Organised cancer screening among women who receive medically assisted reproduction treatments

Problem Statement
There is a lack of published data regarding cancer screening participation among women undergoing medically assisted reproduction (MAR) treatments, such as in-vitro fertilisation (IVF), intrauterine insemination (IUI), and ovulation stimulation (OS). This gap complicates the interpretation of cancer incidence and risk profiles in this population. While there are concerns that MAR hormones may influence cancer development, observational studies face challenges from unmeasured confounding and detection bias. Specifically, if women seeking MAR are more engaged with healthcare services generally, they may participate more frequently in organised cancer screening. This increased screening could lead to higher detection rates of preneoplastic or invasive cancers, potentially confounding the assessment of whether MAR treatments themselves alter cancer risk. Although Australian guidelines recommend cervical screening prior to conception attempts, empirical evidence regarding the actual uptake of both cervical and breast screening in MAR-treated women was previously unavailable.

Methodology
The authors conducted two retrospective cohort studies using linked population-based Australian health registries and administrative datasets covering the period from 1991 to 2016. The study compared organised, publicly funded cervical and breast cancer screening episodes between women who received MAR and matched controls who did not.

• Cohorts:
  • Cervical Screening Cohort: 1,331,193 women aged 21–55 at first MAR treatment.
  • Breast Screening Cohort: 65,304 women aged 43–55 at first MAR treatment.
  • Controls: Up to four non-MAR controls were matched to each MAR-treated woman based on birth year, parity, age at first birth (if applicable), and residential remoteness.
• Exposure Classification: MAR exposure was categorized by the first treatment type received: (1) Assisted Reproductive Technology (ART, including IVF/ICSI); (2) Intrauterine insemination with follicle stimulating hormone or cancelled ART cycles (IUI/OS); and (3) Dispensations of Clomiphene Citrate.
• Statistical Analysis: The study modelled the proportion of women screened and the time since the most recent screening in the three years before and after the first MAR treatment (or matched date). Models were adjusted for age, residential remoteness, parity, area-level socio-economic disadvantage (SEIFA), history of notifiable cancer, and uptake of the alternative screening program.

Key Results
The study found distinct differences in screening patterns between MAR-treated women and matched controls, varying by cancer type:

• Cervical Cancer Screening:
  • A significantly greater proportion of MAR-treated women underwent organised cervical screening compared to non-treated women in the three years prior to treatment (77.3%–84.1% vs. 57.5%–62.0%, depending on treatment type).
  • MAR-treated women showed a marked increase in screening in the year immediately preceding treatment (45.7%–49.8%) compared to the two years prior (34.4%–37.5%), a trend not observed in controls.
  • MAR-treated women had their most recent cervical screen closer to the treatment date (approx. 335–339 days prior) compared to controls (approx. 416–427 days prior).
  • This pattern persisted post-treatment, with 77.0%–78.5% of MAR-treated women screened in the three years following treatment, compared to 68.1%–69.5% of controls.
• Breast Cancer Screening:
  • In contrast to cervical screening, a smaller proportion of MAR-treated women attended organised breast cancer screening compared to controls prior to treatment (7.6%–9.6% vs. 9.3%–10.5%).
  • Specifically, women receiving ART had a significantly lower predicted proportion of breast screening (7.6%) compared to controls (9.3%).
  • The time since the most recent breast screen was similar between groups.
  • Post-treatment, MAR-treated women continued to show lower or similar screening rates compared to controls (11.0%–15.0% vs. 12.8%–14.9%).

Significance and Claims
The authors claim that their findings demonstrate that women receiving MAR have higher participation in organised cervical screening but lower participation in organised breast screening compared to matched peers.

• Cervical Screening: The higher engagement is attributed to alignment with national guidelines and clinical practice, where fertility specialists and general practitioners advise women to be up-to-date with cervical screening prior to conception. The authors note that despite this higher engagement, 1-in-4 to 1-in-6 women were still not up-to-date with screening prior to MAR, representing missed opportunities for cervical cancer prevention.
• Breast Screening: The lower breast screening rates are explained by clinical contraindications; organised mammographic screening is generally contraindicated for women who are pregnant, seeking to conceive, or breastfeeding.
• Implications for Cancer Risk Studies: The paper argues that these screening patterns are crucial for interpreting cancer incidence data. The higher cervical screening rates among MAR-treated women likely contribute to the observed 40% lower incidence of cervical cancer in this group compared to the general population, as increased screening prevents progression to invasive cancer. Conversely, the lower breast screening rates suggest that any observed cancer risks in this group are not artificially inflated by detection bias from screening. The authors conclude that nuance is required when discussing the relationship between MAR and cancer, as engagement with preventive healthcare services varies by cancer type and clinical context.

Limitations
The authors acknowledge limitations, including the restriction to publicly funded screening data (missing private sector screening, which may be more common among higher socioeconomic groups), the use of area-level rather than person-level socio-economic data, and the small subset of women eligible for the breast screening analysis (restricted to those aged 43+ at first MAR treatment).