1B infertility Flashcards
What is the definition of 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 counts as regular intercourse?
Every 2-3 days
What are the 2 types of infertility?
- Primary infertility- when a couple have not had a live birth previously
- Secondary infertility- when a couple have had a live birth >12 months previously
What are the 4 most common causes of infertility in a couple?
1) Male factor- 30%
2) Female factor- 30%
3) Combined male and female factor- 30%
4) Unknown factor- 10%
What is the impact of infertility on the couple?
- Psychological distress
- No biological child
- Impact on couple’s wellbeing
- Impact on larger family
- Investigations
- Treatments (often fail)
What is the impact of infertility on society?
- Less births
- Less tax income
- Investigation costs
- Treatment costs
What pre-testicular causes of infertility are there?
Congenital & acquired endocrinopathies:
- Klinefelters 47XXY
- Y chromosome deletion
- HPG axis issues, testosterone and prolactin issues
What testicular causes of infertility are there?
- Congenital
- Infection (STDs)
- Immunological (antisperm antibodies)
- Vascular (varicocoele)
- Trauma/surgery
- Toxins (chemo/DXT/drugs/smoking)
- Cryptorchidism
What is cryptorchidism?
- Normal pathway of testes development during embryo development is through inguinal canal from abdomen
- In cryptorchidism the testes don’t descend (90% are stuck in inguinal canal)
What post-testicular (after sperm made) causes of infertility are there?
- Congenital (absence of vas deferens in CF)
- Iatrogenic (vasectomy)
- Obstructive azoospermia (obstruction of sperm leaving testicles)
- Erectile dysfunction (retrograde ejaculation, mechanical impairment, psychology)
What pattern of LH, FSH and T would you see in hyperprolactinaemia?
- LH down
- FSH down
- T down
What pattern of LH, FSH and T would you see in primary testicular failure (e.g. in Klinefelters)?
- LH up
- FSH up
- T down
What diseases are there that affect the hypothalamus to cause hypogonadism?
- Congenital hypogonadotrophic hypogonadism e.g. anosmic (Kallmann Syndrome) or normosmic
- Acquired hypogonadotrophic hypogonadism e.g. low BMI, excess exercise, stress
- Hyperprolactinaemia
What do diseases that cause hypogonadism via the hypothalamus do to GnRH, LH + FSH and T?
- GnRH down (not measurable tho)
- LH and FSH down (hypogonadotrophic)
- T down (hypogonadism)
What diseases are there that affect the pituitary to cause hypogonadism?
- Tumour
- Infiltration (e.g. of sarcoid/TB)
- Apoplexy- sudden loss of blood supply
- Surgery
- Radiation
What do diseases that cause hypogonadism via the pituitary do to LH, FSH and T?
- LH down FSH down (hypogonadotrophic)
- T down (hypogonadism)
What diseases are there that affect the gonads to cause male hypogonadism?
- Congenital primary hypogonadism e.g. Klinefelters (47XXY)
- Acquired primary hypogonadism e.g. cryptorchidism, trauma, chemo, radiation
What do diseases that cause hypogonadism via the gonads do to LH, FSH and T?
- LH up FSH up (hypergonadotrophic)
- T down (hypogonadism)
What causes Kallmann’s syndrome?
- Within first 10 weeks of conception, GnRH neurones migrate from the olfactory placode in the primitive nose to the thalamus along with olfactory fibres
- Failure of this migration causes Kallmann’s
- Low GnRH, low FSH and LH, low T
What are the symptoms of Kallmann’s syndrome?
- Anosmia
- Cyptorchidism
- Failure of puberty- lack of testicle development, micropenis, primary amennorhoea
- Infertility
What is Klinefelter’s syndrome?
- Where males have XXY
- 1-2/1000 births- fairly common
- Higher LH and FSH, low T (hypergonadotrophic hypogonadism)
What are the symptoms of Klinefelter’s syndrome?
- Tall stature
- Narrow shoulders
- Wide hips
- Breast development
- Low bone density
- Less facial hair
- Reduced chest hair
- Female-type pubic hair pattern
- Small penis and testes
- Infertility (accounts for up to 3% of cases)
- Mildly impaired IQ
What things do we assess about a patient’s history to diagnose male infertility?
- Duration
- Previous children
- Pubertal milestones
- Associated symptoms (e.g. T deficiency, PRL symptoms, CHH features)
- Medical and surgery history
- Family history
- Social history
- Medications/drugs
What things do we assess as part of a patient examination to diagnose male infertility?
- BMI
- Sexual characteristics
- Testicular volume
- Epididymal hardness
- Presence of vas deferens
- Other endocrine signs
- Syndromic features
- Anosmia
What are the main investigations to diagnose male infertility?
- Semen analysis
- Blood tests
- Microbiology
- Imaging
What are the normal ranges for semen analysis?
- Normal volume is 1.5ml
- Normal sperm conc is 15 million/ml
- Normal total motility is 40%
What do blood tests for male infertility include?
- LH, FSH, PRL
- Morning fasting testosterone
- Karyotyping
What does imaging for infertility in males include?
- Scrotal US/doppler (for varicocoele/obstruction, testicular volume)
- MRI pituitary (if low LH/FSH or high PRL)
What are general lifestyle treatments for infertility in males?
- Optimise BMI
- Smoking cessation
- Alcohol reduction/cessation
What are specific treatments for infertility in males?
- Dopamine agonist for hyper PRL
- Gonadotrophin treatment for fertility (will also increase T)
- Testosterone (for symptoms if no fertility required- as this requires gonadotrophins)
- Surgery (e.g. Micro Testicular Sperm Extraction (micro TESE))
What ovarian causes of infertility are there? (40%)
- Anovulation- access controlling ovarian hormones is defective
- Corpus luteum insufficiency (not enough progesterone to support early pregnancy stages)
What tubal causes are there? (30%)
- Infection
- Trauma
- Endometriosis
What is endometriosis?
- Presence of functioning endometrial tissue outside the uterus
- Occurs in 5% of women
- Responds to oestrogen
What are the symptoms of endometriosis?
- More menstrual pain
- Menstrual irregularities
- Deep dyspareunia- painful intercourse
- Infertility
What is the treatment for endometriosis?
- Hormonal (e.g. continuous OCP, progesterone)
- Laparoscopic ablation
- Hysterectomy (removal of womb)
- Bilateral Salpingo-oophorectomy (take out tubes and ovaries where endometriosis is)
What uterine causes of infertility are there? (10%)
- Adhesions (synechiae)
- Congenital malformation
- Chronic endometritis (TB)
- Fibroids
What are fibroids?
- Benign tumours of myometrium
- Up to 20% of pre-menopausal women get one (increases with age)
- Responds to oestrogen
What are the symptoms of fibroids?
- Usually asymptomatic
- More menstrual pain
- Menstrual irregularities
- Deep dyspareunia
- Infertility
Treatments for fibroids?
- Hormonal (e.g. continuous OCP, progesterone, continuous GnRH agonists)
- Hysterectomy
What cervical causes of infertility are there? (5%)
Ineffective sperm penetration due to:
- Chronic cervicitis
- Immunological (antisperm antibodies)
What pelvic causes of infertility are there? (5%)
- Endometriosis
- Adhesions
What do diseases that affect the hypothalamus to cause hypogonadism do to GnRH, LH + FSH and E2?
- GnRH down (not measurable tho)
- LH and FSH down (hypogonadotrophic)
- E2 down (hypogonadism)
What do diseases that cause hypogonadism via the pituitary do to LH, FSH and E2?
- LH down FSH down (hypogonadotrophic)
- E2 down (hypogonadism)
What diseases are there that affect the gonads to cause female hypogonadism?
- Congenital primary hypogonadism e.g. Turners (45X0), premature ovarian insufficiency (POI)
- Acquired primary hypogonadism e.g. POI, trauma, chemo, radiation, surgery
- Polycystic ovaries syndrome (PCOS)
What do diseases that affect the gonads to cause hypogonadism do to LH, FSH and E2?
- LH up FSH up (hypergonadotrophic)
- E2 down (hypogonadism)
What other diseases (excluding those that affect the pituitary, hypothalamus and gonads) are there that cause hypogonadism in women?
Hyper/hypothyroidism (reduces bioavailable oestradiol)
How do we diagnose PCOS?
Exclude other reproductive disorders then use Rotterdam PCOS diagnostic criteria (need 2 out of 3 criteria):
- Oligo or anovulation
- Clinical and/or biochemical hyperandrogenism
- Polycystic ovaries on ultrasound (by themselves doesn’t mean PCOS)
What does oligo or anovulation mean?
- Less than 21 days or more than 35 day cycles
- Less than 8/9 cycles a year
- More than 90 days for any cycle
- If necessary, anovulation can be proven by lack of progesterone rise or ultrasound
What does clinical and/or biochemical hyperandrogenism mean?
- Clinical- acne, hirsutism (Ferriman-Gallwey score), alopecia (Ludwig score)
- Biochemical- raised androgens (e.g. Testosterone)
What measurement do we need for a diagnoses of PCOS via ultrasound?
- > 20 follicles or >10ml either ovary on TVUS
- Don’t use US until 8 years post-menarche (due to high incidence of multifollicular ovaries at this stage)
What is the worst metabolic risk combination for PCOS?
Oligo or anovulation and clinical +/- biochemical hyperandrogenism
How do we treat irregular menses/amenorrhoea for PCOS?
- Oral contraceptive pill
- Metformin
How do we treat the infertility part of PCOS?
- Clomiphene
- Letrozole
- IVF
How do we treat increased insulin resistance in PCOS?
- Diet and lifestyle
- Metformin
How do we treat hirsutism in PCOS?
- Anti-androgens (e.g. spironolactone)
- Creams, waxing, laser
How common is Turner’s syndrome (45X0)?
Affects 1 in 2500 live female births
How does Turner’s syndrome affect hormone levels?
Increased FSH and LH but lower E2 (hypergonadotrophic hypogonadism)
What are the symptoms of Turner’s syndrome?
What things do we assess about a patient’s history to diagnose female infertility?
- Duration
- Previous children
- Pubertal milestones
- Menstrual history
- Medications/drugs
What things do we assess as part of a patient examination to diagnose female infertility?
- BMI
- Sexual characteristics
- hyperandrogenism signs
- Pelvic examination
- Other endocrine signs
- Syndromic features
- Anosmia
What are the main investigations to diagnose female infertility?
- Pregnancy test
- Blood test
- Microbiology
- Imaging
What does a pregnancy test include?
Urine or serum hCG
What does a blood test for infertility in women include?
- LH, FSH, PRL
- Oestradiol, androgens
- Mid-luteal progesterone (hopeful rise means successful ovulation)
- Karyotyping
What does imaging for infertility in women include?
- Transvaginal ultrasound
- Hysterosalpingogram
- MRI pituitary (if low LH/FSH or high PRL)
What is POI?
Early menopause: Premature Ovarian Insufficiency
- Same Symptoms as per Menopause
- Previously called ‘Premature Ovarian Failure’ POF
- Conception can happen in 20%
What is the diagnosis for POI?
High FSH >25 iU/L (x2 at least 4wks apart)
What are the causes of POI?
- Autoimmune
- Genetic eg Turner’s Syndrome
- Cancer therapy Radio- / Chemo-therapy in the past
