INVESTIGATION OF INFERTILE COUPLE

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INVESTIGATION OF INFERTILE COUPLE
In a climate of
Evidence Based Medicine
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

• GPP Good practice point The view of the
  Guideline Development Group

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Semen analysisThe results of
semen analysis conducted as part of aninitial
assessment should be compared to the
followingWHO 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 shouldbe 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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CONCLUDING REMARKS
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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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The diagnostic process of investigating
infertility has evolved more by discarding old
tests than by finding useful new ones
A simplified approach will lead to a significant
reduction in both the time and cost of
investigating an infertile couple.

• Care must be taken to avoid exploitation of
  the infertile couple with expensive unnecessary
  tests

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THANK YOU FOR YOUR ATTENTION
DR. JEHAD YOUSEF FICS, FRCOG E-mailramoamman_at_yaho
o.co.uk