Abstract Study question Can a novel sperm selection technique (GST) yield higher rates of embryos and offspring of the desired sex in couples undergoing ICSI with PGT-A? Summary answer GST consistently enriched spermatozoa, resulting in a higher proportion of embryos and offspring of the desired sex without impairing clinical outcomes or offspring health. What is known already Although various methods to select sex-specific spermatozoa have been proposed over the years, many of these techniques have been shown to have varying degrees of success in addition to being time-consuming and costly. Moreover, the use of fluorescence and electrical charges in some of these methods has raised concerns about their potential contribution to congenital malformations. Here, we tested a novel sperm selection method aimed at achieving a higher proportion of embryos of the desired sex, without compromising clinical outcome or offspring health. Study design, size, duration Over a 6-year period, ejaculates from male partners of couples (n = 109) undergoing ICSI with PGT-A were processed using GST to enrich spermatozoa for the couples’ preferred sex. Standard sperm processing was carried out for couples undergoing ICSI exclusively to assess conceptus aneuploidy, comprising the control group (n = 1,261). The proportion of male and female spermatozoa in the initial and selected specimens, PGT-A results, and ICSI outcomes were compared between the two groups. Participants/materials, setting, methods A total of 1,370 couples were treated in 2,483 ICSI cycles. Standard sperm processing was performed for 1,261 couples who did not have an offspring sex preference. For 109 consenting couples, GST was used to enrich spermatozoa for their desired sex (IRB 1306014043). To confirm sex enrichment, ≥1,000 sperm cells were screened by fluorescent in-situ hybridization (FISH) for 9 chromosomes. The couples’ PGT-A results and ICSI outcomes were compared between the control and GST cohorts. Main results and the role of chance For the control cohort (n = 1,261), ejaculates were processed in the standard fashion. Spermatozoa sex ratio was unaffected. These couples (maternal age, 37.1±4yrs; paternal age, 39.1±6yrs) underwent 2,356 ICSI cycles (1.2±1), yielding an 80.9% fertilization rate (14,830/18,321). PGT-A results confirmed that 46.6% (n = 760) of their embryos were female and 53.4% (n = 872) were male. They achieved a 76.3% (725/950) implantation rate and a 64.9% (617/950) clinical pregnancy rate resulting in 569 healthy deliveries (48% female, 52% male). From the study cohort (n = 109), 60 couples desired a female and 49 desired a male child. Those who desired female offspring (maternal age, 37.9±4yrs; paternal age, 40.8±6yrs) obtained an 81.6% sperm sex enrichment, per FISH. They underwent 74 ICSI cycles and achieved a 77.6% (592/763) fertilization rate resulting in 78.1% (235/301) female embryos that generated a 79.3% (23/29) implantation rate, yielding 16 singleton deliveries of healthy female offspring that are developing normally. The 49 couples (maternal age, 37.6±3yrs; paternal age, 40.8±5yrs) preferring male offspring obtained an 80.8% sperm sex enrichment. They underwent 53 ICSI cycles and achieved a 74.7% (481/644) fertilization rate with an equivalent proportion of male embryos (231/292, 79.1%). Their implantation rate was 90.9% (20/22), yielding 14 healthy male singletons, all developing normally. Limitations, reasons for caution Although our sperm sex selection method does not guarantee offspring of a specific sex, it allowed couples participating in the study to obtain a greater proportion of conceptuses of their desired genotype. This method does not aim to replace PGT-A, but rather reduce embryo wastage. Wider implications of the findings Semen specimens processed by GST yielded satisfactory fertilization and embryo development, comparable to those from the control cohort. Moreover, offspring health was not negatively affected. These encouraging findings indicate that our method is safe and can consistently enrich for the desired embryo sex in a reliable and ethically palatable manner. Trial registration number n/a