Unexplained Infertility 2009 (Assisted Reproductive Technologies)

Goals and Objectives
Understand
Unexplained Infertility
Evaluate Right
Diagnostic Approach
Management

The etiology of your infertility is due to
an auto-deletion of the Sxrb gene in the
Prospermatogonia cell ine. But not to worry,
With the re-insertion of the deleted gene
Using the eletroporation system your
Spermatogenesis will be fully restored
in no time.
Thanks to the extreme
genetic research
In rodent models

Ovulatory disorders - 20 – 30 %
Tubal Damage - 20 - 35 %
Sperm dysfunction - 10 – 50 %
Endometriosis - 5 - 10 %
Cervical mucus problems - 5 %
Coital dysfunction - 5 %
Unexplained Infertility - 10 – 25 %
Sub fertility in both partners –
30 – 50 % couples
Anu Test Tube Baby Centre

One of the most
frequently made
diagnosis
Diagnosis is one
of exclusion

Is It ‘Unexplained’ Or
‘Undiagnosed’ ?
Reaching specific diagnoses can be
difficult
Multifactorial Infertility
Failure to detect one or more presumed
causes

Validity of Diagnostic Testing
According to ESHRE –
tests divided into 3 categories
Those with „established correlation‟ with the
occurrence of pregnancy
conventional semen analysis
tubal patency tests
tests of ovulation

Those „not consistently‟ showing correlation
Post coital test
Antisperm antibody tests
Zona free Hamster egg penetration test

Those „apparently not correlating‟ with the
occurrence of pregnancy at all
Endometrial biopsy
Varicocele assesment
Chlamydia testing

Unexplained Infertility-

Putative Causes
Sperm & egg
transport or
interaction
Embryonal
development
Implantation
failure
Post-implantation
pregnancy loss

Potential
Difficulties
Ordering correct tests
Performing tests
appropriately &
Correct interpretation
A specific cause of
infertility is never
certain
Initial diagnostic
work ups should
encompass both
partners

Non-diagnosis of UI
Medical conditions
contributing often to
non-diagnosis of
Endometriosis
Tubal disease
Prematurely ageing
ovaries
Sub-clinical
autoimmune disease Anu Test Tube Baby Centre

ENDOMETRIOSIS
Prevalence remains
controversial
As low as 5 – 10 %
As high as 30 – 50 %
Accurate diagnosis can be
difficult
Mild endometriosis can affect
normal function, as well as
other reproductive processes
Endometriosis affects
IVF outcomes in all
aspects Anu Test Tube Baby Centre

Tubal Disease HSG
Less accurate in detecting
and evaluating tubal disease
than laparoscopy
Poorly suited to assess distal
tubal disease and peritubal
disease
Laparoscopy & Hysteroscopy
To evaluate for unexplained
tubal and uterine disease

Prematurely ageing Ovaries
30 – 31 yrs.
37 – 38 yrs.
51 yrs.
Subfertility
Critical point
reached with approx
25,000 follicles
remaining
Follicular count
reaches 1000
Follicles continue to decline from birth

PAO
Accelerated decline in
fertility at age
37 – 38 yrs – 25,000
follicles
51 yrs – menopause,
1000 follicles
Time period between
accelerated decline
in fertility is fixed
at approx. 13.5 yrs
Normal Decline 25000
Accelerated
Decline
Early
Menopause

10 % women experience early menopause before
45 yrs of age & 1 % - before 40 yrs age.
Signs of PAO
Age atypical resistance to
ovarian stimulation
Elevated FSH
Low AMH
Low AFC
F/H of early menopause
IVF
Follicular output in IVF –
diagnostic test for ovarian
function
PAO

Subclinical Autoimmune
Disease
Controversial
association
Preclinical stage of
autoimmune disease
demonstrate decreased
fecundity
Antiphosphatidyl
choline significantly
increases
Statistically well
established association-
to ignore would appear
intellectually dishonest

Treatment
• In absence of
specific medical
cause –
specific
treatment
lacking
• Treatment
empirical

Factors Influencing
Treatment
Age
Duration of
Infertility
Treatment efficacy
Side effect profile
Cost
 Multiple pregnancy

PRINCIPAL TREATMENT OPTIONS
Expectant observation with
Timed intercourse &
Life style changes
CC + IUI
CC + HMG + IUI
IVF
Individualize treatment for a
successful outcome

SPONTANEOUS PREG. IN
UI
COUNSELLING
Probability of Live-birth
Informed decision about
‘to pursue or not to’
Factors to be considered
Age, Cost of
treatmnt,Side effect,
Chance of conception
with treatment
without treatment

Fecundity in general –
85 – 90 % in 1yr

AGE FACTOR
Older women – “don‟t have
unexplained infertility”
Spontaneous pregnancy rates –
much lower

Role Of Obesity
 BMI > 30 - odds of subfertility
- ed risk of miscarriage and
adverse pregnancy outcome
 High risk of subfecundity
- with both members obese
 Treatments less successful & losing wt. increases
chances
 Aim for BMI of 20 – 25 % with balanced diet and
regular exercise

Timing Of Intercourse
0 – 6 days prior to ovulation-Higher
chances
Normal sperm densities with short
abstinence (2 d)
Highest sperm conc. In daily ejaculates –
even in oligospermia men
Frequent IC from 1 – 2 d encouraged

Use Of Lubricants
Water based
lubricants & olive oil
Canola oil, mineral
oil & hydroxyethyl
cellulose based
lubricant
Inhibit sperm
viability
Do not inhibit
sperm viability

Other Lifestyle Choices
Avoid High amounts caffeine (i.e., 5 cups) –
No effect with 1 – 2 cups / day
Smoking
risk of infertility & miscarriage
sperm parameters
Preconception folic acid –to prevent NTD

Role Of Agents
CC alone
CC + IUI
Options
Cost
Female partners
age
Female partner‟s
age
Duration of
infertility
Factors
to
Consider

CC + IUI
• Superior to spontaneous
attempts in UI > 2yrs
duration
• Increasing female age and
poor semen parameters -
Lower success rates More
aggressive treatment
warranted

Adjuvant effect of
preovulatory pertubation + IUI
Lignocaine 0.1
mg/ml in
balanced salt
solution
Reduces sperm
phagocytosis
preg. rates

Limiting Multiple Births
Multiple birth rate with HMG – 15 %
RISK FACTORS
 High initial Gonadotrophin dose
 Large no. of mature follicles (>15 mm) &
 1st stimulation cycle
 To reduce risk of multiple birth
 1 Stimulated follicle should be the goal &
 2 Follicles may be accepted after careful patient
counseling

Stimulation Protocols
Mild
stimulation
To prevent LH
surge
Combination
protocol
CC with HMG More cost
effective
Fewer injections
Gonadotrophins
+ GnRH – 17
%/cycle
Preg. Rate with
Gonadotrophin
alone – 11 %/cyc
GnRH
antagonists +
HMG protocol

*
• 38 – 39 yrs –
6.1 % live
birthrate /
cycle
• No live births
after 2nd cycle *
*
• ≥ 40 yrs –
2 % per
cycle
• No live
births after
1st cycle
Success Rates in HMG + IUI
cycles:- 38 – 40 yrs.
Women over 40 yrs should be considered for IVF
after 1 failed IUI cycle

CONVENTIONAL VS
ACCELERATED TREATMENT
CONVENTIONAL
TREATMENT
3 cycles of CC with
IUI
3 cycles of
Gonadotrophin with
IUI
≤ 6 cycles of IVF
ACCELERATED OR FAST
TRACK TREATMENT
3 cycles of CC + IUI
IVF
Median time to preg.
3m. faster
Couples in accelerated arm conceived more quickly
than those in conventional arm

Summary
„Absence of evidence is not an evidence of absence‟
Thorough and time efficient investigations
Treatments to be individualized
Expectant management
Low cost
Lowest cycle fecundity rate
Option in young women and with good ovarian reserve
IVF
Most expensive
Most successful treatment
Treatment of choice when less expensive and simple modalities failed

Summary (cont.)
 Progress from low tech to high
tech options
 Definite need for multicenter trials
to identify best treatment option
in Unexplained infertillity

Unexplained Infertility 2009 (Assisted Reproductive Technologies)

Unexplained Infertility 2009 (Assisted Reproductive Technologies)

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