رسائل ماجيستير
English
2017
Association of anti mullerian hormone, and Estrogen receptor 1 gene polymorphism with outcome of in vitro fertilization
أحمد محمد علي شاكر مالك, مؤيد عمران الغزالي, ملال محمد الجبوري
كلية الطب-جامعة بابل · العراق
Infertility is the only complex medical problem that affects a couple with important psychological, economic, demographic, and medical implications. Estrogen, as a significant hormone within pregnancy, performs the actions by two types of receptors. Estrogen receptor alpha, encoded by estrogen receptor 1 (ESR1) gene, is present in a larger quantity than the other estrogen receptor, estrogen receptor beta, encoded by estrogen receptor 2 (ESR2) gene. ESR1 exists in all human reproductive systems. Association of ESR1 gene polymorphism has been shown in polycystic ovary syndrome, breast cancer risk, endometriosis-related infertility, and intracytoplasmic sperm injection (ICSI) failure. In this study, the hypothesis is that polymorphisms in the ESR1 gene, anti-Müllerian hormone, and estradiol level in women may be associated with ICSI outcome.
The study included 44 infertile women as the study group, 23 with ICSI failure as the non-pregnant group, and 21 with ICSI success as the pregnant group, and 44 regularly menstruating women as control. Hormonal assays were done for all patients after obtaining blood samples and then centrifuged to get serum for hormonal assays that included the following: testosterone, FSH, LH, prolactin, TSH, AMH, estradiol. DNA was extracted from the whole blood samples by using a genomic DNA purification kit. Then, the extracted DNA was used for amplification of targeted fragments by using PCR. PCR-RFLP was applied for the identification of these SNPs by using XbaI restriction enzymes, respectively, then sequencing was used for verification.
Whole blood samples collected from patients and control group were used to extract DNA for ESR1 gene polymorphism study using PCR-RFLP technique. Statistical analysis was done through χ², by using SPSS software, version 20. Values smaller than 0.05 were considered significant.
The results of the present study refer to frequencies of XbaI genotypes in the control group: 7 (15.9%), 24 (54.5%), and 13 (29.6%) for AA, AG, and GG, respectively. The genotype frequencies were 22 (50%), 18 (40.9%), and 4 (9.1%) for AA, AG, and GG in the infertile group, respectively. Allele frequencies of A and G alleles in the control group were 43% and 57%, respectively, and in the infertile group they were 70% and 30%, respectively.
An association was found between the ESR1 rs9340799 polymorphism and clinical phenotype in the infertile group (P = 0.00026) compared to the control group. In conclusion, ESR1 genotype analysis could help ICSI clinicians in the modification of controlled ovarian stimulation so as to achieve synchronization in follicular development and therefore higher mature oocyte numbers and IVF/ICSI results.