P-108 Does DNA Fragmentation.level significantly impact clinical outcomes in patients undertaking Assisted Reproduction with using donor oocytes?
Authors: McNally A , Harrity C , Marron K 
Published: June 2023

Abstract

Study question
Does an abnormal Sperm DNA Fragmentation Index significantly impact clinical outcomes in patients undergoing Assisted Reproduction with ICSI using donor oocytes?

Summary answer
No statistical difference was seen in pregnancy or miscarriage rates between high or low DNA fragmentation indexes with oocyte donation cycles using intracytoplasmic sperm injection.

What is known already
High levels of sperm DNA fragmentation are proposed to have an adverse impact on reproduction. While subject to debate, generally accepted ranges of &gt; 30% considered high and associated with poorer outcomes, with levels &lt;15% considered normal. Impact in the intermediate range if 15-30% is less understood. Potential interventions for elevated DFI include ICSI, lifestyle changes, antioxidant therapy or more controversially TESE. It is thought that high quality oocytes have the potential to repair sperm DNA damage- thus the use of younger donors with higher fertility in oocyte donation cycles may improve outcome and overcome a high DFI.

Study design, size, duration
A retrospective cohort analysis was performed on our database of donor oocyte FET treatment between January 2016 and December 2020, with 1370 cycles identified Screening to identify those couples where pre- treatment sperm DFI was performed as part of the treatment workup, and DFI was analysed in 9% of these cycle (n = 124). Clinical outcomes were recorded including positive HCG, clinical pregnancy rate, miscarriage rate and ongoing pregnancy rate at 12/40 gestation, and compared between groups.

Participants/materials, setting, methods
Oocyte donation cycles with baseline Sperm DFI measurements in a tertiary academic centre were identified. Donor treatments were chosen to reduce the impact of female factor variation on results. 49 cases had normal DFI(&lt;15%), and were compared to 21 patients in the high group ( &gt; 30). 54 patients were on the intermediate range (15-30%) and were excluded from the analysis. Pregnancy and miscarriage rates were compared between high and low groups to assess impact of DFI.

Main results and the role of chance
Elevated DFI has been proposed to have an abnormal impact on assisted reproduction outcomes. Other studies have suggested that ICSI may compensate for this, or that healthy oocytes may be able to negate any detrimental impact from the sperm. With autologous gamete treatments, large variations in the expected prognosis are due to female characteristics such as age, ovarian reserve or gynaecological disorders such as endometriosis or PCOS. This use of younger egg donors with normal AMH and the exclusion of any identifiable pelvic abnormality allows for some standardisation of the female cohort, therefore allowing a more direct assessment of the impact of any male factor abnormality on the outcome.
Positive HCG rates per embryo transfer were the same between DFI groups.
Normal 53.1% (26/49) vs High 47.65% (10/21) p = 0.68
Similarly there was no difference in Clinical Pregnancy Rates based on DFI level
Normal 44.9% (22/49) vs High 47.7% (10/21) p = 0.83
Miscarriage rates per positive HCG test were again not impacted by male sperm DFI:
Normal 30.7% (8/26) vs High 33.3 (3/10) p = 0.72
The study data demonstrates that in treatment cycles using a combination of ICSI and good quality oocytes, the clinical outcomes do not appear to be impacted by raised DFI

Limitations, reasons for caution
We previously demonstrated that fertilisation and blastulation rates were unaffected by DFI. The study was limited by a relatively small sample size, as DFI analysis was not routinely measured before treatment. Larger multi-centre studies to increase the study population and statistical power would be useful for confirmation of the findings.

Wider implications of the findings
Our data suggests that biochemical, clinical and ongoing pregnancy rates, and also miscarriage rate, were not adversely impacted by high DFI in donor oocyte cycles.This could be attributed to the ability of a high quality oocyte to repair sperm DNA damage when combined with ICSI for sperm selection and fertilisation.

Trial registration number
Not applicable