Clomiphene citrate resistance in relation to follicle-stimulating hormone receptor Ser680Ser-polymorphism in polycystic ovary syndrome

• Published in: Human reproduction (Oxford) Vol. 24; no. 8; pp. 2007 - 2013
• Main Authors: Overbeek, A., Kuijper, E.A.M., Hendriks, M.L., Blankenstein, M.A., Ketel, I.J.G., Twisk, J.W.R., Hompes, P.G.A., Homburg, R., Lambalk, C.B.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01-08-2009; Oxford Publishing Limited (England)
• Subjects: Adult; anovulation; Biological and medical sciences; Clomiphene - therapeutic use; clomiphene citrate; Drug Resistance; Female; FSH receptor; Gynecology. Andrology. Obstetrics; Humans; Medical sciences; Ovulation Induction; polycystic ovary syndrome; Polycystic Ovary Syndrome - genetics; Polycystic Ovary Syndrome - physiopathology; polymorphism; Polymorphism, Genetic; Receptors, FSH - drug effects; Receptors, FSH - genetics; Retrospective Studies; Treatment Outcome; clomiphene citrate; polymorphism; anovulation; FSH receptor; polycystic ovary syndrome; Non steroidal estrogen; Menstruation disorders; Anovulation; Ovulation inducer; Citrate; Female sterility; Gonadotropin; Clomifene; Polycystic ovary; Female genital diseases; Resistance; Ovarian diseases; Vertebrata; Selective estrogen receptor modulator; Mammalia; Adenohypophyseal hormone; Cyst; Benign neoplasm; Follicle stimulating hormone; Polymorphism; Biological receptor
• ISSN: 0268-1161; 1460-2350
• DOI: 10.1093/humrep/dep114

BACKGROUND Clomiphene citrate (CC) response in anovulatory women is difficult to predict and patient-tailored treatment would benefit patient care and time-management. The objective of this study was to evaluate the role of the follicle-stimulating hormone receptor (FSHR) Ser680Ser-polymorphism as a predictor for CC response. METHODS In this retrospective study, 193 patients, diagnosed with polycystic ovary syndrome (PCOS) according to Rotterdam criteria and treated with ovulation induction, were included over a 5-year period in a university hospital in the Netherlands. Data on demographics, BMI, menstrual cycle, laboratory screening (including FSHR genotyping), transvaginal ultrasonography of ovaries and ovulation parameters were collected. Main outcome measures were response to CC and FSHR genotype. RESULTS The frequency distribution of the 680-polymorphism was 26% (Asn/Asn), 50% (Asn/Ser) and 24% (Ser/Ser). No significant differences in basal characteristics were found. Significantly more patients with Ser/Ser-polymorphism were resistant to CC (28%) compared with Asn/Ser (14%) and Asn/Asn group (15%), with an odds ratio for ovulation of 0.44 (95% CI, 0.21–0.97). Patients with higher FSH levels, higher age and lower BMI were significantly more likely to ovulate in univariate analysis. In a multivariate logistic regression model, corrected for age, BMI, mean ovarian, volume, hyperandrogenism, and amenorrhoea, only FSHR and basal FSH levels were predictive for ovulation. CONCLUSIONS Chance of resistance to CC is almost double in women with PCOS harbouring the Ser/Ser genotype.