Transcript Understanding Infertility Basic Sciences

Understanding
Infertility
Basic Sciences
A/Prof R Gyaneshwar
FRANZCOG, MH.Ed
Clinical Director of Obstetrics & Gynaecology
Liverpool Health Service
Conjoint Associate Professor
University of New South Wales
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Acknowledgement

Dr Antony Lighten – IVF Australia

Dr Derek Lok – Sydney IVF
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Reproductive Physiology
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Blocked or damaged
Fallopian tubes eg
Ectopic pregnancy
Fibroids
Endometriosis
Miscarriage
Polycystic
Ovarian
Syndrome
Failure of
Ovulation
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Causes of Infertility
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The Causes of Infertility and
their Approximate Frequency
(adapted from Hull et al 1985)
Causes
Frequency %
Sperm defects or dysfunction
30
Ovulation failure (amenorrhoea or oligomenorrhoea)
25
Tubal infective damage
20
Unexplained infertility
25
Endometriosis (causing damage)
5
Coital failure or infrequency
5
Cervical mucus defects or dysfunction
3
Uterine abnormalities (eg fibroids or abnormalities of
1
shape)
15% of couples have more than one sub-fertility factor
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Infertility
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Definition
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12 months of attempting to conceive
Incidence 1 in 6 couples
 Incidence increases with age
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Natural Cumulative Pregnancy
Rate
24
90
80
% pregnant/month
70
60
5
50
8
10
12
4
40
3
30
20
6
7
9
11
2
1
10
0
1 2 3 4 5 6 7 8 9 10 11 12
24
Months of trying
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Natural Pregnancy Rate
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Ovarian Reserve
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Anovulation
LHRH
Hypothalamopituitary
WHO Type 1:
Hypogonadotrophic
Nearly everyone conceives
LH FSH
Anovulation
WHO Type 2:
Normogonadotrophic
Most women conceive
Ovarian failure
WHO Type 3:
Hypergonadotrophic
Conception remote chance
without donated oocytes
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The Clues
LHRH
Amenorrhoea
Weight loss/Exercise/Stress
Drug-induced
Other disease
LH FSH
Irregular menses
Weight gain
PCOS signs/symptoms
Hot flushes
Irregular/absent periods
Short cycle
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Ovulation Tests – Luteal Progesterone
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Tubal Factor
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Peristalsis
Ciliary dysfunction
Narrowing
Blockage
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Lap / Dye
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Ectopic
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Pelvic Infection and Tubal
Disease
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Pelvic Infection and Tubal
Disease
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Endometriosis
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Minimal / Mild Endometriosis
Monthly fecundity rate 6.1 (laparoscopic surgery) vs 3.2 (diagnostic laparoscopy) per 100 person month
The Canadian Collaborative Group on Endometriosis 1997 NEJM 337:217
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Hysteroscopy
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Septate uterus
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Congenital Anomalies
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Blocked/absent vas deferens
Low sperm
numbers and/or
poor sperm
movement
High numbers of
abnormal shaped
sperm
Antisperm
antibodies
Failure of sperm
production
Erectile dysfunction
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Male Factor
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Primary Testicular Disease
Most common cause of male factor infertility
 Aetiology
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66% unknown
 20% testicular maldescent
 7% trauma and torsion
 5% Klinefelter’s Syndrome
 1% mumps orchitis
 1% chemo
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Male Factor
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Endocrine causes
Hyperprolactinaemia
 Hypogonadotrophic hypogonadism
 Hypothrooidism
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Rare
 Present with sexual dysfunction
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Sperm Count
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Volume
2 – 5 mls
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Density/Concentration
> 20 mill/ml
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Motility
> 50%
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Morphology
> 14% normal
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Male Infertility
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Semen Analysis (WHO 1999)
3 days of abstinence, collection technique, 72
days for sperm to be ejaculated
 Vol > 1 ml
 Concentration > 20 x 106 / mL
 Motility > 50%
 Morphology (WHO Strict Criteria 99) > 15%
normal
 Note: SA best performed in andrology lab; If
abnormal always repeat
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Sperm Count Variation in a
Healthy Man
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Important Concepts
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Age
Duration of infertility
Primary versus secondary infertility
Multiple causes of infertility
Sub-fertility versus sterility
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History
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Duration
Previous pregnancies
Wt / Ht / BMI
Full menstrual history
Androgenising signs
Pelvic pain
Previous investigations
Past medical history
Past surgical history
Medications / cigarettes / alcohol
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History
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Previous paternities
Sexual dysfunction
Mumps / STD
Trauma
Undescended testes
Previous investigations
Past medical history
Past surgical history
Medications / cigarettes/ alcohol
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RANZCOG Statement
C-Obs 3 March 2004
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Tests recommended at the first antenatal visit of
each pregnancy:
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Blood group and antibody screen
Full blood examination
Rubella Antibody status
Syphilis serology
Hepatitis B serology
Midstream urine examination by culture: eg dipslide
HIV serology
Hepatitis C serology
Cervical cytology
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Prognostic Factors
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Age
Duration of infertility
Primary versus secondary infertility
Multiple causes of infertility
Sub-fertility versus sterility
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Duration of Infertility
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The longer the duration of infertility, the
greater the likelihood of a cause of
infertility; ie the less likely that the situation
is due to bad luck
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Treatment is more successful in patients
where a specific treatable cause is found
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Prognosis
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Effect of Multiple Minor
Abnormalities
Number of
Factors
Monthly
Chance
% Pregnancy Mean Years
in 2 years
to Pregnancy
0
20%
93.6
0.3 (4m)
1
5%
63.8
1.5 - 2
2
1%
20.7
7
3
0.2%
4.7
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Investigations
Tubal Patency
HSG
Lap & Dye
Ovulation
Midluteal P4
Testosterone, TSH,
Prolactin, LH, FSH as
indicated
Rubella, Varicella
Hep B, C, HIV, VDRL
Semen Analysis
LH, FSH, Prolactin as
indicated
Karyotype
Hep B, C, HIV, VDRL
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Hormone / Ovulatory Tests
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Day 2-3 hormones
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FSH, LH, Oestradiol
Testosterone, SHBG
Others:
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17-OH P, DHEAS, Androstenedione, cortisol
TSH, prolactin
75g GTT & fasting insulin
Luteal Progesterone
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7 days prior to estimated date of period if regular
If irregular, start 7 days prior to shortest cycle date
and repeat every 5-7 days till next period arrives
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Treatment Options
Advice
Assessment
OI
Ovulation Induction
IUI
Intrauterine Insemination
IVF
In Vitro Fertilisation
ICSI
Intra Cytoplasmic Sperm Injection
SSC
Surgical Sperm Collection
Donor
Sperm, Eggs or Embryos
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Ovulation Induction
PCOS
1st line
Clomiphene – 60% pregnant after 6 months
2nd line
Metformin
FSH
Surgical Ovarian Drilling
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Ovarian Drilling
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Ovarian Induction
Hypothalamic amenorrhoea
FSH
Pulsatile GnRH
Hyperprolactinaemia
Carbergolide
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Intrauterine Insemination
Indications
Unexplained
Mild male factor
Success/Cycle
Natural 10-15%
Stimulated 15-20%
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In Vitro Fertilisation
Indications
Prolonged unexplained
Tubal factor
Severe male factor
Unsuccessful OI / IUI / fertility surgery
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In Vitro Fertilisation
Success / Cycle
40 – 5-%
Single embryo transfer
Now gold standard
Twin rate 1%
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Sperm Preparation
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Day surgery for egg collection
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IVF
(In Vitro Fertilisation)
ICSI
(Intra Cytoplasmic Sperm Injection)
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IVF (In Vitro Fertilisation
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ICSI (Intra Cytoplasmic Sperm Injection)
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Fertilisation
Day 2
Day 4
Day 5
Blastocyst
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Day 3
Day 5
Blastocyst
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Fate of recovered eggs (averages)
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Embryo transfer
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Pregnancy blood test
2 weeks after embryo transfer
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Embryo freezing
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Oocyte
Cryopreservation
Author
Method
Fabbri (2001)
Slow-Freeze
Chen (2005)
Survival
rate, n (%)
Fertilisation
rate, n (%)
No. of
oocytes per
pregnancy
796/1,502 (53)
632/796 (79)
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Slow-Freeze
119/159 (75)
80/119 (67)
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Boldt (2006)
Slow-Freeze
218/361 (60)
124/218 (61)
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Yoon (2003)
Vitrification
325/474 (69)
142/198 (72)
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Kuwayama
(2005)
Vitrification
58/64 (91)
52/58 (90)
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Jain. Fertil Steril 2006
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Any Questions?
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