PGT-A for Severe Male Infertility: Reducing Pregnancy Loss Without Boosting Live Birth Rates

Introduction: The Clinical Dilemma of Male Factor Infertility

Severe male factor infertility, which encompasses conditions such as non-obstructive azoospermia and severe oligoasthenoteratozoospermia, remains one of the most challenging indications in reproductive medicine. While intracytoplasmic sperm injection (ICSI) revolutionized the treatment of these patients, concerns regarding the genetic integrity of embryos derived from poor-quality sperm have persisted. It has been hypothesized that severe male factor infertility might increase the risk of embryonic aneuploidy, leading many clinicians to recommend preimplantation genetic testing for aneuploidy (PGT-A) as an adjunct to ICSI. However, the evidence supporting this practice has been largely observational or based on low-powered studies. A landmark multicentre, open-label, randomized controlled trial recently published in the BMJ (Lin et al., 2025) provides much-needed clarity on whether PGT-A actually improves outcomes for these couples.

Highlighting the Trial’s Core Findings

• PGT-A does not enhance live birth rates after the first embryo transfer or cumulatively over 12 months in couples with severe male infertility.
• The intervention significantly lowers the risk of clinical pregnancy loss, reducing it by more than half compared to ICSI without genetic testing.
• The findings suggest that while PGT-A does not increase the total number of babies born, it may improve the efficiency of the process by avoiding transfers likely to end in miscarriage.

Study Design and Population

This study was a robustly designed multicentre, open-label, randomized controlled trial conducted across four prominent reproductive medicine centers in China. The investigators screened 1,347 couples, ultimately randomizing 450 who met the criteria for severe male factor infertility. These couples were assigned in a 1:1 ratio to either the PGT-A group (n=225) or the no PGT-A group (n=225).

Participants and Interventions

The inclusion criteria focused on couples where the male partner had severe infertility scheduled for ICSI. In the PGT-A group, blastocysts underwent trophectoderm biopsy followed by genetic screening before transfer. In the control group, embryos were selected based on conventional morphological assessment. The primary outcomes were defined as the live birth rate after the first embryo transfer and the cumulative live birth rate within 12 months of randomization, covering up to three transfer cycles.

Key Findings: A Detailed Analysis of Outcomes

The results of the trial provide a comprehensive look at the limits and benefits of genetic screening in this specific population. Analysis was conducted on an intention-to-treat (ITT) basis to ensure the pragmatic relevance of the findings.

Live Birth Rates: No Significant Advantage

In the first embryo transfer, 109 out of 225 couples (48.4%) in the PGT-A group achieved a live birth, compared to 104 out of 225 (46.2%) in the control group. The odds ratio (OR) was 1.09 (95% CI 0.76 to 1.58), with a p-value of 0.64, indicating no statistical difference. Similarly, the cumulative live birth rates at 12 months were nearly identical: 60.4% in the PGT-A group versus 60.9% in the no PGT-A group (OR 0.98, 95% CI 0.67 to 1.43, P=0.92).

Pregnancy Loss: A Striking Reduction

While PGT-A failed to move the needle on live births, it showed a profound impact on pregnancy stability. The rate of pregnancy loss after the first embryo transfer was significantly lower in the PGT-A group at 5.8% (13/225) compared to 19.1% (43/225) in the control group (OR 0.26, 95% CI 0.14 to 0.50, P<0.001). The cumulative pregnancy loss rate followed this trend, with 11.1% in the PGT-A group versus 22.7% in the no PGT-A group (OR 0.43, 95% CI 0.25 to 0.72, P=0.001).

Expert Commentary: Interpreting the Trade-offs

The results of this trial present a nuanced “good news, bad news” scenario for clinicians. The lack of improvement in cumulative live birth rates suggests that PGT-A does not salvage embryos or correct underlying issues; rather, it acts as a more refined selection tool.

Biological Plausibility and Mechanism

The biological rationale for PGT-A in male factor infertility is based on the assumption that compromised spermatogenesis leads to higher rates of aneuploid embryos. However, these results suggest that for many couples, the pool of viable (euploid) embryos remains the same regardless of whether we test them or not. The reduction in pregnancy loss occurs because PGT-A identifies and excludes aneuploid embryos that would have otherwise resulted in a clinical pregnancy followed by a miscarriage.

The Psychological and Clinical Value

From a patient-centered perspective, the reduction in pregnancy loss is not a minor secondary finding. Miscarriage carries a heavy psychological burden, often leading to depression, anxiety, and sometimes the discontinuation of fertility treatments altogether. By reducing the rate of miscarriage, PGT-A may improve the patient experience and potentially shorten the “time to pregnancy” by avoiding unproductive transfers, even if the final “baby-at-home” rate remains unchanged.

Limitations and Generalizability

As an open-label trial, there is a risk of bias in how clinicians and patients managed subsequent cycles. Additionally, the study was conducted in China, where patient demographics and laboratory protocols might differ from those in Western clinics. However, the multicentre nature and the use of the ITT principle lend high internal validity to the findings.

Conclusion: Re-evaluating the Role of PGT-A

The study by Lin et al. (2025) clarifies that PGT-A should not be marketed as a method to increase the chances of having a child for couples with severe male factor infertility. Instead, it should be framed as a tool to minimize the risk of miscarriage and potentially streamline the treatment process. Clinicians should engage in shared decision-making, presenting PGT-A as an option for those who prioritize the avoidance of pregnancy loss over the additional costs and invasive nature of embryo biopsy.

Funding and Trial Registration

This study was supported by various national research grants and institutional funds. The trial is registered with ClinicalTrials.gov under the identifier NCT02941965.

References

Lin X, Wu D, Zhang C, et al. Preimplantation genetic testing for aneuploidy versus no genetic testing in couples undergoing intracytoplasmic sperm injection for severe male infertility: multicentre, open label, randomised controlled trial. BMJ. 2025;391:e084050. doi:10.1136/bmj-2025-084050.