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The purpose of this study was to determine if morphometric parameters that can be measured quantitatively using a time-lapse embryo incubator are associated with aneuploidy. Embryos cultured in a time-lapse incubator and assessed with preimplantation genetic testing for aneuploidy (PGT-A) were analyzed retrospectively. Morphokinetic analysis included timing of cell divisions. Quantitative morphometric measurements included the distance between the second and first polar body, zona pellucida thickness at the pronuclear stage and at the 2-cell stage, and blastomere area at the 2- and 4-cell stages. Symmetry at the 2-cell stage was determined by percent difference between blastomeres; symmetry at the 4-cell stage was the percent difference between the smallest and largest blastomeres. Maternal age, blastocyst grade and day of biopsy were recorded. Euploid embryo characteristics were compared to aneuploid embryos. A receiver operating characteristic (ROC) curve was used to evaluate cell symmetry as a predictor of aneuploidy. Embryos (n = 182) from 21 patients (age 22-43; median = 34) were analyzed. Of the 182 embryos, 45% were euploid. Euploid and aneuploid embryos had similar morphokinetics and morphometry across many measures. As expected, age and blastocyst grade were associated with embryo ploidy. It was notable that, additionally, symmetry at the 4-cell stage (27% vs 31%, p = 0.01) was also associated with embryo ploidy. The optimized cutoff from the ROC curve to predict aneuploidy was determined to be 21%. Embryos with > 21% asymmetry at the 4-cell stage had high rates of aneuploidy while morphokinetic parameters were similar. In conclusion, this suggests that embryo selection models using time-lapse parameters would improve if they incorporate cleavage-stage morphometrics., (© 2021. Society for Reproductive Investigation.)

Objective: To compare neonatal health outcomes after fresh versus frozen ET (FET)., Design: Retrospective analysis of a population-based database of linked clinically assisted reproductive technology (ART) data with state vital records. Multivariable logistic regression was used to model the association between deliveries from fresh versus FET and adverse health outcomes, controlling for maternal characteristics., Setting: Not applicable., Patient(s): Live-born singleton infants born to Massachusetts women who conceived by fresh or FET after ART using autologous oocytes between July 1, 2004, and December 31, 2013., Intervention(s): None., Main Outcome Measure(s): Preterm birth, low birth weight, neonatal mortality, birth defects, organ system conditions., Result(s): Compared with infants conceived from fresh embryos, those born to mothers who underwent FET were less likely to be small for gestational age (adjusted odds ratio [AOR] = 0.56; 95% confidence interval [CI], 0.44-0.70) and low birth weight (AOR = 0.72; 95% CI, 0.59-0.88) but more likely to be large for gestational age (AOR = 1.47; 95% CI, 1.26-1.70) and to experience greater odds of infectious disease (AOR = 1.46; 95% CI, 1.03-2.06), respiratory (AOR = 1.23; 95% CI, 1.07-1.41), and neurologic (AOR = 1.32; 95% CI, 1.04-1.68) conditions. There were no statistically significant differences in preterm birth, neonatal mortality, birth defects, cardiovascular, hematologic, and gastrointestinal/feeding conditions, and for infants ≥ 35 weeks, no statistically significant differences in prolonged hospital stay (>3 days for vaginal delivery, >5 days for cesarean)., Conclusion(s): Compared with infants conceived from fresh ET, those born by FET have higher birth weight but increased odds of infectious disease, hematologic, respiratory, and neurologic abnormalities. These risks should be considered when making decisions on fresh versus FET., (Copyright © 2019 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the effect of frozen, compared with fresh, embryo transfer on neonatal and pediatric weight and weight gain trajectory., Design: Retrospective cohort study., Setting: Academic medical center., Patient(s): Women who underwent fresh or frozen embryo transfer at the Mayo Clinic from 2010 to 2014. All included embryo transfers resulted in a singleton live birth. Children were followed from birth to at least 18 months. When possible, growth was evaluated to 5 years of age., Interventions(s): Fresh versus frozen embryo transfer., Main Outcome Measure(s): Propensity score methodology was used to balance the two groups by maternal characteristics and gestational age before evaluating outcomes. Each infant and childhood growth measurement was compared between the two groups., Result(s): Of the 136 women, 87 underwent a fresh embryo transfer and 49 underwent a frozen embryo transfer. Birth length and head circumference were significantly different in infants delivered after fresh versus frozen embryo transfer. There was a statistically significant difference in birth weight between infants born after fresh versus frozen embryo transfer. However, this difference did not persist when adjusted for gestational age, sex, and maternal factors. Childhood growth measurements including age- and sex-specific weight, and body mass index percentiles were not significantly different between groups., Conclusion(s): This study confirmed an association of frozen embryo transfer and increased birth weight, but the association did not persist when controlling for confounding maternal factors. We found no effect of fresh versus frozen embryo transfer on neonatal weight and childhood weight gain trajectory., (Copyright © 2019 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Children born from fresh in vitro fertilization (IVF) cycles are at greater risk of being born smaller and earlier, even when limited to singletons; those born from frozen cycles have an increased risk of large-for-gestational age (LGA) birthweight (z-score ≥1.28). This analysis sought to overcome limitations in other studies by using pairs of siblings, and accounting for prior cycle outcomes, maternal characteristics, and embryo state and stage., Methods: Pairs of singleton births conceived with IVF and born between 2004 and 2013 were identified from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System database, matched for embryo stage (blastocyst versus non-blastocyst) and infant gender, categorized by embryo state (fresh versus frozen) in 1st and 2nd births (four groups)., Results: The data included 7795 singleton pairs. Birthweight z-scores were 0.00-0.04 and 0.24-0.26 in 1st and 2nd births in fresh cycles, and 0.25-0.34 and 0.50-0.55 in frozen cycles, respectively. LGA was 9.2-9.8 and 14.2-15.4% in 1st and 2nd births in fresh cycles, and 13.1-15.8 and 20.8-21.0% in 1st and 2nd births in frozen cycles. The risk of LGA was increased in frozen cycles (1st births, adjusted odds ratios (AOR) 1.74, 95% CI 1.45, 2.08; and in 2nd births when the 1st birth was not LGA, AOR 1.70, 95% CI 1.46, 1.98 for fresh/frozen and 1.40, 1.11, 1.78 for frozen/frozen)., Conclusions: Our results with siblings indicate that frozen embryo state is associated with an increased risk for LGA. The implications of these findings for childhood health and risk of obesity are unclear, and warrant further investigation., Competing Interests: Compliance with ethical standards This study was approved by the Committees for the Protection of Human Subjects at the Dartmouth College, Michigan State University, and University of Michigan. Conflict of interest BL is a research consultant to the Society for Assisted Reproductive Technology (SART). EW is under contract with SART to maintain the SART CORS database. MBB, JES, JPT, and CCC have no conflicts to declare.

Objective: To evaluate pregnancy rates based on the route of progesterone replacement in frozen embryo transfer (FET) cycles., Study Design: A randomized controlled trial and retrospective analysis. In the randomized group 76 FET cycles were randomized. In the retrospective group 508 FET cycles were reviewed. Intramuscular (IM) proges-erone in oil 100 mg daily or oral micronized progesterone prior to transfer followed by compounded vaginal proges-erone 200 mg 3 times daily (OV). The main outcome measure was the clinical pregnancy rate (CPR)., Results: Baseline characteristics did not vary be-ween groups in either cohort. In the randomized group there were no significant differences in CPR (31.43% vs. 21.05%) or live birth rate (LBR) (31.43% vs. 18.92%) for IM and OV progesterone replacement, respectively. In the retrospective cohort patients there wore also no significant differences in CPR (35.56% vs. 32.35%) or LBR (32.23% vs. 28.51%)f or the IM and OVp rogester-ne replacement groups, respectively., Conclusion: This study demonstrates that either OV or IM progesterone is effective for luteal phase support for FETs.

Background: Cryopreservation of all embryos in stimulated IVF cycles is occasionally necessary. Although it is known that frozen embryo transfer results in lower live birth rates per transfer, there is limited information regarding expected cumulative live birth rates for patients who are in this particular scenario., Methods: The objective was to evaluate long-term outcomes in cycles undergoing pronuclear cryopreservation of all embryos utilizing a retrospective analysis of 154 consecutive recipients from 1995 to 2006., Results: The cumulative rate of first live birth per retrieval was 66.2%, with a 36.4% live birth rate per frozen embryo transfer. Following an average 2.2 +/- 0.98 transfers, 32.6% (17/52) of patients who never delivered had remaining embryos making the cumulative first live birth rate previously stated a conservative estimate. 11.7% of recipients had sibling deliveries from a single retrieval. Over 1/3 of the delivered recipients have remaining cryopreserved embryos and could pursue an additional pregnancy., Conclusion: These results suggest that pronuclear cryopreservation of all embryos in an oocyte donation cycle maintains good cumulative live birth rates, as well as chances for a sibling from a single retrieval. Recipients who must delay transfer can be reassured a high potential for live birth from their first donor retrieval., (Copyright 2010 S. Karger AG, Basel.)

Objective: To describe a unique case of recurrent aneuploidy and the use of preimplantation genetic screening (PGS)., Design: Case report., Setting: Midwest academic medical center., Patient(s): A 36-year-old woman with two trisomy 21 offspring., Intervention(s): Preimplantation genetic screening., Main Outcome Measure(s): Karyotype of embryos, liveborn eukaryotic infant., Result(s): Preimplantation genetic screening was performed on three cryopreserved embryos, followed by a two-embryo transfer yielding a eukaryotic infant., Conclusion(s): Preimplantation genetic screening may prove to be useful as a diagnostic tool to help ensure a euploid pregnancy when termination is not a viable option for a couple.

Objective: To determine the role of saline infusion sonography (SIS) in uterine evaluation before a frozen embryo transfer (FET) cycle., Design: Retrospective cohort analysis., Setting: University hospital., Patient(s): Thirty-six patients who had uterine evaluation by SIS before FET cycle., Intervention(s): The SIS was performed in the follicular phase of the menstrual cycle before the actual FET cycle., Main Outcome Measure(s): The SIS findings, clinical pregnancy rate (PR), ongoing PR, and correlation between positive SIS findings with and without subsequent treatment and pregnancy outcome., Result(s): Positive SIS findings were found in 11/36 patients (30.5%), which included uterine septum (9.0%), endometrial polyp (45.4%), intramural fibroid with normal cavity (9.0%), cystic endometrial changes (9.0%), cervical stenosis (18.1%), and calcification with normal cavity (9.0%). The overall clinical PR in all groups was 51.4%, with an ongoing PR of 45.7%. Patients with positive SIS finding who underwent subsequent hysteroscopic correction (7/11) had a clinical PR of 85.7% as compared to 54.1% in patients with normal uterine cavity (24/35). Patients with positive SIS findings and no operative hysteroscopy (4/11) had a clinical PR of 50% and pregnancy loss rate of 100%., Conclusion(s): Obtaining an SIS before the FET cycle can be helpful in the detection of uterine abnormalities. If time since uterine evaluation has been more than 1-2 years, performing an SIS is recommended as subsequent correction of the anomalies may improve FET outcome.