Significance of a common single nucleotide polymorphism in exon 10 of the follicle-stimulating hormone (FSH) receptor gene for the ovarian response to FSH: a pharmacogenetic approach to controlled ovarian hyperstimulation.
The p.N680S sequence variation of the follicle-stimulating hormone (FSH) receptor gene was previously shown to influence the ovarian response to FSH in normo-ovulatory women undergoing controlled ovarian hyperstimulation. In this prospective, randomized, controlled study, we tested whether the same daily dose of FSH results in lower levels of oestradiol in women homozygous for the p.N680S sequence variation, and whether the difference can be overcome by higher FSH doses. Women undergoing controlled ovarian hyperstimulation for in vitro fertilization or intracytoplasmic sperm injection and homozygous for the wild-type or for the p.N680S FSH receptor were randomly assigned to group I (Ser/Ser, n=24), receiving an FSH dose of 150 U/day, or group II (Ser/Ser, n=25), receiving an FSH dose of 225 U/day. In group III (Asn/Asn, n=44), the FSH dose was 150 U/day. Age and basal FSH levels were not different between groups. At ovulation induction, total FSH doses were comparable in group I (1631+/-96 U) and group III (1640+/-57 U) but significantly higher in group II (2421+/-112 U) (P<0.001). Peak oestradiol levels on the day of human chorionic gonadotrophin (hCG) administration were significantly lower in group I (5680+/-675 pmol/l) compared to group III (8679+/-804 pmol/l) (P=0.028). Increasing the FSH dose from 150 to 225 U/day overcame the lower oestradiol response in women with Ser/Ser (group II, 7804+/-983 pmol/l). In women undergoing controlled ovarian hyperstimulation, the p.N680S sequence variation results in lower oestradiol levels following FSH stimulation. This lower FSH receptor sensitivity can be overcome by higher FSH doses.
Behre
Hermann M
HM
Andrology Unit, Department of Urology, University Hospital, Halle, University Hospital, Münster, Germany.
Greb
Robert R
RR
Mempel
Andrea
A
Sonntag
Barbara
B
Kiesel
Ludwig
L
Kaltwasser
Petra
P
Seliger
Ewald
E
Röpke
Friedrich
F
Gromoll
Jörg
J
Nieschlag
Eberhard
E
Simoni
Manuela
M
D000293:Adolescent; D000328:Adult; D006063:Chorionic Gonadotropin / Q000627:therapeutic use; D004958:Estradiol / Q000378:metabolism; D005091:Exons / Q000235:genetics*; D005260:Female; D043373:Follicle Stimulating Hormone, Human / Q000097:blood / Q000627:therapeutic use*; D005838:Genotype; D006801:Humans; D010053:Ovary / Q000187:drug effects* / Q000502:physiology; D010062:Ovulation Induction; D010597:Pharmacogenetics; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011962:Receptors, FSH / Q000235:genetics*; D011994:Recombinant Proteins / Q000627:therapeutic use
D006063:Chorionic Gonadotropin; D043373:Follicle Stimulating Hormone, Human; D011962:Receptors, FSH; D011994:Recombinant Proteins; D004958:Estradiol