Table 1.
Characteristics of included studies in the meta-analysis of the impact of fertility treatments on breast cancer risk in genetically susceptible women.
| Study publication | Country | Study period | Study types | Types of hereditary factors | Cohort size (genetically susceptible women) | Total number of exposed women | Number of incidence cases | Number of exposed cases | Fertility treatments strategy |
|---|---|---|---|---|---|---|---|---|---|
| Perri et al. (2021) | Israel | 1995-2020 | Historical prospect cohort study | BRCA1/2 mutations | 1,824 | 332 | 687 | 89 | CC, gonadotropins, IVF and combination of these treatments |
| Derks-Smeets et al. (2018) | The Netherlands | 2010-2013 | Retrospective cohort study | BRCA1/2 mutations | 2,514 | 76 | 938 | 15 | Ovarian stimulation for IVF |
| Kotsopoulos et al. (2008) | Canada | 1994-2007 | Case-control study | BRCA1/2 mutations | 2,760 | 137 | 1,380 | 70 | IVF or fertility medication including CC, gonadotropins or other drugs |
| Braga et al. (1996) | Italy | 1991-1994 | Case-control study | Family history of breast cancer | 434 | 12 | 299 | 2 | Infertility treatments |
| Gauthier et al. (2004) | France | 1990-2000 | Prospective cohort study | Family history of breast cancer | 10,221 | 526 | 455 | 32 | Treated by fertility drugs including CC, menotrophin,and chorionic gonadotrophin |
| Pervaiz et al. (2018) | North Cyprus | 2016-2017 | Case-control study | Family history of breast cancer | 358 | 77 | 228 | 59 | Fertility drugs |
| Vassard et al. (2021) | Denmark | 1994-2016 | Retrospective cohort study | Family history of breast cancer | 142,282 | N.R. | 289 | 36 | ART |
| Brinton et al. (2014) | The USA | 1965-2010 | Retrospective cohort study | Family history of breast cancer | 619 | N.R. | 76 | 47 | CC, gonadotropins and combination of these treatments |
| Study publication |
Effect estimates (outcomes) |
Reference group (matching controlling factors) | Adjusting factors | follow-up (years) | Ascertain of exposure | Ascertain of cancer | Risk of bias | ||
| Perri et al. (2021) | HR (breast cancer) | General population(mutation type, parental origin of the mutation, age at menarche, hormone replacement therapy, incidence of cancer diagnosis) | Risk-reducing bilateral salpingo-oophorectomy and/or prophylactic mastectomy, BRCA mutation type, parity, age at menarche, age at first pregnancy, OC use, paternal mutation origin | N.R. | Medical records | Israel National Cancer Registry | Moderate | ||
| Derks-Smeets et al. (2018) | HR (breast cancer) | General population or subfertile population (other invasive cancer diagnosis, bilateral prophylactic mastectomy, subfertility, birth cohort, other fertility treatments including clomid and/or intrauterine insemination, use of OC, parity, age at first birth) | Subfertility, birth year | N.R. | Medical record from the Dutch HEBON study (Hereditary Breast and Ovarian cancer study, the Netherlands) and the national PGD registry | Self-reported, the Dutch national Pathology Database (PALGA) and the Netherlands Cancer Registry (NCR) | Moderate | ||
| Kotsopoulos et al. (2008) | OR (breast cancer) | General population(mutation in the same gene, year of birth, country of residence and parity, diagnosis with other cancers, bilateral mactectomy) | Parity, age at mernache and ethnicity | N.R. | Medical records from 47 participating medical centres in nine countries | Medical records from 47 participating medical centres in nine countries | Moderate | ||
| Braga et al. (1996) | OR (breast cancer) | General population (age at inclusion, area of residence) | Menopausal status, parity, education, age, centre | N.R. | Medical records from the major teaching and general hospitals of study areas | Medical records from the major teaching and general hospitals of study areas | Serious | ||
| Gauthier et al. (2004) | RR (breast cancer) | General population (N.R.) | Parity and age at first full-term pregnancy, age at mernache, personal history of benign breast disease, number of first-degree relatives with a history of breast cancer, BMI at inclusion, active smoking at inclusion, numbers of years school | 9.7 | Medical records from the French E3N cohort(Etude Epidémiologique auprès de femmes de la Mutuelle Générale de l’Education Nationale) | Medical records from the French E3N cohort | Serious | ||
| Pervaiz et al. (2018) | OR (breast cancer) | General population (age) | N.R. | N.R. | Medical records from Near East Hospital and Dr. Burhan Nalbantoglu State Hospital | Medical records from Near East Hospital and Dr. Burhan Nalbantoglu State Hospital | Serious | ||
| Vassard et al. (2021) | HR (breast cancer) | General population (age) | Age(time-varying, stratified in 2-year intervals), education level, partnership status, year, nulliparity (time-varing) | 9.69 | IVF register | Danish Cancer registry | Serious | ||
| Brinton et al.(2014) | HR (breast cancer) | General population (exclusion of diagnosis within first year of fertility treatment) | Study site, calendar year of first infertility evaluation, gravidity at first clinic visit | 30 | Five reproductive enocrinology practices | Cancer registries in the 14 states | Serious |
NR, not reported; HR, hazard ratio; RR, relative risk; OR, odds ratio; CC, clomiphene citrate; IVF, in-vitro fertilization; ART, assisted reproductive technology; OC, oral contraceptive; HMG, human menopausal gonadotropin; PGD, preimplantation genetic diagnosis.