Testicular Sperm Better for Intracytoplasmic Injection

Neil Osterweil

March 16, 2019

BARCELONA, Spain — For women trying to become pregnant using intracytoplasmic sperm injection (ICSI), testicular sperm aspiration is better than ejaculated sperm, results from a new study suggest.

DNA integrity was significantly better with aspiration, which could improve assisted fertilization outcomes, said investigator Jonathan Ramsay, MD, from Imperial College Healthcare NHS Trust in London,

The study participants all had persistent DNA fragmentation in their ejaculated sperm, and a growing body of evidence suggests that the integrity of DNA in sperm is associated with embryo implantation failure and recurrent miscarriages, he explained.

The majority of persistent high levels of DNA fragmentation seems to be single-strand DNA breaks, Ramsay reported here at the European Association of Urology 2019 Congress.

The 59 study participants, almost universally, "had much lower levels of total DNA fragmentation in the testicle, so we wanted to know whether single- or double-strand breaks predominated," he told Medscape Medical News.

He and his colleagues used a sperm DNA assay (SpermComet, Examen) to assess sperm quality and the effects of single- and double-stranded DNA breaks on ICSI outcomes.

They compared sperm from the study participants with that from 76 fertile donors, and compared single-strand DNA breaks with combined single- and double-strand breaks in 10 infertile men.

All study participants had partners who had undergone at least two unsuccessful cycles of ICSI, and all the men underwent testicular sperm extraction after treatment for potential causes of infertility, including infection, varicocele, and oxidative stress.

The average Comet score — which measures average DNA damage per sperm sample — was significantly higher for ejaculated sperm from infertile men than for testicular sperm from the same men and ejaculated sperm from fertile men (39.9 vs 17.9 vs 14.8; P < .001).

The average low DNA damage score — which measures the proportion of sperm in a sample with good DNA needed for a successful pregnancy — was lower for ejaculated sperm from infertile men than for testicular sperm from the same men and ejaculated sperm from fertile men (34.7 vs 77.3 vs 90.2).

The average high DNA damage score — which measures the proportion of sperm in the sample with poor DNA unlikely to lead to a successful natural or assisted pregnancy — was significantly higher for ejaculated sperm from infertile men than for testicular sperm from the same men and ejaculated sperm from fertile men (29.1 vs 8.8 vs 1.9; P < .001).

In all three comparisons, the quality of sperm in the ejaculate of infertile men was significantly worse than that of fertile men (P < .001 for all).

However, there was no significant difference in total DNA damage between the testicular sperm of infertile men and the ejaculated sperm of fertile men.

There was also no significant difference in Comet scores between single-strand DNA breaks alone and single- and double-strand breaks, although double-strand breaks accounted for most of the DNA damage in testicular sperm and only half the damage in ejaculated sperm.

In men with high DNA fragmentation, the question still is where DNA fragmentation is generated.

"In the subgroup, single-stranded DNA breaks predominate, suggesting that DNA damage may occur because of anatomic or physiologic hostility in the genital tract," said lead investigator Lona Vyas, MD, also from Imperial College Healthcare NHS Trust, who presented the data during a poster discussion session.

These results are hypothesis-generating but not sufficient to warrant a change in clinical practice just yet, cautioned Marij Dinkelman-Smit, MD, PhD, from Erasmus University Medical Center in Rotterdam, the Netherlands, who comoderated the session.

"In men with high DNA fragmentation, the question still is where DNA fragmentation is generated," she told Medscape Medical News. "If it is post-testicular, which I presume is the case in some patients, then of course that would make sense. And this study does indicate that there may be more evidence for using testicular sperm," she said.

However, testicular sperm retrieval should be reserved for use only in men with persistent DNA fragmentation for whom other therapies and repeated cycles of ICSI have been tried and failed, said comoderator Suks Minhas, MD, from University College Hospital in London

The study was internally funded. Ramsay, Vyas, Dinkelman-Smit, and Minhas have disclosed no relevant financial relationships.

European Association of Urology (EAU) 2019 Congress: Abstract 247. Presented March 16, 2019.

Follow Medscape on Twitter @Medscape and Neil Osterweil @NeilOsterweil

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