Infertility Flashcards
Investigation and infertility should be started when couple have been trying to conceive without success for __ months
12+ months
*reduces to 6 months if woman >35 yo as ovarian stores reduced and time more precious!
What are causes of infertility?
List the 5 broad options.
Sperm problems Ovulation problems Tubal problems Uterine problems Unexplained problems
*40% of infertile couples have a mix of male and female causes
What are conservative management (advice) for couples trying to get pregnant?
- Woman should take 400mcg folic acid daily
- Aim for healthy BMI
- Avoid smoking + alcohol
- Reduce stress as can affect libido
- Aim for sex every 2-3 days
- Avoid timing intercourse
*timed intercourse to coincide with ovulation is not necessary or recommended as can lead to increased stress and pressure in the relationship!
What are initial investigations for fertility that are performed in primary care?
BMI (low = anovulation, high = PCOS) Chamydia screening Semen analysis Female hormonal testing Rubella immunity in mother
What hormones are tested for in the female during initial investigations for fertility in primary care?
Serum LH/FSH Serum progesterone Anti-Mullerian hormone TFT (when symptoms are suggestive) Prolactin (when galactorrhoea or amenorrhoea exists) - hyperprolactinaemia is cause of anovulation!
High FSH can suggest infertility. Why?
Poor ovarian reserve - pitutary gland produces extra FSH to try and stimulate follicular development
High LH can suggest infertility. Why?
PCOS
High progesterone on day 21 indicates what?
Ovulation has occured, corpus luteum has formed and has started secreting progesterone.
*Not present if no ovulation!
What does anti-Mullerian hormone reveal in regards to female fertility?
Ovarian reserve
released by granulosa cells in follicules and falls as eggs are depleted. High level = good ovarian reserve
What are further investigations for infertility performed in secondary care?
USS Pelvis - polycystic ovaries, structural abnormalities in uterus
Hysterosalpingogram - patency of fallopian tubes
Laparoscopy and dye test - patency of fallopian tubes, adhesions and endometriosis
How is anovulation managed in infertility?
Weight loss (overweight pateints with PCOS)
Clomifene (SERM - stimulate ovulation) or Letrozole - aromatase inhibitor with anti-oestrogen effects
Gonadotrophics (stimulate ovulation in women resistant to clomifene)
Ovarian drilling with laparoscopic surgery. - Improves hormonal profile and results in regular ovulation and fertility (use if PCOS)
Metformin (if insulin insensitivity and obesity - usually with PCOS)
How are tubal factors managed in infertility?
Tubal cannulation during hysterosalpingogram
Laparscopy to remove adhesions or endometriosis
IVF
How are uterine factors managed in infertility?
Surgery - correct polyps, adhesions or structural abnormalities affecting fertility
How are sperm problems managed in infertility?
Surgical sperm retrieval (if blockage)
Surgical correction of obstruction in vas deferens
Intra-uterine insemination - collect and separate out high-quality sperm, then inject into uterus
ICSI (intracytoplasmic sperm ijection) - fertilises eggs. Use if motility issues, low sperm count or other sperm issues
Donor insemination with sperm from another donor
What factors does semen analysis test for?
Quantity, quality of semen and sperm
*(Male factor infertility)
What factors can affect sperm quality or quantity?
Hot baths Tight underwear Smoking/alcohol Caffeine Raised BMI
What results are tested for by semen analysis?
semen volume semen pH concentration of sperm total number of sperm motility of sperm vitality of sperm (active sperm) percentage of normal sperm
What is the difference between cryptozoospermia and azoospermia?
cryptozoospermia - very few sperm in semen sample
azoospermia - complete absence of sperm in semen sample
What are pre-testicular causes of infertility?
Low testosterone (low LH/FSH causes less testosterone):
- pathology of pituitary gland/hypothalamus
- supppression due to stress, chronic conditions or hyperprolactinaemia
- Kallman syndrome
What are the 3 categories of testicular causes of male infertility?
a) Testicular damage
b) Genetic or congenital disorders
c) Post-testicular causes
Testicular damage
Genetic or congenital disorders resulting in defective/absent sperm production
Obstruction preventing sperm from being ejaculated (post-testicular cause)
What are testicular damage causes of male infertility?
- Infertility
- Undescended testes
- Trauma
- Radiotherapy
- Chemotherapy
- Cancer
What are genetic/congenital disorders that can cause male infertility?
Genetic or congenital disorders resulting in defective/absent sperm production:
- Klinefelter syndrome
- Y chromosome deletions
- Sertoli cell-only syndrome
- Anorchia (absent testes)
What are post-testicular causes of male infertility?
Obstruction preventing sperm being ejaculated can be caused by:
- Damage to testicle/vas deferences from trauma, surgery or cancer
- Ejaculatory duct obstruction
- Retrograde ejaculation
- Scarring from epididmyitis - caused by chlamydia
- Absence of vas deferences (may be associated with CF)
- Young’s syndrome (obstructive azoospermia, bronchiectasis, rhinosinusitis)
What investigations can be done for male infertility?
Semen analysis
Further investgations:
- Hormonal testing - LH, FSH, Testosterone
- Genetic testing
- Further imaging - transrectal USS, MRI
- Vasography - ?obstruction
- Testicular biopsy
How is male infertility managed?
Surgical sperm retrieval (if obstruction)
Surgical correction (if obstruction in vas deferens)
Intra-uterine insemination (separate high quality sperm and inject into uterus)
ICSI (intracytoplasmic sperm injection) - inject sperm directly into egg cytoplasm
Donor insemination
What is the NHS limitation on IVF?
Couples are limited to set number of cycles funded by NHS
Very expensive and complicated process
What is the success rate of IVF at producing a live birth?
25-30% per attempt
What are the steps of IVF?
Suppress natural menstrual cycle Ovarian stimulation Oocyte collection Insemination/ICSI Embryo culture Embryo transfer Pregnancy test + USS
In IVF, how is the natural menstrual cycle suppressed?
GnRH agonist or GnRH antagonist
*stop LH/FSH causing follicles to be released without opportunity to collect them
In IVF, how are the ovaries stimulated?
Subcut injections of FSH -> wait for follicles to develop -> stop FSH -> inject hCG (mimics LH, stimulates maturation of follicles)
*FSH stimulates development of follicles. Monitored with transvaginal USS
What is the role of hCG injection in IVG?
Trigger injection - mimics LH and stimulates final maturation of follicles -> ready for collection!
In IVF, how are oocytes collected?
Transvaginal USS guided
Oocytes collected from ovaries using needle through vaginal wall into ovary to aspirate fluid from each follicle
Fluid contains mature oocytes from the follicles
Fluid from follicles then examined under microscope for oocytes
In IVF, how is oocyte insemination performed?
How is this different from ICSI?
Frozen or active sperm sample mixed with egg in culture medium
Thousands of sperm combined with egg oocytes for fertilisation to occur
ICSI used for male factor infertility - highest quality sperm isolated and injected directly into cytoplasm of the egg
During oocyte insemination in IVF, why must thousands of sperm need to be mixed with each oocyte?
To produce enough enzymes (hyaluronic acid) for one sperm to penetrate the corona radiata and zona pellucida and fertilise the egg.
In IVF, when are the embryos cultured until?
Fertilised eggs incubated over 2-5 days (until blastocyst stage)
In IVF, how does embryo transfer occur?
after 2-5 days, highest quality embryo selected for transfer.
Catheter inserted into uterus via cervix
Only single embryo transferred (maybe 2 if older women, 35 yo+)
Remaining embryos can be frozen for future attempts at transfer!
After embryo transferred into woman’s uterus in IVF, what test must be performed?
Pregnancy test
What hormone must be given post-implantation in IVF and why?
Progesterone (Vaginal suppository) - mimics progesterone that would be released by corpus luteum during typical pregnancy.
Given from oocyte collection until 8-10 weeks gestation only
*After 10 weeks, placenta takes over production of progesterone
What imaging investigation must be carried out to check if IVF has worked?
USS early in pregnancy (around 7 weeks)
*check for fetal heartbeat, rule out miscarriage or ectopic pregnancy
What are complications of IVF?
Main complications:
- Failure
- Multiple pregnancy
- Ectopic pregancy
- Ovarian hyperstimulation syndrome (hCG)
Small risk of:
- Pain
- Bleeding
- Pelvic infection
- Damage to bladder or bowel
What is a major complication of giving hCG during IVF treatment?
Ovarian hyperstimulation syndrome
- check renin level as activation of RAAS system occurs
- VEGF is stimulated from granulosa cells of follicles by hCG injection - fluid leaks from capillaries -oedema, ascites, hypovolaemia.
What are risk factors for ovarian hyperstimulation syndrome?
Younger age Lower BMI Raised anti-Mullerian hormone Higher antral follicle count PCOS Raised oestrogen levels during ovarian stimulation
How are women at risk of developing ovarian hyperstimulation syndrome assessed?
During IVF stimulation with gonadotrophins (LH/FSH - these cause VEGF release from follicles), they are monitored for following:
- Serum oestrogen (higher = higher risk)
- USS monitor of follicles (higher number + larger size = higher risk
How may women at risk of developing ovarian hyperstimulation syndrome be managed before they develop it?
Use of GnRH antagonist protocol (instead of GnRH agonist)
Lower doses of gonadotrophins
Lower doses of hCG injection
Alternatives to hCG injection (i.e. GnRH agonist or LH)
What are features of ovarian hyperstimulation syndrome?
Early OHSS - 7 days of hCG injection
Late OHSS - 10 days+ after hCG
injection
Signs/symptoms
- Abdo pain/bloating
- Nausea + vomiting
- Diarrhoea
- Hypotension (VEGF/Renin)
- Hypovolaemia (VEGF)
- Ascites
- Pleural effusion
- Renal failure
- Peritonitis (from rupturing follicles releasing blood)
- Prothrombotic state (DVT/PE risk)
How is ovarian hyperstimulation managed in the clinical setting?
Supportive treatment (with treatment of complications as well)
- Oral fluids
- Monitor urine output
- LMWH (prevent VTE)
- Ascitic fluid removal (paracentesis)
- IV colloids (human albumin solution)
*Monitor haematocrit to assess volume of fluid in intravascular space. Raised haematocrit means less fluid in intravascular space, therefore dehydration!!!!!!!!!!!!!!
