ROSI for Male Infertility (ROSI Trial)
Recruiting in Palo Alto (17 mi)
Overseen ByHooman Sadri, MD, PhD
Age: 18+
Sex: Male
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Wake Forest University Health Sciences
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.
12345Is 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.
12356How 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.
12357Eligibility 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 male partner is 18 years old or older.
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.
Participant Groups
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.
2Treatment groups
Experimental Treatment
Group I: ROSI onlyExperimental Treatment1 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 FertilizationExperimental Treatment1 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
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Carolinas Fertility Institute (CFI)Winston-Salem, NC
Loading ...
Who is running the clinical trial?
Wake Forest University Health SciencesLead Sponsor
Carolinas Fertility Institute (CFI)Collaborator
Wake Forest Institute for Regenerative Medicine (WFIRM)Collaborator
Wake Forest Department of UrologyCollaborator
References
Questioning the utility of round spermatid injections in men with non-obstructive azoospermia. [2022]Data on who among the infertile male population may benefit from round spermatid injections (ROSI) are lacking.
Fourteen babies born after round spermatid injection into human oocytes. [2018]During the human in vitro fertilization procedure in the assisted reproductive technology, intracytoplasmic sperm injection is routinely used to inject a spermatozoon or a less mature elongating spermatid into the oocyte. In some infertile men, round spermatids (haploid male germ cells that have completed meiosis) are the most mature cells visible during testicular biopsy. The microsurgical injection of a round spermatid into an oocyte as a substitute is commonly referred to as round spermatid injection (ROSI). Currently, human ROSI is considered a very inefficient procedure and of no clinical value. Herein, we report the birth and development of 14 children born to 12 women following ROSI of 734 oocytes previously activated by an electric current. The round spermatids came from men who had been diagnosed as not having spermatozoa or elongated spermatids by andrologists at other hospitals after a first Micro-TESE. A key to our success was our ability to identify round spermatids accurately before oocyte injection. As of today, all children born after ROSI in our clinic are without any unusual physical, mental, or epigenetic problems. Thus, for men whose germ cells are unable to develop beyond the round spermatid stage, ROSI can, as a last resort, enable them to have their own genetic offspring.
Clinical values and advances in round spermatid injection (ROSI). [2022]Azoospermia is defined as the complete absence of sperm cells in the ejaculate. Approximately 10-15 % of infertile men display azoospermia. Azoospermia can be subdivided into two types, obstructive azoospermia (OA) and non-obstructive azoospermia (NOA). NOA azoospermia might be the result due to primary testicular damage, secondary testicular damage, or incomplete testicular development. NOA azoospermia accounts for a considerable proportion of male infertility. A significant percentage of men with NOA azoospermia have foci of active spermatogenesis up to the stage of round spermatid. Round spermatid injection (ROSI) is a technique of assisted in-vitro fertilization (IVF) in assisted reproductive technology (ART). ROSI technique involves the injection of haploid germ cells derived from testicular biopsies into the recipient oocytes. The present study demonstrates that more participants and long-term follow-up studies are required to assess the reliability of the ROSI technique. In order to increase the success rate of the ROSI technique, round spermatids should be correctly evaluated and selected. Our study refers to the clinical values, challenges, and innovations in round spermatid injection (ROSI).
Round spermatid injection into human oocytes: a systematic review and meta-analysis. [2021]Many azoospermic men do not possess mature spermatozoa at the time of surgical sperm extraction. This study is a systematic review and meta-analysis evaluating outcomes following round spermatid injection (ROSI), a technique which utilizes immature precursors of spermatozoa for fertilization. An electronic search was performed to identify relevant articles published through October 2018. Human cohort studies in English involving male patients who had round spermatids identified and used for fertilization with human oocytes were included. Fertilization rate, pregnancy rate, and resultant delivery rate were assessed following ROSI. Meta-analysis outcomes were analyzed using a random-effects model. Data were extracted from 22 studies involving 1099 couples and 4218 embryo transfers. The fertilization rate after ROSI was 38.7% (95% confidence interval [CI]: 31.5%-46.3%), while the pregnancy rate was 3.7% (95% CI: 3.2%-4.4%). The resultant delivery rate was low, with 4.3% of embryo transfers resulting in a delivery (95% CI: 2.3%-7.7%). The pregnancy rate per couple was 13.4% (95% CI: 6.8%-19.1%) and the resultant delivery rate per couple was 8.1% (95% CI: 6.1%-14.4%). ROSI has resulted in clinical pregnancies and live births, but success rates are considerably lower than those achieved with mature spermatozoa. While this technique may be a feasible alternative for men with azoospermia who decline other options, couples should be aware that the odds of a successful delivery are greatly diminished and the prognosis is relatively poor.
How to improve the clinical outcome of round spermatid injection (ROSI) into the oocyte: Correction of epigenetic abnormalities. [2023]First successful human round spermatid injection (ROSI) was conducted by Tesarik et al. in 1996 for the sole treatment of nonobstructive azoospermic men whose most advanced spermatogenic cells were elongating round spermatids. Nine offsprings from ROSI were reported between 1996 and 2000. No successful deliveries were reported for 15 years after that. Tanaka et al. reported 90 babies born after ROSI and their follow-up studies in 2015 and 2018 showed no significant differences in comparison with those born after natural conception in terms of physical and cognitive abilities. However, clinical outcomes remain low.
Evaluation of the post-implantation development of mouse embryos derived from round spermatid injection. [2023]Round spermatid injection (ROSI), one of the assistant reproductive technologies, was used to treat partial infertility patients suffering from non-obstructive azoospermia. However, the development efficiency and birth rate of ROSI embryos are extremely low, and it is urgent to investigate the underlying mechanisms of low efficiency to improve the clinical application of ROSI technology. Here, we analyzed and compared the genome stability of the mouse blastocyst and the post-implantation development between ROSI and ICSI embryos. We first sequenced the genome of blastocysts from mouse ROSI embryos that can correctly form male and female pronuclei (2 PN) and found that the genomes of 7 blastocysts were normal. Furthermore, the implantation rate of ROSI 2 PN embryos on embryonic day 7.5 is similar to that of ICSI embryos, and at this time, 37.50% (9/24) of deciduas have no normal gestational sac. The proportion of embryos that survived to embryonic day 11.5 in the ROSI 2 PN group, ROSI non-2 PN group, parthenogenesis group, and ICSI 2 PN group was 51.61%, 7.14%, 0.00%, and 55.00%, respectively. And two smaller fetuses were found in the ROSI 2 PN group, which is not found in the other three groups. In addition, the physiological indexes, including fetus and placenta weight, sex ratio, growth rate, and the natural breeding ability for the offspring obtained from mouse ROSI, were evaluated; ROSI mice exhibited no obvious defect or abnormality and implied that the progeny were safe. Our results provided new evidence to promote the clinical application of ROSI technology.
Spermatid injection into human oocytes. II. Clinical application in the treatment of infertility due to non-obstructive azoospermia. [2019]We have reported recently the first birth after intrauterine transfer of embryos obtained by injection of round spermatids into oocytes in cases of unexpected azoospermia. Here we provide a complete documentation of the series of 11 cases in which this novel method of infertility treatment was employed. In four of these cases, elongated spermatids were identified in the ejaculate, and it was decided to perform elongated spermatid injection (ELSI). In the other six cases, only round spermatids were present, and round spermatid injection (ROSI) was done. In one case, ROSI was given preference to ELSI because of a very poor viability status of elongated spermatids present in the ejaculate. Fertilization of at least one oocyte was achieved in 10 of the 11 treatment cycles; the fertilization rate in these 10 cycles ranged between 7 and 100% with a mean value of 45%. All of the two-pronucleated zygotes cleaved and were transferred to the patient's uterus. A singleton pregnancy was achieved in two ROSI cycles. Both pregnancies developed uneventfully and resulted in the birth of normal infants. These data show the intra-ooplasmic injection of spermatids obtained from the ejaculate may become the treatment of first choice in patients with non-obstructive azoospermia.