Infertility Flashcards
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.’
What is primary infertility?
When you have not had a live birth previously
What is secondary infertility?
When have had a live birth >12 months previously
Describe the epidemiology of infertility?
Affects 1 in 7 couples
But ~ half of these will then conceive in the next 12 months
55% will seek help positive association with socioeconomic status
What is the epidemiology of infertility? i.e which person %
Female 30%
Male 30%
Combined 30%
Unknown 10%
Why might infertility cause psychological distress to a couple?
- No biological child
- Impact on couples wellbeing
- Impact on larger family
- Investigations
- Treatments (often fail)
What is the cost of infertility to the society?
- Less births
- Less tax income
- Investigation costs
- Treatment costs
What three types of causes of infertility in males?
Pre-testicular
Testicular
Post-testistcular
What is pre-testicular infertility?
Congenital & Acquired Endocrinopathies
Klinefelters 47XXY
Y chromosome deletion
HPG, T, PRL
What is testicular infertility?
(Congenital)
Cryptorchidism
Infection
STDs
Immunological
Antisperm Abs
Vascular
Varicocoele
Trauma/Surgery
Toxins Chemo/DXT/Drugs/Smoking
What is post-testicular infertility?
Congenital Absence of vas deferens in CF
Obstructive Azoospermia
Erectile Dysfunction Retrograde Ejaculation Mechanical Impairment Psychological
Iatrogenic Vasectomy
What is CRYPTORCHIDISM?
Undescended testis
90% in inguinal canal
What are the categories of causes in females?
Ovarian causes Tubal causes Uterine causes Cervical causes Pelvic causes
What are ovarian causes?
-Anovulation (Endo)
-Corpus luteum insufficiency
40%
What are tubal causes?
Tubopathy due:
- Infection
- Endometriosis
- Trauma
30%
What are uterine causes?
Unfavourable endometrium due:
- Chronic endometritis (TB)
- Fibroid
- Adhesions (Synechiae)
- Congenital malformation
What are cervical causes?
Ineffective sperm penetration due:
- Chronic cervicitis
- Immunological (antisperm Ab)
5%
What are pelvic causes?
- Endometriosis
- Adhesions
5%
What is endometriosis?
Presence of functioning endometrial tissue outside the uterus
- 5% of women
- Responds to oestrogen
What are symptoms of endometriosis?
Increased Menstrual pain
Menstrual irregularities
Deep dyspareunia
Infertility
What are the treatments for endometriosis?
Hormonal (eg continuous OCP, prog)
Laparascopic ablation
Hysterectomy
Bilateral Salpingo-oophorectomy
What are fibroids?
- 1-20% of pre-menopausal women (increases w age)
- Respond to oestrogen
What are symptoms of fibroids?
Usually asymptomatic Increased Menstrual pain Menstrual irregularities Deep dyspareunia Infertility
What are treatments for fibroids?
Hormonal (eg continuous OCP, prog, continuous GnRH agonists)
Hysterectomy
What pattern of LH/FSH and testosterone would you see in hyper prolactinaemia?
All low
What pattern of LH/FSH and testosterone would you see in Klinefelters?
High FSH/LH
Low T
What can cause endocrine male infertility?
Androgen receptor deficiency (rare)
Hyper/hypothyrodism
What congential causes cause low GnRH?
Congenital Hypogonadotrophic Hypogonadism
-Anosmic (Kallmann Syndrome) or Normosmic
What acquired causes cause low GnRH?
Acquired Hypogonadotrophic Hypogonadism
- Low BMI, XS exercise, Stress
- Hyperprolactinaemia
What are the pituitary causes of Male infertility?
Hypopituitarism
-Tumour, Infiltration, Apoplexy, Surgery, Radiation
What are the gonadal (affects testes, congenital & acquired) causes of male infertility?
Congenital Primary Hypogonadism
-Klinefelters (47XXY)
Acquired Primary Hypogonadism
-Cryptorchidism, Trauma, Chemo, Radiation
What is Kallmann syndrome?
Failure of migration of GnRH neurones with olfactory fibres into the hypothalamus
Low GnRH
Low LH/FSH
Low T
What are the symptoms of Kallmann syndrome?
Cryptorchidism Failure of puberty -Lack of testicle dvlpt -Micropenis -Primary amenorrhoea Infertility
Anosmia
What does prolactin do to cause infertility?
Prolactin binds to receptors on kisspeptin neurons
Inhbits kisspeptin release
Decrease GnRH/LH/FSH/T/Oest
Oligomenhorrea/Amenorrhea/Low libido
How do you treat hyperprolactinaemia?
Dopamine agonist (Cabergoline) Surgery/DXT
What causes hyperprolactinaemia?
Prolactinoma (micro/macro)
Pituitary stalk compression
Pregnancy & Breastfeeding
Medications (Dop antagonists eg anti-emetics and antipsychotics) (Oestrogens eg OCP)
PCOS
Hypothyroidism
What is Kleinfelter’s syndrome? And its’ effects on hormone levels
XXY
Increase LH and FSH
Low T
What are the features/symptoms of Kleinfelters?
Tall Low facial hair Breast development Female-type pubic hair Small penis and testes Infertility Mildy impaired IQ Narrow shoulders Reduced chest hair Wide hips Low bone density
What do you ask when talking an infertility history?
duration previous children pubertal milestones associated symptoms (eg. T deficiency, PRL symptoms, CHH features) medical & surgical history family history social history medications/drugs
What do you examine when looking at infertility? Which features?
including BMI, sexual characteristics, testicular volume, epididymal hardness, presence of vas deferens, other endocrine signs, syndromic features, anosmia
What investigations (tests) can be conducted to determine cause of infertility?
Semen analysis
Blood tests (LH/FSH/PRL)
Micrbiology
Imaging
What blood test are conducted? (male)
LH, FSH, PRL
Morning Fasting Testosterone
Sex Hormone Binding Globulin (SHBG)
Albumin, Iron studies
Also Pituitary/Thyroid profile
Karyotyping
What is azoospermia?
No sperm
What is oligospermia?
Reduced sperm
What microbiology is conducted? (male)
Urine test
Chlamydia swab
What imaging can be conducted to determine cause of male infertility?
Scrotal US/Doppler
(for varicocoele/obstruction, testicular volume)
MRI Pituitary
(if low LH/FSH or high PRL)
What are the general lifestyle treatments for male infertility?
Optimise BMI
Smoking cessation
Alcohol reduction/cessation
What are the specific treatments for male infertility?
Dopamine agonist for hyperPRL
Gonadotrophin treatment for fertility (will also increase testosterone)
Testosterone
(for symptoms if no fertility required – as this requires gonadotrophins)
Surgery
(eg. Micro Testicular Sperm Extraction (micro TESE))
What is POI?
Premature Ovarian Insufficiency
What are the symptoms of POI?
Same as menopause
What causes POI?
Autoimmune
Genetic eg Fragile X Syndrome / Turner’s Syndrome
Cancer therapy Radio- / Chemo-therapy in the past
What causes low GnRH in women? (congenital)
Congenital Hypogonadotrophic Hypogonadism
-Anosmic (Kallmann Syndrome) or Normosmic
What causes low GnRH in women? (acquired)
Acquired
Hypogonadotrophic Hypogonadism
-Low BMI, XS exercise, Stress
Hyperprolactinaemia
What are the pituitary causes of female infertility?
Tumour, Infilatration, Apoplexy, Surgery, Radiation
What causes female infertility at the gonad level?(aquired)
PCOS
Premature Ovarian Insufficiency (POI)
-Surgery, Trauma, Chemo, Radiation
What causes female infertility at the gonad level?(congenital)
- Turners (45X0)
- Premature Ovarian Insufficiency (POI)
What is PCOS? (epidemiology)
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 is the Rotterdam PCOS diagnostic criteria?
2 out of 3
Oligo or Anovulation
Clinical +/- biochemical hyperandrogegism
Polycystic ovaries
How do you assess menstrual frequency?
<21d or >35d cycles
<8-9 cycles/y
>90d for any cycle
How do you assess hyperandrogenism?
CLINICAL
Acne, hirsutism (Ferriman-Gallwey score), alopecia (Ludwig score)
BIOCHEMICAL Raised androgens (eg Testosterone)
How do you assess cysts?
≥20 follicles OR ≥10ml either ovary on TVUS (8 MHz)
Do not use US until 8y post-menarche (due to high incidence of multi-follicular ovaries at this stage)
What is the treatments for PCOS?
Metformin Oral contraceptive pill Anti-androgens Creams, waxing, laser Progesterone courses
What are the symptoms of PCOS?
Irregular menses Infertility Increased insulin resistance Impaired glucose homeostasis Hirtuism Increased endometrial cancer risk
What are the features of Turners?
Short stature Low hairline shield chest Wide-space nipples Short 4th metacarpal Small fingernails Brown nevi Characteristic faces Webbed neck Coarctation of aorta Poor breast development Elbow deformity Underdeveloped reproductive tract Amenorhea
What do you ask in a fertility history? (female)
including duration, previous children, pubertal milestones, breastfeeding?,
Menstrual History: oligomenorrhoea or 1/20 amenorrhoea, associated symptoms (eg. E deficiency, PRL symptoms, CHH features), medical & surgical history, family history, social history, medications/drugs
What is involved in a fertility examination? (female)
including BMI, sexual characteristics, hyperandrogenism signs, pelvic examination, other endocrine signs, syndromic features, anosmia
What blood test are conducted? (female)
LH, FSH, PRL
Oestradiol, Androgens
Foll phase 17-OHP, Mid- Luteal Prog
Sex Hormone Binding Globulin (SHBG)
Albumin, Iron studies
Also Pituitary/Thyroid profile
Karyotyping
What biochemical test are conducted (female infertility)?
Pregnancy Test
(urine or serum HCG
Urine test
Chlamidya swab
What imaging is used to diagnose infertility in women?
US (transvaginal)
Hysterosalpingogram
MRI Pituitary
(if low LH/FSH or high PRL
