Fertility Drugs

Question 1

At what stage can pre-implantation genetic tests be done?

Answer 1

• Blastomeres: cells of pre-implantation embryo
• Totipotent cells at this stage meaning ea cell is able to form all parts of developing organism and placenta contributions
• Lasts until 8 cell stage
• Can remove 1 cell for testing w/o harming embryo (only done if known hx in parents - look for specific gene like CF)

Question 2

What are the overall goals of fertility treatment?

Answer 2

• Stimulate follicles w/ FSH (indirect or direct)

- Then natural or induced LH surge –> ovulation

Question 3

Clomiphene Citrate

Answer 3

• Estrogen Receptor Modulator (looks like tamoxifen)
• MAO: comp inhibitor of ER at hypothalamus –> hypothalamus perceives this as a lack of estrogen –> inc GnRH –> inc FSH and LH
• Given soon after menses (day 3-7 if menses starts on day 1)
• Risks - multiple gestation, hot flashes but no risk congenital anomalies and no inc risk miscarriage

Question 4

Letrozole

Answer 4

• Aromatase Inhibitor
• MAO: block androgen conversion to estrogen –> dec estrogen neg feedback on hypothalamus
• Risks - multiple gestation
• LTZ > CC in PCOS patients

Question 5

How do you induce and LH surge? What is your warning to patients?

Answer 5

• Do not inject LH b/c such short half-life
• Use hCG instead b/c half-life of 24 hrs
• Triggers ovulation and stimulates egg to resume meiosis
• Careful b/c such high dose of hCG that it stays in serum for 7-10 days so may result in false pos preg test in this time period

Question 6

What are the goals of IVF? 4 Steps

Answer 6

• Goal = want synchronous cohort of oocytes (many eggs at once) and want to control ovulation so that you can capture more eggs
• 1- Stimulate Follicle (recombinant GnRH starting on Day 3)
• 2- Suppress normal LH surge (2 options)
  
  • GnRH agonists or GnRH antagonists
• 3- Induce own surge w/ hCG when US determines that follicles are large enough
• 4- Need to create luteal phase - give progesterone or give more hCG to amp signal to corpus luteum

Question 7

GnRH Agonists

Answer 7

• Leuprolide (use shorter acting subQ depot for fertility)
• Can have initial flare (release of LH and FSH stores) then down-regulation
• Giving in mid-luteal phase is time w/ lowest flare b/c lowest stores

Question 8

GnRH Antagonists

Answer 8

• MAO: comp inhibitor of GnRH receptor but does not activate it
• Immediate shut down of LH/FSH (~6 hrs after dose) so use right b/f normal surge in mid-follicular phase b/c so immediate

Question 9

Progesterone Tx

Answer 9

• Daily pill, intravaginal capsule or gel, IM injection (gold std)
• Use daily until either negative preg test or if pregnant then until the placenta takes over for corpus luteal hormone production ( ~ 7 wks)