A case-control study published in BMC Women’s Health has identified specific genetic variants in the CYP27B1 gene that are associated with an increased susceptibility to polycystic ovary syndrome (PCOS) and may influence biological outcomes during in vitro fertilization (IVF) treatments. The research, led by Liang Li and colleagues, examined the relationship between two single nucleotide polymorphisms, rs10877012 and rs4646536, and both the risk of developing PCOS and the response to controlled ovarian hyperstimulation (COH) in women undergoing assisted reproductive technology. The findings suggest that these genetic markers act as a single inherited haplotypic block, providing new insights into the complex genetic architecture underlying PCOS and its impact on reproductive success.

Polycystic ovary syndrome is increasingly recognized as a complex trait influenced by a variety of genetic factors, yet the specific mechanisms linking gene polymorphisms to clinical phenotypes remain under investigation. Prior studies have not fully explored the association of CYP27B1 polymorphisms with PCOS susceptibility or their influence on assisted reproductive technology outcomes. This gap in knowledge prompted the current investigation, which aimed to determine whether specific genotypes within the CYP27B1 gene are associated with PCOS risk and whether these genotypes correlate with IVF outcomes among affected women.

The study design involved a case-control approach, enrolling 129 women diagnosed with PCOS and 150 matched controls. The researchers utilized SNaPshot assays for single nucleotide polymorphism genotyping to identify the specific genetic variants in the CYP27B1 gene. Statistical analyses were conducted to explore genotypes associated with PCOS risk and to assess whether these genotypes were related to controlled ovarian hyperstimulation response and in vitro fertilization outcomes.

After adjusting for age and body mass index, the study found that the GT genotype of rs10877012 remained significantly associated with an increased risk of PCOS, with an adjusted odds ratio of 2.32 and a 95% confidence interval of 1.03 to 5.22. Similarly, the AG genotype of rs4646536 showed a significant association with increased PCOS risk, with an adjusted odds ratio of 2.29 and a 95% confidence interval of 1.02 to 5.15.

Furthermore, the two loci, rs10877012 and rs4646536, exhibited nearly complete linkage disequilibrium, with a D’ value of 1 and an r² value of 0.98. This high degree of linkage disequilibrium suggests that the two variants act as a single inherited haplotypic block rather than independent genetic markers. This finding supports the idea that the CYP27B1 gene region may have a coordinated role in PCOS susceptibility.

In addition to susceptibility, the study examined the impact of these genotypes on IVF outcomes. The rs10877012 GG and rs4646536 AA genotypes were associated with a significantly higher frozen blastocyst formation rate compared to the GT and AG genotypes, with a P-value of 0.012. The higher frozen blastocyst formation rate in women with the GG and AA genotypes could have implications for the success rates of IVF treatments, although further research is needed to confirm these associations in larger cohorts.

The study concludes that the CYP27B1 rs10877012–rs4646536 haplotypic block is associated with PCOS susceptibility and may influence IVF outcomes. However, the authors emphasize that these findings warrant further validation in larger independent cohorts to confirm the observed associations and to determine their clinical utility. The study provides a foundation for future research into the genetic underpinnings of PCOS and its impact on reproductive outcomes.

Subject of Research: Impact of CYP27B1 rs10877012 and rs4646536 polymorphisms on genetic susceptibility and biologic outcomes in polycystic ovary syndrome

Article Title: Impact of CYP27B1 rs10877012 and rs4646536 polymorphisms on genetic susceptibility and biologic outcomes in polycystic ovary syndrome

Article References: Li, L., Gong, Y., Zhao, Y., Xu, B., & Hao, Y. (2026). Impact of CYP27B1 rs10877012 and rs4646536 polymorphisms on genetic susceptibility and biologic outcomes in polycystic ovary syndrome. BMC Women’s Health. https://doi.org/10.1186/s12905-026-05105-7

Image Credits: AI Generated

DOI: 10.1186/s12905-026-05105-7

Keywords: Impact, CYP27B1, rs10877012, rs4646536, polymorphisms, genetic, susceptibility, biologic, outcomes, polycystic, ovary, syndrome