P-041 Enhancing Embryos of the Desired Sex in Couples Undergoing PGT-A while Minimizing Embryo Wastage
Authors: Elias R , Cheung S , Xie P , Rosenwaks Z , Palermo G D 
Published: June 2023

Abstract

Study question
Can we enhance the proportion of euploid embryos of the desired sex for couples undergoing ICSI and PGT-A with sex selection while reducing embryo wastage?

Summary answer
Using a novel sperm selection technique, we generated higher proportions of embryos and offspring of the desired sex without impairing clinical outcomes or offspring health.

What is known already
Although controversial, the wish for offspring of a specific sex is common in the U.S. Many couples, particularly those requiring IVF with PGT-A, request a euploid embryo of a specific sex. This is often associated with the generation of more conceptuses of the unwanted sex, resulting in embryo wastage. We propose utilizing a simple and safe sex selection technique (SST) to skew spermatozoa toward the desired sex so that concurrent embryos can be generated in higher proportions.

Study design, size, duration
Over a 7-year period, ejaculates from male partners of couples (n = 144) undergoing ICSI with PGT-A were processed using SST to enrich spermatozoa for their preferred sex. Standard sperm processing was carried out for couples undergoing ICSI exclusively to assess conceptus aneuploidy, comprising the control group (n = 1,440). The proportion of male and female spermatozoa in the initial and selected specimens, PGT-A results, and ICSI outcomes following frozen embryo transfer (FET) were compared between the two groups.

Participants/materials, setting, methods
A total of 1,584 couples were treated in 2,723 ICSI cycles. Standard sperm processing was performed for 1,440 couples who did not have offspring sex preferences, comprising the control. For 144 consenting couples, SST was used to enrich spermatozoa for either sex (IRB 1306014043). To confirm sex enrichment and ploidy, ≥1,000 sperm cells were screened by fluorescent in-situ hybridization (FISH) for nine chromosomes. Embryology and PGT-A outcomes were compared between the control and SST cohorts.

Main results and the role of chance
Couples (n = 1,440) from the control cohort (maternal age, 37.1±4yrs; paternal age, 39.1±6yrs) underwent 2,541 ICSI cycles, yielding an 80.1% fertilization rate (15,901/19,859). PGT-A confirmed that 46.6%(n = 4,479) of conceptuses were female and 53.4%(n = 5,132) were male. These couples achieved 76.2%(866/1136) implantation and 64.9%(737/1136) clinical pregnancy rates, resulting in 624 healthy deliveries (48% female, 52% male).
From the study cohort (n = 144), 79 desiring female offspring (maternal age, 37.9±4yrs; paternal age, 40.8±6yrs) obtained an 81.6% sperm sex enrichment. They underwent 98 ICSI cycles, achieving a 76.7%(792/1032) fertilization rate, resulting in a greater proportion of female embryos (79.1%, 351/444) than the control (P&lt;0.05), of which 78.6% (276/351) were euploid. Following FET, 39 couples obtained a 79.5% (31/39) implantation rate, yielding 27 clinical pregnancies with deliveries, thus far, of 16 female singletons, all developing normally.
The remaining 65 couples (maternal age, 37.6±3yrs; paternal age, 40.8±5yrs) preferring male offspring obtained 80.8% male sperm enrichment and underwent 84 ICSI cycles, achieving a 74.9%(723/965) fertilization rate with a greater proportion of 79.3%(249/314) male embryos compared with the control (P&lt;0.05), of which 66.3%(165/249) were euploid. Following FET, their implantation rate was 90.0%(36/40), yielding 25 clinical pregnancies that resulted in the deliveries, thus far, of 20 male singletons, all developing normally.

Limitations, reasons for caution
Although SST does not absolutely grant offspring of a specific sex, it allowed couples to obtain a greater proportion of conceptuses of their preferred genotype. This method does not replace PGT-A for sex selection, but rather enhances the generation of embryos of the desired sex, thereby reducing embryo wastage.

Wider implications of the findings
We confirmed a significantly higher proportion of conceptuses of the desired sex. Thus far, embryo developmental competence, aneuploidy rates, delivery rates, and offspring health were not impaired by SST-processed spermatozoa. This supports the safety of SST, rendering it effective and ethically palatable.

Trial registration number
n/a