Experimental Round Spermatid Injection (ROSI) to Treat Infertile Couples

Infertility, Male Clinical Trial

— ROSI  

Official title:

Experimental Round Spermatid Injection (ROSI) to Treat Infertile Couples

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04298255
• Other study ID #: IRB00062898
• Status: Recruiting
• Phase: N/A
• Start date: August 24, 2020
• Est. completion date: December 2024

Study information

• Verified date: September 2023
• Source: Wake Forest University Health Sciences
• Contact: Sachin Vyas, MSc, PhD
• Phone: (336) 713-4098
• Email: svyas[@]wakehealth.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 (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.

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:

1. Incorrect selection of round spermatids (to distinguish from diploid spermatogonia cells)

2. Using round spermatids that were already in the process of degeneration

3. Incomplete imprinting in the round spermatid

4. 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".

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• Males with obstructive azoospermia

• Males with presence an adequate number of elongated spermatids or spermatozoa

Related Conditions & MeSH terms

• Infertility
• Infertility, Male

Intervention

Other:
• Round Spermatid Injection (ROSI)
In Vitro Fertilization using Round Spermatid Injection (ROSI)
• Half ROSI-half Sperm Donor Fertilization
Half ROSI-half Sperm Donor Fertilization

Locations

Country	Name	City	State
United States	Carolinas Fertility Institute (CFI)	Winston-Salem	North Carolina

Sponsors (4)

Lead Sponsor	Collaborator
Wake Forest University Health Sciences	Carolinas Fertility Institute (CFI), Wake Forest Department of Urology, Wake Forest Institute for Regenerative Medicine (WFIRM)

Country where clinical trial is conducted

United States, 

References & Publications (3)

Bradshaw 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. — View Citation

Tanaka 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. Erratum In: Proc Natl Acad Sci U S A. 2016 May 17;113(20):E2872. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Day 1 after round spermatid injection
Secondary	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.	Day 3 to 5 after round spermatid injection
Secondary	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.	Day 3 to 5 after round spermatid injection
Secondary	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.	Post Fertilization 4 Weeks and onwards
Secondary	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.	Post Pregnancy Full Term Average 39 to 40 weeks