Infertility Flashcards
How many couples are affected by infertility in the UK? (1)
~1 in 7 (15%)
What is infertility defined as? (1)
The failure to conceive after 1yr of regular unprotected intercourse
What are the broad causes of infertility? (4)
Mechanical blockage to egg & sperm meeting (bypass this by IVF etc.)
Failure of gamete production or release
Failure of fertilisation/implantation or miscarriage
Unknown (idiopathic)
How can there be a mechanical blockage to egg & sperm meeting? (4)
Infection/occlusion of vas def or uterine tubes e.g. chlamydia
Previous ligation for sterilisation (no straightforward reversal procedure)
Endometriosis (ectopic endometrial tissue)
Congenital defects
How can there be failure of gamete production or release? (4)
Anovulation (hormonal, nutritional, PCOS, maternal age)
Azoospermia (no sperm production)
Athenozoospermia (sluggish, slow swimming sperm)
Teratozoospermia (high % of morphologically abnormal sperm)
How can there be a failure of fertilisation/implantation or miscarriage? (3)
Genetic factors (e.g. embryo has inherited abnormal genes/aneuploidy) Endometrial receptivity Maternal age
What methods of ART are there? (6)
Inducing ovulation with exogenous hormones
Bypassing the uterine tube (IVF)
Direct collection of sperm from the testis/epididymis
Direct insertion of sperm into the egg (ICSI, intra-cytoplasmic sperm injection)
Donor gametes
Combination of the above
How do we induce ovulation? (2)
Using gonadotrophins
Removing -ve oestradiol feedback
How do we induce ovulation using gonadotrophins? (4)
Tx for anovulatory women or women who have oligo/amenorrhoea
Gonadotrophins in the these women is usually normal or slightly elevated (usually PCOS)
Aim to induce single DF
Daily SC injections of exogenous FSH - monitor by ultrasound during the cycle
How do we induce ovulation by removing -ve feedback? (7)
FSH levels normal but not cyclical
Inter-cycle rise in FSH relies on death of CL (i.e. falls in level of prog & oest)
Can’t reduce prog levels as there has been a CL to make any
Follicles in ovary making oestradiol so remove -ve feedback Allows rise of FSH
1. Block E2 receptor on the pituitary gonadotroph cells with SERM (selective estrogen receptor modulators) - clomid/clomphine
2. Stop E2 being made using aromatase inhibitor - letrozole (drugs ending in -zole)
What are the basic principles of IVF? (14)
Turn off normal HPG axis by downregulating GnRH receptors - give GnRH agonist or antagonist
- high sustained oestrogen would cause premature ovulation
Ovarian stimulation (monitor follicles with ultrasound) - superstimulate to get multiple eggs
hCG trigger (mimics LH surge but is cheaper with longer HL)
- completion of meiosis I
- ovulation
Oocyte retrieval & assessment
Semen preparation
Insemination
Assessment of fertilisation
Embryo culture 3-5 days
Embryo or blastocyst transfer
Pregnancy confirmation
Luteal phase support - cyclogest (progesterone
Summary of IVF process? (7)
Give FSH by SC injection - selection of multiple follicles for maturation
- give exogenous FSH everyday and so despite oest the -ve feedback is overcome & multiple follicles are selected
Collect mature eggs from ovary
Fertilise eggs in vitro Fertilisation check after 18hrs
Return dividing embryo (3-5 days) to uterus via cervix
As failures will occur at each stage need as need as many eggs as possible (so hyperstimulate the ovaries)
What happens in oocyte retrieval? (4)
34-38hrs post hCG trigger
Monitored by ultrasound
Introduce catheter into the vagina which goes through vaginal wall to the ovary
Penetrate follicle & suction aspirate (fluid & egg)
Embryologist collects egg
What happens in sperm preparation for IVF or intrauterine insemination (IUI)? (7)
Sperm collected by masturbation
IVF
- density centrifugation - motile fraction
-live sperm are denser & found in bottom layer
IUI
-donor insemination
- sperm washing (i.e. for sero-discordant couples wanting to conceive but not transmit HIV)
What happens in the insemination process? ()
Control factors - nutrients, acidity, humidity, gas composition of air, light exposure
Sperm & egg incubated together (75,000:1) ~4hrs
Duration of this co-incubation is traditionally ~16-18hrs but increasingly now ~1-4hrs
~65% of the eggs will fertilise
What happens in embryo culture? (4)
Cleavage stage (day 2-4) Blastocyst stage (day 5-6) Diving healthy embryos selected for transfer Excess embryos may be cryopreserved for later life
What happens in embryo transfer? (4)
Embryo transferred to uterus through catheter, which passes through the vagina & cervix, usually under ultrasound guidance
Single embryo transfer is the norm
Although 2-3 may be transferred in women 40+ or who have had repeated implantation failure
Multiple births increase risk of every complication of pregnancy
What are the success rates for IVF? (5)
Success rate associated with age of women - <1% success rate in women >4 ~5mil children born worldwide to date 2012 data - ~60,500 cycles in UK - with ~17,000 babies born - ~17% were multiple births
What progress have we made in IVF technology? (11)
GnRH agonists/antagonists Purer urinary FSH/LH preparations Better US monitoring Reduction in ovarian hyperstimulation syndrome (OHSS) Sequential media for blastocyst culture Micromanipulation for ISCA, MESA, TESA Cryopreservation (embryos, sperm, oocytes, ovary) Reduction in transferred embryos Oocyte maturation Pre-implantation diagnosis or screening
What is ICSI? (5)
Intra-cytoplasmic sperm injection
Used in low sperm, low motility or repeated fertilisation failure
Single sperm collected by needle aspiration from epididymis or testis
Inject sperm into egg
Still has tail
Is ICSI safe? (6)
Natural means of sperm selection is bypassed
Some evidence of increased genetic damage but this is equivocal
Other defects = 9.9% (compared to 5% non-ICSI)
Patients may be pushed to ICSI as higher success rates
2013 - more ICSI cycles than IVF
Biggest risk with infertility treatment is still multiple birth
What happens in sperm gamete donation? (4)
Very common
Freezing (cryopreservation) is essential for donor sperm
Reasonable function after thawing
Change in the law may reduce no.
What happens in egg gamete donation? (4)
World-wide shortage of donor eggs
Need to go through IVF cycle to access eggs
Eggs can now be cryopreserved by vitrification
Can be a waiting list/expensive
What are the laws on donor identify + anonymity? (3)
POST-2005 LAWS
Individuals born from donor donations have the right to ask the regulatory body HFEA about the identity of their donor if they were conceived using donated eggs or sperm after 2005
Donors have right to info held by HFEA
1. Whether donation has been successful
2. Number of children born as a result of their donation
3. The sex & year of birth of any child born
Children born in the UK have right to ask the donors identity once they are born
