The Matrix Metalloproteinase-9 (Mmp9) P.Gln279arg Polymorphism Is Associated With Ovarian Reserve And Ovarian Response During Ivf/Icsi Treatment.

To investigate a possible association between an MMP9 gene polymorphism and ovarian response after IVF/ICSI. Prospective cohort study. This study enrolled 135 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 MMP9 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 MMP9p.Glutamine(Gln)279Arginine(Arg)(rs17576) polymorphism was identified. Women with the Gln/Gln genotype had significantly poorer ovarian reserve indicators (lower levels of AMH and AFC), poorer ovarian response to rFSH, and poorer clinical outcomes (implantation rate). Table 1 presents a summary of the resultsTable 1ResultsMMP9 p.Gln279Arg GenotypesGln/GlnGln/ArgArg/ArgPGln/GlnGln/Arg+Arg/ArgPn59.3%(80/135)31.8%(43/135)8.9%(12/135)59.3%(80/135)40/7%(55/135)Age(years)33.6±2.833.3±3.033.5±3.60.8633.6±2.833.4±3.10.57AMH(ng/ml)2.1±3.4a2.6±2.2a3.7±5.6a0.042.1±3.42.8±3.20.04AFC(n)12.4±9.9a,b16.7±8.4a22.3±17.5ba0.001;b0.0212.4±9.917.9±11.10.0004Total dose FSH(UI)2385±1173a1787±950a1854±1006a0.0042385±11731802±9540.002Follicles(n):Total10.8±7.7a16±10.6a15.8±10.5a0.0110.8±7.715.9±10.50.01Follicles(n):≥18mm3.3±2.3a,b4.6±2.8a4.8±2.5ba0.01;b0.043.3±2.34.6±2.70.004Retrieved oocytes:Total7.8±5.311.2±8.210.6±7.00.127.8±5.311.1±7.90.04Retrieved oocytes:MII5.9±4.08.1±6.88.2±6.00.585.9±4.08.1±6.60.21Fertilization66.6%a65.1%b81.9%a,ba,b0.00166.6%68.9%0.49Implantation26.4%a40.2%a30.8%a0.0226.4%38.2%0.04Pregnancy/patient46.3%62.8%58.3%0.8946.3%61.8%0.08Pregnancy/39.8%51.9%50%0.3439.8%51.5%0.14 Open table in a new tab TheMMP9 p.Gln279Arg polymorphism was associated with ovarian reserve and seemed to have affected ovarian response to rFSH and the clinical outcomes of IVF/ICSI cycles. Homozygosity of the Gln allele was associated with significantly poorer results. The identified SNP might provide an additional tool to test patients for ovarian response and thus help in the individualization of ovarian stimulation protocols.