ROSI for Male Infertility

(ROSI Trial)

Overseen By Karla M Oliver

Age: 18+

Sex: Male

Trial Phase: Academic

Sponsor: Wake Forest University Health Sciences

Disqualifiers: Obstructive azoospermia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 1 week

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore a new fertility treatment called Round Spermatid Injection (ROSI) for men with non-obstructive azoospermia, a condition where no mature sperm cells exist, but round spermatids (early-stage sperm cells) are present. The goal is to determine if these spermatids can effectively create a pregnancy using a process similar to IVF. The trial will also assess the safety of ROSI and its effects on embryos. It is suitable for men diagnosed with non-obstructive azoospermia and their female partners. As an unphased trial, this study offers a unique opportunity to contribute to pioneering research in fertility treatments.

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 prior data suggests that the ROSI technique is safe for creating pregnancies?

Research has shown that Round Spermatid Injection (ROSI) has successfully led to the birth of 14 healthy babies. This suggests that ROSI can be safe, though it generally has lower success rates compared to using mature sperm. Uncertainty remains about the long-term health effects on children born through this method, necessitating further research.

For the Half ROSI-half Sperm Donor Fertilization approach, donor sperm has been used in fertility treatments with a clinical pregnancy rate of 22.2% per cycle. Using donor sperm is considered safe and well-established, but combining it with ROSI remains under study.

Overall, the safety of ROSI and the half ROSI-half donor method appears promising but is not fully understood. The trial offers an opportunity to gather more information on the effectiveness and safety of these treatments in creating healthy embryos. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about ROSI (Round Spermatid Injection) for male infertility because it offers a novel way to utilize immature sperm cells, known as round spermatids, to fertilize a partner's egg. Unlike current treatments that often rely on donor sperm when mature sperm are unavailable, ROSI allows for the use of the male partner's genetic material, which could be significant for couples seeking biological parenthood. Additionally, the trial is exploring a combination approach where some eggs are fertilized with donor sperm and others with round spermatids, potentially increasing the chances of successful fertilization. This dual strategy could offer new hope for couples facing tough fertility challenges.

What evidence suggests that this trial's treatments could be effective for male infertility?

Research shows that Round Spermatid Injection (ROSI) can assist men with non-obstructive azoospermia, a condition where no mature sperm are present. Some studies have shown that ROSI has resulted in the birth of children, even without mature sperm. However, success rates are generally lower than those with methods using mature sperm, such as Intracytoplasmic Sperm Injection (ICSI). One study found a fertilization rate of about 44.9% with ROSI, compared to 69% with ICSI. In this trial, participants may receive ROSI only, or they may join the Half ROSI-half Sperm Donor Fertilization arm, where harvested eggs are fertilized with both round spermatids and donor sperm. Despite lower success rates, ROSI provides an option for couples when other methods are not feasible. ^{1 2 6 7 8}

Who Is on the 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

Are You a Good Fit for This Trial?

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

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

My test results show only round spermatids, no mature sperm.

Exclusion Criteria

I am a male diagnosed with obstructive azoospermia.

My sperm test shows a normal count.

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

Interventions

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

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.

How Is the Trial Designed?

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+

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

Citations

1. withpower.com withpower.com/trial/phase-infertility-7-2020-ccf1e

ROSI for Male Infertility (ROSI Trial) 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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4577602/

ICSI treatment of severe male infertility can achieve ... This study analyzed the fertilization ability and the developmental viabilities of the derived embryos after ICSI treatment of the sperm from these patients.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1642431X21000516

Clinical values and advances in round spermatid injection ... ROSI technique involves the injection of haploid germ cells derived from testicular biopsies into the recipient oocytes. The present study demonstrates that ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0015028203011208

Pregnancy outcomes using donor sperm insemination after ... Of the 19 couples that failed an IVF-ICSI procedure, we observed an overall clinical pregnancy rate of 84% and a live birth rate of 88%. The monthly fecundity ...

5. fertstert.org fertstert.org/article/S0015-0282(25)00081-0/pdf

Intracytoplasmic sperm injection alone is the most ... Sperm DNA fragmentation. PRO: Intracytoplasmic sperm injection alone is the most efficacious, effective and efficient treatment for couples with male factor.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7468038/

Reproductive outcomes with donor sperm in couples ... The clinical pregnancy rate per cycle of donor insemination was 22.2% (20/90), and the overall AID clinical pregnancy rate per couple was 44.4% ...

7. asrm.org asrm.org/practice-guidance/practice-committee-documents/intracytoplasmic-sperm-injection-icsi-for-nonmale-factor-indications-a-committee-opinion-2020/

Intracytoplasmic sperm injection (ICSI) for non–male factor ... The study found no statistically significant differences in the primary outcome (fertilization rate 77.2% vs. 82.4%) or in the secondary outcomes of embryo ...

8. ctv.veeva.com ctv.veeva.com/study/experimental-round-spermatid-injection-rosi-to-treat-infertile-couples

Experimental Round Spermatid Injection (ROSI) to Treat ... The purpose of this research study is to evaluate if special types of cells called round spermatids can be gathered from men with ...