Highlights
- Asian women with Polycystic Ovary Syndrome (PCOS) demonstrate a significantly slower age-related decline in Anti-Müllerian Hormone (AMH) levels compared to normo-ovulatory peers.
- In women aged 36 and older, those with PCOS maintained AMH levels more than double those of the control group (44.4 vs 19.3 pmol/l).
- Cumulative pregnancy rates (CPR) following Assisted Reproductive Technology (ART) remained stable at approximately 56% for PCOS patients across age groups, whereas normo-ovulatory women saw a sharp decline to 28.6% after age 36.
- PCOS may represent a unique human model for studying the mechanisms of reproductive longevity and delayed ovarian senescence.
Introduction: The PCOS Paradox and Reproductive Aging
The physiological decline of female fertility is primarily driven by the progressive exhaustion of the ovarian follicle pool, a process traditionally reflected by decreasing levels of Anti-Müllerian Hormone (AMH). While advanced maternal age (AMA) is universally associated with diminished ovarian reserve and poorer outcomes in Assisted Reproductive Technology (ART), certain clinical phenotypes appear to resist this trajectory. Polycystic Ovary Syndrome (PCOS)—typically characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology—has long been viewed through the lens of metabolic and reproductive challenges. However, emerging evidence suggests that the very features that complicate early fertility may confer a late-stage reproductive advantage.
Study Design and Methodology
This study utilized a retrospective observational cohort design, analyzing data from 3,092 women treated at a tertiary-care center in Singapore. After applying rigorous exclusion criteria, a total of 1,249 women were included in the final analysis, categorized into the PCOS group (n = 212) or the normo-ovulatory group (n = 1,037). PCOS was defined according to the 2003 Rotterdam Criteria. The primary objectives were to evaluate clinical demographics, ART protocols, and longitudinal hormone levels. The researchers utilized Modified Poisson Regression to compare ART outcomes, adjusting for potential confounders. The study specifically focused on the multi-ethnic Asian population, a demographic previously underrepresented in PCOS-related reproductive longevity research.
Key Findings: Ovarian Reserve and ART Trajectories
The results of the study provide compelling evidence that the PCOS phenotype alters the standard timeline of reproductive aging.
Superior Ovarian Reserve Maintenance
A hallmark of the findings was the disparity in AMH levels. While both groups experienced a decline in AMH as they aged, the rate of attrition was significantly attenuated in the PCOS group. Most notably, in the advanced maternal age category (36 years and older), women with PCOS exhibited a median AMH of 44.4 pmol/l, compared to just 19.3 pmol/l in normo-ovulatory women. This suggests that the larger initial follicle pool or altered follicular dynamics in PCOS patients provide a “buffer” against the typical effects of aging.
Stability of Cumulative Pregnancy Rates
The most clinically significant finding was the impact on ART success. In the normo-ovulatory group, the cumulative pregnancy rate (CPR) following one ovarian stimulation cycle dropped significantly with age: from 46.0% in the 31-35 age bracket to 28.6% for those 36 and older. In stark contrast, the PCOS group showed remarkable stability. Their CPR was 56.7% for ages 31-35 and remained virtually unchanged at 55.9% for those aged 36 and older. When adjusting for variables, women with PCOS aged 36+ had an adjusted relative risk (aRR) of 1.78 for cumulative pregnancy compared to their normo-ovulatory counterparts. For those specifically undergoing In Vitro Fertilization (IVF), the aRR rose to 2.01, indicating a two-fold increase in the likelihood of success.
Expert Commentary: Mechanistic Insights and Biological Plausibility
The observation that PCOS may extend the reproductive lifespan invites a re-evaluation of the syndrome’s evolutionary and biological role. The delayed decline in the oocyte pool in PCOS might be attributed to lower rates of follicular atresia or a higher baseline of primordial follicles. From a clinical perspective, these findings suggest that the prognosis for older women with PCOS undergoing ART is significantly more optimistic than for the general population. While the hyperandrogenic environment of PCOS is often detrimental in natural conception, the controlled environment of ART appears to leverage the high ovarian reserve effectively. However, clinicians must balance this optimism with the known risks of PCOS, including higher rates of ovarian hyperstimulation syndrome (OHSS) and potential metabolic complications during pregnancy.
Limitations and Considerations for Practice
While the data is robust, the researchers note that the study was limited to an Asian population in Singapore. Given that PCOS phenotypes can vary significantly across different ethnicities (e.g., variations in BMI and metabolic profiles between Caucasian and Asian cohorts), these results may not be directly generalizable to all populations. Additionally, as a retrospective study, it cannot definitively establish a causal link between the PCOS genotype and the mechanisms of cellular longevity, but rather highlights a strong clinical correlation.
Conclusion
This study provides strong support for the hypothesis that women with PCOS possess an enhanced reproductive lifespan. By maintaining a high ovarian reserve into their late 30s and achieving ART success rates that defy the traditional age-related decline, these patients serve as a human model for reproductive longevity. For clinicians, these insights are vital for counseling patients; for researchers, they provide a roadmap for investigating the genetic and molecular pathways that protect the ovarian reserve against the passage of time.
Funding and Disclosures
This research was funded in part by the NUS Bia-Echo Asia Centre for Reproductive Longevity and Equality. The authors declared no competing interests.
References
Yang Q, Benny P, Lee JJN, et al. Asian women with PCOS have enhanced ovarian reserve and ART outcomes, even at an advanced maternal age: a model for reproductive longevity? Hum Reprod Open. 2025;2025(4):hoaf062. doi:10.1093/hropen/hoaf062.
