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

Trial Summary

What is the purpose of this trial?

This trial compares two ways of preparing sperm for fertility treatment. One method spins the sperm to pick out the good ones, while the other uses a special device to sort them naturally. The study aims to see which method leads to better pregnancy outcomes for patients undergoing intrauterine insemination.

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 data supports the effectiveness of the treatment Density gradient centrifugation, Density Gradient Centrifugation, Isopycnic Centrifugation, Rate-Zonal Centrifugation, Zymot Multi sperm separation device, ZyMōt Multi Sperm Separation Device, ZyMōt ICSI Sperm Separation Device for infertility?

Research shows that density gradient centrifugation can improve sperm quality by increasing motility and reducing damage, which is important for successful fertilization. Additionally, the ZyMot Multi device has been shown to improve clinical pregnancy rates in IVF by selecting sperm with better DNA integrity. ^{1 2 3 4 5}

Is sperm preparation using techniques like density gradient centrifugation and ZyMōt devices safe for humans?

The available research suggests that sperm preparation techniques like density gradient centrifugation and ZyMōt devices are generally safe for use in humans, as they are commonly used in assisted reproductive technologies like in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) without reported safety concerns. ^{2 3 4 6 7}

How does the treatment using Density Gradient Centrifugation and ZyMōt Multi Sperm Separation Device differ from other infertility treatments?

The Density Gradient Centrifugation and ZyMōt Multi Sperm Separation Device are unique because they focus on selecting the best quality sperm by separating them based on their density and motility, which can improve the chances of successful fertilization. Unlike some other methods, the ZyMōt device uses microfluidic technology to gently select sperm without the stress of centrifugation, potentially preserving sperm quality better. ^{1 3 4 8 9}

Research Team

Mitchell Rosen, M.D.

Principal Investigator

University of California, San Francisco

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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 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]

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 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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Comparing the clinical outcomes of intrauterine insemination by two different density gradient preparation methods. [2019]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Sperm selection of cryopreserved milt of catfish (Rhamdia quelen) by density gradient centrifugation with AllGrad® 90. [2021]

3. United States 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. [2019]

4. Germany pubmed.ncbi.nlm.nih.gov

Selection of frozen-thawed stallion semen by microfluidic technology. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Comparative Study of Sperm Selection Techniques for Pregnancy Rates in an Unselected IVF-ICSI Population. [2023]

6. France pubmed.ncbi.nlm.nih.gov

[Separation of spermatozoa using Percoll gradients: value for in vitro fertilization]. [2006]

7. United States 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. [2020]

8. Germany pubmed.ncbi.nlm.nih.gov

Comparison of characteristics of human spermatozoa selected by the multiple-tube swim-up and simple discontinuous Percoll gradient centrifugation. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Comparison of centrifugation- and noncentrifugation-based techniques for recovery of motile human sperm in assisted reproduction. [2019]