Fertility Flashcards
When investigate infertility
been trying to conceive without success for 12 months. This can be reduced to 6 months if the woman is older than 35
Causes of infertility
Sperm problems (30%)
Ovulation problems (25%)
Tubal problems (15%)
Uterine problems (10%)
Unexplained (20%)
General lifestyle advice for couples trying for a baby
The woman should be taking 400mcg folic acid daily
Aim for a healthy BMI
Avoid smoking and drinking excessive alcohol
Reduce stress as this may negatively affect libido and the relationship
Aim for intercourse every 2 – 3 days
Avoid timing intercourse
Ix for infertility
Body mass index (BMI) (low could indicate anovulation, high could indicate PCOS)
Chlamydia screening
Semen analysis
Female hormonal testing (see below)
Rubella immunity in the mother
Female hormone testing
What does female hormone testing involve?
Serum LH and FSH on day 2 to 5 of the cycle
Serum progesterone on day 21 of the cycle (or 7 days before the end of the cycle if not a 28-day cycle).
Anti-Mullerian hormone
Thyroid function tests when symptoms are suggestive
Prolactin (hyperprolactinaemia is a cause of anovulation) when symptoms of galactorrhea or amenorrhoea
High FSH
Pcos
Positive that ovulation has occurred
Rise in progesterone on day 21 -corpus luteum secreting
High anti-mullerian hormone
Food ovarian reserve
Beyond hormonal testing, further Ix for infertility
Ultrasound pelvis to look for polycystic ovaries or any structural abnormalities in the uterus
Hysterosalpingogram to look at the patency of the fallopian tubes
Laparoscopy and dye test to look at the patency of the fallopian tubes, adhesions and endometriosis
Hysterosalpingogram what involved and uses
Assess shape of uterus and latency of fallopian tubes
Therapeutic benefit
Can also perform tubal cannulation during procedure (must have Sri screening first)
Mx of anovulation
Weight loss for overweight patients with PCOS can restore ovulation
Clomifene may be used to stimulate ovulation
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 may be used in polycystic ovarian syndrome
Metformin may be used when there is insulin insensitivity and obesity (usually associated with PCOS)
Mx of tubal issues
Tubal cannulation during a hysterosalpingogram
Laparoscopy to remove adhesions or endometriosis
In vitro fertilisation (IVF)
Mx of uterine issues
Surgery may be used to correct polyps, adhesions or structural abnormalities
Mx of sperm production
Surgical sperm retrieval - when block along vas deference preventing sperm to reach ejaculated semen. Collected from epididymis
Surgical correction of obstruction- in vas deferent
Intra uterine insemination - involves collecting and separating out high-quality sperm, then injecting them directly into the uterus
Intracytoplasmic sperm injection -involves injecting sperm directly into the cytoplasm of an egg. These fertilised eggs become embryos, and are injected into the uterus of the woman
Donor insemination
How provide a semen sample
Abstain from ejaculation for at least 3 days and at most 7 days
Avoid hot baths, sauna and tight underwear during the lead up to providing a sample
Attempt to catch the full sample
Deliver the sample to the lab within 1 hour of ejaculation
Keep the sample warm (e.g. in underwear) before delivery
Fx affected semen analysis and sperm quality/quantitiy
Hot baths
Tight underwear
Smoking
Alcohol
Raised BMI
Caffeine
When repeat samples of semen
repeat sample is indicated after 3 months in borderline results or earlier (2 – 4 weeks) with very abnormal results.
Normal semen results
Semen volume (more than 1.5ml)
Semen pH (greater than 7.2)
Concentration of sperm (more than 15 million per ml)
Total number of sperm (more than 39 million per sample)
Motility of sperm (more than 40% of sperm are mobile)
Vitality of sperm (more than 58% of sperm are active)
Percentage of normal sperm (more than 4%)
Define polyspermia
high number of sperm in the semen sample (more than 250 million per ml)
Define normospermia
normal characteristics of the sperm in the semen sample
Define oligospermia
reduced number of sperm in the semen sample. It is classified as:
Mild oligospermia (10 to 15 million / ml)
Moderate oligospermia (5 to 10 million / ml)
Severe oligospermia (less than 5 million / ml)
Define cryptozoospermia
to very few sperm in the semen sample (less than 1 million / ml).
Azoospermia define
absence of sperm in the semen.
Pre testicular causes of poor sperm creating
Testosterone required
low LH and FSH resulting in low testosterone), can be due to:
Pathology of the pituitary gland or hypothalamus
Suppression due to stress, chronic conditions or hyperprolactinaemia
Kallman syndrome
Testicular causes of poor sperm
Testicular damage from:
Mumps
Undescended testes
Trauma
Radiotherapy
Chemotherapy
Cancer
Genetic or congenital disorders resulting in defective or absent sperm production
Klinefelter syndrome
Y chromosome deletions
Sertoli cell-only syndrome
Anorchia (absent testes)
Post testicular causes of low sperm in semen
Obstruction:
Damage to the testicle or vas deferens from trauma, surgery or cancer
Ejaculatory duct obstruction
Retrograde ejaculation
Scarring from epididymitis, for example, caused by chlamydia
Absence of the vas deferens (may be associated with cystic fibrosis)
Young’s syndrome (obstructive azoospermia, bronchiectasis and rhinosinusitis)
Ix for male causes of infertility
Semen analysis
USS of testes
Hormone analysis - LH, FSH, testosterone
Genetic testing
Transrectal Uss or MRI
Vasography
Testicular biopsy
Mx of male causes of infertility
Surgical sperm retrieval where there is obstruction
Surgical correction of an obstruction in the vas deferens
Intra-uterine insemination involves separating high-quality sperm, then injecting them into the uterus
Intracytoplasmic sperm injection (ICSI) involves injecting sperm directly into the cytoplasm of an egg
Donor insemination involves sperm from a donor
Success rate of IVF
25 – 30% success rate at producing a live birth
Intrauterine insemination definition
different from IVF. It is a more straightforward process, and involves injecting sperm into the uterus, avoiding intercourse
IUI indications
donor sperm for same-sex couples, HIV (avoiding unprotected sex) and practical issues with vaginal sex
IVF involves
A cycle of IVF involves a single episode of ovarian stimulation and collection of oocytes (eggs). A single 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. Frozen embryos can potentially be used years later, even after a successful pregnancy
Process of IVF
Suppressing the natural menstrual cycle
Ovarian stimulation
Oocyte collection
Insemination / intracytoplasmic sperm injection (ICSI)
Embryo culture
Embryo transfer
How suppress natural menstrual cycle
GnRH agonists or GnRH antagonists
How GnRH agonist given
an injection of a GnRH agonist (e.g. goserelin) is given in the luteal phase of the menstrual cycle, around 7 days before the expected onset of the menstrual period
How gnrh antagonist given?
daily subcutaneous injections of a GnRH antagonist (e.g. cetrorelix) are given, starting from day 5 – 6 of ovarian stimulation. This suppresses the body releasing LH and causing ovulation to occur.
Why suppress menstrual cycle IVF
Without suppression of the natural gonadotropins (LH and FSH) using one of the above protocols, ovulation would occur and the follicles that are developing would be released before it is possible to collect them.
How does ovarian stimulation work
subcutaneous injections of follicle-stimulating hormone (FSH) over 10 to 14 days
Then
an injection of human chorionic gonadotropin (hCG) is given. This injection of HCG is given 36 hours before collection of the eggs. The hCG works similarly to LH does naturally, and stimulates the final maturation of the follicles, ready for collection. This is referred to as a “trigger injection”.
How Oocyte collection work
Transvaginal USS
needle is inserted through the vaginal wall into each ovary to aspirate the fluid from each follicle. This fluid contains the mature oocytes from the follicles
Sedation
Oocyte insemination how work
The sperm and egg are mixed in a culture medium. Thousands of sperm need to be combined with each oocyte to produce enough enzymes (e.g. hyaluronic acid) for one sperm to penetrate the corona radiata and zona pellucida and fertilise the egg
Intracytoplasmic sperm injection when use
male factor infertility, where there are a reduced number or quality of sperm
How embryo culture works
Dishes containing the fertilised eggs are left in an incubator and observed over 2 – 5 days to see which will develop and grow. They are monitored until they reach the blastocyst stage of development (around day 5).
How embryo transfer work
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)
When pregnancy test performed
Day 16 after egg collection
Could be miscarriage or ectopic if positive
Why progesterone used in IVF
Progesterone is used from the time of oocyte collection until 8 – 10 weeks gestation, usually in the form of vaginal suppositories. This is to mimic the progesterone that would be released by the corpus luteum during a typical pregnancy. From 8 – 10 weeks the placenta takes over production of progesterone, and the suppositories are stopped.
Main complications of IVF
Failure
Multiple pregnancy
Ectopic pregnancy
Ovarian hyperstimulation syndrome
Risks of egg collection procedure
Pain
Bleeding
Pelvic infection
Damage to the bladder or bowel
ovarian hyperstimulation syndrome definition
a complication of ovarian stimulation during IVF infertility treatment. It is associated with the use of human chorionic gonadotropin (hCG) to mature the follicles during the final steps of ovarian stimulation.
ovarian hyperstimulation syndrome patho
increase in vascular endothelial growth factor (VEGF) released by the granulosa cells of the follicles. VEGF 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.
raised renin
indicates OHSS - as activation of renin-angiotensin system
if high - high severity
risk fx of OHSS
Younger age
Lower BMI
Raised anti-Müllerian hormone
Higher antral follicle count
Polycystic ovarian syndrome
Raised oestrogen levels during ovarian stimulation
how monitor OHSS
Serum oestrogen levels (higher levels indicate a higher risk)
Ultrasound monitor of the follicles (higher number and larger size indicate a higher risk)
ways to reduce risk of OHSS developing
Use of the GnRH antagonist protocol (rather than the GnRH agonist protocol)
Lower doses of gonadotrophins
Lower dose of the hCG injection
Alternatives to the hCG injection (i.e. a GnRH agonist or LH)
clinical fx of OHSS
<7 days of hCG injection= early
>10 days = late
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)
severity of OHSS assessed
based on clinic fx
Mild: Abdominal pain and bloating
Moderate: Nausea and vomiting with ascites seen on ultrasound
Severe: Ascites, low urine output (oliguria), low serum albumin, high potassium and raised haematocrit (>45%)
Critical: Tense ascites, no urine output (anuria), thromboembolism and acute respiratory distress syndrome (ARDS)
mx of OHSS
SUPPORTIVE
Oral fluids
Monitoring of urine output
Low molecular weight heparin (to prevent thromboembolism)
Ascitic fluid removal (paracentesis) if required
IV colloids (e.g. human albumin solution)
admit if severe and to ICU if critical
pt develop raised haematocrit following GnRH injection
DEHYDRATION - OHSS
