. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Abstract citation ID: deac106.030 O-248 Cluster Analysis of men with idiopathic and unexplained male infertility identifies FSHB Genotype as relevant diagnostic parameter M. Schubert 1 , H. Krenz 2 , A. Sansone 3 , S. Kliesch 1 , J. Gromoll 4 1 Centre of Reproductive Medicine and Andrology, Department of Clinical and Surgical Andrology- University Mu ¨nster, Mu ¨nster, Germany 2 Institute of Medical Informatics, University of Mu ¨nster, Mu ¨nster, Germany 3 Department of Systems Medicine, Chair of Endocrinology and Medical Sexology- University of Rome Tor Vergata, Rome, Italy 4 Institute of Reproductive and Regenerative Biology, Centre of Reproductive Medicine and Andrology CeRA- University of Mu ¨nster, Mu ¨nster, Germany Study question: In a cohort of idiopathic and unexplained infertile men we aimed to identify subgroups with similar characteristics, and therewith under- lying etiologic factors, by clustering approach. Summary answer: We identified two distinct patient clusters. Across all di- verse phenotypes of infertility, the strongest segregation markers were FSHB c.-211G>T, FSH, and bi-testicular volume. What is known already: In about 30-75% of infertile men no major causa- tive factors can be identified; leading to the diagnose of unexplained (normo- zoospermia) or idiopathic (abnormal semen parameters) male infertility. This cohort of men remains very heterogenous, albeit the detailed andrological characterization that is currently applied in infertility workup. New analysis tools such as machine learning and cluster analysis can pro- vide a more in-depth approach. Such explorative analyses have the potential to uncover hitherto hidden patterns in data that might be difficult to spot for andrologists but become visible by these tools. Study design, size, duration: A Cluster analysis was retrospectively per- formed in a clinically well characterized cohort of 2742 men with unexplained or idiopathic male infertility. These men had visited our Centre within a 10- year period (2008-2018) for infertility workup. Due to the well curated data- base (Androbase V R ) we were able to include up to 37 andrologic parameters in the unbiased cluster analysis. Participants/materials, setting, methods: After applying strict selection criteria 2742, of initially 7627, infertile men remained for cluster analysis (ex- clusion: obstructive -, genetic -, other causative factors, female factor; inclu- sion: azoo- to normozoospermia, FSH  1IU/l, Testosterone  8nmol/l). For subsequent analyses the following parameters were included: somatic/se- men/hormone parameters, testicular sonography and testis volume, genotyp- ing of the FSHB c.-211G>T (rs10835638) single nucleotide polymorphism. For cluster analysis, partitioning around medoids method was employed based on Gower distance between patients. Main results and the role of chance: The applied cluster approach for the study population yielded two separate clusters (average silhouette width 0.12). These clusters showed significantly different distributions in bi-testicu- lar volume, FSH and FSHB genotype. Cluster 1 contained all men homozygous for G (wildtype) in FSHB c.-211G>T (100%), while Cluster 2 contained most patients carrying a T allele (>96.6%). Even in subgroup analysis (Total sperm count (TSC) <1Mill and TSC 1 3 Mill) two clusters each were formed too. Again, the strongest segregation markers between the respective clusters were FSHB c.-211G>T, bitesticular volume, and FSH, supporting the notion of a contributing genetic factor. Surprisingly, sperm parameters like TSC, motility and morphology played a minor role in cluster formation; as well as testicular maldescent, varicocele, smoking, and microlithiasis testes. The genetic parameter of FSHB c.-211G>T in combination with the estab- lished parameters FSH and testicular volume should attract more attention in future clinical workups of infertile men with unknown etiologic factors. Limitations, reasons for caution: Categorical and numeric features con- tribute diversely to the calculation of patient dissimilarity. Potentially, categori- cal features can have a higher impact because patients are rated as completely different if they fall in different categories; for numeric features, the dissimilarity depends on the range of values. Wider implications of the findings: The FSHB SNP was identified as an informative segregation marker; we therefore suggest introducing diagnostic genotyping into clinical routine in men with so far idiopathic or unexplained male infertility. This may reduce the high number of infertile men with so far unknown origin by nearly one-third. Trial registration number: DFG Clinical Research Unit 326 Male Germ Cells Abstract citation ID: deac106.031 O-249 The impact of semen parameters on ICSI and pregnancy outcomes in egg recipient cycles with PGT-A A. Grammatis 1,2 , A. Pappas 3 , G. Kokkali 3 , K. Pantos 3 , N. Vlahos 2 1 Barts Health NHS Trust, Centre of Reproductive Medicine, London, United Kingdom 2 University of Athens, 2nd Department of Obstetrics and Gynaecology- Aretaieio Hospital, Athens, Greece 3 GENESIS ATHENS IVF Unit, IVF Unit, Athens, Greece Study question: To assess the effect of male factor on ICSI and pregnancy outcomes in egg recipient cycles combined with preimplantation aneuploidy testing Summary answer: In egg donor cycles where sperm was obtained from azoospermic men there was a significant effect on ART and clinical outcomes. What is known already: The increased incidence of chromosomal prob- lems in men with azoospermia and its correlation with chromosomally abnor- mal embryos and with adverse pregnancy outcomes has been shown by multiple studies. Nevertheless, few studies in the literature outline the impact of non-obstructive azoospermia in the subgroup of couples who opt to use donated eggs. The egg donation model offers an opportunity to isolate the male factor and evaluate its impact on IVF-ICSI and pregnancy outcomes. The aim of our study was to study the effect of non-obstructive azoospermia(NOA) on ICSI outcomes compared with oligoasthenozoospermia(OATS) and moderate male factor(MMF) infertility, from ART parameters to clinical outcomes. Study design, size, duration: This is a retrospective longitudinal cohort study involving 1,594 ICSI cycles using donor eggs performed between January 2016 and May 2020. The cohort was divided into three groups according to the male partner’s sperm parameters: couples with NOA accounting for 479 cycles (30%); cou- ples with OAT-S (sperm number <5 x 10 6 /ml), accounting for 442 cycles (27.8%); couples with moderate male factor, with sperm number >_5 x 10 6 / ml and <15 x 10 6 /ml, accounting for 673 cycles (42.2%). Participants/materials, setting, methods: Participants: Subfertile couples who opted to use donor eggs. Donor eggs were utilized, due to history of severe female infertility, including low ovarian reserve, poor response to ovarian stimulation, repeated IVF failures or premature ovarian failure. Setting: Private IVF Unit Intervention: ICSI with ejaculated/surgically retrieved sperm, blastocyst culture, PGT-A and frozen-thawed euploid embryo transfer. Outcomes: The primary outcomes were live birth, fertilization, blastocyst development and euploidy rates; the secondary outcomes were clinical pregnancy, miscar- riage rates, preterm labour and SGA. Main results and the role of chance: The fertilization rate was significantly reduced in the NOA group as compared to the OATS and the MMF group: 30.3% versus 63% and 77.3%. Logistic regression analysis adjusted for con- founders highlighted NOA as a negative predictor of obtaining an euploid blastocyst per inseminated oocyte. When the analysis was performed per obtained blastocyst, no correlation between male factor and euploidy rate was observed. The clinical pregnancy rates were similar in the MMF and OATS group, but significantly lower in the NOA group (38.2% versus 36.3% and 29.5% 38th Hybrid Annual Meeting of the ESHRE, Milan — Italy, 3–6 July 2022 i147 Downloaded from https://academic.oup.com/humrep/article/37/Supplement_1/deac106.031/6620391 by guest on 02 July 2022