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. 2019 May 29;2019(5):CD011320. doi: 10.1002/14651858.CD011320.pub4

Kahraman 2013.

Methods Study: completed single‐centre RCT of couples with infertility undergoing ICSI
Country: Turkey
Cause and length of infertility: tubo‐peritoneal factor. Length of infertility not reported.
Oocytes: autologous oocytes
Embryo transfer: single embryo transfer at blastocyst
Informed consent: yes
Total study duration: December 2011 to June 2012 (6 months)
Funding sources: none
Participants A total of 76 couples with infertility undergoing ICSI with autologous oocytes were recruited: 38 were randomised to TLS and 38 were randomised to conventional incubation.
In all, 12 couples withdrew from the study: 7 in the conventional incubation arm and 5 in the TLS arm.
Reasons for withdrawal were documented and data for outcomes such as live birth, adverse events, and clinical pregnancy for these couples were included in this review.
Age (years, mean ± SD, TLS versus conventional incubation): 28.5 ± 3.32 versus 28.5 ± 3.72; P = 0.83
BMI (kg/m2, mean ± SD, TLS versus conventional incubation): 23.92 ± 3.79 versus 23.92 ± 4.42; P = 0.77
Ethnicity: not reported
Inclusion criteria:
  • first or second treatment cycle;

  • age < 35 years, BMI < 28 kg/m2;

  • ≥ 8 oocytes retrieved.


Exclusion criteria:
  • recurrent spontaneous abortions;

  • severe endometriosis;

  • PCOS;

  • hydrosalpinx;

  • uterine pathology;

  • severe male factor (< 5 million motile sperm in total ejaculate);

  • very severe morphological sperm defects (dominantly globozoospermic or macrocephalic samples).

Interventions TLS with conventional morphological assessment of still TLS images (intervention)
Conventional incubation and assessment (control)
Outcomes Live‐birth rates per couple randomised
Clinical pregnancy rate per couple randomised (clinical pregnancy was defined as the presence of a gestational sac detected on ultrasound 3 weeks after the first βhCG test, which was performed 14 days after oocyte retrieval)
Stillbirth and miscarriage per couple randomised
Notes Live‐birth and stillbirth information was available following communication with the author and was not published.
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Low risk Quote: "Computer based randomization list"
Quote: "Randomisation was done according to a list generated on random.org"
Allocation concealment (selection bias) Low risk Communication with author. Quote: "Randomization list was held by one of the investigators who was not involved clinically with the patients. Also, he was not routinely working in the embryology laboratory. The randomization from random.org was printed out into sequentially numbered lists where the groups were masked and not revealed until the recruitment of each patient"
Blinding of participants and personnel (performance bias) 
 All outcomes High risk Communication with author. Quote: "Clinicians were blinded in the study up to the point after the embryo transfer was performed. Also the patients did not know to which group they were allocated. Only the discontinued patients received information about the incubation process once the drop‐out decision was made (Due to the need to inform the patients about their early/cancelled transfers)". It was impossible to blind the embryologist, therefore performance bias deemed high risk.
Blinding of outcome assessment (detection bias) 
 All outcomes Low risk Communication with author. Quote: "Clinicians, those assessing the outcome were not necessarily blinded to the intervention as some of our ART patients prefer to have those controls outside our clinic and report the outcomes to us". The outcomes are objective and are therefore unlikely to be influenced by knowledge of the intervention, therefore detection bias deemed low risk.
Incomplete outcome data (attrition bias) 
 All outcomes Low risk A total of 12 couples discontinued the trial following randomisation secondary to adverse events that were not reported as adverse events or analysed within the main publication. However, on communication with the author, the numbers of discontinued participants in each arm were disclosed, alongside reasons for dropouts. Quote: "embryos transferred day 3, 4 and 5 with single blastocyst developed; total freezing because of ovarian hyperstimulation syndrome (OHSS) risk"
Selective reporting (reporting bias) Low risk Communication with author. Quote: "As reported in our article, we have published all of the outcomes we aimed to assess. Unfortunately, we do not formally prepare a study protocol". On contacting the author, data on live birth and adverse events were made available, although this information was not published.
Other bias Low risk None detected.