We reviewed the evidence for time-lapse systems (TLSs) for embryo incubation and embryo assessment for couples undergoing in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI).
Embryo incubation and assessment are vital steps in IVF and ICSI. Traditionally, embryos are removed from a conventional incubator for assessment of quality and stage of development under a light microscope. In this review, we have called that 'conventional incubation'. TLSs can take digital images of embryos at frequent time intervals. This allows assessment of embryos without removing them from the incubator. The use of a TLS often adds a significant extra cost onto an IVF or ICSI cycle. We wanted to determine whether a TLS would improve the chances of a pregnancy and live born baby, and whether a TLS reduces the risk of miscarriage and stillbirth.
The evidence was current to November 2014. The three included studies involved 994 couples; 62 couples were undergoing IVF and the remainder ICSI. These studies took place in Spain, Hungary and Turkey. One study is ongoing but the other studies were 6 and 17 months in duration. Some couples received donor eggs from younger women. Two studies (138 couples) replaced one embryo at a time, at the blastocyst stage; 856 couples had multiple embryos replaced at a time (1.86 per couple on average), at the cleavage stage or blastocyst stage, in the other study. The age of women ranged between 20 and 38 years. One study disclosed that the instrumentation and utensils used were fully paid for by IVI. IVI is a shareholder in UnisenseFertiliTech A/S, a manufacturer of a TLS, but none of the authors had any economic affiliation with UnisenseFertiliTech A/S.
The results did not demonstrate evidence of a difference in the live birth, miscarriage, stillbirth or clinical pregnancy rate per couple randomly assigned to either a TLS or conventional incubation.
Quality of the evidence
The quality of the evidence was moderate or low. This was due to the scarcity of studies, two of which were very small in terms of numbers of participants, with high risk of bias in the largest study.
There is insufficient evidence of differences in live birth, miscarriage, stillbirth or clinical pregnancy to choose between TLS and conventional incubation. Further data explicitly comparing the incubation environment, the algorithm for embryo selection, or both, are required before recommendations for a change of routine practice can be justified.
Embryo incubation and assessment is a vital step in assisted reproductive technology (ART). Traditionally, embryo assessment has been achieved by removing embryos from a conventional incubator daily for assessment of quality by an embryologist, under a light microscope. Over recent years time-lapse systems (TLSs) have been developed which can take digital images of embryos at frequent time intervals. This allows embryologists, with or without the assistance of computer algorithms, to assess the quality of the embryos without physically removing them from the incubator.
The potential advantages of a TLS include the ability to maintain a stable culture environment, therefore limiting the exposure of embryos to changes in gas composition, temperature and movement. Additionally a TLS has the potential advantage of improving embryo selection for ART treatment by utilising additional information gained through monitoring embryo development.
To determine the effect of a TLS compared to conventional embryo incubation and assessment on clinical outcomes in couples undergoing ART.
A comprehensive search of all the major electronic databases, including grey literature, was undertaken in co-ordination with the Trials Search Co-ordinator of the Cochrane Menstrual Disorders and Subfertility Group in July 2014 and repeated in November 2014 to confirm that the review is up to date.
Two authors (SA and NA) independently scanned the titles and abstracts of the articles retrieved by the search. Full texts of potentially eligible randomised controlled trials (RCTs) were obtained and examined independently by the authors for their suitability according to the review inclusion criteria. In the case of doubt between the two authors, a third author (LC) was consulted to gain consensus. The selection process is documented with a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow chart.
Data were obtained and extracted by two authors. Disagreement was resolved by consensus. Trial authors were contacted by e-mail to obtain further study information and data. All extracted data were dichotomous outcomes and odds ratios (OR) were calculated on an intention-to-treat basis. Where enough data were available, meta-analysis was undertaken.
Three studies involving 994 women were found for inclusion. Data from all three studies were used to address comparison one, TLS with or without cell-tracking algorithms versus conventional incubation. No studies were found to address comparison two, TLS utilising cell-tracking algorithms versus TLS not utilising cell-tracking algorithms.
There was only one study which reported live birth (n = 76). The results demonstrated no conclusive evidence of a difference in live birth rate per couple randomly assigned to the TLS and conventional incubation arms of the study (OR 1.1, 95% CI 0.45 to 2.73, 1 RCT, n = 76, moderate quality evidence).
All three studies reported miscarriage (n = 994). There was no conclusive evidence of a difference in miscarriage rates per couple randomly assigned to the TLS and conventional incubation arms (OR 0.70, 95% CI 0.47 to 1.04, 3 RCTs, n = 994, I2 = 0%, low quality evidence).
Only one study reported stillbirth rates (n = 76). There were equal numbers of stillbirths in both the TLS and conventional incubation arms of the study. Therefore, there was no evidence of a difference in the stillbirth rate per couple randomly assigned to TLS and conventional incubation (OR 1.0, 95% CI 0.13 to 7.49, 1 RCT, moderate quality evidence).
All three studies reported clinical pregnancy rates (n = 994). There was no conclusive evidence of a difference in clinical pregnancy rate per couple randomly assigned to the TLS and conventional incubation arms (OR 1.23, 95% CI 0.96 to 1.59, 3 RCTs, n = 994, I2 = 0%, low quality evidence). None of the included studies reported cumulative clinical pregnancy rates.