Comparison of fsh reseptor polymorphismis between infertile women (Poor responders and good responders after controlled ovarian hyperstimulation) and fertile women

Genes coding FSHR, are on chromosome 2. Any changes occuring at these points will cause changes in amino acid arrengement in FSH receptor genes and this, as a result, will change the function of the gene. While some of these changes will result in an increase in receptor functions, some others result in a decrease in the same functions. Activating mutations may result in FSHR activation at low levels of FSH, or even in the absence of it. Sometimes these activating mutations may result in FSHR responding to other thropic hormones (e.g. TSH). Inactivating mutations may show effect by spoiling receptor ligand interaction; at the same time, these may also be effective by spoiling the signal transmission formed by FSH. The level of this resulting effect is changeable. A total bloc or a minimum effect may form. FSHR inactivating mutations may cause primer or seconder amenorrhea, infertility and premature overian syndrome (POF). On the contrary, activating mutations may cause overian hyperstimulation syndrome (OHSS), whether exogen FSH hormone is given or not. Besides point mutations, when FSHR gene polymorphisms are formed (especially codon 307 and 680), changes in response to exogen FSH hormone are observed. These results in changes in treatment response when artificial reproduction techniques are applied. In our study, we investigated the effect of the response in artificial reproduction techniques and fertility of polymorphism types formed in FSH receptor. The study involved patients at the department of Gynecology and Obstetrics in Akdeniz University between May 2009 – November 2010. Control group involved patients who became pregnant without any controlled ovarian stimulation treatment (COS) before. In all of the control group patients pregnancy occured at most one year later after intercourse. In patients taken into the category as good responder a criterium of having taken an infertility treatment and an oocyte count above 3 obtained as a response to this treatment was sought. Besides, patients without sufficient E2 level (E2 ≤ 660 pg/ml) as a result of infertility treatment were not included in this group. Criterium for being included in the group defined as poor responder was determined as oocyte count 3 or less at the end of controlled ovarian stimulation treatment and E2 levels less than 660 pg/ml after treatment. In all groups age interval was 23-39. Genomic DNA's of the patients was isolated from venous blood by modified non-enzymatic method. PCR reaction was carried out using Bio-Rad (MyCycler) and PCR Systems 9700 (Gene Amp) PCR instruments. Denaturated PCR products were loaded to ABI 3130 serial instrument and the results were evaluated using ABI squence analysis V3.1 software package. Data were analyzed using SPSS (version 18.0) (spss Inc., Chicago, USA). To evaluate the model definitional statistics such as frequency distribution, mean, standard variation were used. When disfferences were found, Bon ferronni correction was applied and Mann-Whithney test was used to determine different groups. Related to demographic features, in comparing the values, difference test between two means or Mann-Whitney U test was used. In comparing genotypes according to groups Ki-square test was used. To determine the differences in analysis 95% significance level (or α=0.05 error level) was used. When Ala307Thr polymorphism and also the Ser680Asn polymorphism seen in control groups were evaluated in itself, it was determined that heterozygot polymorphism was more frequent. Frequency of occurence for G/A genotype in Ala307Thr polymorphism in the control group was 51%, whereas this value was 53% for Ser680Asn polymorphism [Ser680Asn G/A polymorphism significantly (p=0.001) higher, Ala307Thr G/A polymorphism significantly (p=0.001) higher]. In our study, we determined that in good responder group, homozygot polymorphism ratio in Ala307Thr polymorphism was statistically less frequently seen in a significant way (p=0.013). It was also determined that in good responder group homozygot genotype (A/A) in Ser680Asn polymorphism was statistically less frequently seen in a significant way (p=0.013). Patient numbers in poor responder group was also statistically compared. In poor responder group heterozygot polymorphism in Ser680Asn polymorphism was significantly higher (p=0.031). When polymorphisms between control groups, good responder and poor responder groups were compared statistically significant differences were found. In good responder group in both Ser680Asn and Ala307Thr polymorphisms, homozygot polymorphism were seen less frequently (p<0.05). Statistically significant difference were found between high homozygot polymorphism ratio seen in poor responder group and the low occurence of overian response given to stimulation. Ages of patients having only G/A polymorphism was seen to be statistically significant higher (p=0.003). At the older ages occurence of G/A type polymorphism increases. In good responder group in Ala307Thr genotype duration of treatment was statistically significant found to be longer in patients with (A/A+G/A) polymorphism (p=0.024). Longer treatment duration seen in patients with polymorphism in good responder group, statistically was not found to be longer in poor responder group in a significant way. When poor responder and good responder groups were compared, it was seen that A/A polymorphism was higher in poor responder group (p<0.05). As a result, in poor responder group related to both Ser680Asn and Ala307Thr polymorphism, occurence of homozygot genotype was statistically significant high. However, the high value of occurence of homozygot genotype in control group prevents making a generalization about formation of FSH receptor response in sufficiency of homozygot polymorphism.