P-039 Male age is associated with sperm DNA integrity: Selection of high DNA integrity sperm by microfluidics sorting is critical to clinical outcomes in older patients
Authors: Morishita N , Miura M , Kobayashi Y , Matsunaga R , Maeda T , Ochi M , Horiuchi T 
Published: June 2022

Abstract

Study question
Does sperm DNA integrity affect clinical outcomes of ICSI?

Summary answer
Use of high DNA integrity sperm selected by microfluidics sperm sorting results in lower miscarriage rates in the patients of 39-years old and more.

What is known already
High sperm DNA damage is associated with decreased normal fertilization, embryo development and pregnancy rates, and an increased miscarriage rate. On the other hand, oocytes from older women have decreased pregnancy rate, and increased miscarriage rate because of possibility of low ability to repair sperm with DNA fragmentation, and dramatical increases of aneuploidy as women age. A microfluidic sperm selection chamber (MSS, ZyMōt™; DxNow) is a device designed to collect sperm with higher chromatin integrity than density gradient centrifugation (DGC).

Study design, size, duration
Sperm analysis was performed by sperm chromatin dispersion (SCD) test and comet assay in the same sample of 15 cases between October 2020 and February 2021. ICSI outcomes by DGC and MSS were compared with blastocyst development, and pregnancy rates in vitrified-thawed single blastocyst transfers cycle for 518 cases between August 2018 and May 2021.

Participants/materials, setting, methods
SCD test was optimized as a rapid procedure, with sperm showing a halo deemed normal, and those without a halo abnormal. Comet assay results were analyzed using CometScore 2.0, with comparison of %Tail DNA. ICSI outcomes were analyzed using multiple logistics regressions of male and female ages.

Main results and the role of chance
We found a positive correlation between male age and sperm DNA fragmentation rates in raw semen using SCD test (r = 0.70) and Comet assay (r = 0.42). Higher DNA integrity sperm could select using MSS than DGC. In this study with ICSI outcomes, 170 of 318 (53.5%) blastocyst transfers resulted in pregnancy, and 49 (28.8%) subsequently miscarried. The data were classified according to less than or more than 39 years old of male age detected by multiple logistics regressions. In patients with ≥39 years of male age, the female age was significantly higher and blastocyst and pregnancy rates were significantly lower, and the miscarriage rate was significantly higher than &lt;39 years of male age. Since sperm DNA fragmentation increased in accordance with male age, we compared MSS and DGC in the patients with male age ≥39 years. There was no significant difference in blastocyst, pregnancy, and miscarriage rates in female age &lt;39 years. While in ≥ 39 years of female age, blastocyst and pregnancy rates in MSS were not significantly different from DGC, but the miscarriage rate in MSS was significantly lower than in DGC (27.3 vs. 57.1%).

Limitations, reasons for caution
The sample size for each study was small. Analysis of sperm DNA fragmentation and samples in ICSI outcomes were not the same. The retrospective nature of ICSI outcomes in this study does not allow controlling of unknown confounders.

Wider implications of the findings
Sperm DNA fragmentation depended on male age affected fertility outcomes. However, when male age is higher, masking the effect of male age by female age. In this study, we found out the improvement of ICSI outcome by using high DNA integrity sperm selected by MSS in both ≥39 years.

Trial registration number
Not applicable