Infertility basics

c/o Prof Raphael RonEl

University Asaf Tel Aviv

Definition
Infertility is inability of a couple to
conceive after one year of sexual
intercourse without contraception

How frequently do people

conceive?
Natural pregnancy rates
(best rates at age 22-23 y.o., decline
significantly after 35, abruptly after 40)

ART pregnancy rates

(try to) Look for the diagnosis!

There is a very long list of investigations
for the diagnosis of infertility, however
there is no consensus on which tests
are essential before reaching the exact
diagnosis

What are you looking for?

Is the woman ovulating? How is the
fertility potential?
Is there a mechanical factor? Are the
tubes patent?
Is there a male factor? What is the
quality of the sperm?

(never forget the) Male Factor

Conventional semen analysis
A variety of sperm function tests such
as in vitro mucous penetration test,
hamster egg penetration test and post
coital test.

Assessment of ovulation
Basal body temperature
Mid luteal serum progesterone
Endometrial biopsy
Ultrasound monitoring of ovulation (detects
timing).

Tubal factor
Hysterosalpingography
Laparoscopy
Falloscopy
Hysterosonography
Hydrolaparoscopy.

Others
The peritoneal factors are assessed by
laparoscopy
The uterine factor by
hysterosalpingography and
hysteroscopy.
Immunological factors are evaluated by
a variety of special tests.

Controverses
A lack of agreement exists among
trained infertility specialists with regard
to the diagnostic tests to be performed
and their prognostic utility as well as
criteria of normality

Opinion Based Practice

consulting senior colleagues or by

reading text books with lack of sufficient
time available for searching the
specialized journals.
Little is paid to evidence derived from
research the Scientific Factor.

Evidence-based medicine (EBM)

EBM brings the best available evidence
from clinical research to clinical
practice.
gets our knowledge up to date by
tracking the recent clinical research
results.

Sources of Evidence Based

Infertility investigations
Cochrane Library
Journal of Evidence Based Obstetrics and
Gynecology
Evidence based recommendations of the
Royal College of Obstetrics & Gynecology

Take Care
Care must be taken to avoid
exploitation of the infertile couple with
expensive unnecessary tests
( ESHRE Capri Workshop 1996)

Concept to keep in mind

A simplified approach will lead to a
significant reduction in both the time
and cost of investigating an infertile
couple.
(Strandell 2000)

So what EBM tells us?!!

Diagnostic tests for infertility should be
categorized into three categories based
on the correlation with pregnancy rates

The first category

includes tests which have an established
correlation with pregnancy as:
Semen analysis
Tubal patency by hysterography or
laparoscopy
Mid luteal progesterone for the
diagnosis of ovulation.

Semen analysis
Remains the mainstay in investigating
male fertility potential.
Serial semen samples (at least two)
should be assessed in the same
laboratory
(WHO,1999)

Criteria
+ According to the WHO the lower limit of the normal
semen testing is
> 20 million/mL.
>40% progressive motility
>30% normal forms
+ Kruger morphology criteria

WHO,1999

Collection of semen sample

by masturbation
after min 3 days abstinence, max 7 days
temp (15C to 38C)
deliver quickly
As many as 25% of proven fertile men
have sperm concentration
below 20 million/ml

CASA vs. conventional analysis

In a randomized controlled trial, the
determination of motility characteristics
as obtained by CASA systems is of
limited value
CASA (computer assisted semen
analysis) is not superior to conventional
semen analysis
(Krause ,1995 )

Testicular biopsy
For selected cases
Only in tertiary centers
Needs semen retrieval and
cryopreservation facilities

Hysterosalpingography
Although HSG is of low sensitivity, its high
specificity makes it a useful screening test
for ruling in tubal obstruction.
In case of abnormal finding, diagnostic
laparoscopy with dye transit (e.g. methyl
blue test) is the procedure of choice
(Swart et al, 1995)

Advantages
HSG is cheaper
Performed as an outpatient procedure
Although often painful has a low
incidence of complications
RCOG, 1999

Serum chlamydial antibodies vs HSG

Chlamydia
antibody
testing
has
comparable estimates of tubal pathology
but
provides no details on the anatomy of
uterus and tubes.
(Mol et al, 1997)

Conception after HSG

HSG has a low prognostic value, the outcome of
HSG adds little to predicting the occurrence of
pregnancy.
However, when HSG shows bilateral obstruction,
the chance of getting pregnant is only minimal .
(Maas et al, 1997)
Some evidence that conception rates increase
during the 6 mths following HSG.

Confirmation of Ovulation
The only true proof of ovulation is the
recovery of an ovum
Or
pregnancy .

Confirmation of Ovulation
Serum progesterone in the mid-luteal phase on
day 22-26 is the method of choice
Endometrial biopsy is not a routine step in the
investigations of infertility .
(Peters et al,1992 / Templeton,2001)

However, Ultrasonography
US examination of the pelvis is useful
especially for the ovary.
Transvaginal sonography is the method of
choice for women who are having
ovulation induction
(Templeton 2001)

The second category

Includes tests which are not consistently
correlated with pregnancy as
zona-free hamster egg penetration tests
post coital test
antisperm antibodies assays.

Sperm function tests

should not be routine investigations
complex
expensive
not always provide clinically useful
information)
(Oehninger et al 2000)

Postcoital test
Comparing impact of infertility investigations
with and without the postcoital test showed
closely similar cumulative pregnancy rates
at 24 months, the postcoital test is not an
essential procedure
(Oei et al, 1998)

The third category

Includes tests which seem not to correlate
with pregnancy as:
endometrial dating
varicocele assessment
chlamydial testing.
(ESHRE Capri workshop 2000)

Endometrium
The prognostic value of endometrial
thickness is not universally accepted
(Schild et al 2001)

Thyroid / Prolactin assay

Recommended, although there is no
statistical value in measuring thyroid
function or prolactin in women with a
regular menstrual cycle, in the absence of
galactorrhoea or symptoms of thyroid
disease.
(Templeton,2001)

BBT/LH
There is no evidence that the use of BBT
charts and luteinizing hormone detection
methods to time intercourse improves
outcome.
(Leader,1992 / Guermandi,2001)

Hysteroscopy
HSC is not a routine investigation of
infertile couples as there is no evidence
linking treatment of uterine abnormalities
with enhanced fertility.
(RCOG,1999)

Precaution
Before uterine instrumentation (as HSG
or
HSC)
appropriate
antibiotic
prophylaxis against chlamydia should
be given
RCOG,1999

CA-125 in endometriosis
The performance of serum CA-125
measurement in the diagnosis of
endometriosis grade I/II is limited, whereas
its performance in the diagnosis of
endometriosis grade III/IV is better.

Better in predicting recurrence

(Mol et al, 1998)

How to judge a new diagnostic

test

Sensitivity: to produce few false negatives.

Specificity: to produce few false positives.
Positive predictive value.
Negative predictive value.
Invasiveness: with the possibility of harmfulness
Cost

3-D US: another model

As effective as two-dimentional US
Very expensive
No specific advantage in infertility over
2-D

No role in infertility yet

N.B: Bicornuate ut. Vs septate ut

Summary for investigations

From the above data, it seems that

serum progesterone for detection of ovulation

day 3 FSH and estradiol for fertility potential
hysterography for tubal patency
semen analysis

are the basic essential tests for diagnosis

of infertility.

 Other tests may have a role in special

situations or as a part of clinical trials
Laparoscopy should be reserved as a
further diagnostic procedure or in
combination with endoscopic surgery

Testing until uncertainty

vanishes may delay treatment
AGING process

What next?
Management basics

What next?
General advice
Weight loss for BMI > 30
Beware of low BMIs and nutritional habits
Give up smoking! Women (B) and
men(C).
Regular intercourse throughout the
cycle,rather than the use of temperature
charts and LH detection (C)

Male Subfertility
Oligo/asthenospermia
Drug treatments are ineffective in the
treatment of idiopathic male infertility.
Gonadotrophin is effective for treatment for
male hypogonadotrophic hypogonadism,
which is very rare.

Male Subfertility
Oligo/asthenospermia
IUI offers couples with male subfertility benefit
over timed intercourse, both in natural cycles
and in cycles with ovarian stimulation.
Mild
ovarian
hyperstimulation
with
gonadotrophins is advised in cases with less
severe
semen
defects
(motile
sperm
concentration
>
10
million).

Male Subfertility
Oligo/asthenospermia
Intrauterine insemination with or without ovarian
stimulation is an effective treatment where the man has
abnormalities of semen quality, but it has to be
remembered that the pregnancy rates even after
treatment remain very low (A)

Varicocele
Varicocele treatment should be offered
when all of the following are present:
1. A varicocele is palpable.
2. The couple has documented infertility.
3. The female has normal fertility or potentially
correctable infertility.
4. The male partner has one or more abnormal
semen parameters .

Obstructive Azoospermia
Vasectomy reversal and surgical
correction of epididymal blockage
(microsurgical)can be considered in
cases of obstructive azoospermia .
It needs Expert hands.
RCOG Guidelines : Grade B Recommendation

ICSI
Intracytoplasmic sperm injection (ICSI) is
indicated in
Severe deficits in semen quality
Obstructive azoospermia .
Non-obstructive azoospermia .
Previous IVF cycle with failed or very
poor fertilisation.
RCOG Guidelines : Grade A Recommendation

Ovulation Disorders
Clomiphene C. is an effective treatment for
anovulation in appropriately selected women.
(A)
Up to 12 cycles of treatment should be
considered (B).

RCOG Guidelines

Ovulation Disorders
FSH and hMG are both effective
for
ovulation
induction
in
women
with
clomiphene
resistant
polycystic
ovarian
syndrome.

RCOG Guidelines : Grade A Recommendation

Hyperprolactinaemia
Dopamine agonists are effective
and safe treatment for women
with anovulation due to
hyperprolactinaemia
RCOG Guidelines : Grade A Recommendation

PCO:Laparoscopic Drilling"
Laparoscopic ovarian drilling with
either diathermy or laser is an
effective treatment for anovulation in
women with clomiphene-resistant
PCOS

RCOG Guidelines : Grade A

PCO: Laparoscopic Drilling"

There is insufficient evidence of a
difference in pregnancy rates between :
Laparoscopic ovarian drilling after 6-12 m
follow up
&
Gonadotrophins 3-6 cycles .
Multiple pregnancy are considerably reduced
after
laparoscopic
drilling.
.

Endometriosis :Minimal &Mild

Surgical ablation of minimal

And mild endometriosis
improves fertility in subfertile
women

RCOG Guidelines : Grade A Recommendation

Endometriosis : Mild
. CONTROVERSY: ovarian
stimulation with IUI is more
effective for them than either
no treatment or IUI alone.
RCOG Guidelines : Grade A Recommendation

Endometriosis :
Moderate to Severe

Endometriosis :Moderate to Severe

Surgical treatment may improve

fertility but controlled studies and
comparisons with assisted
reproduction techniques are
required (B).
RCOG Guidelines : Grade B Recommendation

Endometriosis-associated
infertility
Hormonal therapy for ovulation
suppression cannot be recommended as
a standard therapy for endometriosisassociated infertility.
So drug treatments dont improve conception rate.

RCOG Guidelines : Grade A Recommendation

Microsurgical Tubal
Surgery
Mild distal tubal disease

Micro scissor
Cutting fimbrial
band

Dissection of
fimbriae
adherent to the
uterus

Cutting fimbrioomental band

Tubal Catheterization
Where proximal tubal
obstruction is suspected,
and there are no other tubal
abnormalities, a tubal
catheterisation procedure
may be attempted
RCOG Guidelines : Grade B Recommendation

Tubal Catheterization

R. Ovary
Bilateral Cornual Block

R. fimbria

Cornual catheterization

Moderate to Severe Distal tubal

Disease
. IVF should be considered
as the first line treatment
for moderate to severe
distal tubal disease

RCOG Guidelines : Grade B Recommendation

Hydrosalpinges & IVF,

Laparoscopic
salpingectomy should
be considered for all
women with
hydrosalpinges prior
to IVF treatment
Johnson et al., March 2002(Cochrane Review). In: The
Cochrane Library, Issue 2 2002. Oxford: Update Software.

Unexplained Infertility

Expectant management (no

treatment) for up to three years
of trying should be considered,
taking into consideration the
woman's age.
RCOG Guidelines : GradeC Recommendation

Unexplained Infertility

The effective treatment for

unexplained infertility is
ovarian stimulation in
conjunction with IUI . If
failed IVF is recommended.
RCOG Guidelines : Grade A Recommendation