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Endocrinology > Reproduction and Fertility > Flashcards

Reproduction and Fertility Flashcards

1
Q

How many couples are affected by infertility

A

1:6 - 15%

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2
Q

List possible causes of the increase in incidence of infertility

A

Older women
Rise in chlamydia infection
Increasing obesity
Increasing male infertility

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3
Q

What is the definition of infertility

A

failure to achieve a clinical pregnancy after 12 months of more of regular unprotected sexual intercourse (in absence of known reason) in a couple who have never had a child

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4
Q

What is the difference between primary or secondary

A

Primary - couple have never had a child

Secondary - previously conceived but pregnancy may not have been successful

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5
Q

What gives a good prognosis for conceiving with treatment

A

age < 30yrs, short duration of infertility and secondary infertilty

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6
Q

What gives a bad prognosis for conceiving with treatment

A

male infertility, endometriosis and tubal factor infertility

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7
Q

Which factors lead to an increased chance of conception

A 
Women aged under 30 
Previous pregnancy 
Less than 3 years trying to conceive 
Intercourse around ovulation 
BMI in healthy range 
Non-smokers - both partners 
Low caffeine intake - less than 2 cups per day 
No recreational drug use
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8
Q

Fertility decreases with age - true or false

A

TRUE

incidence of spontaneous abortion also increases

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9
Q

Which physiological states can lead to anovulatory infertility

A

Before puberty
Pregnancy
Lactation
Menopause

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10
Q

Which pathological states can lead to anovulatory infertility

A

Hypothalamic - anorexia/bulimia, excessive exercise
Pituitary - hyperprolactinaemia, tumours, Sheehan syndrome
Ovarian: PCOS, premature ovarian failure
Systematic: chronic renal failure
Endocrine: testosterone secreting tumours, congenital adrenal hyperplasia
Drugs - OCP

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11
Q

What are the clinical features of anorexia nervosa

A 
Low BMI 
Loss of hair 
Low pulse and BP 
Anaemia 
Low FSH, LH and oestradiol
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12
Q

What is the cause of PCOS

A

Inherited condition

Exacerbated by weight gain

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13
Q

What are the clinical features of PCOS

A 
Obesity 
Hirsutism or acne 
Cycle abnormalities 
Infertility 
High free androgens 
High LH 
Impaired glucose tolerance
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14
Q

How do you diagnose PCOS

A

Score 2 out of three:
chronic anovulation
polycystic ovaries
hyperandrogenism

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15
Q

What causes premature ovarian failure

A

Can be idiopathic
Genetic - Turner’s or fragile X
Chemotherapy
Radiotherapy

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16
Q

What are the clinical features of premature ovarian failure

A 
Hot flushes 
Night sweats 
Atrophic vaginitis 
High FSH and LH 
Low oestradiol
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17
Q

What are the infective causes of tubal disease

A

PID - caused by chlamydia, gonorrhoea etc
Transperitoneal spread from appendicitis or intra-abdominal abscess
Following a procedure - IUD, hysteroscopy etc

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18
Q

What are the non-infective causes of tubal disease

A 
endometriosis
surgical (sterilisation, ectopic pregnancies)
fibroids
polyps
congenital
salpingitis isthmica nodosa
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19
Q

What are the clinical features of hydrosalpinx (blockage) due to PID

A 
abdominal/pelvic pain febrile
vaginal discharge dyspareunia
cervical excitation menorrhagia
dysmenorrhoea
infertility
ectopic pregnancy
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20
Q

What is endometriosis

A

presence of endometrial glands outside uterine cavity

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21
Q

What are the potential causes of endometriosis

A

Retrograde menstruation is most likely cause
Altered immune function
Abnormal cellular adhesion molecules
Genetic

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22
Q

What are the clinical features of endometriosis

A 
dysmenorrhoea (classically before menstruation),
Dysparenuia
Menorrhagia
Painful defaecation
Chronic pelvic pain
Uterus may be fixed and retroverted
Scan may show characteristic ‘chocolate’ cysts on ovary
Infertility
Asymptomatic
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23
Q

List some of the causes of male infertility

A 
Endocrine: Hypothyroidism, Hypogonadism
Erectile dysfunction 
Genetics: Klinefelter syndrome, Y deletion 
Infections 
Heat, drugs, chemo 
Torsion 
CF 
Duct obstruction 
Vasectomy
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24
Q

Which drugs decrease sperm count

A 
Alcohol
Tobacco 
Weed 
Testosterone supplements 
Chemo drugs
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25
Q

Which drugs cause hormone imbalances that can lead to male infertility

A

Weed
Testosterone supplements
Anabolic steroids

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26
Q

Which drugs can lead to decreased sex drive in men

A

Excessive alcohol

SSRI antidepressants

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27
Q

Which drugs can cause erectile dysfunction

A

Excessive alcohol
Tobacco
Cocaine

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28
Q

Which drugs can decrease the ability of sperm to fertilize the egg

A

CCB
Tetracycline antibiotics
Drugs for gout

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29
Q

What are the clinical features of non-obstructive male infertility

A 
Low testicular volume 
Reduced secondary sexual characteristics 
Vas deferens present 
High LH, FSH 
Low testosterone
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30
Q

List non-obstructive causes of male infertility

A

47 XXY (Klinefelter’s)
Chemo or radiotherapy
Undescended testes
Idiopathic

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31
Q

List obstructive causes of male infertility

A

Congenital abscess - CF
Infection
Vasectomy

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32
Q

What are the clinical features of obstructive male infertility

A

Normal testicular volume
Normal secondary sexual characteristics
Vas deferens may be absent
Normal LH, FSH and testosterone

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33
Q

Which examinations would you do in a female in an infertility case

A

BMI
General examination, assessing body hair distribution, galactorrhoea
Pelvic examination, assessing for uterine and ovarian abnormalities/tenderness/mobility

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34
Q

Which examinations would you do in a male in an infertility case

A

BMI
General examination
Genital examination, assessing size/position testes, penile abnormalities, presence vas deferens, presence varicoceles

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35
Q

Which investigations are needed in a female with infertility

A 
Swab for chlamydia 
Cervical smear test 
Blood for rubella immunity 
Mid-luteal progesterone 
Test of tubal patency 
if indicated: hysteroscopy, ultrasound scan, endocrine profile and chromosomes
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36
Q

When is a hysterectomy indicated

A

Only performed in cases where suspected or known endometrial pathology:
i.e. uterine septum, adhesions, polyp

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37
Q

When would you perform a pelvic ultrasound

A

when abnormality on pelvic examination: e.g. enlarged uterus /adnexal mass
Or when required from other investigations: e.g. possible polyp seen on other investigation

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38
Q

Which endocrine tests would you do if there is anovulatory cycles or infrequent periods

A 
Urine HCG
Prolactin
TSH
Testosterone and SHBG
LH, FSH and oestradiol
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39
Q

Which endocrine tests would you do if the patient is hirsute

A

Testosterone and SHBG

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40
Q

Which endocrine tests would you do if there is amenorrhea

A 
endocrine profile (as in anovulatory cycle)
 chromosome analysis
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41
Q

How do you carry out semen analysis

A

Two tests over 6 weeks apart

Look at volume, pH, concentration, motility, morphology and WBC

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42
Q

Which other assessments are needed if the semen analysis is abnormal

A

LH and FSH
Testosterone
Prolactin
Thyroid function

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43
Q

Which other assessments are needed if the semen analysis is severely abnormal or azoospermic

A

endocrine profile (as in abnormal semen)
chromosome analysis and Y chromosome microdeletions
screen for cystic fibrosis
testicular biopsy

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44
Q

Which other assessments are needed if the genital examination is abnormal

A

Scrotal ultrasound

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45
Q

What is the average length of a menstrual cycle

A

Mean is 28 days
Ranges from 21-35
Day 1 is the first day of bleeding

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46
Q

On which day does ovulation normally occur

A

14

Can vary due to differences in length of follicular phase

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47
Q

Describe the follicular phase

A

Begins when oestrogen levels are low
Anterior pituitary secretes FSH and LH stimulation follicle to develop
A leading follicle develops
Granulosa cells around egg enlarge, releasing oestrogen
This causes this uterine lining to thicken

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48
Q

Describe ovulation

A

Happens at the peak of follicular growth in response to LH surge
Follicles grow so oestradiol levels increase which cause LH surge
34-36hrs after the LH peak, the oocyte is released
Several proteolytic enzymes and prostaglandins are activated- digestion of the follicle wall collagen
Follicle ruptures, releasing ova into the Fallopian tubes

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49
Q

Describe the luteal phase

A

The secretory phase starts after ovulation
The remaining granulosa cells are now called the corpus luteum and produce progesterone
Peak progesterone production is noted 1 week after ovulation takes place
Progesterone switched off LH production
If pregnant, embryo will release hormones to preserve corpus luteum

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50
Q

Describe menstruation

A

Occurs after luteal phase if there is no embryo
the corpus luteum begins to disintegrate
Progesterone levels drop, uterine lining detaches, menstruation can begin
Tissue, blood, unfertilized egg all discharged
Can take from 3-7 days

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51
Q

Which cells in the hypothalamus produce GnRH

A

Arcuate nucleus

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52
Q

Where are FSH and LH released from

A

anterior pituitary

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53
Q

Describe the structure and location of the ovaries

A

In the pelvis
Attached to pelvic side wall by IP ligament
Made up of outer cortex an inner medulla (cortex has follicles)

54
Q

Describe the structure of the uterus

A

Fibro muscular organ
Contains the body of the uterus and the cervix
Endometrium - basal layer and superficial layer
Endometrium thickens in response to oestrogen
Lack of hCG and progesterone – endometrium sloughs off

55
Q

Describe GnRH (structure and function)

A

Is a deca peptide hormone
3 types of GnRH hormone
GnRH 1 is responsible for the reproductive function
Responsible for release of FSH and LH
Released in a pulsatile manner - increased by oestrogen and decreased by progesterone
Constant level in men
Half life is 2- 4 minutes

56
Q

Describe FSH (structure and function)

A

FSH is a glycoprotein contains 2 subunits
Half life of several hours
FSH is responsible for recruiting the dominant follicle
It is also responsible for granulosa cell growth and activates aromatase activity
In men is causes sperm production secretion

57
Q

Describe the action of oestrogen

A

Acts synergistically with FSH
Induces FSH and LH receptors
Increase thickness of vaginal wall
Regulate LH surge
Regulate vaginal pH through lactic acid production
Decrease viscosity of cervical mucus to facility sperm penetration

58
Q

Describe the function of inhibin

A

Local peptide in the follicular fluid
-ve feed back on pituitary FSH secretion
Locally enhances LH-induced androstenedione production

59
Q

Describe the function of activin

A

Found in follicular fluid

Stimulates FSH induced estrogen production

60
Q

Which cells make up the tubular components of the testes and what are their functions

A

Sertoli cells - Support germ cells in development
- Have FSH receptors

Germ cells - develop sperm (Spermatogonia)

61
Q

Which cells make up the interstitial components of the testes

A

Leydig cells - have LH receptors to cause testosterone secretion
Capillaries - have a blood/testes barrier

62
Q

When do GnRH levels peak in men

A

peak at night in men: peak testosterone in the morning causes erections

63
Q

What is folliculogenesis

A

Growth of follicle
Have a fixed set at birth which are converted to follicles during menstrual cycle
Once follicle reaches a certain size it needs FSH to continue
5/6 are recruited per cycle but only one ovulates - dominant

64
Q

Describe the functions of progesterone

A 
Pro-gestational hormone (maintain pregnancy) 
Maintains thickness of endometrium 
Responsible for infertile thick mucus (prevent sperm transport and help prevent infection) 
Relaxes myometrium (smooth muscle)
65
Q

How long does spermatogenesis take

A

70 days

66
Q

Describe the function of testosterone

A

Maintains integrity of blood-testes barrier

Release mature spermatozoa

67
Q

Why are eggs so much larger than sperm

A

They carry the cytoplasm and organelles necessary for cell division and growth
(yolk protein, ribosomes, t-RNA, m-RNA etc)
Sperm just a nucleus

68
Q

Which changes must occur in the female genital tract prior to fertilisation

A

Changes in the cervical mucus – becomes thin
Muscular contractions of the uterus and the fallopian tube
The fimbrial end comes into contact with the ovary
Peristaltic movements brings it to the ampulla

69
Q

Which process must sperm undergo before they can fertilise and egg

A

Capacitation

Occurs in the female genital tract

70
Q

Describe the steps of fertilisation

A

Chemotaxis - around the egg there are specific receptors that produces exocytosis
Release of acrosomal enzymes
Binding of sperm
Passage through the extracellular envelope
Fusion of the pronuclei

71
Q

Describe the reactions that occur once sperm has made contact with the egg

A

increase in calcium levels - this triggers further changes
Triggers the egg to complete meiosis
Triggers a cytoplasmic rearrangement
Causes a sharp increase in protein synthesis and metabolic activity in general

72
Q

What is the function of LH

A

in female: peaks stimulate ovulation, stimulates corpus luteum development, thickens endometrium

In men: stimulates Leydig cells, testosterone secretion, spermatogenesis

73
Q

what is oligomenorrhea

A

cycle lasting more than 35 days

associated with ovulatory disorders

74
Q

where is oestrogen secreted from

A

Primarily by the ovaries
Adrenal cortex
Placenta in pregnancy

75
Q

Do regular or irregular cycles suggest ovulation

A

Regular - very suggestive

If irregular cycles then probably not ovulating and needs further hormone testing

76
Q

How do you confirm ovulation

A

Confirm by midluteal (D21) serum progesterone (>30 nmol/L) X 2 samples

77
Q

What is amenorrhea

A

absent menstruation

associated with ovulatory disorders

78
Q

What is azoospermia

A

no sperm production

79
Q

What do you analyse in semen tests

A

sperm count
motility
morphology

80
Q

In what percentage of infertile couples is ovulatory dysfunction the issue

A

25%

81
Q

What are the 3 WHO classifications of ovulatory disorders

A

Group 1 - hypothalamic pituitary failure
Group 2 - hypothalamic pituitary dysfunction
Group 3 - ovarian failure

82
Q

Describe hypothlamaic pituitary failure

A

Hypogonadotropic hypogonadism - low GnRH and LH/FSH
Causes 10% of ovulatory disorders
Have oestrogen deficiency - negative progesterone challenge test
Normal prolactin
Amenorrhea

83
Q

What is a progesterone challenge test

A

Checks oestrogen response
Give progesterone for 5 days then stop
Should have withdrawal bleed in response if oestrogen is normal
If no bleed then oestrogen is low

84
Q

List causes of hypothlamaic pituitary failure

A 
Stress
Excessive exercise
Anorexia / low BMI
Brain / pituitary tumours
Head trauma / RTX
Kallman’s syndrome
Drugs (steroids, opiates)
85
Q

How do you manage hypothlamaic pituitary failure

A

Stabilise weight

Hormone therapy - pulsatile GnRH or gonadotrophin injections

86
Q

Describe hypothalamic pituitary dysfunction

A 
Normal gonadotrophins 
Excess LH 
Normal oestrogen levels
Associated with oligo/amenorrhea  
Includes PCOS
87
Q

Describe the signs of PCOS

A

Must have 2/3 of:
Oligo/amenorrhoea
Polycystic ovaries on US (increased volume, can be uni or bilateral)
Clinical or biochemical signs of hyperandrogenism - acne or hirsutism

88
Q

What effect does insulin have on levels of sex hormone binding globulin

A

Lowers the level

Increases free testosterone which leads to hyperandrogenism

89
Q

PCOS is associated with insulin resistance - true or false

A

True
seen in 50-80% of PCOS cases
Get a diminished biological response to a given level of insulin
Normal pancreatic reserve so get hyperinsulinaemia

90
Q

What factors need to be considered before starting fertility treatment

A

Weight loss
Stop smoking and drinking
Take folic acid 400mcg or up to 5mg daily (higher dose for higher BMI)
Check prescribed drugs are safe for pregnancy
Rubella immunity
Semen analysis

91
Q

Which drugs are used for ovulation induction in PCOS

A

Clomifene citrate - Clomid

Gonadotrophin injections

92
Q

What are the risks of gonadotrophin injections

A

Multiple pregnancy

Overstimulation of ovary

93
Q

How is laparoscopic ovarian diathermy used

A

Deliver heat treatment directly to the ovary
Used in PCOS to induce ovulation
Risk of ovarian destruction

94
Q

How is metformin used in ovulation induction

A 
Improves insulin resistance 
Reduced androgen production 
Increased SHBG 
Restores menstruation and ovulation 
May improve sensitivity to clomifene
95
Q

What are the risks of ovulation induction

A

Ovarian hyperstimulation
Multiple pregnancy - more risky for mum and babies
May have risk of ovarian cancer

96
Q

What risk does multiple pregnancy pose to the mother

A 
Hyperemesis
Anaemia
4 x hypertension 
3 x pre-eclampsia
3 x risk gestational diabetes
Mode of delivery 
Post-partum haemorrhage 
Postnatal depression / stress
97
Q

What risk does multiple pregnancy pose to the baby

A 
Early and late miscarriage
Low birth weight (<2.5kg)
Prematurity
Disability
Stillbirth / neonatal death 
Twin-twin transfusion syndrome
98
Q

What is twin-twin transfusion syndrome

A

Specific to those that share a placenta but have their own amniotic sac
Get an imbalance of vascular communication (one twin receives a much greater share)
Is fatal if not treated
Can do laser treatment of vessels to rebalance or create connection between the two sacs

99
Q

What are the early problems associated with prematurity

A

Many will end up in neonatal intensive care
May need respiratory support
6% suffer from respiratory distress syndrome

100
Q

What are the long term problems associated with prematurity

A 
In 7.4% of twin pregnancies at least one child is affected with disability 
6x increase in cerebral palsy 
Impaired sight 
congenital heart disease 
low IQ, ADHD etc
101
Q

How does ovulation induction affect your risk of ovarian cancer

A

Putative risk of borderline ovarian tumours if used longer than 12 months
Not fully supported but to be safe you don’t treat for over 12 months

102
Q

Describe the signs of ovarian failure

A

High levels of gonadotrophins
Low oestrogen levels
Amenorrhea
Menopausal before 40

103
Q

List potential causes of premature ovarian failure

A

Genetic: turner syndrome, XX gonadal agenesis, fragile X
Autoimmune
Bilateral oophorectomy
Pelvic radiotherapy or chemo

104
Q

How do you treat premature ovarian failure

A

Hormone replacement therapy
Egg or Embryo donation if they want to get pregnant
Ovary / egg / embryo cryopreservation prior to chemo/radiotherapy where POF anticipated
Counselling/ Support network

105
Q

List some potential causes of testicular failure

A

genetic: Klinefelter’s syndrome 47 XXY, Y chromosome microdeletion
Orchidectomy / undescended testes
Testicular trauma / torsion / mumps orchitis
Testicular cancer
Pelvic radiotherapy, chemotherapy
Autoimmune disease

106
Q

What are the signs and symptoms of hyperprolactinaemia

A 
Amenorrhoea
Galactorrhoea
Some medications can cause - dopamine antagonists 
Normal LH/FSH but low oestrogen 
Raised serum prolactin
107
Q

How do you treat hyperprolactinaemia

A

Dopamine agonist
Long acting = cabergoline 2x week
Or bromocriptine

108
Q

How is ultrasound used in infertility consultation

A

Routine test
transvaginal route
Looks at pelvic anatomy: uterus, ovarian morphology
Fallopian tubes hard to identify

109
Q

If semen tests came back abnormal what further investigations would you do

A

Check LH, FSH, testosterone, prolactin

Karyotype, CF mutation, Y microdeletions

110
Q

What lifestyle advice should be given to couples having fertility issues

A

Both need to stop smoking
Achieve a healthy BMI (at least under 30)
Reduce or stop alcohol intake
Take caffeine containing drinks in moderation
Stop recreational drugs
Stop methodone

111
Q

How does increased weight affect fertility in women

A

Increased risk of fertility problems
Increased miscarriage rate
Less success for fertility treatments

112
Q

How does increased weight affect fertility in men

A

Increased incidence of fertility issues
May damage DNA in sperm
Increased chance of erectile dysfunction

113
Q

After how long trying should you consult a fertility expert

A

12 months

114
Q

What general advice should be given to couples struggling to conceive

A

Reassure that 84% of couples conceive in the first year
Advice sexual intercourse every 2-3 days rather than using ovulation tests or trying to sync with cycle
Consider psychosexual problems
Consider any needed pre-conception counselling for existing conditions

115
Q

Which supplements would you suggest for those trying to conceive and/or for pregnant women

A

Folic acid - 400mcg pre-pregnancy and in first 12 weeks
5mg pre and in early stages for those with risk of neural tube defects

Vitamin D - 10mcg for pregnant and lactating women

116
Q

Which blood screening tests should be done in pre or early stages of pregnancy

A

Blood rubella Immunity - give vaccine if non-immune and not pregnant (live vaccine dangerous in pregnancy)
Screen for chlamydia and gonorrhoea - treat if positive

117
Q

What is rubella syndrome

A

Abnormalities that develop in a baby if their mother contracted rubella whilst pregnant
Can result in microcephaly, patent ductus arteriosus, cataracts and rash

118
Q

List the potential causes of infertility that can be treated by surgery

A

Pelvic adhesions
Grade 1& 2 Endometriosis
Chocolate cysts in Ovary
Tubal Block

119
Q

When is surgery for tubal disease effective

A

Success depends on amount of healthy tube, whether both proximal and distal tubal disease, condition of tubal wall and the presence of adhesions
Effective in mild disease

120
Q

How do you treat a proximal tubal obstruction

A

Selective salpingography (removal of tube) plus tubal catheterisation, or hysteroscopic tubal cannulation

121
Q

How do you treat hydropsalpinges

A

Salpingectomy (tubal removal) , preferably by laparoscopy, before IVF treatment to improve chance of live birth

122
Q

What is a Hydrosalpinx

A

When the fallopian tube becomes blocked by fluid
Harder to get pregnant
Sometimes the fluid can become toxic and damage pregnancy so can be clipped

123
Q

At what point in IVF treatment would a hysteroscopy be needed

A

If IVF keeps failing (3 attempts) then you probably do a hysteroscopy to see if there is an internal problem

124
Q

How would you manage an intrauterine polyp

A

Myosure polypectomy

Slices the polyp and then sucks it to get rid of it

125
Q

How would you manage an uterine septum

A

Metroplasty - removing the septum increases rate of pregnancy

126
Q

What are fibroids and what are the 4 different types

A 
Benign lump growing in the wall of the uterus 
Penduculated - on stalk 
Subserous - under serous layer 
Submucous - under mucosa
Intramural - within the wall
127
Q

How are submucosal fibroids managed

A

should be treated hysteroscopically to improve conception rates

128
Q

How do subserosal fibroids affect fertility

A

unlikely to have any major impact on fertility.

129
Q

What criteria must be met to be eligible for NHS IVF

A

Woman’s BMI must be under 30
Must have lived together for at least 2 years
Must be non-smokers
No tubal block

Will get 3 cycles if eligible

130
Q

How does age impact the success of IVF

A

The younger the woman, the better the egg quality and the higher the chance of success

Endocrinology (13 decks)

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