Follicle-stimulating hormone receptor polymorphism affects the outcome of ovulation induction in normogonadotropic (World Health Organization class 2) anovulatory subfertility

Olivier Valkenburg; Evert J P van Santbrink; Tamar E. König; Axel P N Themmen; André G. Uitterlinden; Bart C J M Fauser; Cornelis B. Lambalk; Joop S E Laven

doi:10.1016/j.fertnstert.2015.01.002

Follicle-stimulating hormone receptor polymorphism affects the outcome of ovulation induction in normogonadotropic (World Health Organization class 2) anovulatory subfertility

Olivier Valkenburg
, Evert J P van Santbrink
, Tamar E. König
, Axel P N Themmen
, André G. Uitterlinden
, Bart C J M Fauser
, Cornelis B. Lambalk
, Joop S E Laven

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

OBJECTIVE: To assess whether an FSH receptor polymorphism (Asn680Ser, rs6166) can affect the outcome of ovulation induction in normogonadotropic (World Health Organization class 2 [WHO2]) anovulatory subfertile women.

DESIGN: Prospective, longitudinal, cohort study.

SETTING: University-based fertility unit.

PATIENT(S): A total of 240 consecutive women diagnosed with WHO2 anovulatory subfertility who underwent ovulation induction therapy. Results were replicated in a retrospective cohort of 185 patients with polycystic ovary syndrome (PCOS) (Rotterdam criteria).

INTERVENTION(S): Ovulation induction using clomiphene citrate (CC) as first-line and exogenous gonadotropins (exFSH) as second-line therapy.

MAIN OUTCOME MEASURE(S): Clomiphene-resistant anovulation (CRA), clomiphene failure (CCF), and ongoing pregnancy rate.

RESULT(S): Genotyped patients (n = 159) were similar to nongenotyped women (n = 81) regarding clinical characteristics and outcomes of ovulation induction. The 680(Ser) allele was associated with CRA. A pooled analysis of both cohorts showed an 89% higher chance of CRA after CC treatment (odds ratio 1.9 [95% confidence interval 1.1-3.3]) in homozygous carriers of the FSH receptor variant (680(Ser/Ser)). A lower chance of ongoing pregnancy (hazard ratio 0.51 [95% confidence interval 0.27-0.98]) was observed among these patients during CC treatment in the prospective cohort.

CONCLUSION(S): An FSH receptor polymorphism is associated with CRA during treatment with clomiphene citrate. These data may be used to design a treatment algorithm that is more efficacious and better tailored to the individual patient.

Original language	English
Pages (from-to)	1081-1088
Number of pages	8
Journal	Fertility and Sterility
Volume	103
Issue number	4
DOIs	https://doi.org/10.1016/j.fertnstert.2015.01.002
Publication status	Published - 1 Apr 2015

Keywords

FSHR
ovulation induction
polymorphism
rs6166
WHO2

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10.1016/j.fertnstert.2015.01.002

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Valkenburg, O., van Santbrink, E. J. P., König, T. E., Themmen, A. P. N., Uitterlinden, A. G., Fauser, B. C. J. M., Lambalk, C. B., & Laven, J. S. E. (2015). Follicle-stimulating hormone receptor polymorphism affects the outcome of ovulation induction in normogonadotropic (World Health Organization class 2) anovulatory subfertility. Fertility and Sterility, 103(4), 1081-1088. https://doi.org/10.1016/j.fertnstert.2015.01.002

@article{0d78947de42a4187afaf0257d73b6c38,

title = "Follicle-stimulating hormone receptor polymorphism affects the outcome of ovulation induction in normogonadotropic (World Health Organization class 2) anovulatory subfertility",

abstract = "OBJECTIVE: To assess whether an FSH receptor polymorphism (Asn680Ser, rs6166) can affect the outcome of ovulation induction in normogonadotropic (World Health Organization class 2 [WHO2]) anovulatory subfertile women.DESIGN: Prospective, longitudinal, cohort study.SETTING: University-based fertility unit.PATIENT(S): A total of 240 consecutive women diagnosed with WHO2 anovulatory subfertility who underwent ovulation induction therapy. Results were replicated in a retrospective cohort of 185 patients with polycystic ovary syndrome (PCOS) (Rotterdam criteria).INTERVENTION(S): Ovulation induction using clomiphene citrate (CC) as first-line and exogenous gonadotropins (exFSH) as second-line therapy.MAIN OUTCOME MEASURE(S): Clomiphene-resistant anovulation (CRA), clomiphene failure (CCF), and ongoing pregnancy rate.RESULT(S): Genotyped patients (n = 159) were similar to nongenotyped women (n = 81) regarding clinical characteristics and outcomes of ovulation induction. The 680(Ser) allele was associated with CRA. A pooled analysis of both cohorts showed an 89\% higher chance of CRA after CC treatment (odds ratio 1.9 [95\% confidence interval 1.1-3.3]) in homozygous carriers of the FSH receptor variant (680(Ser/Ser)). A lower chance of ongoing pregnancy (hazard ratio 0.51 [95\% confidence interval 0.27-0.98]) was observed among these patients during CC treatment in the prospective cohort.CONCLUSION(S): An FSH receptor polymorphism is associated with CRA during treatment with clomiphene citrate. These data may be used to design a treatment algorithm that is more efficacious and better tailored to the individual patient.",

keywords = "FSHR, ovulation induction, polymorphism, rs6166, WHO2",

author = "Olivier Valkenburg and \{van Santbrink\}, \{Evert J P\} and K{\"o}nig, \{Tamar E.\} and Themmen, \{Axel P N\} and Uitterlinden, \{Andr{\'e} G.\} and Fauser, \{Bart C J M\} and Lambalk, \{Cornelis B.\} and Laven, \{Joop S E\}",

year = "2015",

month = apr,

day = "1",

doi = "10.1016/j.fertnstert.2015.01.002",

language = "English",

volume = "103",

pages = "1081--1088",

journal = "Fertility and Sterility",

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Valkenburg, O, van Santbrink, EJP, König, TE, Themmen, APN, Uitterlinden, AG, Fauser, BCJM, Lambalk, CB & Laven, JSE 2015, 'Follicle-stimulating hormone receptor polymorphism affects the outcome of ovulation induction in normogonadotropic (World Health Organization class 2) anovulatory subfertility', Fertility and Sterility, vol. 103, no. 4, pp. 1081-1088. https://doi.org/10.1016/j.fertnstert.2015.01.002

Follicle-stimulating hormone receptor polymorphism affects the outcome of ovulation induction in normogonadotropic (World Health Organization class 2) anovulatory subfertility. / Valkenburg, Olivier; van Santbrink, Evert J P; König, Tamar E. et al.
In: Fertility and Sterility, Vol. 103, No. 4, 01.04.2015, p. 1081-1088.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Follicle-stimulating hormone receptor polymorphism affects the outcome of ovulation induction in normogonadotropic (World Health Organization class 2) anovulatory subfertility

AU - Valkenburg, Olivier

AU - van Santbrink, Evert J P

AU - König, Tamar E.

AU - Themmen, Axel P N

AU - Uitterlinden, André G.

AU - Fauser, Bart C J M

AU - Lambalk, Cornelis B.

AU - Laven, Joop S E

PY - 2015/4/1

Y1 - 2015/4/1

N2 - OBJECTIVE: To assess whether an FSH receptor polymorphism (Asn680Ser, rs6166) can affect the outcome of ovulation induction in normogonadotropic (World Health Organization class 2 [WHO2]) anovulatory subfertile women.DESIGN: Prospective, longitudinal, cohort study.SETTING: University-based fertility unit.PATIENT(S): A total of 240 consecutive women diagnosed with WHO2 anovulatory subfertility who underwent ovulation induction therapy. Results were replicated in a retrospective cohort of 185 patients with polycystic ovary syndrome (PCOS) (Rotterdam criteria).INTERVENTION(S): Ovulation induction using clomiphene citrate (CC) as first-line and exogenous gonadotropins (exFSH) as second-line therapy.MAIN OUTCOME MEASURE(S): Clomiphene-resistant anovulation (CRA), clomiphene failure (CCF), and ongoing pregnancy rate.RESULT(S): Genotyped patients (n = 159) were similar to nongenotyped women (n = 81) regarding clinical characteristics and outcomes of ovulation induction. The 680(Ser) allele was associated with CRA. A pooled analysis of both cohorts showed an 89% higher chance of CRA after CC treatment (odds ratio 1.9 [95% confidence interval 1.1-3.3]) in homozygous carriers of the FSH receptor variant (680(Ser/Ser)). A lower chance of ongoing pregnancy (hazard ratio 0.51 [95% confidence interval 0.27-0.98]) was observed among these patients during CC treatment in the prospective cohort.CONCLUSION(S): An FSH receptor polymorphism is associated with CRA during treatment with clomiphene citrate. These data may be used to design a treatment algorithm that is more efficacious and better tailored to the individual patient.

AB - OBJECTIVE: To assess whether an FSH receptor polymorphism (Asn680Ser, rs6166) can affect the outcome of ovulation induction in normogonadotropic (World Health Organization class 2 [WHO2]) anovulatory subfertile women.DESIGN: Prospective, longitudinal, cohort study.SETTING: University-based fertility unit.PATIENT(S): A total of 240 consecutive women diagnosed with WHO2 anovulatory subfertility who underwent ovulation induction therapy. Results were replicated in a retrospective cohort of 185 patients with polycystic ovary syndrome (PCOS) (Rotterdam criteria).INTERVENTION(S): Ovulation induction using clomiphene citrate (CC) as first-line and exogenous gonadotropins (exFSH) as second-line therapy.MAIN OUTCOME MEASURE(S): Clomiphene-resistant anovulation (CRA), clomiphene failure (CCF), and ongoing pregnancy rate.RESULT(S): Genotyped patients (n = 159) were similar to nongenotyped women (n = 81) regarding clinical characteristics and outcomes of ovulation induction. The 680(Ser) allele was associated with CRA. A pooled analysis of both cohorts showed an 89% higher chance of CRA after CC treatment (odds ratio 1.9 [95% confidence interval 1.1-3.3]) in homozygous carriers of the FSH receptor variant (680(Ser/Ser)). A lower chance of ongoing pregnancy (hazard ratio 0.51 [95% confidence interval 0.27-0.98]) was observed among these patients during CC treatment in the prospective cohort.CONCLUSION(S): An FSH receptor polymorphism is associated with CRA during treatment with clomiphene citrate. These data may be used to design a treatment algorithm that is more efficacious and better tailored to the individual patient.

KW - FSHR

KW - ovulation induction

KW - polymorphism

KW - rs6166

KW - WHO2

UR - https://www.scopus.com/pages/publications/84930810440

U2 - 10.1016/j.fertnstert.2015.01.002

DO - 10.1016/j.fertnstert.2015.01.002

M3 - Article

C2 - 25721191

AN - SCOPUS:84930810440

SN - 0015-0282

VL - 103

SP - 1081

EP - 1088

JO - Fertility and Sterility

JF - Fertility and Sterility

IS - 4

ER -

Follicle-stimulating hormone receptor polymorphism affects the outcome of ovulation induction in normogonadotropic (World Health Organization class 2) anovulatory subfertility

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Keywords

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