9. Endocrine Infertility Flashcards
Outline the male hypothalamo-pituitary-gonadal axis
- GnRH pulses from hypothalamus
- Stimulation of LH + FSH release from pituitary
- LH stimulates leydig cells to produce testosterone
- FSH stimulates sertoli cells in seminiferous tubules to produce sperm and inhibin A + B
- Inhibin has negative feedback on pituitary FSH secretion
What are the phases of the menstrual cycle?
- Follicular phase
- Ovulation
- Luteal phase
Describe the follicular phase
- GnRH pulses stimulate LH + FSH
- LH stimulates production of oestradiol and progesterone in the ovaries
- FSH stimulates follicular development and inhibin
- Around day 10, leading follicle => Graffian Follicle
- Oestrogen initially has negative feedback on LH + FSH secretion
Describe ovulation and the luteal phase
- Once oestrogen reaches a certain level, it switches from negative to positive feedback
- Increases GnRH release and LH sensitivity to GnRH
- Mid-cycle LH surge
- Triggers ovulation from the leading follicle
- Progestrone rises
- If no implantation - endometrium is shed
Define infertility, and the proportion of couples it can affect
- Inability to conceive after 1 year of regular unprotected sex
- 1/6 couples can be affected
- Abnormalities - 30% males, 45% females, 25% unknown
What does primary gonadal failure lead to?
- Testes/ovaries not producing testosterone/oestrogen
- No negative feedback on HPG axis
- High GnRH and high LH + FSH
What is hypothalamic/pituitary disease?
- Secondary gonadal failure/hypopituitarism
- Inability of pituitary to produce FSH + LH - low levels
- Therefore, low oestradiol/testosterone
What are the clinical features of male hypogonadism?
- Loss of libido
- Impotence
- Small testes
- Decreased muscle bulk
- Osteoporosis (testosterone has anabolic action in the bone)
What are the causes of hypothalamic-pituitary disease?
- Hypopituitarism - secondary gonadal failure
- Kallmann Syndrome - anosmia and low GnRH, due to failure of GnRH and olfactory neurones to migrate from back of brain in development
- Illness/underweight - low levels of leptin
Give congenital and acquired causes of primary gonadal disease
- Congenital: Klinefelters Syndrome (XXY)
* Acquired: Testicular torsion, chemotherapy
What effect can hyperprolactinaemia have on the gonads?
Inhibit gonadal function
How else can low testosterone levels/insensitivity be referred to and why?
- Hypoandrogenism
- Testosterone = androgen
- Androgen receptor deficiency is a rare congenital cause of hypogonadism
How do you investigate male hypogonadism?
- LH, FSH and testosterone - if low, MRI of pituitary
- Prolactin
- Sperm count: azoospermia = absence, oligospermia = reduced numbers
- Chromosomal analysis
What is an ICSI?
- Intracytoplasmic sperm injections
* Combats infertility in someone with oligospermia
How can male hypogonadism be treated?
- All patients: replacement testosterone for all patients
- Hypothalamic/pituitary disease: subcutaneous gonadotrophin injections, inducing spermatogenesis for fertility
- Hyperprolactinaemia: dopamine agonist, (main influence) negative effect on prolactin release