Over the last several years, the field of Assisted Reproductive Technology
(ART) has advanced rapidly in providing assistance to couples with male factor
infertility. In couples that are having difficulty trying to conceive a child,
approximately 40% will be diagnosed with a male problem. A routine semen analysis
is used to determine the adequate number and quality of sperm to predict the
fertilization potential.
When sperm are produced by ejaculation but in very low numbers, In-vitro Fertilization
(IVF) along with an assisted fertilization technique called "ICSI" (Intracytoplasmic
Sperm Injection) has helped many couples achieve a pregnancy. A cycle of IVF
involves daily injections for approximately 8-10 days to stimulate a woman to
produce many mature eggs that are retrieved in a minor outpatient procedure.
ICSI is then performed by directly injecting a single sperm into a one egg
using microscopic instruments. The next day, the injected eggs are checked for
fertilization and, within several days, a select number of embryos are transferred
to the woman's uterus in hopes of achieving a pregnancy.
Until the mid 1990's, donor sperm was the only treatment for absence of sperm
in the ejaculate (azoospermia). Some men have a condition where their reproductive
ducts may be absent or blocked (obstructive azoospermia or OA), whereas others
may have no sperm production with normal anatomy (non-obstructive azoospermia
or NOA). A minor outpatient procedure called "TESA" (TEsticular Sperm
Aspiration) may be offered to obtain sperm directly from the testes where it
is produced. If successful, the sperm can then be used with IVF/ICSI. Using a
serum FSH and palpating the male reproductive ducts and size of the testis, urologists
can usually distinguish between OA and NOA. Specifically, an elevated FSH and
small testicular size is consistent with NOA.
Azoospermia is found in 10% of male infertility cases. Patients with OA, due
to congenital bilateral absence of the vas deferens (CBAVD) or those in whom
reconstructive surgery fails, have historically been considered infertile. Men
who cannot produce sperm in their testes with apparent absence of spermatogenesis
diagnosed by testicle biopsy are classified as NOA. This article will discuss
advances in the surgical treatment of azoospermia and does not include hormonal
disorders such as hypogonadotropic hypogonadism.
Surgical retrieval of spermatozoa from testes combined with ART has given
new hope to those patients previously considered infertile. In cases of surgically
irreparable AO or in cases of CBAVD, Microsurgical Epididymal Sperm Aspiration
(MESA) with standard IVF has been shown to yield fertilization and pregnancy.
However, the results were poor and unpredictable. TESA is now a well-accepted
technique in the treatment of men diagnosed with OA or NOA but requires ICSI
due to the immature fertilization potential of testicular sperm. Since testicular
biopsy is an invasive procedure, the efficient use of TESA would reduce surgical
aspirations to a single sperm retrieval by including cryopreservation (see below).
Recently, Dr. Bin Wu's group has defined an optimal technique for fresh and
frozen-thawed testicular sperm for ICSI in azoospermic patients. This technique
involves in vitro maturation of fresh and frozen testicular sperm. Although TESA
is used frequently to obtain sufficient sperm for ICSI, few free spermatozoa
demonstrate twitching motility and most are completely immotile in the initial
testicular biopsied samples. This research demonstrates that less than 3% sperm
motility is observed following the initial collection of testicular biopsy samples.
In most cases of NOA, it is very difficult to find sufficient motile sperm in
the initial fresh or frozen-thawed sample for ICSI.
When Dr. Wu's group performed testicular biopsied tissue in-vitro culture
for 24 hrs, the number of motile sperm showed a remarkable increase and reached
a maximum motility rate between 48 and 72 hours. Based on these observations,
after 24 hours of in vitro culture, there are enough motile sperm including "twitching" sperm
for ICSI. Therefore, it appears that the optimal time for ICSI using testicular
sperm is after 24-48 hours of culture. This may allow TESA to be performed one
or two days before oocyte retrieval and provides flexibility in scheduling these
procedures in clinical practice.
Cryopreservation of TESA specimens can avoid repeated testicular biopsies
in azoospermic patients in whom the only source of spermatozoa is the biopsy.
Testicular sperm cryopreservation using a simple freezing protocol is promising
in patients with AO and NOA augmenting the overall success achieved after surgical
sperm retrieval. This study indicates that the frozen-thawed testicular sperm
displayed a similar motility to fresh samples during culture. As a result, the
cryopreservation of testicular biopsy specimens routinely is recommended in clinical
practice. Nevertheless, there remains controversy in the medical literature regarding
the optimal processing of sperm with NOA, namely using freshly retrieved vs.
frozen sperm.
In summary, TESA with ICSI has successfully treated azoospermia and offers
approximately a 40% live birth rate from OA and NOA patients. The freezing and
in vitro maturation of testicular biopsy specimens are useful approaches to the
management of testicular biopsy samples from both AO and NOA patients. These
techniques offer the possibility of several attempts at IVF/ICSI from a single
testicular biopsy sample. One to three days of in-vitro culture for fresh or
frozen samples before an oocyte retrieval may increase the availability of motile
spermatozoa for ICSI. Testicular biopsy freezing and subsequent culture may be
a reliable alternative for patients undergoing TESA on the same day of oocyte
retrieval, allowing for flexibility in scheduling patients for clinical procedures.
David Heinkel is the IVF Embryology Laboratory Director of Fertility C.A.R.E.
(Center of Assisted Reproduction and Endocrinology). Dr. Mark P. Trolice is the
Director of Fertility C.A.R.E and is Board-certified in Reproductive Endocrinology
and Infertility (REI). He is also the Division Director of REI at Arnold Palmer
Hospital for Children and Women in Orlando. Please direct any inquiries by calling
407-672-1106 or email info@myfertilitycare.com
Mark P. Trolice, M.D., FACOG, FACS is Director of Fertility C.A.R.E. (Center of Assisted Reproduction & Endocrinology in the Orlando, Florida area and Director of Reproductive Endocrinology & Infertility at Arnold Palmer Hospital for Children & Women.
© Copyright Mark P. Trolice
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