Table 1

- Study characteristics (N=15).

Study ID	Sites	Study designs	Inclusion criterias	Conclusion
Taheripanah et al¹⁵	Iran	Case control	Patients who had been referred to the radio-oncotherapy clinic of Shahid Beheshti University of Medical Sciences with a diagnosis of BC in either teaching or general hospitals were analyzed. Only histopathologically confirmed female BC patients, diagnosed within one year prior to the interview, were included in the study.	No apparent association was observed between BC risk and ovulation induction drugs, however rise in BC patients using fertility medications over six months was also observed.
Orgéas et al¹⁶	Sweden	Cohort	During the period between 1961 and 1976, women who were receiving treatment for subfertility-related issues at major obstetrics and gynecology clinics (Gothenburg, Stockholm, and Uppsala, Sweden), were the focus of a study.	Increased overall risk of BC associated with infertility treatment was not observed. However, patients received clomiphene citrate therapy for non-ovulatory with high dose heightened risk for developing BC.
Calderon-Margalit et al¹⁷	Israel	Cohort	The study involved 567 women who utilized drugs to stimulate ovulation.	This study was performed for the assessment of association of infertility treatment using ovulation induction with risk of developing cancer (uterine cancer). However, still lacking the understanding regarding the dose and durations of clomiphene and its association with cancer.
Lerner-Geva et al¹⁸	Israel	Cohort	Women were identified from medical records of the infertility clinic of Sheba Medical Center situated in Tel Hashomer, Israel. These women were diagnosed with primary or secondary infertility between January 1, 1964, and December 31, 1974.	The findings pertaining to the potential connection between infertility, drugs like ovulation induction, and invasive ovarian cancer suggest a lack of increased risk, which is comforting. The higher risk of borderline ovarian tumors might be attributed to inherent traits of these tumors or surveillance bias.
Bildircin et al¹⁹	Turkey	Cohort	Women who used drugs to induce ovulation.	The use of controlled OS does not present a risk for the development of BC. The employment of anti-estrogen agents in stimulation protocols has demonstrated effectiveness, with a correspondingly low increase in estradiol levels. The utilization of Gonadotrophin Releasing Hormone antagonists can be utilized to initiate baseline ovarian conditions, thereby circumventing the delay typically associated with the initiation of OS. Importantly, ovarian reserves and responses are often lower in women who have been diagnosed with BC.
Basudan et al²⁰	Saudi Arabia	Retrospective analysis	Among the patients diagnosed with BC in Saudi Arabia, those of all age groups and residing in all administrative regions have been identified.	The findings suggest that there has been arise in incidence of BC in Saudi Arabian population, which can be attributed to the changing their lifestyle and followed more westernized lifestyle. For the prevention of BC incidence, following measures should be considered. For instance, prevent the use of tobacco in any form, management of body weight and awareness for the benefits of physical activity, and establishment of an effective programs BC screening.
Gauthier et al²¹	French	Cohort	The study population comprised of 98,997 French women (40-65 years) and health expenditures covered by the MGEN insurance agency. A total of 4,567 and 239 women with a history of cancer other than basal cell carcinoma at the baseline and whom the date of diagnosis was unavailable, respectively were excluded. Additionally, 1636 women never engaged in sexual intercourse were also excluded. Ultimately, 92,555 women were selected.	The impact of infertility treatment on the risk of developing BC is unclear, and more research is required to draw definitive conclusions. However, it is worth noting that family history of BC had utmost role in the development of the disease, and further investigation into this potential interaction is warranted.
Kotsopoulos et al²²	Canada	Non-RCT	Individuals possessing a BRCA1 or BRCA2 mutation and utilizing fertility medications or undergoing IVF	According to the findings, the employment of fertility treatments appears to have no detrimental impact on the likelihood of developing BC in individuals who have inherited BRCA gene mutations.
Jensen et al²³	Denmark	Non-RCT	In the timeframe of 1965 to 1998, all women were identified through medical records, who experienced infertility (primary and secondary) and mentioned to either Danish hospitals or private fertility clinics.	The analysis of all fertility drug groups revealed no associations between duration or number of cycles used since first use and the risk of BC. However, among nulliparous women, gonadotrophins may have a more pronounced impact on BC risk.
Reigstad et al²⁴	Norway	Non-RCT	MBRN recorded all female residents of Norway who gave birth to a child (gestation >22 weeks) between January 1, 1984, and December 31, 2010. While, women diagnosed with BC prior to the commencement of study were excluded from the analysis.	All Norwegian women who had given birth and were followed for 27 years demonstrated a higher risk of developing BC underwent ART than no ART.
Burkman et al²⁵	Metropolitan Atlanta, Detroit, Los Angeles, Philadelphia, and Seattle.	Non-RCT	Histologically confirmed women (35-64 years), primary invasive BC and had no prior history for invasive or in situ BC. Ability to understand the English language.	The prolonged administration of specific infertility medications may possibly increase the risk of developing BC.
Terry et al²⁶	Boston	Non-RCT	Female participants aged between 25 and 42 years who reported having cancer at the time of enrollment (excluding non-melanoma skin cancer) were not eligible for inclusion in the study.	The data imply a negative correlation between BC and infertility resulting from ovulatory disorders, but not from other sources of infertility.
Stewart et al²⁹	Australia	Non-RCT	The demographic of focus for this study is all women aged 20 to 44 from Western Australia, who were investigated and treated for infertility during 1983 and 2002.	The commencement of IVF at a youthful age has been found to be correlated with a higher incidence of BC.
Doyle et al²⁷	UK	Non-RCT	Ladies who were permanent residents of United Kingdom and received treatment at the clinic between beginning of 1975 and the end of 1989, and had undergone infertility treatment for at least one cycle and at least 20 years old at the time of treatment.	No correlation was observed between treatment for infertility by using OS and the development of breast, uterine, or ovarian cancer during the follow-up period investigated.
Cooley et al²⁸	USA	Non-RCT	Infertile women treated for infertility and outcomes were followed for 30 years and now, the mean age was 62.7 years at te end of follow-up.	The findings from the preclinical study suggest that ER-positve BC cells can be impacted indirectly by the estrogenic effects of infertility treatments and validate the potential protective effect of exposure to hCG during pregnancy.

RCT: randomized controlled trial, BC: breast cancer, IVF: in vitro fertilization, MBRN: the Medical Birth Registry of Norway, OS: ovarian stimulation, ER: estrogen receptor, hCG: human chorionic gonadotropin