Infertility Flashcards by Elizabeth Akeju

What is infertility?

‘A disease of the reproductive system defined by the failure to achieve a clinical pregnancy after ≥12 months of regular unprotected sexual intercourse.’
WHO 2009
Regular intercourse = every 2-3 days

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What is the difference between primary and secondary infertility?

Primary: Not had a live birth previously
Secondary: Not had a live birth >12 months previously

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How common is infertility?

Affects 1 in 7 couples (= 14% of couples)
But ~ half of these will then conceive in the next 12 months (ie at 24months ~ 7% of couples)

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What is the most common cause of infertility in a couple?

Male factor - 30%
Female factor - 30%
Male & female factor - 30%
Unknown - 10%

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What are some psychological impacts of infertility on couples?

No biological child
Impact on couples wellbeing
Impact on larger family
Investigations
Treatments (often fail)

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What are some impacts of infertility on society?

Less births
Less tax income
Investigation costs
Treatment costs

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What are some pre-testicular causes of infertility in males?

Congenital & Acquired Endocrinopathies:
- Klinefelters 47XXY
- HPG, T, PRL issues

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What are some testicular causes of infertility in males?

Congenital
Cryptorchidism
Infection: STDs
Immunological: antisperm Abs
Vascular: varicocoele
Trauma/surgery
Toxins: chemo/DXR/drugs/smoking

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What are some post-testicular causes of infertility in males?

Congenital: absence of vas deferens in cystic fibrosis
Obstruction azoospermia
Erectile dysfunction: retrograde ejaculation, mechanical impairment and psychological
Iatrogenic: vasectomy

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What happens in cryptorchidism?

Undescended testis - 90% in inguinal canal

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What are the pelvic causes of female infertility?

Endometriosis
Adhesions

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What are the tubal causes of female infertility?

Infection
Endometriosis
Trauma

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What are the ovarian causes of female infertility?

Anovulation
Corpus luteum insufficiency

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What are the uterine causes of female infertility?

Unfavourable endometrium due:
-Congenital malformations
-Infection/Inflammation/Scarring (adhesions)
- Fibroids

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What are the cervical causes of female infertility?

Ineffective sperm penetration due:
- Infection/Inflammation
- Immunological (antisperm Ab)

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What is endometriosis and how common is it?

Presence of functioning endometrial tissue outside the uterus
Occurs in 5% of women
Responds to oestrogen

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What are the symptoms of endometriosis?

↑ Menstrual pain
Menstrual irregularities
Deep dyspareunia (painful intercourse)
Infertility

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What are fibroids?

Benign tumours of the myometrium
Occur in 1-20% of pre-menopausal women (increases with age)
Respond to oestrogen

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What are the symptoms of fibroids?

Usually asymptomatic
↑ Menstrual pain
Menstrual irregularities
Deep dyspareunia
Infertility

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How would you describe GnRH and LH levels?

Pulsatile

How would you describe sex steroid levels?

Follow a diurnal rhythm

What would you expect to happen to LH, FSH and testosterone levels in hyperprolactinaemia?

Down, down, down
Hypogonadotrophic hypogonadism

What would you expect to happen to LH, FSH and testosterone levels in Primary Testicular Failure?

LH/FSH- Up
Testosterone- Down
Hypergonadotrophic hypogonadism

What are the causes of hypothalamic (low GnRH) hypogonadotrophic hypogonadism?

Congenital HH:
- Anosmic (Kallman Syndrome or Normosmic)
Acquired HH:
- Low BMI, excessive exercise, stress
Hyperprolactinaemia

What are the pituitary causes of hypogonadotrophic hypogonadism?

Hypopituitarism: - tumour - infiltration - apoplexy - surgery - radiation

What are the causes of hypergonadotrophic hypogonadism in men?

Congenital primary hypogonadism: - Klinefelters (47XXY) Acquired primary hypogonadism: - Cryptorchidism - Trauma - Chemo - Radiation

What is the pathophysiology of Kallmann Syndrome?

Failure of migration of GnRH neurons with olfactory fibres causing anosmia and hypogonadotrophic hypogonadism

What are the reproductive features of Kallmann Syndrome?

Failure of puberty Infertility

How does hyperprolactinaemia cause hypogonadatrophic hypogonadism?

Prolactin binds to prolactin receptors on kisspeptin neurons in hypothalamus - inhibits kisspeptin release Decreases downstream GnRH/LH/FSH/T/Oest Causes: - Oligo (>35d menses) or amenorrhoea (3-6m no menses) - Low libido (and other hypogonadal symptoms) - Infertility - Osteoporosis

What is the treatment of hyperprolactinaemia?

Dopamine agonist (Cabergoline) Surgery/DXT

What is Klinefelters Syndrome and what are the features?

XXY causing hypergonadotrophic hypogonadism Features: Tall stature Reduced facial hair Breast development Female-type pubic pattern Small penis and testes Infertility Mildly impaired IQ Narrow shoulders Reduced chest hair Wide hips Low bone density

What must be considered when taking an initial history for male infertility?

Duration Previous children Pubertal milestones Associated symptoms (testosterone deficiency, PRL symptoms, CHH features) Medications/drugs

What are some key examinations for male infertility?

BMI Sexual characteristics Testicular volume Anosmia

What are some key investigations for male infertility?

Semen analysis Blood tests: - LH, FSH, PRL - Morning fasting testosterone - Karyotyping Imaging: - Scrotal US/Doppler - Pituitary MRI

What are typical findings in semen analysis and what are the terms used to describe no/reduced sperm?

1.5 mL 15 million sperm /mL 40% motility Azospermia - no sperm Oligospermia - reduced sperm

What are conservative treatments for male infertility?

Optimise BMI Smoking cessation Alcohol reduction/cessation

What are the medical treatments for male infertility?

Dopamine agonist - hyperprolactinaemia Gonadotrophin treatment for fertility (also increases testosterone) Testosterone (no fertility required) Surgery (e.g. Micro Testicular Sperm Extraction - micro TESE)

What is Premature Ovarian Insufficiency?

Same symptoms as menopause (but at an earlier age) Conception can happen in 20% Diagnosis - high FSH >25 iU/L (x2 at least 4wks apart)

What are the causes of Premature Ovarian Insufficiency?

Autoimmune Genetic eg Turner’s Syndrome Radio-/chemo-therapy in the past

What are the causes of hypergonadotrophic hypogonadism in women?

Congenital Primary Hypogonadism -Turners (45X0) -Premature Ovarian Insufficiency (POI) Acquired Primary Hypogonadism -Premature Ovarian Insufficiency (POI) -Surgery, Trauma, Chemo, Radiation Polycystic Ovarian Syndrome

Describe the epidemiology of PCOS

Affects 5-15% of women of reproductive age (frequent family history) Most common endocrine disorder in women Most common cause of infertility in women

What makes up the Rotterdam PCOS Diagnostic Criteria and when is it used?

Used after other reproductive disorders have been excluded Criteria (2 out of 3): - Oligo/anovulation - Clinical (acne, hirsutism, alopecia) +/- biochemical hyperandrogenism (raised androgens) - Polycystic ovaries (ultrasound)

What are the characteristics of PCOS?

Irregular menses/amenorrhea - infertility Increased insulin resistance - T2DM/gestational DM Hirsutism Increased endometrial cancer risk (x2-6)

What drugs are used in the treatment of PCOS?

What is Turner’s Syndrome and what are the symptoms?

45 X0 Hypergonadotrophic hypogonadism

What are the key points covered in an initial history of female infertility?

Duration Previous children Pubertal milestones Menstrual history Medication/drugs

What key examinations are done for female infertility?

BMI Sexual characteristics Hyperandrogenism signs Anosmia

What key investigations are done for female infertility?

Blood tests: - LH, FSH, PRL - Oestradiol, androgens - Mid-luteal Prog - Karyotyping Pregnancy Test (urine or serum HCG) Imaging: - Transvaginal US - Hysterosalpingogram - Pituitary MRI