2. Fertility and Sterility®
Semen Analysis ICSI in those having isolated abnormalities in strict
Semen analysis is the cornerstone of the laboratory evalua- morphology has been questioned (14).
tion of the infertile male and helps to define the severity of Clinical reference ranges have been established for sperm
the male factor. Physicians should provide patients with stan- concentration, motility, and morphology to help classify men
dardized instructions for semen collection, including a defined as fertile or sub-fertile (15). The semen parameters of men
pre-test abstinence interval of two to five days. Although with documented fertility have been compared to those of
a standard duration of abstinence is important for evaluation infertile men among couples participating in a clinical trial
of semen parameters, some men with severe oligospermia can of superovulation and intrauterine insemination (IUI). Sperm
have equal or better sperm concentration with a short (hours) parameters that predicted male fertility were a sperm concen-
period of abstinence, supporting the potential use of multiple tration greater than 48 million/mL, sperm motility greater
semen analyses during assisted reproductive technology than 63%, and sperm morphology greater than 12% normal
(ART) treatment cycles (5–7). Semen can be collected by (strict criteria). Parameters that predicted male subfertility
masturbation into a specimen cup or by intercourse using were a sperm concentration less than 13.5 million sperm/
special semen collection condoms that do not contain mL, sperm motility less than 32%, and sperm morphology
substances toxic to sperm. Ideally, the specimen should be less than 9% normal. Values between the fertile and subfertile
collected at the laboratory. If collected at home, the thresholds were considered ‘‘indeterminate’’ (16). Although
specimen should be kept at room or body temperature each sperm parameter could predict fertility and subfertility,
during transport and examined in the laboratory within one none was a powerful discriminator. It is important to empha-
hour of collection. To ensure accurate results, the laboratory size that normal reference values for semen parameters do not
should have a quality control program for semen analysis reflect normal sperm concentration in the general population,
that conforms to the standards outlined in the Clinical nor do they equate with the minimum values required for con-
Laboratory Improvement Amendments (CLIA); additional ception; men with semen variables outside the reference
information including proficiency testing can be found on ranges may be fertile and, conversely, men having values
the CLIA website (8). within the reference range still may be infertile.
The semen analysis provides information on semen vol-
ume as well as sperm concentration, motility, and morphol- COMPONENTS OF A COMPLETE EVALUATION
ogy (Table 1) (9). Methods for semen analysis are discussed FOR MALE INFERTILITY
in many textbooks, and detailed laboratory protocols have When the initial screening evaluation reveals an abnormal
been published by the World Health Organization (WHO) male reproductive history or demonstrates abnormal semen
(10). The diagnosis of azoospermia can be established only parameters, a thorough evaluation by a urologist or other
after the specimen is centrifuged (preferably at 3000 g) for specialist in male reproduction is indicated. More detailed
15 minutes and the pellet is examined. The current WHO cri- evaluation of the male partner also should be considered in
teria for evaluating sperm morphology (10) are similar to the couples with unexplained infertility and those who remain
‘‘strict criteria’’ described by Kruger (Tygerberg) (11, 12), in infertile after successful treatment of identified female infer-
that relatively few sperm are classified as having normal tility factors.
morphology, even in semen obtained from fertile men. The more thorough evaluation for male infertility should
Strict sperm morphology has been used to identify couples expand on the screening evaluation by including a complete
at risk for poor or failed fertilization using standard in vitro medical history and physical examination performed by
fertilization (IVF) techniques (11) and thus to identify those a urologist or other specialist in male reproduction. Based
who may be candidates for intracytoplasmic sperm on the results obtained, additional tests and procedures may
injection (ICSI) (13). However, the value and necessity for be recommended including serial semen analyses, endocrine
evaluation, post-ejaculatory urinalysis, ultrasonography,
specialized tests on semen and sperm, and genetic screening.
TABLE 1
Medical History
Lower limits of the accepted reference values for semen analysis. The patient's medical history can identify risk factors and
On at least two occasions Reference value behaviors or lifestyles that could have significant impact on
Ejaculate volume 1.5 mL
male infertility. In addition to all of the elements of the repro-
pH 7.2 ductive history described above, the medical history should be
Sperm concentration 15 Â 106 spermatozoa/mL expanded to include 1) a complete review of systems; 2) fam-
Total sperm number 39 Â 106 spermatozoa/ejaculate ily reproductive history; and 3) a detailed social history, in-
Percent motility 40%
Forward progression 32% cluding any past or current use of anabolic steroids,
Normal morphology 4% normal recreational drugs, tobacco, and alcohol.
And
Sperm agglutination absent
Viscosity %2 cm thread post-liquefaction Physical Examination
Note: Data taken from World Health Organization, 2010 (10).
A general physical examination is an integral part of the
Practice Committee. Evaluation of the infertile male. Fertil Steril 2012.
evaluation of infertile men. Particular attention should be
VOL. 98 NO. 2 / AUGUST 2012 295
3. ASRM PAGES
directed to the genitalia including 1) examination of the pe- should be obtained in men who require a more thorough en-
nis, noting the location of the urethral meatus; 2) palpation docrine evaluation.
and measurement of the testes; 3) the presence and consis- Recently, the serum inhibin B concentration has emerged
tency of both the vasa and epididymides; 4) the presence or as a marker for spermatogenesis. Inhibin B levels are signifi-
absence of a varicocele; 5) secondary sex characteristics, in- cantly lower in infertile men than in fertile men and correlate
cluding body habitus, hair distribution, and breast develop- better with sperm parameters than FSH levels (17). Given the
ment; and 6) digital rectal examination where indicated. significantly greater cost of measuring inhibin B, FSH cur-
The diagnosis of congenital bilateral aplasia of the vasa def- rently remains the preferred test for screening purposes.
erentia (CBAVD) is established by physical examination;
scrotal exploration is unnecessary.
Post-ejaculatory Urinalysis
OTHER PROCEDURES AND TESTS FOR A low-volume or absent antegrade ejaculate suggests incom-
plete semen collection, retrograde ejaculation, lack of emis-
ASSESSING MALE INFERTILITY
sion, ejaculatory duct obstruction, hypogonadism, or
Endocrine Evaluation CBAVD. To exclude retrograde ejaculation, a post-
Hormonal abnormalities of the hypothalamic-pituitary- ejaculatory urinalysis should be performed in men having
testicular axis are well-recognized, but uncommon, causes an ejaculate volume less than 1.0 mL, except in those diag-
of male infertility. Endocrine disorders are extremely uncom- nosed with hypogonadism or CBAVD. It also is important to
mon in men with normal semen parameters. determine whether an improper or incomplete collection or
An endocrine evaluation is indicated for men having: 1) a very short abstinence interval (less than 1 day) might be
abnormal semen parameters, particularly when the sperm the cause.
concentration is below 10 million/mL; 2) impaired sexual The post-ejaculatory urinalysis is performed by centri-
function; or 3) other clinical findings that suggest a specific fuging the urine specimen for 10 minutes at 300 g, followed
endocrinopathy. Some experts believe that all infertile males by microscopic examination of the pellet at 400Â magnifica-
merit an endocrine evaluation, but there is no established tion. In men with azoospermia or aspermia, the presence of
consensus of opinion. The minimum initial hormonal any sperm in the post-ejaculatory urinalysis suggests retro-
evaluation should include measurement of serum follicle- grade ejaculation. In men with low ejaculate volume and oli-
stimulating-hormone (FSH) and total testosterone concen- gospermia, ‘‘significant numbers’’ of sperm must be observed
trations. When the total testosterone level is low (<300 to support the diagnosis of retrograde ejaculation; there is no
ng/mL), a more extensive evaluation is indicated and should consensus of expert opinion on the minimum number
include a second measurement of total testosterone and required.
measurements of serum free testosterone, luteinizing hor-
mone (LH), and prolactin. Although serum gonadotropin Ultrasonography
concentrations vary because they are secreted in a pulsatile
manner, a single measurement usually is sufficient to deter- Because nearly the entire male genital tract can be imaged
mine the clinical endocrine status. The relationships among easily and accurately, ultrasonography is a useful tool for
serum testosterone, LH, FSH, and prolactin concentrations detecting abnormalities of the male genital tract that may
help to provide an understanding of the source of abnormal adversely affect fertility. However, ultrasonography is only
total testosterone levels (Table 2). Whereas many men with indicated for a minority of infertile male patients.
abnormal spermatogenesis have a normal serum FSH level, Transrectal ultrasonography. Normal seminal vesicles are
a markedly elevated serum FSH concentration clearly indi- usually less than 1.5 cm in antero posterior diameter (18).
cates an abnormality in spermatogenesis. In individuals Transrectal ultrasonography (TRUS) revealing dilated semi-
with an FSH level in the upper normal range, there may nal vesicles or ejaculatory ducts and/or midline cystic pros-
be impaired spermatogenesis as well. Measurement of the tatic structures suggests, but does not by itself establish, the
thyroid-stimulating hormone (TSH) concentration also diagnosis of complete or partial ejaculatory duct
TABLE 2
Basal hormone levels in various clinical states.
Clinical condition FSH LH Testosterone Prolactin
Normal spermatogenesis Normal Normal Normal Normal
Hypogonadotropic hypogonadism Low Low Low Normal
Abnormal spermatogenesisa High/normal Normal Normal Normal
Complete testicular failure/ High High Normal/low Normal
hypergonadotropic hypogonadism
Prolactin-secreting pituitary tumor Normal/low Normal/low Low High
a
Many men with abnormal spermatogenesis have a normal serum FSH, but a marked elevation of serum FSH is clearly indicative of an abnormality in spermatogenesis.
Practice Committee. Evaluation of the infertile male. Fertil Steril 2012.
296 VOL. 98 NO. 2 / AUGUST 2012
4. Fertility and Sterility®
obstruction (19). Affected men typically produce a low- to large quantities of sperm antigens or after vasectomy. Risk
volume, acidic ejaculate containing no sperm or fructose. factors for ASA formation include trauma, torsion, biopsy,
Men with CBAVD may exhibit similar findings because orchitis, testicular cancer, and vasectomy. Whereas indirect
they often have absent or atrophic seminal vesicles. Men antibody agglutination assays are used to detect ASA in
with partial ejaculatory duct obstruction often, but not al- serum or seminal plasma, a direct immunobead test is used
ways, exhibit low semen volume, oligo-asthenospermia, to detect ASA (IgG and IgA) bound to the sperm head or
and poor progressive motility. Some experts recommend tail. Sperm-bound antibodies are thought to be clinically
routine TRUS for oligospermic men having low volume important because they can decrease motility, block penetra-
ejaculates, palpable vasa, and normal testicular size with tion of the cervical mucus and prevent fertilization and
normal serum testosterone. thereby decrease the likelihood for conception (22). Although
Scrotal ultrasonography. Careful physical examination can some have suggested ASA testing for couples with unex-
identify most scrotal pathology, including varicoceles, sper- plained infertility, the clinical utility of the test in such cou-
matoceles, absent vasa, epididymal induration, and testicular ples is uncertain, and ASA testing is unnecessary if ICSI is
masses. Scrotal ultrasonography can identify occult varico- planned (23). One recent study has suggested that detection
celes that are not palpable, but such lesions have no demon- of serum ASA correlates with the presence of spermatogenesis
strated clinical significance (20). Scrotal ultrasonography can in men with azoospermia and can obviate the need for diag-
be helpful for better defining vague or ambiguous physical nostic testicular biopsy to help determine whether obstruction
examination findings or abnormalities (including apparent is present. Men with azoospermia and ASA are likely to have
masses) and can be performed in men having testes located reproductive tract obstruction (24).
in the upper scrotum, a small scrotal sac, or other anatomy
that hinders physical examination. Testicular ultrasonogra- Sperm Viability Tests
phy also should be considered for men presenting with infer-
tility and risk factors for testicular cancer, such as Sperm viability can be assessed by mixing fresh semen with
cryptorchidism or a previous testicular neoplasm. a supravital dye such as eosin Y or trypan blue, or by the
use of the hypoosmotic swelling (HOS) test (10). These assays
determine whether non-motile sperm are viable by identify-
Specialized Clinical Tests on Semen and Sperm
ing which sperm have intact cell membranes. In dye tests, vi-
In some cases, semen analyses have failed to predict fertility able sperm actively exclude the dye and remain colorless,
accurately, spurring a search for other methods that might while non-viable sperm readily take up the stain. Unfortu-
improve the diagnostic evaluation of the infertile male. Gen- nately, sperm judged viable by dye tests cannot be used for
erally, such specialized clinical tests should be reserved for IVF. In the HOS test, viable non-motile sperm, which swell
circumstances where results clearly will help to direct when incubated in a hypoosmotic solution, can be used suc-
treatment. cessfully for intracytoplasmic sperm injection (25). Viable
non-motile sperm can also be identified by incubation in pen-
Quantitation of Leukocytes in Semen toxifylline. Viable sperm will develop motility after exposure
to pentoxifylline (26).
Increased numbers of white blood cells in semen have been
associated with deficiencies in sperm function and motility.
Under wet mount microscopy, leukocytes and immature Sperm DNA Fragmentation Tests
germ cells appear quite similar and are properly called ‘‘round
DNA integrity is important for normal embryo development.
cells.’’ Unfortunately, many laboratories improperly report all
Sperm DNA integrity is maintained in part by the effect of di-
round cells as ‘‘white blood cells’’ and, in men with such find-
sulfide cross-links between protamines that allow for the
ings, the clinician must ensure that the two types of cells are
compaction of chromatin in the nucleus. Sperm DNA damage
differentiated. A number of methods are available to distin-
can occur as a result of intrinsic factors, such as protamine
guish leukocytes from immature germ cells, including tradi-
deficiency and mutations affecting DNA compaction, or
tional cytologic staining and immunohistochemical
from extrinsic factors such as heat, radiation, and gonadotox-
techniques (21). Men with true pyospermia (greater than 1
ins. The term ‘‘DNA fragmentation’’ refers to denatured or
million leukocytes per mL) should be specifically evaluated
damaged sperm DNA that cannot be repaired. A number of
to exclude genital tract infection or inflammation.
clinical tests have been developed to measure sperm DNA
fragmentation rates. Direct methods, such as the single-cell
Tests for Anti-sperm Antibodies gel electrophoresis assay (Comet) and terminal deoxynucleo-
Anti-sperm antibodies (ASA) are a rare cause of male subfer- tidyl transferase dUTP nick end labeling (TUNEL) assays, spe-
tility that do not require routine testing and are typically cifically analyze the number of breaks in the DNA. Indirect
treated with ICSI. Testing for ASA has historically been tests like the Sperm Chromatin Structure Assay (SCSA) define
done when the semen analysis reveals isolated asthenosper- abnormal chromatin structure as an increased susceptibility
mia (with normal sperm concentration) or sperm agglutina- of sperm DNA to acid-induced denaturation in situ (27).
tion. ASAs can be found in the serum, seminal plasma, or Threshold values used to define an abnormal test are greater
bound directly to sperm. ASAs can form when there is a breach than or equal to 25% to 27% for the SCSA (28) and greater
in the blood-testis barrier and the immune system is exposed than or equal to 36% for TUNEL assays (29).
VOL. 98 NO. 2 / AUGUST 2012 297
5. ASRM PAGES
Sperm DNA damage is more common in infertile men and membrane conductance regulator (CFTR) gene. When indi-
may contribute to poor reproductive performance in some cated, efforts to identify genetic causes for infertility can
couples. Sperm DNA damage is also associated with sponta- have a major impact on the choice and outcome of treatment.
neous recurrent miscarriage. However, existing data relating Cystic fibrosis gene mutations. There is a strong association
to the relationship between abnormal DNA integrity and between CBAVD and mutations of the CFTR gene, which is
reproductive outcomes are too limited to routinely recom- located on chromosome 7 (37). Almost all men with clinical
mend any of these tests for males in an infertile couple, but cystic fibrosis exhibit CBAVD. Additionally, as many as
the effect of abnormal sperm DNA fragmentation on the value 80% of men with CBAVD have documented mutations of
of IUI or IVF and ICSI results may be clinically informative the CFTR gene. Failure to detect a CFTR abnormality in men
(30). Although no treatment for abnormal DNA integrity with CBAVD does not exclude the presence of a mutation
has proven of clinical value, varicocele repair and antioxidant that cannot be identified with currently available methods.
use may affect sperm DNA integrity. Sperm retrieved from the Therefore, men with CBAVD should be assumed to have
testis tend to have better sperm DNA quality in men with a CFTR gene mutation. To determine the risk of conceiving
abnormal ejaculated sperm DNA integrity. Because the prog- a child affected with CF, it is important to test the female part-
nostic clinical value of DNA integrity testing may not affect ner of an affected man. Even if the female partner is negative
treatment of couples, the routine use of DNA integrity tests by currently available testing, the couple remains at some risk
in the clinical evaluation of male factor infertility is contro- because some of the less common mutations may be missed
versial (31). unless the entire gene is sequenced.
The prevalence of CFTR mutations also is increased
Less Commonly Used Specialized Tests among men with azoospermia related to congenital bilateral
Numerous other tests of sperm function have been employed obstruction of the epididymides and those with unilateral
predominantly in research studies. Sperm penetration assays vasa agenesis. Consequently, genetic evaluation should be
may detect defects in sperm-fertilizing capacity and could considered for those having either abnormality. Some men
identify patients who will benefit from application of ICSI. presenting with either unilateral or bilateral vasal agenesis
However, since ICSI is routinely used during IVF for male- and unilateral renal agenesis have the mesonephric duct ab-
factor infertility couples, this test is rarely of any clinical normalities associated with hereditary renal adysplasia
value. The acrosome reaction of human sperm can be detected (HRA) which has an autosomal dominant form of inheritance
using specialized staining techniques. Rates of spontaneous with incomplete penetrance and variable expression. These
acrosome reactions and acrosome reactions induced by patients do not have CFTR mutations and require genetic
agents such as calcium ionophore and progesterone have counseling prior to IVF (38, 39).
been measured. Sperm from infertile men tend to demonstrate Karyotypic chromosomal abnormalities. The prevalence of
higher acrosome levels spontaneously, but lower levels in the chromosomal abnormalities is increased in infertile men
presence of inducers (32). A number of biochemical tests of and inversely proportional to sperm count; the prevalence is
sperm function have been studied, including measurements 10%–15% in azoospermic men (40), approximately 5% in
of sperm creatine kinase (33) and reactive oxygen species men with severe oligospermia (<5 million/mL), and less
(ROS). ROS appear to be generated by both seminal leukocytes than 1% in men with normal sperm concentrations (41).
and sperm cells and can interfere with sperm function by per- Sex chromosomal aneuploidy (Klinefelter syndrome;
oxidation of sperm lipid membranes and creation of toxic 47,XXY) accounts for about two-thirds of all chromosomal
fatty acid peroxides (34). Other tests and procedures have abnormalities observed in infertile men (42). The prevalence
been used to select sperm for ICSI and may identify gametes of structural autosomal abnormalities, such as inversions
with better quality, including hyaluronic acid binding, mem- and balanced translocations, also is higher in infertile men
brane maturity testing, apoptotic evaluation, and magnified than in the general population (43). Couples wherein the
sperm examination (35). However, these tests have a very lim- male has a gross karyotypic abnormality are at increased
ited role in the evaluation of male infertility because they risk for miscarriages and for having children with chromo-
have limited clinical utility and typically do not affect somal and congenital defects. Therefore, men with non-
treatment. obstructive azoospermia or severe oligospermia should be
evaluated with a high-resolution karyotype before using their
Genetic Screening sperm to perform ICSI.
Genetic abnormalities can cause infertility by affecting sperm Y-chromosome microdeletions. Microdeletions of clinically
production or sperm transport. Men with non-obstructive relevant regions of the Y chromosome have been found in
azoospermia and severe oligospermia (<5 million/mL) are at 7% of infertile men with severely impaired spermatogenesis
increased risk for having a genetic abnormality compared to compared with 2% of normal men. However, the percentage
fertile men (36). The most common genetic abnormalities of men with Y-chromosome microdeletions increases to
found in such men are numerical and structural chromosomal 16% in men with azoospermia or severe oligospermia (44).
aberrations that impair testicular function, and Y-chromo- Such microdeletions are too small to be detected by standard
some microdeletions that are associated with isolated defects karyotyping, but can be identified using polymerase chain re-
in spermatogenesis. In addition, men with CBAVD can be action techniques to analyze sequence tagged sites that have
assumed to have an abnormality of the cystic fibrosis trans- been mapped along the entire length of the Y chromosome.
298 VOL. 98 NO. 2 / AUGUST 2012
6. Fertility and Sterility®
Most deletions causing azoospermia or oligospermia occur in a meaningful risk assessment to couples based on the test
regions of the long arm of the Y chromosome (Yq11) known results (55).
as the Azoospermia Factor (AZF) regions, designated as
AZFa (proximal), AZFb (central), and AZFc (distal). It appears
that these regions, and possibly other regions of the Y chro- SUMMARY
mosome, contain multiple genes necessary for spermatogen- An initial screening evaluation of the male partner of an
esis. For example, the DAZ (deleted in azoospermia) gene, infertile couple is indicated when pregnancy has not
which encodes a transcription factor usually present in men occurred after 12 months of unprotected intercourse or
with normal fertility, is located in the AZFc region. after 6 months of failure to conceive when the female is
The specific location of the deletion along the Y chromo- greater than 35 years. Earlier evaluation may be warranted
some influences its impact on spermatogenesis. Many men when medical history and physical findings indicate or
with a microdeletion in the AZFc region of the Y chromosome suggest specific male or female infertility risk factors and
have severe oligospermia. Others with AZFc region deletions for men who question their reproductive potential.
are azoospermic but still may produce sufficient numbers of A thorough evaluation by a urologist or other specialist in
sperm to allow testicular sperm extraction. Sperm production male reproduction, including a complete medical and
in such men appears to be stable over time, and the results of reproductive history and physical examination, should be
ICSI are not affected adversely by the AZFc deletion (45). In performed if the initial screening evaluation reveals an
contrast, deletions involving the entire AZFb region appear abnormal male reproductive history or demonstrates
to predict a very poor prognosis for sperm retrieval (46). The abnormal semen parameters. Additional tests aimed at
same may be true for men having deletions involving the defining the cause may be required.
entire AZFa region of the Y chromosome (47).
Sons of individuals with Y-chromosome microdeletions
will inherit the abnormality and, therefore, also may be infer- CONCLUSIONS
tile (48). Although a microdeletion of the Y chromosome is not
known to be associated with other health problems, few data The initial evaluation for male factor infertility should
exist regarding the phenotypes of the sons of fathers with include a reproductive history and at least one properly
such genetic abnormalities. A recent report showed that performed semen analysis, if normal.
some men with Y-chromosome microdeletions had abnor- Endocrine evaluation is indicated for men having: 1)
malities of the pseudoautosomal regions (PARs) of the Y chro- abnormal semen parameters, particularly when the sperm
mosome. Although most of these men had some sperm concentration is below 10 million/mL; 2) impaired libido
production, 16% of men had genetic aberrations of the or sexual function; or 3) other clinical findings that suggest
short-stature-homeo-box (SHOX) gene, the best known a specific endocrinopathy. At a minimum, initial evalua-
gene in PAR1. SHOX gene abnormalities are associated with tion should include measurement of the serum testosterone
short stature, mental retardation and arm and wrist defor- and FSH concentrations.
mities (49). It is important to note that a negative Y-chromo- A post-ejaculatory urinalysis is indicated for men having
some microdeletion test result does not necessarily exclude an ejaculate volume less than 1.0 mL, except in those diag-
a genetic abnormality, because there may be other, currently nosed with hypogonadism or CBAVD.
unknown, gene sequences on the Y or other chromosomes Trans-rectal ultrasonography (TRUS) for diagnosis of ejac-
that also might be required for normal spermatogenesis. Con- ulatory duct obstruction is indicated for men with azoo-
versely, some Y-chromosome microdeletions are rarely found spermia, palpable vasa, and low ejaculate volumes. TRUS
in fertile or subfertile males who have fathered children (44, also is indicated for men with oligospermia, low volume
50). Y-chromosome analysis should be offered to men who ejaculates, palpable vasa, and normal testicular size.
have non-obstructive azoospermia or severe oligospermia Scrotal ultrasonography is indicated for men whose phys-
before performing ICSI with their sperm. ical examination is difficult or inadequate and when a tes-
ticular mass is suspected.
Less commonly used specialized tests on semen (sperm
SPERM CHROMOSOME ANEUPLOIDY DNA fragmentation testing, acrosome reaction, ROS) are
Sperm DNA aneuploidy can be assessed by fluorescent in situ useful investigative tools but are not recommended for
hybridization (FISH) technology (51). One study has reported the routine evaluation of infertile men. Such tests may be
that up to 6% of men presenting with infertility and a normal considered in the evaluation of unexplained infertility
karyotype had an increased frequency of meiotic alterations but generally have little clinical utility.
detectable in their sperm (52). Men with the highest risk of Genetic testing for CFTR mutations (to rule out the possibil-
sperm aneuploidy are those with karyotypic abnormalities, ity of offspring affected with cystic fibrosis) should be
severely abnormal sperm morphology, and non-obstructive offered to the female partner of men with CBAVD before
azoospermia (51). Patients with recurrent pregnancy loss proceeding with treatments that use sperm from the
and recurrent IVF failure may also benefit from sperm aneu- affected man.
ploidy testing (53, 54). Currently, limitations to the routine Men with non-obstructive azoospermia or severe oligo-
use of this technology include cost, inability to screen the spermia (5 million/mL) are at increased risk for having
actual sperm used in ICSI, and difficulty in assigning a definable genetic abnormality and should be offered
VOL. 98 NO. 2 / AUGUST 2012 299
7. ASRM PAGES
karyotype and Y-chromosome analysis before performing 10. World Health Organization. WHO laboratory manual for the examination
ICSI using their sperm. Genetic counseling may be offered and processing of human semen, 2010. Available at: http://www.who.int
/reproductivehealth/publications/infertility/9789241547789/en/index.html.
when a genetic abnormality is suspected in either the male
Last accessed May 24, 2012.
or female partner and should be provided whenever a ge- 11. Kruger TF, Acosta AA, Simmons KF, Swanson RJ, Matta JF, Oehninger S.
netic abnormality is detected. Predictive value of abnormal sperm morphology in in vitro fertilization. Fertil
Steril 1988;49:112–7.
Acknowledgments: This report was developed under the 12. Menkveld R, Stander FS, Kotze TJ, Kruger TF, van Zyl JA. The evaluation of
morphological characteristics of human spermatozoa according to stricter
direction of the Practice Committee of the American Society
criteria. Hum Reprod 1990;5:586–92.
for Reproductive Medicine as a service to its members and 13. Pisarska MD, Casson PR, Cisneros PL, Lamb DJ, Lipshultz LI, Buster JE, et al.
other practicing clinicians. Although this document reflects Fertilization after standard in vitro fertilization versus intracytoplasmic
appropriate management of a problem encountered in the sperm injection in subfertile males using sibling oocytes. Fertil Steril 1999;
practice of reproductive medicine, it is not intended to be 71:627–32.
the only approved standard of practice or to dictate an exclu- 14. Keegan BR, Barton S, Sanchez X, Berkeley AS, Krey LC, Grifo J. Isolated
sive course of treatment. Other plans of management may be teratozoospermia does not affect in vitro fertilization outcome and is not
an indication for intracytoplasmic sperm injection. Fertil Steril 2007;88:
appropriate, taking into account the needs of the individual
1583–8.
patient, available resources, and institutional or clinical prac- 15. Cooper TG, Noonan E, von Eckardstein S, Auger J, Baker HW, Behre HM,
tice limitations. The Practice Committee and the Board of et al. World Health Organization reference values for human semen charac-
Directors of the American Society for Reproductive Medicine teristics. Hum Reprod Update 2010;16:231–45.
have approved this report. 16. Guzick DS, Overstreet JW, Factor-Litvak P, Brazil CK, Nakajima ST,
The following members of the ASRM Practice Committee Coutifaris C, et al. Sperm morphology, motility, and concentration in fertile
and infertile men. N Engl J Med 2001;345:1388–93.
participated in the development of this document. All Com-
17. Kumanov P, Nandipati K, Tomova A, Agarwal A. Inhibin B is a better marker
mittee members disclosed commercial and financial relation- of spermatogenesis than other hormones in the evaluation of male factor
ships with manufacturers or distributors of goods or services infertility. Fertil Steril 2006;86:332–8.
used to treat patients. Members of the Committee who were 18. Carter SS, Shinohara K, Lipshultz LI. Transrectal ultrasonography in disorders
found to have conflicts of interest based on the relationships of the seminal vesicles and ejaculatory ducts. Urol Clin North Am 1989;16:
disclosed did not participate in the discussion. Samantha Pfei- 773–90.
fer, M.D.; Marc Fritz, M.D.; Jeffrey Goldberg, M.D.; R. Dale 19. Jarow JP. Transrectal ultrasonography of infertile men. Fertil Steril 1993;60:
1035–9.
McClure, M.D.; Michael Thomas, M.D.; Eric Widra, M.D.;
20. Practice Committee of American Society for Reproductive M. Report on var-
Glenn Schattman, M.D.; Mark Licht, M.D.; John Collins, icocele and infertility. Fertil Steril 2008;90:S247–9.
M.D.; Marcelle Cedars, M.D.; Catherine Racowsky, Ph.D.; 21. Wolff H, Anderson DJ. Immunohistologic characterization and quantitation
Owen Davis, M.D.; Kurt Barnhart, M.D., M.S.C.E.; Clarisa Gra- of leukocyte subpopulations in human semen. Fertil Steril 1988;49:
cia, M.D., M.S.C.E.; William Catherino, M.D., Ph.D.; Robert 497–504.
Rebar, M.D.; Andrew La Barbera, Ph.D. 22. Ayvaliotis B, Bronson R, Rosenfeld D, Cooper G. Conception rates in couples
where autoimmunity to sperm is detected. Fertil Steril 1985;43:739–42.
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