Assessment of FSHR variants and antimüllerian hormone in infertility patients with a reduced ovarian response to gonadotropin stimulation

Capsule:
FSHR variants such as Asn680Ser and Ile160Thr may be cofactors for infertility in women who respond poorly to ovarian stimulation, but low ovarian reserve appears to be the main cause.

Authors:
Helge Binder, M.D., Reiner Strick, Ph.D., Olga Zaherdoust, M.D., Ralf Dittrich, Ph.D., Miklos Hamori, M.D., Matthias W. Beckmann, M.D., Patricia G. Oppelt, M.D.
Volume 97, Issue 5, Pages 1169-1175.e1, May 2012

Objective:
To study women with a poor response to ovarian hormone stimulation, known as low responders. Genetic defects in the FSH receptor gene (FSHR) were analyzed as well as antimüllerian hormone (AMH) for ovarian reserve.

Design:
Retrospective cohort study.

Setting:
University hospital.

Patient(s):
Two hundred fifty-nine patients total: 74 low responders; 88 patients receiving assisted reproduction therapy (ART) with a normal ovarian response; and 97 women with a normal fertility status.

Intervention(s):
DNA from patients was analyzed using real-time polymerase chain reaction. Serum concentrations of AMH were assessed using ELISA.

Main Outcome Measure(s):
The FSHR variants Asn680Ser (rs6166), Ala189Val (rs121909658), Ile160Thr (rs121909659), Thr449Ile (rs28928870) and the serum AMH concentrations were assessed.

Result(s):
With the exception of the frequent Asn680Ser polymorphism, no homozygotic SNPs of FSHR were found. In the group of ART patients, Thr160/Ile160 variants were more frequent in comparison with women with normal fertility. The Ser680/Ser680 was more frequent in ART patients than in women with normal reproductive function. The rate of live births was markedly reduced, particularly in the low responder group. No difference was noted in the distribution of the Ala189Val and Thr449Ile variant. Low serum AMH values were observed in 75% of the low responder group.

Conclusion(s):
FSHR gene variations such as Asn680Ser, Ala189Val, Thr449Ile, and Ile160Thr did not seem to be a decisive factor of poor response to fertility treatment, whereas the low ovarian reserve determined by AMH is considered more crucial.

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