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INVESTIGATION OF INFERTILE
COUPLE
Evidence Based Medicine
In a climate of
DR. JEHAD YOUSEF
FICS , FRCOG
ALHAYAT ART CENTRE
AMMN, JORDAN
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Very long list of tests, have been
advocated to assist in determining the
cause of the infertility in the diagnostic
evaluation of infertile couple.
The necessity and cost effectiveness of
performing many of these tests and
correcting the abnormalities found by
them have not been demonstrated.
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Investigations of Male Factor
Conventional semen analysis
Computer- assisted sperm analysis (CASA)
Strict sperm morphology "Tygerberg strict criteria
A variety of sperm function tests
- The acrosome reaction test
- Hypo-osmotic swelling test
- Measurement of generation of Reactive oxygen species
- Sperm capacitation assays
- Hemizona-binding assay
- Hamster penetration test
- Human sperm-zona penetration assay
- etc.
A variety of imaging techniques for detection of varicocele




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Assessment of ovulation
Basal body temperature
Urine LH kits
Mid luteal serum progesterone
Routine hormonal profile: FSH, LH, Prolactin,TSH
Endometrial biopsy
Serial pelvic Ultrasonography.
A variety of tests for assessment of ovarian reserve such as D3
FSH & E2, Inhibin B, Clomid challenge test, Gondotropin
agonist stimulation test, TVS for ovarian volume, antral follicle
count and Stromal blood flow.

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Investigations of tubal factor
Hysterosalpingography (HSG)
Hysterosonography
Laparoscopy
Hydrolaparoscopy.
Falloscopy

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Other investigations
PCT for assessment of the cervical factor.
Hysteroscopy and 3 D US for assessment of the
uterine factor.
Laparoscopy for assessment of the peritoneal
factors.
Chlamydia trachomatis antibodies for assessment of
possible tubo-ovarian adhesions.
CA-125 blood testing for assessment of possible
endomtetriosis.
Immunological factors are evaluated by a variety of
special tests.

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Controverses
Lack of agreement exists among
trained infertility speicalists with regard
to prognostic utility as well as criteria of
normality of many of these tests?
There is no consensus on which tests
are essential before reaching the exact
diagnosis ?



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Investigations of infertile couple
Evidence Medicine Based Era
National Evidence-Based Clinical Guidelines
Assessment and treatment for people with fertility problems
developed by the National Collaborating Centre

for
Women and Children's Health on behalf of
the National Institute

for Clinical Excellence (NICE)
February 2004
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Grading Evidence Based Recommendations
A
recommendation
I evidence
B
recommendation
II evidence
C
recommendation
III evidence
D
recommendation
IV evidence
I a- meta-analysis
of RCTs trials,
I b- at least one
RCT.
II a - at least one
controlled study
without
randomisation
II b - at least one
other type of
quasi-
experimental
study

non-experimental
descriptive
studies, such as
comparative
studies,
correlation
studies and case
control studies
from expert
committee reports
or opinions and/or
clinical experience
of respected
authorities

GPP Good practice point : The view of the Guideline Development
Group
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Semen analysis
The results of semen analysis conducted as part of an
initial assessment should be compared to the following
WHO reference values :
volume: 2.0 ml
liquefaction time: within 60 minutes
pH: 7.2
sperm concentration: 20 million per ml
total sperm number: 40 million per ejaculate
motility: 50% (grades a and b) or 25% or more with progressive motility
(grade a) within 60 minutes of ejaculation
vitality : 75% or more live
white blood cells: fewer than 1 million per ml
normal morphology: 30% or 15% (based on strict morphological criteria)


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Semen analysis
If the result of the first semen analysis is abnormal,
a repeat confirmatory test should be offered.
(Grade B)
Repeat confirmatory tests should ideally be
undertaken 3 months after the initial analysis to allow
time for the cycle of spermatozoa formation to be
completed. However, if a gross spermatozoa
deficiency (azoospermia or severe oligozoospermia)
has been detected the repeat test should be
undertaken as soon as possible. (GPP)




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Semen analysis
CASA is not superior to conventional semen
analysis (Grade A)
Screening for antisperm antibodies should not be
offered because there is no evidence of effective
treatment to improve fertility. (GPP)



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Assessment of Ovulation
Women with fertility problems should
be asked about the frequency and regularity of
menstrual cycles.
Women with regular monthly menstrual cycles are
likely to be ovulating. (Grade B)
The use of basal body temperature charts to confirm
ovulation does not reliably predict ovulation and is
not recommended. (Grade B)





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Assessment of Ovulation
Women with regular menstrual cycles and more
than 1 years infertility are offered a blood test to
measure serum progesterone in the mid-luteal
phase of their cycle (day 21 of a 28-day cycle) to
confirm ovulation. (Grade B)

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Assessment of Ovulation
Women with prolonged irregular menstrual cycles
should be offered a blood test to measure serum
progesterone. Depending on the timing of
menstrual periods, this test may need to be
conducted later in the cycle (for example day 28 of a
35-day cycle) and repeated weekly thereafter until
the next menstrual cycle starts. (GPP)
For such women direct or indirect measurement of
progesterone is unnecessary until after therapy is
initiated.



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Assessment of Ovulation
Women with irregular menstrual cycles should be
offered a blood test to measure serum FSH & LH (GPP).
Blood test for prolactin should only be offered to
women who have an ovulatory disorder, galactorrhoea
or a pituitary tumour. (Grade C)


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Assessment of Ovulation
Tests of ovarian reserve currently have limited
sensitivity and specificity in predicting fertility.
However, women who have high levels of
gonadotrophins should be informed that they are
likely to have reduced fertility. (Grade C)
The value of assessing ovarian reserve using
Inhibin B is uncertain and is therefore not
recommended. (Grade C)


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Assessment of Ovulation
Women with possible fertility problems are no more
likely than the general population to have thyroid
disease and the routine measurement of thyroid
function should not be offered. Estimation of
thyroid function should be confined to women with
symptoms of thyroid disease. (Grade C).

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Assessment of Ovulation
Women should not be offered an endometrial
biopsy to evaluate the luteal phase as part of the
investigation of fertility problems because there is
no evidence that medical treatment of luteal phase
defect improves pregnancy rates (Grade B).


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Assessment of tubal factor
The results of semen analysis and assessment of ovulation
should be known before a test for tubal patency is performed.
Women who are not known to have co-morbidities
(such as pelvic inflammatory disease, previous
ectopic pregnancy or endometriosis) should be
offered HSG to screen for tubal occlusion because
this is a reliable test for ruling out tubal occlusion,
and it is less invasive and makes more efficient use
of resources than laparoscopy. (Grade B)

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Assessment of tubal factor
Where appropriate expertise is available, screening
for tubal occlusion using hysterosalpingo-contrast-
ultrasonography should be considered because it is
an effective alternative to HSG for women who are
not known to have co-morbidities (Grade A)
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Assessment of tubal factor
Women who are thought to have co-morbidities
should be offered laparoscopy and dye so that tubal
and other pelvic pathology can be assessed at the
same time. (Grade B)


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Screening for Chlamydia
trachomatis
Before undergoing uterine instrumentation women should
be offered screening for Chlamydia trachomatis using an
appropriately sensitive technique. (Grade B)
If the result of a test for Chlamydia trachomatis is positive,
women and their sexual partners should be referred for
appropriate management with treatment and contact tracing.
(Grade C)
Prophylactic antibiotics should be considered before uterine
instrumentation (including HSG), if screening has not been
carried out. (GPP)



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Assessing uterine abnormalities
Women should not be offered hysteroscopy on its
own as part of the initial investigation unless
clinically indicated, because the effectiveness of
surgical treatment of uterine abnormalities on
improving pregnancy rates has not been
established. (Grade B)

women with infertility and a normal HSG had no
abnormalities of the uterine cavity when
subsequently examined by hysteroscopy.
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Post-coital testing of cervical
mucus
The routine use of post-coital testing of cervical
mucus in the investigation of fertility problems is
not recommended because it has no predictive
value on pregnancy rate. (Grade A)

. The post-coital test may be of value in the diagnosis of sexual dysfunction
and ejaculatory problems.
. Results of post-coital testing may have little influence on treatment strategy
in the light of the widespread use of IUI for fertility problems associated with
sperm-cervical mucus interaction.
. The lack of effective treatment for anti-sperm antibodies may render PCT
unnecessary.
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Until it is demonstrated conclusively
that treatment of abnormalities
diagnosed by any of infertility
testing, results in a significantly
better pregnancy rate than placebo
or no treatment, the advisability of
performing such test, remains
unproven and should not be
performed.

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Conventional Semen analysis.
Assessment of utero-tubal status by
HSG and indicated laparoscopy.
Mid luteal progesterone for the
diagnosis of ovulation
Are useful tests, and correlate directly
with the likelihood of conception.
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Post-coital test.
Sperm penetration into cervical mucus.
Hysteroscopy.
Sperm antibody tests.
Varicocele assessment.
Endometrial biopsy.
The sperm penetration assay in the zona-
free hamster oocyte.
Are less useful tests, as their results are
not correlated with pregnancy.
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It is not cost effective to perform a diagnostic
laparoscopy as part of the initial infertility evaluation
in women in whom, history, and physical examination,
TVS, HSG, antibodies to Chlamydia trachomatis and
CA-125 level are all normal.
Provided the woman is under age 35 and having
ovulatory cycles and patent tubes, and there are more
than 5 million motile sperm in the ejaculate of the male
partner, 4-6 cycles of IUI COH should be undertaken
before performing a diagnostic laparoscopy and
resorting to ARTs.
Such approach has been shown to increase
fecundability rates to 10 - 25% per cycle and is thus
useful initial approach for subfertile couples.
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Research could help improve treatment
results in female infertility by discovering as-
yet-unknown causes of infertility that coexist
with recognized diagnoses.
Such unknown causes may include post-
fertilization defects that cannot by definition
respond to the pre-fertilization interventions
that comprise many of the available
treatments.
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Care must be taken to avoid exploitation of the
infertile couple with expensive unnecessary tests
A simplified approach will lead to a significant
reduction in both the time and cost of
investigating an infertile couple.
The diagnostic process of investigating infertility
has evolved more by discarding old tests than by
finding useful new ones
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DR. JEHAD YOUSEF
FICS, FRCOG
E-mail:ramoamman@yahoo.co.uk