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Purpose: Our aim was to evaluate if maternal age at transfer following autologous oocyte cryopreservation is associated with live birth rate (LBR)., Methods: We performed a retrospective cohort study of all patients who thawed autologous oocytes and then underwent a single frozen euploid embryo transfer between 2011 and 2021 at a large urban university-affiliated fertility center. Each oocyte thaw patient was matched 2:1 to in vitro fertilization (IVF) patients who underwent single embryo transfer < 1 year after retrieval. Primary outcome was LBR. Secondary outcomes included implantation rates (IR) and spontaneous abortion rates (SABR)., Results: A total of 169 oocyte thaw patients were matched to 338 IVF patients. As expected, oocyte thaw patients were older (median age 42.5 vs. 37.6 years, p < 0.001) and waited longer between retrieval and transfer than in vitro fertilization patients (median time 59 vs. 1 month, p < 0.001). In univariate analysis, implantation and LBR differed among oocyte thaw and IVF patients (p < 0.05), but SABR did not (p = 0.57). Transfer outcomes in oocyte thaw patients did not differ based on transfer age group (IR: p = 0.18; SABR: p = 0.12; LBR: p = 0.24). In a multiple logistic regression model, age at transfer was not predictive of live birth when controlling for age at retrieval, embryo morphology, and day of blastulation., Conclusions: Maternal age at transfer after oocyte cryopreservation is not predictive of LBR; this suggests that "an aging womb" does not impair LBR after oocyte thaw and empowers patients to return for transfer when ready for childbearing., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Purpose: To assess the experiences of two large fertility clinics in which embryos with positive results following preimplantation genetic testing for monogenic disorders (PGT-M) were transferred upon patient request, in order to explore the nature of the conditions for which these requests have been made and review ethical considerations., Methods: Retrospective review of previous embryo transfers at the NYU Langone Fertility Center and ORM Fertility was performed. Embryo transfers prior to May 2019 in which embryo biopsy and PGT-M occurred were reviewed, and transferred embryos that were positive for a monogenic disorder (excluding autosomal recessive carriers) were identified., Results: Seventeen patients were identified who elected to transfer 23 embryos that tested positive for nine different monogenic disorders. Most of the embryos transferred were positive for disorders that are autosomal dominant (15/23), are adult-onset (14/23), are associated with reduced penetrance (16/23), and have available management to lessen symptom severity (22/23). Transfer of positive embryos most commonly occurred for hereditary cancer susceptibility syndromes (9/23 embryos), particularly hereditary breast and ovarian cancer syndrome., Conclusions: When unaffected embryos are not produced following in vitro fertilization with PGT-M, some patients request to transfer embryos with positive test results. The majority of transfers were for embryos positive for adult-onset, reduced penetrance diseases. As these requests will likely increase over time, it is essential to consider the practical and ethical implications.

Objective: To assess patient decisions regarding mosaic embryos and their impact on clinical outcomes., Design: Review of patients who had genetic counseling regarding mosaic embryos., Setting: Academic department., Patient(s): Ninety-eight patients who had mosaic embryos but no euploid embryos., Intervention(s): Genetic counseling to discuss mosaic-embryo transfer (MET) after preimplantation genetic testing for aneuploidy., Main Outcome Measure(s): Patient decisions regarding MET. Outcomes for patients who pursued MET were compared with those for patients who pursued additional in vitro fertilization or intrauterine insemination cycles. Decisions regarding prenatal testing after MET were assessed., Result(s): Initially, 29.6% of patients pursued MET and 41.8% attempted a new treatment cycle. Only 6.1% of patients discarded their mosaic embryos without further treatment. Of the remaining patients, 2.0% transported their mosaic embryos to a different facility and 20.5% had not taken further action while their embryos remain stored. Patients who pursued additional cycles were more likely to have an ongoing pregnancy compared with those who pursued MET (51.2% vs. 27.6%; P<.05); however, there was no statistically significant difference in the percentage of patients who had at least one biochemical pregnancy or spontaneous abortion. Ultimately, 32.7% of patients underwent MET, and 54.5% of pregnant patients pursued amniocentesis., Conclusion(s): MET is desired by a substantial proportion of patients who do not have euploid embryos. Patients who opt for additional treatment cycles have a greater chance of achieving an ongoing pregnancy compared with those who pursue MET; however, future studies are needed to compare the cost-effectiveness for both options., (Copyright © 2018 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To determine whether undetected aneuploidy contributes to pregnancy loss after transfer of euploid embryos that have undergone array comparative genomic hybridization (aCGH)., Design: Case-control study., Setting: University-based fertility center., Patient(s): Cases included 38 patients who underwent frozen euploid ET as determined by aCGH, resulting in miscarriage. Controls included 38 patients who underwent frozen euploid ET as determined by aCGH, resulting in a live birth., Intervention(s): Next-generation sequencing (NGS) protocols were internally validated. Saved amplified DNA samples from the blastocyst trophectoderm biopsies previously diagnosed as euploid by aCGH were reanalyzed using NGS. Cytogenetic reports of the products of conception for 20 of the pregnancies resulting in miscarriage were available for comparison., Main Outcome Measure(s): The incidence of aneuploidy and mosaicism using NGS within embryos resulting in miscarriage and live birth., Result(s): Of euploid embryos analyzed by aCGH resulting in miscarriage, 31.6% were mosaic and 5.2% were polyploid by NGS. The rate of chromosomal abnormalities was significantly higher in embryos resulting in miscarriage (36.8%) than in those resulting in live births (15.8%). The rate of mosaicism was twice as high among embryos resulting in miscarriage than those resulting in live birth, but this was not statistically significant. Next-generation sequencing detected more cases of mosaicism than cytogenetic analysis of products of conception., Conclusion(s): Undetected aneuploidy may increase the risk of first trimester pregnancy loss. Next-generation sequencing may detect mosaicism and triploidy more frequently than aCGH, which could help to identify embryos at high risk of miscarriage. Mosaic embryos, however, should not be discarded as some can result in live births., (Published by Elsevier Inc.)

Purpose: Preimplantation genetic screening (PGS) and diagnosis (PGD) with euploid embryo transfer is associated with improved implantation and live birth rates as compared to routine in vitro fertilization. However, misdiagnosis of the embryo is a potential risk. The purpose of this study was to investigate the clinical discrepant diagnosis rate associated with transfer of trophectoderm-biopsied blastocysts deemed to be euploid via array comparative genomic hybridization (aCGH)., Methods: This is a retrospective cohort study including cycles utilizing PGS or PGD with trophectoderm biopsy, aCGH, and euploid embryo transfer at a large university-based fertility center with known birth outcomes from November 2010 through July 2014 (n = 520)., Results: There were 520 embryo transfers of 579 euploid embryos as designated by aCGH. Five discrepant diagnoses were identified. Error rate per embryo transfer cycle was 1.0 %, 0.9 % per embryo transferred, and 1.5 % per pregnancy with a sac. The live birth (LB) error rate was 0.7 % (both sex chromosome errors), and the spontaneous abortion (SAB) error rate was 17.6 % (3/17 products of conception tested, but could range from 3/42 to 7/42). No single gene disorders were mistakenly selected for in any known cases. , Conclusions: Although aCGH has been shown to be a highly sensitive method of comprehensive chromosome screening, several possible sources of error still exist. While the overall error rate is low, these findings have implications for counseling couples that are contemplating PGS and PGD with aCGH.

Purpose: To determine if day of embryo transfer (ET) affects gestational age (GA) and/or birth weight (BW) at a single university fertility center that primarily performs day 5/6 ET., Methods: Retrospective cohort study of 2392 singleton live births resulting from IVF/ICSI at a single large university fertility center from 2003 to 2012. Patients were stratified by day 3 or day 5/6 ET. Outcome variables included patient age, gravidity, prior miscarriages, prior assisted reproduction technology cycles, number of embryos transferred, number of single ET, infertility diagnosis, neonatal sex, GA at birth, and BW. Subanalyses were performed on subgroups of preterm infants. A comparison was made between the study data and the Society of Assisted Reproductive Technologies (SART) published data., Results: There was no difference in GA at birth (39 ± 2.1 weeks for day 3 ET, 39 ± 1.9 weeks for day 5/6 ET) or BW between ET groups (3308 ± 568 g for day 3 ET, 3268 ± 543 g for day 5/6 ET). There was also no difference in the number of preterm deliveries (8.5 % for day 3 ET vs. 10.8 % for day 5/6 ET). The day 5/6 ET study data had significantly fewer pre-term deliveries than the SART day 5/6 ET data., Conclusion: In contrast to published SART data, GA and BW were not influenced by day of ET. Data may be more uniform at a single institution. Day 5/6 ET continues to offer improved pregnancy rates without compromising birth outcomes.

Objective: To compare the efficiency of oocyte cryopreservation (OC) and IVF using the metric "live births per mature oocyte retrieved.", Design: Retrospective analysis., Setting: University-based fertility center., Patient(s): Forty women who underwent OC with thaw attempt between 2004 and 2010; 25 autologous and 15 donor-oocyte treatments were included. One thousand nine hundred eight women underwent their first, fresh conventional IVF treatment between 2004 and 2010; 1,392 used autologous oocytes, and 516 used donor oocytes. Autologous and donor-oocyte cycles were analyzed separately. All oocytes were obtained from women

Objective: To review a center's experience with cryopreserved embryos generated from donor eggs and to analyze their long-term disposition., Design: Retrospective analysis of donor egg cycles with cryopreserved embryos., Setting: University-based IVF program., Patient(s): Eight hundred twenty-nine women undergoing oocyte donation., Intervention(s): N/A., Main Outcome Measure(s): Factors affecting the decision regarding disposition of donor frozen embryo transfer (dFET) and the association between fresh and dFET cycles., Result(s): From January 2000 to December 2004, donor egg recipients underwent 829 fresh embryo transfer cycles that resulted in a 54% live birth rate. Of the 444 recipients who delivered, 177 (40%) also cryopreserved embryos at transfer; however, only 37 (21%) returned for a dFET by August 2009 and only 18 women had children from fresh and frozen transfers. In contrast, 128 of the 385 recipients who failed the fresh transfer (33%) cryopreserved embryos and 111 (87%) returned for a dFET. Of these, 44 had children from the dFET. Frozen cycle success rates between these recipient groups did not depend on fresh cycle outcome or prior parity., Conclusion(s): Donor oocyte recipients often initiate treatment with a desire to cryopreserve embryos for future use and family expansion. However, our data demonstrates that most recipients with a child from the fresh transfer do not return to use their cryopreserved embryos. Although fresh transfer success correlated with embryo disposition, it did not correlate with the outcome of thawed embryo transfer., (Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To report a case of a heterotopic primary abdominal pregnancy after two-blastocyst IVF-ET., Design: Case report., Setting: University-based IVF program., Patient(s): A woman with a heterotopic abdominal pregnancy after IVF-ET., Intervention(s): Pituitary down-regulation with luteal antagon, ovulation induction with menotropins, IVF-ET, progesterone in oil for luteal support, dilation and curettage for missed abortion, laparoscopy, and resection of abdominal gestation., Main Outcome Measure(s): Human chorionic gonadotropin levels, pelvic ultrasound examinations, and laparoscopic and pathologic findings., Result(s): A heterotopic abdominal pregnancy occurred after a two-blastocyst IVF-ET. The concurrent intrauterine gestation resulted in a miscarriage., Conclusion(s): The number of embryos transferred has been identified as a powerful risk factor for heterotopic pregnancy; however, heterotopic pregnancy can occur following a two-embryo, blastocyst stage transfer.

To assess whether the use of extended embryo culture can reduce the incidence of high-order multiple gestations, a retrospective analysis of 7,418 fresh ETs performed in a university-based IVF clinic from 1997-2003 was conducted, comparing program results before and after institution of a protocol to select patients for extended culture of in vitro fertilized embryos. The incidence of triplet pregnancies was significantly reduced in patients at highest risk for high-order multiple gestations, i.e., those at <35 years of age (16.8% versus 6.8%), those at 35-37 years of age (13.0% versus 5.6%), and recipients of donated oocytes (11.2% versus 4.5%).

Objective: To assess the clinical value of transabdominal ultrasound (TAS)--assisted embryo transfer on outcomes of in vitro fertilization--embryo transfer (IVF-ET) in comparison to the "clinical touch" method of transcervical embryo transfer by one physician and to determine if transabdominal ultrasound should be applied to all cases of embryo transfer in this practice., Design: A retrospective comparison study., Setting: A university-based IVF practice., Patient(s): Two hundred forty-nine patients who underwent transcervical transfer of fresh embryos created using autologous oocytes performed by the same physician from July 1, 2003, to June 30, 2004., Intervention(s): On selected days, at time of embryo transfer, transabdominal ultrasound was performed to guide catheter placement depth approximately 1 cm from the uterine fundus., Main Outcome Measure(s): The presence of at least one gestational sac on ultrasound was compared in the two study groups; additionally, the clinical pregnancy rate (presence of fetal cardiac activity observed on ultrasound), the ectopic pregnancy rate, the biochemical pregnancy rate, and the implantation rate (number of gestational sacs identified on ultrasound per number of embryos transferred) between groups was evaluated. Characteristics of the two cohorts were analyzed to verify similarities between the treatment and control groups, including age of recipient, prior IVF history, day of transfer (day 3 or day 5 after retrieval), difficulty of transfer, the use of a tenaculum, and the quality and number of embryos transferred., Result(s): No statistical difference was seen in the presence or number of gestational sacs following embryo transfer with or without transabdominal ultrasound guidance., Conclusion(s): No additional advantage is conferred when using transabdominal ultrasound to perform embryo transfer. In experienced hands, the "clinical touch" method of embryo transfer yields equivalent results to transabdominal ultrasound-guided embryo placement. However, in patients with a prior history of difficult uterine sounding or embryo transfer, transabdominal ultrasound guidance may still play a role.

Purpose: Our aim was to describe the reproductive decisions and outcomes of BRCA-positive patients who used preimplantation genetic testing for monogenic disorders (PGT-M). Methods: We performed a retrospective case series of all PGT-M cycles for BRCA variants between 2010–2021 at a large urban academic fertility center. All patients who underwent ≥ 1 cycle of IVF with PGT-M for BRCA1 or BRCA2 were included. The primary outcome was total number of BRCA-negative euploid embryos per patient. Results: Sixty four patients underwent PGT-M for BRCA variants. Forty-five percent (29/64) were BRCA1-positive females, 27% (17/64) were BRCA2-positive females, 16% (10/64) were BRCA1-positive males, 11% (7/64) were BRCA2-positive males, and one was a BRCA1 and BRCA2-positive male. There were 125 retrieval cycles with PGT-M, and all cycles included PGT for aneuploidy (PGT-A). Eighty-six percent (55/64) of patients obtained at least one BRCA- negative euploid embryo, with median of 1 (range 0–10) BRCA-negative euploid embryo resulted per cycle and median 3 (range 0–10) BRCA-negative euploid embryos accumulated per patient after a median of 2 (range 1–7) oocyte retrievals. Sixty-four percent (41/64) of patients attempted at least one frozen embryo transfer (FET) with a total of 68 FET cycles. Fifty-nine percent (40/68) of embryos transferred resulted in live births. Subgroup analysis revealed different reproductive pathways for BRCA1-positive females, BRCA2-positive females, and BRCA1/2-positive males (p < 0.05). Conclusion: PGT-M is a viable option for BRCA-positive patients to avoid transmission while building their families. Most patients in our cohort achieved pregnancy with BRCA-negative euploid embryos. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the outcomes of planned oocyte cryopreservation patients most likely to have a final disposition.Design: Retrospective cohort study of all patients who underwent at least 1 cycle of planned oocyte cryopreservation between Jan 2005 and December 2009.Setting: Large urban University-affiliated fertility center PATIENT(S): All patients who underwent ≥1 cycle of planned oocyte cryopreservation in the study period.Intervention(s): None MAIN OUTCOME MEASURE(S): Primary outcome was the disposition of oocytes at 10-15 years. Secondary outcomes included thaw/warming types, laboratory outcomes, and live birth rates. Outcomes and variables treated per patient.Result(s): A total of 231 patients with 280 cycles were included. The mean age at the first retrieval was 38.2 years (range 23-45). A total of 3,250 oocytes were retrieved, with an average of 10 metaphase II frozen/retrieval. To date, the oocytes of 88 patients (38.1%) have been thawed/warmed, 109 (47.2%) remain in storage, 27 (11.7%) have been discarded, and 7 (3.0%) have been transported elsewhere. The return rate (patients who thawed/warmed oocytes) was similar by Society for Assisted Reproductive Technology age group. The mean age of patients discarding oocytes was 47.4 years (range, 40-57). Of the 88 patients who thawed/warmed oocytes, the mean age at the time of thaw/warming was 43.9 years (range, 38-50) with a mean of 5.9 years frozen (range, 1-12). Nine patients (10.2%) thawed/warmed for secondary infertility. A total of 62.5% of patients created embryos with a partner, and 37.5% used donor sperm. On average, 14.3 oocytes were thawed/warmed per patient, with 74.2% survival (range, 0%-100%) and a mean fertilization rate of 68.8% of surviving oocytes. Of 88 patients, 39 (44.3%) planned a fresh embryo transfer (ET); 36 of 39 patients had at least 1 embryo for fresh ET, and 11 had a total of 14 infants. Forty-nine of 88 patients (55.7%) planned for preimplantation genetic testing for aneuploidy, with a mean of 4.2 embryos biopsied (range, 0-14) and a euploidy rate of 28.9%. Of the 49 patients, 17 (34.7%) had all aneuploidy or no embryos biopsied. Twenty-four patients underwent a total of 36 single euploid ET with 18 live births from 16 patients. Notably, 8 PGT-A patients had a euploid embryo but no ET, affecting the future cumulative pregnancy rate. Overall, 80 patients with thaw/warming embryos had a final outcome. Of these, 20 had nothing for ET (arrested/aneuploid), and of the 60 who had ≥1 ET, 27 had a total of 32 infants, with a live birth rate of 33.8% (27/80).Conclusion(s): We report the final outcomes of patients most likely to have returned, which is useful for patient counseling: a utilization rate of 38.1% and a no-use rate of 58.9%, similar across age groups. Further studies with larger cohorts as well as epidemiologic comparisons to patients currently cryopreserving are needed. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to report the results of IVF with trophectoderm biopsy and preimplantation genetic screening (PGS) following delayed intracytoplasmic sperm injection (ICSI). Methods: Patients undergoing IVF with PGS and delayed ICSI were included in the study. Indications for delayed ICSI included absent or poor fertilization via standard insemination or more than 50 % immature oocytes, noted post-cumulus stripping for standard ICSI procedure. Delayed ICSI was performed the day after retrieval due to absent or poor fertilization. The immature oocytes were kept in extended culture, and if demonstrated maturity, ICSI was performed. Primary outcome included fertilization rate and blastocyst stage formation, defined by the number of blastocysts for biopsy. Secondary outcome included aneuploidy rate and pregnancy outcomes following single thawed euploid embryo transfers (STEET). Results: Sixteen patients with delayed ICSI were included in the study. Twelve were due to poor fertilization and four secondary to immature oocytes. A total of 219 oocytes were retrieved; ten were frozen upon patient request, 168 had standard insemination, and 13 had routine ICSI on the day of retrieval. A total of 129 oocytes underwent delayed ICSI. Sixty-three (49 %) fertilized, 19 (14.7 %) reached blastocysts for biopsy; fivw of which were chromosomally normal (26.3 %). Three patients underwent STEET of a delayed ICSI embryo; all three resulted in live births, including one embryo biopsied on day 8 of development. Conclusion: Fertilization failure or an excessive proportion of immature oocytes in an IVF cycle, necessitating delayed ICSI, showed equivalent fertilization and blast formation rates. With the implementation of trophectoderm biopsy and PGS, these embryos can lead to healthy live born babies. [ABSTRACT FROM AUTHOR]

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.[, ]) 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 [, ]. 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. [ABSTRACT FROM AUTHOR]

Purpose: We determined whether the use of intracytoplasmic sperm injection in couples who previously underwent intracytoplasmic sperm injection cycles elsewhere could be decreased without compromising the pregnancy rate. Materials and Methods: At our university in vitro fertilization-embryo transfer center we retrospectively analyzed the records of 149 fresh, in vitro fertilization-embryo transfer cycles in patients who underwent intracytoplasmic sperm injection elsewhere and subsequent fertilization by insemination only (all insemination group) or half insemination and half intracytoplasmic sperm injection at our center. We compared fertilization, implantation, clinical pregnancy and live birth rates. Results: The fertilization rate was 74% and 73% for the all insemination and the half intracytoplasmic sperm injection groups, respectively. In the latter group 69% of inseminated and 78% of intracytoplasmic sperm injected oocytes were fertilized. No cycle showed complete fertilization failure. No statistically significant difference in the live birth rate was found between the 2 groups. Conclusions: More stringent criteria for intracytoplasmic sperm injection do not compromise the clinical outcome and reasonable fertilization can be achieved whether or not intracytoplasmic sperm injection is performed. Thus, although intracytoplasmic sperm injection is one of the greatest advances in our field, it is overused and should only be done for clinically proven indications. [ABSTRACT FROM AUTHOR]

Mosaic results obtained through preimplantation genetic testing for aneuploidy pose ongoing challenges to clinical practice. Thorough genetic counseling for patients considering mosaic embryo transfer is consistently recommended by many best-practice statements, and providers are charged with the task of assessing and explaining potential prenatal, neonatal, and long-term risks. However, an increasing amount of outcome data from transferred embryos with mosaic results do not show any evidence of increased risk to ongoing pregnancies or newborns. This article examines how to reconcile these data with the current practices for patient education about preimplantation genetic testing for aneuploidy and mosaic embryo risk assessment, through an evidence-based lens. [ABSTRACT FROM AUTHOR]

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

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

Objective: To validate and apply a strategy permitting parallel preimplantation genetic testing (PGT) for mitochondrial DNA (mtDNA) disease and aneuploidy (PGT-A).Design: Preclinical test validation and case reports.Setting: Fertility centers. Diagnostics laboratory.Patients: Four patients at risk of transmitting mtDNA disease caused by m.8993T>G (Patients A and B), m.10191T>G (Patient C), and m.3243A>G (Patient D). Patients A, B, and C had affected children. Patients A and D displayed somatic heteroplasmy for mtDNA mutations.Interventions: Embryo biopsy, genetic testing, and uterine transfer of embryos predicted to be euploid and mutation-free.Main Outcome Measures: Test accuracy, treatment outcomes, and mutation segregation.Results: Accuracy of mtDNA mutation quantification was confirmed. The test was compatible with PGT-A, and half of the embryos tested were shown to be aneuploid (16/33). Mutations were detected in approximately 40% of embryo biopsies from Patients A and D (10/24) but in none from Patients B and C (n = 29). Patients B and C had healthy children following PGT and natural conception, respectively. The m.8993T>G mutation displayed skewed segregation, whereas m.3243A>G mutation levels were relatively low and potentially impacted embryo development.Conclusions: Considering the high aneuploidy rate, strategies providing a combination of PGT for mtDNA disease and aneuploidy may be advantageous compared with approaches that consider only mtDNA. Heteroplasmic women had a higher incidence of affected embryos than those with undetectable somatic mutant mtDNA but were still able to produce mutation-free embryos. While not conclusive, the results are consistent with the existence of mutation-specific segregation mechanisms occurring during oogenesis and possibly embryogenesis. [ABSTRACT FROM AUTHOR]

Objective: To study how the attributes of mosaicism identified during preimplantation genetic testing for aneuploidy relate to clinical outcomes, in order to formulate a ranking system of mosaic embryos for intrauterine transfer.Design: Compiled analysis.Setting: Multi-center.Patient(s): A total of 5,561 euploid blastocysts and 1,000 mosaic blastocysts used in clinical transfers in patients undergoing fertility treatment.Intervention(s): None.Main Outcome Measure(s): Implantation (gestational sac), ongoing pregnancy, birth, and spontaneous abortion (miscarriage before 20 weeks of gestation).Result(s): The euploid group had significantly more favorable rates of implantation and ongoing pregnancy/birth (OP/B) compared with the combined mosaic group or the mosaic group affecting only whole chromosomes (implantation: 57.2% vs. 46.5% vs. 41.8%; OP/B: 52.3% vs. 37.0% vs. 31.3%), as well as lower likelihood of spontaneous abortion (8.6% vs. 20.4% vs. 25%). Whole-chromosome mosaic embryos with level (percent aneuploid cells) <50% had significantly more favorable outcomes than the ≥50% group (implantation: 44.5% vs. 30.4%; OP/B: 36.1% vs. 19.3%). Mosaic type (nature of the aneuploidy implicated in mosaicism) affected outcomes, with a significant correlation between number of affected chromosomes and unfavorable outcomes. This ranged from mosaicism involving segmental abnormalities to complex aneuploidies affecting three or more chromosomes (implantation: 51.6% vs. 30.4%; OP/B: 43.1% vs. 20.8%). Combining mosaic level, type, and embryo morphology revealed the order of subcategories regarding likelihood of positive outcome.Conclusion(s): This compiled analysis revealed traits of mosaicism identified with preimplantation genetic testing for aneuploidy that affected outcomes in a statistically significant manner, enabling the formulation of an evidence-based prioritization scheme for mosaic embryos in the clinic. [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether the use of next generation sequencing (NGS) for preimplantation genetic screening (PGS) in single thawed euploid embryo transfer (STEET) cycles improves pregnancy outcomes compared with array comparative genomic hybridization (aCGH).Design: Retrospective cohort study.Setting: Single university-based fertility center.Patient(s): A total of 916 STEET cycles from January 2014 to December 2016 were identified. Cases included 548 STEET cycles using NGS for PGS and controls included 368 STEET cycles using aCGH for PGS.Intervention(s): Patients having a STEET after undergoing IVF and PGS with either NGS or aCGH.Main Outcome Measure(s): Primary outcomes were implantation rate, ongoing pregnancy/live birth rate (OP/LBR), biochemical pregnancy rate (PR), and spontaneous abortion (SAB) rate.Result(s): The implantation rate was significantly higher in the NGS group compared with the aCGH group (71.6% vs. 64.6%). The OP/LBR was also significantly higher in the NGS group (62% vs. 54.4%), and there were significantly more biochemical pregnancies in the aCGH group compared with the NGS group (15.1% vs. 8.7%). After adjustment for confounding variables with a multiple logistic regression analysis, OP/LBR remained significantly higher in the NGS group. The SAB rate was not significantly different in the NGS group compared with the aCGH group (12.4% vs. 12.7%).Conclusion(s): Preimplantation genetic screening using NGS significantly improves pregnancy outcomes versus PGS using aCGH in STEET cycles. Next-generation sequencing has the ability to identify and screen for embryos with reduced viability such as mosaic embryos and those with partial aneuploidies or triploidy. Pregnancy outcomes with NGS may be improved due to the exclusion of these abnormal embryos. [ABSTRACT FROM AUTHOR]

Objective: To determine the pregnancy outcome potential of mosaic embryos, detected by means of preimplantation genetic screening (PGS) with the use of next-generation sequencing (NGS).Design: Retrospective study.Setting: Genetics laboratories.Patient(s): PGS cycles during which either mosaic or euploid embryos were replaced.Intervention(s): Blastocysts were biopsied and processed with the use of NGS, followed by frozen embryo transfer. Trophectoderm (TE) biopsies were classified as mosaic if they had 20%-80% abnormal cells.Main Outcome Measure(s): Implantation, miscarriage rates, and ongoing implantation rates (OIRs) were compared between euploid and types of mosaic blastocysts.Result(s): Complex mosaic embryos had a significantly lower OIR (10%) than aneuploidy mosaic (50%), double aneuploidy mosaic (45%), and segmental mosaic (41%). There was a tendency for mosaics with 40%-80% abnormal cells to have a lower OIR than those with <40% (22% vs. 56%). However, few embryos (n = 34) with a mosaic error in 40%-80% of the TE sample were replaced. There was no difference between monosomic and trisomic mosaics or between entire chromosome mosaicism or segmental mosaicism. Implantation rates were significantly higher (70% vs. 53%), miscarriage rates lower (10% vs. 25%), and OIRs higher (63% vs. 40%) after euploid embryo transfer than after mosaic embryo transfer.Conclusion(s): Forty-one percent of mosaic embryos produced an ongoing implantation. Complex mosaic blastocysts had a lower OIR than other mosaics. Mosaic monosomies performed as well as mosaic trisomies and mosaic segmental aneuploidies. The results suggest that embryos with >40% abnormal cells and those with multiple mosaic abnormalities (chaotic mosaics) are likely to have lower OIRs and should be given low transfer priority. [ABSTRACT FROM AUTHOR]