MANAGEMENT OF

INFERTILITY
CURRENT GUIDELINES

DR NOSHABA RAFIQ
M.B.B.S. M.C.P.S. F.C.P.S.
 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

couples 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 couples 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, womens 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 womans
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 gonadotrophin-

releasing 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 couples 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
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