The TP53 gene (rs1625895) C>T polymorphism is associated with ovarian reserve and ovarian response to recombinant FSH during IVF/ICSI treatment

Fertility and Sterility(2019)

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Abstract
To investigate a possible association between a TP53 gene polymorphism and ovarian response after IVF/ICSI cycles. Prospective cohort study. This study included 136 women submitted to IVF/ICSI cycles. The enrolled individuals met the following inclusion criteria: age ≤37years; normal karyotype; having two ovaries as evinced in ultrasound examination; no history of ovarian surgery, endometriosis, hydrosalpinx, infection, or endocrine disorders.DNA extracted from peripheral blood was sequenced on MiSeq(Illumina) to find single nucleotide polymorphisms (SNPs) in the TP53 gene. SNPs were identified using the TruSeq Custom Amplicon (TSCA) Panel (DesignStudio Illumina).The findings from sequencing were associated with age, anti-Müllerian hormone (AMH) levels, antral follicle counts (AFC), total dose of recombinant FSH (r-FSH), follicle size, number of retrieved oocytes, and clinical outcome of IVF/ICSI cycles. The TP53 (rs1625895) C>T SNP were identified. Women with the TT genotype had significantly poorer ovarian reserve indicators (lower levels of AMH and AFC), poorer ovarian response to rFSH, and poorer clinical outcomes (implantation rate and clinical pregnancy rate/patient). Table 1 presents a summary of the results.Table 1ResultsTP53 (rs1625895) GenotypesCCTCTTPn62 (45.6%)28 (20.6%)46 (33.8%)Age (years)33.3±2.833.3±7.433.9±3.00.46AMH (ng/ml)3.0±3.7a2.9±4.11.2±1.6aa0.01AFC (n)17.8±12.1a15.8±10.1b9.4±6.2a,ba<0.0001;b0.01Total dose of rFSH (IU)1840±1083a2036±1101b2642±1027a,ba<0.0001;b0.007Follicles (n):Total15.5±9.9a13.6±10.69.1±5.5aa0.005Follicles (n):≥18 mm4.2±2.7a.4.1±2.83.2±1.9aa0.02Retrieved oocytes:Total11.0±7.5a9.3±7.96.7±2.4aa0.01Retrieved oocytes:Metaphase II8.2±6.1a6.8±5.94.9±2.6aa0.01Fertilization rate66.5%67.3%69.7%0.66Implantation rate36.8%a32.8%22.0%aa0.01Pregnancy rate/transfer50.7%45.5%35.3%0.23Pregnancy rate/patient61.3%a53.5%39.1%aa0.03Values within rows with the same superscript letter were significantly different. Open table in a new tab Values within rows with the same superscript letter were significantly different. TP53 (rs1625895) C>T polymorphism was associated with ovarian reserve and apparently affected ovarian response to rFSH and the clinical outcomes of IVF/ICSI cycles. Homozygosity of the T allele was associated with significantly poorer results. The identified SNP might provide an additional tool to test patients for ovarian reserve/response and thus help in the individualization of ovarian stimulation protocols. To the best of our knowledge, this was the first study to associate this SNP and ovarian response to gonadotropins.
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Key words
tp53 gene,ovarian response,ovarian reserve,recombinant fsh,ivf/icsi
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