| Methods |
Multi‐centre open‐label 3‐arm parallel‐group randomised controlled non‐inferiority trial |
| Participants |
602 couples seeking fertility treatment after ≥ 12 months of unprotected intercourse, with the female partner between 18 and 38 years, an unfavourable prognosis for natural conception and a diagnosis of unexplained or mild male subfertility. Exclusion criteria included anovulation, double‐sided tubal disease, severe endometriosis, premature ovarian failure and known endocrine disorders (e.g. Cushing syndrome, adrenal hyperplasia) |
| Interventions |
Three cycles of IVF‐SET (plus subsequent cryo‐cycles), six cycles of modified natural cycle IVF and six cycles of IUI‐COH within 12 months after randomisation. Any additional treatments provided during this period were included at follow‐up |
| Outcomes |
Main outcome measures: The primary outcome was birth of a healthy child resulting from a singleton pregnancy conceived within 12 months after randomisation. Secondary outcomes included live birth, clinical pregnancy, ongoing pregnancy, multiple pregnancy, time to pregnancy, pregnancy complications and neonatal morbidity and mortality |
| Notes |
States: "During our trial the results of a pilot study, randomising women to three cycles of IUI‐COH or one cycle of IVF‐SET, were published. This pilot study demonstrated that the policy of transferring two embryos when no good quality embryos are available is not effective in preventing multiple pregnancies. The study protocol was amended, and from February 2010, after allocation of 48 women to the IVF‐SET group, a strict single embryo transfer policy (i.e. single embryo transfer was performed irrespective of embryo quality) was implemented" |
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) |
Low risk |
Randomisation was performed with an "online randomisation program, using biased coin minimisation, stratified for study centre" |
| Allocation concealment (selection bias) |
Low risk |
"A web based program generated a unique number with allocation code after entry of the patient’s initials and date of birth. Neither the recruiters nor the trial project group could access the randomisation sequence" |
| Blinding (performance bias and detection bias)
All outcomes |
Unclear risk |
Blinding was not possible because of the nature of the interventions |
| Incomplete outcome data (attrition bias)
All outcomes |
Low risk |
602/602 randomly assigned women were included in the ITT analysis |
| Selective reporting (reporting bias) |
Low risk |
All expected outcomes were reported |
| Other bias |
Low risk |
None was suspected |
