The ovarian response to standard gonadotrophin stimulation depends on FSHR, SHBG and CYP19 gene synergism.
OBJECTIVE
Follicle stimulating hormone, sex hormone-binding globulin and cytochrome P450 aromatase play crucial roles in the regulation of mammalian reproduction. The synergistic effect of FSHR 307(T/A)/FSHR 680(N/S), SHBG(TAAAA)                   (                     n                   ) and CYP19(TTTA)                   (                     n                   ) genotypes on ovarian response to standard gonadotrophin stimulation of women undergoing medically assisted reproduction (IVF/ICSI) was explored.


METHODS
The study population consisted of 300 women under IVF/ICSI treatment and 300 women with at least with at least one successful child birth as controls. The polymorphisms were genotyped while the follicular size, the follicle and oocyte numbers were recorded during oocyte retrieval.


RESULTS
The genotype analysis, excluding heterozygotes for each particular polymorphism, revealed eight combined homozygotic FSHR/SHBG/CYP19 genotypes. A gradual reduction in the number of follicles and oocytes from FSHR 307Thr/680Asn allele/long SHBG allele/long CYP19 allele homozygotes to FSHR 307Ala/680Ser allele/short SHBG allele/short CYP19 allele homozygotes was observed (20.36 ± 6.74 vs. 8.05 ± 2.47, p < 0.008 and 13 ± 4.63 vs. 6.1 ± 2.32, p < 0.02, respectively).


CONCLUSIONS
FSHR/SHBG/CYP19 combined genotypes are associated with ovarian response to standard gonadotrophin stimulation of women undergoing medically assisted reproduction.
Genetics and IVF Unit, Department of Obstetrics and Gynecology, Medical School, University of Ioannina, 45110, Ioannina, Greece.
Leandros A
LA
Lazaros
Elissavet G
EG
Hatzi
Christina E
CE
Pamporaki
Prodromos I
PI
Sakaloglou
Nectaria V
NV
Xita
Sophia I
SI
Markoula
Theodoros I
TI
Stefos
Konstantinos A
KA
Zikopoulos
Ioannis A
IA
Georgiou
D000328:Adult; D001141:Aromatase / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005307:Fertilization in Vitro; D005838:Genotype; D006062:Gonadotropins / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D054315:Oocyte Retrieval; D006080:Ovarian Follicle; D010053:Ovary / Q000378:metabolism; D010062:Ovulation Induction / Q000379:methods; D011110:Polymorphism, Genetic; D011962:Receptors, FSH / Q000235:genetics* / Q000378:metabolism; D012738:Sex Hormone-Binding Globulin / Q000235:genetics* / Q000378:metabolism; D020554:Sperm Injections, Intracytoplasmic
D006062:Gonadotropins; D011962:Receptors, FSH; D012738:Sex Hormone-Binding Globulin; D001141:Aromatase