Embryo selection using time-lapse analysis (Early Embryo Viability Assessment) in conjunction with standard morphology: a prospective two-center pilot study.

STUDY QUESTION: Does prospective embryo selection using the results from the Eava Test (Early Embryo Viability Assessment) in combination with standard morphology increase the pregnancy rate of IVF and ICSI patients compared to embryo selection based on morphology only? SUMMARY ANSWER: Embryo selection using the Eeva Test plus standard morphology on Day 3 results in comparable pregnancy rates as conventional morphological embryo selection. WHAT IS KNOWN ALREADY: Time-lapse monitoring of embryo development may represent a superior way to culture and select embryos in vitro. The Eeva Test records the development of each embryo with a cell-tracking system and predicts the likelihood (High, Medium or Low) that an embryo will form a blastocyst based on an automated analysis of early cell division timings. STUDY DESIGN, SIZE, DURATION: This trial was designed as a prospective, observational, two-center pilot study with a propensity matched control group. The analysis involved 280 of 302 enrolled patients who were included in the Eeva Test group in 2013 and 560 control patients who were treated in the years 2011-2013. The majority of transfers (98%) were single embryo transfers. PARTICIPANTS/MATERIALS, SETTING, METHODS: Two academic hospitals (VUmc Amsterdam and UZ Gent) enrolled patients <41 years old, with <3 previous attempts and ≥5 normally fertilized eggs. Propensity matching was used to identify a propensity matched control group from a cohort of 1777 patients based on age, cycle number, oocyte number and number of fertilized oocytes. MAIN RESULTS AND THE ROLE OF CHANCE: There was no difference in patient baseline characteristics between the two groups. The ongoing pregnancy rate (OPR) of patients enrolled in the Eeva Test group (34.3%; 96/280) did not differ significantly from the OPR in the propensity matched control group (34.6%, 194/560; P = 0.92). However, significantly less top quality embryos (eight-cell embryos with ≤25% fragmentation) were transferred in the Eeva Test group compared to the propensity matched control group (70.4% vs. 82.3%; P < 0.001). The transfer of Eeva High and Medium embryos resulted in a significantly higher OPR of 36.8% (89/242) compared to 18.4% (7/38) for Eeva Low embryos (P = 0.02). LIMITATION, REASONS FOR CAUTION: This pilot study is limited by its nonrandomized design with a concurrent and historical control. WIDER IMPLICATIONS OF THE FINDINGS: Our pilot data did not reveal significant differences between time-lapse based and conventional embryo selection. Interestingly, the pregnancy rates were comparable in both groups even though the morphological quality of the transferred embryos was significantly lower in the Eeva Test group compared to the propensity matched control group. A sufficiently powered three-armed randomized controlled trial (RCT) with a solid design should be performed to generate decisive evidence in the future. STUDY FINDING/COMPETING INTERESTS: Progyny Inc., formerly Auxogyn provided the Eeva scopes, software and technical support for this study. The funding sources did neither influence data collection, management, analysis and interpretation of the data, nor the preparation of the manuscript. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT01671644.

Predictive value of sperm morphology and progressively motile sperm count for pregnancy outcomes in intrauterine insemination.

OBJECTIVE: To investigate the value of sperm parameters to predict an ongoing pregnancy outcome in couples treated with intrauterine insemination (IUI), during a methodologically stable period of time. DESIGN: Retrospective, observational study with logistic regression analyses. SETTING: University hospital. PATIENT(S): A total of 1,166 couples visiting the fertility laboratory for their first IUI episode, including 4,251 IUI cycles. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Sperm morphology, total progressively motile sperm count (TPMSC), and number of inseminated progressively motile spermatozoa (NIPMS); odds ratios (ORs) of the sperm parameters after the first IUI cycle and the first finished IUI episode; discriminatory accuracy of the multivariable model. RESULT(S): None of the sperm parameters was of predictive value for pregnancy after the first IUI cycle. In the first finished IUI episode, a positive relationship was found for ≤4% of morphologically normal spermatozoa (OR 1.39) and a moderate NIPMS (5-10 million; OR 1.73). Low NIPMS showed a negative relation (≤1 million; OR 0.42). The TPMSC had no predictive value. The multivariable model (i.e., sperm morphology, NIPMS, female age, male age, and the number of cycles in the episode) had a moderate discriminatory accuracy (area under the curve 0.73). CONCLUSION(S): Intrauterine insemination is especially relevant for couples with moderate male factor infertility (sperm morphology ≤4%, NIPMS 5-10 million). In the multivariable model, however, the predictive power of these sperm parameters is rather low.

In vitro development of donated frozen-thawed human embryos in a prototype static microfluidic device: a randomized controlled trial.

OBJECTIVE: To compare the development of human embryos in microfluidic devices with culture in standard microdrop dishes, both under static conditions. DESIGN: Prospective randomized controlled trial. SETTING: In vitro fertilization laboratory. PATIENT(S): One hundred eighteen donated frozen-thawed human day-4 embryos. INTERVENTION(S): Random allocation of embryos that fulfilled the inclusion criteria to single-embryo culture in a microfluidics device (n = 58) or standard microdrop dish (n = 60). MAIN OUTCOME MEASURE(S): Blastocyst formation rate and quality after 24, 28, 48, and 72 hours of culture. RESULT(S): The percentage of frozen-thawed day-4 embryos that developed to the blastocyst stage did not differ significantly in the standard microdrop dishes and microfluidic devices after 28 hours of culture (53.3% vs. 58.6%) or at any of the other time points. The proportion of embryos that would have been suitable for embryo transfer was comparable after 28 hours of culture in the control dishes and microfluidic devices (90.0% vs. 93.1%). Furthermore, blastocyst quality was similar in the two study groups. CONCLUSION(S): This study shows that a microfluidic device can successfully support human blastocyst development in vitro under static culture conditions. Future studies need to clarify whether earlier stage embryos will benefit from the culture in microfluidic devices more than the tested day-4 embryos because many important steps in the development of human embryos already take place before day 4. Further improvements of the microfluidic device will include parallel culture of single embryos, application of medium refreshment, and built-in sensors. DUTCH TRIAL REGISTRATION NUMBER: NTR3867.

Day 3 embryo selection by metabolomic profiling of culture medium with near-infrared spectroscopy as an adjunct to morphology: a randomized controlled trial.

STUDY QUESTION: Is the selection of a single Day 3 embryo by metabolomic profiling of culture medium with near-infrared (NIR) spectroscopy as an adjunct to morphology able to improve live birth rates in IVF, compared with embryo selection by morphology alone? SUMMARY ANSWER: The live birth rate after embryo selection by NIR spectroscopy and morphology is not significantly different compared with the live birth rate after embryos were selected by morphology alone. WHAT IS KNOWN ALREADY: The elevated incidence of pregnancy and neonatal problems associated with a high-twinning rate after IVF can only be successfully reduced by the transfer of one embryo. Current embryo assessment methods are unable to accurately predict the reproductive potential of an individual embryo. Today, a number of techniques are said to be more accurate at selecting the best embryo. One of these new technologies is metabolomic profiling of spent embryo culture media with the use of NIR spectroscopy. STUDY DESIGN, SIZE AND DURATION: A double-blind, randomized controlled trial was conducted between 2009 and 2011, and included 417 couples undergoing IVF with a single embryo transfer. Randomization was performed centrally just before Ovum Pick-Up (OPU), using a computerized randomization program. Both patient and physician were unaware of the treatment allocation. To ensure blinding, the allocations were placed in consecutively numbered, opaque envelopes. Patients were randomized (1:1) into either the control group (embryo selection by morphology only) or the treatment group (embryo selection by morphology plus NIR spectroscopy of embryo culture medium). PARTICIPANTS/MATERIALS, SETTING AND METHODS: At OPU, 208 patients were randomized to the morphology only group and 209 patients were randomized to the morphology plus viability score group. On Day 3, 163 patients in the control group and 146 patients in the treatment group met the inclusion criteria. The study was conducted in an academic hospital with IVF laboratory and three non-academic hospitals. MAIN RESULTS AND THE ROLE OF CHANCE: Patient demographics and baseline characteristics were distributed equally over the two groups, except for embryo fragmentation, which was significantly higher in the treatment group. In the intention to treat analysis, the live birth rates were 31.7 and 26.8% for the control group and the treatment group, respectively (relative risk 0.84; 95% confidence interval 0.63-1.14, P=0.27). In the per protocol analysis, the live birth rates were 31.3 and 29.5% for the control group and the treatment group, respectively (relative risk 0.94; 95% confidence interval 0.67-1.32, P=0.73). For the treatment group, the embryological technician's independent choice (by morphology) of which embryo to transfer was recorded 138 times. In 75.4% (104 of 138) of the transfers, the embryo with the best morphology did not have the highest viability score. The live birth rate of these 104 transferred embryos was 30.8%. LIMITATIONS, REASONS FOR CAUTION: A possible limitation of our study is the pre-selection of all embryos by morphology and dividing the cohort of available embryos into two groups: good quality embryos and poor quality embryos. As a consequence, we have probably selected for a better prognosis patient group. WIDER IMPLICATIONS OF THE FINDINGS: To avoid the use of incompetent embryo selection tools at the expense of the patient, an evidence-based proof of clinical usefulness is essential before the implementation of new diagnostic tools in IVF laboratories. TRIAL REGISTRATION NUMBERS: Dutch Trial Registry, registry number NTR1178.