Yang 2018.
Methods | Study: completed single‐centre RCT of couples with infertility undergoing IVF and ICSI Country: China Cause and length of infertility: quote: "good prognosis patients". Length of infertility not reported. Oocytes: autologous oocytes Embryo transfer: single embryo transfer; day 3 transfer of embryos in intervention group and day 5 transfer in control group Informed consent: obtained from all participants Total study duration: October 2015 to April 2017 (18 months) Funding sources: study funded by Ferring |
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Participants | A total of 600 couples with infertility undergoing IVF or ICSI with autologous oocytes: 300 couples were randomised to TLS utilising embryo selection software, and 300 couples were randomised to conventional incubation and morphology. In all, 15 couples were excluded from the study for the purpose of modified intention‐to‐treat analysis: 10 in the TLS arm (6 refused day 3 and time‐lapse algorithm; 3 had instrument breakdown; and 1 had an unforeseen medical condition) and 5 in the conventional incubation arm (3 refused day 5 and conventional morphological assessment, and 2 did not receive time‐lapse observation). Age (years, mean ± SD, TLS versus conventional incubation): not reported BMI (kg/m2, mean ± SD, TLS versus conventional incubation): not reported Ethnicity: not reported Inclusion criteria:
Exclusion criteria:
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Interventions | TLS utilising embryo selection software (intervention) Conventional incubation and assessment (control) |
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Outcomes | Live birth per couple randomised (provided following email communication with authors) Miscarriage rate per couple randomised (clinical (gestational sac) pregnancy losses) Clinical pregnancy (defined as presence of gestational sac seen at 4 weeks after embryo transfer) Stillbirth (provided following email communication with authors) |
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Notes | Note differing days of embryo transfer (day 3 for intervention group and day 5 for control). All embryos cultured in TLS to day 3, then control embryos transferred to conventional incubator to day 5. Embryos in control arm evaluated by routine morphological assessment. |
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Risk of bias | ||
Bias | Authors' judgement | Support for judgement |
Random sequence generation (selection bias) | Low risk | Quote: "Patients were randomised in a 1:1 ratio via online‐generated blocks (www.random.org) once they had 2PN (>/=6 normally fertilized oocytes) on Day 1 of the cycle." |
Allocation concealment (selection bias) | Low risk | Quote: "The study investigators (YLL and XYK) created the randomization list and study nurses who were unaware of the study protocol enveloped the randomised allocation in a consecutive order. The investigator (YLL) assessed the patient's eligibility and performed the randomization by opening the sealed envelopes." |
Blinding of participants and personnel (performance bias) All outcomes | High risk | Communication with authors. Quote: "The study was not blinded because study participants and clinic staff were aware of which group they were following" |
Blinding of outcome assessment (detection bias) All outcomes | Low risk | Quote: "clinic staff were not blinded" The outcomes are objective and are therefore unlikely to be influenced by knowledge of the intervention, therefore detection bias deemed as low risk. |
Incomplete outcome data (attrition bias) All outcomes | Low risk | Low number of dropouts, and reasons for attrition given. Quote: "The subject was excluded from the study post‐randomization if she did not undergo fresh transfer due to any unforeseen reason including ovarian hyper‐stimulation or uterine disorder." |
Selective reporting (reporting bias) | Low risk | All study outcomes were published. |
Other bias | High risk | Variation between arms of study in day of transfer (day 3 for intervention and day 5 for control). |
AMA: advanced maternal age
ASRM: American Society for Reproductive Medicine
ART: assisted reproductive technology
βhCG: beta human chorionic gonadotropin
BMI: body mass index
CI: confidence interval
ET: embryo transfer
FSH: follicle‐stimulating hormone
ICSI: intracytoplasmic sperm injection
IU: international units
IVF: in vitro fertilisation
OHSS: ovarian hyperstimulation syndrome
PCOS: polycystic ovarian syndrome
RCT: randomised controlled trial
SD: standard deviation
SET: single embryo transfer
TLS: time‐lapse system
2D: two‐dimensional
3D: three‐dimensional