Follicle-stimulating hormone receptor gene polymorphism and ovarian responses to controlled ovarian hyperstimulation for IVF-ET

Abstract

This study was performed to investigate the association between FSH receptor (FSHR) gene polymorphism at position 680 and the outcomes of controlled ovarian hyperstimulation (COH) for in vitro fertilization and embryo transfer (IVF-ET) in Korean women. Two hundred and sixty-three patients under 40 years of age who underwent IVF-ET procedures were included in this study. Patients with polycystic ovary syndrome, endometriosis, or a previous history of ovarian surgery were excluded. Following extraction of genomic DNA, the FSHR polymorphism at position 680 was determined by polymerase chain reaction and restriction fragment length polymorphism analysis. The FSHR genotype distribution was 41.8% for Asn/ Asn, 45.6% for Asn/Ser, and 12.5% for Ser/Ser FSHR genotype groups. Although there was no difference among the three genotype groups in terms of the age and infertility diagnosis of study subjects, the basal levels of FSH (day 3) were significantly different [5.7 ± 0.3 IU/l (mean±SEM), 6.0 ± 0.3 IU/l, and 8.2 ± 0.9 IU/l for Asn/Asn, Asn/Ser, and Ser/Ser groups, respectively. The Ser/Ser group tended to require a higher dose of gonadotropins for COH, and tended to show lower serum estradiol levels at the time of hCG administration than the other two groups, though these differences did not reach statistical significance. The numbers of oocytes retrieved tended to be different for the three groups (9.6 ± 0.6, 10.2 ± 0.6, and 7.9 ± 0.8 for Asn/Asn, Asn/Ser, and Ser/Ser groups, respectively). Clinical pregnancy rate was significantly higher in Asn/Asn, compared to the others (45.7 vs. 30.5%, P=0.013). The homozygous Ser/Ser genotype of FSHR polymorphism at position 680 may be associated with a reduced ovarian response to COH for IVF-ET, while Asn/Asn genotypes showed a higher pregnancy rate.

Follicle stimulating hormone receptor gene variants in women with primary and secondary amenorrhea

“…G −29 A, A 919 G (Thr 307 Ala) and A 2039 G (Asn 680 Ser) polymorphisms have been extensively studied by different investigators. It was reported that the polymorphism A 2039 G is associated with high basal FSH levels in women undergoing Assisted Reproductive Technology (ART) programme [17][18][19][20][21][22]. Recently, we have reported association of FSHR gene polymorphism (A 919 G, G −29 A) with altered ovarian response in subjects undergoing gonadotropin treatment during ART programme [23,24].…”

“…However, a few studies have refuted this view [22,33]. We have recently reported that alteration at 919 position (Thr 307 Ala) of FSHR gene, is associated with hyper ovarian response [23].…”

“…Primary amenorrhea subjects (n=48) Secondary amenorrhea subjects (n=38) response of the ovary to exogenous FSH [17,18,20,22]. However, a few studies have refuted this view [22,33].…”

“…It has been reported earlier that certain polymorphisms in the FSHR gene are associated with altered responsiveness to FSH in women undergoing ART programme. It has been shown that Ser 680 substitution is associated with hyporesponse of the ovary to exogenous FSH [17,18,20,22]. However, a few studies have refuted this view [22,33].…”

FSH-receptor Ala307Thr polymorphism is associated to polycystic ovary syndrome and to a higher responsiveness to exogenous FSH in Italian women

“…The relationship between allelic variants at these positions, the presence of polycystic ovary syndrome (PCOS), and the responsiveness to exogenous FSH have been studied in some ethnic groups [3]. A different responsiveness to FSH according to the allelic variant at position 680 has been repeatedly reported, Ser680 homozygote women being more FSHresistant than women with homozygote Asn680, and heterozygote (Ser680Asn) patients showing an intermediate responsiveness [4][5][6][7].…”