Dos Santos Silva 2009.

Methods	Retrospective cohort.
Participants	Cohort of 9152 study subjects were identified through 2 case series of women who attended reproductive endocrinology practices in 2 hospitals in London. Of these, 7444 were traced and flagged through national registry to ascertain their vital status, and to obtain information on site‐specific cancer incidence, cause‐specific mortality and migrations. Eighty‐nine subjects were excluded because flagging was considered to be unreliable (n = 8), they were no longer National Health Service patients at the time they joined the cohort (n = 79), or they had subsequently undergone a sex change operation (n = 2). Further excluding women with missing information on treatment resulted in the inclusion of 7129 women, of which 3180 were exposed to fertility treatment. Mean follow‐up, 21.4 years.
Interventions	Only clomiphene citrate, only gonadotropins, both clomiphene citrate and gonadotropins. Data on dosages, number of fertility treatment cycles, and years since time at first fertility treatment was available.
Outcomes	Endometrial cancer. Incident cases in total cohort, 30; in exposed cohort, 18.
Notes	Causes of subfertility included polycystic ovarian syndrome, male factor, thyroid disease, anovulation, irregular ovulation, amenorrhoea, weight‐related ovulatory disorders, hyperprolactinaemia.
Risk of bias
Bias	Authors' judgement	Support for judgement
Selection bias (comparability)	High risk	Comment: Exclusion of endometrial cancer cases at the beginning of the study was not reported. Comment: Non‐exposed women drawn from the same population as exposed cohort. Comment: No comparability on cause of subfertility, diabetes mellitus, polycystic ovary syndrome (PCOS), and obesity was ensured.
Selection bias (confounding)	High risk	Quote: "Two approaches were used to compare study groups within the cohort. In the first, the risk of dying from a particular cause, or of developing a certain site‐specific cancer, among patients ‘exposed’ to a given characteristic (e.g. treatment type) relative to the risk among those ‘unexposed’ was estimated as the ratio between the two corresponding SMRs, or SIRs, to take into account calendar period and age effects". Comment: Analyses adjusted only for age.
Performance bias	High risk	Quote: "From the meticulous clinical notes kept by the founders of these case series, a trained abstractor extracted and computerised relevant data, including information on signs and symptoms at presentation, final diagnosis, treatments prescribed (with number of cycles and dose) and their outcome. Hospital records (mainly on microfilms) and computer databases were also reviewed". Comment: Exposure to ovary‐stimulation drugs was ascertained by medical records. Blindness regarding the allocated interventions not guaranteed.
Detection bias	Low risk	Quote: "Study subjects were followed through the National Health Service Central Register (NHSCR) in England and Wales to ascertain their vital status, and to obtain information on site‐specific cancer incidence, cause‐specific mortality and migrations". Comment: Outcome was ascertained by record linkage.
Attrition bias	Low risk	Quote: "Weaknesses of our study include the fact that follow‐up was possible only for 80% of the original cohort; however, there was no evidence that those untraced through the NHSCR differed from those who were traced". Comment: Completeness of follow‐up was considered adequate.
Selective reporting (reporting bias)	High risk	Comment: Results of Cox regression models not reported for endometrial cancer.
Other bias	High risk	Quote from Table 1: "Mean follow‐up of 21.4 years". Comment: Length of follow‐up was considered adequate. Comment: Non‐RCT study.