Experimental Round Spermatid Injection (ROSI) to Treat Infertile Couples

Wake Forest University (WFU)

Status: Enrolling

Conditions: Infertility, Male

Treatments: Other: Round Spermatid Injection (ROSI); Other: Half ROSI-half Sperm Donor Fertilization

Study type: Interventional

Funder types: Other

Identifiers

NCT04298255

IRB00062898

Details and patient eligibility

About

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.

Full 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".

Enrollment: 50 estimated patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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50 participants in 2 patient groups

ROSI only

Experimental group

Description:

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

Treatment:

Other: Round Spermatid Injection (ROSI)

Half ROSI-half Sperm Donor Fertilization

Experimental group

Description:

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

Treatment:

Other: Half ROSI-half Sperm Donor Fertilization