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19 February 2013

INFERTILITY
Dr. Vera
OUTLINE
I.
II.
III.
IV.
V.
VI.
VII.
VIII.
IX.
X.
XI.
XII.

Introduction
Diagnostic Evaluation
Ovulatory Dysfunction
Ovulatory Dysfunction Treatments
Ovarian Reserve Test
Multiple Pragnancy Risks
Cervical Factor
Uterine Abnormalities
Tubal Patency Test
Male Subfertility
Summary
Conclusion

Note: Minor rearrangements are done to facilitate smooth


discussion of the topic. - transcribers

INTRODUCTION
12% of all couples are childless
Monthly
pregnancy
rate
in
couples
with
unexplained sub-fertility after 18 months duration
is 1.5-3.0%.
Cumulative pregnancy rate for couples with
unexplained sub-fertility for 1 year and 3 years
after the first visit are 13% and 40% respectively
the shorter the duration of infertility, the higher the
cumulative pregnancy rate
Approximately 50% of healthy women become
clinically pregnant during the first 2 cycles, and
between 80% and 90% during the first 6 months.
Definition
Infertility is a disease defined as the inability to
achieve a pregnancy after a year of timed,
unprotected intercourse. Before, they were not
convinced that infertility is a disease. The latest
consensus guideline of the American Society of
Reproductive Medicine says that infertility is a
disease defined as the inability to achieve a
pregnancy after a year of time of unprotected
intercourse.
Primary infertility is the condition when no
pregnancy has been achieved in the past.
Secondary infertility is when there was a previous
pregnancy.
60% of the cause of infertility is attributed to the
female partner and 40% to the male partner.
Fecundability: conception rate usually per month
(normal: 20%; 38 years old with 3 years of
infertility 2%)
Fecundity: birth rate per month. the ability of a
woman to conceive per month
Etiology
Causes of infertility %
Female factor (single)
36
o Tubal factor
o Endometriosis
o Ovulatory dysfunction
o Diminished ovarian reserve
9

14
6
6

o Uterine factor
Male factor (single)
Other causes
7
o Immunologic problems
o Chromosomal abilities
o Cancer chemotheraphy
o Serious illness
o Unexplained cause

1
17

Maternal Age
The most important factor causing female
infertility
Fertility decreases with maternal age
AGE
<30%
30-35 years old
35-40 years old
>40 >90%

SUB-FERTILE %
25%
33%
50
>90%

Remember this: Women should have their first


pregnancy at an optimal age of 25 years of age
because the perimenopausal age of a woman starts
at 35 years of age. If you want to have a healthy
baby and if you want to get pregnant with just
one intercourse, have it when youre age 25. At
age 25, that is the peak fertility of the woman then it
suddenly drops.
Reproductive Ageing
Natural fertility rate by age

The joining organization from different countries shows


that the peak fertility of a woman is when she is 2125 years of age. When she reaches 31-35, there is a
sudden drop of fertility. When she reaches 36-40,
this starts her peri-menopausal years. When she is
about 41 the natural fertility rate of a woman is
almost zero until she reaches the age of menopause
which is 51 years of age. So please remember this,
do not delay your child bearing if you really
want to have a baby. Ofcourse the reason for you
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Ibana, Ilao, Isaac-Lim, Jacinto

getting married is not for procreation but


rather you are attracted to each other so
that if you dont have a baby, dont curse
yourself because God has reasons why he
didnt give you a child. Having a child is
not the right of the couple; it is a GIFT
from God.

by and as your child is growing you will see


that this is not your child; it is your sisters
child.
Sometimes
there
arises
the
psychological conflict to tell that this is not
your child. Some patients who undergo
assisted reproduction, we counsel them that
they have to tell their children how they
came forth to this world, either naturally,
spontaneously or by assisted reproduction. At
a certain age, you have to tell the child.

Even the live birth rate by age in in vitro


fertilization (IVF) cycle, we will know that the
highest live birth rate is achieved when the
woman is less than 35 years of age and it
gradually drops to the point that at 40, you
almost have about just 10% of having live
birth rate and at the time you reached 44 its
almost zero.

Even if you compare the oocyte of a woman at


age 40 using her own oocyte, you will know
that the live birth rate by age really drops.
But if you use a donor egg, the live birth rate
is the same even if you use about 43-45. This
comes to a point on what we call oocyte
donation but we dont do that. It is against
our faith and it is not a good option for
women to go for oocyte donation. So, have
your child when you are young. Do not use
the egg of another woman which you dont
even know, even your sister. Psychologically
youll accept it initially but as the times goes

DIAGNOSTIC EVALUATION
A diagnostic evaluation for infertility is
indicated for women who fail to achieve a
successful pregnancy after 12 months or
more of regular unprotected intercourse.
85% of couples maybe expected to achieve
a pregnancy within this interval without
medical
assistance
(spontaneous
pregnancy), however evaluation maybe
indicated for 15 minutes.
Earlier evaluation is warranted after 6
months of unsuccessful efforts to conceive in
women over age 35 years and those with
the ff. Conditions:
o History of oligo- or amenorrhea
o Known or suspected uterine/
tubal/ Peritoneal disease or stage
III-IV endometriosis
o Known
or
suspected
male
subfertility
If you have these conditions, please dont
wait for one year. Have your work-up
immediately within 6 months time from the
time you get married. Do not delay
evaluation and diagnostic work-up if you
have these conditions especially if your
girlfriend is already 35 years old.
Diagnostic evaluation should be done in a
systematic, expeditious, and cost-effective
manner so as to identify all relevant
problems that may have to be addressed
and to detect the most common causes of
infertility
History and Physical Examination
90-97% of a working impression in any
disease condition is based on a very good
clinical history and physical examination
The initial condition should be scheduled to
allow
sufficient
time
to
obtain
a
comprehensive medical, reproductive, and
family history and to perform a thorough
physical examination
This is also the opportune time to counsel
patients regarding preconception care and
screening for relevant genetic conditions
The initial visit should be done having both
husband and wife together. Dont do your
initial consultation without one of them.
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Ibana, Ilao, Isaac-Lim, Jacinto

Relevant History Includes the Following

Duration of infertility and results of any


previous evaluation and treatment.

Menstrual history (age at menarche, cycle


length, and characteristics, presence of
molimina(premenstrual syndrome), onset
and severity of dysmenorrhea) in a clinical
history lets say, you have a menarche very
early at the age of 9 you will expect an early
menopause. If she has dysmenorrhea
especially progressive of that, you suspect
that
this
woman
might
be
having
endometriosis.

Pregnancy
history
(gravidity,
parity,
pregnancy,
outcome,
and
associated
complications)

Previous methods of contraception Why?


As I said, secondary infertility involves that
the woman has had pregnancy before but
why is she having a difficult time to get
another pregnancy. Thats why it is
important to know the pregnancy history.
Most probably during the first pregnancy she
was delivered by caesarean section and
there were severe adhesions of the tubes to
the uterus thats now causing her inability to
get pregnant.

Coital frequency and sexual dysfunction.


Probably they are mating only once a month
and yet it is not the fertile period of the
woman. Or when the husband only comes
home every 1-2 years. Or the woman
doesnt even reach the climax.

Past surgeries (procedures, indications and


outcomes), previous hospitalization, serious
illnesses or injuries, pelvic inflammatory
disease, or exposure to sexually transmitted
infections.

Thyroid disease, galactorrhea, hirsutism,


pelvic or abdominal pain and dyspareunia

Previous
abnormal
pap
smears
and
subsequent treatment. you may have
severe dysplasia

Current
medications
and
allergies

antihypertensives can produce infertility in a


woman

Family history, of birth defects, mental


retardation,
early
menopause,
or
reproductive failure or compromise.

Occupation
and
exposure
to
known
environmental hazards sometimes the
husband is exposed to heat. The testicles
are like orchids. They have to be hanging
and they should be in the cold. In fact we
even advice our real patients that at home
they should only use boxer shorts and no
briefs because this is a cause of problem in a
decrease sperm count in the male.

Use of tobacco, alcohol, and recreational or


illicit drugs. baby might succumb early
because of decreased diameter of the head
or there might be some problems with the

neonate later in life. These should not be


taken if you want to have a healthy baby.
Physical Examination

Weight, body mass index, blood pressure


and pulse rate

Thyroid enlargement and presence of any


nodules or tenderness

Breast secretions and their character if a


woman is secreting milk even if she is not
pregnant,
you
have
to
rule
out
hyperprolactenemia or a pituitary gland
tumor.

Signs of androgen excess such as


production of excess hair around the lips,
hair in the axilla, hyperpigmentation around
the neck.

Vaginal or cervical abnormality, secretions,


or dischargeany infection in the woman
whether it is in the past, in the present, I
dont know in the future() contributes to
the cause of infertility.

Pelvic or abdominal tenderness, organ


enlargement, or masses.

Uterine size, shape, position and mobility

Adnexal masses or tenderness

Cul-de-sac masses, tenderness, or nodularity

OVULATORY DYSFUNCTION
Ovulatory dysfunction will be identified in
15% of all infertile couples and accounts for
up to 40% of infertility in women.
You may be anovulatory but you dont know,
but again, we need to go to the specific
menstrual history of the woman. A woman
who
menstruates
every
month,
the
probability that she is ovulating or releasing
the egg is very high! as compared to a
woman who is menstruating every 3
months, every 6 months, or once a year,
that woman is not ovulating any egg. All the
cycles mentioned are anovulatory.
Causes of ovulatory dysfunction:
1. PCOS or Polycystic Ovary Syndrome is
one of the foremost causes of infertility
among women.
2. Obesity
3. Weight gain or loss do you know that
athletes do not menstruate and they are
not ovulating? This is because of the
extreme effort/exercise. So dont engage
too much in badminton or in any sports
that will make you amenorrheic.
4. Strenuous exercise
5. Thyroid dysfunction if you have thyroid
dysfunction whether hypothyroidism or
hyperthyroidism,
you
will
not
menstruate.
6. Hyperprolactinemia if the prolactin
level is higher than 100 ng/ml, suspect a
macroadenoma or pituitary gland tumor.
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Ibana, Ilao, Isaac-Lim, Jacinto

She
might
have
some
visual
disturbances because the tumor is
already encroaching on the optic
chiasm. Now if it is less than 100ng/ml,
she has microadenoma which usually
responds to medical therapy.

Methods For Evaluating Ovulatory Dysfunction


Menstrual History
Body Basal History before, traditionally,
this was being used! but because of the
cumbersome method like when a woman
wakes up in the morning, the first thing that
she should do is to get a thermometer to
get her temperature. But the moment she
lifts her finger, that is no longer basal
because she has some movements already.
Biphasic
body temperature connotes
ovulation. But there are times when
a
woman is ovulating but the temperature is
still down why? Because she had some
movements before she was able to get her
temperature.
Short Luteal Phase the luteal phase in a
woman is about 10-14 days. If it is less than
that, then it is a short luteal phase and is
another problem/factor contributing to
infertility.
Progesterone level a week prior to onset of
menses is very important to determine
whether she ovulated or not.
Urinary LH there are several kits being
marketed today to see whether you will
ovulate or not. And then you have to do the
intercourse at the time the LH surge is high.
Endometrial Biopsy there are characteristic
changes during the time of ovulation.
However, this method is very invasive and at
the same time expensive because you need
a pathologist to interpret the endometrial
sample and so this method was abandoned.
Transvaginal Ultrasound we can actually
look on the growth of the follicle, the
collapse of the follicle, and see the follicular
fluid tripling down the pouch of douglas
very good signs indicating thatth ovulation
has taken place.
TSH, Prolactin, FSH, Estradiol. these are
not all for ovulation but for us to determine
later on if the womans cycle is ovulatory or
not.

Menstrual History

Ovulatory if regular and predictable,


occurring at intervals of 25-35 days, and
exhibiting consistent flow characteristics,
and accompanied by a consistent pattern of
moliminal symptoms.
Body Basal Temperature

Fertility 7 days prior to mid-cycle rise in BBT.


A
biphasic
BBT
indicates
ovulation,
monophasic anovulation.
Short luteal phase (<10 days of temperature
elevation) may identify women with more
subtle ovulatory dysfunction.
The test cannot reliably define the time of
ovulation and can become tedious, hence
not the preferred method for evaluating
ovulatory function in infertile women.

Urinary Luteinizing Hormone Test

Ovulation predictor kits can identify the


midcycle LH surge that precedes ovulation
by 1 to 2 days.

Results generally correlate well with the


peak in serum LH

However, accuracy, ease of use, and


reliability vary among products, and testing
may yield the false positive or false negative
results.(meaning urinary LuteinizingTest is
not a very reliable test for ovulation)
Endometrial Biopsy

Endometrial
biopsy
can
demonstrate
secretory endometrial development, results
from the action of progesterone and thus
implies ovulation.

Dating the endometrium was long


considered gold standard for evaluating
luteal function, but because it cannot
distinguish fertile from infertile women, it is
no longer use to test ovulation.
It has long been considered to be the gold
standard, but because it cannot distinguish
between fertile and infertile women, it is no
longer used to test ovulation.
Transvaginal Ultrasound

Transvaginal
ultrasound
can
provide
presumptive evidence of ovulation by
demonstrating progressive follicular growth,
sudden collapse of the pre-ovulatory follicle,
a loss of clearly defined follicular margins,
the appearance of internal echoes, and an
increase in cul de sac fluid volume.
Because of its accessibility, and also its
much cheaper than sending an endometrial
sample to the laborator. This is what we are
using now.
Other Evaluations

Serum Thyroid-Stimulating hormones (TSH)


and Prolactin determinations can identify
thyroid disorders and/or hyperprolactenemia
which may require specific treatment.

In women with amenorrhea, serum folliclestimulating hormone (FSH) and estradiol


measurements can distinguish women with
ovarian failure (high FSH, low estradiol) who
may be candidates for oocyte donation, from
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Ibana, Ilao, Isaac-Lim, Jacinto

those with hypothalamic amenorrhea (low or


normal FSH, low estradiol) who will require
exogenous gonadotropin stimulation for
ovulation induction.
In anovulatory infertile women, who fails to
be pregnant after 3-6 cycles of successful
ovulation induction should be viewed as an
indication to perform additional diagnostic
evaluation, or if evaluation is complete to
consider alternative treatment.
So you dont have to wait for so long or for
centuries before you can say Oh you wont
get pregnant. Its 3-6 cycles only! And if
she doesnt respond or produce eggs or
ovulate, then it is an indication that you
have to do further testings OR you have to
consider
alternative
treatments/optios
already which include what? Assisted
Reproductive Technology (ART) that uses In
Vitro
fertilization,
embryo
transfer,
Intracytoplasmic Sperm Injection.
OVULATORY DYSFUNCTION TREATMENTS
Treat
endocrine
abnormalities:
bromocryptine: thyroid replacement.
if youre able to point out that theres an
endocrine
abnormality
such
as
hypothyroidism/hyperthyroidism
(give
thyroid replacement) or hyperprolactinemia
(give bromocriptine).
Induce ovulation:
o Note fertility drugs used in nulligravid
women is associated with borderline
serous tumor but not with invasive
histologic subtypes. (Ness et. al 2002)
o Drugs used to induce ovulation:
clomiphene citrate, glucocorticoids
recombinant FSH, Letrozole.
CLOMIPHENE CITRATE
Available
as
3:2
ratio
of
two
triphenylethylene
derivative
geometric
isomers given for 5days starting day 3 or 5
of cycle.
o Do not give it after day 5, it is past
recruitment phase
o After day 5, selection phase
o Day 9, dominant follicle already in a
normal spontaneous cycle
o In patients with Polycystic ovaries:
1st line: clomiphene citrate, 2nd line:
gonadotropins,
3rd:
laparoscopy
(ovarian drilling), 4th line: embryo
transfer IVF,
Body weight and hyperandrogenemia are the
predominant predictors for ovulation after
CC whereas age and cycle history dictates
pregnancy chances in ovulatory women
(Imani at al, 1999)
o Actually, Frontliner: REDUCE! Loss
of 10% of total body weight of the
woman and you will note that she

Ibana, Ilao, Isaac-Lim, Jacinto

will menstruate spontaneously and


with regular periods, she is ovulating
already
o Difficult to lose weight so add
insulin sensitizing agent, Metformin
hydrochloride, start at 500 mg/day,
increase to twice a day, until 1.5
g/day total.
Ovulation rate by dose: 50mg (52%), 100mg
(22mg), 200mg (7%), 250mg (5%). (Gysler
et al, 1982) - Only dose that will cause
ovulation is 50 mg, NO USE TO INCREASE
DOSAGE. If she doesnt improve with such
dose then good bye, you have to try another
alternative treatment.
Clomiphene Citrate Failure vs. conception
(Inami et al1999)
o Age (<30 increasesfecundity by
10%)
o Cycle
history
(amenorrhea
increases fecundity by 46%
o Baseline pregnancy rates of 12% in patients with unexplained
infertility may be enhanced by 24 per cycle with CC (Hughes et al
2002)
o 2/3 of patients conceived within
the 3 ovulatory CC treatment
cycle.
o Irreversible visual changes with
CC are rare.

LETROZOLE (Femara@)

Reduces
FSH
dose
and
eliminates
antiestrogenic
effect
of
CC
on the
endometrium. Pregnancy rate equivalent to
FSH only.

Given at 5mg, starting day 3-7 and FSH


injection 50-150 IU/day starting on day 7
until the day of HCG 10,000 IU.

Letrozole 75% ovulation, 25% pregnancy


rate.
o Day 3-7, this is the recruitment phase
o You get as much follicles in the phase
and then there is selection on how many
will be dominant
o Then you give your FSH injection,
because this is orally given, this one is
injectible, parenteral, 50-150 IU starting
on day 7 until the day of your HCG
injection.
Glucocorticoid

steroid treatment appear to be related to


suppression to excessive androgen levels
(Steinberger et al, 1979)

increases pregnancy rate to 75% in


clomiphene resistant patient (Daly et al1984,
Parnanezhad et al 2002)

Treatment of infertility usually does not make


the difference between conceiving and not
conceiving:
the
difference
lies
in
Page 5 of 11

conceiving sooner rather than later. The


risk of the sooner option in terms of multiple
pregnancy,
ovarian
hyperstimulation
syndrome, emotional stress, and financial
costs may be unacceptably high. - So you
have to make them pregnant right away!

OVARIAN RESERVE TEST


The concept of ovarian reserve views
reproductive potential as a function of the
number and quality of remaining oocytes.
As I showed you awhile ago that when a
woman reaches the age of 35, the number
of the quality eggs and the functional
capacity of the ovary to produce these
good eggs really goes down. Its like a
slide! You are on the top and then you
abruptly drop in terms of the number of
quality eggs as a woman reaches the age of
35.
Decreased or diminished ovarian reserve
(DOR) describes women of reproductive age
having regular menses whose response to
ovarian stimulation or fecundity is reduced
compared to those women of comparable
age.

Aims of Ovarian reserve Testing(Brockmanns et al.


2006)

Identify women at risk for poor response


because you have to induce ovulation to
them and when you see that the ovarian
reserve is really bad, no matter how much of
the fertility drugs that you will give to these
women, they will not produce or have good
responses.

Identify women with good prognosis if the


ovarian reserve is still okay then you can
induce ovulation to these women.

Data should inform us beyond age alone is


there a problem to this woman even if she is
35, how come there is already diminished in
the number of the ovarian reserve?

the ovulatory follicle. As they grow, only one


dominant follicle is given the chance to be
released. This is in a normal cycle.

Ovarian
Reserve
Test
measures
the
primordial follicle pool, the growing follicle
population, and it can also tells us/detects

Indications For Ovarian reserve testing


Women over age 35 years - So if youre 35
now, and youre planning to get pregnant
next year, have an ovarian reserve testing.
Have a family history of early menopause An early menarche is equated to an early
menopause.
Have a single ovary or previous ovarian
surgery, chemotherapy, or pelvic radiation
therapy
Unexplained infertility
Poor response to gonadotropin stimulation
Those for assisted reproductive technology
Remember this, if youre patient has one of
these categories, strictly subject them to
ovarian reserve testing.
Ovarian reserve Tests
Day 3 FSH and estradiol measurements
Clomiphene citrate challenge test
An early follicular antral follicle count (via
transvaginal ultrasound)
Serum anti-mullerian hormone (AMH) level
This is the latest! And all these things that I
am telling you are just being released by the
American Society of Reproductive Medicine
published in January of 2013. So very
recent! We are in February pa lang. You are
updated as far as infertility is concerned.
(Tayo na ang updated yey! )
Day 3 FSH and Estradiol Level
FSH values of 10-20 IU/L have been
associated with both poor ovarian response
and the failure to conceive. - So lets say this
is your day 3 of menstrual flow and youre
already doubting whether youll get
pregnant or not, then have your FSH taken.
If it turns out to be about 10 then oh my God
you have to rush!!!
Assays standardized against WHO 2nd
standard demonstrate high specificity (83100%) for predicting response to stimulation
defined as (<2-3 follicles or < than 4
retrieved oocytes) - So if you have 2-3
follicles and you will give fertility drugs then
that would be a poor response. And if its
less than 4 oocytes then that is also a poor
response. Because we still dont know the
qualities of the eggs, then we should be
more objective, more investigations, and
sometimes the eggs that we get are
fragmented.
Basal estradiol alone should not be used to
screen for DOR (Diminished Ovarian
Reserve). - It should be coupled with your
Day 3 FSH.
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Ibana, Ilao, Isaac-Lim, Jacinto

The test has value only as an aid to correctly


interpret a normal basal FSH.
When the estradiol level is elevated (>60-80
pg/ml) with a normal basal FSH, there is
limited evidence for an association with poor
response, increased cancellation rates and
lower pregnancy rates. - So you dont use
estradiol level alone to predict the ovarian
reserve of a woman. It is then not accurate.
It is measured coupled with your basal FSH.
Clomiphene Citrate Challenge Test
The CCCT involves measurement of serum
FSH before and after treatment with
clomiphene citrate (100mg/day) from days
5-9 typically on days 3-10.
Elevated
FSH
concentrations
after
clomiphene administration suggests DOR.
Day 10 FSH levels have higher sensitivity
and lower specificity compared to day 3 FSH
Antral Follicle Count (AFC)
Antral follicles measuring 2-10 mm in both
ovaries during the early follicular phase of
the cycle observed with transvaginal
ultrasound is predictive of ovarian response.
AFC of 3-10 in both ovaries is associated
with poor response and with failure to
achieve a pregnancy.
The newest ovarian reserve testing that we
are using now. In fact this is the most
accurat, but you will see later that this test
is being challenged by your Anti-Mullerian
Hormone Level.
So per ovary you should have at least 15
antral follicle count plus the ovary 15 so a
total of 30 and this will tell you that the
ovarian reserve of a woman is not low.

ANTRAL FOLLICLE COUNT

AFC: which cohort to measure

Prediction of poor response


Antral
follicle
size (mm)
2-5
2-6
2-8
2-10

This is actual
SONO-AVC, you can color code the follicle.
And you will able to see all the follicles and
count them. It takes about 20 seconds to
measure them.
ANTRAL FOLLICLE COUNT: 3D method

There was a cohort study of what follicular


size should we put together in order for us to
really count the exact number of follicles per
cycle. And all of these contributors said that
the accuracy of antral follicle count is best
read when you measure 2-10mm size of
follicles.

Odds ration
(mean & 95%CI)
0.658 (0.4970.871)
0.693 (0.5630.868)
0.701 (0.5720.858)
0.749 (0.6350.884)

Pvalue

AUC

<0.01

0.812

0.001

0.829

0.001

0.852

0.001

0.826

When you measure 2-10mm the prediction


of poor response shows higher results.

AFC Reproducibility: 2D vs 3D

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Ibana, Ilao, Isaac-Lim, Jacinto

each follicle according to color and size and


you will be able to track all the follicles. Lets
say a 10mm is color green and 8mm is
orange and 5 mm is yellow. So you will be
able to count how many follicles and of what
diameter they are. And this would make our
follicle monitoring even

W
hat is the reproducibility of 2D vs 3D using
AFC? Of course it will be higher. The
confidence interval is higher when you use
3D.

AFC validity: 2D vs 3D

What is the validity of AFC using 2D vs 3D


vsSono AVC? The validity increases as you
shift from 2D to 3D to Sono AVC. So
theonfidence interval increases.
SonoAVC (Sono-Autonomic Volume Calculation
Count)

Is a new software program that identifies


and
0.15%
Singleton (General
prevalence)
1.3%
Twins
8%

Triplets

43%

Quadrulets

quantifies hypoechoic regions within a 3-D


dataset and provides automatic estimation
of their absolute dimension, mean diameter,
and volume.
Each individual volume is given a specific
color and are displayed in descending order
from the largest to the smallest.
An unlimited number of volumes can be
quantified which make it an ideal tool for
follicle tracking.
To date it has been used to assess
stimulated ovaries only.
(S. Deb et al. Ultrasound ObstetGynecol
2009)
Sono AVC can be used only in stimulating
cycles. This is new software that identifies

Anti-Mullerian Hormone (AMH) Level


AMH is produced by the granulosa cells of
early follicles, are gonadotropin independent
and therefore remain relatively consistent
within and between cycles in both normal
young ovulating women and in women with
infertility. Therefore, it can be measured on
any day of the menstrual cycle.
An AMH level of <1ug/ml has been
associated with poor responses to ovarian
stimulation, poor embryo quality and poor
pregnancy outcome in IVF.
What is the edge therefore of AMH against
AFC? You can get the level anytime. We
dont have to refer to the cycle of the
woman. So even if shes already in midcycle
or in the secretory phase or follicular phase,
you can already get the level of AMH. That is
the only benefit because you dont prepare
the woman and you are able to categorize
this woman early saying that her reserve
has been diminished. Whereas in AFC, you
wait for the early follicular phase of the
cycle.
In our country, theres only one institution
who offers AMH and that is Global City! And
the cost is also high but, it will give you an
accurate estimate of ovarian reserve of a
woman. Im directing you to a right place,
because if you keep on doing FSH (which is
also alright) but the certainty of the test per
laboratory is not equally accurate.
MULTIPLE PREGNANCY RISKS
Cerebral Palsy incidence in multiple
pregnancies

o
o

(Yokohama
Shimizu, 1995)
We dont want multiple pregnancies,
why? Because of the incidence of
cerebral palsy.
Higher multiplicity, higher incidence of
CP (you give them a child, but theyre
not healthy and you have an
obligation to take of that child despite
that)
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Even in singleton pregnancy, there is a


risk for CP, what more for triplets,
quadruplets, etc.

CERVICAL FACTOR
Abnormalities of cervical mucus production
or sperm/mucus interaction are rarely the
cause of infertility
The post coital test used for this interaction
is no longer recommended for the evaluation
of infertile couple because of its subjectivity,
has a poor reproducibility and inconvenience
to the patient.
o Before, they thought that a post coital
test, cervical mucus and interplay of the
sperm is a very important test but its so
cumbersome to do ask couple to
mate at home 2 hours after, ask them
to go to clinic to check if the sperm has
entered the cervix because the
cervical mucus might be hostile to the
sperm
o Test is abandoned because it is
inaccurate!
UTERINE ABNORMALITIES
Uterine abnormalities are not common
causes of infertility but has to be excluded.
Evaluation
of
the
uterus
include:
hysterosalpingography
(HSG),
ultrasonography,
sonohysterography,
hysteroscopy - you look inside the
endometrial cavity.
These
procedures
define
uterine
developmental anomaly (septate, bicornuate
and unicornuate) acquired anomalies such
as
polyps,
submucousmyomas
and
synechiaes.
Even young ones now, we are seeing polyps,
I dont know what is happening Dr. Vera
TUBAL PATENCY TEST
Evaluation of tubal patency is a key
component of the diagnostic evaluation of
the infertile women.
Methods used to evaluate the tubes are:
hyterosalpingography (HSG) this is x-ray,
saline infusion sonography (SIS) this is by
ultrasound and laparoscopy when you look
inside the pelvic cavity.
All these methods have technical limitations
that must be considered when interpreting
test results.
It is important that the one doing these
procedures must be adept at doing them or
else youll get false results.
Tubal Patency And Uterine Abnormalities
Ultrasound:
look
for
fibrinoids/polyps,
location of ovaries, hydrosalpinx.

Sonohysterogram or flexible hysteroscopy to


assess uterine cavity.
Laparoscopy
for
pelvic
adhesions,
hydrosalpinx - remove or clip if present
because it reduces pregnancy rate by 50%
and increases spontaneous abortion 2x fold
(Camus et al 1999).

Mechanism Of Adverse Effect Of Hydrosalpinx


Decrease nutrients in hydrosalpinx fluid
Toxic effect of fluid on embryos and or sperm
(Schadvev et al 1997, Ng et al 2000).

Wash out effect from fluid

Increase endometrial peristalsis due to


hydrosalpinx fluid
Therefore,
you
HAVE
TO
REMOVE
HYDROSALPINX especially if scheduled for
IVF!

Uterine Abnormalities Treatments


Hysteroscopic
resection
of
septum,
submucosal leiomyoma, polyp if > 0.5cm.
Laparotomy for removal of multiple myomas
- now you can do them via laparoscopy even
with multiple/plenty of myomas
Endometriosis
Endometriosis is the presence of ectopic
endometrium in all places in the pelvic
cavity or even the lungs, colon, bladder, etc.
Medical therapy: suppressive not curative
o Given for a long period of time
o GnrH agonist: give it only for 3-6
months, you cannot give it further
because it decreases mineral bone
density, you give it with estrogen as an
adjunct therapy
Surgical therapy: reccurrence, 5-20% per
year; 40%/year after 5 years.
o Even after removal of uterus or ovaries,
the presence of ectopic endometrial
implants in the pelvic cavity can still
cause adenocarcinoma in your patient
even without her uterus/ovaries
o Do not give estrogen to your patients
who suffer from postmenopausal
symptoms because of surgical removal
of ovaries because endometriosis is an
inflammatory process that is estrogen
dependent.
You
can
give
you
progestins or combined.
Chlamydia Antibody Test (Cat)
The CAT test has limited value as compared
to laparoscopy for detection of tubal disease
which is the pathology associated with
chlamydia infection.
Laparoscopy is better because the attack of
chlamydia is in the tube!
Peritoneal Factor
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Ibana, Ilao, Isaac-Lim, Jacinto

Peritoneal factors such as endometriosis,


and pelvic or adnexal adhesions may cause
or contribute to infertility.
Laparoscopy, with direct visual examination
of the pelvis is the only method of choice to
diagnose peritoneal factors that may cause
infertility.
MALE SUBFERTILITY
Male factor is solely responsible in
approximately 20% of sub-fertile couples
and contributory in another 17%
Causes of male factor sub-fertility can be
divided in four main areas:
o Idiopathic (40-50%)
o Testicular (30-40%)
o Post-testicular (10-20%)
o Pre-testicular (1-2%)
Evaluation Of The Male

History and Physical examination

Semen analysis

Decrease count, Decrease motility, Decrease morphology

Hormone Treatment,

Azoospermia

Sperm EnhancementTesticular Aspiration

*GOLD STANDARD: Semen Analysis!

Dont give hormone treatment now, we just


enhance the sperm by double washing it
with an equal amount of your human tubal
fluid and putting it in a water bath after the
3rd washing and wait for the sperm to swim
up only the sperm that swims up will be
given to the partner
EVALUATION OF THE INFERTILE MALE
Semen analysis is the cornerstone of
laboratory evaluation of the male factor
Accepted reference values for semen
analysis done on at least 2 occasions:

Ejaculate volume: 1.5 mL


pH: 7.2
Sperm
concentration:
15M
spermatozoa/mL
o Total
sperm
number:
39M
spermatozoa/ejaculate
o Percent motility: 40%
o Forward progression: 32%
No good if it swims around and
around!
o Normal morphology: 4%
o Sperm agglutination: absent
o Viscosity:
<2cm
thread
postliquefaction
Endocrine evaluation is indicated for the
following:
o Sperm concentration is < 10
million/mL
- You have to do karyotyping in this
patient
o Impaired libido or sexual function
A post ejaculatory urinalysis is indicated for
men having an ejaculate volume of < 1.0
mL,
except
those
diagnosed
with
hypogonadism.
Trans-rectal
ultrasonography
for
the
diagnosis of ejaculatory duct obstruction is
indicated for men with azoospermia,
palpable vasa and low ejaculate volume.
Men with non-obstructive azoospermia or
severe
oligospermia
should
have
karyotyping and Y chromosome analysis
before
doing
intracytoplasmic
sperm
injection (ICSI).
o
o
o

Goals Of Evaluation
Goals are to identify:
o Potentially correctable conditions
o Irreversible conditions that are
amenable to ART
o Life or health threatening conditions
that may underlie the sub-fertility
and require medical attention.
o Genetic abnormalities that may
affect the health of offspring if ART is
used.
Total Count
If 10-20 million intrauterine insemination
(IUI) may be of help
5-10 million in vitro fertilization (IVF)
< 5 million - ICSI

ABNORMAL
PARAMETERS
<10 M/mL
<20% motility
<1% normal
morphology
AZOOSPERMIA

FURTHER
TESTS
Karyotyping

MANAGEMENT
IUI
IVF

FSH,
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Ibana, Ilao, Isaac-Lim, Jacinto

dec. FSH, dec.


testosterone
*normal FSH,
dec.
testosterone
Normal FSH,
normal
testosterone
1. Obstruction
2. Congenital
absence of
vas

testosterone
Karyotype
Testicular (+)
sperm
Biopsy:
(-)
sperm

Gonadotropins
IVF + ICSI
Donor
insemination

Cystic fibrosis
testing

Surgical
Correction
Epididymal
sperm aspiration
(TESA, MESA)

prior to IVF-ICSI

*hormones responsible for problems in males:


FSH, testosterone (so you have to measure
them)

SUMMARY
The more complex dilemma for clinicians
managing infertility is the need to define the
scope of the infertility issues and to
determine what problems can be realistically
managed.
Care for infertile patients is a challenging
commitment but can also be a very
rewarding feature of an obstetrics and
gynecology practice.
CONCLUSION
A careful history and physical examination
can identify a specific cause of infertility and
help to focus the diagnostic evaluation on
the most likely causes.
A committee opinion of the ASRM published
in 2012, August Steril. Fertility J.

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Ibana, Ilao, Isaac-Lim, Jacinto

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