ROSI for Male Infertility

(ROSI Trial)

Overseen by Hooman Sadri, MD, PhD

Age: 18+

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Wake Forest University Health Sciences

Disqualifiers: Obstructive azoospermia, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial is testing a procedure that uses immature sperm cells to help men who can't produce mature sperm have biological children. The process involves selecting these cells and injecting them into an egg, with extra steps to ensure the egg is ready to develop. This technique has been explored as an alternative for men who cannot produce mature sperm.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Half ROSI-half Sperm Donor Fertilization, Round Spermatid Injection (ROSI) for male infertility?

Research shows that ROSI has led to the birth of children in cases where men have no mature sperm, but the success rates are much lower compared to using mature sperm. While some children have been born healthy using this method, the overall chances of a successful pregnancy and delivery are relatively low. ^{1 2 3 4 5}

Is ROSI safe for humans?

Studies have shown that children born after ROSI do not have any unusual physical, mental, or genetic problems compared to those born naturally. However, more participants and long-term follow-up studies are needed to fully assess the safety of the ROSI technique. ^{1 2 3 5 6}

How does the treatment Half ROSI-half Sperm Donor Fertilization differ from other treatments for male infertility?

This treatment is unique because it involves injecting round spermatids (immature sperm cells) directly into an egg, which is a novel approach for men with non-obstructive azoospermia (a condition where no sperm is present in the ejaculate). Unlike traditional sperm donation, this method allows men to potentially have their own genetic offspring even when mature sperm are not available. ^{1 2 3 5 7}

Research Team

Hooman Sadri, MD, PhD

Principal Investigator

Wake Forest Institute for Regenerative Medicine (WFIRM)

Hooman Sadri, MD, PhD

Principal Investigator

Wake Forest University Health Sciences

Eligibility Criteria

This trial is for couples facing male infertility due to non-obstructive azoospermia, where the man lacks mature sperm in his semen. Men must have round spermatids present and be over 18 years old. Women partners should be between 18-38 years or have an AMH level above 2 ng/ml.

Inclusion Criteria

My female partner is between 18 and 38 years old, or has an AMH level over 2 ng/ml.

My male partner is 18 years old or older.

I am a male diagnosed with a condition where I produce no sperm.

Exclusion Criteria

I am a male diagnosed with obstructive azoospermia.

My sperm test shows a normal count.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Round Spermatid Injection (ROSI) procedure is performed to fertilize oocytes using round spermatids or a combination of round spermatids and donor sperm

1 week

1 visit (in-person)

Embryo Development and Monitoring

Embryo development is monitored, including blastocyst formation and aneuploidy evaluation

1 week

Daily monitoring (in-person)

Follow-up

Participants are monitored for pregnancy outcomes, including chemical pregnancy and live birth rate

39-40 weeks

Regular visits (in-person)

Treatment Details

Interventions

• Half ROSI-half Sperm Donor Fertilization (Procedure)
• Round Spermatid Injection (ROSI) (Procedure)

Trial Overview The study tests if injecting round spermatids directly into eggs (ROSI) can lead to pregnancy in cases of severe male infertility. It compares ROSI with using half donor sperm to see which is safer and more effective at creating viable embryos.

Participant Groups

Group I: ROSI only Experimental Treatment 1 Intervention

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

Group II: Half ROSI-half Sperm Donor Fertilization Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

Dr. L. Ebony Boulware

Wake Forest University Health Sciences

Chief Medical Officer since 2022

MD from Duke University School of Medicine, MPH from Johns Hopkins Bloomberg School of Public Health

Dr. Julie Ann Freischlag

Wake Forest University Health Sciences

Chief Executive Officer since 2020

BS from University of Illinois, MD from Rush University

Carolinas Fertility Institute (CFI)

Collaborator

Trials

1

Recruited

50+

Wake Forest Institute for Regenerative Medicine (WFIRM)

Collaborator

Trials

1

Recruited

50+

Wake Forest Department of Urology

Collaborator

Trials

1

Recruited

50+

Findings from Research

In a study of 457 men with azoospermia, 342 were diagnosed with non-obstructive azoospermia (NOA), but only 43% had retrievable spermatozoa, indicating that many men may not benefit from round spermatid injections (ROSI).

Among the 194 men with NOA who had no spermatozoa, 75% were diagnosed with Sertoli cell-only syndrome, suggesting that round spermatids suitable for ROSI were rare, highlighting the need to reassess the clinical value of this intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Questioning the utility of round spermatid injections in men with non-obstructive azoospermia. Barda, S., Mano, R., Lehavi, O., et al.[2022]

Round spermatid injection (ROSI) has resulted in the successful birth and development of 14 children from 12 women, demonstrating its potential as a viable option for men with severe infertility issues where traditional sperm retrieval methods fail.

All children born through ROSI have shown no unusual physical, mental, or epigenetic problems, indicating that this method may be safe for producing genetically related offspring in cases where other options are not available.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fourteen babies born after round spermatid injection into human oocytes. Tanaka, A., Nagayoshi, M., Takemoto, Y., et al.[2018]

Non-obstructive azoospermia (NOA) is a significant cause of male infertility, with many affected men having some active spermatogenesis, which can be utilized in assisted reproductive techniques like round spermatid injection (ROSI).

The ROSI technique, which involves injecting round spermatids from testicular biopsies into oocytes, shows promise but requires more participants and long-term studies to confirm its reliability and improve success rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical values and advances in round spermatid injection (ROSI). Tekayev, M., Vuruskan, AK.[2022]

Round spermatid injection (ROSI) can lead to fertilization and pregnancies in azoospermic men, with a fertilization rate of 38.7% based on a meta-analysis of 22 studies involving 1099 couples.

However, the overall success rates are low, with only 4.3% of embryo transfers resulting in live births, indicating that while ROSI is a potential option, couples should be aware of the significantly reduced chances of successful delivery compared to using mature sperm.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Round spermatid injection into human oocytes: a systematic review and meta-analysis. Hanson, BM., Kohn, TP., Pastuszak, AW., et al.[2021]

Round spermatid injection (ROSI) has led to the birth of 90 babies, with follow-up studies showing no significant differences in physical and cognitive abilities compared to naturally conceived children, indicating its potential safety.

Identifying and correcting epigenetic abnormalities may enhance the clinical outcomes of ROSI, which have historically been low, suggesting that addressing these issues could improve embryonic development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How to improve the clinical outcome of round spermatid injection (ROSI) into the oocyte: Correction of epigenetic abnormalities. Tanaka, A., Watanabe, S.[2023]

The study found that round spermatid injection (ROSI) can produce embryos with normal genomes and similar implantation rates to ICSI embryos, indicating potential for effective use in treating non-obstructive azoospermia.

Despite lower overall development efficiency, ROSI-derived offspring showed no significant defects or abnormalities, suggesting that the progeny are safe and supporting the clinical application of ROSI technology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the post-implantation development of mouse embryos derived from round spermatid injection. Zhu, H., Chen, Y., Wei, J., et al.[2023]

In a series of 11 cases of infertility treatment using spermatid injection, fertilization was achieved in 10 cycles, demonstrating a mean fertilization rate of 45%, indicating the method's efficacy.

The successful births of normal infants from two pregnancies achieved through round spermatid injection (ROSI) suggest that this technique could become a preferred treatment for men with non-obstructive azoospermia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spermatid injection into human oocytes. II. Clinical application in the treatment of infertility due to non-obstructive azoospermia. Tesarik, J., Rolet, F., Brami, C., et al.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Questioning the utility of round spermatid injections in men with non-obstructive azoospermia. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Fourteen babies born after round spermatid injection into human oocytes. [2018]

3. Poland pubmed.ncbi.nlm.nih.gov

Clinical values and advances in round spermatid injection (ROSI). [2022]

4. China pubmed.ncbi.nlm.nih.gov

Round spermatid injection into human oocytes: a systematic review and meta-analysis. [2021]

5. Japan pubmed.ncbi.nlm.nih.gov

How to improve the clinical outcome of round spermatid injection (ROSI) into the oocyte: Correction of epigenetic abnormalities. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Evaluation of the post-implantation development of mouse embryos derived from round spermatid injection. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Spermatid injection into human oocytes. II. Clinical application in the treatment of infertility due to non-obstructive azoospermia. [2019]