11 - Infertility Flashcards
What is infertility and when is it investigated?
Inability of a couple to become pregnant despite regular unprotected intercourse for a year
1 in 7 struggle to concieve
If over 35 or known fertility diseases (e.g PCOS) refer for investigations after 6 months rather than a year
What are the main causes of infertility?
- Sperm problems (30%)
- Ovulation problems (25%)
- Tubal problems (15%)
- Uterine problems (10%)
- Unexplained (20%)
40% have a mixture of male and female fertility issues.
Can be primary or secondary (conceived before)
What is some general advice to give a couple when trying to conceive? (both men and women)
- 400mcg folic acid daily
- Aim for healthy BMI
- Avoid smoking and drinking excessive alcohol. (Passive included)
- Reduce stress as this may negatively affect libido and the relationship
- Aim for intercourse every 2 – 3 days
- Avoid timing intercourse with ovulation
Apart from medical investigations, who else should be involved in the care of a couple undergoing infertility investigations?
Counselling throughout by someone who is not involved in the medical side of it
Can refer to fertility support group
When should a woman using artificial insemination be referred for infertility investigations?
If she does not conceive after 6 cycles
How are men investigated for infertility issues and what advice should you give them before their investigation?
Semen analysis (look at quantity and quality of sperm and semen)
A repeat sample may be required in 3 months if sample was borderline
What are some lifestyles factors that can affect the quality/quantity of sperm?
- Hot baths
- Tight underwear
- Smoking
- Alcohol
- Raised BMI
- Caffeine
What are some of the things looked at on semen analysis and what are ‘normal’ results?
- Semen volume: 1.5 ml or more
- pH: 7.2 or more
- Sperm concentration: 15 million per ml or more
- Total sperm number: 39 million per ejaculate or more
- Total motility: 40% or more motile or 32% or more with progressive motility
- Vitality: 58% or more live spermatozoa
- Sperm morphology (percentage of normal forms): 4% or more
What is the meaning of the following terms:
- Polyspermia
- Oligospermia
- Cryptozoospermia
- Azoospermia
Polyspermia: high number of sperm in the semen sample (more than 250 million per ml)
Oligospermia: reduced number of sperm in the
Mild (10 to 15 million / ml)
Moderate (5 to 10 million / ml)
Severe (less than 5 million / ml)
Cryptozoospermia: very few sperm in the semen sample (less than 1 million / ml)
Azoospermia is the absence of sperm in the semen
What are some causes of male infertility?
Pre-Testicular
- Pathology of pituitary or hypothalamus
- Suppression due to stress, chronic conditions or hyperprolactinaemia
- Kallman syndrome
Testicular
- Mumps
- Undescended testes
- Trauma
- Cancer, Radio, Chemo
- Genetic: Klinefelter, Sertoli Cell-Only, Y chromosome deletions
Post-Testicular
- Damage to the testicle or vas deferens from trauma, surgery or cancer
- Ejaculatory duct obstruction
- Retrograde ejaculation
- Scarring from epididymitis e.g by chlamydia
- Absence of vas deferens (CF)
- Young’s syndrome (obstructive azoospermia)
If a semen analysis is abnormal, what other investigations can be done into a male’s fertility?
Take a history, exam, repeat sample and US testes first
Refer to urologist
What are some management options for male infertility?
- Surgical sperm retrieval: if obstruction
- Surgical correction of an obstruction
- Intra-uterine insemination
- Intracytoplasmic sperm injection (ICSI)
- Donor insemination involves sperm from a donor
What are some initial investigations done for female infertility in primary care?
- Calculate BMI
- Hormone testing
- Chlaymydia Screening
- Rubella Immunity
What is included in female hormone testing in primary care, and when should you take these blood samples?
FSH and LH are particularly done if irregular periods
- Serum LH and FSH: day 2 to 5 of the cycle
- Serum progesterone: day 21 of the cycle (or 7 days before the end of the cycle if not 28-day cycle).
- Anti-Mullerian hormone
- TFTs: if symptoms are suggestive
- Prolactin: when symptoms of galactorrhea or amenorrhoea, high can be anovulation
What do high levels of the following indicate:
- FSH
- LH
- Progesterone Day 21
- Anti-Mullerian Hormone
- High FSH: poor ovarian reserve
- High LH: may suggest PCOS
- High progesterone: ovulation has occurred, corpus luteum formed
- High Anti-Mullerian: good ovarian reserve, released by granulosa cells
How do you predict the likely ovarian response to gonadotrophin stimulation in IVF?
- Woman’s age
- Total antral follicle count: <4 low response, >16 high response
- Anti-Müllerian hormone: <5.4 pmol/l low response, >25.0 pmol/l high response
- FSH: >8.9 IU/l low response, <4 IU/l high response
What further investigations are done apart from hormone testing for infertile females?
- US pelvis: look for polycystic ovaries or any structural abnormalities of uterus
- Hysterosalpingogram: look at the patency of the fallopian tubes
- Laparoscopy and dye test: done for same reason as above but if woman has PID, endometriosis or previous ectopic
If a couple wants to try for a baby and they have HIV, what advice should you give them about viral transmission?
Risk of transmission from man to woman via unprotected sex is low if:
- man is compliant with highly active antiretroviral therapy (HAART)
- man has a viral load <50 copies/ml for more than 6 months
- there are no other infections present
- unprotected intercourse is limited to the time of ovulation
- woman uses PrEP
If not compliant with HAART then recommend sperm washing but this can lower the quality of sperm
If a women has been found to be susceptible to rubella on fertility screening, what should you do?
Give vaccination then do not get pregnant for a month
What screening needs to be offered before uterine instrumentation?
Chlamydia screen
What happens in a hysterosalpingogram and a laparoscopy and dye?
Hysterosalpingogram
- Aids diagnosis and is therapeutic intervention
- Tubal cannulation under xray guidance to open up the tubes
- Small tube inserted into cervix and contrast injected through tube and fills the uterine cavity and fallopian tubes. If dye does not fill tube this shows occlusion
- Screen for Chlamydia and Gonorrhea first
- Prophylactic abx if previous PID
Laparoscopy and Dye
- Dye injected into the uterus and should be seen entering the fallopian tubes and spilling out at the ends of the tubes. Not seen when tubal obstruction
- During laparoscopy can also assess for endometriosis or pelvic adhesions and treat these.
What is the medical and surgical management of male infertility?
Medical
- If hypogonadotrophic hypogonadism offer gonadotrophin drugs
Surgical
- Surgical repair of obstruction
- Surgical sperm retrieval from epididymis to use for intrauterine insemination or Intracytoplasmic sperm injection (ICSI)
- Donor Insemination
What are some female causes of infertility?
Ovarian Problem
- Age
- PCOS
- Pituitary tumours
- Sheehan’s syndrome
- Hyperprolactinaemia
- Turner’s
- Cushing’s syndrome
- Premature ovarian failure
Tubular, Uterine and Cervical problem
- PID secondary to chlamydia or gonorrhoea
- Asherman’s syndrome
- Uterine structural abnormalities (e.g. bicornate uterus, fibroids)
- Endometriosis
- Cervical damage (e.g. after cone biopsy)
What are the three different types of ovarian infertility and how are they managed in general?
Hypogonadotrophic hypogonadism:
- Increase BMI >19 and moderate high levels of exercise
- Pulsatile GnRH to stimulate ovulation
Hypothalamic-pituitary-ovarian dysfunction (usually PCOS)
- Lower BMI to less than 30
- 1st line: Offer clomifene and/or metformin
- 2nd line: Laparoscopic Ovarian Drilling, Gonadotrophins
- If hyperprolactinaemia offer dopamine agonist Bromocriptine
Ovarian failure
How long can you take clomifene for?
6 months
Need US monitoring in first cycle using to make sure on lowest dose to prevent multiple pregnancy
What are the management options for anovulation (particularly due to PCOS) in infertility?
- Weight loss
- Clomifene
- Letrozole: may be used instead of clomifene to stimulate ovulation (aromatase inhibitor with anti-oestrogen effects)
- Gonadotropins: may be used to stimulate ovulation in women resistant to clomifene
- Ovarian drilling: in PCOS
- Metformin: PCOS
How do clomifene and laparoscopic ovarian drilling improve fertility?
Clomifene: SERM anti-oestrogen. Given on days 2 to 6 of the menstrual cycle.
Stops the negative feedback of oestrogen on the hypothalamus, resulting in a greater release of GnRH and subsequently FSH and LH.
Ovarian drilling: multiple holes in the ovaries using diathermy or laser therapy. Improves woman’s hormonal profile and result in regular ovulation and fertility
How can tubal factors of infertility be managed?
- Tubal cannulation during a hysterosalpingogram
- Laparoscopy to remove adhesions or endometriosis
- In vitro fertilisation (IVF)
How can uterine factors of infertility be managed?
Surgery to correct polyps, adhesions or structural abnormalities affecting fertility.
When is intrauterine insemination considered?
- People who are unable to/find it difficult to have vaginal intercourse because of a clinically diagnosed physical disability or psychosexual problem who are using partner or donor sperm
- After sperm washing in HIV man
- People in same-sex relationships
What are some predictors of IVF success?
- Woman’s age
- Number of previous treatment cycles
- Previous pregnancy history
- BMI 19-30
- Maternal and Paternal smoking
- Caffeine consumption
- Alcohol >1 unit a day
What is classed as one cycle of IVF?
Each attempt has a 25-30% chance of resulting in live birth
Single episode of ovarian stimulation and collection of oocytes (eggs).
One cycle may produce several embryos. Each of these embryos can be transferred separately in multiple attempts at pregnancy, all during one “cycle” of IVF
Embryos that are not used immediately may be frozen to be used at a later date, even after a successful pregnancy
How many cycles of IVF should somebody be offered?
If aged less than 40 and not conceived after 2 years of unprotected intercourse or 12 cycles of artificial insemination:
- Offer 3 cycles (inc self-funded)
- If turn over 40 in this time finish cycle on and do not offer anymore
Aged 40-42 with same as above:
- Offer 1 full cycle
- Must not have had IVF before, must have good ovarian reserve and must have had risks of pregnancy/IVF explained
What are the stages of IVF?
- Suppressing the natural menstrual cycle
- Ovarian stimulation
- Oocyte collection
- Insemination/intracytoplasmic sperm injection (ICSI)
- Embryo culture
- Embryo transfer
How is the natural menstrual cycle suppressed in IVF?
GnRH agonists or GnRH antagonists to allow ovaries to fully respond to artificial gonadotrophin and so follicles are not released before had a chance to collect them
GnRH agonist protocol
Injection of goserelin given in luteal phase around 7 days before the expected onset of the menstrual period
Initially stimulates pituitary gland to secrete a large amount of FSH and LH. However, after this initial surge in FSH and LH, there is negative feedback to the hypothalamus, and the natural production of GnRH is suppressed
GnRH antagonist protocol
Daily subcutaneous injections of Cetrorelix starting from day 5 – 6 of ovarian stimulation. This suppresses the body releasing LH
How are the ovaries stimulated in IVF after menstrual cycle suppression?
Subcutaneous injections of FSH on day 2 of cycle to promote follicle growth
Monitored with TVUS
When enough follicles have developed to an adequate size (usually around 18 millimetres), the FSH is stopped, and an injection of human chorionic gonadotropin (hCG) is given 36 hours before collection of the eggs
hCG works like LH and causes final maturation of eggs before collection. ‘Trigger injection’
How are oocytes collected in IVF?
Under the guidance of TVUS
Needle inserted through vaginal wall into each ovary to aspirate the fluid from each follicle.
This fluid contains the mature oocytes from the follicles
Performed under sedation, not GA
What is the difference between oocyte insemination and Intracytoplasmic Sperm Injection?
Oocyte insemination: thousands of sperm mixed with oocyte and left to fertilise
ICSI: Used for male infertility when reduced quality of sperm. Highest quality sperm injected
What happens during embryo culture and transfer in IVF?
Culture: Fertilised eggs are left in an incubator and observed over 2 – 5 days to see which will develop and grow. Monitored until they reach the blastocyst stage of development (around day 5)
Embryo Transfer: After 2 – 5 days, the highest quality embryos are selected for transfer. A catheter is inserted under ultrasound guidance through the cervix into the uterus. A single embryo is injected through the catheter into the uterus, and the catheter is removed. Generally, only a single embryo is transferred. Two embryos may be transferred in older women (i.e. over 35 years).
Any remaining embryos can be frozen for future attempts at transfer.
After embryo transfer what happens next in IVF?
Progesterone vaginal suppositories given from time of oocyte collection until 8 – 10 weeks gestation when placenta can take over. Mimics the progesterone that would be released by the corpus luteum during a typical pregnancy
Pregnancy Test on Day 16
Ultrasound scan around 7 weeks to check for fetal heartbeat, rule out miscarriage or ectopic pregnancy, if healthy return to normal pathway of pregnancy care
During ovarian stimulation what monitoring needs to be done?
US monitoring
What is the maximum number of embryos that can be transferred at once in IVF?
2
Offer cryopreservation for any additional ones
What are some complications of IVF?
- Failure
- Multiple pregnancy
- Ectopic pregnancy
- Ovarian hyperstimulation syndrome
Egg collection: pain, bleeding, infection, damage to the bladder or bowel
What is ovarian hyperstimulation syndrome?
Complication of ovarian stimulation during IVF treatment
Ovaries may enlarge to such an extent that they put pressure on the surrounding structures causing bloating and abdominal discomfort
What is the pathophysiology of ovarian hyper stimulation syndrome?
FSH and LH cause lots of follicles to form that produce VEGF. When hCG/trigger injection given more VEGF released
Increase in VEGF by granulosa cells of the follicles, increases vascular permeability, causing fluid to leak from capillaries.
Fluid moves from the intravascular space to the extravascular space. This results in oedema, ascites and hypovolaemia.
There is also activation of the renin-angiotensin system. A notable finding in patients with OOH is a raised renin level
What are some risk factors for developing ovarian hyper stimulation syndrome?
- Younger age
- Lower BMI
- Raised anti-Müllerian hormone
- Higher antral follicle count
- Polycystic ovarian syndrome
- Raised oestrogen levels during ovarian stimulation
How is OHSS prevented in IVF?
During stimulation with gonadotrophins, they are monitored with:
- Serum oestrogen levels (higher levels, higher risk)
- US monitor of the follicles (higher number and larger size higher risk)
If at high risk:
- Use of the GnRH antagonist protocol
- Lower doses of gonadotrophins
- Lower dose of the hCG injection
- Alternatives to the hCG injection
How may OHSS present?
Early if within 7 days of injection, Late if 10 days after injection
- Abdominal pain and bloating
- Nausea and vomiting
- Diarrhoea
- Hypotension
- Hypovolaemia
- Ascites
- Pleural effusions
- Renal failure
- Peritonitis from rupturing follicles releasing blood
- Prothrombotic state (risk of DVT and PE)
How do we classify the severity of OHSS?
Mild: Abdominal pain and bloating
Moderate: Nausea and vomiting with ascites seen on ultrasound
Severe: Ascites, oliguria, low serum albumin, high potassium and raised haematocrit (>45%)
Critical: Tense ascites, anuria, thromboembolism and acute respiratory distress syndrome (ARDS)
How is OHSS managed?
- Oral fluids
- Monitoring of urine output
- LMWH to precent DVT
- Ascitic fluid removal (paracentesis) if required
- IV colloids
If mild to moderate outpatient, severe inpatient, critical ICU
Monitor Haematocrit, if rising means more dehydration
What are some causes of coital infertility?
- Erectile dysfunction
- Premature ejaculation
- Anejaculation (SSRIs, psychosexual etc)
- Retrograde ejaculation
- Penile deformities (e.g. Peyronie’s disease, hypospadias)
What questions do you need to ask in a history for a couple presenting with infertility?
Need to ask both about
- Sexual intercourse
- Sexual history
- Diet, Alcohol, Smoking
- DHx
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