAfter transfer of embryos created from autologous oocytes with maternal age less than 35 years at oocyte retrieval the live birth rate per euploid embryo was 70.0% (49/70) compared to 52.5% (53/101) for untested embryos for a rate difference of 17.5% (95% CI 3.0\\u0026ndash;32.0%, p\\u0026thinsp;=\\u0026thinsp;0.03).\\u003c/p\\u003e \\u003cp\\u003eOverall analysis with data from both groups combined showed the live birth rate per euploid embryo was 70.2% (73/104) compared to 43.3% (88/203) for untested embryos for a rate difference of 26.8% (95% CI 15.7\\u0026ndash;38.0%, p\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.01) as shown in Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e.\\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e\"},{\"header\":\"Discussion\",\"content\":\"\\u003cp\\u003eThere are multiple factors that need to be considered when analyzing euploid embryo transfer data and determining when PGT-A is clinically beneficial. One consideration is if PGT-A correctly identifies which embryos will progress to live birth. Although most PGT-A platforms have not performed clinical validation studies, clinical data from one center suggests that aneuploid embryos rarely progress to live birth [\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e]. Another consideration is if embryo biopsy causes a loss of implantations or live births. One group of investigators found that biopsy protocols can affect live birth rates [\\u003cspan citationid=\\\"CR17\\\" class=\\\"CitationRef\\\"\\u003e17\\u003c/span\\u003e]. It is likely that different biopsy protocols and embryologist experience contribute to variable rates of loss of implantations between clinics. At present, loss of implantations from embryo biopsy seems to be clinically insignificant at some centers and significant at others. This makes it challenging to interpret data from multicenter studies [\\u003cspan citationid=\\\"CR10\\\" class=\\\"CitationRef\\\"\\u003e10\\u003c/span\\u003e]. Centers with significant loss of implantations from embryo biopsy may be less likely to publish their data than other centers where the PGT-A data looks more favorable.\\u003c/p\\u003e \\u003cp\\u003eIf there is some loss of implantations with embryo biopsy then we would anticipate a smaller than expected increase in ongoing pregnancy for embryos that are euploid by PGT-A testing. In good prognosis patients with high euploid rates, the benefit of selecting euploid embryos may be negated by loss of implantations from the biopsy procedure. However, if there is minimal loss of implantations from the biopsy procedure, we would anticipate increased ongoing pregnancy and live birth rates from euploid embryos at all ages. Looking at our overall analysis we found a 43% live birth rate for untested embryos. With PGT-A and no loss of implantations from the biopsy procedure we would expect this live birth rate to increase proportionally to the euploidy rate. Based on age, approximately 70% of the untested embryos in this study are expected to be euploid [\\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e]. We expect a live birth rate of 0.43/0.70 or 61% for PGT-A tested embryos. Indeed 61% falls within our 95% CI for live birth rate per embryo for PGT-A tested embryos (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e). Embryo mosaicism factors somewhat into the equation but since less than 2% of embryos are reported as mosaic by our testing platform this has minimal impact on calculating the expected increase in live birth rate with PGT-A [\\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e].\\u003c/p\\u003e \\u003cp\\u003eBased on this data, PGT-A is a cost-effective approach for our patients. Going from a 40% to a 60% live birth rate per embryo would decrease the average number of single embryo transfers needed to achieve a live birth from 2.5 to 1.7 transfers as shown in Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig3\\\" class=\\\"InternalRef\\\"\\u003e3\\u003c/span\\u003e. At a cost of \\u003cspan\\u003e$\\u003c/span\\u003e4,000 per embryo transfer that would be a \\u003cspan\\u003e$\\u003c/span\\u003e3,200 savings on average per live birth. The current cost for embryo biopsy and PGT-A is approximately equal to the cost of one frozen embryo transfer cycle. Many good prognosis patients have more than 1 live birth per retrieval and they would have greater cost savings. Based on the current costs of embryo biopsy and PGT-A, the procedure seems approximately cost neutral at worst and cost effective at best for patients who have enough embryos for more than 1 live birth. Cost effectiveness studies based on data more than 5 or 10 years old or data from multiple centers may not be applicable to current practice at centers proficient in embryo biopsy and PGT-A [\\u003cspan citationid=\\\"CR18\\\" class=\\\"CitationRef\\\"\\u003e18\\u003c/span\\u003e].\\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e \\u003cp\\u003eThere are some other considerations when deciding if PGT-A is a good option for a specific patient. Insurance may not cover PGT-A in younger patients due to lack of published literature supporting PGT-A use at younger ages. This may change with more clinical experience and more data being published each year. Although live birth rate per embryo is currently the main clinical consideration, euploid embryo transfer is also associated with decreased rates of spontaneous abortion and genetically abnormal pregnancy [\\u003cspan additionalcitationids=\\\"CR2\\\" citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e].\\u003c/p\\u003e \\u003cdiv id=\\\"Sec8\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eLimitations\\u003c/h2\\u003e \\u003cp\\u003eCouples at our center who purchase 6 vitrified donor oocytes for a frozen oocyte embryo transfer cycle typically transfer 1 embryo fresh without PGT-A and cryopreserve any additional embryos. On the other hand, couples using fresh donor oocytes are more likely have PGT-A testing performed since there are often excess embryos expected and this testing helps select embryos for transfer. With fresh donor oocyte cycles, typically there are 10\\u0026ndash;20 oocytes retrieved which in general is expected to result in higher quality embryos than cycles starting with only 6 frozen donor oocytes. There may be some uncorrected confounding between PGT-A and use of fresh oocytes. Despite this, transfer of embryos from donor oocytes using PGT-A actually had worse morphology than embryos from donor oocytes not using PGT-A due to the deselection of morphology that occurs with PGT-A testing and culture of embryos to expansion stage 2 before embryo biopsy (Table\\u0026nbsp;\\u003cspan refid=\\\"Tab2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e). Regardless, prospective studies are needed from centers proficient in embryo biopsy and PGT-A to verify our retrospective data.\\u003c/p\\u003e \\u003cp\\u003eIn this analysis we included use of embryos from fresh and frozen oocytes, fresh and frozen embryo transfer, transfers to gestational carriers, and single and double embryo transfers. Inclusion of these diverse types of transfers makes the data broadly applicable. However, this analysis is less controlled than ideal. Limiting the analysis to single frozen embryo transfers of embryos created from fresh oocytes would add more control but based on our dataset the numbers would have been too small to have sufficient statistical power. In the analysis in Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e the numerator is the total number of live births and the denominator is the total numbers of embryos transferred. We are essentially assuming that each embryo in a double embryo transfer implants independently of the other. This assumption is reasonable since most major endometrial factors are detected with modern ultrasound monitoring and uterine cavity imaging. We routinely performed saline infusion sonograms on all patients prior to embryo transfer. At least one study supports this conventional thinking that embryos implant independently of other embryos transferred concurrently [\\u003cspan citationid=\\\"CR19\\\" class=\\\"CitationRef\\\"\\u003e19\\u003c/span\\u003e].\\u003c/p\\u003e \\u003c/div\\u003e\"},{\"header\":\"Conclusion\",\"content\":\"\\u003cp\\u003ePGT-A of embryos from good prognosis patients likely increases the live birth rate per embryo transferred if loss of embryo implantations from the biopsy is low. This data supports the use of PGT-A in good prognosis patients at centers with data to support proficiency in this technique.\\u003c/p\\u003e\"},{\"header\":\"Declarations\",\"content\":\"\\u003cp\\u003e\\u003cstrong\\u003eAcknowledgements:\\u0026nbsp;\\u003c/strong\\u003eNone.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAuthor Contributions\\u003c/strong\\u003e MS Awadalla: protocol/project development, data collection, data analysis, manuscript writing/editing. R Agarwal: protocol/project development, data collection, manuscript writing/editing. JR Ho: manuscript writing/editing. LK McGinnis: manuscript writing/editing. A Ahmady: manuscript writing/editing.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eFunding\\u0026nbsp;\\u003c/strong\\u003eThe authors declare that no funds, grants, or other support were received during the preparation of this manuscript.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eCompeting Interests\\u0026nbsp;\\u003c/strong\\u003eThe authors have no relevant financial or non-financial interests to disclose.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eEthics approval\\u003c/strong\\u003e This study was approved by the University of Southern California IRB (HS-21-00206).\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConsent to participate\\u003c/strong\\u003e Not applicable.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConsent for publication\\u003c/strong\\u003e Not applicable.\\u003c/p\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003col\\u003e\\n\\u003cli\\u003eTiegs AW, Tao X, Zhan Y et al (2021) A multicenter, prospective, blinded, nonselection study evaluating the predictive value of an aneuploid diagnosis using a targeted next-generation sequencing-based preimplantation genetic testing for aneuploidy assay and impact of biopsy. Fertil Steril 115:627\\u0026ndash;637. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003ehttps://doi.org/10.1016/j.fertnstert.2020.07.052\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e\\n\\u003cli\\u003eMurugappan G, Ohno MS, Lathi RB (2015) Cost-effectiveness analysis of preimplantation genetic screening and in vitro fertilization versus expectant management in patients with unexplained recurrent pregnancy loss. Fertil Steril 103:1215\\u0026ndash;1220. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003ehttps://doi.org/10.1016/j.fertnstert.2015.02.012\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e\\n\\u003cli\\u003eSacchi L, Albani E, Cesana A et al (2019) Preimplantation Genetic Testing for Aneuploidy Improves Clinical, Gestational, and Neonatal Outcomes in Advanced Maternal Age Patients Without Compromising Cumulative Live-Birth Rate. J Assist Reprod Genet 36:2493\\u0026ndash;2504. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003ehttps://doi.org/10.1007/S10815-019-01609-4\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e\\n\\u003cli\\u003eMcDaniel KE, Awadalla MS, McGinnis LK, Ahmady A (2020) Transfer the Best and Biopsy the Rest? Blastocyst Euploidy Rates Vary Based on Morphology and Day of Biopsy. Arch Gynecol Obs 303:249\\u0026ndash;258. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003ehttps://doi.org/10.1016/j.fertnstert.2020.02.061\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e\\n\\u003cli\\u003eDoyle N, Gainty M, Eubanks A et al (2020) Donor oocyte recipients do not benefit from preimplantation genetic testing for aneuploidy to improve pregnancy outcomes. Hum Reprod 35:2548\\u0026ndash;2555. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003ehttps://doi.org/10.1093/humrep/deaa219\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e\\n\\u003cli\\u003eBarad DH, Darmon SK, Kushnir VA et al (2017) Impact of preimplantation genetic screening on donor oocyte-recipient cycles in the United States. Am J Obstet 217:576. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003ehttps://doi.org/10.1016/j.ajog.2017.07.023\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e\\n\\u003cli\\u003eMasbou AK, Friedenthal JB, McCulloh DH et al (2019) A Comparison of Pregnancy Outcomes in Patients Undergoing Donor Egg Single Embryo Transfers With and Without Preimplantation Genetic Testing. Reprod Sci 26:1661\\u0026ndash;1665. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003ehttps://doi.org/10.1177/1933719118820474\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e\\n\\u003cli\\u003eKang H-JJ, Melnick AP, Stewart JD et al (2016) Preimplantation genetic screening: who benefits? Fertil Steril 106:597\\u0026ndash;602. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003ehttps://doi.org/10.1016/j.fertnstert.2016.04.027\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e\\n\\u003cli\\u003eYang Z, Liu J, Collins GS et al (2012) Selection of single blastocysts for fresh transfer via standard morphology assessment alone and with array CGH for good prognosis IVF patients: results from a randomized pilot study. Mol Cytogenet 5:24. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003ehttps://doi.org/10.1186/1755-8166-5-24\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e\\n\\u003cli\\u003eMunn\\u0026eacute; S, Kaplan B, Frattarelli JL et al (2019) Preimplantation genetic testing for aneuploidy versus morphology as selection criteria for single frozen-thawed embryo transfer in good-prognosis patients: a multicenter randomized clinical trial. Fertil Steril 112:1071\\u0026ndash;1079. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003ehttps://doi.org/10.1016/j.fertnstert.2019.07.1346\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e\\n\\u003cli\\u003ePaulson RJ (2017) Preimplantation genetic screening: what is the clinical efficiency? Fertil Steril 108:228\\u0026ndash;230. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003ehttps://doi.org/10.1016/j.fertnstert.2017.06.023\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e\\n\\u003cli\\u003eAwadalla MS, Ingles SA, Ahmady A (2021) Design and validation of a model for quality control monitoring of dichotomous in vitro fertilization outcomes. Fertil Steril 116:453\\u0026ndash;461. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003ehttps://doi.org/10.1016/j.fertnstert.2021.02.002\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e\\n\\u003cli\\u003eAwadalla MS, Park KE, Latack KR et al (2021) Influence of Trophectoderm Biopsy Prior to Frozen Blastocyst Transfer on Obstetrical Outcomes. Reprod Sci 28:3459\\u0026ndash;3465. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003ehttps://doi.org/10.1007/S43032-021-00552-Z\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e\\n\\u003cli\\u003eLi M, Kort J, Baker VL (2021) Embryo biopsy and perinatal outcomes of singleton pregnancies: an analysis of 16,246 frozen embryo transfer cycles reported in the Society for Assisted Reproductive Technology Clinical Outcomes Reporting System. Am J Obstet Gynecol 224:500.\\n\\u003cdiv class=\\\"ExternalRefDOI\\\"\\u003ee1-500.e18. https://doi.org/10.1016/J.AJOG.2020.10.043\\u003c/div\\u003e\\n\\u003c/li\\u003e\\n\\u003cli\\u003eAwadalla MS, Vestal NL, McGinnis LK et al (2021) Effect of age and morphology on sustained implantation rate after euploid blastocyst transfer. Reprod Biomed Online 43:395\\u0026ndash;403. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003ehttps://doi.org/10.1016/j.rbmo.2021.06.008\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e\\n\\u003cli\\u003eGardner DK, Schoolcraft WB (1999) In vitro culture of human blastocysts. In: Jansen R, Mortimer D, eds. Towards Reproductive Certainty: Fertility and Genetics beyond. 378\\u0026ndash;388\\u003c/li\\u003e\\n\\u003cli\\u003eRubino P, Tapia L, Ruiz de Assin Alonso R et al (2020) Trophectoderm biopsy protocols can affect clinical outcomes: time to focus on the blastocyst biopsy technique. Fertil Steril 113:981\\u0026ndash;989. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003ehttps://doi.org/10.1016/j.fertnstert.2019.12.034\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e\\n\\u003cli\\u003eFacadio Antero M, Singh B, Pradhan A et al (2021) Cost-effectiveness of preimplantation genetic testing for aneuploidy for fresh donor oocyte cycles. F\\u0026amp;S Rep 2:36\\u0026ndash;42. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003ehttps://doi.org/10.1016/J.XFRE.2020.11.005\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e\\n\\u003cli\\u003eHill MJ, Eubanks AE, Csokmay JM et al (2020) Is transferring a lower-quality embryo with a good-quality blastocyst detrimental to the likelihood of live birth? Fertil Steril 114:338\\u0026ndash;345. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003ehttps://doi.org/10.1016/j.fertnstert.2020.03.027\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e\\n\\u003c/ol\\u003e\"}],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":true,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":false,\"hideJournal\":false,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":true,\"isAuthorSuppliedPdf\":false,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":true,\"isPdf\":false,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"archives-of-gynecology-and-obstetrics\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":false,\"externalIdentity\":\"arch\",\"sideBox\":\"Learn more about [Archives of Gynecology and Obstetrics](https://www.springer.com/journal/404)\",\"snPcode\":\"\",\"submissionUrl\":\"https://www.editorialmanager.com/arch/default.aspx\",\"title\":\"Archives of Gynecology and Obstetrics\",\"twitterHandle\":\"\",\"acdcEnabled\":true,\"dfaEnabled\":true,\"editorialSystem\":\"em\",\"reportingPortfolio\":\"Springer Hybrid\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":false},\"keywords\":\"in vitro fertilization, trophectoderm biopsy, preimplantation genetic testing, euploid embryo\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-1359116/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-1359116/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003cp\\u003e\\u003cstrong\\u003ePurpose: \\u003c/strong\\u003eTo determine if blastocyst trophectoderm biopsy for PGT-A is associated with an increased rate of live birth per embryo in good prognosis IVF patients at a single center.\\u003c/p\\u003e\\u003cp\\u003e\\u003cstrong\\u003eMethods: \\u003c/strong\\u003eWe performed a retrospective cohort study of good prognosis embryo transfer cycles at a single center from 1/1/2017 through 12/31/2019. We evaluated the rate of live birh per embryo with and without PGT-A for transfer of embryos in two groups of good prognosis patients: embryos from donor oocytes and embryos from autologous oocytes with maternal age less than 35 years at oocyte retrieval. 2-sided Fisher’s exact tests were used for comparisons between groups.\\u003c/p\\u003e\\u003cp\\u003e\\u003cstrong\\u003eResults: \\u003c/strong\\u003eAfter transfer of embryos created from donor oocytes the live birth rate per euploid embryo was 70.6% (24/34) compared to 34.3% (35/102) for untested embryos for a rate difference of 36.3% (95% CI 18.4-54.1%, p \\u0026lt; 0.01). After transfer of embros created from autologous oocytes with maternal age less than 35 years at oocyte retrieval the live birth rate per euploid embryo was 70.0% (49/70) compared to 52.5% (53/101) for untested embryos for a rate difference of 17.5% (95% CI 3.0-32.0%, p = 0.03).\\u003c/p\\u003e\\u003cp\\u003e\\u003cstrong\\u003eConclusion: \\u003c/strong\\u003eIn good prognosis patients at our center the live birth rate per euploid blastocyst was higher than for untested blastocysts.\\u003c/p\\u003e\",\"manuscriptTitle\":\"Effect of Trophectoderm Biopsy for PGT-A on Live Birth Rate per Embryo in Good Prognosis Patients\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2022-03-07 16:40:35\",\"doi\":\"10.21203/rs.3.rs-1359116/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0},{\"type\":\"editorInvitedReview\",\"content\":\"\",\"date\":\"2022-03-04T11:10:57+00:00\",\"index\":0,\"fulltext\":\"\"},{\"type\":\"reviewersInvited\",\"content\":\"\",\"date\":\"2022-03-04T09:46:40+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"editorInvited\",\"content\":\"Archives of Gynecology and Obstetrics\",\"date\":\"2022-02-28T11:44:25+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"editorAssigned\",\"content\":\"\",\"date\":\"2022-02-15T04:20:59+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"submitted\",\"content\":\"Archives of Gynecology and Obstetrics\",\"date\":\"2022-02-14T11:45:47+00:00\",\"index\":\"\",\"fulltext\":\"\"}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"archives-of-gynecology-and-obstetrics\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":false,\"externalIdentity\":\"arch\",\"sideBox\":\"Learn more about [Archives of Gynecology and Obstetrics](https://www.springer.com/journal/404)\",\"snPcode\":\"\",\"submissionUrl\":\"https://www.editorialmanager.com/arch/default.aspx\",\"title\":\"Archives of Gynecology and Obstetrics\",\"twitterHandle\":\"\",\"acdcEnabled\":true,\"dfaEnabled\":true,\"editorialSystem\":\"em\",\"reportingPortfolio\":\"Springer Hybrid\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":false}}],\"origin\":\"\",\"ownerIdentity\":\"4b4390a1-86e0-48d9-a553-f556ff793834\",\"owner\":[],\"postedDate\":\"March 7th, 2022\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"under-review\",\"subjectAreas\":[],\"tags\":[],\"updatedAt\":\"2022-06-19T13:13:51+00:00\",\"versionOfRecord\":[],\"versionCreatedAt\":\"2022-03-07 16:40:35\",\"video\":\"\",\"vorDoi\":\"\",\"vorDoiUrl\":\"\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-1359116\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-1359116\",\"identity\":\"rs-1359116\",\"version\":[\"v1\"]},\"buildId\":\"GqpaHPwrfC8PjnIFayRh5\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}