Objective:To validate the performance of our laboratory-developed whole-genome screening assay within clinical preimplantation genetic testing environments.Design:Perform a laboratory-developed whole-genome assay on both cell lines and trophectoderm biopsies, subsequently employing the next-generation sequencing procedure to reach a sequencing depth of 30X. Adhere to the Genome Analysis Toolkit best practices for accuracy, sensitivity, specificity, and precision calculations by comparing samples with references. Our assay was then applied to cell lines and biopsies harboring known pathogenic variants, aiming to ascertain these changes solely from the next-generation sequencing data, independent of parental genome information.Settings:Clinical laboratory.Patients:Coriell cell lines and research embryos with known chromosomal or genetic variants. Research trophectoderm biopsies from a couple that are heterozygous carriers for distinct variants in the same autosomal recessive gene (HOGA1).Intervention:Not applicable.Main Outcome Measures:Accuracy, sensitivity, specificity, and precision were assessed by comparing the samples to their references. For samples with known variants, we calculated our sensitivity to detecting established variants. For the research embryos, noncarrier, carrier, and compound heterozygous states of inherited HOGA1 variants were distinguished independently of parental samples.Results:Amplification of DNA from cell lines and embryos yielded success rates exceeding 99.9% and 98.2%, respectively, although maintaining an accuracy of >99.9% for aneuploidy assessment. The accuracy (99.99%), specificity (99.99%), sensitivity (98.0%), and precision (98.1%) of amplified genome in the bottle (reference NA12878) and embryo biopsies were comparable to results on genomic DNA, including mitochondrial heteroplasmy. Using our assay, we achieved >99.99% sensitivity when examining samples with known chromosomal and genetic variants. This encompassed pathogenic CFTR, BRCA1, and other variants, along with uniparental isodisomies and microdeletions such as DiGeorge syndrome. Our research study identified noncarrier, carrier, and compound heterozygous states within trophectoderm biopsies while simultaneously screening for 1,300 other severe monogenic diseases.Conclusion:To our knowledge, this is the first clinical validation of whole-genome embryo screening. In this study, we demonstrated high accuracy for aneuploidy calls (>99.9%) and genetic variants (99.99%), even in the absence of parental genomes. This assay demonstrates advancements in genomic screening and an extended scope for testing capabilities in the realm of preimplantation genetic testing.

Women selecting elective fertility preservation (EFP) often ask about the ‘ideal’ number of oocytes to store for future use. As preimplatation genetic testing (PGT) becomes more popular, many couples may request PGT for their egg thaw cycles. However, current predictive models do not take PGT into consideration, when considering the number of oocytes needed to freeze for a succesful outcome. The purpose of the present study was to provide an evidence-based tool to counsel patients on the ideal number of oocytes to freeze in order to have at least one euploid blastocyst. Additional analyses on frozen egg donor cycles is also provided. Retrospective cohort study. The data from 186 cycles (Jan 2017 to Dec 2018) with vitrified/warmed oocytes were retrospectively analyzed. Only cycles with PGT performed on all available blastocysts were included. A sensitivity analysis on the probability to obtain at least one euploid blastocyst (positive result) in relation to the number of thawed oocytes was conducted. Patients were categorized into four groups according to their age at freezing: egg donors (n=52), < 36 (n=54), between 36 and 39 (n=50), >39 (n=30). All donors were from an in-house program. The sliding window method was used to calculate the probability of a positive result for different numbers of thawed oocytes. The dimension of the window was 5 oocytes and was centered on the number of thawed oocytes to test. The mean age of the women was 33.0 ± 6.6 (min: 23; max: 47). The minimum number of thawed oocytes was 1 while the maximum was 65 (median [IQR]: 11 [7-17]). A total of 2832 oocytes were thawed, 2464 survived (87.0%) 1783 fertilized (72.3%) and 777 (43.6%) reached the blastocyst stage (blastulation rate for fresh cycles in the same study period: 62.5% p<0.01). The number of thawed oocytes needed to obtain 90% probability of a positive result for donors and women with age <36 was 9 and 12, respectively. For the other age groups no number of thawed oocytes guaranteed a 90% probability of a positive result. The threshold to reach the positive result with a probability of 80% was also evaluated: 5, 11 and 14 oocytes were needed, respectively, for the donor, <36 and 36-39 age groups. The group with age >39 did not reach a 80% probability of a positive result with any number of thawed oocytes. Finally, the best result achievable for each age groups was analyzed: for donors a probability of 100% required 11 oocytes, for the <36 group a probability of 100% required 12 oocytes, for the 36-39 group a probability of 89% required 15 oocytes and for the >39 group a probability of 60% required 15 oocytes. The number of oocytes needed to obtain at least 1 euploid blastocyst in PGT cycles with frozen oocytes was higher than the number that the models predicts for fresh oocytes (1). In agreement with previous studies (2), our cryopreserved oocytes showed a significantly lower blastulation rate compared with our fresh oocytes possibly explaining our findings. Data on PGT in egg frozen cycles are minimal in the literature and our results may be used to provide counseling for women desiring EFP.

Objective: To examine the efficacy and safety of frozen-thawed embryo transfer (FTET) cycles with supernumerary embryos cryopreserved during a randomized clinical trial (PURSUE).Design: Follow-up clinical study.Setting: In vitro fertilization (IVF) centers.Patient(s): Infertile women 35 to 42 years of age.Intervention(s): In PURSUE, women were randomized to a single injection of 150 mu g of corifollitropin alfa (n = 694) or daily 300 IU of recombinant follicle-stimulating hormone (recombinant FSH; n = 696) for the first 7 days of controlled ovarian stimulation (COS) in a gonadotropin-releasing hormone (GnRH) antagonist protocol.Main Outcome Measure(s): Cumulative vital pregnancy rate per-patient by treatment group, cumulative live-birth rate per-patient by treatment group, and occurrence of adverse events in (pregnant) women and their fetuses/infants and the incidence of congenital malformations in the infants.Result(s): Of the 1,390 treated women in PURSUE, 307 were enrolled in the FTET study. In PURSUE or a subsequent FTET cycle, the cumulative vital pregnancy rate (per patient) was 31.1% (95% confidence interval [CI], 27.7%; 34.7%) with corifollitropin alfa versus 33.0% (95% CI: 29.6%; 36.7%) with recombinant FSH; treatment difference, -1.8% (95% CI, -6.5%; 3.0%), and the cumulative live-birth rate (per patient) was 28.2% (95% CI, 24.9%; 31.8%) with corifollitropin alfa versus 29.5% (95% CI, 26.1%; 33.0%) with recombinant FSH; treatment difference, -1.2% (95% CI, -5.7%; 3.4%). There were no clinically relevant differences in safety outcomes collected from pregnant women or their infants after transfer of cryopreserved embryos obtained by treatment with corifollitropin alfa or recombinant FSH.Conclusion(s): The cumulative vital pregnancy and live-birth rates (from fresh cycles and FTET) were similar in women treated with corifollitropin alfa and recombinant FSH. No new safety signals were detected in this follow-up FTET study. (C) 2016 by American Society for Reproductive Medicine.

A meta-analysis was conducted of individual patient data (n = 3292) from three randomized controlled trials of corifollitropin alfa versus rFSH: Engage (150 mu g corifollitropin alfa n = 756; 200 IU rFSH n = 750), Ensure (100 mu g corifollitropin alfa n = 268; 150 IU rFSH n = 128), and Pursue (150 mu g corifollitropin alfa n = 694; 300 IU rFSH n = 696). Women with regular menstrual cycles aged 18-36 and body weight >60 kg (Engage) or <= 60 kg (Ensure), or women aged 35-42 years and body weight >= 50 kg (Pursue), received a single injection (100 mu g or 150 mu g) of corifollitropin alfa (based on body weight and age) or daily rFSH. The difference (corifollitropin alfa minus rFSH) in the number of oocytes retrieved was +1.0 (95% CI: 0.5-1.5); vital pregnancy rate: -2.2% (95% CI: -5.3%-0.9%); ongoing pregnancy rate: -1.7% (95% CI: -4.7%-1.4%); and live birth rate: -2.0% (95% CI: -5.0%-1.1%). The odds ratio for overall OHSS was 1.15 (95% CI: 0.82-1.61), and for moderate-to-severe OHSS: 1.29 (95% CI: 0.81-2.05). A single dose of corifollitropin alfa for the first 7 days of ovarian stimulation is a generally well-tolerated and similarly effective treatment compared with daily rFSH. (C) 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Background: There is a paucity of data evaluating the efficacy of vaginal progesterone replacement in both fresh and frozen transfers of recipients of oocyte donors. Method: This was a multicenter, IRB approved, retrospective analysis from January 2009 through June 2013 of 255 cycles among women less than 55 years of age who were oocyte recipients in an anonymous donor program. Oocyte recipients from fresh and frozen cycles received vaginal progesterone gel (Crinone 8%) 90 mg twice daily and oral estradiol 2 mg 2–3 times daily in a step-up protocol. The comparative groups of fresh and frozen donor oocyte cycles took progesterone intramuscular 50 mg once a day, 5 days prior to transfer, Progesterone 200 mg vaginal capsule beginning the day of transfer and Estrogen 2 mg orally three times daily continuing until the tenth week of pregnancy. Subjects were monitored via transvaginal ultrasound, serum estradiol and progesterone levels, both on baseline and the week prior to transfer. A serum beta-hCG, estradiol, and progesterone were obtained 10 days after Blastocyst transfer. Hormone levels and pregnancy rates were summarized with descriptive statistics. Results: It was showed that the fertility interventions did not significantly differ with regard to number of positive pregnancy tests, χ²(3)=4.41, p=0.220. Results also showed that the fertility interventions did not significantly differ with regard to number of clinical pregnancies, χ²(3)=4.68, p=0.196. Conclusion: Preparing the endometrium with oral estradiol and vaginal progesterone gel among recipients treated in a contemporary donor oocyte program is highly effective.

Objective: To compare corifollitropin alfa with recombinant FSH treatment in terms of the vital pregnancy rate in older patients undergoing IVF.Design: Phase 3 randomized, double-blind, noninferiority trial.Setting: Multicenter trial.Patient(s): A total of 1,390 women aged 35-42 years.Intervention(s): A single injection of 150 mu g of corifollitropin alfa or daily 300 IU of recombinant FSH for the first 7 days then daily recombinant FSH until three follicles reach >= 17 mm in size. Ganirelix was started on stimulation day 5 up to and including the day of recombinant hCG administration. If available, two good quality embryos were transferred on day 3.Main Outcome Measure(s): Vital pregnancy rate (PR), number of oocytes, and live birth rate.Result(s): Vital PRs per started cycle were 23.9% in the corifollitropin alfa group and 26.9% in the recombinant FSH group, with an estimated difference (95% confidence interval) of -3.0% (-7.4 to 1.4). The mean (SD) number of recovered oocytes per started cycle was 10.7 (7.2) and 10.3 (6.8) in the corifollitropin alfa and the recombinant FSH groups, respectively, with an estimated difference of 0.5 (-0.2 to 1.2). The live birth rates per started cycle were 21.3% in the corifollitropin alfa group and 23.4% in the recombinant FSH group, with an estimated difference (95% confidence interval) -2.3% (-6.5 to 1.9). The incidence of serious adverse events was 0.4% versus 2.7% in the corifollitropin alfa and recombinant FSH groups, respectively, and of ovarian hyperstimulation syndrome (OHSS; all grades) was 1.7% in both groups.Conclusion(s): Treatment with corifollitropin alfa was proven noninferior to daily recombinant FSH with respect to vital PRs, number of oocytes retrieved, and live birth rates, and was generally well tolerated. (C)2015 by American Society for Reproductive Medicine.

ART has evolved over time and frozen-thawed embryo transfer (FET) is now a frequently performed, successful option. During the last decade, cryopreservation techniques have received considerable interest, whereas interest in the priming and preparation of the endometrium prior to and after embryo transfer was more limited. The available evidence for the rationale and timing of progesterone supplementation as well as an understanding of the differences among progesterone formulations with respect to efficacy, optimum use, and patient preference is worth examining. A Summit was convened to review the literature on progesterone supplementation in ART and after FET and to provide guidance on the most clinically relevant issues. Utilizing an innovative consensus-building model to examine the evidence, Summit faculty drafted summit statements prior to the meeting, completed a literature search, and created a presentation based on this. At the conclusion of their discussion the faculty developed final summit statements, evaluating the strength of the evidence supporting each statement, and rating their level of support for each statement. The clinically relevant topic areas were the rationale for progesterone supplementation, timing and appropriate dosing, whether progesterone sérum levels reflect outcomes, and distinguishing among progesterone formulations with respect to efficacy, tolerability, and patient preference/satisfaction.

Computer-automated time-lapse analysis has been shown to improve embryo selection by providing quantitative and objective information to supplement traditional morphology. In this multi-centre study, the relationship between such computer-derived outputs (High, Medium, Low scores), embryo implantation and clinical pregnancy were examined. Data were collected from six clinics, including 205 patients whose embryos were imaged by the Eeva(TM) System. The Eeva scores were blinded and not considered during embryo selection. Embryos with High and Medium scores had significantly higher implantation rates than those with Low scores (37% and 35% versus 15%; P < 0.0001; P = 0.0004). Similar trends in implantation rates were observed in different IVF centres each using their own protocols. Further analysis revealed that patients with at least one High embryo transferred had significantly higher clinical pregnancy rates than those with only Low embryos transferred (51% versus 34%; P = 0.02), although patients' clinical characteristics across groups were comparable. These data, together with previous research and clinical studies, confirm that computer-automated Eeva scores provide valuable information, which may improve the clinical outcome of IVF procedures and ultimately facilitate the trend of single embryo selection.

Objective: To assess the first computer-automated platform for time-lapse image analysis and blastocyst prediction and to determine how the screening information may assist embryologists in day 3 (D3) embryo selection.Design: Prospective, multicenter, cohort study.Setting: Five IVF clinics in the United States.Patient(s): One hundred sixty women >= 18 years of age undergoing fresh IVF treatment with basal antral follicle count >= 8, basal FSH < 10 IU/mL, and >= 8 normally fertilized oocytes.Intervention(s): A noninvasive test combining time-lapse image analysis with the cell-tracking software, Eeva (Early Embryo Viability Assessment), was used to measure early embryo development and generate usable blastocyst predictions by D3.Main Outcome Measure(s): Improvement in the ability of experienced embryologists to select which embryos are likely to develop to usable blastocysts using D3 morphology alone, compared with morphology plus Eeva.Result(s): Experienced embryologists using Eeva in combination with D3 morphology significantly improved their ability to identify embryos that would reach the usable blastocyst stage (specificity for each of three embryologists using morphology vs. morphology plus Eeva: 59.7% vs. 86.3%, 41.9% vs. 84.0%, 79.5% vs. 86.6%). Adjunctive use of morphology plus Eeva improved embryo selection by enabling embryologists to better discriminate which embryos would be unlikely to develop to blastocyst and was particularly beneficial for improving selection among good-morphology embryos. Adjunctive use of morphology plus Eeva also reduced interindividual variability in embryo selection.Conclusion(s): Previous studies have shown improved implantation rates for blastocyst transfer compared with cleavage-stage transfer. Addition of Eeva to the current embryo grading process may improve the success rates of cleavage-stage ETs. ((c) 2013 by American Society for Reproductive Medicine.)

ObjectiveTo examine the efficacy and safety of a single injection of corifollitropin alfa (CFA) vs daily rFSH for ovarian stimulation in women aged 35–42 years.DesignPhase 3 randomized, double-blind, double-dummy, active-controlled, noninferiority trial.Materials and methods1390 women were randomized and treated at 33 IVF centers in the USA (NCT01144416). During the first 7 days of ovarian stimulation, 694 women received a single injection of 150 μg CFA and 696 were treated with daily 300 IU rFSH. When required, they continued the cycle with daily rFSH (maximally 300 IU) until 3 follicles reached ≥17 mm. Ganirelix acetate (0.25 mg) was started on stimulation day 5 and recombinant human chorionic gonadotropin was given to trigger oocyte maturation. Three days after oocyte pick-up 2 embryos were transferred. The primary end point was vital pregnancy (≥1 fetus with heart activity ≥35 days after embryo transfer) and the predefined noninferiority margin was –8%. Secondary end points included number of oocytes retrieved, ongoing pregnancy rate (≥70 days after embryo transfer), and safety evaluations.ResultsVital pregnancy and ongoing pregnancy rates per started cycle were 23.9% and 22.2% in the CFA group and 26.9% and 24.0% in the rFSH group. The estimated differences and 95% confidence intervals were –3.0% [–7.4 to 1.4] for the vital pregnancy rate and –1.9% [-6.1 to 2.3] for the ongoing pregnancy rate. The mean (standard deviation) number of recovered oocytes was 10.7 (7.2) and 10.3 (6.8) in the CFA and rFSH groups, respectively, with an estimated difference of +0.5 [–0.2 to 1.2] oocytes. The incidence of serious adverse events (SAEs) was 0.4% vs 2.6% in the CFA and rFSH groups, respectively. The incidence of AEs (SAEs) of moderate/severe ovarian hyperstimulation syndrome (OHSS) was 0.7% (0%) vs 1.4% (0.7%), respectively.ConclusionCFA was proven noninferior to rFSH in terms of efficacy and was well tolerated in women aged 35–42 years. ObjectiveTo examine the efficacy and safety of a single injection of corifollitropin alfa (CFA) vs daily rFSH for ovarian stimulation in women aged 35–42 years. To examine the efficacy and safety of a single injection of corifollitropin alfa (CFA) vs daily rFSH for ovarian stimulation in women aged 35–42 years. DesignPhase 3 randomized, double-blind, double-dummy, active-controlled, noninferiority trial. Phase 3 randomized, double-blind, double-dummy, active-controlled, noninferiority trial. Materials and methods1390 women were randomized and treated at 33 IVF centers in the USA (NCT01144416). During the first 7 days of ovarian stimulation, 694 women received a single injection of 150 μg CFA and 696 were treated with daily 300 IU rFSH. When required, they continued the cycle with daily rFSH (maximally 300 IU) until 3 follicles reached ≥17 mm. Ganirelix acetate (0.25 mg) was started on stimulation day 5 and recombinant human chorionic gonadotropin was given to trigger oocyte maturation. Three days after oocyte pick-up 2 embryos were transferred. The primary end point was vital pregnancy (≥1 fetus with heart activity ≥35 days after embryo transfer) and the predefined noninferiority margin was –8%. Secondary end points included number of oocytes retrieved, ongoing pregnancy rate (≥70 days after embryo transfer), and safety evaluations. 1390 women were randomized and treated at 33 IVF centers in the USA (NCT01144416). During the first 7 days of ovarian stimulation, 694 women received a single injection of 150 μg CFA and 696 were treated with daily 300 IU rFSH. When required, they continued the cycle with daily rFSH (maximally 300 IU) until 3 follicles reached ≥17 mm. Ganirelix acetate (0.25 mg) was started on stimulation day 5 and recombinant human chorionic gonadotropin was given to trigger oocyte maturation. Three days after oocyte pick-up 2 embryos were transferred. The primary end point was vital pregnancy (≥1 fetus with heart activity ≥35 days after embryo transfer) and the predefined noninferiority margin was –8%. Secondary end points included number of oocytes retrieved, ongoing pregnancy rate (≥70 days after embryo transfer), and safety evaluations. ResultsVital pregnancy and ongoing pregnancy rates per started cycle were 23.9% and 22.2% in the CFA group and 26.9% and 24.0% in the rFSH group. The estimated differences and 95% confidence intervals were –3.0% [–7.4 to 1.4] for the vital pregnancy rate and –1.9% [-6.1 to 2.3] for the ongoing pregnancy rate. The mean (standard deviation) number of recovered oocytes was 10.7 (7.2) and 10.3 (6.8) in the CFA and rFSH groups, respectively, with an estimated difference of +0.5 [–0.2 to 1.2] oocytes. The incidence of serious adverse events (SAEs) was 0.4% vs 2.6% in the CFA and rFSH groups, respectively. The incidence of AEs (SAEs) of moderate/severe ovarian hyperstimulation syndrome (OHSS) was 0.7% (0%) vs 1.4% (0.7%), respectively. Vital pregnancy and ongoing pregnancy rates per started cycle were 23.9% and 22.2% in the CFA group and 26.9% and 24.0% in the rFSH group. The estimated differences and 95% confidence intervals were –3.0% [–7.4 to 1.4] for the vital pregnancy rate and –1.9% [-6.1 to 2.3] for the ongoing pregnancy rate. The mean (standard deviation) number of recovered oocytes was 10.7 (7.2) and 10.3 (6.8) in the CFA and rFSH groups, respectively, with an estimated difference of +0.5 [–0.2 to 1.2] oocytes. The incidence of serious adverse events (SAEs) was 0.4% vs 2.6% in the CFA and rFSH groups, respectively. The incidence of AEs (SAEs) of moderate/severe ovarian hyperstimulation syndrome (OHSS) was 0.7% (0%) vs 1.4% (0.7%), respectively. ConclusionCFA was proven noninferior to rFSH in terms of efficacy and was well tolerated in women aged 35–42 years. CFA was proven noninferior to rFSH in terms of efficacy and was well tolerated in women aged 35–42 years.

Objective: To compare live birth rates after fresh embryo transfer (ET) and cumulative ongoing pregnancy rates after fresh ET and frozen-thawed (ET) between continents and overall after one treatment cycle with corifollitropin alfa or recombinant FSH.Design: Double-blind, multicenter, randomized controlled trial.Setting: Fourteen centers in North America (NA); 20 in Europe (EU).Patient(s): 804 NA patients and 702 EU patients.Intervention(s): Patients >60 kg received a single dose of corifollitropin alfa or daily rFSH for the first 7 days of controlled ovarian stimulation.Main Outcome Measure(s): Live birth rates.Result(s): Within each continent no differences were noted between the two treatment groups; however, between continents, the cumulative ongoing pregnancy rate and live birth rate were considerably higher in NA than in EU. The live birth rate in NA was 39.2% in both treatment groups compared with 31.5% and 28.8% in EU after corifollitropin alfa and rFSH treatment, respectively. Considering the number of embryos transferred, the live birth rate per ET was still higher in NA than in EU (42.7% v. s 36.8% with corifollitropin alfa and 41.6% vs. 30.9% with rFSH). Overall live birth rates after fresh ET were 35.6% and 34.4% (estimated difference 1.1% [95% confidence interval -3.7-5.8]), and the estimated cumulative live birth rates were 43.4% and 41.3% with corifollitropin alfa and rFSH, respectively.Conclusion(s): Live birth rates and cumulative pregnancy rates were higher in NA than in EU after treatment with either corifollitropin alfa or daily rFSH; both treatment protocols provided equal success rates.ClinicalTrials.gov Identifiers: NCT00703014 and NCT00702273. (Fertil Steril (R) 2012;97:1351-8. (C) 2012 by American Society for Reproductive Medicine.)

Purpose: To compare the incidence of monozygotic twins following blastocyst versus day-3 embryo transfer (ET).

Paulson, Richard J.; Boostanfar, Robert; Saadat, Peyman; Mor, Eliran; Tourgeman, David E.; Slater, Cristin C.; Francis, Mary M.; Jain, John K.

As a result of oocyte donation, women in their sixth decade of life are now able to conceive and carry pregnancies to term. However, little is known about pregnancy outcomes in this population.To describe pregnancy outcomes in women aged 50 years or older who conceived after in vitro fertilization with donor oocytes.Retrospective analysis of cycles conducted at a US university assisted reproduction program during calendar years 1991-2001.Seventy-seven postmenopausal women with no chronic medical conditions (mean [SD] age, 52.8 [2.9] years; range, 50-63 years) who underwent 121 embryo transfer procedures (89 fresh and 32 frozen). Pregnancy outcomes were ascertained by chart review and telephone follow-up.Maternal and neonatal outcomes.There were 55 clinical pregnancies for a total pregnancy rate of 45.5%. The live birth rate was 37.2%. Of the 45 live births, 31 were singletons, 12 were twins, and 2 were triplets, for which the mean (SD) gestational ages at delivery were 38.4 (2.1) weeks, 35.8 (2.8) weeks, and 32.2 weeks, respectively. Mean (SD) birth weights were 3039 g (703 g), 2254 g (581 g), and 1913 g, respectively. Apgar scores at 1 and 5 minutes were 8.2 (0.9) and 9.1 (0.5), respectively. Of singletons, 68% were delivered by cesarean, and all multiples were delivered by cesarean. Mild preeclampsia was noted in 25% of patients and severe preeclampsia in 10%. Gestational diabetes required diet modification in 17.5%, and 2.5% required insulin.Appropriately screened women aged 50 years or older can successfully conceive via oocyte donation and experience similar pregnancy rates, multiple gestation rates, and spontaneous abortion rates as younger recipients. During pregnancy, they appear at increased risk of preeclampsia and gestational diabetes. A majority can expect to deliver via cesarean. However, there does not appear to be any definitive medical reason for excluding these women from attempting pregnancy on the basis of age alone.

Purpose: To determine prognostic significance of blastomere number on Day 3 of culture upon subsequent blastocyst (BL) development.