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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. Acknowledgement. Dr Antony Lighten – IVF Australia Dr Derek Lok – Sydney IVF.

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Understanding infertility basic sciences l.jpg

Understanding InfertilityBasic 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

A/Prof R Gyaneshwar


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Reproductive Physiology

A/Prof R Gyaneshwar


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Blocked or damaged Fallopian tubes eg Ectopic pregnancy

Fibroids

Endometriosis

Miscarriage

Polycystic Ovarian Syndrome

Failure of Ovulation

A/Prof R Gyaneshwar


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Causes of Infertility

A/Prof R Gyaneshwar


The causes of infertility and their approximate frequency adapted from hull et al 1985 l.jpg
The Causes of Infertility and their Approximate Frequency (adapted from Hull et al 1985)

A/Prof R Gyaneshwar


Infertility l.jpg
Infertility

  • Definition

    • 12 months of attempting to conceive

      • Incidence 1 in 6 couples

      • Incidence increases with age

A/Prof R Gyaneshwar


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24

90

12

80

11

% pregnant/month

10

70

9

8

7

60

6

5

50

4

40

3

30

2

20

1

10

0

1

2

3

4

5

6

7

8

9

10

11

12

24

Natural Cumulative Pregnancy Rate

Months of trying

A/Prof R Gyaneshwar


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Natural Pregnancy Rate

A/Prof R Gyaneshwar


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Ovarian Reserve

A/Prof R Gyaneshwar


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LHRH

LH

FSH

Anovulation

A/Prof R Gyaneshwar


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LHRH

LH

FSH

The Clues

A/Prof R Gyaneshwar


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Ovulation Tests – Luteal Progesterone

A/Prof R Gyaneshwar


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Tubal Factor

  • Peristalsis

  • Ciliary dysfunction

  • Narrowing

  • Blockage

A/Prof R Gyaneshwar


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Lap / Dye

A/Prof R Gyaneshwar


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Ectopic

A/Prof R Gyaneshwar




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Endometriosis

A/Prof R Gyaneshwar


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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

A/Prof R Gyaneshwar


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Hysteroscopy

A/Prof R Gyaneshwar


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Septate uterus

A/Prof R Gyaneshwar


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Congenital Anomalies

A/Prof R Gyaneshwar


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Blocked/absent vas deferens

Low sperm numbers and/or poor sperm movement

High numbers of abnormal shaped sperm

Failure of sperm production

Antisperm antibodies

Erectile dysfunction

A/Prof R Gyaneshwar


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Male Factor

  • Primary Testicular Disease

    • Most common cause of male factor infertility

    • Aetiology

      • 66% unknown

      • 20% testicular maldescent

      • 7% trauma and torsion

      • 5% Klinefelter’s Syndrome

      • 1% mumps orchitis

      • 1% chemo

A/Prof R Gyaneshwar


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Male Factor

  • Endocrine causes

    • Hyperprolactinaemia

    • Hypogonadotrophic hypogonadism

    • Hypothrooidism

      • Rare

      • Present with sexual dysfunction

A/Prof R Gyaneshwar


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Sperm Count

  • Volume 2 – 5 mls

  • Density/Concentration > 20 mill/ml

  • Motility > 50%

  • Morphology > 14% normal

A/Prof R Gyaneshwar


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Male Infertility

  • 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 abnormalalways repeat

A/Prof R Gyaneshwar




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Important Concepts

  • Age

  • Duration of infertility

  • Primary versus secondary infertility

  • Multiple causes of infertility

  • Sub-fertility versus sterility

A/Prof R Gyaneshwar


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History

  • Duration

  • Previous pregnancies

  • Wt / Ht / BMI

  • Full menstrual history

  • Androgenising signs

  • Pelvic pain

  • Previous investigations

  • Past medical history

  • Past surgical history

  • Medications / cigarettes / alcohol

A/Prof R Gyaneshwar


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History

  • Previous paternities

  • Sexual dysfunction

  • Mumps / STD

  • Trauma

  • Undescended testes

  • Previous investigations

  • Past medical history

  • Past surgical history

  • Medications / cigarettes/ alcohol

A/Prof R Gyaneshwar


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RANZCOG Statement C-Obs 3 March 2004

  • Tests recommended at the first antenatal visit of each pregnancy:

    • 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

A/Prof R Gyaneshwar


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Prognostic Factors

  • Age

  • Duration of infertility

  • Primary versus secondary infertility

  • Multiple causes of infertility

  • Sub-fertility versus sterility

A/Prof R Gyaneshwar


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Duration of Infertility

  • 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

  • Treatment is more successful in patients where a specific treatable cause is found

A/Prof R Gyaneshwar


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Prognosis

A/Prof R Gyaneshwar



Investigations l.jpg

Tubal Patency

HSG

Lap & Dye

Ovulation

Midluteal P4

Testosterone, TSH,Prolactin, LH, FSH asindicated

Rubella, Varicella

Hep B, C, HIV, VDRL

Semen Analysis

LH, FSH, Prolactin as indicated

Karyotype

Hep B, C, HIV, VDRL

Investigations

A/Prof R Gyaneshwar


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Hormone / Ovulatory Tests

  • Day 2-3 hormones

    • FSH, LH, Oestradiol

    • Testosterone, SHBG

    • Others:

      • 17-OH P, DHEAS, Androstenedione, cortisol

      • TSH, prolactin

      • 75g GTT & fasting insulin

  • Luteal Progesterone

    • 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

A/Prof R Gyaneshwar


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Treatment Options

A/Prof R Gyaneshwar


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Ovulation Induction

PCOS

1st line

Clomiphene – 60% pregnant after 6 months

2nd line

Metformin

FSH

Surgical Ovarian Drilling

A/Prof R Gyaneshwar


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Ovarian Drilling

A/Prof R Gyaneshwar


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Ovarian Induction

Hypothalamic amenorrhoea

FSH

Pulsatile GnRH

Hyperprolactinaemia

Carbergolide

A/Prof R Gyaneshwar


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Intrauterine Insemination

Indications

Unexplained

Mild male factor

Success/Cycle

Natural 10-15%

Stimulated 15-20%

A/Prof R Gyaneshwar


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In Vitro Fertilisation

Indications

Prolonged unexplained

Tubal factor

Severe male factor

Unsuccessful OI / IUI / fertility surgery

A/Prof R Gyaneshwar


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In Vitro Fertilisation

Success / Cycle

40 – 5-%

Single embryo transfer

Now gold standard

Twin rate 1%

A/Prof R Gyaneshwar


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Sperm Preparation

49

A/Prof R Gyaneshwar


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50

A/Prof R Gyaneshwar


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51

A/Prof R Gyaneshwar


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52

A/Prof R Gyaneshwar


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Day surgery for egg collection

53

A/Prof R Gyaneshwar


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IVF(In Vitro Fertilisation)ICSI (Intra Cytoplasmic Sperm Injection)

54

A/Prof R Gyaneshwar


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IVF(In Vitro Fertilisation

55

A/Prof R Gyaneshwar


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ICSI (Intra Cytoplasmic Sperm Injection)

56

A/Prof R Gyaneshwar


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Fertilisation

Day 2

Day 3

Day 5

Blastocyst

Day 5

Blastocyst

Day 4

A/Prof R Gyaneshwar


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Fate of recovered eggs (averages)

58

A/Prof R Gyaneshwar


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Embryo transfer

59

A/Prof R Gyaneshwar


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Pregnancy blood test

2 weeks after embryo transfer

60

A/Prof R Gyaneshwar


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Embryo freezing

61

A/Prof R Gyaneshwar


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Oocyte Cryopreservation

Jain. Fertil Steril 2006

62

A/Prof R Gyaneshwar


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Any Questions?

63

A/Prof R Gyaneshwar


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