The Evaluation of the Azoospermic Male: AUA Best Practice Statement
Intracytoplasmic sperm injection outcomes of obstructive and nonobstructive azoospermic men
Transcript of Intracytoplasmic sperm injection outcomes of obstructive and nonobstructive azoospermic men
REPRODUCTIVE MEDICINE
Intracytoplasmic sperm injection outcomes of obstructiveand nonobstructive azoospermic men
Ayse Celikten • Sertac Batioglu • Ayse Nur Cakir Gungor •
Erkan Ozdemir
Received: 4 February 2012 / Accepted: 12 March 2013 / Published online: 23 March 2013
� Springer-Verlag Berlin Heidelberg 2013
Abstract
Purpose We aimed to compare the outcomes of intracy-
toplasmic sperm injection (ICSI) cycles in ostructive and
nonobstructive azoospermic men.
Methods In this retrospective study, we searched the first
ICSI cycle parameters of 211 azoospermic men. Our main
outcomes were the average fertilization rate, implantation
rate, pregnancy and miscarriage rates.
Results The results of this study showed that although the
males with obstructive azoospermia had better fertilization
and biochemical pregnancy rates than the ones with non-
obstructive azoospermia, clinical pregnancy and miscar-
riage rates among the groups were similar.
Conclusion ICSI overcomes the obstacles related to the
sperm in its function as a carrier but it cannot alter the
message carried by the male gamete.
Keywords Obstructive azoospermia � Nonobstructive
azoospermia � Intracytoplasmic sperm injection
Introduction
Azoospermia defined as the absence of spermatozoa in the
ejaculate after the assessment of centrifuged semen on at
least two occasions, and it is observed in 1 % of the general
population and in 10–15 % of infertile men [1]. For a better
pathophysiological understanding of azoospermia, this
condition has been grossly divided into two groups:
obstructive azoospermia (OA) and nonobstructive azoo-
spermia (NOA). Sperm can be retrieved in almost all cases
of OA, but only in 50 % of NOA when no preliminary
selection of patients on the basis of histopathology has been
performed [2].
Although ICSI gives hope to azoospermic men to father
their biological babies, the success rates according to the
etiology of azoospermia is not clarified yet. We aimed to
compare the ICSI success of the first cycles of the OA and
NOA men.
Materials and methods
A retrospective analysis of 211 cases of azoospermia pre-
senting between July 2004 and December 2007 was under-
taken. All males were diagnosed using at least two samples
for semen analysis. Clinical parameters including age, his-
tory of infertility, previous infection, and relevant surgical
procedures were recorded. They were counseled for need of
further workup including genetic testing and histologic
examination. Patients with genetic abnormalities were
excluded. Patients were divided into two groups. Those
(n = 78) in OA group, sperms formed in the testis are unable
to get ejaculated through semen mainly due to obstruction
either in the epididymis, vas deferens or ejaculatory ducts.
Those (n = 133) in NOA group were men with testicular
failure having sertoli cell-only pattern, maturation arrest or
hypospermatogenesis on the testis biopsy.
Percutaneous epididymal sperm aspiration (PESA) or
microepididymal sperm aspiration (MESA) technique was
done, if no spermatozoon was found, testicular sperm
extraction (TESE) was performed under the same local
anesthesia. It has been shown that hormone level and tes-
ticular histology are unable to predict which men with
A. Celikten � S. Batioglu � A. N. C. Gungor (&) � E. Ozdemir
Dr. Zekai Tahir Burak Women Health and Research Hospital,
Ankara, Turkey
e-mail: [email protected]
123
Arch Gynecol Obstet (2013) 288:683–686
DOI 10.1007/s00404-013-2799-7
azoospermia will have sperm retrieved by PESA or TESE
[3]. PESA was performed under the local anesthesia with a
21-gauge needle and a syringe containing 0.5 ml sperm
preparation medium (MediCult a/s Mollehaven 12,4040
Jyllinge, Denmark). The needle was inserted into the head
of the epididymis, with up to four passes per side and the
aspirate was passed through the needle into a sterile plastic
tube and examined for spermatozoa immediately by the
clinical embryologist. Open TESE was performed through
a transverse scrototomy. Four 3-mm biopsies were taken in
a spiral manner around the testis, the orchiectomies were
closed with 5/0 PDS, and a layered closure was performed
with 3/0 monocryl.
Ovarian stimulation was achieved using long protocol
with a starting dose depending on the patient’s age and
basal serum hormone levels. Oocytes were collected 36 h
after hCG injection. Cumulus cell removal was achieved by
placing the oocytes briefly in medium (G1, Vitrolife,
Sweden), the remaining cells were removed with a fine
boer pipette. Only oocytes which had extruded a polar body
were selected for ICSI (metaphase II: M2). Microinjection
was carried out on an Olympus inverted microscope. A
single morphologically normal motile sperm was selected,
immobilized, and aspirated into the injection needle. Each
oocyte was firmly attached to the holding pipette with the
polar body at 6 o’clock. The injection needle entered the
oocyte at 3 o’clock and the breakage of the oolemma was
achieved with a gentle aspiration followed by a careful
deposition of the sperm into the cytoplasm.
Fertilization was confirmed 24 h later and the embryo
transfer was performed on day 3 or 5 of ovum pick-up. The
number of embryos transferred was 2–3 per cycle. Only
high quality embryos (grade 1 and 2) were transferred.
Pregnancy was defined as a spontaneous rise in a bhCG
concentration at least 10 days post transfer. Clinical preg-
nancy implied the presence of intrauterine gestational sac
and fetal heart beat on an ultrasound performed at 7 weeks
of gestation.
The Shapiro–Wilk test was used to verify if the data
followed normal distribution. A one-way ANOVA or
Fisher exact test was used to compare the clinical and the
laboratory parameters between groups when appropriate.
The Chi-square test was used to compare the other non
parametric parameters, with P \ 0.05 considered signifi-
cant. Statistical analysis was performed by SPSS software
version 13 (SPSS Inc, Chicago, Ill, USA).
Results
Demographic characteristics of the azoospermic men were
given in Table 1. A total of 211 men underwent their first
microsurgical procedures, those were 66.4 % TESE, 26.1 %
PESA, 6.6 % TESE ? PESA, 0.5 % TESA ? PESA, and
0.5 % MESA procedures. While sperm retrieval was
achieved by TESE in all patients with NOA, majority of the
patients with OA yielded sperm by PESA (70.5 %).
Demographic and clinical characteristics and the average
fertilization rate, implantation rate, pregnancy, and miscar-
riage rates were given in Table 2. Although number of
retrieved mature oocytes, fertilization rates, number of
transferred embryos and biochemical pregnancy rates were
significantly higher in OA group than NOA group, clinical
pregnancy rates and miscarriage rates were similar in two
groups. Fertilization rate, implantation rate, clinical preg-
nancy rate, and miscarriage rates were 59.3, 33.3, 20.5, and
12.8 % for OA group and 49.8, 31.6, 19.5, and 12 % for
NOA group, respectively. When the groups subdivided
according to the sperm retrieval technique, there was no
significant difference on either implantation rates or clinical
pregnancy rates.
Discussion
The development of ICSI and the techniques for sperm
recovery have enabled certain azoospermic males to father
their biological children. OA and NOA are often used to
determine the probability of retrieval, but these can only be
confidently diagnosed with testicular histology [4]. Tes-
ticular biopsy is now rarely performed prior to surgical
sperm retrieval, so the use of this terminology in the
clinical situation can result in inaccuracies when counsel-
ing patients. For giving accurate information azoospermic
males were divided into subgroups based on the clinical
parameters. Sperm retrieval rates were given 50–60 % for
NOA in different studies [1, 2].
De Croo et al. [4] compared 139 OA patients with 54
NOA patients and concluded that fertilization rates were
lower in NOA (67.8 % versus 74.5 % p 0.0167) but
implantation and clinical pregnancy rates were similar in
in-between the groups. In that study, there were significant
differences between the ages of female and male patients.
Table 1 Demographic characteristics of the azoospermic men
Age (years, mean ± SD) 32.8 ± 6.5
Height (cm, mean ± SD) 173.6 ± 6.9
Smoking (n, %) 71 (33.6 %)
Mumps orchitis (n, %) 3 (1.4 %)
Cryptorchitism (n, %) 9 (4.2 %)
Retrograde ejaculation (n, %) 4 (1.9 %)
Varicocele (n, %) 34 (16.1 %)
Unilateral orchiectomy (n, %) 4 (1.9 %)
Inguinal hernia operation (n, %) 5 (2.4 %)
Agenesis of the vas deferens (n, %) 21 (9.9 %)
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Verza et al. [5] compared 39 OA men with 54 NOA men
and concluded that OA men had significantly better fer-
tilization rates and clinical pregnancy rates.
A meta-analysis evaluated 9 reports comparing OA and
NOA and concluded that although fertilization and clinical
pregnancy rates were significantly lower in NOA group,
the live birth rates did not differ significantly in in-between
groups [6].
Our results indicate that sperm from men with severely
altered spermatogenesis, such as testicular sperm in NOA,
have decreased the fertility potential after ICSI. Lower
fertilization rates, as observed in our study for the testicular
sperm from NOA men, are explained by the early paternal
effects which include alterations in the spermatic cytosolic
factor and are responsible for the completion of the oocyte
meiotic division as well as alterations on the sperm cen-
triole, which participate in the formation of embryo mitotic
fuses in early cellular divisions [7].
Similar to the previous studies, this study showed that
although biochemical pregnancy rates in NOA group were
lower significantly there was no significant difference in
the clinical pregnancy and miscarriage rates following ICSI
in OA and NOA men.
Most studies evaluating ICSI and azoospermia regard
only the sperm source but not the type of azoospermia. These
studies tend to have a better outcome when epididymal
spermatozoa are used, but these findings can be justified by
the fact that epididymal sperm are always from obstructive
azoospermia, while the testicular sperm can be from both
types of azoospermia [8, 9].TESE is currently the most fre-
quently used technique in azoospermic men. A single
extended incision or multiple incisions can be made for
TESE. Similar mean weights of testicular tissue removed and
sperm retrieval rates were comparable between both tech-
niques [10].
Naru et al. [11] also compared PESA, TESE, and ejac-
ulated sperm cycles. They evaluated 69 PESA cycles of 53
couples, 47 TESE cycles of 43 couples and 437 ejaculated
sperm cycles of 421 oligospermic men and found that there
was no significant difference among groups on pregnancy
and miscarriage rates.
It has been shown that the age of the female partner has
an influence on the success of the ICSI treatment. Some
researchers reported low delivery rate in woman aged more
than 37 [12], others older than 40 [13, 14]. Of the other
factors considered for the prediction of successful ICSI
cycles are hormone profile, testicular volume, and histo-
pathology findings; few studies have reported that these
parameters are unable to predict which procedure would be
successful in azoospermic men [11].
Adequate fertilization, cleavage and pregnancy rates are
to be expected when ICSI is performed to azoospermic
men with a normal sperm production, such as OA ones.
However, lower fertilization rates are achieved when ICSI
performed with sperm from men with NOA. Although ICSI
overcomes the obstacles related to the sperm in its function
as a carrier, it cannot alter the message carried by the male
gamete.
Conflict of interest We declare that we have no conflict of interest.
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Table 2 ICSI cycle properties
and outcomes of study groupsOA (n = 78) NOA (n = 133) p
Female age 29.2 ± 5.4 28.2 ± 5.2 0.168
Male age 33.5 ± 6.7 32.4 ± 6.3 0.245
Infertility duration 8.5 ± 5.7 7.1 ± 4.6 0.061
Basal FSH (mIU/ml) 6.2 ± 1.7 7 ± 3.6 0.055
Basal LH (mIU/ml) 4.5 ± 2.3 5.2 ± 2 0.022
Basal E2 (pg/ml) 44.3 ± 17.5 44.5 ± 16.1 0.923
Basal PRL (ng/ml) 19.7 ± 8.4 19.6 ± 9.3 0.900
Ovulation E2 (pg/ml) 2,453 ± 1,259 2,507 ± 1,135 0.745
Ovulation progesterone (pg/ml) 0.85 ± 0.36 0.89 ± 0.40 0.448
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Fertilization rate 59.3 % 49.8 % 0.026
Biochemical pregnancy rate 26 (33.3 %) 42 (31.6 %) 0.01
Clinical pregnancy rate 16 (20.5 %) 26 (19.5 %) 0.966
Miscarriage 10 (12.8 %) 16 (12 %) 0.899
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