A breakthrough reproductive technique is offering new hope for couples facing non-obstructive azoospermia
For the millions of couples struggling with infertility worldwide, the diagnosis of non-obstructive azoospermia (NOA)—a condition where no sperm are produced in the testes—often comes as a devastating blow.
Until recently, their only options for biological parenthood were donor sperm or adoption. However, a groundbreaking reproductive technique is changing this reality: Round Spermatid Injection (ROSI). This innovative procedure uses the earliest immature precursors to sperm, called round spermatids, to fertilize eggs and create embryos. The birth of ninety healthy babies in Japan through ROSI has ignited both hope and scientific curiosity, offering new possibilities for couples who once had none 4 .
Affects approximately 7% of all men, with NOA being one of the most challenging forms to treat.
Uses immature round spermatids to achieve fertilization when no mature sperm are available.
90 healthy babies born through ROSI demonstrate the viability of this approach.
To appreciate the significance of ROSI, one must first understand how sperm are normally made. Spermatogenesis, the process of sperm production, is a complex, multi-stage journey:
In men with NOA, this process halts at the round spermatid stage, which ROSI utilizes for fertilization.
For about half of men with NOA, the most advanced cell that can be found in their testes is the round spermatid—a cell that has completed meiosis and contains a full haploid set of chromosomes, but has not yet developed the familiar shape and function of a sperm cell 1 2 . ROSI harnesses the genetic potential of these round spermatids.
ROSI is a variation of Intracytoplasmic Sperm Injection (ICSI), where a single sperm is directly injected into an egg. However, ROSI presents unique challenges.
Using high-magnification microscopy (400x), embryologists search for round cells approximately 6-8 µm in diameter that lack distinct nucleoli. A key test of viability is whether the cell's membrane ruptures when gently aspirated into and out of the injection pipette—a characteristic of genuine round spermatids 3 .
The selected round spermatid is injected directly into the cytoplasm of a mature egg retrieved from the female partner. This requires extreme precision as the immature cell lacks the structural features of mature sperm.
The following data compiles information from various clinical studies to provide a clear picture of ROSI's efficacy and safety.
| Technique | Fertilization Rate | Live Birth Rate |
|---|---|---|
| ROSI (Historical) | 21.8% - 38.7% | 4.3% |
| ROSI (Tanaka) | Up to 76.4% | 90 cumulative births |
| ELSI | 48.4% - 71.4% | Not specified |
| ICSI (Mature Sperm) | ~57% | ~24% |
| Reagent | Function in ROSI | Description |
|---|---|---|
| Hyaluronidase | Oocyte Preparation | An enzyme used to break down the hyaluronic acid in the cumulus complex, removing granulosa cells to isolate the bare oocyte for injection 6 . |
| Polyvinylpyrrolidone (PVP) | Spermatid Handling | A viscous solution used to slow down and manage the round spermatid during micromanipulation 6 . |
| Calcimycin | Artificial Oocyte Activation | A chemical that increases calcium levels inside the oocyte, triggering embryonic development 3 . |
| KSOMaa Medium | Embryo Culture | A specialized culture medium designed to support the development of the early embryo 6 . |
Despite recent successes, ROSI remains a treatment of last resort. The American Reproductive Medicine Practice Committee still classifies it as an experimental procedure 1 .
Studies are investigating whether administering drugs like aromatase inhibitors (e.g., anastrozole) to men before sperm retrieval can improve the quality and viability of the round spermatids retrieved 3 .
Scientists are exploring the "reprogramming" of round spermatids. Research in mice suggests that factors from the egg's germinal vesicle can help reprogram the spermatid, leading to healthier embryos 8 .
Techniques like fluorescence-assisted cell sorting (FACS) are being explored to more accurately and efficiently isolate live, haploid round spermatids from a mix of testicular cells 1 .
ROSI is not yet a mainstream fertility treatment and is primarily offered at specialized research centers. Patients considering this option should consult with reproductive specialists who have experience with the technique and understand its experimental nature.
The story of the ninety babies born via ROSI is more than a statistical success; it is a testament to scientific perseverance.
It demonstrates that the most immature male germ cell, once considered inadequate for fertility treatments, holds the potential to create new life. While challenges remain and the procedure is not yet mainstream, ROSI has firmly shifted from a theoretical possibility to a concrete, evolving option. It offers a profound gift: the chance for genetic parenthood to couples who once faced a biological dead end, turning the smallest of cells into the greatest of hopes.
Healthy Babies Born
Max Fertilization Rate
Of NOA Patients May Benefit