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. 2017 Jun 1;12(6):e0178720. doi: 10.1371/journal.pone.0178720

Table 1. Characteristics of included randomized controlled studies.

Study/country/enrollment/incubation and embryo selection of two groups Inclusion criteria/Exclusion criteria Implantation rate/Age (year) (TLI group vs. control group) ART, embryo transfer and oocyte source TLI system and culture characteristics Control group culture characteristicsa Sample size calculation
Studies randomized oocytes
Nakahara 2010/Japan/April 2007 to September 2008/ TLI incubation + conventional selection vs. conventional incubation and selection NR/NR NA/average 36.8 years for all included patients. ICSI; 1–2 embryos for transfer on Day 3; fresh or vitrified embryo transfer not reported; autologous or donation cycles not reported. SANYO In Vitro Live Cell Imaging Incubation System; 37°C,5% CO2 and 95% air atmosphere; embryos were not removed from the incubator for assessment; images were obtained every 15 min. 37°C,5% CO2 and 95% air atmosphere. No sample size calculation.
Cruz 2011/Spain/study duration not reported/ TLI incubation + conventional selection vs. conventional incubation and selection Patients aged 32–45 years old./Patients with pathologies like endometriosis, hydrosalpynx, obesity (BMI>30), uterine pathology, recurrent pregnancy loss, or age >45 years old. NA/not reported Both ICSI and IVF; included both Day 3 and Day 5 embryo transfer; number of transferred embryos not reported; included only donation cycles. EmbryoScope; 37°C, 6% CO2, pH 7.2–7.4; embryos were removed from the incubator for assessment; images were obtained every 20 min. 37°C, 6% CO2, pH 7.2–7.4. Based on blastocyst rate.
Kirkegaard 2012/Denmark/June 2010 to April 2011/ TLI incubation + conventional selection vs. conventional incubation and selection Second or third treatment cycle with a normal fertilization rate (≥50%) and embryo development in the first cycle, age <38 years, ≥8 oocytes retrieved./NR NA/32.2±3.3 years for all included patients. Both ICSI and IVF; 1–2 fresh blastocysts for transfer on Day 5; included autologous cycles only. EmbryoScope; 37°C, 6% CO2, 20% O2; embryos were removed from the incubator for assessment; time interval between image acquisition not reported. 37°C, 6% CO2, 20% O2;. Based on 4-cell proportion among inseminated oocytes.
Wu 2016 (Part B)/USA/December 2014 to March 2015/ TLI incubation + conventional selection vs. conventional incubation and selection NR/NR NA/27.8±1.4 years for all included patients. ICSI; all embryo transfer were carried out on Day 3; number of transferred embryos not reported; fresh or vitrified embryos for transfer not reported; included donation cycles only. EmbryoScope; 37°C,5% CO2, 5% O2 and 90% N2 atmosphere; embryos were not removed from the incubator for assessment; images were obtained every 10 min. 37°C, 5% CO2 and 90% N2. No sample size calculation.
Studies randomized women
Park 2015/Sweden/ May 2010 to February 2014/ TLI incubation + conventional selection vs. conventional incubation and selection Female patient ≤40 years undergoing their first IVF cycle and at least 1 oocyte was retrieved./Patients undergoing egg donation. 27.9% vs. 31.6% (P = 0.32)/31.8±4.3 vs. 31.8±4.1 ICSI; 1–2 fresh embryos for transfer on Day 2 (3.3% patients received 2 embryos) for both groups; included autologous oocytes only. EmbryoScope; 37°C, 6% CO2 and atmospheric O2 concentration; embryos were not removed from the incubator for assessment; images were obtained every 20 min. 37°C, 6% CO2 and atmospheric O2 concentration. Based on good quality embryo on Day 2 rate.
Wu 2016 (Part A)/USA/ December 2014 to March 2015/ TLI incubation + conventional selection vs. conventional incubation and selection Willing to participate (all patients involved were poor prognosis patients)./Patients with no mature oocytes or no fertilization, transfer on D2, IVF cycles, IVF for embryo banking. 9.7% vs. 11.5% (P>1.0)/38.8±1.0 vs. 40.4±1.8 ICSI; all transferrable embryos obtained in a cycle were transferred; fresh embryo transfer on Day 3 for both groups; included autologous oocytes only. EmbryoScope; 37°C, 5% CO2, 5% O2 and 90% N2; embryos were not removed from the incubator for assessment; images were obtained every 10 min. 37°C, 5% CO2 and 90% N2. No sample size calculation.
Kahraman 2013/Turkey/ December 2011 to June 2012/ TLI incubation and selection vs. conventional incubation and selection Patients undergoing their first or second treatment cycle, with no recurrent spontaneous miscarriages, age <35years, BMI <28 Kg/m2, and ≥8 ooocytes retrieved./Patients with severe endometriosis, polycystic ovary syndrome, hydrosalpynx, uterine pathology, or severe male factor and very severe morphological sperm defects. NR/28.5±3.32 vs. 28.5±3.72 ICSI; single Day 5 blastocyst transfer for both groups; included both fresh and vitrified transfers; included autologous oocytes only. EmbryoScope; 37°C, 5% O2, 6% CO2; embryos were not removed from the incubator for assessment; images were obtained every 20 min. 37°C, 5% O2, 6% CO2. Not reported.
Insua 2015/ Spain/February 2012 to July 2013/ TLI incubation and selection vs. conventional incubation and selection Patients aged 20–38 years old, 1st/2nd ICSI cycle, BMI 18–25 Kg/m2./Severe male factor, hydrosalpinx, uterine diseases, endocrinopathies, recurrent pregnancy loss, endometriosis, or patients receiving concomitant medication as a treatment that might interfere with the results of the study. 44.9% vs. 37.1% (P = 0.02) /30.4±5.5 vs. 30.0±5.5 ICSI; 1–2 embryos for transfer on Day 3/5 (74% were Day 3 transfers); included both fresh and vitrified embryo transfers; included both donation and autologous cycles (48% were donation cycles). EmbryoScope; 37°C, 5.5% CO2, atmospheric O2; embryos were not removed from the incubator for assessment; images were obtained every 15–20 min. 37°C, 5.5% CO2, atmospheric O2. Based on clinical pregnancy rate.
Matyas 2015/Hungary/ ongoing (since 2013)/ TLI incubation and selection vs. conventional incubation and selection Patients <36 years with normal ovarian reserve, underwent 1st/2nd cycle, had at least 3 good morphological embryos on day 3 and accepted SET./NR NR/NR IVF; single Day 5 blastocyst transfer for both groups; fresh or vitrified embryos for transfer not reported; included autologous cycles only. PrimoVision; culture characteristics not reported. Same incubator with TLI group. Not reported.
Goodman 2016/USA/March 2014 to May 2015/ TLI incubation and selection vs. TLI incubation + conventional selection Patients aged 18–34 years, accepted fresh cycles, had at least 4 normal fertilized zygotes./Patients had plans to undergo preimplantation genetic testing or underwent IVF for fertility preservation; 51.0% vs. 45.2% (P = 0.21)/33.6±4.0 vs. 33.3±3.9 ICSI for matured oocytes and coincubation with sperm for immature oocytes; 1–3 embryos for transfer on Day 3/5 (more than 75% were Day 5 transfers); included autologous cycles only. EmbryoScope; 37°C, 6% CO2, 5.5% O2; embryos were not removed from the incubator for assessment; images were obtained every 10 min. Same incubator with TLI group; embryos were not removed from the incubator for assessment Based on clinical pregnancy rate.

a All embryos incubated in conventional incubators were removed from incubator for assessment.

ART, assisted reproductive technology; TLI, time-lapse imaging; ICSI, intracytoplasmic sperm injection.

NR, not reported; NA, not available.