Rubio 2014.

Methods	Study: completed multicentre RCT of couples with infertility undergoing ICSI Country: Spain Cause and length of infertility: not reported Oocytes: autologous and donor Embryo transfer: multiple embryo transfer (1.86 per couple, 95% CI 1.8 to 1.9) on day 3 and day 5 Informed consent: not reported Total study duration: February 2012 to July 2013 (17 months) Funding sources: the instrumentation, disposables, and utensils used in this study were fully paid for by IVI. IVI is a minor shareholder in Unisense FertiliTech A/S, but none of the authors have any economic affiliation with Unisense FertiliTech A/S.
Participants	A total of 856 couples with infertility undergoing IVF with autologous and donor oocytes: 444 couples were randomised to TLS and 412 to conventional incubation. In all, 13 couples were excluded from the study: 6 in the TLS arm (reasons: 2 had cancelled oocyte donation, and 4 had their embryos vitrified) and 7 in the conventional incubation arm (reasons: 1 woman had endometrial bleeding; 2 had cancelled oocyte donation; and 4 couples had their embryos vitrified). Age (years, mean ± SD, TLS versus conventional incubation): 34.7 ± 2.7 versus 34.6 ± 2.7 BMI (kg/m2, mean ± SD, TLS versus conventional incubation): 23.2 ± 3.7 versus 23.04 ± 2.8 Ethnicity: not reported Inclusion criteria: autologous or oocyte donation. Those receiving oocyte donation had 1 of the following diagnoses: failure to achieve pregnancy after at least 3 cycles of ART, genetic female or chromosomal disorders, or low response to controlled ovarian hyperstimulation. Donors were: aged 18 to 34 years; BMI 18 to 25 kg/m2; had received no endocrine treatment (including gonadotropins and oral contraception) for the last 3 months preceding the study and had a normal uterus and ovaries at transvaginal ultrasound scan (no signs of PCOS). Inclusion criteria for both arms of study: age 20 to 38 years; first or second ICSI cycle; BMI of > 18 and < 25 kg/m2. Exclusion criteria: severe male factor (total motile sperm < 1 million); hydrosalpinx; presenting uterine diseases after 2D ultrasound evaluation and/or 3D (if in doubt) or hysteroscopy (for acquired or congenital uterine abnormalities); endocrinopathies (thrombophilia); recurrent pregnancy losses; endometriosis; patients receiving concomitant medications as a treatment for any other condition that might interfere with the results of the study. For autologous oocyte patients: low‐responder patients (fewer than 6 metaphase II per cycle) or those with an FSH basal determination > 12 or an anti‐M üllerian hormone concentration of < 1.7 pmol/L (based on authors' own experience) were also excluded.
Interventions	TLS utilising cell‐tracking algorithms (intervention) Conventional incubation and assessment (control)
Outcomes	Miscarriage per couple randomised Clinical pregnancy rate per couple randomised Live birth (obtained from Insua 2015 and Insua 2017)
Notes	October 2015: following clarification from authors of comments on this review, it has been made aware to us that the pregnancy data from this study are a combination of biochemical and ongoing pregnancy, therefore the miscarriage data may also include miscarriages from biochemical pregnancies.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	High risk	Despite adequate random sequence generation, participants were able to request the intervention in some cases, and this was granted. See evidence below: Quote: "Patients were allocated to either TMS (study group) or SI (control group) using a computer generated randomization table which was handled by the embryologist at the laboratory in charge the day before the oocyte retrieval or oocyte donation. The randomization was not perfectly performed as the patient distribution to the two groups would have been expected to be 50:50 ratio than the reported 51.9:48.1. The main reason for this deviation was limited patient requests for TMS culture"
Allocation concealment (selection bias)	High risk	In some cases allocation was non‐random (see above).
Blinding of participants and personnel (performance bias) All outcomes	High risk	Gynaecologist and statistician were blinded. Participants and embryologist were not blinded. Quote: "The study is considered double blind because 1) the gynaecologist (evaluating the primary effect) did not know to which group the patients had been assigned, and 2) the statistician evaluating the results only knew the incubators by a binary code, not by type" Communication with author. Quote: "The intention was to do triple blinded, but we discovered that some of our patients were informed (because they asked) of the group they were in. Therefore blinding failed in some of our patients. We then decided to describe it as double blind because patients blinding partially failed"
Blinding of outcome assessment (detection bias) All outcomes	Low risk	The gynaecologist evaluating the primary effect was blinded.
Incomplete outcome data (attrition bias) All outcomes	Low risk	A total of 13 participants were excluded from study after randomisation as they suffered adverse events (cancelled oocyte donation, embryos vitrified, and endometrial bleeding). Not included in intention‐to‐treat, but all excluded participants were accounted for, therefore low risk of attrition bias.
Selective reporting (reporting bias)	Low risk	Reported all outcomes declared on ClinicalTrials.gov On communication with the author: "We are currently collecting data on live birth and stillbirth"
Other bias	Low risk	None detected.