# FSH Receptor Asn680Ser Polymorphism Modulates Intrafollicular Nitric Oxide Bioavailability and Ovarian Responsiveness During IVF

**Authors:** Charalampos Voros, Diamantis Athanasiou, Despoina Mavrogianni, Ntilay Soyhan, Georgia Panagou, Maria Sakellariou, Georgios Papadimas, Fotios Chatzinikolaou, Eleni Sivylla Bikouvaraki, Georgios Daskalakis, Kalliopi Pappa

PMC · DOI: 10.3390/ijms27052452 · 2026-03-06

## TL;DR

This study shows that a genetic variation in the FSH receptor affects ovarian response during IVF, possibly through changes in nitric oxide levels in follicles.

## Contribution

The study links the FSHR Asn680Ser polymorphism to ovarian responsiveness and intrafollicular nitric oxide bioavailability during IVF.

## Key findings

- Ser/Ser homozygotes had higher oocyte counts and better fertilization outcomes than Asn allele carriers.
- Ser/Ser individuals showed elevated intrafollicular NO2-NO3 concentrations, though not statistically significant.
- The polymorphism is associated with differing ovarian responsiveness during IVF.

## Abstract

In vitro fertilisation (IVF) has significant hurdles due to individual differences in ovarian response during controlled ovarian stimulation. The Asn680Ser polymorphism of the follicle-stimulating hormone receptor (FSHR) is linked to varying ovarian sensitivity to FSH. However, its relationship with intrafollicular redox signalling remains unclear. Nitric oxide (NO) is a crucial compound that functions inside follicles and participates in angiogenesis, steroidogenesis, and oocyte competence. This prospective observational research classified women undergoing IVF into Asn allele carriers (Asn/Asn and Asn/Ser) and Ser/Ser homozygotes, according to the FSHR Asn680Ser polymorphism. The groups were assessed according to follicular fluid nitric oxide metabolites (NO2-NO3), fertilisation results, ovarian response indicators, and hormonal profiles. No substantial variation was seen between baseline and trigger-day hormone levels. In contrast, Ser/Ser individuals had a significantly higher total count of recovered oocytes, an elevated number of metaphase II oocytes, and enhanced fertilisation outcomes relative to carriers. The Ser/Ser group demonstrated increased intrafollicular NO2-NO3 concentrations. This difference was not statistically significant. These results link FSH receptor genetics to functional follicular competence, indicating that the FSHR Asn680Ser polymorphism is associated with differing ovarian responsiveness during IVF and may affect intrafollicular nitric oxide bioavailability.

## Linked entities

- **Genes:** FSHR (follicle stimulating hormone receptor) [NCBI Gene 2492]
- **Chemicals:** nitric oxide (PubChem CID 145068)

## Full-text entities

- **Genes:** FSHR (follicle stimulating hormone receptor) [NCBI Gene 2492] {aka FSHR1, FSHRO, LGR1, ODG1}
- **Chemicals:** NO (MESH:D009569), NO2-NO3 (-)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Mutations:** Ser/Ser, Asn680Ser, Asn/Ser, Asn/Asn

## Figures

1 figure with captions in the complete paper: https://tomesphere.com/paper/PMC12985945/full.md

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Source: https://tomesphere.com/paper/PMC12985945