Sperm DNA FragmentationSPERMNCT03085433
Sperm Selection by Microfluidic Separation Improves Embryo Quality
A study testing Microfluidic Sperm Sorting and in vitro fertilization in people with Sperm DNA Fragmentation and Embryo Quality, run by University of California, San Francisco at 1 site in United States.
Trial summary
This is a randomized controlled trial of couples with a history of poor embryo quality undergoing a repeat in vitro fertilization (IVF) cycle for unexplained infertility. Couples will be randomized to sperm selection by the clinical standard of centrifugation and density-gradient processing compared to the… Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Sperm DNA Fragmentation, Embryo Quality, Fertility Disorders
- What is being tested?
- Microfluidic Sperm Sorting and in vitro fertilization
- Type of treatment
- Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 393 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Jun 2017to 30 Apr 2022
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- The target population includes couples planning in vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI).
- Subjects with and without a history of prior IVF cycles will be included.
- All eligible couples where both partners are >=18 years of age will be asked to join the study.
Who cannot join
- Male partner with severe oligoasthenospermia (concentration < 5 x 10^6 spermatozoa/mL; motility< 10%)
- Female partner with anovulation (PCOS, FHA)
- Female partner age >41
- Female partner AFC< 7
- Female partner with obstructed fallopian tubes (assessed in all patients prior to IVF)
- Use of oocyte donor
Show all 14Show fewer
- Either Partner:
- Cancer diagnosis in either partner
- Any significant disease or psychiatric disorder that would interfere with consenting process
- Treatment History:
- o History of >1 prior cycle cancellation due to poor response
- Treatment Plan:
- Embryo co-culture
- Use of adjunctive non-gonadotropin medications to improve embryo quality: growth hormone, sildenafil
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California San Francisco
San Francisco, California, 94158
About this study
This is a randomized controlled trial of couples with a history of poor embryo quality undergoing a repeat in vitro fertilization (IVF) cycle for unexplained infertility. Couples will be randomized to sperm selection by the clinical standard of centrifugation and density-gradient processing compared to the microfluidic sperm sorting chip.
Read the detailed description
More than 70 million couples worldwide are infertile and up to 40 million are actively seeking infertility care. In the year 2013, a total of 160,521 assisted reproductive technology (ART) procedures were performed in the United States. Isolation of motile and morphologically normal sperm is an integral part of assisted reproduction. Traditional sperm processing for assisted reproduction involves centrifugation and "swim up" techniques that employ a density gradient to isolate motile sperm. This technique involves several steps of centrifugation (200-1800g) with colloidal silica particles. In this process, sperm and other material form distinct bands. It is thought that this procedure allows for elimination of abnormal/immotile sperm as well as debris, thereby isolating motile human sperm. Nevertheless, the centrifugation process has been shown to induce DNA damage and produce reactive oxygen species, thereby potentially compromising sperm quality and subsequent laboratory outcomes such as fertilization rate and embryo quality. Increased sperm DNA damage has been associated with poor outcomes in assisted reproduction, including lower fertilization rates, impaired embryo progression, and decreased pregnancy rates. The details of the density gradient centrifugation process are not regulated by the FDA.
In contrast, microfluidic-based sperm sorting has the capability of selectively isolating highly motile, morphologically normal sperm with high DNA integrity from an unprocessed semen sample. Microfluidic technology isolates healthy sperm by laminar flow, creating gradients through channels. The microfluidic chip we plan to study in our randomized clinical trial utilizes space-constrained microfluidic sorting to select highly motile and morphologically normal sperm in a flow and chemical-free design. Unlike the standard of density gradient centrifugation, no manipulation of sperm is required in this process. Raw semen is introduced into the inflow and only motile and morphologically normal sperm are able to swim through the chip to the outflow where it is collected for use.
In semen samples from healthy male volunteers split into standard processing via centrifugation and swim-up procedure compared with microfluidic sperm sorting, a significantly higher percent motility and lower rate of sperm DNA fragmentation was detected with microfluidic sperm sampling. The microfluidic sperm sorting technique has thus proven to be an efficient and reliable means of sperm preparation compared with the centrifugation and swim-up procedure. While this microfluidic chip has been used clinically in Mexico, Turkey, South Africa, Italy, Greece, and Switzerland resulting in over 5,000 live births, its use in clinical practice has not been rigorously studied. We aim to compare traditional preparation and microfluidic sperm sorting on assisted reproductive technology outcomes including oocyte fertilization and embryo quality in subjects with a history of poor embryo quality electing to undergo a repeat in vitro fertilization cycle for infertility.
- Conditions
- Sperm DNA Fragmentation, Embryo Quality, Fertility Disorders, Infertility, Infertility, Male, Infertility Unexplained
- Being tested
- Microfluidic Sperm Sorting, in vitro fertilization
- Medical subject headings
- Infertility, Infertility, Male
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Microfluidic Sperm SortingDevice
Also called FERTILE device
Microfluidic technology isolates healthy sperm by laminar flow, creating gradients through channels. The microfluidic chip we plan to study in our randomized clinical trial utilizes space-constrained microfluidic sorting to select highly motile and morphologically normal sperm in a flow and chemical-free design. Unlike the standard of density gradient centrifugation, no manipulation of sperm is required in this process. Raw semen is introduced into the inflow and only motile and morphologically normal sperm are able to swim through the chip to the outflow where it is collected for use.
in vitro fertilizationProcedure or surgery
ivf/icsi
| Study group | Role | What they receive |
|---|---|---|
| Microfluidic sperm sorting | Experimental | Couples undergoing in vitro fertilization randomized to microfluidic sperm sorting will have raw semen sorted by the microfluidics chip prior to fertilization with IVF/ICSI. Receives: Device: Microfluidic Sperm Sorting; Procedure: in vitro fertilization |
| Conventional sperm preparation | Active comparator | Couples undergoing in vitro fertilization randomized to conventional methods for sperm processing will undergo separation of semen by density gradient centrifugation prior to IVF/ICSI. Receives: Procedure: in vitro fertilization |
What is being measured
The primary outcome is the main question the study is designed to answer.
Day 3 High Quality Embryo Percentage
The primary outcome for intent to treat analysis. Day 3 high quality embryo percentage rate will be defined as the percentage of all viable 2PN embryos on day 3 with at least 6 cells and fragmentation/symmetry scores of 1-2. Scale: 1-6 for either fragmentation or symmetry. Lower scores are better. Calculated as ( the number of high-qualify-grade embryos yielded by a participant / the number of all viable 2PN embryos yielded by the participant x 100)
Measured: 3 days following fertilization
Secondary outcomes (2)
Egg Fertilization Rate
Number of eggs successfully fertilized (2PN embryo count) per number of mature eggs (MII egg count) retrieved per participant. 2PN grade indicates a successfully fertilized embryo. MII grade indicates a metaphase II stage egg which is mature enough to undergo fertilization. (The percentage is calculated for each participant as the number of 2PN embryos obtained / the number of MII eggs obtained x100). The resulting percentages were then averaged to determine the average fertilization rate for participants in each study arm.
Measured: 1 day following fertilization
Pregnancy Rate
Pregnancy rate will be defined as achieving a clinical pregnancy ( an ultrasound demonstrating gestational sac with yolk sac) per embryo transfer procedure attempt.
Measured: 14 days following embryo transfer
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Mar 2017
- Study start20 Jun 2017
- Primary completion30 Oct 2021
- Study completion30 Apr 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Sperm DNA FragmentationStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 393 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mitchell Rosen, M.D, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03085433
- Sponsor's protocol ID
- 16-21273
- Acronym
- SPERM
- Status last verified
- Dec 2025
- First submitted
- 19 Mar 2017
- Last updated
- 31 Dec 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Quinn MM, Ribeiro S, Juarez-Hernandez F, Simbulan RK, Jalalian L, Cedars MI, Rosen MP. Microfluidic preparation of spermatozoa for ICSI produces similar embryo quality to density-gradient centrifugation: a pragmatic, randomized controlled trial. Hum Reprod. 2022 Jun 30;37(7):1406-1413. doi: 10.1093/humrep/deac099.
PubMed 35522187
Study at a glance
From the registry record, last updated by the sponsor on 31 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sperm Selection by Microfluidic Separation Improves Embryo Quality
- ClinicalTrials.gov ID
- NCT03085433
- Acronym / sponsor ID
- SPERM / 16-21273
- Conditions
- Sperm DNA Fragmentation, Embryo Quality, Fertility Disorders, Infertility, Infertility, Male, Infertility Unexplained
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 393 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Study start
- 20 Jun 2017 (actual)
- Primary completion
- 30 Oct 2021 (actual)
- Study completion
- 30 Apr 2022 (actual)
- First posted
- 21 Mar 2017 (actual)
- Results
- Posted 31 Dec 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a randomized controlled trial of couples with a history of poor embryo quality undergoing a repeat in vitro fertilization (IVF) cycle for unexplained infertility. Couples will be randomized to sperm selection by the clinical standard of centrifugation and density-gradient processing compared to the microfluidic sperm sorting chip.
Detailed description
More than 70 million couples worldwide are infertile and up to 40 million are actively seeking infertility care. In the year 2013, a total of 160,521 assisted reproductive technology (ART) procedures were performed in the United States. Isolation of motile and morphologically normal sperm is an integral part of assisted reproduction. Traditional sperm processing for assisted reproduction involves centrifugation and "swim up" techniques that employ a density gradient to isolate motile sperm. This technique involves several steps of centrifugation (200-1800g) with colloidal silica particles. In this process, sperm and other material form distinct bands. It is thought that this procedure allows for elimination of abnormal/immotile sperm as well as debris, thereby isolating motile human sperm. Nevertheless, the centrifugation process has been shown to induce DNA damage and produce reactive oxygen species, thereby potentially compromising sperm quality and subsequent laboratory outcomes such as fertilization rate and embryo quality. Increased sperm DNA damage has been associated with poor outcomes in assisted reproduction, including lower fertilization rates, impaired embryo progression, and decreased pregnancy rates. The details of the density gradient centrifugation process are not regulated by the FDA.
In contrast, microfluidic-based sperm sorting has the capability of selectively isolating highly motile, morphologically normal sperm with high DNA integrity from an unprocessed semen sample. Microfluidic technology isolates healthy sperm by laminar flow, creating gradients through channels. The microfluidic chip we plan to study in our randomized clinical trial utilizes space-constrained microfluidic sorting to select highly motile and morphologically normal sperm in a flow and chemical-free design. Unlike the standard of density gradient centrifugation, no manipulation of sperm is required in this process. Raw semen is introduced into the inflow and only motile and morphologically normal sperm are able to swim through the chip to the outflow where it is collected for use.
In semen samples from healthy male volunteers split into standard processing via centrifugation and swim-up procedure compared with microfluidic sperm sorting, a significantly higher percent motility and lower rate of sperm DNA fragmentation was detected with microfluidic sperm sampling. The microfluidic sperm sorting technique has thus proven to be an efficient and reliable means of sperm preparation compared with the centrifugation and swim-up procedure. While this microfluidic chip has been used clinically in Mexico, Turkey, South Africa, Italy, Greece, and Switzerland resulting in over 5,000 live births, its use in clinical practice has not been rigorously studied. We aim to compare traditional preparation and microfluidic sperm sorting on assisted reproductive technology outcomes including oocyte fertilization and embryo quality in subjects with a history of poor embryo quality electing to undergo a repeat in vitro fertilization cycle for infertility.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Microfluidic sperm sorting | Experimental | Device: Microfluidic Sperm Sorting, Procedure: in vitro fertilizationCouples undergoing in vitro fertilization randomized to microfluidic sperm sorting will have raw semen sorted by the microfluidics chip prior to fertilization with IVF/ICSI. |
| Conventional sperm preparation | Active comparator | Procedure: in vitro fertilizationCouples undergoing in vitro fertilization randomized to conventional methods for sperm processing will undergo separation of semen by density gradient centrifugation prior to IVF/ICSI. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- The target population includes couples planning in vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI).
- Subjects with and without a history of prior IVF cycles will be included.
- All eligible couples where both partners are >=18 years of age will be asked to join the study.
Key exclusion criteria (14 listed)
- Male partner with severe oligoasthenospermia (concentration < 5 x 10^6 spermatozoa/mL; motility< 10%)
- Female partner with anovulation (PCOS, FHA)
- Female partner age >41
- Female partner AFC< 7
- Female partner with obstructed fallopian tubes (assessed in all patients prior to IVF)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Microfluidic Sperm SortingAlso: FERTILE deviceMicrofluidic technology isolates healthy sperm by laminar flow, creating gradients through channels. The microfluidic chip we plan to study in our randomized clinical trial utilizes space-constrained microfluidic sorting to select highly motile and morphologically normal sperm in a flow and chemical-free design. Unlike the standard of density gradient centrifugation, no manipulation of sperm is required in this process. Raw semen is introduced into the inflow and only motile and morphologically normal sperm are able to swim through the chip to the outflow where it is collected for use. | Device | Microfluidic sperm sorting |
| in vitro fertilizationivf/icsi | Procedure or surgery | Conventional sperm preparation, Microfluidic sperm sorting |
Primary outcome
Day 3 High Quality Embryo Percentage
Time frame: 3 days following fertilization
The primary outcome for intent to treat analysis. Day 3 high quality embryo percentage rate will be defined as the percentage of all viable 2PN embryos on day 3 with at least 6 cells and fragmentation/symmetry scores of 1-2. Scale: 1-6 for either fragmentation or symmetry. Lower scores are better. Calculated as ( the number of high-qualify-grade embryos yielded by a participant / the number of all viable 2PN embryos yielded by the participant x 100)
2 secondary outcomes
Egg Fertilization Rate
Time frame: 1 day following fertilization
Pregnancy Rate
Time frame: 14 days following embryo transfer
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Dec 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35522187Quinn MM, Ribeiro S, Juarez-Hernandez F, Simbulan RK, Jalalian L, Cedars MI, Rosen MP. Microfluidic preparation of spermatozoa for ICSI produces similar embryo quality to density-gradient centrifugation: a pragmatic, randomized controlled trial. Hum Reprod. 2022 Jun 30;37(7):1406-1413. doi: 10.1093/humrep/deac099.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mitchell Rosen, M.D principal investigator
University of California, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Microfluidic Sperm Sorting and in vitro fertilization in people with Sperm DNA Fragmentation and Embryo Quality, run by University of California, San Francisco at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 31 Dec 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Day 3 High Quality Embryo Percentage (time frame: 3 days following fertilization). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03085433, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Dec 2025.