Relationship of sperm DNA fragmentation (TUNEL) to blastulation and euploidy after IVF

Abstract

To determine if elevated sperm DNA fragmentation is related to embryo euploidy and blastulation rates. Retrospective cohort study. 86 IVF cycles in couples where the male partner had a TUNEL assay performed on unprocessed semen samples from 1/2011- 12/2015 were analyzed for percent blastulation and results of comprehensive chromosomal screening (CCS) by trophectoderm biopsy. Only cycles, in which the partner underwent a prior semen evaluation for DNA fragmentation with the Terminal deoxynucleotidyl transferase-mediated d-UTP Nick End Labeling (TUNEL) assay were included for analysis. Donor egg cycles were excluded. Results were analyzed according to whether TUNEL results were normal or abnormal (≥7%). Data was further stratified according to female age categories. Fisher exact t test and Chi-square were used to analyze data and p<0.05 was considered significant. Mean age of patients in the study cohort was 36.8 ± 5.1 for the female and 43.2 ± 10.2 for the male partner. Ninety-one percent of the embryos were fertilized with ejaculated sperm and the remaining with surgically retrieved sperm. Of 678 embryos evaluated, 305 reached the blastocyst stage and 93% of blastocysts underwent PGS. The mean TUNEL result in the study cohort was 8.9 ± 7.4%. Overall, the rate of euploidy in the PGS group according to age was 64% (age ≤ 37), 32.8% (age 38-40), 16.6% (age 41), and 6.8% (age ≥ 42). There was no correlation between the rate of aneuploidy and abnormal TUNEL result except for women of age ≤ 37 years, p=0.003. Overall blastulation rates were 64.7% (age ≤ 37), 52.9% (age 38-40), 48.4% (age 41), 30.6% (age ≥ 42), which did not correlate with abnormal TUNEL for any age group. Elevated sperm DNA fragmentation may correlate with decreased euploidy for younger women ≤ 37 undergoing IVF, but does not likely correlate with blastulation rates. The relationship between sperm DNA fragmentation and early IVF outcomes of embryo development and ploidy should be further evaluated in studies powered to detect a difference in outcomes. Sperm DNA fragmentation may affect pregnancy and ongoing pregnancy rates through mechanisms beyond early embryo development.Tabled 1Rates of aneuploidy and blastulation as compared with TUNEL assayAgeTunelEuploidAneuploidp-valueBlastocystNo Blastocystp-value≤ 37n=135n=76*0.003n=242n=1320.28% embryos abnormal TUNEL55.2%44.8%62.7%37.3%% embryos normal TUNEL74.7%25.3%68.1%31.9%38-40n=21n=430.14n=63n=560.51% embryos abnormal TUNEL47.1%52.9%58.1%41.9%% embryos normal TUNEL27.7%72.3%45.9%43.9%≥ 41n=8n=660.26n=68n=1170.14% embryos abnormal TUNEL16.7%83.3%54.2%45.8%% embryos normal TUNEL8.5%92.0%30.7%14.6%Total164185373305*statistical significance. Open table in a new tab