High gonadotropin dosage does not affect euploidy and pregnancy rates in IVF PGS cycles with single embryo transfer.

STUDY QUESTION: Does high gonadotropin dosage affect euploidy and pregnancy rates in PGS cycles with single embryo transfer? SUMMARY ANSWER: High gonadotropin dosage does NOT affect euploidy and pregnancy rates in PGS cycles with single embryo transfer. WHAT IS KNOWN ALREADY: PGS has been proven to be the most effective and reliable method for embryo selection in IVF cycles. Euploidy and blastulation rates decrease significantly with advancing maternal age. In order to recruit an adequate number of follicles, the average dosage of gonadotropins administered during controlled ovarian stimulation in IVF cycles often increases significantly with advancing maternal age. STUDY DESIGN, SIZE, AND DURATION: A retrospective study of SNP (Single Nucleotide Polymorphism) PGS outcome data from blastocysts biopsied on day 5 or day 6 was conducted to identify differences in euploidy and clinical pregnancy rates. Seven hundred and ninety four cycles of IVF treatment with PGS between January 2013 and January 2017 followed by 651 frozen embryo transfers were included in the study (506 patients, maternal age (y.o.) - 37.2 ± 4.31). PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 4034 embryos were analyzed (5.1 ± 3.76 per case) for euploidy status. All embryos were vitrified after biopsy, and selected embryos were subsequently thawed for a hormone replacement frozen embryo transfer cycle. All cycles were analyzed by total gonadotropin dosage (<3000 IU, 3000-5000 IU and >5000 IU), by number of eggs retrieved (1-5, 5-10, 10-15 and >15 eggs) and patient's age (<35, 35-37, 38-40 and ≥41 y.o.). Clinical pregnancy rate was defined by the presence of a fetal heartbeat at 6-7 weeks of gestation. MAIN RESULTS AND THE ROLE OF CHANCE: Euploidy rates within the same age group were not statistically different regardless of the total dosage of gonadotropins used or the number of eggs retrieved. In the youngest group of patients (<35 y.o. - 187 IVF cycles) euploidy rates ranged from 62.3% (<3000 IU were used in the IVF cycle) to 67.5% (>5000 IU were used in the IVF cycle) (OR = 0.862, 95% CI 0.687-1.082, P = 0.2) and from 69.5% (1-5 eggs retrieved) to 60.0% (>15 eggs retrieved) (OR = 0.658, 95% CI 0.405-1.071, P = 0.09). Similar data were obtained in the oldest group of patients (≥41 y.o. - 189 IVF cycles): euploidy rates ranged from 30.7 to 26.4% (OR = 0.811, 95% CI 0.452-1.454, P = 0.481) when analyzed by total dosage of gonadotropins used in the IVF cycle and from 40.0 to 30.7% (OR = 0.531, 95% CI 0.204-1.384, P = 0.19), when assessed by the total number of eggs retrieved. Ongoing pregnancy rates were similar, not only within particular age groups, but also between different age groups regardless of the total dosage of gonadotropins used: ranging from to 63.6% (<3000 IU, < 35 y.o.) to 54.8% (>5000 IU, ≥41 y.o) (OR = 0.696, 95% CI 0.310-1.565, P = 0.38). LIMITATIONS, REASONS FOR CAUTION: Retrospective study and heterogeneity of patients included. WIDER IMPLICATIONS OF THE FINDINGS: These data are reassuring for the common practice of increasing gonadotropin dosages in PGS cycles, particularly in older woman. STUDY FUNDING/COMPETING INTEREST(S): No formal funding has been received for this study. TRIAL REGISTRATION NUMBER: N/A.

Association between growth dynamics, morphological parameters, the chromosomal status of the blastocysts, and clinical outcomes in IVF PGS cycles with single embryo transfer.

PURPOSE: The purpose of the present study is to examine interconnection between speed of embryo development, the genetic status of the blastocysts, and clinical outcomes in IVF preimplantation genetic screening (PGS) cycles with single embryo transfer (SET). METHODS: The retrospective comparative study has been performed between January 2013 and January 2016. Seven hundred thirty-seven cycles of IVF treatment with PGS, followed by 503 SETs, were included in the study. Normally fertilized oocytes were hatched on day 3, were cultured to the blastocyst stage, and were biopsied only when at least three to seven cells were herniating from zona pellucida on the morning of day 5 (≤118 h) or day 6 (≥139 h). A total of 3705 embryos were analyzed for euploidy rates and blastocyst morphology. All embryos were vitrified after the biopsy, and selected embryos were subsequently thawed for a hormone replacement frozen embryo transfer cycle. RESULTS: The euploidy rate was significantly higher among embryos biopsied on day 5 versus day 6: 59.44 ± 4.1 and 48.19 ± 3.8, respectively, p < 0.05. The difference in euploidy rates between embryos biopsied on day 5 versus day 6 in matched age groups increased from 5.83 to 25.46% with advancing maternal age. Our data demonstrated no statistically significant difference in euploidy rates between good-quality embryos biopsied on day 5 in the group of patients <38 years old and embryos in PGS cycles using donor oocytes: 71.12% (336/472) and 75.68% (221/292), respectively, p = 0.174, χ 2 = 1.848. In 270 out of 503 SETs, transferred embryos were biopsied on day 5 (ongoing pregnancy rate was 64.6% in a group of patients <38 years old, and in a group of patients ≥38 years old, ongoing PR was 64.2%). In 233 out of 503 cycles, transferred embryos were biopsied on day 6 (ongoing PR was 46.6% in a group of patients <38 years old, and in a group of patients ≥38 years old, ongoing PR was 50.8%). In all study groups, the ongoing pregnancy rate was higher when the transferred embryo was available for biopsy on day 5. CONCLUSIONS: Good- and fair-quality embryos available for biopsy on day 5 have higher euploidy rates and have a higher chance to result in an ongoing pregnancy. Euploidy rate has significant variations within the same age group depending on the morphology of the blastocysts.

Computer-automated time-lapse analysis results correlate with embryo implantation and clinical pregnancy: a blinded, multi-centre study.

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.

The in vitro fertilization laboratory: teamwork and teaming.

Delivery of fertility treatment involves both teamwork within a discipline as well as teaming across multiple work areas, such as nursing, administrative, laboratory, and clinical. In contrast to small autonomous centers, the in vitro fertilization (IVF) laboratory team in large clinics must function both as a team with many members and a constellation of teams to deliver seamless, safe, and effective patient-centered care. Although this review primarily focuses on teamwork within the IVF laboratory, which comprises clinical laboratory scientists and embryologists who perform both diagnostic and therapeutic procedures, it also discusses the laboratory's wider role with other teams of the IVF clinic, and the role of teaming (the ad hoc creation of multidisciplinary teams) to function highly and address critical issues.

Atypical embryo phenotypes identified by time-lapse microscopy: high prevalence and association with embryo development.

OBJECTIVE: To characterize atypical dynamic embryo phenotypes identified by time-lapse microscopy, evaluate their prevalence, and determine their association with embryo development. DESIGN: Retrospective multicenter cohort study. SETTING: Five IVF clinics in the United States. PATIENT(S): Sixty-seven women undergoing IVF treatment with 651 embryos. INTERVENTION(S): Embryo videos were retrospectively analyzed for atypical phenotypes. MAIN OUTCOME MEASURE(S): Identification of four groups of atypical embryo phenotypes: abnormal syngamy (AS), abnormal first cytokinesis (A1(cyt)), abnormal cleavage (AC), and chaotic cleavage (CC). Prevalence and association with embryo morphology and development potential were evaluated. RESULT(S): A high prevalence of atypical phenotypes was observed among embryos: AS 25.1% (163/649), A1(cyt) 31.0% (195/639), AC 18% (115/639) and CC 15% (96/639). A high percentage of embryos with atypical phenotype(s) had good quality on day 3 (overall grade good or fair): AS 78.6% (70/89); A1(cyt) 79.7% (94/119), AC 86.4% (70/81), and CC 35.2% (19/54), but the blastocyst formation rates for these embryos were significantly lower compared with their respective control groups: AS 21.5% vs. 44.9%, A1(cyt) 21.7% vs. 44.6%, AC 11.7% vs. 43.1%, and CC 14.0% vs. 42.3%. CONCLUSION(S): Embryos exhibiting atypical phenotypes are highly prevalent in human embryos and show significantly lower developmental potential than control embryos. CLINICAL TRIAL REGISTRATION NUMBER: NCT01369446.

Improving embryo selection using a computer-automated time-lapse image analysis test plus day 3 morphology: results from a prospective multicenter trial.

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.