A Multicenter Randomized Controlled Non-Inferiority Trial Comparing SwimCount Harvester® to Standard Sperm Preparation Methods in IVF Cycles With PGT-A
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 1,600
- 试验地点
- 1
- 主要终点
- Useable Blastocyst Rate
研究概览
简要总结
The goal of this prospective, multicenter randomized controlled clinical trial is to evaluate whether the SwimCount Harvester microfluidic sperm preparation device can achieve equivalent or superior clinical outcomes compared to standard sperm preparation methods (density gradient centrifugation and swim-up) in couples undergoing in vitro fertilization (IVF) with preimplantation genetic testing for aneuploidy (PGT-A).
The study population includes adult couples (female partner age 21-45 years; male partner age ≥21 years) undergoing IVF with PGT-A who meet minimum semen eligibility criteria on the day of oocyte retrieval: pre-processing volume ≥1mL, sperm concentration ≥1 million/mL, and progressive motility ≥10%. A total of 1,600 patients will be randomized 1:1 across 15-25 high-volume IVF centers to receive either Harvester or the site's predominant standard-of-care sperm preparation method. Patients with surgical sperm retrieval requirements or those currently using SwimCount Harvester as standard of care are excluded.
The main questions it aims to answer are:
Does the SwimCount Harvester demonstrate noninferiority to standard sperm preparation methods on blastocyst utilization rate? The primary endpoint is blastocyst utilization rate, calculated as the number of usable blastocysts (operationalized as biopsied blastocysts per clinic standard operating procedures) divided by the number of normally fertilized oocytes (2PN) at the patient level. Noninferiority will be concluded if the lower bound of the two-sided 95% confidence interval for the risk difference (Harvester minus standard of care) is greater than -2.0 percentage points, using a site-stratified Mantel-Haenszel analysis. If noninferiority is met, superiority may be reported as supportive evidence when the lower confidence bound exceeds zero.
Does the SwimCount Harvester demonstrate noninferiority to standard sperm preparation methods on the probability of obtaining at least one euploid embryo per retrieval? The key secondary endpoint assesses whether patients have at least one euploid embryo (yes/no) based on PGT-A results from a single blinded reference laboratory (NOVA Genomics). This will be analyzed as a site-stratified Mantel-Haenszel risk difference with a two-sided 95% confidence interval, with an optional noninferiority margin of -2.5 percentage points presented as supportive evidence.
Additional supportive and exploratory questions include:
- How does progressive motility change from pre- to post-preparation with each method? Progressive motility will be summarized descriptively pre- and post-preparation as a supportive laboratory measure without hypothesis testing.
- Do outcomes differ in clinically important subgroups? Pre-specified exploratory analyses will examine advanced maternal age (≥40 years) and severe oligospermia (<5 million/mL), populations that may derive differential benefit from advanced sperm selection.
- What are the practical implementation considerations? An independent protocol complexity analysis will assess procedural steps, equipment requirements, and standardization benefits by comparing site standard-of-care protocols to the Harvester Instructions for Use.
The study addresses a critical evidence gap by providing multicenter, adequately powered data on whether advanced microfluidic sperm preparation translates into meaningful clinical improvements in IVF success metrics.
详细描述
DETAILED DESCRIPTION Scientific Background and Rationale Infertility affects 10-15% of couples globally, with male factors contributing to nearly half of cases. Sperm preparation is a critical laboratory step in assisted reproductive technology (ART) that directly influences clinical outcomes beyond baseline semen quality. Density gradient centrifugation (DGC) and swim-up have been the prevailing sperm preparation techniques for decades, but both methods are labor-intensive, require multiple procedural steps, and can generate inter-laboratory variation due to technique-dependent factors.
DNA Fragmentation and Sperm Selection The clinical advantage of modern sperm separation techniques stems from reductions in sperm DNA fragmentation. Meta-analyses of microfluidic sperm selection demonstrate significant improvements in DNA fragmentation (mean difference -9.98%, p<0.00001), progressive motility (mean difference +14.50%, p=0.04), and fertilization rates (OR 1.22, p=0.04). Crucially, these gains are independent of baseline semen metrics, suggesting that preparation method choice can compensate for poor starting material-particularly relevant for severe oligospermia populations.
Progressive Motility as a Surrogate Biomarker Progressive motility serves as more than a functional measure; it acts as a surrogate for sperm genomic integrity and predicts embryo developmental trajectory. High-motility sperm reliably exhibit lower DNA fragmentation, superior chromatin organization, and optimized mitochondrial function. Published evidence demonstrates that higher post-preparation progressive motility significantly enhances blastocyst formation rates in ICSI cycles (42.7% vs 28.2%, p=0.015), and motility correlates closely with fertilization (p=0.012), pregnancy (p=0.001), and live birth rates (p=0.001) in IVF.
Severe Oligospermia as a Distinct Clinical Challenge Multicenter studies demonstrate that men with severe oligospermia (<5 million/mL) face 12-15% lower fertilization and 18-22% lower blastulation rates, even after adjustment for female age and other variables. Their sperm also exhibit worse DNA fragmentation and chromatin quality, creating a distinct pathophysiological state that may derive differential benefit from advanced sperm selection technologies.
Study Design and Methodology Trial Architecture This is a prospective, multicenter, randomized (1:1), parallel-arm, noninferiority trial with PGT-A laboratory blinding. The trial compares the SwimCount Harvester microfluidic sperm preparation device to each site's predominant standard-of-care method across 15-25 high-volume IVF centers. Sites where DGC or swim-up constitute ≥90% of standard practice will comprise the primary analysis cohort; sites already using microfluidic devices as standard of care will be analyzed exploratorily to capture real-world diversity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 21 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •• Sperm sample available on day of egg retrieval
- •Female partner age 21-45 years undergoing IVF with PGT-A
- •Male partner age ≥ 21 years
- •Pre-processing volume ≥1mL
- •Pre-processing sperm concentration ≥1 million/mL
- •Pre-processing progressive motility ≥10%
- •Signed informed consent from both partners
排除标准
- •• Surgical sperm retrieval required
- •Current standard of care with the SwimCount Harvester device
研究组 & 干预措施
Control group; standard sperm preparation and selection
This arm is the control group and patients randomized to this arm of the study will have semen processed according to standard operating procedures.
Study group - microfluidics device for sperm preparation
Patients randomized to this arm will have their semen processed using the SpermHarvest device which is an FDA approved microfluidics device for semen processing.
干预措施: microfludics semen processing device (Device)
结局指标
主要结局
Useable Blastocyst Rate
时间窗: One week - from the day of oocyte retrieval through the last day of embryo assessment.
Percentage of blastocysts cryopreserved per number of fertilized oocytes.
次要结局
- Number of euploid blasts per cycle(From the start of an IVF cycle through its completion at 15-28 days.)