L8: Clinical overview of IVF Flashcards

1
Q

What percentage of IVF cycles fail for unknown reasons?

A
  • ~40%
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2
Q

4 male factors for infertility:

A
  • Oligospermia
  • Asthenospermia
  • Teratospermia
  • Azoospermia (obstructive or non-obstructive)
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3
Q

Sources of sperm for IVF procedures:

A
  • Ejaculate (can require electroejaculation in some nervous system conditions)
  • PESA: Percutaneous epididymal sperm aspiration
  • TESE: Testicular sperm extraction (surgical)
  • Urine (in case of retrograde ejaculation; will require alkaline solution to be drunk, protecting sperm from acidic conditions)
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4
Q

3 methods for sperm selection in IVF clinics:

A
  • Density gradient (isolates highest quality sperm under centrifugation) aka sperm capacitation
    • Microfluidics e.g. Zymot chip
  • CASA -> computational quality assessment
  • PICSI: Test of physiological binding capacity using hyaluronic acid
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5
Q

What is the purpose of controlled ovarian hyperstimulation?

A
  • Increases window through which FSH levels are high enough to stimulate progression to graafian follicles
  • Improves chances of successful ovulation
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6
Q

Consequences of over and understimulation of ovaries:

A
  • Too low: anovulatory phenotype, no egg to collect
  • Too high: Patient develops OHSS
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7
Q

What is OHSS?

A
  • Ovarian hyperstimulation syndrome
  • Iatrogenic condition due to excess FSH stimulation
  • Women will have excess follicles developing simultaneously, resulting in amplification of pregnancy symptoms
  • e.g.: Fatigue, mood swings, nausea, cramps, can be fatal
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8
Q

Mechanism behind OHSS:

A
  • Large number of developing follicles -> FSH threshold reached very early
  • Results in premature release of LH by pituitary gland (trying to ovulate)
  • LH induces pregnancy side effects
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9
Q

How can OHSS be managed/controlled:

A
  • Prevent LH secretion upstream of pituitary (hypothalamus)
  • GnRH antagonist: Blocks GnRH receptor with immediate suppression of LH
  • GnRH agonist: Downregulates receptor, with initial LH flair followed by suppression
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10
Q

What are the 4 stages in controlled ovarian hyperstimulation protocol?

A
  • Choice of protocol
  • Choice of dose (based on BMI, age, ovarian reserve based on baseline FSH level)
  • Follicular monitoring (scans, serum oestrogen/progesterone)
  • Triggering of ovulation -> induces nuclear maturation of egg into a haploid zygote, with half of genetic material ejected in polar body
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11
Q

What are the criteria for egg collection? (x2)

A
  • 3+ follicles over 17mm diameter
  • 10,000 iu hCG
  • -> Will then carry out trans-vaginal oocyte recovery after 36hrs (often under sedation)
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12
Q

Broad outline of ART procedure:

A
  • Ovarian stimulation and monitoring (2 weeks)
  • Egg collection
  • Insemination/ICSI
  • Fertilisation check
  • Embryo culture
  • Embryo transfer
  • Luteal support
  • Pregnancy test
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13
Q

Explain why day 3 embryos used to be implanted vs updated protocol:

A
  • Historically used day 3 embryos, as technology to culture to blastocyst stage was lacking -> had to transfer more eggs at an earlier stage, increasing risk of multiple pregnancies and thus risking complications.
  • Day 5 now used; they have better success as embryonic genomic division occurs in this window (d3 - 5) and will be aberrant in 50% of blastocysts (switches on metabolism due to depletion of maternal nutrient provision) -> acts to select out incompetent embryos
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14
Q

Why will luteal support often be provided after embryo transfer?

A
  • Exogenous progesterone supplements lost progesterone production capacity
  • During collection procedure, some of corpus luteum will be excised due to suction, and the corpus luteum is essential for progesterone procedure up until the 12 week point where the placenta takes over
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15
Q

Features of embryo transfer procedure and success rates:

A
  • Abdominal USS guided
  • Success often depends on operator experience due to sensitivity of technique
  • Variety of catheters may be used depending on individual anatomy with no proven difference in efficacy
  • Transferred 1 - 2cm from fundus
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16
Q

Why may endometrial defects impact IVF success (both extremes):

A
  • Too stringent: Recurrent implantation failure (failure to implant competent blastocysts)
  • Too lenient: Recurrent miscarriage (implanting incompetent blastocysts)
17
Q

Early pregnancy assessments following IVF:

A
  • hCG tests: +14 days from ovulation and +21 days
  • Repetition if levels low (every 48hrs)
  • Scans at 6 - 8 weeks -> ante-natal referral if successful
18
Q

Different types of clinical success rate (x3) with periods (x3):

A
  • Pregnancy rate (chemical)
  • Clinical pregnancy rate
  • Take home baby rate
  • Per cycle started
  • Per oocyte retrieval
  • Per embryo
19
Q

Types of lab success rate (x3):

A
  • Fertilisation rate
  • Cleavage rate
  • Blastocyst formation rate
20
Q

Potential complications of IVF cycle: (x6)

A
  • Multiple pregnancy
  • Ectopic pregnancy
  • Miscarriage
  • Dissapointment
  • RARE: Infection
  • RARE: OHSS
21
Q

Other techniques applied with IVF (case by case):

A
  • Time-lapse morphokinetics
  • PGD / PGS (with reasonable suspicion of an approved condition)
22
Q

Areas of advancement in IVF:

A
  • Embryo culture systems
  • Metabolomics/proteomics for non-invasive quality assessment of blastocysts
  • Epigenetics
  • Embryo-endometrial dialogue
23
Q

In ICSI procedure, why is it important to implant at 6 or 12’oclock from the polar body?

A
  • Minimises chance of disrupting the mitotic spindle
  • Damage to this structure would have catastrophic impacts on the cells ability to divide
24
Q

What is TFF in ICSI?

A
  • TFF: Total fertilisation failure
  • All oocytes collected within one cycle of stimulation fail to form pronuclei
  • Oocyte activation deficiency thought to be the primary cause of these failures (e.g. via absence of PLC-sigma on surface -> sperm cannot initiate Ca wave -> no activation)