Hi Owen,
Jargon-free writing is not one of the strong points of
scientific researchers! There are 2 components of this reply: the
first is my take on what this study means for RISUG, while the second
is a translation of the abstract with some additional information
from the full paper.
FYI -- The full article that Ben provided a link to is a
different one. It reports on the Phase III clinical trials of RISUG
in humans and was published last year.
(1) The point of this study was to determine the reversibility of
RISUG's contraceptive effect after an extended period of use. The
researchers have already successfully tested a method of reversal in
monkeys, so the mechanics of reversal are no problem. Now they're
figuring out the biology. What happens in the testes at a cellular
level when you use RISUG for over a year? They found that the
effects of RISUG are quite different from the effects of a
vasectomy.
After a vasectomy, sperm build up inside the tubules where
they're manufactured. Granulomas, or tiny nodules of inflamed
tissue, form in the tubules as your immune system tries to break down
the excess sperm. Your immune system is forced to treat the sperm
like a foreign substance. This is why vasectomy reversal is
difficult; reconnecting the vas deferens is relatively
straightforward procedure, but your body still thinks of sperm as
something to attack.
These researchers found the RISUG does not cause an immune
system reaction to sperm. They found no granulomas. They found
sperm production was continuous in throughout the study. But they
also found that some of the tubules where sperm are produced,
particularly in the center of the testes, showed signs of cellular
distress. These cells lost their usual patterns of organization and
stopped making new sperm. It's not clear if this effect would stay
localized, or if it would spread given more time. They did not
quantify the amount of damaged tissue.
The researchers conclude that despite the observed damage,
RISUG would be easier to reverse than a vasectomy. It's not clear if
they expect that the damaged tissue would recover, or if they assume
that enough tubules would remain functional and therefore maintain
fertility. I hope these researchers will report next on how monkeys
with long term RISUG recover once it's removed.
(2) This team of researchers injected RISUG into the vasa
deferentia of 10 monkeys and observed its effects over 18 months.
They did semen and blood tests each month. They found that all the
monkeys stopped producing sperm from the 4th month onward. From
month 2 to 3, all the sperm was malformed and not functional. Blood
tests showed that RISUG was not toxic to the monkeys. They found
normal levels of sperm antibodies, which shows that the monkeys'
immune systems were not attacking their sperm. They also found
normal levels of testosterone. Using a syringe, the researchers took
samples of cells from different parts of the testes after 6, 10, 12,
13, 14 and 18 months. These samples showed that spermatogenesis, or
the production of new sperm, was continuous throughout the study.
All the stages of spermatogenesis were normal until the 12th month.
At this point, the structure of some of the tubules began to change,
with no clear lumen (central cavity) or epithelium (membrane lining
the cavity). The tubules contained only very immature sperm. From
the 14th month to the end of the study, the tubules in the center of
each testis stopped producing new sperm. The appearance of vacuoles,
or little sacks of fluid, inside the cells that make sperm indicates
a build up of waste products and some sort of degeneration. They
conclude that 18 months after injecting RISUG, there are localized
areas of the testes that stop functioning. They found no
granulomas.
Hope this doesn't contain too much second level jargon. Let
me know if something isn't clear.
Regards,
Kirsten