Adherence to embryo transfer guidelines in favorable-prognosis patients aged less than 35 years using autologous oocytes and in recipients using donor oocytes: a Society for Assisted Reproductive Technology Clinic Outcome Reporting System study.

OBJECTIVE: To measure the consequences of nonadherence with the 2013 American Society for Reproductive Medicine elective single embryo transfer (eSET) guidelines for favorable-prognosis patients. DESIGN: Retrospective cohort. SETTING: In vitro fertilization clinics. PATIENT(S): A total of 28,311 fresh autologous, 2,500 frozen-thawed autologous, and 3,534 fresh oocyte-donor in vitro fertilization cycles in 2014-2016 at Society for Assisted Reproductive Technology-reporting centers. INTERVENTION(S): Patients aged <35 years or using donors aged <35 years underwent first blastocyst transfer. MAIN OUTCOME MEASURE(S): Singleton birth rate, gestational age at delivery, and birth weight were compared between the eSET and non-eSET groups using the chi-square or Fisher's exact test or t-tests. RESULT(S): Among fresh transfers, 15,643 (55%) underwent eSET. Live births after non-eSETs were less likely singletons (38.0% vs. 96.5%; adjusted relative risk [aRR], 0.56) and more likely complicated by preterm delivery (55.0% vs. 20.1%; aRR, 2.39) and low birth weight (<2,500 g) (40.1% vs. 10.6%; aRR, 3.4) compared with those after eSET. Among frozen-thawed transfers, 1,439 (58%) underwent eSET. Live births after non-eSETs were less likely singletons (41.9% vs. 95.2%; aRR, 0.69; 95% confidence interval, 0.66-0.73) and more likely complicated by preterm delivery (56.4% vs. 19.5%; aRR, 2.6; 95% confidence interval, 2.2-3.1) and low birth weight (38.0% vs. 8.9%; aRR, 3.9) compared with those after eSET. Among fresh donor oocyte transfers, 1,946 (55%) underwent eSET. Live births after non-eSETs were less likely singletons (31.3% vs. 97.3%; aRR, 0.48) and more likely complicated by preterm delivery (61.1% vs. 25.7%; aRR, 2.09) and low birth weight (44.3% vs. 11.7%; aRR, 3.39) compared with those after eSET. CONCLUSION(S): Nonadherence with transfer guidelines was associated with dramatically increased multiple pregnancies, preterm births, and low birth weights.

Characterization of an artificial intelligence model for ranking static images of blastocyst stage embryos.

OBJECTIVE: To perform a series of analyses characterizing an artificial intelligence (AI) model for ranking blastocyst-stage embryos. The primary objective was to evaluate the benefit of the model for predicting clinical pregnancy, whereas the secondary objective was to identify limitations that may impact clinical use. DESIGN: Retrospective study. SETTING: Consortium of 11 assisted reproductive technology centers in the United States. PATIENT(S): Static images of 5,923 transferred blastocysts and 2,614 nontransferred aneuploid blastocysts. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Prediction of clinical pregnancy (fetal heartbeat). RESULT(S): The area under the curve of the AI model ranged from 0.6 to 0.7 and outperformed manual morphology grading overall and on a per-site basis. A bootstrapped study predicted improved pregnancy rates between +5% and +12% per site using AI compared with manual grading using an inverted microscope. One site that used a low-magnification stereo zoom microscope did not show predicted improvement with the AI. Visualization techniques and attribution algorithms revealed that the features learned by the AI model largely overlap with the features of manual grading systems. Two sources of bias relating to the type of microscope and presence of embryo holding micropipettes were identified and mitigated. The analysis of AI scores in relation to pregnancy rates showed that score differences of ≥0.1 (10%) correspond with improved pregnancy rates, whereas score differences of <0.1 may not be clinically meaningful. CONCLUSION(S): This study demonstrates the potential of AI for ranking blastocyst stage embryos and highlights potential limitations related to image quality, bias, and granularity of scores.

Impact of body mass index (BMI) on the success rate of fresh embryo transfer in women undergoing first in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment.

OBJECTIVE: To investigate the impact of body mass index (BMI) on the success rate and prenatal outcomes of fresh embryo transfer in women undergoing their first in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment. METHODS: It is a post-hoc analysis of a prospective observational cohort study. 2569 Chinese women were grouped in quintiles of BMI and according to the official Chinese classification of body weight. IVF/ICSI and pregnancy outcomes were compared between groups. RESULTS: BMI was not associated with IVF/ICSI pregnancy outcomes including hCG positive rate, clinical pregnancy rate, implantation rate, ectopic pregnancy rate, ongoing pregnancy rate, early miscarriage rate, and live birth rate. However, it was negatively related to some pregnancy complications such as gestational diabetes mellitus (GDM) and hypertension. Additionally, the proportion of Cesarean-section was increased with BMI. As for prenatal outcomes, the current results showed no statistical difference in the number of male and female newborn, the proportion of low live birth weight (<2500 g), macrosomia (≥4000 g) (both in all live birth and full-term live birth), and premature delivery (<37 weeks). CONCLUSIONS: The current study showed that BMI was not associated with embryo transfer outcomes after fresh embryo transfer in women undergoing their first IVF/ICSI treatment, whereas BMI was associated with GDM and gestational hypertension.

Outcomes of embryo transfers performed by Reproductive Endocrinology and Infertility fellows vs. faculty: an 11-year retrospective review.

OBJECTIVE: To compare the clinical pregnancy rate (CPR) and live birth rate (LBR) of embryo transfer episodes (ETEs) performed by Reproductive Endocrinology and Infertility fellows vs. those of ETEs performed by faculty physicians. DESIGN: Retrospective cohort analysis. SETTING: Academic reproductive endocrinology and infertility practice. PATIENT(S): In total, 3,073 ETEs for 1,488 unique patients were performed by fellows or faculty physicians between January 2009 and January 2020. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate and LBR. RESULT(S): Fifteen fellows performed 1,225 (39.9%) of 3,073 ETEs after completing 30 mock transfers. On comparing outcomes among fellowship years (FY1, FY2, and FY3), CPR (44.1% vs. 43.2% vs. 45.7%, respectively, P = .83) and LBR (39.1% vs. 38.1% vs. 38.4%, respectively, P = .97) were not significantly different. Fellowship year 1 fellows' initial 30 ETEs vs. all the remaining FY1 ETEs had a significantly higher CPR (48.1% vs. 40.5%, respectively, P = .030) and LBR (45.4% vs. 34.3%, respectively, P = .001). There were no significant differences between faculty versus fellow ETEs in terms of CPR (43.0% vs. 45.0%, respectively, P = .30) or LBR (37.3% vs. 39.8%, respectively, P = .16), even after adjusting for patient age, body mass index, primary infertility diagnosis, autologous vs. donor oocyte, fresh vs. frozen embryo, number of embryos transferred, type of transfer catheter, and year of transfer (P = .32 for CPR, P = .22 for LBR). CONCLUSION(S): Appropriately trained FY1 fellows had success rates maintained throughout all FYs. There were no significant differences in clinical outcomes between fellow- and faculty-performed transfers. These data demonstrated that allowing fellows to perform live embryo transfers is not detrimental to clinical outcomes.

Retrospective comparison of pregnancy outcomes of fresh and frozen-warmed single blastocyst transfer: a 5-year single-center experience.

PURPOSE: To assess whether live birth rates (LBR) and maternal/neonatal complications differed following single fresh and frozen-warmed blastocyst transfer. METHODS: The present retrospective observational study analyzed 4,613 single embryo transfers (SET) (646 fresh and 3,967 frozen) from January 1, 2014, to December 31, 2018. Fresh embryo transfer at blastocyst stage was considered according to the age of the patient and her prognosis. In case of the risk of ovarian hyperstimulation syndrome, premature progesterone rise, non-optimal endometrial growth, or supernumerary embryos, cryopreservation with subsequent frozen embryo transfer (FET) was indicated. RESULTS: No differences in LBR were recorded. Fresh embryo transfers yielded an increase both in neonatal complications OR 2.15 (95% CI 1.20-3.86, p 0.010), with a higher prevalence of singletons weighting below the 5th percentile (p 0.013) and of intrauterine growth retardation (p 0.015), as well as maternal complications, with a higher placenta previa occurrence OR 3.58 (95% CI 1.54-8.28, p 0.003), compared to FET. CONCLUSION: LBR appears not to be affected by the transfer procedure preferred. Fresh embryo transfer is associated with higher risk of neonatal complications (specifically a higher prevalence of singletons weighting below the 5th percentile and of intrauterine growth retardation) and placenta previa. Reflecting on the increased practice of ART procedures, it is imperative to understand whether a transfer procedure yields less complications than the other and if it is time to switch to a "freeze-all" procedure as standard practice. TRIAL REGISTRATION: Clinical Trial Registration Number: NCT04310761. Date of registration: March 17, 2020, retrospectively registered.

Do live birth rate and obstetric outcomes vary between immediate and delayed embryo transfers following freeze-all cycles?

RESEARCH QUESTION: Do live birth rates (LBR), obstetric and perinatal outcomes vary between women who underwent frozen embryo transfer (ET) in the immediately subsequent menstrual cycle, and with those who underwent delayed frozen ET. DESIGN: Retrospective cohort study (n = 198) consisting of 119 women who underwent immediate transfer within 30 days of oocyte retrieval (OR) and 79 women who underwent delayed transfer which was performed after >30 days following OR. Either flexible antagonist or flexible progestin-primed ovarian stimulation protocols were started after a baseline ultrasonography on the second or third day of menstrual cycle. Only freeze all cycles were included in the study and all transfers were with hormonal endometrial preparation. Main outcome measures were LBR, birth weight, gestational day at birth and pregnancy complications. RESULTS: Peak estradiol level on trigger day (2746 vs 2081 pg/ml) and number of metaphase-two oocytes (13 vs 10) were significantly higher in the immediate transfer group. Clinical pregnancy rate per ET was similar between the groups (50.4% vs 44.3%). However, miscarriage rate per positive pregnancy was significantly higher (12.3% vs 31.1%) while LBR per ET was significantly lower (42.9% vs 26.6%) in the delayed transfer group. Median gestational age at delivery were 267.5 and 268 days in the immediate and delayed transfer groups. Median birthweight was significantly higher in the delayed transfer group (3520 vs 3195 g). Adjusted analyses also suggest similar LBR with immediate and delayed transfer. CONCLUSION(S): Frozen ET in the immediate menstrual cycle and delayed ET, after a freeze all strategy did not show significant difference in terms of LBR after adjustment. Obstetric and perinatal outcomes of frozen ET in the immediate menstrual cycle appear reassuring.

A fine tuning of embryo loading technique by eliminating the air bubble in the outer sheath of embryo catheter among women undergoing IVF treatment.

OBJECTIVES: The role of air bubbles in bracketing the embryo-containing medium in inner catheter during embryo transfer (ET) has already been established. However, the role of air bubbles in outer catheter (OC) during implantation is yet to be determined. This study aimed to compare the implantation rates between women who have undergone ET with or without ASP (Vitrolife®; Sweden), a medium use for oocyte retrieval and rinsing in OC embryo catheter. The purpose of introducing the ASP medium to the OC was to eliminate air bubbles in that space during implantation. METHODS: A total of 312 women were randomly divided into two groups with 156 participants each group. In Group A, ASP medium was used during ET, whereas in Group B, no ASP medium was utilized. Positive implantation was defined as serum beta-hCG level >5 mIU/mL taken on the 7th day following ET. RESULTS: The average age of the majority of the participants was 30-39 years and had at least 4-5 years of subfertility. The unexplained subfertility was the prominent cause of ET failure in both groups. In most of the participants in both groups, ET was done using fresh embryo cycles with good to excellent embryo grades. After the ASP medium was manipulated in the OC in both groups, the positive implantation rate was not different in both groups (p>0.05). CONCLUSIONS: The elimination of air bubbles in OC by using the ASP medium during ET did not confer an additional benefit nor exert a negative impact on implantation rate.

Guidance on the limits to the number of embryos to transfer: a committee opinion.

On the basis of American Society for Reproductive Medicine and Society for Assisted Reproductive Technology data, the American Society for Reproductive Medicine's guidelines for the limits on the number of embryos to be transferred during in vitro fertilization cycles have been further refined in continuing efforts to promote singleton gestation and reduce the number of multiple pregnancies. This version replaces the document titled "Criteria for number of embryos to transfer: a committee opinion" that was published most recently in August of 2017 (Fertil Steril 2017;107:901-3).

Live birth rates in different subgroups of poor ovarian responders according to Bologna and POSEIDON group classification criteria.

PURPOSE: The present study was designed to compare the live birth rates (LBRs) according to Bologna criteria or Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number (POSEIDON) group classifications to determine the important predictive factors for LBR in patients with POR. BASIC PROCEDURES: In this cross-sectional study, the database of Royan Institute (Tehran, Iran) from December 2015 to December 2017 was evaluated and the fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles outcomes for all the patients with at least one POR after standard controlled ovarian stimulation were collected. The patients divided into five subgroups according to Bologna criteria and four groups on the basis of POSEIDON group classification. MAIN FINDING: 812 patients with POR diagnosis were assessed which 517 (63.6%) of them were underwent embryo transfer (ET) during the last treatment cycle. According to Bologna criteria, 41 patients were not included in any subgroup and the patients in Bologna group II had highest LBR (19.8%). In terms of POSEIDON classification, all of the patients were classified into subgroups and the women in POSEIDON group III had the highest LBR (27%). According to multivariable regression analysis, the significant independent predictive factors for LBR were the number and morphology (good and excellent) of the embryos transferred, and POSEIDON group III classification. PRINCIPAL CONCLUSION: The results indicated that the POSEIDON group classification could be more comprehensive and practical than Bologna criteria for categorizing POR patients and predicting their outcome. Moreover, the number and morphology of transferred embryos were the most important prognostic factors for live births in these patients.

Should we look for a low-grade threshold for blastocyst transfer? A scoping review.

Embryo quality is a key determinant of the success of IVF. Although the focus has been on selecting the best embryo for transfer, the classification of low-grade blastocysts (LGB) in existing scoring systems has received less attention. This is worrisome; embryo freezing allows optimal use of all created embryos, thus maximizing the cumulative live birth rate, which is arguably the most important outcome for infertile couples. A PubMed search was conducted in August 2020, using '((('poor-quality' OR 'poor quality') OR ('low-grade' OR 'low grade')) AND ('embryo' OR 'blastocyst')) AND ('pregnancy' OR 'live birth')'. This scoping review shows that LGB have similar euploidy and pregnancy success rates after implantation and have no adverse effects on pregnancy or perinatal outcomes. Evidence for pregnancy outcomes is lacking for different grades of LGB, with most studies clustering all LQB as one to compare with optimal blastocysts.

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.

OBJECTIVE: To determine the predictive value of an aneuploid diagnosis with a targeted next-generation sequencing-based preimplantation genetic testing for aneuploidy (PGT-A) assay in prognosticating the failure of a successful delivery. DESIGN: Prospective, blinded, multicenter, nonselection study. All usable blastocysts were biopsied, and the single best morphologic blastocyst was transferred before genetic analysis. Preimplantation genetic testing for aneuploidy was performed after clinical outcome was determined. Clinical outcomes were compared to PGT-A results to calculate the predictive value of a PGT-A aneuploid diagnosis. SETTING: Fertility centers. PATIENT(S): Couples undergoing their first in vitro fertilization cycle without recurrent pregnancy loss, antral follicle count < 8, or body mass index ≥ 35 kg/m2. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The primary outcome was the ability of the analytical result of aneuploid to predict failure to deliver (clinical result). A secondary outcome was the impact of the trophectoderm biopsy on sustained implantation. RESULT(S): Four hundred two patients underwent 484 single, frozen, blastocyst transfers. The PGT-A aneuploid diagnosis clinical error rate was 0%. There was no difference in sustained implantation between the study group and an age-matched control group, where biopsy was not performed (47.9% vs. 45.8). CONCLUSION(S): The PGT-A assay evaluated was highly prognostic of failure to deliver when an aneuploid result was obtained. Additionally, the trophectoderm biopsy had no detectable adverse impact on sustained implantation. CLINICAL TRIAL REGISTRATION NUMBERS: NCT02032264 and NCT03604107.

Simulation training for embryo transfer: findings from the American Society for Reproductive Medicine Embryo Transfer Certificate Course.

OBJECTIVE: To assess the value of the American Society for Reproductive Medicine Embryo Transfer Certificate Course in confidence and skill building for performing a live embryo transfer (ET). DESIGN: Prospective cohort study. SETTING: Two-day simulation workshops of reproductive endocrine and infertility (REI) fellows from American Board of Obstetrics and Gynecology-approved training programs, using four different uterine models (A-D). PATIENT(S): None. INTERVENTION(S): Didactic and hands-on simulation training program. MAIN OUTCOME MEASURE(S): Primary outcomes included ET simulation scores of all exercises analyzed at various points of the training and self-assessed confidence before and after the completion of the Embryo Transfer Certificate Course based on a 6-point Likert scale and association of both with extent of prior live ET experience and year of fellowship. RESULT(S): Data were collected for 78 REI fellows who completed the Embryo Transfer Certificate Course and demonstrated significant improvements in both skill and confidence. The data for a subset of 58 fellows who performed five direct transfers on both Embryo Transfer Certificate Course uterine models A and B demonstrated significant overall improvement in ET simulation scores between the first and fifth direct transfers. A separate data subset of 57 fellows who performed five afterload transfers for each exercise on all four uterine models demonstrated differences in difficulty among them. Embryo transfer simulation using the uterine A model was consistently the easiest. The ET simulation scores for fellows using the uterine B and C models showed a progressive and significant increase across the five afterload ETs. When using the uterine D model, ET simulation scores increased significantly between the first and second transfers but remained at the same level for the remaining three transfers. Except for uterus A, a significant increase in ET simulation scores between the first and last transfers was observed for fellows overall in all afterload transfers and for those fellows with <50 prior live transfers. Data for all 78 fellows demonstrate a significant gain of self-confidence for all parameters, with the highest overall increase (78%) observed for first-year fellows as well as for fellows of any year with no prior live transfer experience (109%). Fellows with the largest number of prior live ET experience started with higher confidence, which also increased significantly, although they had a lower gain in confidence compared with fellows with less experience. CONCLUSION(S): The American Society for Reproductive Medicine Embryo Transfer Certificate Course data analysis demonstrates the effectiveness of simulator-based ET training for REI fellows across the 3 years of training, regardless of prior experience with live ET.

A New Day 4 Grading System to Assess Embryo Quality in Frozen Embryo Transfer Cycles.

To present a new day 4 (D4) embryo grading system to assess embryos in frozen-thawed embryo transfer (FET) cycles. A new grading system (grades A-E) was developed from the 2011 ESHRE Istanbul Consensus for D4 embryos in FET cycles. Embryos with complete compaction were classified as grade A; those with partial compaction were assigned as grade B; and those without compaction were classified as grades C, D, and E according to their different blastomere number ratio (BNR; number of embryo blastomeres on D4/number of embryo blastomeres on D3, D4/D3). Embryos with a BNR of ≥ 1.5 were defined as grade C, those with a BNR of ≥ 1.2 and < 1.5 were defined as grade D, and those with a BNR of ≥ 1.0 and < 1.2 were defined as grade E. Using this proposed grading model, 5460 embryos with known implantation data were retrospectively analyzed after D4 transfer in FET cycles. The transferred embryos exhibited a similar declining trend in implantation and live birth rates from the top grade A to the lowest grade E. The in vitro fertilization group showed increased implantation rates of grade B and E embryos compared with the intracytoplasmic sperm injection group (grade B: 41.99%, 34.63%, χ2 = 5.84, p < 0.05 and grade E: 18.98%, 14.08, χ2 = 75.62, p < 0.01). Receiver-operating characteristic analysis revealed that our proposed model predicted the implantation outcomes and live birth rates of all embryos (area under the curve = 0.65; 95% confidence interval [CI],0.63-0.66; p < 0.01 and AUC = 0.73; 95%CI, 0.65-0.84; p < 0.001, respectively). This study demonstrates that the new grading system provided by us can be a useful tool for assisting embryo selection via changes in embryo morphology. D4 embryo transfer provides a simple and applicable method for FET cycles in daily practice.

Electronic whiteboard implementation as a quality management tool optimizes IVF laboratory standardization and improves clinical outcomes.

PURPOSE: To test whether an electronic whiteboard in the IVF laboratory increases the likelihood that critical evaluation procedures are performed within optimum pre-set time ranges. METHODS: A retrospective cohort study of oocyte retrievals in our IVF clinic between 06/01/2012 and 05/31/2018 was included. The electronic whiteboard was introduced on 04/06/2014. Prior to implementation, embryologists strived to adhere to the set evaluation times without a formal guide. The primary outcomes were the proportion of embryologist evaluations performed in optimum time ranges and the proportion of usable embryos per patient. RESULTS: A total of 4645 retrievals met inclusion criteria. Implementation of the whiteboard was associated with (1) an increase in the proportion of fertilization checks performed within the optimum time range for ICSI cycles (+ 5.1%, RR = 1.06, CI = 1.02-1.10); (2) an increase in the proportion of day 3 evaluations performed within the optimum time range, whether assisted hatching was performed (+ 23.6%, RR = 1.48, CI = 1.36-1.60) or not (+ 13.8%, RR = 1.23, CI = 1.12-1.35); and (3) an increase in the proportion of day 5 evaluations within the optimum time range (+ 15.5%, RR = 1.23, CI = 1.12-1.35). Additionally, the mean number of usable embryos per patient increased from 2.8 to 4.5 after the whiteboard was implemented (RR = 1.25, CI = 1.19-1.31). CONCLUSION: The use of an electronic whiteboard that posts optimum times for performing critical procedures significantly increases the proportion of evaluations that occur within these ranges. Such improved standardization led to positive downstream effects on the number of usable embryos per patient. We suggest that electronic whiteboard implementation driven by real-time data collection should be considered in all IVF laboratories.

Does the transfer of a poor quality embryo with a good quality embryo benefit poor prognosis patients?

BACKGROUND: While single embryo transfer (SET) is widely advocated, double embryo transfer (DET) remains preferable in clinical practice to improve IVF success rate, especially in poor prognosis patients with only poor quality embryos (PQEs) available in addition to one or no good quality embryos (GQEs). Furthermore, previous studies suggest PQE might adversely affect the implantation of a GQE when transferred together. This study aims to evaluate the effect of transferring an additional PQE with a GQE on the outcomes in poor prognosis patients. METHODS: A total of 5037 frozen-thawed blastocyst transfer (FBT) cycles between January 2012 and May 2019 were included. Propensity score matching was applied to control for potential confounders, and we used generalized estimating equations (GEE) models to identify the association between the effect of an additional PQE and the outcomes. RESULTS: Overall, transferring a PQE with GQE (Group GP) achieved significantly higher pregnancy rate (PR), live birth rate (LBR) and multiple pregnancy rate (MPR) than GQE only (group G). The addition of a PQE increased LBR in patients aged 35 and over and in patients who received over 3 cycles of embryo transfer (ET) (48.1% vs 27.2%, OR:2.56, 95% CI: 1.3-5.03 and 46.6% vs 35.4%, OR:1.6, 95% CI: 1.09-2.35), but not in women under 35 and in women who received less than 3 cycles of ET (48.7% vs 43.9%, OR:1.22, 95% CI: 0.93-1.59 and 48.3% vs 41.4%, OR:1.33, 95% CI: 0.96-1.85). Group GP resulted in significantly higher MPR than group G irrespective of age and the number of previous IVF cycles. CONCLUSIONS: An additional PQE does not negatively affect the implantation potential of the co-transferred GQE. Nevertheless, the addition of a PQE contributes to both live birth and multiple birth in poor prognosis patients. Physicians should still balance the benefits and risks of DET.

Aneuploid embryo transfer: clinical policies and provider opinions at United States fertility clinics.

OBJECTIVE: To describe institutional clinical policies and individual provider opinions regarding aneuploid embryo transfer (aET). DESIGN: A survey about clinical policies was electronically sent to Society for Assisted Reproductive Technology (SART) member laboratory directors, and a separate survey about personal opinions was electronically sent to all SART members. SETTING: Not applicable. PATIENTS: Patients pursuing preimplantation genetic testing for aneuploidy (PGT-A). INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Current clinical policies about aET were described. Individual provider opinions about aET in the context of specific aneuploidies and mosaicism were also described. RESULTS: A total of 48 laboratory directors and 212 individual providers responded to their respective surveys. Twelve (25%) clinics report that they do not have a policy regarding aET, but clinics performing PGT-A in >100 cycles per year were more likely to have a policy. Half of the individual providers agree that an embryo with trisomy 21 should be available for aET, but most disagreed with aET of embryos with other aneuploidies and most were either unsure about or unwilling to transfer embryos with mosaicism. Those who worked in primarily patient-facing roles held more agreeable opinions regarding aET. CONCLUSION: There is no consensus regarding ideal clinical policies for aET. The wide range of current clinical practices and individual provider opinions regarding under what circumstances, if any, aET should be available to patients indicates that this is a divisive issue among ART providers, and there is a clear need for specific professional guidelines to address this issue.

Delayed versus immediate frozen embryo transfer after oocyte retrieval: a systematic review and meta-analysis.

PURPOSE: This systematic review and meta-analysis aimed to compare pregnancy outcomes between immediate frozen embryo transfer (FET) performed within the first menstrual cycle after oocyte retrieval and delayed FET following subsequent cycles. METHODS: PubMed, EMBASE, and Web of Science were searched for eligible studies through January 2020. The main outcome measures were clinical pregnancy rate (CPR), live birth rate (LBR), and pregnancy loss rate (PLR). The effect size was estimated as risk ratio (RR) with 95% confidence interval (CI) using a random effects model. Inter-study heterogeneity was assessed by the I2 statistic. RESULTS: Twelve retrospective cohort studies involving 18,230 cycles were included. The pooled results revealed no significant differences between delayed and immediate FET in CPR (RR 0.94, 95% CI 0.87-1.03; I2 = 67.9%), LBR (RR 0.94, 95% CI 0.85-1.03; I2 = 67.5%), and PLR (RR 1.05, 95% CI 0.87-1.26; I2 = 42.7%). Subgroup analyses of freeze-all cycles showed a marginal decrease of CPR in delayed FET (RR 0.93, 95% CI 0.86-1.00; I2 = 53.6%), but no significant changes were observed regarding LBR (RR 0.93, 95% CI 0.85-1.02; I2 = 65.2%) and PLR (RR 1.09, 95% CI 0.84-1.41; I2 = 59.1%). No statistical differences were found in effect estimates among other subgroup analyses by ovarian stimulation protocol, trigger agent, endometrial preparation regimen, and embryo stage. CONCLUSION: Timing of the first FET after oocyte retrieval was not significantly associated with pregnancy outcomes. This finding refutes the current common practice to delay FET after oocyte retrieval and reassures patients who wish to proceed with FET at their earliest convenience. Due to the high heterogeneity and observational nature of included studies, further randomized controlled trials are needed to confirm the results.

The 2019 PGDIS position statement on transfer of mosaic embryos within a context of new information on PGT-A.

BACKGROUND: A recently published Position Statement (PS) by the Preimplantation Genetics Diagnosis International Society (PGDIS) regarding utilization of preimplantation genetic testing for aneuploidy (PGT-A) in association with in vitro fertilization (IVF) contained inaccuracies and misrepresentations. Because opinions issued by the PGDIS have since 2016 determined worldwide IVF practice, corrections appear of importance. METHODS: The International Do No Harm Group in IVF (IDNHG-IVF) is a spontaneously coalesced body of international investigators, concerned with increasing utilization of add-ons to IVF. It is responsible for the presented consensus statement, which as a final document was reached after review of the pertinent literature and again revised after the recent publication of the STAR trial and related commentaries. RESULTS: In contrast to the PGDIA-PS, we recommend restrictions to the increasing, and by IVF centers now often even mandated, utilization of PGT-A in IVF cycles. While PGT-A has been proposed as a tool for achieving enhanced singleton livebirth outcomes through embryo selection, continued false-positive rates and increasing evidence for embryonic self-correction downstream from the testing stage, has led IDNHG-IVF to conclude that currently available data are insufficient to impose overreaching recommendations for PGT-A utilization. DISCUSSION: Here presented consensus offers an alternative to the 2019 PGDIS position statement regarding utilization of preimplantation genetic testing for aneuploidy (PGT-A) in association with in vitro fertilization (IVF). Mindful of what appears to offer best outcomes for patients, and in full consideration of patient autonomy, here presented opinion is based on best available evidence, with the goal of improving safety and efficacy of IVF and minimizing wastage of embryos with potential for healthy births. CONCLUSIONS: As the PGDIS never suggested restrictions on clinical utilization of PGT-A in IVF, here presented rebuttal represents an act of self-regulation by parts of the IVF community in attempts to control increasing utilization of different unproven recent add-ons to IVF.

Minimum standards for practices offering assisted reproductive technologies: a committee opinion.

This document is designed to provide a framework for assisted reproductive technology (ART) programs that meet or exceed the requirements suggested by the Centers for Disease Control and Prevention (CDC) for certification of ART laboratories. This document replaces the document, "Revised Minimum Standards for Practices Offering Assisted Reproductive Technologies: A Committee Opinion," published in 2014.

Clinical error rates of next generation sequencing and array comparative genomic hybridization with single thawed euploid embryo transfer.

We investigated clinical error rates with single thawed euploid embryo transfer (STEET) diagnosed by next generation sequencing (NGS) and array comparative genomic hybridization (aCGH). A total of 1997 STEET cycles after IVF with preimplantation genetic testing for aneuploidy (PGT-A) from 2010 to 2017 were identified; 1151 STEET cycles utilized NGS, and 846 STEET cycles utilized aCGH. Any abortions, spontaneous or elective, in which products of conception (POCs) were collected were reviewed. Discrepancies between chorionic villus sampling, amniocentesis, or live birth results and PGT-A diagnosis were also included. Primary outcomes were clinical error rate per: ET, pregnancy with gestational sac, live birth, and spontaneous abortion with POCs available for analysis. Secondary outcomes included implantation rate (IR), spontaneous abortion rate (SABR), and ongoing pregnancy/live birth rate (OPR/LBR). The clinical error rates in the NGS cohort were: 0.7% per embryo, 1% per pregnancy with gestational sac, and 0.1% rate per OP/LB. The error rate per SAB with POCs was 13.3%. The IR was 69.1%, the OPR/LBR was 61.6%, and the spontaneous abortion rate was 10.2%. The clinical error rates in the aCGH cohort were: 1.3% per embryo, 2% per pregnancy with gestational sac, and 0.4% rate per OP/LB. The error rate per SAB with POCs was 23.3%. The IR was 63.8%, the OPR/LBR was 54.6%, and the SAB rate was 12.4%. Our findings demonstrate that, although NGS and aCGH are sensitive platforms for PGT-A, errors still occur. Appropriate patient counseling and routine prenatal screening are recommended for all patients undergoing IVF/PGT-A.