Clinical trial NCT04298255: Experimental Round Spermatid Injection (ROSI) to Treat Infertile Couples
Official title: Experimental Round Spermatid Injection (ROSI) to Treat Infertile Couples
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Infertility, Male
Keywords: IVF
Fertility
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
Collaborators: name: Carolinas Fertility Institute (CFI)
name: Wake Forest Institute for Regenerative Medicine (WFIRM)
name: Wake Forest Department of Urology
First posted: 2020-03-06
Enrollment: 50
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: Infertile Male with round spermatid (but not elongated spermatids and spermatozoa) in their testes. Couples can choose either option 1 or 2.
Primary purpose: TREATMENT

Brief 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.

Detailed 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".

Eligibility criteria: 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

Primary outcomes:
measure: Fertility rate
timeFrame: Day 1 after round spermatid injection
Secondary outcomes:
measure: Blastocyst formation
timeFrame: Day 3 to 5 after round spermatid injection
measure: Aneuploidy rate
timeFrame: Day 3 to 5 after round spermatid injection
measure: Chemical Pregnancy with Positive human chorionic gonadotropin (hCG)
timeFrame: Post Fertilization 4 Weeks and onwards
measure: Live Birth Rate
timeFrame: Post Pregnancy Full Term Average 39 to 40 weeks
Other outcomes:
Locations:
city: Winston-Salem
country: United States
facility: Carolinas Fertility Institute (CFI)
state: North Carolina
Study officials:
affiliation: Wake Forest Institute for Regenerative Medicine (WFIRM)
name: Hooman Sadri, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Wake Forest University Health Sciences
name: Hooman Sadri, MD, PhD
role: STUDY_DIRECTOR
References:
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.
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.
citation: 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.