FSHR rs6165: Understanding the Thr307Ala Variant and Fertility
The rs6165 variant is a common genetic change in the FSHR gene that results in a threonine-to-alanine substitution at position 307 of the protein. It is frequently studied for its potential role in influencing how a woman's ovaries respond to follicle-stimulating hormone during assisted reproductive cycles.
What each genotype means
Potential increased FSH requirement
Research suggests this genotype may be associated with a higher total dose of recombinant FSH required during ovarian stimulation for IVF/ICSI procedures. Because this variant influences how your body responds to gonadotropin stimulation, you should discuss your specific stimulation protocol and dosing needs with your fertility specialist or pharmacist.
This genotype is common, appearing in a significant portion of the population depending on ancestral background.
Typical ovarian response profile
This genotype represents a heterozygous state for the Thr307Ala variant. Studies on ovarian response to stimulation show mixed results regarding the clinical impact of this variant, and it is often considered to have minimal clinical relevance for predicted normal responders. Please consult with your clinician regarding how your genetic profile may inform your personalized fertility treatment plan.
This is a very common genotype found across diverse global populations.
Typical ovarian response profile
This genotype is often considered the reference state in many studies of the FSHR gene. While some research investigates its role in ovarian stimulation, the clinical impact of this specific variant on fertility outcomes remains limited and inconsistent. You should discuss any concerns regarding ovarian stimulation or medication response with your fertility specialist.
Carried by a large percentage of the population, with frequencies varying significantly by ancestry, reaching up to 35% in some studied cohorts.
What is the rs6165 Variant?
The rs6165 variant, also known as the Thr307Ala polymorphism, is a single nucleotide change located within the FSHR gene. Specifically, it involves a substitution where the amino acid threonine is replaced by alanine at position 307 of the follicle-stimulating hormone receptor protein. This variant is situated in exon 10 of the gene. Because this change occurs in the coding region, it has the potential to alter the structure or function of the receptor. In many populations, rs6165 is found in linkage disequilibrium with another common variant, rs6166 (Asn680Ser). This means these two variants are often inherited together, creating specific combinations of receptor types that researchers analyze to understand their collective impact on reproductive physiology.
The Role of the FSHR Gene
The FSHR gene provides instructions for making the follicle-stimulating hormone receptor, which is a G-protein-coupled receptor found primarily on the surface of granulosa cells in the ovaries. This receptor is essential for the action of follicle-stimulating hormone (FSH), a hormone released by the pituitary gland that regulates the development of ovarian follicles and the production of sex hormones. By binding to its receptor, FSH triggers signaling pathways that promote follicle maturation and egg development. Because the receptor is the gateway for this hormonal signal, variations in the gene that encodes it may theoretically influence how sensitive the ovaries are to both natural FSH and the synthetic FSH often administered during fertility treatments like in vitro fertilization (IVF).
Research and Evidence Strength
Research into rs6165 has primarily focused on its association with ovarian response during controlled ovarian stimulation. Some studies suggest that individuals with certain genotypes may require different doses of gonadotropins to achieve an optimal number of retrieved oocytes. However, the evidence remains limited and sometimes conflicting. While some clinical cohorts have reported that specific genotypes are associated with higher FSH consumption or variations in oocyte yield, other studies have found no significant difference in clinical outcomes. It is important to note that ovarian response is a complex trait influenced by many factors, including age, baseline ovarian reserve, and environmental influences. Consequently, the clinical utility of testing for rs6165 as a standalone predictor of fertility treatment success is not currently established in standard medical practice.
Population Frequency
The frequency of the rs6165 variant varies significantly across different ancestral groups. In European populations, the minor allele frequency is typically observed between 0.40 and 0.50. In contrast, the variant is less common in East Asian populations, where the minor allele frequency generally ranges from 0.05 to 0.15. These differences highlight the importance of considering ancestry when interpreting genetic data, as the prevalence of specific genotypes can differ widely depending on a person's genetic background.
What This Information Means for You
If you have encountered information about your rs6165 genotype, it is important to view it within the context of your overall health and reproductive goals. Genetic variants like rs6165 are common and are not considered diagnostic for infertility or any specific medical condition. Because the scientific evidence regarding the impact of this variant on fertility treatment is mixed and the effect sizes are generally small, this information should not be used to make independent medical decisions. If you are undergoing fertility treatment or have concerns about your reproductive health, please discuss your genetic profile and any questions you have with your reproductive endocrinologist or a qualified fertility specialist. They can provide personalized guidance based on your clinical history and current medical standards.
How common is this variant?
The minor allele frequency for rs6165 is approximately 0.40–0.50 in European populations and 0.05–0.15 in East Asian populations.
Frequently asked questions
Does the rs6165 variant cause infertility?
No, the rs6165 variant is a common genetic polymorphism and is not a cause of infertility. It is simply a variation in the genetic code that may influence how the body responds to hormone stimulation.
Should I change my IVF medication dose based on my rs6165 genotype?
You should never change your medication dosage based on genetic information without consulting your doctor. Any adjustments to fertility treatment protocols must be managed by your reproductive endocrinologist.
Is rs6165 the same as rs6166?
No, they are two different variants in the same gene. However, they are often inherited together due to linkage disequilibrium, meaning they are frequently studied as a pair.
Can I use this test to predict my chances of IVF success?
Current scientific evidence does not support using the rs6165 variant as a reliable predictor of IVF success. Ovarian response is influenced by many factors, and this variant has only a limited, often debated, impact.
Sources & further reading
Educational information only, last refreshed 9/26/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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