Reproduction and Fertility Flashcards
How many couples are affected by infertility
1:6 - 15%
List possible causes of the increase in incidence of infertility
Older women
Rise in chlamydia infection
Increasing obesity
Increasing male infertility
What is the definition of infertility
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
What is the difference between primary or secondary
Primary - couple have never had a child
Secondary - previously conceived but pregnancy may not have been successful
What gives a good prognosis for conceiving with treatment
age < 30yrs, short duration of infertility and secondary infertilty
What gives a bad prognosis for conceiving with treatment
male infertility, endometriosis and tubal factor infertility
Which factors lead to an increased chance of conception
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
Fertility decreases with age - true or false
TRUE
incidence of spontaneous abortion also increases
Which physiological states can lead to anovulatory infertility
Before puberty
Pregnancy
Lactation
Menopause
Which pathological states can lead to anovulatory infertility
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
What are the clinical features of anorexia nervosa
Low BMI Loss of hair Low pulse and BP Anaemia Low FSH, LH and oestradiol
What is the cause of PCOS
Inherited condition
Exacerbated by weight gain
What are the clinical features of PCOS
Obesity Hirsutism or acne Cycle abnormalities Infertility High free androgens High LH Impaired glucose tolerance
How do you diagnose PCOS
Score 2 out of three:
chronic anovulation
polycystic ovaries
hyperandrogenism
What causes premature ovarian failure
Can be idiopathic
Genetic - Turner’s or fragile X
Chemotherapy
Radiotherapy
What are the clinical features of premature ovarian failure
Hot flushes Night sweats Atrophic vaginitis High FSH and LH Low oestradiol
What are the infective causes of tubal disease
PID - caused by chlamydia, gonorrhoea etc
Transperitoneal spread from appendicitis or intra-abdominal abscess
Following a procedure - IUD, hysteroscopy etc
What are the non-infective causes of tubal disease
endometriosis surgical (sterilisation, ectopic pregnancies) fibroids polyps congenital salpingitis isthmica nodosa
What are the clinical features of hydrosalpinx (blockage) due to PID
abdominal/pelvic pain febrile vaginal discharge dyspareunia cervical excitation menorrhagia dysmenorrhoea infertility ectopic pregnancy
What is endometriosis
presence of endometrial glands outside uterine cavity
What are the potential causes of endometriosis
Retrograde menstruation is most likely cause
Altered immune function
Abnormal cellular adhesion molecules
Genetic
What are the clinical features of endometriosis
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
List some of the causes of male infertility
Endocrine: Hypothyroidism, Hypogonadism Erectile dysfunction Genetics: Klinefelter syndrome, Y deletion Infections Heat, drugs, chemo Torsion CF Duct obstruction Vasectomy
Which drugs decrease sperm count
Alcohol Tobacco Weed Testosterone supplements Chemo drugs
Which drugs cause hormone imbalances that can lead to male infertility
Weed
Testosterone supplements
Anabolic steroids
Which drugs can lead to decreased sex drive in men
Excessive alcohol
SSRI antidepressants
Which drugs can cause erectile dysfunction
Excessive alcohol
Tobacco
Cocaine
Which drugs can decrease the ability of sperm to fertilize the egg
CCB
Tetracycline antibiotics
Drugs for gout
What are the clinical features of non-obstructive male infertility
Low testicular volume Reduced secondary sexual characteristics Vas deferens present High LH, FSH Low testosterone
List non-obstructive causes of male infertility
47 XXY (Klinefelter’s)
Chemo or radiotherapy
Undescended testes
Idiopathic
List obstructive causes of male infertility
Congenital abscess - CF
Infection
Vasectomy
What are the clinical features of obstructive male infertility
Normal testicular volume
Normal secondary sexual characteristics
Vas deferens may be absent
Normal LH, FSH and testosterone
Which examinations would you do in a female in an infertility case
BMI
General examination, assessing body hair distribution, galactorrhoea
Pelvic examination, assessing for uterine and ovarian abnormalities/tenderness/mobility
Which examinations would you do in a male in an infertility case
BMI
General examination
Genital examination, assessing size/position testes, penile abnormalities, presence vas deferens, presence varicoceles
Which investigations are needed in a female with infertility
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
When is a hysterectomy indicated
Only performed in cases where suspected or known endometrial pathology:
i.e. uterine septum, adhesions, polyp
When would you perform a pelvic ultrasound
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
Which endocrine tests would you do if there is anovulatory cycles or infrequent periods
Urine HCG Prolactin TSH Testosterone and SHBG LH, FSH and oestradiol
Which endocrine tests would you do if the patient is hirsute
Testosterone and SHBG
Which endocrine tests would you do if there is amenorrhea
endocrine profile (as in anovulatory cycle) chromosome analysis
How do you carry out semen analysis
Two tests over 6 weeks apart
Look at volume, pH, concentration, motility, morphology and WBC
Which other assessments are needed if the semen analysis is abnormal
LH and FSH
Testosterone
Prolactin
Thyroid function
Which other assessments are needed if the semen analysis is severely abnormal or azoospermic
endocrine profile (as in abnormal semen)
chromosome analysis and Y chromosome microdeletions
screen for cystic fibrosis
testicular biopsy
Which other assessments are needed if the genital examination is abnormal
Scrotal ultrasound
What is the average length of a menstrual cycle
Mean is 28 days
Ranges from 21-35
Day 1 is the first day of bleeding
On which day does ovulation normally occur
14
Can vary due to differences in length of follicular phase
Describe the follicular phase
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
Describe ovulation
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
Describe the luteal phase
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
Describe menstruation
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
Which cells in the hypothalamus produce GnRH
Arcuate nucleus
Where are FSH and LH released from
anterior pituitary
Describe the structure and location of the ovaries
In the pelvis
Attached to pelvic side wall by IP ligament
Made up of outer cortex an inner medulla (cortex has follicles)
Describe the structure of the uterus
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
Describe GnRH (structure and function)
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
Describe FSH (structure and function)
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
Describe the action of oestrogen
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
Describe the function of inhibin
Local peptide in the follicular fluid
-ve feed back on pituitary FSH secretion
Locally enhances LH-induced androstenedione production
Describe the function of activin
Found in follicular fluid
Stimulates FSH induced estrogen production
Which cells make up the tubular components of the testes and what are their functions
Sertoli cells - Support germ cells in development
- Have FSH receptors
Germ cells - develop sperm (Spermatogonia)
Which cells make up the interstitial components of the testes
Leydig cells - have LH receptors to cause testosterone secretion
Capillaries - have a blood/testes barrier
When do GnRH levels peak in men
peak at night in men: peak testosterone in the morning causes erections
What is folliculogenesis
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
Describe the functions of progesterone
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)
How long does spermatogenesis take
70 days
Describe the function of testosterone
Maintains integrity of blood-testes barrier
Release mature spermatozoa
Why are eggs so much larger than sperm
They carry the cytoplasm and organelles necessary for cell division and growth
(yolk protein, ribosomes, t-RNA, m-RNA etc)
Sperm just a nucleus
Which changes must occur in the female genital tract prior to fertilisation
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
Which process must sperm undergo before they can fertilise and egg
Capacitation
Occurs in the female genital tract
Describe the steps of fertilisation
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
Describe the reactions that occur once sperm has made contact with the egg
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
What is the function of LH
in female: peaks stimulate ovulation, stimulates corpus luteum development, thickens endometrium
In men: stimulates Leydig cells, testosterone secretion, spermatogenesis
what is oligomenorrhea
cycle lasting more than 35 days
associated with ovulatory disorders
where is oestrogen secreted from
Primarily by the ovaries
Adrenal cortex
Placenta in pregnancy
Do regular or irregular cycles suggest ovulation
Regular - very suggestive
If irregular cycles then probably not ovulating and needs further hormone testing
How do you confirm ovulation
Confirm by midluteal (D21) serum progesterone (>30 nmol/L) X 2 samples
What is amenorrhea
absent menstruation
associated with ovulatory disorders
What is azoospermia
no sperm production
What do you analyse in semen tests
sperm count
motility
morphology
In what percentage of infertile couples is ovulatory dysfunction the issue
25%
What are the 3 WHO classifications of ovulatory disorders
Group 1 - hypothalamic pituitary failure
Group 2 - hypothalamic pituitary dysfunction
Group 3 - ovarian failure
Describe hypothlamaic pituitary failure
Hypogonadotropic hypogonadism - low GnRH and LH/FSH
Causes 10% of ovulatory disorders
Have oestrogen deficiency - negative progesterone challenge test
Normal prolactin
Amenorrhea
What is a progesterone challenge test
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
List causes of hypothlamaic pituitary failure
Stress Excessive exercise Anorexia / low BMI Brain / pituitary tumours Head trauma / RTX Kallman’s syndrome Drugs (steroids, opiates)
How do you manage hypothlamaic pituitary failure
Stabilise weight
Hormone therapy - pulsatile GnRH or gonadotrophin injections
Describe hypothalamic pituitary dysfunction
Normal gonadotrophins Excess LH Normal oestrogen levels Associated with oligo/amenorrhea Includes PCOS
Describe the signs of PCOS
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
What effect does insulin have on levels of sex hormone binding globulin
Lowers the level
Increases free testosterone which leads to hyperandrogenism
PCOS is associated with insulin resistance - true or false
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
What factors need to be considered before starting fertility treatment
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
Which drugs are used for ovulation induction in PCOS
Clomifene citrate - Clomid
Gonadotrophin injections
What are the risks of gonadotrophin injections
Multiple pregnancy
Overstimulation of ovary
How is laparoscopic ovarian diathermy used
Deliver heat treatment directly to the ovary
Used in PCOS to induce ovulation
Risk of ovarian destruction
How is metformin used in ovulation induction
Improves insulin resistance Reduced androgen production Increased SHBG Restores menstruation and ovulation May improve sensitivity to clomifene
What are the risks of ovulation induction
Ovarian hyperstimulation
Multiple pregnancy - more risky for mum and babies
May have risk of ovarian cancer
What risk does multiple pregnancy pose to the mother
Hyperemesis Anaemia 4 x hypertension 3 x pre-eclampsia 3 x risk gestational diabetes Mode of delivery Post-partum haemorrhage Postnatal depression / stress
What risk does multiple pregnancy pose to the baby
Early and late miscarriage Low birth weight (<2.5kg) Prematurity Disability Stillbirth / neonatal death Twin-twin transfusion syndrome
What is twin-twin transfusion syndrome
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
What are the early problems associated with prematurity
Many will end up in neonatal intensive care
May need respiratory support
6% suffer from respiratory distress syndrome
What are the long term problems associated with prematurity
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
How does ovulation induction affect your risk of ovarian cancer
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
Describe the signs of ovarian failure
High levels of gonadotrophins
Low oestrogen levels
Amenorrhea
Menopausal before 40
List potential causes of premature ovarian failure
Genetic: turner syndrome, XX gonadal agenesis, fragile X
Autoimmune
Bilateral oophorectomy
Pelvic radiotherapy or chemo
How do you treat premature ovarian failure
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
List some potential causes of testicular failure
genetic: Klinefelter’s syndrome 47 XXY, Y chromosome microdeletion
Orchidectomy / undescended testes
Testicular trauma / torsion / mumps orchitis
Testicular cancer
Pelvic radiotherapy, chemotherapy
Autoimmune disease
What are the signs and symptoms of hyperprolactinaemia
Amenorrhoea Galactorrhoea Some medications can cause - dopamine antagonists Normal LH/FSH but low oestrogen Raised serum prolactin
How do you treat hyperprolactinaemia
Dopamine agonist
Long acting = cabergoline 2x week
Or bromocriptine
How is ultrasound used in infertility consultation
Routine test
transvaginal route
Looks at pelvic anatomy: uterus, ovarian morphology
Fallopian tubes hard to identify
If semen tests came back abnormal what further investigations would you do
Check LH, FSH, testosterone, prolactin
Karyotype, CF mutation, Y microdeletions
What lifestyle advice should be given to couples having fertility issues
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
How does increased weight affect fertility in women
Increased risk of fertility problems
Increased miscarriage rate
Less success for fertility treatments
How does increased weight affect fertility in men
Increased incidence of fertility issues
May damage DNA in sperm
Increased chance of erectile dysfunction
After how long trying should you consult a fertility expert
12 months
What general advice should be given to couples struggling to conceive
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
Which supplements would you suggest for those trying to conceive and/or for pregnant women
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
Which blood screening tests should be done in pre or early stages of pregnancy
Blood rubella Immunity - give vaccine if non-immune and not pregnant (live vaccine dangerous in pregnancy)
Screen for chlamydia and gonorrhoea - treat if positive
What is rubella syndrome
Abnormalities that develop in a baby if their mother contracted rubella whilst pregnant
Can result in microcephaly, patent ductus arteriosus, cataracts and rash
List the potential causes of infertility that can be treated by surgery
Pelvic adhesions
Grade 1& 2 Endometriosis
Chocolate cysts in Ovary
Tubal Block
When is surgery for tubal disease effective
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
How do you treat a proximal tubal obstruction
Selective salpingography (removal of tube) plus tubal catheterisation, or hysteroscopic tubal cannulation
How do you treat hydropsalpinges
Salpingectomy (tubal removal) , preferably by laparoscopy, before IVF treatment to improve chance of live birth
What is a Hydrosalpinx
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
At what point in IVF treatment would a hysteroscopy be needed
If IVF keeps failing (3 attempts) then you probably do a hysteroscopy to see if there is an internal problem
How would you manage an intrauterine polyp
Myosure polypectomy
Slices the polyp and then sucks it to get rid of it
How would you manage an uterine septum
Metroplasty - removing the septum increases rate of pregnancy
What are fibroids and what are the 4 different types
Benign lump growing in the wall of the uterus Penduculated - on stalk Subserous - under serous layer Submucous - under mucosa Intramural - within the wall
How are submucosal fibroids managed
should be treated hysteroscopically to improve conception rates
How do subserosal fibroids affect fertility
unlikely to have any major impact on fertility.
What criteria must be met to be eligible for NHS IVF
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
How does age impact the success of IVF
The younger the woman, the better the egg quality and the higher the chance of success
