P-016 WHO 2021-based comprehensive appraisal of sperm factor parameters’ association with embryological and clinical outcomes. A single center study of 4013 PGT-A cycles
Authors: Mazzilli R , Cimadomo D , Dovere L , Innocenti F , Maggiulli R , Albricci L , Ginesi S , Esposito A , Vallefuoco R , Ferrero S , Vaiarelli A , Ubaldi F M , Ferlin A , Rienzi L 
Published: June 2023

Abstract

Study question
What is the impact of sperm parameters and paternal age on all embryological and clinical outcomes during ICSI-cycles with aneuploidy testing?

Summary answer
Reduced basal/post swim-up motility and patients with concentration+morphology+motility &lt;5th-percentile (based on WHO-2021) are associated with poorer embryological outcomes and cumulative-live-birth-rate per concluded PGT-A cycle.

What is known already
Previous studies reported an association between oligoasthenoteratozoospermia (OAT), obstructive azoospermia (OA) and non-obstructive azoospermia (NOA) and poorer fertilization/blastulation rates, but no impact on euploidy rates at the blastocyst stage. Similarly, the clinical outcomes were mostly independent from sperm characteristics when euploid blastocysts are transferred. The data about paternal age effect are controversial, varying between absent and severe embryological/clinical impact. Moreover, little is known about the association between each semen analysis parameters and embryological/clinical outcomes. Lastly, most of the evidence to date was based on WHO 2010 criteria, recently updated by WHO 2021, and did not mention cumulative-live-birth-rates (CLBR) per cycle.

Study design, size, duration
Retrospective study at a single private center involving 4013 ICSI+PGT-A cycles with own-oocytes conducted by 3101 couples (2013-2021). The primary embryological outcome was euploid-blastocyst-rate (EBR) per cohort of inseminated oocytes. The primary clinical outcome was CLBR per concluded cycle (i.e., LB achieved or no transferable/all transferred blastocysts). Intermediate embryological/clinical outcomes were also tested. All parameters were analyzed as continuous variables. For some analyses we categorized paternal age (&lt;38/38-44/&gt;44 years) and sperm factor (WHO-2021 parameters&lt;5th percentile).

Participants/materials, setting, methods
GnRH-antagonist ovarian-stimulation, ICSI, trophectoderm biopsy without zona-pellucida drilling in day3, qPCR/NGS-based analysis to report non-mosaic aneuploidies (segmental aneuploidies reported from 2017 onwards; N = 1991 cycles) and vitrified-warmed euploid single-blastocyst-transfers were conducted. Semen analysis (volume, concentration, total sperm per ejaculate, basal/post swim-up motility, morphology), sperm characteristics (ejaculated/FNA/TESE; fresh/frozen), DNA-fragmentation-index (DFI, outlined via Tunel-test; N = 188 cycles), paternal BMI and age were investigated for their association with embryological/clinical outcomes adjusted for confounders via linear/logistic regressions.

Main results and the role of chance
Maternal and paternal age were 38.9±3.2(range:23-45) and 41.9±5.7(25-72) years, 10±6.3(1-44) cumulus-oocyte-complexes were retrieved and 7.3±4.6(1-32) metaphase-II oocytes inseminated. Cycles showing all parameters &gt;5th-percentile were 47.1%(N = 1890), concentration&lt;5th-percentile were 3.7%(N = 149), motility&lt;5th-percentile were 3.9%(N = 155), morphology&lt;5th-percentile were 10.1%(N = 405), concentration+motility&lt;5th-percentile were 1.7%(N = 70), concentration+morphology&lt;5th-percentile were 6.2%(N = 248), motility+morphology&lt;5th-percentile were 5.0%(N = 70), concentration+motility+morphology&lt;5th-percentile were 19.9%(N = 797), OA and NOA were 1.4%(N = 56) and 1.0%(N = 41), respectively. The only confounder upon EBR per cohort of metaphase-II oocytes was maternal age. Only basal/post swim-up motility was associated with this outcome. When categorized, only concentration+morphology&lt;5th-percentile (-2.7%,95%CI -5.1 to -0.3%, adjusted-p=0.03), concentration+morphology+motility&lt;5th-percentile (-4.0%,95%CI -5.5 to -2.6%, adjusted-p&lt;0.01), OA (-5.5%,95%CI -10.3 to -0.7%, adjusted-p=0.03) and NOA (-5.8%,95%CI -11.4 to -0.1%, adjusted-p=0.05) showed significantly poorer results. Maternal age and number of metaphase-II oocytes were the confounders upon the chance to obtain ≥1 euploid blastocyst and ≥1 LB among concluded cycles. Only basal/post swim-up motility was associated with this outcome. When categorized, only concentration+morphology+motility&lt;5th-percentile showed significantly lower chances (multivariate-OR:0.74,95%CI 0.61-0.90, adjusted-p&lt;0.01 and multivariate-OR:0.74,95%CI 0.59-0.92, adjusted-p&lt;0.01). No association was reported between semen parameters/sperm factor categories and 1PN/³3PN rates, day5-7 blastocyst-rate, morphological quality, outcomes per euploid transfer. Paternal age categories were associated with day5-blastocyst (N = 1131/3308,34.2%, N = 1179/3644,32.4%, and N = 919/3127,29.4%) and AA-blastocyst rates (N = 1732/3308,52.4%, N = 1815/3644,49.8%, and N = 1387/3127,44.4%) in men &lt;38/38-44/&gt;44 years, respectively (p &lt; 0.01).

Limitations, reasons for caution
Some confounders were unbalanced among the study groups but accounted for in linear/logistic regressions. 9% of the cycles were not concluded by the time of abstract drafting. The sample size in the groups of surgically-retrieved sperm is limited, in part because NOA patients due to genetic causes were not included.

Wider implications of the findings
By comprehensively accounting for sperm factor characteristics, this report provides reproductive professionals with useful figures to counsel infertile couples about their chance of success during IVF. These estimates are useful for the decision-making process regarding the most effective clinical strategies to apply. Further studies including more NOA/OA patients are warranted.

Trial registration number
not applicable