Authors: M. Kaye1, K. Kaskar2, K. Silverberg1, M. VerMilyea2 1Texas Fertility Center, Reproductive Medicine, Austin, USA 2Ovation Fertility Austin, Embryology and Andrology Laboratories, Austin, USA

Study question:
Are there differences in fertilization, blastocyst development, or euploidy rates when comparing ICSI versus conventional insemination among patients with male and non-male factor infertility?

Summary answer:
Fertilization rate was lower for male factor ICSI. There were no differences in blastocyst development. Euploidy rate was lower for non-male factor ICSI.

What is known already:
ICSI was developed for male factor infertility due to its requirement for a very small number of viable sperm. Its use has expanded beyond male factor due to some studies suggesting enhanced fertilization, and lower risks of failed fertilization or inadvertent contamination of embryo biopsy specimens. There are potential risks associated with ICSI, including imprinting disorders, birth defects, and significantly increased cost. It is also unclear whether ICSI contributes to genetic abnormalities by bypassing the egg’s natural sperm selection and potentially disrupting the meiosis apparatus.

Study design, size, duration:
This retrospective cohort study of 576 patients was conducted at a single clinic from January 2021 to December 2021. Patients were grouped into (1) ICSI with male factor (n=201), (2) ICSI with non-male factor (n=160), and (3) conventional insemination with non-male factor (n=215). Primary outcome was ploidy status, determined by calculating the percentage of euploid, aneuploid, and mosaic (both low and high mosaic) among the three groups. Secondary outcomes included fertilization and blastocyst development rates.

Participants/materials, setting, methods:
Patients undergoing autologous IVF at a single clinic, with PGT-A performed at a single lab were included. Fertilization rate was defined as the percentage of 2PNs per number of mature eggs injected/inseminated. Blastocyst rate was defined as the percentage of blastocysts per 2PNs. Ploidy rate was defined as the percentage of euploid/aneuploid/mosaic blastocysts per total biopsied blastocysts for which a result was obtained. Percentage data was compared using N-1 Chi-squared test.

Main results and the role of chance:
There were no significant differences in patient age, number of oocytes retrieved, or number of mature oocytes among the three groups.
Fertilization rate for male factor ICSI was significantly lower compared to both non-male factor ICSI (74.2% vs 77.8%, p=0.005) and conventional insemination (74.2% vs 76.8%, p=0.018). There was no significant difference in fertilization rate between non-male factor ICSI and conventional insemination.
There were no significant differences between blastocyst rates on Day 5, 6, or 7, or total blastocyst rate among the three groups.
The euploidy rate for conventional insemination was significantly higher than that for non-male factor ICSI (53.4% vs 46.8%; p=0.008). Non-male factor ICSI yielded lower euploidy rate than male factor ICSI (46.8% vs 52.4%, p=0.034). Aneuploidy rate for non-male factor ICSI was significantly higher than both male factor ICSI (36.1% vs 31.0%, p=0.041) and conventional insemination (36.1% vs 31.0%, p=0.030).
Mosaicism levels were similar between the three groups.
There were no significant differences in number of biopsied embryos with no results: 5 for ICSI male factor group (0.59%), 6 for ICSI non-male factor (0.96%), and 10 for conventional insemination (0.89%).

Limitations, reasons for caution:
This was a retrospective analysis of patients from a single clinic, with a relatively small sample size so results may not be generalizable to all populations. Extensive demographic information and baseline characteristics (including reason for ICSI performed among non-male factor patients) were not analyzed so there may be confounding factors.

Wider implications of the findings:
This is the first study that we are aware of to investigate the ploidy status of embryos created among non-male factor patients undergoing ICSI. Conservative use of ICSI can significantly decrease the cost of IVF. Larger studies are needed to further elucidate the role for ICSI among these patients.