MANAGEMENT OF
INFERTILITY
CURRENT GUIDELINES
OBJECTIVES
 To present the recent concepts in the
management of infertility
 To draw clinically relevant conclusions based on:
META-ANALYSIS
RANDOMISED CONTROLLED TRIALS
GUIDELINES AND PROTOCOLS
 To discuss the best possible clinical
management options with local perspective
BACKGROUND INFORMATION
 At puberty there are 300,000 primordial




follicles
Dominant follicle produces oestradiol
which leads to LH surge
Ovulation occurs 24-36 hours later
The fertilization life span of the ovum is
24-36 hours
The receptivity of the endometrium is days
16-19 of a 28 day cycle
BACKGROUND INFORMATION
 Infertility is rarely absolute so the term
sub-fertility may be more appropriate
 About 84% of couples would conceive
within one year of trying for a pregnancy
 Another 8% would conceive in the next
year giving a cumulative pregnancy rate of
92% at the end of two years
 Subfertility is defined as the inability to
conceive within 12-24 months of trying
BACKGROUND INFORMATION
 The single most important determinant of a
couple’s fertility is the age of the female
partner:
At the age of up to 25 years CCR is 60% at
six months and 85% at one year
At the age of 35 years or more the CCR is
60% at one year and 85% at two years
BACKGROUND INFORMATION
 The other factors influencing the likelihood of a
spontaneous pregnancy are:
Duration of subfertility
Occurrence of a previous pregnancy
 The effect of age on male fertility, however is
less clear
 Any change in the prevalence of subfertility in
recent years is a difficult question to answer but
the male fertility is declining
CURRENT GUIDELINES
 The current clinical approach to the
investigations and the management of
infertility is backed by the evidence-based
guidelines issued by:
Royal College of Obstetricians and
Gynaecologists (RCOG)
American Society of Reproductive
Medicine (ASRM)
European Society of Human
Reproduction and Embryology (ESHRE)
INVESTIGATIONS
 The male partner should normally have
two semen analyses performed during the
initial investigation.
 Laboratories that perform semen analysis
should undertake this according to
recognised WHO methodology.
 Laboratories should also practice internal
quality control and belong to an external
quality control scheme .
INVESTIGATIONS
 While regular menstruation is strongly
suggestive of ovulation, this should be confirmed
by the measurement of serum progesterone in
the mid-luteal phase
 There is no value in measuring thyroid function
or prolactin in women with a regular menstrual
cycle, in the absence of galactorrhoea or
symptoms of thyroid disease
INVESTIGATIONS
 Early follicular phase estimation of
FSH and LH is only performed if
clinically indicated
 The female partner should normally
have a test of tubal patency during the
initial investigation of infertility
INVESTIGATIONS
 A hysterosalpingogram may be used as a
screening test for tubal patency in low risk
couples
 When an evaluation of the pelvis is
required, however, a diagnostic
laparoscopy with dye transit is the
procedure of choice
INVESTIGATIONS
 Ultrasound scan and hydrotubation has
not been widely adopted.
 The images obtained by falloposcopy are
not yet of sufficiently good quality to
provide useful clinical information.
INVESTIGATIONS
Before any uterine instrumentation,
consideration should be given either to
screening women for Chlamydia
trachomatis, using an appropriately
sensitive
technique,
or
using
appropriate antibiotic prophylaxis .
INVESTIGATIONS
 Endometrial biopsy to evaluate the luteal phase
should not be performed as part of the routine
investigation of the infertile couple
 The postcoital test is not recommended in the
routine investigation of the infertile couple
 Sperm function tests are specialised tests and
should not be used in the routine investigation of
the infertile couple .
INVESTIGATIONS
 Routine testing for antisperm antibodies in semen
is not recommended
 Hysteroscopy should not be considered as a
routine investigation in the infertile couple as
there is no evidence linking the treatment of
uterine abnormalities with enhanced fertility
 An ultrasound examination of the endometrium is
unnecessary in the initial investigation of infertility.
However, ultrasound evaluation of the ovaries may
be useful
DIAGNOSIS OF PCOS
 The debate was resolved in Rotterdam in
May 2003 At PCOS consensus workshop
 It was agreed that two of the following
three criteria were essential to establish
diagnosis:
1. OVARIAN DYSFUNCTION
2. CLINICAL OR BIOCHEMICAL EVIDENCE OF
HYPERANDROGENISM
3. POLYCYSTIC OVARIAN MORPHOLOGY ON
ULTRASOUND
DIAGNOSIS OF PCOS
 Ultrasound is the gold standard for
the diagnosis of PCO.
The diagnostic criteria is of 10 discrete
follicles of <10mm usually peripherally
arranged around an enlarged,
hyperechogenic central stoma
WHICH INVESTIGATIONS?
 Diagnostic tests for infertility were classified
into following three categories by ESHRE
Capri workshop in 2000
Tests which have an established
correlation with pregnancy
Tests which are not consistently
correlated with pregnancy
Tests which seem NOT to correlate with
pregnancy
Tests which have an established
correlation with pregnancy
 Semen analysis
 Tubal patency test by HSG or
Laparoscopy
 Mid luteal serum progesterone for
the diagnosis of ovulation
Tests which are not consistently
correlated with pregnancy
 Zona free hamster egg penetration
tests
 Post-coital test
 Antisperm antibodies assays
Tests which seem NOT to correlate
with pregnancy
 Endometrial dating
 Varicocoel assessment
 Chlamydial testing
MAY HAVE A ROLE IN SPECIAL SITUATIONS
MANAGEMENT
The management of infertility should
take place in a dedicated infertility
clinic staffed by an appropriately
trained professional team with
facilities
for
investigating
and
managing problems in both partners.
MANAGEMENT
 Both partners should be seen together
 Privacy and sufficient clinical time
 Classical history taking with emphasis on
exploring a couple’s anxieties
 Counseling is very important and
essential
 Routine examination is not necessary
unless indicated by the history
MANAGEMENT
 Each stage in the investigation and
treatment of infertility should be fully
explained to the couple.
 Written information in a range of
languages should be available where
appropriate.
 Environmental factors can affect fertility
and therefore an occupational history
should be taken.
MANAGEMENT
 The management of the individual couple
should always be discussed in the context
of their particular clinical situation.
 Patients should be fully involved in
decisions regarding their treatment.
 Couples should also have access to
infertility counselors outside the clinical
team, and to patient support groups
GENERAL ADVICE TO THE COUPLE
 Sexual intercourse every 2-3 days
 Timed intercourse to coincide with ovulation
causes stress and not to be recommended
 Smoking reduces both, women’s fertility as
well as semen quality
 Excessive alcohol is detrimental to semen
quality and may cause erectile dysfunction
GENERAL ADVICE TO THE COUPLE
 A body mass index of more than 29 is
associated with reduced fertility in both
men and women
 Folic acid supplement prior to conception
and up to 12 weeks of conception
 Rubella immunity should be checked
 If vaccinated then advise to avoid
pregnancy for at least one month after
vaccination
MALE INFERTILITY
 In considering the results of semen analysis for
the individual couple, it is important to take into
account the duration of infertility, the woman’s
age and the previous pregnancy history .
 Further investigations of the male partner should
be preceded by a clinical examination including
an assessment of secondary sexual
characteristics and testicular size .
MALE INFERTILITY
 Further investigations of the male partner may
include endocrine tests, microbiological
assessment of the semen and imaging of the
genital tract but should be initiated in the context
of a specialist infertility clinic.
 Laboratories reporting semen analysis results
should establish normal ranges for their own
populations and indicate these on report sheets .
MALE INFERTILITY
 Certain in vitro tests of sperm function can
be of use in predicting fertility . However,
at this stage, their use and interpretation
should be restricted to those few centres
with relevant expertise.
 Surgery on the male genital tract should
be carried out only in centres where there
are appropriate facilities and trained staff.
MALE INFERTILITY
 Testicular biopsy should be performed only in
the context of a tertiary service where there are
facilities for sperm recovery and cryostorage.
 Vasectomy reversal is an effective treatment for
men who want to reverse their sterilisation.
 Surgical correction of epididymal blockage can
be considered in cases of obstructive
azoospermia.
 Where a diagnosis of hypogonadotrophic
hypogonadism is made in the male partner the
use of gonadotrophin drugs is an effective
fertility treatment.
MALE INFERTILITY
 Bromocriptine is an effective treatment for
sexual dysfunction in men with
hyperprolactinaemia.
 Intrauterine insemination is an effective
treatment where the man has mild abnormalities
of semen quality.
 Infection of the male genital tract should be
treated if present, but there is no evidence that
this will improve fertility.
MALE INFERTILITY
 Anti-oestrogens, androgens, bromocriptine
and kinin-enhancing drugs have not been
shown to be effective in the treatment of
Male infertility
 Antioxidants, mast cell blockers and alpha
blockers need further evaluation.
 The use of systemic corticosteroids for
treatment of antisperm antibodies can only
be recommended in the context of further
research.
MALE INFERTILITY
 There is no evidence that semen
quality and pregnancy rates improves
in men with normal sperm count after
surgical treatment of a clinically
apparent varicocele
 The benefits of the treatment of a
varicocele in oligozoospermic men is
less certain
MALE INFERTILITY
 IVF and ICSI are effective treatments for
men with moderate to severe semen
abnormalities
 ICSI has made it possible for men with
only few sperms to become fathers
 Sperms for ICSI can be obtained by TSA
are directly from testicular biopsy as well
as aspiration from epididymus
TUBAL INFERTILITY
 Tubal surgery should be carried out only in centres where
there are appropriate facilities and trained staff.
 Where proximal tubal obstruction is suspected this should
be confirmed by selective salpingography and a tubal
catheterisation procedure may be attempted.
 Tubal surgery may be appropriate for selected cases of
mild distal tubal disease or proximal tubal obstruction.
 If pregnancy has not occurred within 12 months of tubal
surgery, IVF should be discussed .
TUBAL INFERTILITY
 When distal tubal surgery is performed, a
microsurgical approach using magnification should
be used.
 A laparoscopic approach can be used for
adhesiolysis but the use of this approach for
salpingostomy needs more evaluation .
 IVF should be considered as the first line
treatment for moderate to severe distal tubal
disease .
TUBAL INFERTILITY
 The presence of hydrosalpinges is
associated with reduced pregnancy rates
following IVF.
 Tubal reanastomosis is an effective
treatment for women who want to reverse
their sterilisation.
 High success rates can be achieved when
reversing mechanical tubal occlusion using
a microsurgical approach .
TUBAL INFERTILITY
 IVF should be considered first line
treatment for moderate to severe tubal
disease
 Both surgery and IVF should be discussed
without bias
 There is no randomised comparison
between IVF and tubal surgery
OVULATION DISORDERS
 Before ovulation induction is considered,
further investigations will be necessary and
these should be carried out only in a
specialist clinic .
 In undertaking ovulation induction, centres
should adopt protocols which minimise the
risk of multiple pregnancy and ovarian
hyperstimulation .
OVULATION DISORDERS
 Patients undergoing ovulation
induction must be given
information about the risks of
multiple pregnancy, ovarian
hyperstimulation and the
possibility of fetal reduction.
OVULATION DISORDERS
 Clomiphene is an effective treatment for
anovulation in appropriately selected women
 Cumulative Pregnancy Rate continues to rise until
ten cycles of treatment. RCOG recommends that
up to 12 cycles of treatment should be considered
 Ovulation induction with clomiphene should only
be performed in circumstances which allow access
to ovarian ultrasound monitoring.
OVULATION DISORDERS
 With clomiphene ovulation occurs in 70-80%
and the cumulative rate over six months is 60%
 Seventy percent achieve pregnancy at doses of
100 mgs or less
 Most evidence point towards less pregnancy
rate above 100 mgs.
OVULATION DISORDERS
 FSH and hMG are both effective for ovulation
induction in women With clomiphene-resistant
polycystic ovarian syndrome (PCOS).
 There is no advantage in routinely using
gonadotrophin-releasing hormone analogues in
conjunction with gonadotrophins for ovulation
induction in women with clomiphene-resistant
PCOS. Furthermore, their use may be associated
with an increased risk of ovarian hyperstimulation .
OVULATION DISORDERS
 Laparoscopic ovarian drilling with either
diathermy or laser is an effective treatment for
anovulation in women with clomiphene-resistant
PCOS. However, more research is needed into
the sequelae of causing ovarian damage in this
way.
 The pulsatile administration of gonadotrophinreleasing hormone is an effective treatment for
women with anovulation due to hypothalamic
factors.
OVULATION DISORDERS
 Dopamine agonists are effective treatment
for women with anovulation due to
hyperprolactinaemia
 Ovulation induction with gonadotrophins
should only be performed in circumstances
which permit daily monitoring of ovarian
response .
 The criteria for abandoning ovulation
induction cycles must be carefully defined in
each specialist centre.
OVULATION DISORDERS
 The association between ovarian cancer risk and
gonadotrophins or prolonged clomiphene use
remains uncertain.
 There is no evidence to suggest an increased risk
of ovarian cancer when clomiphene is used for
less than 12 cycles.
 Patients should be counseled about the putative
risks of ovarian cancer associated with ovulation
induction therapy. Practitioners should confine the
use of gonadotrophins to the lowest effective dose
and duration of use .
ENDOMETRIOSIS ASSOCIATED
INFERTILITY
 Endometriosis should be classified using the revised AFS
system of classification, until such time as a proven
functional classification is approved .
 Surgical ablation of minimal and mild endometriosis
improves fertility in subfertile women.
 Medical treatment of minimal and mild endometriosis does
not enhance fertility in subfertile women
ENDOMETRIOSIS ASSOCIATED
INFERTILITY
 Ovarian stimulation with intrauterine insemination
is more effective than either no treatment or lUl
alone in subfertile women with minimal or mild
endometriosis.
 There is no evidence that medical treatment of
moderate and severe endometriosis either alone
or as an adjunct to surgery improves fertility.
 Surgical treatment of moderate and severe
endometriosis may improve fertility but controlled
studies and comparisons with assisted
reproduction techniques are required.
ENDOMETRIOSIS ASSOCIATED
INFERTILITY
 In cases of moderate and severe
endometriosis, assisted reproduction
techniques should be considered as an
alternative to, or following unsuccessful
surgery.
 Where large ovarian endometriotic cysts are
detected, consideration should be given to
their surgical treatment because this may
enhance spontaneous pregnancy rates and
improve access if IVF is considered.
UNEXPLAINED INFERTILITY
 Unexplained infertility is a diagnosis of
exclusion
 Spontaneous pregnancy rate are high in
first three years of trying
 Clomiphene encourages multifollicular
ovulation and increases the chances of
pregnancy in couple’s with unexplained
infertility
UNEXPLAINED INFERTILITY
 Ovarian stimulation with intrauterine
insemination is an effective treatment for
couples with unexplained infertility.
 GIFT is an effective treatment for couples
with unexplained infertility.
 IVF may be preferred because of the
additional diagnostic information it provides
and because it avoids laparoscopy
ASSISTED REPRODUCTION
 These techniques have revolutionized the
management of infertile couples
 Entry guidelines should be followed
 The women should be less than 40 years
old and in good health
 The couple should be aware of the
emotional and financial strain
ASSISTED REPRODUCTION
 The most common techniques used are:
Intrauterine Insemination
In-vitro fertilisation
Intracytoplasmic sperm injection
 The success rate of the clinic should be told to
the patient
 The take home baby rate is roughly around 20%
 There is no increase in the incidence of the
congenital abnormalities
P0INT TO REMENBER
ONE SATISFIED PATIENT IS
WORTH THOUSANDS OF
GUIDELINES AND
PROTOCALS
THANK YOU
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MANAGEMENT OF INFERTILITY CURRENT GUIDELINES