Male And Female Infertility Flashcards
What are the 6 main reproductive hormones
Gonadotropin releasing hormone: hypothalamus ; decapeptide
Follicle stimulating hormone - anterior pituitary
Lutenizing hormone - anterior pituitary
Oestradiol - ovary (oestrogens, oestradiol, oestrone)
Progesterone - ovary
Testosterone - testes, adrenal glands, ovary
What happens in menstrual cycle days 0-14 (follicular phase)
Surge in gonadotropin releasing hormone
Stimulates FSH and LH (pituitary)
FSH acts on follicle causing oestradiol to be produced by granulosal cells
Why do oestradiol levels rise when FSH and LH levels have dropped
Oestrogens bind to receptors in granulosa cells
This stimulates proliferation of granulosa cells and more oestrogen receptors so more oestrogen produced
What is the corpus luteum
Formed from the collapsed follicle
Maintained by LH
Secretes progesterone
Oestradiol levels begin to drop (progesterone inhibits oestradiol synthesis)
Death of corpus luteum
Corpus luteum degenerates Decrease in progesterone and oestradiol levels Increase in FSH and LH levels Allows new follicles to mature Onset of ovulation
What happens in females 2-4 years prior to menarche
Increase in steroid hormones from ovary and adrenal glands
Ovarian oestrogens regulate growth of breast and female genitalia
Androgens from ovary and adrenal control growth of pubic and axillary hair
What happens in puberty in males
Increase in steroid hormones from gonads and adrenal glands
Testicular androgens control development of genitalia and body hair as well as enlargement of larynx and laryngeal muscles
What is the effect of FSH and LH in days 0-14
FSH acts on granulosal cells of the follicles to increase synthesis of oestradiol
LH acts on thecal cells of the follicles to produce androgens
What is the role of cholesterol
Used to produce the androgens and eostrogens but also the glucocorticoids and mineralocorticoids in the adrenal cortex
How is androstendione produced
LH binds to its receptor in thecal cells and causes cholesterol to produce androstenidione. Only the thecal cells contain receptors to LH and granulosa cells to FSH in early stages
Synthesis of oestradiol
Granulosa cells do not have enzymes to produce androstenedione. Aromatase activity in granulosa cells allows androstenedione to form estradiol when FSH binds
Why do oestradiol levels rise when FSH and LH levels have dropped
Oestradiol increases proliferation of granulosal cells - more oestradiol produced
Oestrogen bind to receptors in granulosa cells
They are stimulated to proliferate and produce more oestrogen receptors
Positive feedback: where oestrogen stimulates further oestrogen output and a surge in circulating oestrogens
What does the production of oestradiol allow
Allows the new follicle to develop and grow into the Graafian follicle
What happens to the negative feedback loop mid cycle
Becomes positive allowing a short surge of LH to be released due to the high oestradiol levels (late follicular phase) acting on the pituitary
High oestradiol together with FSH cause change in action of LH
What happens after the action of LH is changed at ovulation
The appearance of LH receptors on granulosal cells is stimulated which increases progesterone synthesis
Oocyte is released
Recruitment of 5-9 new follicles
What is the corpus luteum
Formed from the collapsed follicle
Maintained by LH
Secretes progesterone
Oestradiol levels begin to drop (progesterone inhibits oestradiol synthesis)
Role of progesterone in latter half of menstrual cycle
Progesterone causes a decrease in gonadotropin secretion (suppresses GnRH secretion)
FSH and LH levels are low so no new follicles develop
Order of events in menstrual cycle
Menstruation
Release of recruited follicles. One to develop
Proliferation of granulosal cells, development of Graafian follicle
Proliferation of endometrium and myometrium
Ovulation (5-9 follicles recruited)
Growth of corpus luteum
Endometrium secretory
Inhibition of developing follicles
Death of corpus luteum
Final contraction of spiral arteries in endometrium
How does hormonal contraception work
Suppresses ovulation by negative feedback of progesterone on the pituitary and hypothalamus
Decrease in GnRH secretion resulting in low FSH and LH levels - no new follicles develop
How does the combined oral contraceptive work
Contains oestrogen and progesterone
Monocyclic
21 days on (output of GnRH, FSH, LH suppressed)
7 days off (endometrium breaks stimulating menstruation)
Estrogen: progesterone vary in different pills
How does the progesterone only contraception work
Needs to be taken continuously
Oral pill - compliance is essential
Injectable forms 8-12 weeks
Why does menstrual cycle not occur during pregnancy
No menstrual cycle occurs as high levels of progesterone are present
Inhibits secretion of pituitary gonadotropins
What happens at menopause
At around 50 years the menstrual cycle becomes less regular as ovaries lose the ability to respond to FSH and LH
Low oestradiol levels
What causes the onset of puberty
Activation of GnRH pulses to anterior pituitary (maturation within CNS)
Increase in LH and FSH
Increase in oestradiol and androgen synthesis
What occurs prior to puberty in males
Increase in steroid hormones from gonads and adrenal glands
Testicular androgens control development of genitalia and body hair as well as enlargement of larynx and laryngeal muscles
Function of the testes
Production and temporary storage of spermatozoa
Synthesis and secretion of testosterone, oestrogen, activin, inhibin, oxytocin
Role of ductal system in male genitals
Carriage of spermatozoa to the exterior ; maturation of spermatozoa
Role of secretory glands in the male genital system
Secrete seminal fluids and nutrients to support and nourish spermatozoa
Where does testes descend from
Posterior abdominal wall to scrotum outside the body at 7th month gestation. Keeps gametes to 2-3c below core body temperature; essential for spermatogenesis. Highly vascular
Describe the testes
4-5cm long, 11-17g weight
Right slightly larger and heavier
Fibrous septa from TA divides the testis into 250-350 lobules. Each lobule contains 1-4 coiled seminiferous tubules. Each 80cm long, 150 micron diameter
Closed loops, both ends open into rete testis
Role of Sertoli cells
Interconnect with each other to create the blood testes barrier. Results in a basal, adlumenal and lumenal compartment
They put out baso-lateral cytoplasmic extensions to each other which make tight junctions with each other. Thus there is a meshwork created (blood testis barrier)
This forms
What are the ablumenal and lumenal compartments
Ablumenal: this is where, upon release of spermatogonium, spermatocytes undergo spermatogenesis
Lumenal: spermatids are found on the lumenal surface. Fully formed spermatozoa are found in the lumen of the seminiferous tubules
What is the importance of the blood-testis barrier
Tight junctions cause complete apposition of adjacent plasma membranes forbidding movement of solutes from the basal to the adlumenal compartment and vice versa
Isolates the adlumenal from the basal compartment. Interstitial fluid cannot get in
Only unidirectional movement of germ cells are allowed through the tight junctions
TJs open transiently and allow spermatogonia to enter the adlumenal compartment
Consequences of the blood testis barrier
Body cannot elicit an immune reaction and create antibodies against sperm antigens revealed during spermatogenesis
Protects the developing spermatocytes from pathogens and mutagens
What is spermatogenesis
Mitotic proliferation - produces large number of cells
Meiotic division - generates genetic diversity and halves the chromosome number
Spermiogenesis- packaging of chromosomes for effective delivery to the oocyte. Formation of head, neck and tail, loss of cytoplasm
Production rate: 300-600 spermatozoa per gram of testis per second
How is sperm production continuous not cyclical
Spermatogonia divide in sequence every 16 days
Before one set have completed maturation, a new entry into spermatogenesis by other cells start (staggered entry) this ensures continuous release of spermatozoa
It takes 64 days to develop a mature spermatozoan
Endocrine support of spermatogenesis
LH stimulates leydig cells to produce testosterone which binds to receptors on Sertoli cells
Testosterone induces receptors for FSH on Sertoli cells
FSH from pituitary now stimulates Sertoli cells to produce androgen binding protein which binds and carries testosterone in testicular fluid to the entire ductal system
Sertoli cells also produce inhibin which is part of a negative feedback loop. It inhibits FSH production by the pituitary gland
Importance of the spermatic cord
Site for sperm storage
Epididymis connects to the vas deferens which runs through the spermatic cord. The testicular artery runs along with it
The veins in this system form an unusual plexus around the testicular artery. The spermatic cord is encased in cremaster muscle
Vascular supply of the spermatic cord
Pampiniform veins form a complex interconnecting plexus around the testicular artery. Excellent for heat exchange, protects contents of vas deferens from overheating. These veins are difficult to distinguish from arteries as they have muscular walls
What are seminal vesicles
Mucosal folds create vast surface area
Secretes seminal fluid
60% of semen volume is seminal fluids
Contraction of seminal vesicle propels secretion into ejaculatory ducts which open into the prostatic urethra
What is the prostate gland
Collection of concentric secreting glands which open into the urethra. Secretes citric acid, proteolytic enzymes, clotting enzymes, prostate specific antigen
What are bulbourethral glands
Opens into the membranous urethra
Produces watery fluid rich in galactose and sialic acid
Acts as lubricant and neutralises acidic urine in urethra and vaginal fluids
Precedes semen during emission
What is the erectile tissue of the penis made of
2 dorsal cylinders (corpora cavernosa) highly vascular
1 ventral cylinder (corpus spongiosum) which contains the penile urethra
Erectile physiology (flaccid state)
Sinusoidal smooth muscle fibres remain contracted and blood flows from the internal pudenal arteries via central deep artery and helicine arteries to vascular cavernous spaces and out through the open emissary veins. Low volume low pressure
Erectile physiology erect state
Closure of arteriovenous shunts - more blood flow into helicine arteries which straighten and dilate, smooth muscles of sinusoids relax, blood flows into the enlarged lacunar spaces. The resultant pressure compresses the emissary veins reducing venous outflow. Large volume high pressure
What is the EDRF
Endothelium derived relaxant factor
Was identified as nitric oxide
Produced by blood vessels
How do endothelial cells produce NO
Metabolise aa L -arginine by nitric oxide synthase to produce NO which then fizzes out of the endothelium and acts on vascular smooth muscle to active enzyme Guanlyl Cyclase which causes vasorelaxation
Mode of action of sildenafil (viagra)
Increases levels of cyclic GMP and leads to vasodilation
Originally for angina but patients complained of penile erection as a side effect
Side effects of viagra
Headache
Visual disturbances
Causes of erectile dysfunction
Cardiovascular disease (damage to blood vessels and nerves in penis)
Smoking
Diabetes
Psychogenic
Drugs: thiazides, prazosin, antidepressants, antipsychotics
Function of prostate gland
Accessory sex gland
Adds nutrients and enzymes to seminal fluid
Notable contents of seminal fluid
PSA Prostaglandins Fructose Zinc Citrate
Lower urinary tract voiding symptoms
Slow to start = hesitancy
Slow to go = poor stream
Slow to finish = post micturition dribble
(Obstruction)
Lower urinary tract storage symptoms
Frequency Urgency Incontinence Nocturia (Bladder dysfunction)
Define menopause
The permanent cessation of mensruation
Caused by loss of ovarian function / follicular activity
Average age in uk is 51
Associated with physical / psychological and social changes
Other causes of menopause
Surgical menopause Hysterectomy or removal of ovaries Chemotherapy / radiotherapy Premature ovarian insufficiency Genetic causes -Turner syndrome
What is perimenopause
Can have symptoms of menopause but still having periods (can be more irregular)
What is post menopause
When you have gone a year with no periods
Symptoms of menopause
Difficulty sleeping Memory loss Reduced muscle mass Hot flushes Vaginal dryness and pain Mood changes Palpitations Changing periods Headaches Joint stiffness, aches and pains Night sweats Recurrent UTIs
Diseases associated with menopause
Breast cancer (HRT)
Ischaemic heart disease
Stroke
Osteoporosis
Menopause treatment
Conservative management / education
Diet / exercise
Supplements-oil of evening primrose / black cohosh / agnus castus
Hormone replacement therapy
What is sequential combined cyclical HRT
Estrogen daily plus progesterone / progesterone for 10-14 days every 28-30 days cycle
What is sequential long cycle HRT
Estrogen daily for 12 weeks plus progesterone added in the last 14 days
What is continuous combined HRT
Estrogen plus progesterone administered together continuously
How does HRT help Osteoporosis
Trial data suggests there are 23 fewer fragility fractures per 1000 in post menopausal HRT users
Benefit might continue in women taking HRT for longer and the protection stops when HRT stops
Summary of effects of HRT
Reduces vasomotor symptoms but effect is temporary
Reduces vaginal dryness symptoms but local therapy is better
Prevents osteoporosis
Increases breast cancer and stroke
No effect on myocardial infarction, memory or quality of life
Current advice for HRT
Use only for debilitating symptoms in the lowest dose for the shortest time possible
Individualise the care
Discuss lifestyle issues
Refer to a specialist clinic and seek a second opinion
What does obstruction of bladder lead to
Painful distension of bladder, hydronephorsis, irritated bladder = urgency, frequency, nocturia
Residual urine in bladder = infection
Acute urinary retention :
- one of the most common surgical emergencies however risk is low
Palpable bladder
What is prostatits
Acute infection with E. coli or other gram -ve rods
Neutrophilic infiltrate, oedema, within glands initially, then stroma
Chronic: either same bacteria as acute or diagnosed by increased leucocytes in prostatic secretions but no bacteria found
Symptoms: dysuria, frequency, lower back pain, pelvic pain and enlarged tender prostate
What is benign prostatic hyperplasia
Proliferation of both stroma and epithelial elements (initially in the central zone)
An imbalance between proliferation and apoptosis
Very common. Affects 90% of men over 70
Androgens have a role may be a consequence of age related oestrogen increase
Symptoms: lower UT obstruction, hesitancy, interruption of flow. Smooth and enlarged by DRE
Describe prostate cancer
2nd highest cause of cancer death in men
Increases with age. Rare below 60 very common over 80
Adenocarcinoma
Occurs initially often in peripheral zones
Often found as clinically silent on biopsy for suspected hyperplasia
Symptoms: similar to BPH, hard, craggy, fixed prostate can spread to bone (back pain), lung, liver, brain and rarely kidney
How to diagnose a prostate tumour
Trans rectal ultrasound and biopsy (tube inserted into rectum)
Antibiotics usually given prior
Complications: septicaemia and bleeding
Treatment options for prostate cancer
Active monitoring - no treatment
Surgery (lots of complications)
Radiotherapy
New modalities eg bracytherapy (radioactive beads into prostate that release local radiation - less side effects)
Palliative: hormone manipulation to slow thing, radiotherapy for bones, pain relief, deal with obstructive renal failure
Consequences of radiotherapy, bracytherapy and surgery (prostate cancer)
Impotence Incontinence Stricture Death Failure
How can PSA (prostate specific antigen) be used as a way of screening for prostate cancer
Produced normally by prostate
4.0ng/ml is upper limit of normal
More than 10mg/ml is more than likely to be cancer
Is not always elevated in cancer but is elevated in hyperplasia and infection due to disruption of normal glandular architecture
Types of disorders of ovulation
1) hypothalamic pituitary failure: failure to produce required amount of LH and FSH resulting in anovulation
2) hypothalamic pituitary ovulation dysfunction: the result of PCOS (the most common cause of female infertility)
3) ovarian failure: normal hypothalamic and pituitary function but insuffiecnet numbers of follicles within th ovary so less oestrogen produced and follicles do not develop fully. Results in anovulatory cycles
What is sheehans syndrome
Hypopituitarism caused by ischaemic necrosis of the pituitary. Occurs as the result of severe hypotension or haemorrhagic shock secondary to massive post partum haemorrhage
Tubal causes of infertility
Delicate structure of Fallopian tubes makes them more susceptible to damage. Most common cause is pelvic inflammatory disease which is usually secondary to chlamydia or gonorrhoea
Others:
Previous sterilisation
Endometriosis
Previous pelvic surgery
Uterine / peritoneal causes of infertility
Endometriosis which causes inflammation and adhesions in the pelvis that can distort pelvic anatomy
- cervical mucus dysfunction or defect
- previous pelvic or cervical surgery
- uterine fibroids
- ashermans syndrome
- previous abdominal infections which have resulted in adhesions
- congenital abnormalities
What are the 3 types of male infertility
Obstructive infertility - a problem with sperm delivery
Non obstructive infertility - a problem with sperm production
Coital infertility - infertility secondary to sexual dysfunction
What fertility investigations may be done in males
Semen analysis - assesses sperm count, motility, morphology, vitality, concentration and volume
Chlamydia screen
