Infertility, MaleROSINCT04298255
Experimental Round Spermatid Injection (ROSI) to Treat Infertile Couples
A study testing Round Spermatid Injection (ROSI) and Half ROSI-half Sperm Donor Fertilization in people with Infertility, Male, run by Wake Forest University Health Sciences at 1 site in United States.
Trial summary
The purpose of this research study is to evaluate if special types of cells called round spermatids can be gathered from men with non-obstructive azoospermia and used (in absence of elongated spermatids and spermatozoa) to reliably and effectively create pregnancy with a procedure called Round Spermatid Injection… Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Infertility, Male
- What is being tested?
- Round Spermatid Injection (ROSI) and Half ROSI-half Sperm Donor Fertilization
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Aug 2020to Jul 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males with no elongated spermatids or spermatozoa present but with round spermatids present on TESE (Testicular Sperm Extraction)
- Male diagnosed with non-obstructive Azoospermia
- Male partner ≥18
- Female partner greater than 18 years of age and less than 38 years of age or Anti Mullerian Hormone (AMH) greater than 2 ng/ml.
Who cannot join
- Males with obstructive azoospermia
- Males with presence an adequate number of elongated spermatids or spermatozoa
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Carolinas Fertility Institute (CFI)
Winston-Salem, North Carolina, 27103
Tamer Yalcinkaya, MD
Hooman Sadri, MD, PhD
About this study
The purpose of this research study is to evaluate if special types of cells called round spermatids can be gathered from men with non-obstructive azoospermia and used (in absence of elongated spermatids and spermatozoa) to reliably and effectively create pregnancy with a procedure called Round Spermatid Injection (ROSI). This process is similar to In Vitro Fertilization, or 'IVF'. In addition, this study wants to test the safety of ROSI and see what effects (good and bad) it has on embryo created from this method.
Read the detailed description
Azoospermia is defined as the absence of sperm in the ejaculate. Around 1% of general population suffers from azoospermia. Men who were rendered infertile due to a non-obstructive azoospermia, who have been subjected to Testicular Sperm Extraction (TESE) surgery and found to be lacking elongated spermatids or spermatozoa, are commonly advised to consider utilizing a sperm donor or apply for adoption. It is reported that ~30% of men with non-obstructive azoospermia lack elongated spermatids and spermatozoa but may still produce round spermatids (less mature form of haploid germ cells) in their testicles. Round Spermatid Injection (ROSI) technology to fertilize oocytes is not a brand-new technology, however, it is plagued with notoriously low efficiency. Despite this limitation, it has been reported that most of these patients still desire to have the ROSI procedure instead of applying directly for other options, i.e. sperm donation or adoption.
High failure rate of traditional ROSI has been attributed to a few potential causes:
- Incorrect selection of round spermatids (to distinguish from diploid spermatogonia cells)
- Using round spermatids that were already in the process of degeneration
- Incomplete imprinting in the round spermatid
- Incomplete activation of oocytes Recently Tanaka and colleagues in Japan established a new ROSI method and reported over 90 babies born via this method1. They described a new method of round spermatid selection and oocyte activation using NEPA21 super electroporator (10 minutes prior to round spermatid injection).
Babies born from this new ROSI method in Japan have been evaluated for developmental and cognitive differences for 2 years1. Babies conceived with ROSI were found to have a shorter gestation times, and lower body weight at 12 and 18 months when compared to their naturally conceived counterparts, but also showed an increased birth weight and showed no body weight differences at 24 months of age. No diseases resulting from genetic anomalies have been reported thus far, but the relatively small sample sizes present in the literature needs to be tested in larger cohorts. Therefore, this effective ROSI method should still be considered as an "experimental fertility treatment".
- Conditions
- Infertility, Male
- Being tested
- Round Spermatid Injection (ROSI), Half ROSI-half Sperm Donor Fertilization
- Keywords
- IVF, Fertility
- Medical subject headings
- Infertility, Male
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Round Spermatid Injection (ROSI)Other
In Vitro Fertilization using Round Spermatid Injection (ROSI)
Half ROSI-half Sperm Donor FertilizationOther
Half ROSI-half Sperm Donor Fertilization
| Study group | Role | What they receive |
|---|---|---|
| ROSI only | Experimental | Option 1: injecting extracted round spermatids (less mature form of haploid germ cells than elongated spermatid or spermatozoon) from male partner into the harvested egg of a female partner Receives: Other: Round Spermatid Injection (ROSI) |
| Half ROSI-half Sperm Donor Fertilization | Experimental | Option 2: Harvested eggs from the female partner will be separated in two groups, with one group being fertilized with round spermatids and the other group fertilized with donor sperm Receives: Other: Half ROSI-half Sperm Donor Fertilization |
What is being measured
The primary outcome is the main question the study is designed to answer.
Fertility rate
Egg fertilization comparison between the groups undergoing the procedure with spermatids only vs spermatids and donor sperms.This fertilization process will be recorded by EmbryoScope under supervision of dedicated clinical embryologist.All the process will be followed and documented according to America Society of Reproductive Medicine (ASRM) guidelines. All the process will be followed and documented according to American Society for Reproductive Medicine (ASRM) guidelines.
Measured: Day 1 after round spermatid injection
Secondary outcomes (4)
Blastocyst formation
Blastocyst comparison between the groups undergoing the procedure with spermatids only vs spermatids and donor sperms.Embryo grow and blastocyst formation will be recorded by EmbryoScope under supervision of dedicated clinical embryologist.All the process will be followed and documented according to American Society for Reproductive Medicine (ASRM) guidelines.
Measured: Day 3 to 5 after round spermatid injection
Aneuploidy rate
Aneuploidy comparison and evaluation of abnormality between the groups undergoing the procedure with spermatids only vs spermatids and donor sperms. Aneuploidy will be tested using polymerase chain reaction amplification (PCR) based Preimplantation genetic diagnosis (PGD) and fluorescent in situ hybridization (FISH) analyses. All the process will be followed and documented according to American Society for Reproductive Medicine (ASRM) guidelines.
Measured: Day 3 to 5 after round spermatid injection
Chemical Pregnancy with Positive human chorionic gonadotropin (hCG)
Pregnancy Rate between the groups undergoing the procedure with spermatids only vs spermatids and donor sperms. Blood test to measure beta-hCG (chemical pregnancy) and follows by Ultrasound (clinical pregnancy). All the process will be followed and documented according to American Society for Reproductive Medicine (ASRM) guidelines.
Measured: Post Fertilization 4 Weeks and onwards
Live Birth Rate
Live Birth comparison between the groups undergoing the procedure with spermatids only vs spermatids and donor sperms. Pregnancy will be followed as high risk and health of born children will be evaluated by a dedicated neonatologist/Pediatrician. All the process will be followed and documented according to American Society for Reproductive Medicine (ASRM) guidelines.
Measured: Post Pregnancy Full Term Average 39 to 40 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2020
- Study start24 Aug 2020
- Primary completionJul 2028 (estimated)
- Study completionJul 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Infertility, MaleStudies of the same condition, open and under way.
- More trials run by Wake Forest University Health SciencesThe 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
- Non-randomised
- Intervention model
- Single group
- Model description
- Infertile Male with round spermatid (but not elongated spermatids and spermatozoa) in their testes. Couples can choose either option 1 or 2.
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Wake Forest University Health Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- Carolinas Fertility Institute (CFI), Wake Forest Institute for Regenerative Medicine (WFIRM), Wake Forest Department of Urology
- Responsible party
- Sponsor
- Investigators
- Hooman Sadri, MD, PhD, Principal investigator, Wake Forest Institute for Regenerative Medicine (WFIRM)Hooman Sadri, MD, PhD, Study director, Wake Forest University Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04298255
- Sponsor's protocol ID
- IRB00062898
- Acronym
- ROSI
- Status last verified
- Sep 2026
- First submitted
- 4 Mar 2020
- Last updated
- 17 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual Participant Data will be available to research teams of Carolinas Fertility Institute and Wake Forest University. It will not be shared with others. Data will be available in the form of electronic charts at the Carolinas Fertility Institute, and limited hard copies at the Wake Forest University Urology Department.
Publications
Tanaka A, Suzuki K, Nagayoshi M, Tanaka A, Takemoto Y, Watanabe S, Takeda S, Irahara M, Kuji N, Yamagata Z, Yanagimachi R. Ninety babies born after round spermatid injection into oocytes: survey of their development from fertilization to 2 years of age. Fertil Steril. 2018 Aug;110(3):443-451. doi: 10.1016/j.fertnstert.2018.04.033.
PubMed 30098696Tanaka A, Nagayoshi M, Takemoto Y, Tanaka I, Kusunoki H, Watanabe S, Kuroda K, Takeda S, Ito M, Yanagimachi R. Fourteen babies born after round spermatid injection into human oocytes. Proc Natl Acad Sci U S A. 2015 Nov 24;112(47):14629-34. doi: 10.1073/pnas.1517466112. Epub 2015 Nov 2.
PubMed 26575628Bradshaw AW, Nikmehr B, Halicigil C, Stogner-Underwood K, Sadri-Ardekani H. Optimum identification of round spermatid in men with non-obstructive azoospermia: A commentary. Andrology. 2021 Nov;9(6):1817-1818. doi: 10.1111/andr.13113. Epub 2021 Oct 14. No abstract available.
PubMed 34618410
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Experimental Round Spermatid Injection (ROSI) to Treat Infertile Couples
- ClinicalTrials.gov ID
- NCT04298255
- Acronym / sponsor ID
- ROSI / IRB00062898
- Conditions
- Infertility, Male
- Keywords
- IVF, Fertility
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Wake Forest University Health SciencesUniversity, hospital or other
- Collaborators
- Carolinas Fertility Institute (CFI), Wake Forest Institute for Regenerative Medicine (WFIRM), Wake Forest Department of Urology
- Study start
- 24 Aug 2020 (actual)
- Primary completion
- Jul 2028 (estimated)
- Study completion
- Jul 2028 (estimated)
- First posted
- 6 Mar 2020 (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.
The purpose of this research study is to evaluate if special types of cells called round spermatids can be gathered from men with non-obstructive azoospermia and used (in absence of elongated spermatids and spermatozoa) to reliably and effectively create pregnancy with a procedure called Round Spermatid Injection (ROSI). This process is similar to In Vitro Fertilization, or 'IVF'. In addition, this study wants to test the safety of ROSI and see what effects (good and bad) it has on embryo created from this method.
Detailed description
Azoospermia is defined as the absence of sperm in the ejaculate. Around 1% of general population suffers from azoospermia. Men who were rendered infertile due to a non-obstructive azoospermia, who have been subjected to Testicular Sperm Extraction (TESE) surgery and found to be lacking elongated spermatids or spermatozoa, are commonly advised to consider utilizing a sperm donor or apply for adoption. It is reported that ~30% of men with non-obstructive azoospermia lack elongated spermatids and spermatozoa but may still produce round spermatids (less mature form of haploid germ cells) in their testicles. Round Spermatid Injection (ROSI) technology to fertilize oocytes is not a brand-new technology, however, it is plagued with notoriously low efficiency. Despite this limitation, it has been reported that most of these patients still desire to have the ROSI procedure instead of applying directly for other options, i.e. sperm donation or adoption.
High failure rate of traditional ROSI has been attributed to a few potential causes:
- Incorrect selection of round spermatids (to distinguish from diploid spermatogonia cells)
- Using round spermatids that were already in the process of degeneration
- Incomplete imprinting in the round spermatid
- Incomplete activation of oocytes Recently Tanaka and colleagues in Japan established a new ROSI method and reported over 90 babies born via this method1. They described a new method of round spermatid selection and oocyte activation using NEPA21 super electroporator (10 minutes prior to round spermatid injection).
Babies born from this new ROSI method in Japan have been evaluated for developmental and cognitive differences for 2 years1. Babies conceived with ROSI were found to have a shorter gestation times, and lower body weight at 12 and 18 months when compared to their naturally conceived counterparts, but also showed an increased birth weight and showed no body weight differences at 24 months of age. No diseases resulting from genetic anomalies have been reported thus far, but the relatively small sample sizes present in the literature needs to be tested in larger cohorts. Therefore, this effective ROSI method should still be considered as an "experimental fertility treatment".
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Infertile Male with round spermatid (but not elongated spermatids and spermatozoa) in their testes. Couples can choose either option 1 or 2.
| Arm | Type | Receives |
|---|---|---|
| ROSI only | Experimental | Other: Round Spermatid Injection (ROSI)Option 1: injecting extracted round spermatids (less mature form of haploid germ cells than elongated spermatid or spermatozoon) from male partner into the harvested egg of a female partner |
| Half ROSI-half Sperm Donor Fertilization | Experimental | Other: Half ROSI-half Sperm Donor FertilizationOption 2: Harvested eggs from the female partner will be separated in two groups, with one group being fertilized with round spermatids and the other group fertilized with donor sperm |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Males with no elongated spermatids or spermatozoa present but with round spermatids present on TESE (Testicular Sperm Extraction)
- Male diagnosed with non-obstructive Azoospermia
- Male partner ≥18
- Female partner greater than 18 years of age and less than 38 years of age or Anti Mullerian Hormone (AMH) greater than 2 ng/ml.
Key exclusion criteria (2 listed)
- Males with obstructive azoospermia
- Males with presence an adequate number of elongated spermatids or spermatozoa
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 |
|---|---|---|
| Round Spermatid Injection (ROSI)In Vitro Fertilization using Round Spermatid Injection (ROSI) | Other | ROSI only |
| Half ROSI-half Sperm Donor FertilizationHalf ROSI-half Sperm Donor Fertilization | Other | Half ROSI-half Sperm Donor Fertilization |
Primary outcome
Fertility rate
Time frame: Day 1 after round spermatid injection
Egg fertilization comparison between the groups undergoing the procedure with spermatids only vs spermatids and donor sperms.This fertilization process will be recorded by EmbryoScope under supervision of dedicated clinical embryologist.All the process will be followed and documented according to America Society of Reproductive Medicine (ASRM) guidelines. All the process will be followed and documented according to American Society for Reproductive Medicine (ASRM) guidelines.
4 secondary outcomes
Blastocyst formation
Time frame: Day 3 to 5 after round spermatid injection
Aneuploidy rate
Time frame: Day 3 to 5 after round spermatid injection
Chemical Pregnancy with Positive human chorionic gonadotropin (hCG)
Time frame: Post Fertilization 4 Weeks and onwards
Live Birth Rate
Time frame: Post Pregnancy Full Term Average 39 to 40 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2026.
- Background: PubMed 30098696Tanaka A, Suzuki K, Nagayoshi M, Tanaka A, Takemoto Y, Watanabe S, Takeda S, Irahara M, Kuji N, Yamagata Z, Yanagimachi R. Ninety babies born after round spermatid injection into oocytes: survey of their development from fertilization to 2 years of age. Fertil Steril. 2018 Aug;110(3):443-451. doi: 10.1016/j.fertnstert.2018.04.033.
- Background: PubMed 26575628Tanaka A, Nagayoshi M, Takemoto Y, Tanaka I, Kusunoki H, Watanabe S, Kuroda K, Takeda S, Ito M, Yanagimachi R. Fourteen babies born after round spermatid injection into human oocytes. Proc Natl Acad Sci U S A. 2015 Nov 24;112(47):14629-34. doi: 10.1073/pnas.1517466112. Epub 2015 Nov 2.
- Background: PubMed 34618410Bradshaw AW, Nikmehr B, Halicigil C, Stogner-Underwood K, Sadri-Ardekani H. Optimum identification of round spermatid in men with non-obstructive azoospermia: A commentary. Andrology. 2021 Nov;9(6):1817-1818. doi: 10.1111/andr.13113. Epub 2021 Oct 14. No abstract available.
- Individual participant dataSharing planned: No. Individual Participant Data will be available to research teams of Carolinas Fertility Institute and Wake Forest University. It will not be shared with others. Data will be available in the form of electronic charts at the Carolinas Fertility Institute, and limited hard copies at the Wake Forest University Urology Department.
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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.
Hooman Sadri, MD, PhD principal investigator
Wake Forest Institute for Regenerative Medicine (WFIRM)
Hooman Sadri, MD, PhD study director
Wake Forest University Health Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Round Spermatid Injection (ROSI) and Half ROSI-half Sperm Donor Fertilization in people with Infertility, Male, run by Wake Forest University Health Sciences 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 4 inclusion and 2 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: looking for participants now, as of the sponsor's last update on 17 Sep 2026. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Karla M Oliver (336-713-3123, kaoliver@wakehealth.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Fertility rate (time frame: Day 1 after round spermatid injection). 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 NCT04298255, which also lists 3 linked publications.
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 17 Sep 2026.