Improved implantation rates of day 3 embryo transfers with the use of an automated time-lapse-enabled test to aid in embryo selection.

OBJECTIVE: To determine if an automated time-lapse test (TL-test) combined with traditional morphology for embryo selection and day 3 transfer results in improved clinical outcomes. DESIGN: Prospective concurrent-controlled pilot study. SETTING: IVF clinic and laboratory. PATIENT(S): A total of 319 female patients <41 years old, with day 3 embryo transfer, fewer than three failed IVF cycles, and at least four zygotes (2-pronuclear) on day 1. INTERVENTION(S): Automated time-lapse embryo assessment combined with morphologic assessment in the study (test) group compared with morphologic assessment only (control group). MAIN OUTCOME MEASURE(S): Embryo implantation, pregnancy, and multiple pregnancy rates. Subanalysis of implantation potential of embryos based on the TL-test (TL-high vs. TL-low) scores. RESULT(S): Implantation and clinical pregnancy rates were significantly higher in the test group compared with the control group (implantation rates 30.2% vs. 19.0%, clinical pregnancy rates 46.0% vs. 32.1%, respectively). Multiple pregnancy rates were not statistically different (26.7% vs. 18.3%). Test group patients receiving at least one TL-high embryo had significantly higher implantation rates than patients receiving only TL-low embryos (36.8% vs. 20.6%). TL-high compared with TL-low embryos had significantly higher implantation rates (44.7% vs. 20.5%). Among morphologically good embryos, TL-high embryos were more likely to implant than TL-low embryos (44.1% vs. 20.6%). CONCLUSION(S): This is the first report demonstrating improved implantation rates in patients receiving day 3 embryo transfers based on the combined use of a TL-test along and traditional morphology. Our findings confirm that the noninvasive TL-test adds valuable information to traditional morphologic grading. CLINICAL TRIAL REGISTRATION NUMBER: NCT01671657.

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.

Relationship between reproductive history, anthropometrics, lifestyle factors, and the likelihood of persistent chemotherapy-related amenorrhea in women with premenopausal breast cancer.

OBJECTIVE: To determine the association between patient characteristics at diagnosis of premenopausal breast cancer, including gravidity, parity, age at menarche, age at first birth, alcohol use, smoking history, weight, height, and body mass index (BMI), with the development of persistent chemotherapy-related amenorrhea (CRA) in follow-up. DESIGN: Retrospective cohort study. SETTING: Dana Farber Cancer Institute and Brigham and Women's Hospital. PATIENT(S): Premenopausal women with breast cancer. INTERVENTION(S): We identified all premenopausal women who received standard adjuvant chemotherapy during 1997-2005 for whom menstrual data were available. Multivariable logistic regression models evaluating persistent amenorrhea at ≥6 month after completion of chemotherapy were conducted. MAIN OUTCOME MEASURE(S): Persistent chemotherapy-related amenorrhea (CRA) at ≥6 months from completion of chemotherapy. RESULT(S): A total of 431 women met eligibility criteria and had ≥6-months' follow-up. Women with older (>13 years) vs. younger (12-13 years) age at menarche were more than twice as likely to remain amenorrheic. Current smokers had 2.4 greater odds of CRA vs. never smokers, although this association was not statistically significant (95% confidence interval, 0.86-6.75). CONCLUSION(S): Few identifiable factors contribute to the variability in CRA among premenopausal women after adjuvant chemotherapy for breast cancer. Further research to improve the prediction of CRA, premature menopause, and infertility in young breast cancer survivors is warranted.

Menopausal symptoms and fertility concerns in premenopausal breast cancer survivors: a comparison to age- and gravidity-matched controls.

OBJECTIVE: Many young breast cancer survivors experience menopausal symptoms and feel concerned about infertility due to oncologic treatment. However, there has been little research to date comparing young survivors' concerns and symptoms with those of young women of the same age and gravidity in the general population. METHODS: We surveyed breast cancer survivors with regular menses after adjuvant chemotherapy and compared them with age-matched, gravidity-matched controls as part of a study to evaluate the effects of chemotherapy on ovarian reserve. All survivors were 1 year or more from diagnosis of early-stage breast cancer, without evidence of recurrence. The survey assessed menopausal symptoms and infertility concerns. RESULTS: The study was stopped after a planned interim analysis of the first 20 matched pairs revealed significantly diminished measures of ovarian reserve in survivors compared with controls. Mean age was 37 years for both groups(range, 31-43 y). Eighty percent of survivors and 25% of controls expressed some concern regarding fertility at the time of the survey (P = 0.001). Survivors were more likely to report bothersome menopausal symptoms than were controls (P = 0.05). An exploratory analysis revealed that menopausal symptoms were greatest in the survivor staking tamoxifen. CONCLUSIONS: Young women who remained premenopausal after breast cancer chemotherapy expressed greater concern about fertility and reported more menopausal symptoms than did age- and gravidity-matched controls. This may have been due to cancer diagnosis or treatment, or it may reflect other differences between the survivors and controls in this study. Additional research is warranted to determine how to most effectively address fertility concerns and reduce symptom burden in this population.

The effects of paclitaxel, dose density, and trastuzumab on treatment-related amenorrhea in premenopausal women with breast cancer.

BACKGROUND: Little information is available regarding the effects of new adjuvant treatment regimens on menstrual functioning in premenopausal women with early breast cancer. METHODS: The authors conducted a retrospective review of data from premenopausal women who received treatment for early breast cancer to evaluate the rates of amenorrhea in follow-up. The women who were included received treatment with either doxorubicin and cyclophosphamide (AC) or combined AC and paclitaxel (T) (AC-T) given either every 3 weeks, or as a dose-dense (DD) regimen, or as AC followed by weekly T with trastuzumab or followed by trastuzumab (AC-T+trastuzumab). A multivariate logistic regression analysis was conducted to evaluate amenorrhea during follow-up. RESULTS: Of 431 patients who were eligible for analysis, the average age at diagnosis was 13 years (range, 25-55 years), 61% of women received AC only, and 39% received AC-T. Of the 39% who received AC-T, 49% of women received DD therapy, 14% received AC-T+trastuzumab, and 71% of all patients received tamoxifen (TAM). The median follow-up was 33 months (range, 6-114 months). After adjusting for age, weight, gravidity, parity, age at menarche, smoking, alcohol use, TAM use, type and regimen of chemotherapy, and use of trastuzumab, the likelihood of remaining amenorrheic was not statistically different in patients who received AC-T versus AC (odds ratio [OR], 1.59; 95% confidence interval [CI], 0.8-3.2), DD treatment versus treatment every 3 weeks (OR, 0.56; 95% CI, 0.25-1.3), or AC-T + trastuzumab (OR, 0.6; 95% CI, 0.22-1.61). Amenorrhea was associated significantly with TAM use and age at diagnosis. CONCLUSIONS: Recent advances in the adjuvant treatment of early breast cancer do not appear to have increased the risk of amenorrhea in premenopausal women.

Geographic distribution of reproductive endocrinology and infertility (REI) fellowships in the United States.

OBJECTIVE: To examine in detail the geographic distribution of reproductive endocrinology and infertility (REI) fellowships in the United States. DESIGN: Ecological. SETTING: University-based REI fellowship program. PATIENT(S): None. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Number and location of REI fellowship positions. RESULT(S): A significant association was found between the number of REI fellowship positions and the number of categorical postgraduate year-1 (PGY-1) obstetrics and gynecology (OBGYN) residency positions within states. No association was observed among the land area, population, or population density within states. However, despite the fact that in the East, as in the United States overall, there was no association between population density and number of fellowships, West of the Mississippi River, as the population density increased, the number of REI fellowships increased linearly (test for heterogeneity = 0.007). CONCLUSION(S): First-year REI fellowship positions in the United States are correlated with the number of categorical PGY-1 OBGYN residency positions within a state. The geographically uneven distribution of fellowship positions may limit the choices for OBGYN residents wishing to pursue further training in REI.

Assessment of United States fertility clinic websites according to the American Society for Reproductive Medicine (ASRM)/Society for Assisted Reproductive Technology (SART) guidelines.

OBJECTIVE: To evaluate SART-member fertility clinic websites for their compliance with the 2004 ASRM/SART guidelines for advertising (which is deemed mandatory for clinic membership), to survey the general characteristics of the websites, and to assess differences between academic and private clinic websites. DESIGN: Cross-sectional evaluation. SETTING: The Internet. PATIENTS: None. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Eleven objective criteria based on 2004 ASRM/SART guidelines for advertising and eight objective criteria for general characteristics of fertility clinic websites. RESULTS: All 384 SART-registered clinics were evaluated; 289 (75.3%) had functional websites (211 private, 78 academic). Success rates were published on 51% of websites (117 private, 31 academic), the majority of which were private clinics (p=.025). The percentage of fertility clinic websites adhering to ASRM/SART guidelines was low in all categories (ranging from 2.8%-54.5% in private centers and 1.3%-37.2% in academic centers). No statistically significant difference was found in the services offered at private versus academic clinics. CONCLUSION: A significant proportion of SART-member fertility clinics, both private and academic, that have websites are not following the ASRM/SART guidelines for advertising. Increased dissemination and awareness of the guidelines is warranted.