Counseling couples with MFI on their chances with testicular sperm in IVF/ICSI cycles: What tools do we have?

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Counseling couples with male
factor infertility on their
chances with testicular sperm
in in vitro fertilization/
intracytoplasmic sperm
injection cycles: What tools do
we have?
There is no doubt that couples struggling with infertility
choosing to undergo in vitro fertilization (IVF) with intracy-
toplasmic sperm injection (ICSI) sustain a significant amount
of emotional burden associated with navigating the field of
reproductive health. In addition, the financial investment
can be preclusive and provides an additional layer of stress
for couples. There remains no clear set of guidelines on
optimizing success of an IVF/ICSI cycle for a couple with
primary male factor infertility (MFI) such as the use of
ejaculated vs. extracted testicular sperm, testicular vs. epidid-
ymal sperm, or fresh vs. frozen sperm. Part of the issue is that
there is likely no ‘‘one size fits all’’ approach to the infertile
couple. Although there remains no clear consensus on these
parameters, some studies are emerging to provide us with
tools to have customized counseling conversations with
couples to set appropriate expectations.
In this issue, Lee et al. (1) provide their results on retro-
spective assessment of oocyte to blastocyst attrition rates in
couples with MFI, undergoing IVF with ICSI using testicular
sperm. Interestingly, they found a lower fertilization rate in
all testicular sperm extraction (TESE) patients than in couples
using ejaculated sperm. After further categorizing the TESE
patients into good, moderate, and poor prognosis tranches
by MFI etiology, the investigators found worse blastocyst pro-
gression rates in the moderate and poor TESE groups than in
controls: 37.7% and 22.1%, respectively, vs. 50.6%.
The discussion surrounding ejaculated vs. extracted
testicular sperm is ongoing. As we know, not all oocytes
can be fertilized, and not all fertilized embryos become
quality blastocysts. Some studies suggest that using sperm
extracted from the testis, thus eliminating epididymal travel,
reduces oxidative damage and lower DNA fragmentation (2).
However, on the flip side, sperm retrieval is not without its
own faults, such as procedural risks of TESE, success of
extraction, and risks of damage during processing and
handling of sperm after extraction. It is difficult to quantify
to couples what the benefit of this additional procedure may
provide to their fertility success, and there remains confusion
on the clinical relevance of elevated DNA fragmentation in
IVF/ICSI outcomes in testicular vs. ejaculated sperm (3).
Regarding attrition, TESE sperm has been shown to have
lower fertilization rates and blastocyst success than
ejaculated sperm (4).
Degree of MFI is also an important component of conver-
sations with patients. There is no consensus on impact or even
definite correlation of severity of MFI on IVF success because
there are many potential confounders, yet patients commonly
will ask what their individual chances are. The indeterminate
results further support the need for customized conversations
with these families.
The findings from this larger sample size study by Lee
et al. (1) are clinically significant and allow us to better
balance the scales. For one, it is reassuring that there were
no differences in fertilization or blastocyst development
when comparing the fresh vs. frozen TESE groups. Lower
fertilization rates in all TESE groups and worse blastocyst
development in the moderate and poor TESE groups suggest
that couples with these factors require multiple cycles to build
the family they desire. The ability to provide a road map for
couples helps to better prepare financially, logistically, and
emotionally.
CRediT Authorship Contribution Statement
Rachel Passarelli: Writing –review & editing. Danielle Velez
Leitner: Writing –review & editing, Writing –original draft,
Conceptualization.
Declaration of Interests
R.P. has nothing to disclose. D.V.L. has nothing to disclose.
Rachel Passarelli, M.D.
Danielle Velez Leitner, M.D.
Division of Urology, Rutgers Robert Wood Johnson Medical
School, New Brunswick, New Jersey
https://doi.org/10.1016/j.xfre.2025.01.012
REFERENCES
1. Lee S, Kendall Rauchfuss LM, Helo S, Ainsworth AJ, Babayev S, Paff
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spermatozoa have statistically significantly lower DNA damage compared
with ejaculated spermatozoa in patients with unsuccessful oral antioxidant
treatment. Fertil Steril 2010;93:1142–6.
3. Kendall Rauchfuss LM, Kim T, Bleess JL, Ziegelmann MJ, Shenoy CC. Testic-
ular sperm extraction vs. ejaculated sperm use for nonazoospermic male fac-
tor infertility. Fertil Steril 2021;116:963–70.
4. Karavani G, Kan-Tor Y, Schachter-Safrai N, Levitas E, Or Y, Ben-Meir A, et al.
Does sperm origin-ejaculated or testicular-affect embryo morphokinetic pa-
rameters? Andrology 2021;9:632–9.
VOL. 6 NO. 1 / MARCH 2025 15
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