Effect of Abnormal Semen Parameters on ICSI: Morphokinetics and Cumulative Clinical Outcomes of 10,623 Embryos

Testicular sperm extraction cut live birth rates vs. ejaculated sperm in ICSI — but only cumulative, not first-transfer outcomes

Journal: Reproductive BioMedicine Online | Published: 2025-09-20 | Type: Retrospective cohort study | PMID: 41720045 Authors: Quintana-Vehí A et al. (Eugin Clinic, Barcelona; Eugin Group; Biogenesi, Monza, Italy; Ghent University Hospital) Funding/COI: Not listed for either

Summary

Using time-lapse microscopy across 10,623 embryos at a single Barcelona IVF clinic, this retrospective study found that sperm origin matters — but only if you look beyond the first embryo transfer. TESE-derived embryos had lower fertilization rates, aberrant cleavage timing, and worse blastocyst quality. When cumulative outcomes across all transfers were tallied, TESE patients had significantly lower implantation, pregnancy, and live birth rates. Ejaculated sperm with moderate impairment largely escaped major penalties.

Claims

• Normal fertilization (2PN) rate: normozoospermia 74.6% vs. TESE 59.6% (P ≤ 0.042 for all comparisons vs. normozoospermia)
• Non-fertilized oocytes: 9.8% (normozoospermia) vs. 22.1% (TESE) (P ≤ 0.012)
• 1PN zygotes more frequent with TESE (7.2%) vs. normozoospermia (4.8%) (P = 0.019)
• TESE embryos showed accelerated cleavage from pronuclear fading through the 5-cell stage (P ≤ 0.027)
• Blastocyst quality reduced in TESE and severe oligoasthenozoospermia groups
• First-transfer clinical outcomes were comparable across all groups
• Cumulative implantation, pregnancy, and live birth rates per embryo transferred were lower for TESE (P ≤ 0.031)

Study Quality

Retrospective cohort design from a single center over four years (2019–2023) — adequate for generating hypotheses but structurally incapable of establishing causation. The groups are badly imbalanced: normozoospermia contributed 8,799 embryos while TESE contributed only 541, which inflates the statistical power of the normozoospermia comparisons and could mask effects in smaller groups. Time-lapse morphokinetics adds objective developmental data that pure outcome studies lack, which is the main methodological strength here.

The analysis distinguishes first-transfer from cumulative outcomes — a meaningful choice, since single-transfer snapshots routinely flatter suboptimal embryo cohorts by cherry-picking the best embryo first. The cumulative approach gives a truer picture of what a patient population actually achieves across a complete cycle.

Red Flags

• Single-center data from a private IVF group (Eugin); patient selection and lab protocols may not generalize
• Funding and COI not disclosed — Eugin is a commercial IVF network; authors are employed by or affiliated with Eugin Group
• Severe group imbalance: normozoospermia n=8,799 vs. TESE n=541; the smallest group drives the most important conclusions
• Retrospective design introduces selection bias — TESE patients are clinically distinct in ways not fully captured by semen parameters alone
• No paternal age adjustment reported; TESE cases may skew older, confounding developmental outcomes
• Clinic-specific time-lapse thresholds and grading criteria are not standardized across centers

Strengths

• Large absolute embryo count (10,623) with 14,568 inseminated oocytes
• Four distinct sperm-origin groups allow dose-response-style comparisons
• Time-lapse morphokinetics provides granular developmental timing data beyond standard D3/D5 grading
• Cumulative outcome analysis avoids the common bias of first-transfer-only reporting
• Four-year consecutive dataset reduces temporal selection bias

Verdict

This paper earns its place in the literature for one reason: it uses cumulative outcomes, not just first-transfer snapshots, and finds that TESE-derived sperm is genuinely associated with worse IVF trajectories even when the first transfer looks fine. That's a clinically meaningful distinction. But the single-center, industry-affiliated, retrospective design with badly imbalanced groups means these numbers are hypothesis-generating, not practice-changing. The undisclosed funding from a commercial IVF network is the loudest red flag — not necessarily disqualifying, but the absence of any COI statement from a study conducted entirely within that network's clinics is a transparency failure.