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Male And Female Infertility Flashcards

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1
Q

What are the 6 main reproductive hormones

A

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

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2
Q

What happens in menstrual cycle days 0-14 (follicular phase)

A

Surge in gonadotropin releasing hormone

Stimulates FSH and LH (pituitary)

FSH acts on follicle causing oestradiol to be produced by granulosal cells

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3
Q

Why do oestradiol levels rise when FSH and LH levels have dropped

A

Oestrogens bind to receptors in granulosa cells

This stimulates proliferation of granulosa cells and more oestrogen receptors so more oestrogen produced

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4
Q

What is the corpus luteum

A

Formed from the collapsed follicle
Maintained by LH
Secretes progesterone
Oestradiol levels begin to drop (progesterone inhibits oestradiol synthesis)

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5
Q

Death of corpus luteum

A 
Corpus luteum degenerates 
Decrease in progesterone and oestradiol levels 
Increase in FSH and LH levels 
Allows new follicles to mature 
Onset of ovulation
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6
Q

What happens in females 2-4 years prior to menarche

A

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

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7
Q

What happens in puberty in males

A

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

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8
Q

What is the effect of FSH and LH in days 0-14

A

FSH acts on granulosal cells of the follicles to increase synthesis of oestradiol

LH acts on thecal cells of the follicles to produce androgens

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9
Q

What is the role of cholesterol

A

Used to produce the androgens and eostrogens but also the glucocorticoids and mineralocorticoids in the adrenal cortex

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10
Q

How is androstendione produced

A

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

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11
Q

Synthesis of oestradiol

A

Granulosa cells do not have enzymes to produce androstenedione. Aromatase activity in granulosa cells allows androstenedione to form estradiol when FSH binds

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12
Q

Why do oestradiol levels rise when FSH and LH levels have dropped

A

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

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13
Q

What does the production of oestradiol allow

A

Allows the new follicle to develop and grow into the Graafian follicle

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14
Q

What happens to the negative feedback loop mid cycle

A

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

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15
Q

What happens after the action of LH is changed at ovulation

A

The appearance of LH receptors on granulosal cells is stimulated which increases progesterone synthesis
Oocyte is released
Recruitment of 5-9 new follicles

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16
Q

What is the corpus luteum

A

Formed from the collapsed follicle
Maintained by LH
Secretes progesterone

Oestradiol levels begin to drop (progesterone inhibits oestradiol synthesis)

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17
Q

Role of progesterone in latter half of menstrual cycle

A

Progesterone causes a decrease in gonadotropin secretion (suppresses GnRH secretion)
FSH and LH levels are low so no new follicles develop

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18
Q

Order of events in menstrual cycle

A

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

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19
Q

How does hormonal contraception work

A

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

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20
Q

How does the combined oral contraceptive work

A

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

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21
Q

How does the progesterone only contraception work

A

Needs to be taken continuously
Oral pill - compliance is essential
Injectable forms 8-12 weeks

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22
Q

Why does menstrual cycle not occur during pregnancy

A

No menstrual cycle occurs as high levels of progesterone are present
Inhibits secretion of pituitary gonadotropins

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23
Q

What happens at menopause

A

At around 50 years the menstrual cycle becomes less regular as ovaries lose the ability to respond to FSH and LH
Low oestradiol levels

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24
Q

What causes the onset of puberty

A

Activation of GnRH pulses to anterior pituitary (maturation within CNS)
Increase in LH and FSH
Increase in oestradiol and androgen synthesis

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25
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
26
Function of the testes
Production and temporary storage of spermatozoa | Synthesis and secretion of testosterone, oestrogen, activin, inhibin, oxytocin
27
Role of ductal system in male genitals
Carriage of spermatozoa to the exterior ; maturation of spermatozoa
28
Role of secretory glands in the male genital system
Secrete seminal fluids and nutrients to support and nourish spermatozoa
29
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
30
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
31
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
32
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
33
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
34
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
35
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
36
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
37
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
38
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
39
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
40
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
41
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
42
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
43
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
44
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
45
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
46
What is the EDRF
Endothelium derived relaxant factor Was identified as nitric oxide Produced by blood vessels
47
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
48
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
49
Side effects of viagra
Headache Visual disturbances
50
Causes of erectile dysfunction
Cardiovascular disease (damage to blood vessels and nerves in penis) Smoking Diabetes Psychogenic Drugs: thiazides, prazosin, antidepressants, antipsychotics
51
Function of prostate gland
Accessory sex gland | Adds nutrients and enzymes to seminal fluid
52
Notable contents of seminal fluid
``` PSA Prostaglandins Fructose Zinc Citrate ```
53
Lower urinary tract voiding symptoms
Slow to start = hesitancy Slow to go = poor stream Slow to finish = post micturition dribble (Obstruction)
54
Lower urinary tract storage symptoms
``` Frequency Urgency Incontinence Nocturia (Bladder dysfunction) ```
55
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
56
Other causes of menopause
``` Surgical menopause Hysterectomy or removal of ovaries Chemotherapy / radiotherapy Premature ovarian insufficiency Genetic causes -Turner syndrome ```
57
What is perimenopause
Can have symptoms of menopause but still having periods (can be more irregular)
58
What is post menopause
When you have gone a year with no periods
59
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 ```
60
Diseases associated with menopause
Breast cancer (HRT) Ischaemic heart disease Stroke Osteoporosis
61
Menopause treatment
Conservative management / education Diet / exercise Supplements-oil of evening primrose / black cohosh / agnus castus Hormone replacement therapy
62
What is sequential combined cyclical HRT
Estrogen daily plus progesterone / progesterone for 10-14 days every 28-30 days cycle
63
What is sequential long cycle HRT
Estrogen daily for 12 weeks plus progesterone added in the last 14 days
64
What is continuous combined HRT
Estrogen plus progesterone administered together continuously
65
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
66
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
67
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
68
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
69
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
70
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
71
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
72
How to diagnose a prostate tumour
Trans rectal ultrasound and biopsy (tube inserted into rectum) Antibiotics usually given prior Complications: septicaemia and bleeding
73
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
74
Consequences of radiotherapy, bracytherapy and surgery (prostate cancer)
``` Impotence Incontinence Stricture Death Failure ```
75
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
76
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
77
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
78
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
79
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
80
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
81
What fertility investigations may be done in males
Semen analysis - assesses sperm count, motility, morphology, vitality, concentration and volume Chlamydia screen

Med 3 (10 decks)

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