The Evidence Does Not Support a Specific Percentage of Ovarian Cancer Following Infertility Treatment
The available evidence does not provide a definitive percentage of women who develop ovarian cancer after infertility treatment, but research suggests the absolute risk remains very low at approximately 0.5% globally among women with infertility history, with most increased risk likely attributable to underlying infertility rather than the treatments themselves.
Understanding the Baseline Risk Context
Before examining infertility treatment specifically, it's essential to understand that ovarian cancer has a low baseline incidence in the general population. The age-adjusted incidence is approximately 17 per 100,000 women, with a lifetime risk of about 1.3-1.6% 1, 2. This low prevalence makes it challenging to detect small increases in risk and means that even modest relative risk increases translate to small absolute risk changes.
What the Research Actually Shows
Global Prevalence Data
A 2025 systematic review and meta-analysis examining infertility and ovarian cancer found that the global prevalence of ovarian cancer among women with a history of infertility was 0.5% 3. This represents the actual observed rate rather than a theoretical risk calculation.
Comparative Risk Studies
The most recent and highest-quality evidence comes from a 2023 Nordic registry-based cohort study 4 that followed 3,303,880 initially nulliparous women across four countries. Among women who gave birth after assisted reproductive technology (ART):
- 135 developed ovarian cancer after ART conception
- Incidence rate: 11.6 per 100,000 person-years
- Hazard ratio of 1.70 compared to natural conception
- Mean follow-up: 14.4 years
A 2021 Dutch nationwide cohort study 5 with 24 years median follow-up of 30,625 ART-treated women found:
- 158 invasive ovarian cancers observed
- Standardized incidence ratio of 1.43 compared to general population
- However, when compared to subfertile women not treated with ART, the hazard ratio was 1.02 (not statistically significant)
- Risk decreased with higher parity and more successful ART cycles
Critical Interpretation: Infertility vs. Treatment
The key finding across multiple studies is that the increased ovarian cancer risk appears primarily related to the underlying infertility itself, particularly nulliparity, rather than the fertility treatments 5, 6.
Evidence Supporting This Distinction:
- Women who successfully conceived after ART had similar or lower risk compared to those who remained nulligravid 6
- Risk decreased with increasing number of successful ART cycles resulting in childbirth 5
- No dose-response relationship was found between number of ART cycles and cancer risk 5
- Unexplained infertility itself was associated with increased ovarian and uterine cancer risk even without treatment 7
The Nulligravid Exception
One important caveat: Women who used clomiphene citrate and remained nulligravid showed substantially elevated risk (RR 3.63) compared to those who successfully conceived (RR 0.88) 6. This suggests that persistent infertility, rather than the medication itself, drives the association.
Borderline Ovarian Tumors
A separate consideration is borderline ovarian tumors, which showed a more consistent association with ART:
- Standardized incidence ratio of 2.20 compared to general population 5
- Hazard ratio of 1.84 compared to non-ART subfertile women 5
- However, no dose-response relationship was observed, raising questions about causality
Practical Clinical Implications
Counseling Patients
When discussing ovarian cancer risk with women considering or undergoing infertility treatment:
Absolute risk remains very low: Even with a relative risk increase of 1.4-1.7, the absolute risk over 15-24 years is less than 1%
Successful pregnancy appears protective: Women who achieve pregnancy through ART do not show increased risk compared to subfertile controls
Underlying infertility matters more than treatment: The evidence consistently points to nulliparity and infertility etiology as the primary risk factors
Long-term surveillance is not indicated: Given the low absolute risk and lack of effective screening (per USPSTF recommendations against routine ovarian cancer screening 1), special surveillance protocols are not warranted
Common Pitfalls to Avoid
- Do not conflate relative and absolute risk: A hazard ratio of 1.70 sounds alarming but translates to approximately 6 additional cases per 100,000 person-years
- Do not attribute causality prematurely: The association may reflect confounding by indication (infertility itself) rather than treatment effects
- Do not recommend special screening: Standard guidelines recommend against routine ovarian cancer screening even in this population, as the positive predictive value remains extremely low (approximately 2%) 1
The Bottom Line for Clinical Practice
Rather than quoting a specific percentage, counsel patients that:
- Ovarian cancer remains rare even after infertility treatment (well under 1% over 15-24 years)
- Any increased risk appears primarily related to the infertility itself, especially if pregnancy is not achieved
- Successful conception through ART appears to normalize or reduce risk
- No special screening or surveillance is recommended beyond standard gynecologic care
- The benefits of achieving pregnancy likely outweigh the minimal absolute increase in ovarian cancer risk
The evidence does not support withholding or modifying infertility treatment based on ovarian cancer concerns, but it does emphasize the importance of achieving successful pregnancy when possible.