Ben‐Rafael 1995

Methods	Parallel randomised controlled trial Prospective participant recruitment Consecutive participant sampling Multi‐centre trial in the Hasharon Hospital of the Rabin Medical Center and in the Sackler School of Medicine of Tel Aviv University in Israel Inclusion criteria: at least three embryos ready for transfer and no more than three previous treatment cycles Exclusion criteria: fewer than three embryos ready for transfer No power calculation was performed Participants were included in the trial with only one treatment cycle Participants were recruited over a period of six months Length of follow‐up per participant was until delivery No intention‐to‐treat analysis was performed Study was not supported by any commercial funding sources
Participants	Age (years): mean 34.2, SD 4.9 Patients were admitted for oocyte retrieval if two or more follicles of at least 18 mm mean diameter were present and the hormone profile was satisfactory Not reported whether primary or secondary subfertility Causes of subfertility were mechanical, male subfertility and combined causes. Duration of subfertility ranged from three to 21 years (mean 8.3 ± 6.9) Previous IVF or ICSI was not reported, although participants could have had no more than three previous cycles Participants underwent IVF Age analysis: subgroups of < 31 years, 31 to 38 years and 39 to 42 years 211 patients who were admitted to the IVF unit were recruited for the trial, and all were randomly assigned: 101 to the treatment group and 110 to the control group. In total, 759 embryos were transferred: 368 in the treatment group and 391 in the control group. No participants were lost to follow‐up, so 211 participants were analysed
Interventions	Embryo transfer using a two‐component fibrin sealant versus transfer in regular medium, consisting of EBSS‐P‐SR2 with 10 mg/ml human serum albumin, manufactured by MediCult. The fibrin sealant was made of two components. The first consisted of fibrinogen, fibronectin and an aprotinin solution. The second component consisted of thrombin and a calcium chloride solution The sealant was manufactured by Immuno AG Randomisation was performed between fertilisation check and day of embryo transfer Exposure time to fibrin sealant was not stated Timing of transfer was early in embryo development, 48 to 50 hours after oocyte retrieval Inclusion of oocyte donations was unclear Unclear whether embryos were frozen‐thawed or fresh Two different culture and transfer medium brands: MediCult (culture medium and transfer medium control group) and Immuno AG (treatment group) Mean number of embryos transferred: treatment group 3.64, control group 3.55 Method of pregnancy determination: demonstration of gestational sac on ultrasound scan
Outcomes	Secondary outcomes Clinical pregnancy rate: stated as percentage with number of transferred embryos as denominator Adverse event rate: number of ectopic pregnancies, stated per participant Additional outcomes Implantation rate: stated as percentage of implantations from total number of embryos transferred
Notes	Additional data were retrieved after contact with the original investigators, although raw data such as numbers of multiple pregnancies and live births could no longer be retraced
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Participants were randomly divided into treatment and control groups, method of randomisation was not stated
Allocation concealment (selection bias)	Unclear risk	Centralised randomisation by lab technician, who decided who would go into treatment or control group, unclear how this decision was made
Blinding (performance bias and detection bias) All outcomes	Low risk	Both participant and doctor were blinded. Embryologist was not
Incomplete outcome data (attrition bias) All outcomes	High risk	No live births were reported, even though length of follow‐up was until delivery. No intention‐to‐treat analysis was performed
Selective reporting (reporting bias)	Unclear risk	Proposed results were not prespecified in Materials and Methods section
Other bias	High risk	No commercial funding. Different transfer media brands were used in both arms of the trial. No multiple pregnancy rate was reported, although multiple embryos have been replaced in each treatment cycle