Sperm Preparation Techniques for Infertility

(PIoUS Trial)

Overseen By Elena Hoskin

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of California, San Francisco

Disqualifiers: Significant disease, Psychiatric disorder, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 3 months

270 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines two methods for preparing sperm for intrauterine insemination (IUI), a treatment that aids pregnancy. Researchers aim to determine whether density gradient centrifugation or the Zymot sperm separation device yields better pregnancy outcomes. The trial suits individuals assigned female at birth, under 41, planning their first IUI, and comfortable communicating in English. As an unphased trial, it allows participants to contribute to innovative fertility research that could enhance future IUI outcomes.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications.

What prior data suggests that these sperm preparation techniques are safe for infertility treatment?

Research has shown that both density gradient centrifugation and the Zymot sperm separation device are well-tolerated methods for preparing sperm.

Density gradient centrifugation reduces DNA damage in sperm, selecting healthier sperm and indicating safety. Studies also show it can improve sperm quality, even from less-than-ideal samples.

The Zymot sperm separation device uses microfluidics to sort sperm without spinning them. This method has shown promise in selecting sperm with less DNA damage. The device is approved for use in fertility treatments, indicating it meets safety standards.

Overall, both methods have been studied and appear safe for preparing sperm for fertility treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores two innovative sperm preparation techniques for infertility: density gradient centrifugation and the Zymot Multi sperm separation device. Unlike traditional methods that might not effectively filter out poor-quality sperm, these techniques aim to enhance the selection of high-quality sperm, potentially increasing the success rates of assisted reproductive technologies. By comparing these two methods, the trial seeks to determine which technique offers better outcomes, providing new insights that could lead to improved fertility treatments.

What evidence suggests that these sperm preparation techniques are effective for infertility?

This trial will compare two sperm preparation techniques: density gradient centrifugation and the Zymot sperm separation device. Studies have shown that density gradient centrifugation effectively selects sperm with better DNA quality, which is important for successful pregnancies. This method also increases the number of motile sperm, crucial for fertilization, and helps recover more sperm, especially from samples with low sperm counts.

In contrast, the Zymot sperm separation device is gaining popularity for its ability to select high-quality, motile sperm through a simpler process. This device has proven effective in assisted reproductive technologies, showing positive results in selecting healthy sperm. Both methods in this trial aim to improve pregnancy chances by ensuring only the best sperm are used. ^{2 3 6 7 8}

Who Is on the Research Team?

Mitchell Rosen, M.D.

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for individuals assigned female at birth, under the age of 41, who are undergoing intrauterine insemination due to anovulation or unexplained infertility. It's not suitable for those with significant diseases or psychiatric disorders that affect consent, users of frozen donor sperm, non-English speakers, or those with prior intrauterine inseminations.

Inclusion Criteria

Patients who are getting intrauterine insemination.

I am a woman under 41 years old.

Exclusion Criteria

I am using frozen donor sperm for conception.

Non-English speaker

You have had a previous intrauterine insemination.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo intrauterine insemination treatment with either density gradient centrifugation or Zymot sperm separation device over three cycles

3 months

Multiple visits as per treatment cycle

Follow-up

Participants are monitored for pregnancy outcomes until referred for prenatal care at 8-10 weeks of pregnancy

5 months

What Are the Treatments Tested in This Trial?

Interventions

• Density gradient centrifugation
• Zymot Multi sperm separation device

Trial Overview The study compares two methods of preparing sperm before intrauterine insemination: Zymot Multi (a microfluidic sorting device) and density gradient centrifugation. The goal is to see which method leads to better pregnancy outcomes in a randomized controlled setting.

How Is the Trial Designed?

Group I: Density gradient centrifugation Active Control 1 Intervention

Patients will undergo sperm preparation by density gradient centrifugation

Group II: Zymot sperm separation device Active Control 1 Intervention

Patients will undergo sperm preparation by the Zymot sperm separation device

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

Published Research Related to This Trial

The novel non-centrifugation-based dual-chamber capillary dish (Zech device) showed a trend towards higher recovery of motile sperm compared to the standard density gradient centrifugation method, although it resulted in fewer absolute numbers of higher velocity sperm.

This new technique minimizes potential centrifugation stress on sperm, which could be beneficial for sperm viability, but further refinements are needed before it can match the effectiveness of traditional methods for sperm recovery in fertility treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of centrifugation- and noncentrifugation-based techniques for recovery of motile human sperm in assisted reproduction. Sills, ES., Wittkowski, KM., Tucker, MJ., et al.[2019]

In a study involving 121 women undergoing intrauterine insemination, both PureSperm and Percoll density gradient methods were found to be equally effective in recovering sperm with progressive motility.

The clinical pregnancy rates were similar for both methods, with 12.5% for PureSperm and 13.8% for Percoll, indicating that PureSperm is a viable alternative for sperm preparation in fertility treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparing the clinical outcomes of intrauterine insemination by two different density gradient preparation methods. Tsai, YC., Lin, MY., Chen, SH., et al.[2019]

The study compared the efficacy of the new Multi-ZSC system for separating human sperm against the traditional double-wash swim-up method.

Results indicated that the double-wash swim-up method selects sperm with superior head shape and better ability to undergo acrosome reaction, suggesting it may be more effective for certain fertility applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparing the Multi-ZSC one-step standardized swim-up method to the double-wash swim-up method with regard to the effects of sperm separation on morphology, head morphometry, and acrosome reaction inducibility. Lampiao, F., du Plessis, SS.[2019]

The ZSC swim-up technique for sperm recovery demonstrated acceptable fertilization and pregnancy rates in IVF and ICSI procedures, indicating its effectiveness in assisted reproductive technology.

Compared to the traditional Percoll method, the ZSC technique is less time-consuming and simplifies the sperm preparation process, making it a potentially preferred method in ART programs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcome of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) using human sperm prepared via a new standardized swim-up technique fit for office use. Zarmakoupis-Zavos, PN., Correa, JR., Clark, W., et al.[2020]

In a study involving 239 couples undergoing IVF, the microfluidic sperm selection method (ZyMot-ICSI) showed a significant improvement in blastocyst rates (p = 0.046) and clinical pregnancy rates (p = 0.049) compared to the traditional gradient centrifugation method, despite no difference in fertilization rates (p = 0.87).

The results suggest that microfluidic sperm selection may enhance IVF outcomes by improving embryo quality and consistency, indicating its potential for broader application in ICSI and standard IVF procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Study of Sperm Selection Techniques for Pregnancy Rates in an Unselected IVF-ICSI Population. Zaha, I., Naghi, P., Stefan, L., et al.[2023]

Centrifugation on a discontinuous Percoll density gradient is an effective method for selecting motile sperm in IVF cycles, particularly for men with oligo-asthenospermia, resulting in a cleavage rate of 63% and a pregnancy rate of 22%.

This method also effectively removes bacterial contaminants from semen, achieving a cleavage rate of 66% and a pregnancy rate of 35%, making it a valuable technique for improving IVF outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Separation of spermatozoa using Percoll gradients: value for in vitro fertilization]. Mathieu, C., Guérin, JF., Gille, Y., et al.[2006]

The multiple-tube swim-up (MT-SU) and discontinuous Percoll gradient centrifugation methods both effectively improve sperm quality parameters, such as motility, morphology, and viability, in normospermic semen samples.

Both methods demonstrated comparable efficacy in enhancing the functional integrity of sperm and their in vitro fertilizing capacity, making them suitable for assisted reproductive technologies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of characteristics of human spermatozoa selected by the multiple-tube swim-up and simple discontinuous Percoll gradient centrifugation. Chan, SY., Chan, YM., Tucker, MJ.[2019]

The ZyMot Multi (850 μl) device effectively selects high-quality sperm from frozen-thawed semen of stallions, improving key characteristics like motility and membrane integrity, which are crucial for fertility.

In a study involving 15 stallions classified by fertility rates, the device showed a significant increase in total motility and membrane functionality after sperm recovery, indicating its potential as a reliable tool for predicting fertility in equine artificial reproduction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selection of frozen-thawed stallion semen by microfluidic technology. Vigolo, V., Gautier, C., Falomo, ME., et al.[2023]

Density gradient centrifugation using 90% AllGrad® effectively reduces cryoprotectant levels in cryopreserved milt of Rhamdia qhelen, resulting in a higher percentage of normal spermatozoa (22.25% compared to 13% in non-centrifuged samples).

The method not only improves sperm motility and reduces head damage but is also easy to adapt and apply, making it a promising tool for enhancing the quality of cryopreserved sperm in this species.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sperm selection of cryopreserved milt of catfish (Rhamdia quelen) by density gradient centrifugation with AllGrad® 90. Pérez-Atehortúa, M., Galuppo, A., Rodrigues, RB., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9233458/

The Effectiveness of Sperm Preparation Using Density Mini ... Although sperm preparation by density gradient centrifugation is considered to result in better sperm recovery than the swim-up method (6, 7), for oligospermia ...

2. mefj.springeropen.com mefj.springeropen.com/articles/10.1186/s43043-022-00108-4

Efficacy of density gradient centrifugation technique (DGC) in ... Our study shows that semen processing by density gradient centrifugation is useful in selecting sperm with higher double-strand DNA integrity.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT07004309

Microfluidics Versus Density Gradient Centrifugation for ... Primary outcomes included live birth rate and DFI reduction; secondary outcomes included sperm motility and morphology, fertilization rate, ...

4. nature.com nature.com/articles/s41598-020-59347-y

Sperm enrichment from poor semen samples by double ... Our results showed that double DGC (DDGC) is effective at increasing the sperm recovery rate from poor semen samples.

5. sciencedirect.com sciencedirect.com/science/article/pii/S0015028207041349

swim-up versus gradient-density centrifugation technique The concentration of progressive motile sperm was significantly higher after density-gradient centrifugation compared with swim-up preparation (Table 1).

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4250460/

Assessment of density gradient centrifugation (DGC) and ... Our data indicate that DGC can reduce the DNA fragmentation rate, significantly reducing the probability that sperm with low DNA integrity will be selected for ...

7. intechopen.com intechopen.com/chapters/1198694

A Comparative Analysis of Gradient Centrifugation and ... This chapter evaluates the advantages and disadvantages of sperm selection methods from the past to the present, with a particular focus on DGC and microfluidic ...

8. link.springer.com link.springer.com/article/10.1007/s42452-025-07316-3

Comparative analysis of density gradient centrifugation ... In conclusion, MACS appears to be a safe and effective method for sperm selection, consistently producing good results. This technique may ...