Infertility, MaleNCT06524102
The Aim of This Study is to Determine the Incidence of Alterations in Fluorescent In Situ Hybridisation (FISH) of Spermatozoa and to Evaluate the Efficacy of the Use of Annexin Columns (MACS®) in Patients With Altered FISH Undergoing In Vitro Fertilisation Techniques
A study testing Magnetic Activated Cell Sorting in people with Infertility, Male, run by Instituto de Investigación Sanitaria y Biomédica de Alicante at 1 site in Spain.
Trial summary
250 petitions for FISH of spermatozoa were requested, determining the total and particular incidence in each of the indications collected. The effect of annexin columns was evaluated in 10 couples with altered FISH. In each of the couples, oocytes were pseudo-randomised to the control group and MACS®. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Infertility, Male
- What is being tested?
- Magnetic Activated Cell Sorting
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteSpain
- Study dates
- 1 Jan 2018to 31 Mar 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Women between 18 and 40 years of age. Men between 18 and 55 years of age.
- Couples without any common, previous and healthy children.
- Couples with indication of IVF-ICSI cycle with Preimplantation Genetic Test for Aneuploidy (PGT-A).
- Men with altered sperm FISH results.
Who cannot join
- Prior voluntary sterilization.
- Existence of documented medical contraindication for infertility treatment.
- Existence of documented medical contraindication to pregnancy.
- Existence of a documented medical situation that seriously interferes with the development of the offspring.
- Impossibility to comply with the treatment for health-related reasons or other family or social environment-related reasons.
- Existence of a documented situation referring to any other circumstance that may seriously interfere with the development of the offspring submitted for consideration to a health care ethics committee or similar body.
- One or both partners with positive serology for HIV, HBV and VDRL.
- One or both partners with partner with altered karyotype.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Evaluation of the Efficacy of Annexin Columns (MACS) in Patients With Altered Sperm FISH Undergoing Assisted Reproductive Techniques
250 petitions for FISH of spermatozoa were requested, determining the total and particular incidence in each of the indications collected. The effect of annexin columns was evaluated in 10 couples with altered FISH. In each of the couples, oocytes were pseudo-randomised to the control group and MACS®. All couples received experimental treatment. Mixed logistic regression model were adjusted to evaluate the effect of MACS® on the response variables studied.
Read the detailed description
Prospective pseudo-randomised study carried out in the reproduction unit of the Hospital General Universitario Dr. Balmis in Alicante. The study was divided into two phases, with both being conducted in parallel. The research was approved by the Ethics Committee for Research on Medicines (CEIm) of the Alicante Department of Health. The treatment and use of the clinical data required for this study complied with current legislation, preserving the anonymity of the patients.
Phase I. A total of 250 sperm FISH tests were requested for different indications in men aged 18-55 years with normal karyotype. Of the total number of tests requested, 16 could not be performed due to low sperm count. Finally, 234 samples were analysed, of which 20 had altered sperm FISH.
Phase II. From the previous phase, not all patients with an altered FISH test were included in the second phase of the study, some of them were lost for different reasons (n=10). A total of 10 couples with no previous children in common, negative serology and normal karyotype were included. Females were aged less than 40 years and males less than 50 years at the time of treatment.
The semen sample of each couple was capacitated by density gradient centrifugation (DGC) and swim up, forming the control group. An aliquot was taken that was destined to pass through the annexin columns (MACS® ART, Miltenyl Biotic GmbH, Germany) constituting the study group. The oocytes obtained in each of the couples were pseudo-randomized and inseminated by ICSI with sperm from the study group and the control group. All couples benefited from the experimental treatment since they had the opportunity to inseminate their oocytes with sperm from both groups, thus excluding treatment bias or asymmetry.
To evaluate the efficacy of MACS® on laboratory outcome, fertilization rates, abnormal fertilization, biopsiable embryos and euploid embryos were compared between the study and control group.
- Conditions
- Infertility, Male
- Being tested
- Magnetic Activated Cell Sorting
- Keywords
- In Vitro Fertilization, sperm FISH, annexin columns, MACS, Preimplantation Genetic Testing for aneuploidies
- Medical subject headings
- Infertility, Male
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Magnetic Activated Cell SortingDevice
Also called MACS
The MACS® ART Annexin V System has been designed for the in vitro elimination of apoptotic human spermatozoa in fresh, cryopreserved or otherwise manipulated semen samples. Samples processed by this technique can be subsequently used in any assisted reproduction procedure.
Annexin V recognizes externalized phosphatidylserine (ePS) on the plasma membrane of apoptotic spermatozoa. Depletion of the altered sperm begins with magnetic tagging of the sperm. The system selectively retains unwanted sperm by utilizing the natural ability of annexin V to recognize the ePS on the plasma membrane of the altered sperm, because annexin V is conjugated to metal microspheres. The labeled cells pass through a separation column in a fixed magnetic field. Unwanted (altered) spermatozoa are selectively retained in the separation column. Unlabeled spermatozoa pass through the column where they are collected for later use.
| Study group | Role | What they receive |
|---|---|---|
| MACS | Experimental | Oocytes corresponding to this group were inseminated by spermatozoa selected after the use of MACS. Receives: Device: Magnetic Activated Cell Sorting |
| Control | No intervention | Oocytes corresponding to this group were inseminated with spermatozoa obtained after density gradient centrifugation. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Euploid embryo rate
Embryos without chromosomal alterations in relation to the total number of those that were informative.
Measured: This variable was taken 2 days after obtaining the genetic result of the embryo biopsy.
Secondary outcomes (2)
Fertilization rate
Number of correctly fertilized zygotes among the total number of mature oocytes inseminated
Measured: This variable was taken 17-20 hours after oocyte insemination.
Biopsiable embryo rate
Number of biopsied embryos versus the total number of correctly fertilized zygotes
Measured: This variable was taken on the 3rd day of embryonic development, at the time of the embryo biopsy. .
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jul 2024
- Study start1 Jan 2018
- Primary completion31 Mar 2022
- Study completion31 Mar 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Infertility, MaleStudies of the same condition, open and under way.
- 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
- Model description
- A total of 10 couples with no previous children in common, negative serology and normal karyotype were included. Females were aged less than 40 years and males less than 50 years at the time of treatment. The semen sample of each couple was capacitated by density gradient centrifugation (DGC) and swim up, forming the control group. An aliquot was taken that was destined to pass through the annexin columns (MACS® ART, Miltenyl Biotic GmbH, Germany) constituting the study group. The oocytes obtained in each of the couples were pseudo-randomized and inseminated by ICSI with sperm from the study group and the control group. All couples benefited from the experimental treatment since they had the opportunity to inseminate their oocytes with sperm from both groups, thus excluding treatment bias or asymmetry.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Instituto de Investigación Sanitaria y Biomédica de Alicante
- Sponsor type
- Research network
- Responsible party
- Principal investigator, Borja Tejero Llinares, Instituto de Investigación Sanitaria y Biomédica de Alicante
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06524102
- Sponsor's protocol ID
- 190767
- Status last verified
- Jul 2024
- First submitted
- 21 Jul 2024
- Last updated
- 29 Jul 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Tejero B, Martinez JC, Eleno I, Matallin P, Fernandez-Peinado A, Bernabeu-Egea I, Valdes J, Quereda F. Quasi-randomized pilot clinical trial comparing the use of annexin columns in patients with abnormal sperm FISH undergoing IVF techniques. Sci Rep. 2025 Nov 14;15(1):39966. doi: 10.1038/s41598-025-23728-y.
PubMed 41238709
Study at a glance
From the registry record, last updated by the sponsor on 29 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Efficacy of Annexin Columns (MACS) in Patients With Altered Sperm FISH Undergoing Assisted Reproductive Techniques
- ClinicalTrials.gov ID
- NCT06524102
- Acronym / sponsor ID
- 190767
- Conditions
- Infertility, Male
- Keywords
- In Vitro Fertilization, sperm FISH, annexin columns, MACS, Preimplantation Genetic Testing for aneuploidies
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Instituto de Investigación Sanitaria y Biomédica de AlicanteResearch network
- Study start
- 1 Jan 2018 (actual)
- Primary completion
- 31 Mar 2022 (actual)
- Study completion
- 31 Mar 2022 (actual)
- First posted
- 29 Jul 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
250 petitions for FISH of spermatozoa were requested, determining the total and particular incidence in each of the indications collected. The effect of annexin columns was evaluated in 10 couples with altered FISH. In each of the couples, oocytes were pseudo-randomised to the control group and MACS®. All couples received experimental treatment. Mixed logistic regression model were adjusted to evaluate the effect of MACS® on the response variables studied.
Detailed description
Prospective pseudo-randomised study carried out in the reproduction unit of the Hospital General Universitario Dr. Balmis in Alicante. The study was divided into two phases, with both being conducted in parallel. The research was approved by the Ethics Committee for Research on Medicines (CEIm) of the Alicante Department of Health. The treatment and use of the clinical data required for this study complied with current legislation, preserving the anonymity of the patients.
Phase I. A total of 250 sperm FISH tests were requested for different indications in men aged 18-55 years with normal karyotype. Of the total number of tests requested, 16 could not be performed due to low sperm count. Finally, 234 samples were analysed, of which 20 had altered sperm FISH.
Phase II. From the previous phase, not all patients with an altered FISH test were included in the second phase of the study, some of them were lost for different reasons (n=10). A total of 10 couples with no previous children in common, negative serology and normal karyotype were included. Females were aged less than 40 years and males less than 50 years at the time of treatment.
The semen sample of each couple was capacitated by density gradient centrifugation (DGC) and swim up, forming the control group. An aliquot was taken that was destined to pass through the annexin columns (MACS® ART, Miltenyl Biotic GmbH, Germany) constituting the study group. The oocytes obtained in each of the couples were pseudo-randomized and inseminated by ICSI with sperm from the study group and the control group. All couples benefited from the experimental treatment since they had the opportunity to inseminate their oocytes with sperm from both groups, thus excluding treatment bias or asymmetry.
To evaluate the efficacy of MACS® on laboratory outcome, fertilization rates, abnormal fertilization, biopsiable embryos and euploid embryos were compared between the study and control group.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
- Model description
- A total of 10 couples with no previous children in common, negative serology and normal karyotype were included. Females were aged less than 40 years and males less than 50 years at the time of treatment. The semen sample of each couple was capacitated by density gradient centrifugation (DGC) and swim up, forming the control group. An aliquot was taken that was destined to pass through the annexin columns (MACS® ART, Miltenyl Biotic GmbH, Germany) constituting the study group. The oocytes obtained in each of the couples were pseudo-randomized and inseminated by ICSI with sperm from the study group and the control group. All couples benefited from the experimental treatment since they had the opportunity to inseminate their oocytes with sperm from both groups, thus excluding treatment bias or asymmetry.
| Arm | Type | Receives |
|---|---|---|
| MACS | Experimental | Device: Magnetic Activated Cell SortingOocytes corresponding to this group were inseminated by spermatozoa selected after the use of MACS. |
| Control | No intervention | –Oocytes corresponding to this group were inseminated with spermatozoa obtained after density gradient centrifugation. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Women between 18 and 40 years of age. Men between 18 and 55 years of age.
- Couples without any common, previous and healthy children.
- Couples with indication of IVF-ICSI cycle with Preimplantation Genetic Test for Aneuploidy (PGT-A).
- Men with altered sperm FISH results.
Key exclusion criteria (8 listed)
- Prior voluntary sterilization.
- Existence of documented medical contraindication for infertility treatment.
- Existence of documented medical contraindication to pregnancy.
- Existence of a documented medical situation that seriously interferes with the development of the offspring.
- Impossibility to comply with the treatment for health-related reasons or other family or social environment-related reasons.
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 |
|---|---|---|
| Magnetic Activated Cell SortingAlso: MACSThe MACS® ART Annexin V System has been designed for the in vitro elimination of apoptotic human spermatozoa in fresh, cryopreserved or otherwise manipulated semen samples. Samples processed by this technique can be subsequently used in any assisted reproduction procedure. Annexin V recognizes externalized phosphatidylserine (ePS) on the plasma membrane of apoptotic spermatozoa. Depletion of the altered sperm begins with magnetic tagging of the sperm. The system selectively retains unwanted sperm by utilizing the natural ability of annexin V to recognize the ePS on the plasma membrane of the altered sperm, because annexin V is conjugated to metal microspheres. The labeled cells pass through a separation column in a fixed magnetic field. Unwanted (altered) spermatozoa are selectively retained in the separation column. Unlabeled spermatozoa pass through the column where they are collected for later use. | Device | MACS |
Primary outcome
Euploid embryo rate
Time frame: This variable was taken 2 days after obtaining the genetic result of the embryo biopsy.
Embryos without chromosomal alterations in relation to the total number of those that were informative.
2 secondary outcomes
Fertilization rate
Time frame: This variable was taken 17-20 hours after oocyte insemination.
Biopsiable embryo rate
Time frame: This variable was taken on the 3rd day of embryonic development, at the time of the embryo biopsy. .
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jul 2024.
- Derived from this study: PubMed 41238709Tejero B, Martinez JC, Eleno I, Matallin P, Fernandez-Peinado A, Bernabeu-Egea I, Valdes J, Quereda F. Quasi-randomized pilot clinical trial comparing the use of annexin columns in patients with abnormal sperm FISH undergoing IVF techniques. Sci Rep. 2025 Nov 14;15(1):39966. doi: 10.1038/s41598-025-23728-y.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Magnetic Activated Cell Sorting in people with Infertility, Male, run by Instituto de Investigación Sanitaria y Biomédica de Alicante at 1 site in Spain.
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 4 inclusion and 8 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 29 Jul 2024. 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 Spain. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Euploid embryo rate (time frame: This variable was taken 2 days after obtaining the genetic result of the embryo biopsy.). 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 NCT06524102, 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 29 Jul 2024.