ROSI (Round Spermatid Injection): A Hope for Men with Severe Male Infertility

In short: ROSI is the injection of round spermatids, the cells that come just before mature sperm, into the egg. It is used in men with azoospermia when no mature sperm can be found. The pregnancy rate was 13.4% per couple and the birth rate 8.1%, lower than with mature sperm; studies have not shown more abnormalities in the children born.

ROSI (round spermatid injection) is an advanced fertility technique in which round spermatids — early precursor cells of sperm, obtained either from an ejaculated sample or through testicular sperm extraction (TESE) — are injected directly into the egg. This is used in place of a mature sperm cell, and is generally considered a last-resort option for couples facing severe male infertility.

Men diagnosed with azoospermia (the absence of sperm in the ejaculate) are usually referred to a male fertility specialist, who may recommend a surgical sperm retrieval procedure to try to find usable sperm. Unfortunately, even with these procedures, some men do not have mature sperm cells that can be successfully identified or isolated.

Approximately 1 in 100 men experience azoospermia, and about 70–80% of these cases are classified as non-obstructive azoospermia. Micro-TESE remains the main surgical method used to search for sperm in these cases. Testicular sperm are found in roughly 30–60% of attempts, though about half of the sperm retrieved may be immotile or structurally abnormal.

For men with non-obstructive azoospermia in whom neither mature sperm nor late-stage spermatids can be found, research suggests that around 30% will still have round spermatids present in their testicular tissue samples — which is where ROSI may offer an additional option.

How Does ROSI Work?

The scientific basis for ROSI is that round spermatids, having already completed both stages of meiosis, carry the same number of chromosomes and the same DNA content as a mature sperm cell.

Like mature sperm, a round spermatid contains a single (haploid) set of 23 chromosomes and 1N DNA content. In theory, if a round spermatid is injected directly into an egg using a technique similar to ICSI, it may be able to fertilize the egg and support the development of a pregnancy.

Round spermatids can be collected either from ejaculated fluid or from testicular tissue. Those obtained from ejaculate are generally considered less suitable for ROSI, since they are more prone to degenerative (apoptotic) changes compared with spermatids retrieved directly from testicular tissue.

What Do the Studies Show?

Published research on ROSI reports a pregnancy rate per couple of around 13.4%, with a live birth rate per couple of about 8.1%. ROSI has led to successful pregnancies and healthy live births, but overall success rates remain considerably lower than those seen with treatments using mature sperm.

Available follow-up data suggests that children conceived through ROSI generally show typical physical, cognitive, and developmental progress, without an increased rate of unusual epigenetic findings reported so far.

In one follow-up study looking at the physical and cognitive development of ROSI-conceived children, their development was comparable to naturally conceived children overall. A difference was noted only in babies’ responsiveness during parent interaction between 12–18 months of age. Weight gain was also similar to naturally conceived infants, although male ROSI babies were noted to be somewhat lighter at 1.5 years of age — a difference that resolved by around 2 years old.

So far, the small number of children followed up has not shown an increase in chromosomal, genetic or congenital abnormalities, but the data are limited and mostly come from one centre. International guidelines (EAU) still regard ROSI as an experimental technique. For some men facing otherwise untreatable infertility, it may offer a chance to have a biological child after careful counselling.

Dr. Najeeb Layyous’ Experience with ROSI

Dr. Najeeb Layyous began working with this technique in the early 2000s (2001–2002). At that time, a total of 1,170 ROSI cases were performed in Jordan; however, none resulted in a successful ongoing pregnancy — only early biochemical pregnancies were observed — and the technique was subsequently set aside.

In recent years, new laboratory methods, such as artificial (electrical) activation of the egg after spermatid injection, have been reported to improve outcomes in some centres. As a result, the technique is being offered again in selected cases, although it is still considered experimental and success rates remain low.

If you or your partner have been told that no mature sperm could be found during a fertility work-up, it may be worth discussing all available options, including ROSI, with a fertility specialist familiar with this technique. Dr. Najeeb Layyous and his clinical team are available to help review your individual situation and explain which options may be suitable for you.

Dr Najeeb Layyous F.R.C.O.G

Consultant Obstetrician, Gynecologist and Infertility Specialist