P-071 Assessing the integrity of the male gamete genome to improve ART clinical outcomes
Authors: Kocur O , Xie P , Sung C , Souness S , Rosenwaks Z , Palermo G 
Published: June 2022

Abstract

Study question
Does screening for sperm chromatin fragmentation (SCF) benefit and help guide the treatment of patients with subtle male factor infertility?

Summary answer
In patients with abnormal SCF, an enhanced sperm selection or surgical sampling procedures improved clinical outcomes, demonstrating the value of assessing the male genome.

What is known already
Standard infertility workups include an assessment of the female genital tract, ovarian reserve, ovulation, and a semen analysis. Nevertheless, pregnancy failure is still encountered in couples with a young female partner with patent tubes and normal ovulation profile, and a male partner with normal semen analysis. SCF has previously been described as responsible for recurrent miscarriages and persistent ART failure. Therefore, the observed presence and degree of SCF may help guide treatment utilizing microfluidic sperm selection (MFSS) or Intracytoplasmic Sperm Injection (ICSI) with testicular spermatozoa, where in both cases, spermatozoa with higher genomic integrity were isolated, yielding improved clinical outcomes.

Study design, size, duration
From 2010 to 2021, we included 76 couples who had disappointing clinical outcomes; the female partners were relatively young with negative infertility workups, and the male partners had adequate semen parameters and were screened for SCF. The couples were then counseled to undergo a subsequent cycle utilizing either surgically retrieved spermatozoa or semen specimens processed by microfluidics. Clinical outcomes were measured and compared between history and post-treatment cycle(s).

Participants/materials, setting, methods
A total of 76 couples with poor clinical outcomes were included. Semen parameters were deemed adequate for ICSI with an average concentration of 33x106/mL and 33% motility. A minimum of 500 spermatozoa per sample were assessed by TUNEL assay with a 15% threshold. Fertilization, implantation, clinical pregnancy, delivery, and pregnancy loss rates were compared between history and post treatment cycle(s). Paired t and Chi-square tests were used to compare semen parameter and clinical outcomes, respectively.

Main results and the role of chance
In 168 cycles, 76 couples had poor clinical outcome results with a 67.1% fertilization rate and an 8.5% implantation rate, leading to a 16.6% clinical pregnancy rate and a 52.3% pregnancy loss rate. In these couples, testing for SCF resulted in an average DNA fragmentation of 21.6%. In efforts to reduce DNA fragmentation, 63 couples underwent microfluidics and 13 underwent surgical sperm retrieval. In an immediate post-treatment cycle, there was improvement in implantation (23.5%) (P &lt; 0.001), clinical pregnancy (39.2%) (P &lt; 0.01), and ongoing/delivery (37.3%) (P &lt; 0.001), with a concurrent reduction in the pregnancy loss rate from 52.3% to 5.0% (P &lt; 0.01).
Patients were stratified according to their level of SCF. In the moderate category (15-30%, n = 60), there was meaningful improvement in implantation (24.3%) (P &lt; 0.001), clinical pregnancy (40.4%) (P &lt; 0.01), and ongoing/delivery rates (36.2%) (P &lt; 0.001), that yielded a reduced pregnancy loss rate of 10.5% (P &lt; 0.01) compared to the history cycle. In the severe SCF category (&gt;30%, n = 16), there was also a meaningful improvement in implantation (15.4%), clinical pregnancy (21.7%), and ongoing/delivery rates (21.7%), as well as a reduction in the pregnancy loss rate (0%), albeit not significant.

Limitations, reasons for caution
In this cohort, we were able to identify a subtle male factor that was missed in the initial semen evaluation to guide treatment. However, this cohort was arbitrarily selected by the initial unexpected outcome and is a relatively small sample size.

Wider implications of the findings
The presence of a subtle male factor may explain disappointing clinical outcomes in some couples who have otherwise negative infertility evaluations. In these cases, screening for SCF can be a beneficial tool to help guide treatment and maximize the chances of a successful pregnancy.

Trial registration number
not applicable