Infertility Flashcards
How many couples will experience infertility
1 in 6
Around half will go onto conceive spontaneously whilst the other half will need assisted conception
Why might the incidence of assisted conception be on the rise
Increasing parental age Increasing chlamydia Increasing obesity Male factor infertility rising Increasing range of ACT and awareness of it Improved success rates Same sex couples and surrogacy
What are some of the indications for assisted conception treatment
When at least one partner has no biological children Male factor infertility
Tubal diseases
Endometriosis
Ovulation disorders
PIGD for inherited disorders is needed
Fertility preservation in cancer patients
Single, same-sex or transgender parents
What must the patient do before they start IVF
Limit alcohol intake to 4 units per week - F
Stop smoking - must have not smoked for at least 3 months
Optimal weight in both M and F - BMI between 19 and 29 is optimal
Start taking folic acid - 0.4mg/day prior to conception then up to 12 weeks
Get rubella vaccine if not already had it
Reduce occupational hazards if possible
Check smears are up to date
Screen for BBV
How much folic acid should you take if wanting to get pregnant
0.4mg per day from before conception up until 12 weeks of pregnancy
5mg if you are a high risk mum - obese or diabetic
What checks should the doctor do before referring someone for IVF
Take a full history Check female rubella status and immunize if not already Check cervical smears are up to date Swab for chlamydia and gonorrhea Screen for blood borne viruses Check occupation and advise if there are any hazards Check the drugs they are on are safe Assess ovarian reserve
What are the indications for intra-uterine insemination
Sexual problems Same sex relationship Discordant BBV Abandoned IVF Mild male factor infertility
What is intrauterine uterine insemination
Prepared semen inserted into uterine cavity around time of ovulation
What are the indications for IVF
Unexplained infertility for over 2 years
Pelvic disease - fibroids, endometriosis
Anovulatory infertility - after failed induction
Failed insemination (6 cycles)
How are oocytes grown and collected for IVF treatment
Down regulation of natural cycle with GnRH analogues - takes a few weeks
Then ovarian stimulation with FSH/LH to cause follicular development - can be self-admin
Monitor ovary response to drugs via US - see follicles developing
HCG injection to cause ovulation - done at final stage of oocyte maturation
Collection of oocytes in theatre under US guidance
What are the side effects of GnRH analogues
Hot flushes Mood swings Nasal irritation Headaches Basically an artificial menopause
How is a semen sample collected
Need to be abstinent for 72 hours before
Produce sample in ward or at home (need to get it to hospital within 1 hr)
Advised to keep it close to body to maintain temperature
Ideally caffeine and alcohol should be avoided in the days
leading up to the test.
How do you assess semen
Volume in ml
Density - concentration of sperm (should be over 15 million)
Total sperm number
Motility - what proportion are moving (should be at least 32%)
Progression - how well they move
Sperm morphology
pH
What are the risks of oocyte collection
Bleeding
Pelvic infection
Failure to obtain oocytes
Damage to the viscera
At what day are the embryos transferred or preserved
Day 5 - blastocyst stage
Usually only transfer 1 embryo
What are the indications for ICSI
Severe male factor infertility
Previous failed fertilisation with IVF
Preimplantation genetic diagnosis
If the father has azoospermia how do you get sperm
Surgical Sperm Aspiration
Taken from epididymis if obstructive
Taken directly from testicular tissue if not
What are some of the complication of assisted conception
Ovarian hyper-stimulation syndrome Multiple pregnancy Ectopic pregnancy Increased miscarriage risk Surgical risk of oocyte collection
How does Ovarian hyper-stimulation syndrome present
Deranged bloods - release of inflammatory markers and vasoactive substances
Hyponatremia and hyperkalaemia
This leads to fluid shift causing: Abdominal pain and bloating N and V Ascites - clinical or on US Large ovaries
Severe cases can cause VTE and ARDS
How do reduce risk of ovarian hyper-stimulation syndrome after embryo transfer
Monitor with scans and bloods
Reduce thrombosis risk - stockings, fluids etc
Analgesia
How can you reduce the risk of ovarian hyper-stimulation syndrome
Low dose protocols
Use an antagonist for suppression
How can you manage ovarian hyperstimulation syndrome
Analgesia
Hospital admission if required IV fluids/more intensive monitoring/paracentesis
How can we reduce the incidence of multiple pregnancy from IVF
Move to blastocyst transfer
Improved cryopreservation
Only do single embryo transfer
What is the success rate of IVF
around 35%
Success is age dependant as well
What is the key to sexual differentiation
The SRY region of the Y chromosome
If present it triggers male development
Describe what happens to the Wolffian and Mullerian ducts in males
W = forms the reproductive tract (epididymis, vas deferens etc)
M - degenerates
Describe what happens to the Wolffian and Mullerian ducts in women
W = degenerate
M = forms the reproductive tract - uterus, fallopian tubes etc
What is responsible for the formation of the external genitalia
DHT - form of testosterone
Its presence causes male genitals to form
It’s absence leads to female genitals
At what point can you determine sex on an US
From 16 weeks
Describe androgen insensitivity syndrome
It’s a congenital insensitivity to androgens - X-linked
Will have male karyotype and testis but female external genitalia
Often thought to be girls and present with primary amenorrhea or lack of pubic hair
What is the blood supply to the testes
Testicular artery - branch of aorta
Testicular veins - drain into left renal vein, right drains straight into the IVC
Why do the testes need to descend
Need to be kept at a lower temperature, outside of the body
Which muscles are responsible for thermal regulation of the testes
Dartos and cremaster muscle
Cause contraction of scrotum to lower/raise the testes
What connects the testes to the body
Spermatic cord - contains arteries, veins, lymphatics and the vas deferens
What covers the testes
A double layer of the tunica vaginalis (peritoneal remnant)
Then the tunica albuingea – firm fibrous covering
What is cryptorchidism
Undescended testes in adolescence/adult
When should the testes have descended
By 6-9 months of age
What is the treatment for crytochidism
Orchidopexy - surgery to move teste into scrotum
Needs to be done by 12 months to prevent infertility and by 12 years to reduce cancer risk
If undescended in an adult consider removing the teste (orchiectomy ) due to high cancer risk
What is the corpus cavernosum
Two columns of tissue running along the sides of the penis.
Blood fills this tissue to cause an erection
What is the corpus spongiosum
A column of sponge-like tissue running along the front of the penis and ending at the glans penis
It fills with blood during an erection, keeping the urethra, which runs through it, open
What are the functions of the Sertoli cells
Forms the blood-testes barrier - protects the spermatozoa from antibodies
Provides nutrients
Phagocytosis of defective sperm
Secretes the seminiferous tubule fluid - needed to carry sperm to epididymus
Secretes androgen binging globulin
Secretes inhibin and activin hormones - regulates sperm production
What is the function of androgen binging globulin
Binds testosterone so concentration remains high in lumen
Essential for sperm production
How is GnRH released
Released from hypothalamus in bursts every 2-3 hours
This starts at age 8-12
Under negative feedback control from testosterone
What is the function of GnRH
Stimulates anterior pituitary to produce LH and FSH
In females this is cyclical but in men it is not
What is the function of LH in men
Acts on the Leydig cells to regulate testosterone secretion
What is the function of FSH in men
Acts on Sertoli cells to enhance spermatogenesis
Regulates by negative feedback from inhibin released from the sertoli cells
How is testosterone produced
Its a steroid hormone derived from cholesterol
Produced in the Leydig cells
Secreted into blood and seminiferous tubules for sperm production
Negative feedback on hypothalamus and pituitary gland
What is the function of testosterone before birth
It masculinises reproductive tract and promotes descent of testes
What is the function of testosterone during puberty
Promotes puberty and male characteristics
Growth and maturation male reproductive system
What is the function of testosterone in adulthood
Controls spermatogenesis - stimulates it
Secondary sexual characteristics - male body shape, deep voice
Libido and erections
Aggressive behaviour
Where are inhibin and activin produced
Secreted by the Sertoli cells
What are the functions of inhibin and activin
Inhibin inhibits FSH release
Activin stimulates it
Where does fertilisation take place
The ampullary region of the fallopian tube
What are the functions of the epididymis and vas deferens
Exit route from testes to urethra - sperm pass into epididymis then into vas deferens
Epididymus also concentrates and store sperm
Site for sperm maturation
What are the functions of the seminal vesicles
Produce seminal fluid and releases into ejaculatory duct Supply fructose - nourish sperm Secrete prostaglandins (stimulates motility) Secrete fibrinogen (clot precursor)
What are the functions of the prostate gland
Produces alkaline fluid (neutralizes vaginal acidity)
Produces clotting enzymes to clot semen within female
What are the functions of the bulbourethral glands
Secrete mucus to act as lubricant and neutralises any acidity, prior to
ejaculation
Describe the path of sperm from the testes to the female
Testes → epididymis → vas deferens → ejaculatory duct → urethra
Contraction of the sex glands and vas deferens expels semen into the urethra
The smooth muscles of the urethra and erectile muscles contract lead to ejaculation
What is the definition of male infertility
Infertility resulting from failure of the sperm to normally fertilise the egg
The presence of one or more abnormalities in the
semen analysis or the presence of inadequate sexual or ejaculatory function
What fraction of infertility cases are due to male factor
Approximately 1/3
What is the trend in male infertility
It is on the rise
What causes male infertility
Most commonly idiopathic
Obstructive or non obstructive defects
Give examples of obstructive causes of male infertility
Vasectomy
Cystic fibrosis - lack of vas deferens
Infections - can lead to fibrosis and block pathway
Give examples of non-obstructive causes of male infertility
Cryptorchidism - undescended testes
Mumps orchitis - reduced spermatogenesis
STIs - can cause epididymitis and orchitis
Chemo/radiotherapy
Testicular tumour
Genetic disorders - Klinefelter’s or Y microdeletions
Semen abnormality - e.g. low count/motility or absent sperm
Robertsonian Translocation - any type increases infertility risk
List some endocrine causes of male infertility
Hypothalamic causes: idiopathic, tumours, Kalman’s syndrome, anorexia
Pituitary tumours: acromegaly, Cushing’s disease, hyperprolactinaemia
Thyroid Disorders: hyper or hypo
Diabetes - decreases testosterone and sexual function
CAH - increases testosterone
Androgen insensitivity
Steroid abuse
How would you examine an infertile male
General - look for secondary sexual characteristic, gynaecomastia
Genital exam - Testicular volume, presence of vas and epi, scrotal swelling, evidence of surgery
Take bloods for hormone levels
Take a semen sample
What is considered normal testicular volume
Pre-puberty = 1-3mls Adults = 12-25mls
Measured with an orchidometer
A low testicular volume makes infertility likely - true or false
TRUE
If below 5ml unlikely to be fertile
What are the clinical features of obstructive azoospermia
Normal testicular volume
Normal secondary sexual characteristics
Vas deferens may be absent
What are the endocrine features of obstructive azoospermia
Normal LH, FSH and testosterone levels
What are the features of non-obstructive azoospermia
Low testicular volume
Reduced secondary sexual characteristics
Vas deferens present
High LH, FSH and low/normal testosterone
How can you treat male infertility
Treat any specific cause e.g. reversal of vasectomy if vasectomy
May need intrauterine insemination (mild cases) or ICSI (more severe) to conceive
Donor insemination if sperm are non viable or no sperm
What lifestyle changes can improve male fertility
Frequency sexual intercourse: 2-3 X per week Avoid lubricants that are toxic to sperm Alcohol: < 5 units per week Stop smoking Get BMI below 30
Are vasectomies reversible
Yes
Success rate decreases the longer you leave it though
Fibroids in which location are the most likely to cause difficulty conceiving
Submucosal
They lie in the uterine cavity and disrupt the process of embryo implantation
Which questions should be asked of both partners in an infertility history
BMI Smoking and alcohol PMHx = particularly previous pelvic infections/STI Drug history Intercourse regularity Sexual function Family history Environmental risks - exposure to pesticides or excessive heat on the testes
Which female specific questions should be asked in an infertility history
Obstetric history
Gynae history including menstrual cycle
Previous contraception
Which male specific questions should be asked in an infertility history
Previously fathered any children/ caused a pregnancy
Previous testicular trauma
Are they able to get and maintain an erection and ejaculate
What examination would you perform on the female partner in an infertility history
BMI
Check for secondary sexual characteristics
Bimanual and speculum pelvic exam
Check they are up to date with smears - offer if due
Swab for STIs
What examination would you perform on the male partner in an infertility history
BMI
Check for secondary sexual characteristics
Testicular volume
Genital examination
What is oligospermia
A low sperm count
Your sperm count is considered lower than normal if you have fewer than 15 million sperm per milliliter of semen
Which investigations should be performed on an infertile male to establish cause
Hormone profile - LH,FSH and testosterone
High FSH signifies spermatogenesis
failure
Genetic testing- cystic fibrosis screening and y
chromosome deletion
How do you induce ovulation in a patient with PCOS
Clomiphene induction
Will need hystersalpingogram prior to clomiphene
induction to ensure tubal patency.
Also need to ensure BMI is within range to be eligible
What is the definition of subfertility
Failure to conceive despite regular sex over 12 months in the absence of known reproductive pathology
What is primary subfertility
The couple have never been able to conceive
What is secondary subfertility
Couple has previously conceived but is no longer able to
Includes miscarriages, ectopics and stillbirths
Which factors increase the risk of infertility
Increased female age (>35)
Longer duration of infertility, Lack of previous pregnancy
The cause of the subfertility
What is the risk of rubella infection in the 1st trimester
50% of babies will develop congenital rubella syndrome
Presents with microcephaly, PDA, cataracts and rashes
How can you prevent congenital rubella syndrome
Give a booster MMR to unvaccinated mums during pregancy
List some of the short term consequences of PID
Tubo-ovarian abscess
Salphigitis, endometritis, oophoritis etc.
Peritonitis
Fitz-Hugh-Curtis syndrome - inflammation of peritoneum, liver capsule and diaphragm
List some of the long term consequences of PID
Chronic pelvic pain
Infertility - scarring and narrowing of tubes
Ectopic - increased risk due to scarring
Caused by blockage/damage to the tube
How are progesterone levels used in fertility assessment
Corpus luteum produces progesterone - rises in second half of cycle
Progesterone level is used as evidence of egg release
You test the midluteal progesterone level (day 21 if 28 day cycle or 7 days prior to expected period)
What is the purpose of ovarian drilling in the treatment of infertility
Ovarian drilling aims to allow release of the egg
Destroys stroma which reduces androgen-secreting tissue leading a restoration of the normal LH:FSH ratio and a fall in androgens.
Effective for 8-10 months following treatment
Which drugs are used for ovulation induction in PCOS
Anti-oestrogens - clomiphene citrate or tamoxifen
Taken daily from day 2 of cycle for 5 days
Other option is aromatase inhibitors - letrozole/anastrozole
What is the 1st line fertility treatment in PCOS
Ovulation induction - usually with clomifene citrate
Ovulation occurs in 70-80% but 40-50% conceive
How does the obesity seen in PCOS contribute to infertility
PCOS causes central obesity which leads to insulin insensitivity which in turn contributes to anovulation
Weight loss can improve fertility
Metformin can also be added to treatment to help
Regular cycles are suggestive of ovulation - true or false
True
Irregular is more suggestive of anovulation
Ovulation kits are not recommended by the fertility specialists - true or false
True
Neither is temperature monitoring or mucus consistency
The WHO splits ovulatory disorders into how many groups
3 main groups
Group 1 = hypothalamic causes
Group 2 - hypothalamic pituitary dysfunction
Group 3 - ovarian failure
List causes of infertility in the Group 1 = hypothalamic causes
Stress, excessive exercise
Anorexia/bulimia
Kalman’s syndrome - GnRH deficiency (genetic)
Isolated gonadotrophin deficiency
If infertility is caused by a hypothalamic disorder (group 1) what will the hormone levels be
Low FSH and oestrogen levels
Normal prolactin
Negative progesterone challenge
List causes of infertility in Group 2 = hypothalamic pituitary dysfunction
PCOS - normogonadotrophic normo-oestrogenic anovulation
Hyperprolactinaemia
Sheehan’s Syndrome (post-partum hypopituitarism)
Pituitary adenomas
List causes of infertility in Group 3 = ovarian failure
Any form of ovarian failure or resistant ovary
If infertility is caused by ovarian failure (group 3 ) what will the hormone levels be
High gonadotrophins - LH/FSH
Low oestrogen
How does a polycystic ovary present on US
Increased ovarian volume (>10mls)
More than 12 follicles between 2-8mm
Can be unilateral or bilateral
If infertility is caused by PCOS (group 2 ) what will the hormone levels be
Elevated serum LH LH/FSH ratio >2 Normal estradiol Low progesterone Normal or slightly high prolactin Raised testosterone - main clue Impaired glucose tolerance.
Which lifestyle changes can help treat the infertility seen in PCOS
Weight loss and exercise to decrease BMI
Must get BMI under 30 before ovulation treatment can be started
How does clomifene citrate work to increase fertility
It is a selective oestrogen receptor modulator which blocks oestrogen negative feedback effect on hypothalamus resulting in more pulsatile GnRH secretion and therefore FSH and LH
How can metformin aid fertility in PCOS patients
It is an nsulin-sensitiser so improves glucose tolerance, decreases androgen levels and improves ovulation rate.
When is IVF used to treat infertility in PCOS
When 1st or 2nd line treatment have not worked
What are some of the side effects of clomifene citrate
hot flushes and sweating
Increased risk of multiple pregnancy
Risk of ovarian cancer (with long term use)
List factors which increase your chance of conceiving
Young maternal age
Healthy BMI
Being a non-smoker
Timing intercourse with ovulation
Why are men with CF often infertile
In the majority there is an obstruction or absence of the vas deferens bilaterally - Congenital Bilateral Absence of Vas Deferens (CABVD)
No way for sperm to be transported an meet semen
Sperm still produced normally though
Why does cryptorchidism lead to infertility
The testes are not in the ideal environment for the development of the testes and the production of spermatozoa - e.g. increased temperature inside the body
How can infections lead to male factor infertility
If severe can cause fibrosis and blockages
Mumps and STIs can cause orchitis/epididymitis which can damage the
seminiferous tubules and affect the process of sperm cell production
STIs can also affect the motility, morphology and quantity of the sperm
What is globozoospermia
Specific sperm abnormality
where the spermatozoa have rounded heads, instead of the usual
oval shape, and no acrosome
Without the acrosome they are unable to fuse with the ovum
What are the endocrine features of non-obstructive male factor infertility
High LH and FSH and low testosterone.
How does hyperprolactinaemia cause infertility
High levels of prolactin can prevent ovulation from occurring
Similar to it’s role in pregnancy and breastfeeding
How does hyperprolactinaemia cause infertility
High levels of prolactin can prevent ovulation from occurring
Similar to it’s role in pregnancy and breastfeeding
How does PCOS present
Anovulation - oligomenorrhea or amenorrhea
Polycystic Ovaries - seen on US
Hyperandrogenism (clinical or biochemical) - hirsutism, weight gain, acne etc .
Why does PCOS cause infertility
The overproduction of oestrogen by ovaries cause them not to release an ovum
In the long term, increased levels of testosterone can also impair ovum quality and mean that any ovum that are released are of poorer quality
Women with PCOS also have an increased
risk of ovarian torsion - true or false
True
How does premature ovarian failure present
Hot flushes and night sweats
Atrophic vaginitis Oligomenorrhea, or amenorrhea
Basically menopause
What can cause premature ovarian failure
Often cause is unknown
Can be caused by genetic
disorders - Turner’s syndrome and fragile X syndrome
Exposure to chemotherapy or radiotherapy - toxin-induced ovarian failure
Autoimmune response to ovarian tissue.
Where in the body does spermatogenesis take place
In the seminiferous tubules, located
inside the testes
What is the purpose of the acrosome in sperm cells
Found around the sperm head
Contains enzymes for penetrating the ovum - allows it to bind to the zona pellucida
What is tubal factor infertility
Where disease of the fallopian tubes is the underlying cause
There is a blockage (complete or partial) of the tube/tubes preventing sperm from meeting the ovum
Can be infective or non-infective
List infective causes of tubal factor infertility
PID
Trans-peritoneal spread
of infection, such as appendicitis or intra-abdominal abscess,
Iatrogenic source of
infection, such as following IUD insertion or hysteroscopy
What causes PID
Usually a bacterial infection that spreads from the vagina or cervix into the uterus and fallopian tubes
Commonly STI like chlamydia or gonorrhea
How does PID present
Abdominal and/or pelvic pain Dyspareunia Dysmenorrhea Intermenstrual bleeding Unusual vaginal discharge
If severe it can present with severe abdominal pain, fever and
nausea and vomiting.
How can you treat PID
Course of Metronidazole and Ofloxacin
If tubes get blocked - laparoscopic removal of scarring and adhesions after the acute inflammation
has been resolved
List non-infective causes of tubal factor infertility
Endometriosis - can block/scar the tubes
Salpingitis Isthmica Nodosa - nodular scarring of the fallopian tube due to infalmmation
Uterine polyps
Uterine fibroids
Why do polyps/fibroids cause infertility
Can develop at the opening of the fallopian tubes and ca n block these tubes
If in the endometrium they can interfere with the process of implantation
How do you investigate tubal patency
Laparoscopy - preferred where there is possible tubal disease or pelvic
inflammation
If there are no known risk factors for tubal or pelvic disease and laparoscopy is
contraindicated then a hysterosalpingogram can be
performed.
What is the indication for hysteroscopy in infertility
Indicated if known or suspected endometrial pathology
What is the indication for scrotal US in infertility
Indicated if abnormality on male genital examination
How many cycles of IVF are offered in the NHS
Up to 3 cycles
How long after IVF do you take a pregnancy test
16 days after oocyte recovery.
