Healthy live births achieved from embryos diagnosed as non-mosaic segmental aneuploid.

PURPOSE: To investigate pregnancy outcomes resulting from transfer of embryos with non-mosaic (NM) segmental aneuploid (SA) results following preimplantation genetic testing for aneuploidy (PGT-A). METHODS: All patients who underwent frozen embryo transfer (FET) of at least one embryo with a NM-SA between March 2021 and April 2024 were retrospectively reviewed. Primary outcomes included live birth rate (LBR) and results of prenatal diagnosis. Embryos with NM-SA results were also compared to those with NM whole chromosome aneuploid (WCA) and mosaic SA results. RESULTS: Out of 25 NM-SA embryos transferred, the LBR was 24%. Prenatal diagnosis by amniocentesis and/or chorionic villus sampling was performed in 3/6 pregnancies, and results were normal. Embryos with duplications produced more live births compared to those with deletions. NM-SA embryos had a significantly higher ongoing pregnancy (OP)/LBR compared to embryos with NM-WCA results and a significantly lower OP/LBR compared to embryos with mosaic SA results; however, when compared to embryos with high-level SA mosaicism > 40%, the OP/LBR was not significantly different. CONCLUSION: Embryos with NM-SAs can result in euploid live births, albeit at reduced rates compared to those with mosaic SAs. These data can be used to aid in patient counseling about PGT-A results and embryo transfer decisions.

Planned oocyte cryopreservation: the state of the ART.

The objective of this review is to provide an update on planned oocyte cryopreservation. This fertility preservation method increases reproductive autonomy by allowing women to postpone childbearing whilst maintaining the option of having a biological child. Oocyte cryopreservation is no longer considered experimental, and its use has increased dramatically in recent years as more women delay childbearing for personal, professional and financial reasons. Despite increased usage, most patients who have undergone oocyte cryopreservation have not yet warmed their oocytes. Most women who cryopreserve oocytes wait years to use them, and many never use them. Studies have demonstrated that oocyte cryopreservation results in live birth rates comparable with IVF treatment using fresh oocytes, and does not pose additional safety risks to offspring. Based on current evidence, cryopreserving ≥20 mature oocytes at <38 years of age provides a 70% chance of one live birth. However, larger studies from a variety of geographic locations and centre types are needed to confirm these findings. Additional research is also needed to determine the recommended age for oocyte cryopreservation, recommended number of oocytes to cryopreserve, return and discard/non-use rates, cost-effectiveness, and how best to distribute accurate and up-to-date information to potential patients.

Utilization of standardized preimplantation genetic testing for aneuploidy (PGT-A) via artificial intelligence (AI) technology is correlated with improved pregnancy outcomes in single thawed euploid embryo transfer (STEET) cycles.

PURPOSE: To investigate the role of standardized preimplantation genetic testing for aneuploidy (PGT-A) using artificial intelligence (AI) in patients undergoing single thawed euploid embryo transfer (STEET) cycles. METHODS: Retrospective cohort study at a single, large university-based fertility center with patients undergoing in vitro fertilization (IVF) utilizing PGT-A from February 2015 to April 2020. Controls included embryos tested using subjective NGS. The first experimental group included embryos analyzed by NGS utilizing AI and machine learning (PGTaiSM Technology Platform, AI 1.0). The second group included embryos analyzed by AI 1.0 and SNP analysis (PGTai2.0, AI 2.0). Primary outcomes included rates of euploidy, aneuploidy and simple mosaicism. Secondary outcomes included rates of implantation (IR), clinical pregnancy (CPR), biochemical pregnancy (BPR), spontaneous abortion (SABR) and ongoing pregnancy and/or live birth (OP/LBR). RESULTS: A total of 24,908 embryos were analyzed, and classification rates using AI platforms were compared to subjective NGS. Overall, those tested via AI 1.0 showed a significantly increased euploidy rate (36.6% vs. 28.9%), decreased simple mosaicism rate (11.3% vs. 14.0%) and decreased aneuploidy rate (52.1% vs. 57.0%). Overall, those tested via AI 2.0 showed a significantly increased euploidy rate (35.0% vs. 28.9%) and decreased simple mosaicism rate (10.1% vs. 14.0%). Aneuploidy rate was insignificantly decreased when comparing AI 2.0 to NGS (54.8% vs. 57.0%). A total of 1,174 euploid embryos were transferred. The OP/LBR was significantly higher in the AI 2.0 group (70.3% vs. 61.7%). The BPR was significantly lower in the AI 2.0 group (4.6% vs. 11.8%). CONCLUSION: Standardized PGT-A via AI significantly increases euploidy classification rates and OP/LBR, and decreases BPR when compared to standard NGS.

Clinical implications of mitochondrial DNA quantification on pregnancy outcomes: a blinded prospective non-selection study.

STUDY QUESTION: Can quantification of mitochondrial DNA (mtDNA) in trophectoderm (TE) biopsy samples provide information concerning the viability of a blastocyst, potentially enhancing embryo selection and improving IVF treatment outcomes? SUMMARY ANSWER: This study demonstrated that euploid blastocysts of good morphology, but with high mtDNA levels had a greatly reduced implantation potential. WHAT IS KNOWN ALREADY: Better methods of embryo selection leading to IVF outcome improvement are necessary, as the transfer of chromosomally normal embryos of high morphological grade cannot guarantee the establishment of an ongoing pregnancy. The quantity of mtDNA in embryonic cells has been proposed as a new biomarker of viability-higher levels of mtDNA associated with reduced implantation potential. STUDY DESIGN, SIZE, DURATION: mtDNA was quantified in 199 blastocysts, previously biopsied and shown to be chromosomally normal using preimplantation genetic testing for aneuploidy (PGT-A). These were generated by 174 couples (average female age 37.06 years). All patients underwent IVF in a single clinic. The study took place in a blinded, non-selection manner-i.e. mtDNA quantity was not known at the time of single embryo transfer. The fate of the embryos transferred was subsequently compared to the mtDNA levels measured. PARTICIPANTS/MATERIALS, SETTING, METHODS: Embryos were biopsied at the blastocyst stage. The TE samples obtained were subjected to whole genome amplification followed by comprehensive chromosome analysis via next generation sequencing. The same biopsy specimens were also tested using quantitative PCR, allowing highly accurate mtDNA quantification. After blastocyst transfer, the code used for blinding was broken and analysis undertaken to reveal whether the amount of mtDNA had any association with embryo implantation. MAIN RESULTS AND THE ROLE OF CHANCE: mtDNA analysis of the 199 blastocysts revealed that 9 (5%) contained unusually high levels of mtDNA. All embryo transfers involved a single chromosomally normal blastocyst of good morphology. Of these, 121 (60%) led to ongoing pregnancies, 11(6%) led to biochemical pregnancies, and 10 (5%) spontaneously miscarried. All (100%) of these blastocysts had mtDNA levels considered to be normal/low. The remaining 57 (29%) blastocysts failed to implant. Among these non-viable embryos there were 9 (16%) with unusually high levels of mtDNA. This meant that the ongoing pregnancy rate for morphologically good, euploid blastocysts, with normal/low levels of mtDNA was 64% (121/190). In contrast, the ongoing pregnancy rate for the same type of embryos, but with elevated mtDNA levels, was 0/9 (0%). This difference was highly statistically significant (P < 0.0001). LIMITATIONS REASONS FOR CAUTION: To determine the true extent of any clinical benefits a randomized clinical trial will be necessary. Research is needed to improve understanding of the biology of mtDNA expansion. WIDER IMPLICATIONS OF THE FINDINGS: This is the first investigation to evaluate the clinical impact of increased mtDNA in a prospective blinded manner. Results confirm that embryos with elevated mtDNA rarely implant, supporting its use as a viability biomarker. A total of 64% of euploid blastocysts with normal/low mtDNA implanted versus 60% for the cohort as a whole. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by institutional funding (Reprogenetics UK and Reprogenetics). DW is supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre Programme. None of the authors have any competing interests.

Deliveries from trophectoderm biopsied, fresh and vitrified blastocysts derived from polar body biopsied, vitrified oocytes.

This longitudinal study reports preliminary findings of six patients who underwent first polar body biopsy followed by oocyte vitrification. All oocytes were warmed, inseminated by intracytoplasmic sperm injection and cultured to blastocyst. All suitable blastocysts underwent trophectoderm biopsy for aneuploidy screening, and supernumerary blastocysts were vitrified. Euploid blastocysts were transferred either fresh or in a subsequent programmed cycle. Of the 91 metaphase II oocytes, 30 had euploid first polar bodies. Development to blastocyst was more likely in oocytes with a euploid first polar body (66.7% versus 24.6%; P < 0.001). Nineteen euploid blastocysts were produced: 10 from oocytes with a euploid first polar body and nine from oocytes with an aneuploid first polar body. Five out of six patients (83%) had a live birth or ongoing pregnancy at the time of analysis. Eleven euploid blastocysts have been transferred and seven implanted (64%). Although the chromosomal status of the first polar body was poorly predictive of embryonic ploidy, an association was found between chromosomal status of the first polar body and development to blastocyst. Further study is required to characterize these relationships, but proof of concept is provided that twice biopsied, twice cryopreserved oocytes and embryos can lead to viable pregnancies.

In vitro fertilization with preimplantation genetic screening improves implantation and live birth in women age 40 through 43.

PURPOSE: In Vitro Fertilization is an effective treatment for infertility; however, it has relatively low success in women of advanced maternal age (>37) who have a high risk of producing aneuploid embryos, resulting in implantation failure, a higher rate of miscarriage or birth of a child with chromosome abnormalities. The purpose of this study was to compare the implantation, miscarriage and live birth rates with and without preimplantation genetic screening (PGS) of embryos from patients aged 40 through 43 years. METHODS: This is a retrospective cohort study, comparing embryos screened for ploidy using trophectoderm biopsy and array comparative genomic hybridization to embryos that were not screened. We compared pregnancy outcomes for traditional fresh IVF cycles with day 5 embryo transfers, Frozen Embryo Transfer (FET) cycles without PGS and PGS-FET (FET of only euploid embryos) cycles of patients with maternal ages ranging from 40 to 43 years, undergoing oocyte retrievals during the period between 1/1/2011 and 12/31/2012. RESULTS: The implantation rate of euploid embryos transferred in FET cycles (50.9%) was significantly greater than for unscreened embryos transferred in either fresh (23.8%) or FET (25.4%) cycles. The incidence of live birth per transferred embryo for PGS-FET (45.5%) was significantly greater than for No PGS fresh (15.8%) or No PGS FET (19.0 %) cycles. The incidences of live birth per implanted sac for PGS FET cycles (89.3%), No PGS fresh cycles (66.7%) and No PGS FET cycles (75.0%) were not significantly different. CONCLUSIONS: The present data provides evidence of the benefits of PGS with regard to improved implantation and live birth rate per embryo transferred.

Assessing morphokinetic parameters via time lapse microscopy (TLM) to predict euploidy: are aneuploidy risk classification models universal?

PURPOSE: To determine if Aneuploidy Risk Classification Models are predictive of euploidy/aneuploidy amongst IVF facilities. METHODS: We retrospectively applied key time lapse imaging events of embryos (Campbell et al.[5, 6]) to stratify embryos into 3 groups: low, medium and high risk of aneuploidy. The actual ploidy results (from array comparative genomic hybridization) were compared with expectations [5, 6]. Sources of variability in morphokinetic parameters were determined using Analysis of Variance (ANOVA). RESULTS: The model failed to segregate euploid embryos from aneuploid embryos cultured at our facility. Further analysis indicated that the variability of embryos among patients was too great to allow selection of euploid embryos based on simple morphokinetic thresholds. Clinical selection of embryos based on morphokinetics alone is unlikely to identify euploid embryos accurately for transfer or yield higher rates of live delivery. CONCLUSIONS: The use of non-invasive morphokinetics is unlikely to discriminate aneuploid from euploid embryos. Further, it does not approach the accuracy of preimplantation genetic screening with array comparative genomic hybridization.

Blinded rebiopsy and analysis of noneuploid embryos with 2 distinct preimplantation genetic testing platforms for aneuploidy.

OBJECTIVE: To determine how often a noneuploid result from a single trophectoderm (TE) biopsy tested with the next-generation sequencing (NGS)-based preimplantation genetic testing for aneuploidy (PGT-A) is concordant with rebiopsies tested with a single-nucleotide polymorphism (SNP) array-based PGT-A platform. DESIGN: Blinded prospective cohort study. SETTING: University-affiliated fertility center. PATIENT(S): One hundred blastocysts were chosen from donated samples; on TE biopsy with NGS-based PGT-A, 40 had at least one whole chromosome full copy number aneuploidy alone, 20 had a single whole chromosome intermediate copy number ("whole chromosome mosaic"), 20 had a single full segmental aneuploidy (segA), and 20 had a single segmental intermediate copy number ("segmental mosaic"). INTERVENTIONS: Four rebiopsies were collected from each embryo: 3 TE biopsies and the remaining embryo. Each rebiopsy was randomized, blinded, and assessed with an SNP array-based PGT-A platform that combines copy number and allele ratio analyses, without mosaicism reporting. MAIN OUTCOME MEASURE(S): Concordance between the NGS result and rebiopsy results and within each embryo's blinded rebiopsy results. RESULT(S): Next-generation sequencing-diagnosed whole chromosome aneuploidy (WCA) was reconfirmed in 95% (95% confidence interval [CI], 83%-99%) of embryos; 2 embryos with NGS-diagnosed WCA were called euploid on all conclusive rebiopsies. Among embryos with NGS-diagnosed whole chromosome mosaicism, 35% (95% CI, 15%-59%) were called euploid and 15% (95% CI, 3%-38%) were called whole chromosome aneuploid on all conclusive rebiopsies. A total of 30% (95% CI, 12%-54%) of embryos with NGS-diagnosed segA and 65% (95% CI, 41%-85%) of embryos with NGS-diagnosed segmental mosaicism were called euploid on all conclusive rebiopsies. In total, 13% (95% CI, 6%-25%) of embryos with NGS-diagnosed full copy number aneuploidy and 50% (95% CI, 34%-66%) of embryos with NGS-diagnosed mosaicism had uniformly euploid SNP results. Conversely, all embryos with at least one noneuploid SNP result (n = 72) either had SNP-diagnosed aneuploidy on another rebiopsy from the same embryo or NGS-diagnosed aneuploidy/mosaicism involving the same chromosome. CONCLUSION(S): Next-generation sequencing-diagnosed WCA is highly concordant with rebiopsies tested with an SNP array-based PGT-A; however, whole chromosome mosaicism, segA, and segmental mosaicism are less concordant, reinforcing that embryos with these results may have reproductive potential and be suitable for transfer.

The Landscape of Telomere Length and Telomerase in Human Embryos at Blastocyst Stage.

The telomere length of human blastocysts exceeds that of oocytes and telomerase activity increases after zygotic activation, peaking at the blastocyst stage. Yet, it is unknown whether aneuploid human embryos at the blastocyst stage exhibit a different profile of telomere length, telomerase gene expression, and telomerase activity compared to euploid embryos. In present study, 154 cryopreserved human blastocysts, donated by consenting patients, were thawed and assayed for telomere length, telomerase gene expression, and telomerase activity using real-time PCR (qPCR) and immunofluorescence (IF) staining. Aneuploid blastocysts showed longer telomeres, higher telomerase reverse transcriptase (TERT) mRNA expression, and lower telomerase activity compared to euploid blastocysts. The TERT protein was found in all tested embryos via IF staining with anti-hTERT antibody, regardless of ploidy status. Moreover, telomere length or telomerase gene expression did not differ in aneuploid blastocysts between chromosomal gain or loss. Our data demonstrate that telomerase is activated and telomeres are maintained in all human blastocyst stage embryos. The robust telomerase gene expression and telomere maintenance, even in aneuploid human blastocysts, may explain why extended in vitro culture alone is insufficient to cull out aneuploid embryos during in vitro fertilization.

Disaster preparedness in assisted reproductive technology.

The American Society for Reproductive Medicine compels centers providing reproductive medicine care to develop and implement an emergency preparedness plan in the event of a disaster. Reproductive care is vulnerable to disruptions in energy, transportation, and supply chains as well as may have potential destructive impacts on infrastructure. With the relentless progression of events related to climate change, centers can expect a growing number of such disruptive events and must prepare to deal with them. This article provides a case study of the impact of Hurricane Sandy on one center in New York City and proposes recommendations for future preparedness and mitigation.

Fifteen years of autologous oocyte thaw outcomes from a large university-based fertility center.

OBJECTIVE: To review the outcomes of patients who underwent autologous oocyte thaw after planned oocyte cryopreservation. DESIGN: Retrospective cohort study. SETTING: Large urban university-affiliated fertility center. PATIENT(S): All patients who underwent ≥1 autologous oocyte thaw before December 31, 2020. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The primary outcome was the final live birth rate (FLBR) per patient, and only patients who had a live birth (LB) or consumed all remaining inventory (cryopreserved oocytes and resultant euploid/untested/no result embryos) were included. The secondary outcomes were laboratory outcomes and LB rates per transfer. RESULT(S): A total of 543 patients underwent 800 oocyte cryopreservations, 605 thaws, and 436 transfers. The median age at the first cryopreservation was 38.3 years. The median time between the first cryopreservation and thaw was 4.2 years. The median numbers of oocytes and metaphase II oocytes (M2s) thawed per patient were 14 and 12, respectively. Overall survival of all thawed oocytes was 79%. Of all patients, 61% underwent ≥1 transfer. Among euploid (n = 262) and nonbiopsied (n = 158) transfers, the LB rates per transfer were 55% and 31%, respectively. The FLBR per patient was 39%. Age at cryopreservation and the number of M2s thawed were predictive of LB; the FLBR per patient was >50% for patients aged <38 years at cryopreservation or who thawed ≥20 M2s. A total of 173 patients (32%) have remaining inventory. CONCLUSION(S): Autologous oocyte thaw resulted in a 39% FLBR per patient, which is comparable with age-matched in vitro fertilization outcomes. Studies with larger cohorts are necessary.

Retrospective analysis of outcomes following transfer of previously cryopreserved oocytes, pronuclear zygotes and supernumerary blastocysts.

Oocyte cryopreservation still bears the experimental label. Remarkable innovation in this field has led to immense improvement in clinical outcomes and has even resulted in outcomes comparable to those achieved following fresh embryo transfers. Such success has prompted this centre to investigate outcomes of cryopreservation options (oocyte versus pronuclear zygote versus supernumerary day-5 blastocyst after fresh embryo transfer). This study retrospectively analysed 200 cryopreservation cycles which were divided into three groups according to cryopreservation option, which were all cultured to blastocyst-stage post thaw/warming from January 2005 to December 2008, and compared them with 400 fresh embryo transfer cycles from the same time period. When compared with fresh embryo transfer, frozen embryo transfers originating from previously cryopreserved oocytes or pronuclear zygotes resulted in similar implantation, pregnancy and live-birth rates; however, frozen embryo transfers originating from supernumerary day-5 blastocysts resulted in lower outcomes. Thus, oocyte and/or pronuclear zygote cryopreservation appear to be the most viable options for women desiring fertility preservation. Cryopreservation of supernumerary blastocysts may lead to a slightly lower live-birth rate since the best-quality blastocysts are generally transferred during the fresh embryo transfer attempt.

Evaluation of clinical parameters as predictors of monozygotic twins after single frozen embryo transfer.

OBJECTIVE: To determine if recent evolutions in laboratory protocols, including the increased use of natural cycles and the use of a hyaluronan-containing transfer medium, affected the rate of monozygotic twin (MZT) pregnancies after single frozen embryo transfer (FET). DESIGN: Retrospective cohort study. SETTING: Urban university-based fertility center. PATIENTS: Patients who underwent single FET between January 2016 and December 2018 resulting in an intrauterine pregnancy. INTERVENTIONS: Transition to a transfer protocol with a hyaluronan-containing transfer medium in July 2017. MAIN OUTCOME MEASURES: Number of MZT pregnancies. RESULTS: There were 1,619 cycles that met the inclusion criteria and 31 (1.9%) resulted in MZT pregnancies. A hyaluronan-containing transfer medium was used in 875 (54.1%) cycles. Programmed cycles were used for 1,385 (85.5%) FETs and 234 (14.5%) cycles were natural. The mean age at FET, oocyte age, endometrial echo thickness, inner cell mass grade, trophectoderm grade, expansion, and day of blastocyst vitrification were similar between the groups. The use of a hyaluronan-containing transfer medium resulted in fewer MZTs. After controlling potential confounders with a multivariate regression, the use of the hyaluronan-containing medium still resulted in fewer MZTs. Monozygotic twins were colinear with preimplantation genetic testing (PGT), so PGT was excluded as a variable in our regression. A regression of PGT only cycles showed that the use of the hyaluronan-containing medium was still associated with a reduction in MZT pregnancies. CONCLUSIONS: The use of a hyaluronan-containing transfer medium was associated with a lower rate of MZTs. Other clinical parameters, including cycle type, were not associated with changes in the number of MZTs. The use of PGT needs to be further investigated as a risk factor for MZTs.

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.

Impact of developmental stage at cryopreservation and transfer on clinical outcome of frozen embryo cycles.

Although several early IVF successes were achieved after transferring fully formed blastocysts, the majority of embryos replaced worldwide over the past 30 years have been at the cleavage stage. The programme at this study centre has previously found that delaying an embryo transfer to day 5 can reduce the chance for a high-order multiple gestation without compromising the pregnancy rate because fewer embryos can be replaced. To evaluate the impact of transfer day and embryonic stage at cryopreservation on cycle outcome, 6069 fresh and 706 frozen transfers from 2000-2006 performed at this study centre were retrospectively analysed. Approximately half of the fresh transfers were performed on day 3, with a shift to day-5 transfer over the study period with no change in cryopreservation incidence. Implantation, clinical pregnancy and live birth rates were significantly higher following day-5 transfer. When frozen-thawed embryos (2-cell to day-6 blastocysts) were transferred, acceptable pregnancy and live birth rates were achieved at all stages but thawed embryos transferred as day-5 blastocysts generated consistently higher clinical pregnancy and live birth rates. Transfer of embryos frozen on day 6 had the highest miscarriage and lowest live birth rates. Barring government regulation, an IVF programme's day for cryopreservation generally depends on its management of and success with fresh embryo transfer.

A Comparison of Pregnancy Outcomes in Patients Undergoing Donor Egg Single Embryo Transfers With and Without Preimplantation Genetic Testing.

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

Embryo biopsy: the fate of abnormal pronuclear embryos.

This study assessed 1908 embryos, including those with abnormal numbers of pronuclei, in IVF cycles from July 2001 to December 2006 in which preimplantation genetic screening (PGS) was performed on day 3 post-retrieval and 'euploid' embryos transferred the following day. PGS-intracytoplasmic sperm injection and PGS-translocation cycles were excluded. At 18 h post-insemination, the zygote distribution was 19% 0PN, 4% 1PN, 69% 2PN and 8% 3PN. No pregnancy occurred following 0PN or 1PN embryo transfers. A retrospective, blinded morphological ranking of all embryos on day 3 was performed and the results compared with PGS; no 0PN or 1PN embryo would have been chosen for transfer based on morphological superiority alone. Blastocyst formation occurred in 1PN embryos (29%) but not in 0PN embryos when evaluated on day 5. Euploid karyotypes were reported for biopsies of 0PN (3%), 1PN (5%) and 2PN (19%) embryos (P = 0.015, 1PN versus 2PN). A Y chromosome was observed in 0PN (17%) and 1PN (32%) embryos; surprisingly, 91% of these Y chromosome-bearing embryos were aneuploid. Many different meiotic and fertilization errors can result in 0PN or 1PN zygotes; these results indicate that the resultant embryos should not be transferred, especially when normally fertilized embryos are available.