Drugs for Infertility

jmanderson's version from 2016-01-03 19:16

PPT Objectives


Question Answer
Gonadal (primary) hypogonadism labslow sex steroids, high FSH, LH, GnRH
Pituitary (secondary) hypogonadism labslow sex steroids, low FSH, LH, high GnRH
Hypothalamic (tertiary) hypogonadism labslow sex steroids, low FSH, LH, low GnRH
Make sure to release GnRH in a _____ fashionpulsatile
Continuous administration of exogenous GnRH (not normal) does what to gonadotropins?inhibits LH
Pulsatile administration GnRH (normal) does what to gonadotropins?stimulates FSH and LH
continuous administration of GnRH agonists and administration of GnRH antagonists ______ LHdecrease
Continuous GnRH agonist mechanism of LH loweringinhibits gonadotropin release, typically used as part of a ‘long’ protocol for IVF, LONG latency to act
GnRH antagonist mechanism of LH loweringinhibit endogenous GnRH preventing premature “LH surge” during ovarian hyperstimulation, typically used as part of ‘short’ protocol for IVF, relatively SHORT latency
Give the one endocrinological condition where estradiol has a positive feedback effect on LH.Just before ovulation, estradiol has a positive feedback effect on LH (“surge”) responsible for ovulation
Give the effect of FSH on the ovary.Recruits oocytes to be ovulated in the next cycle
Give the effect of loss of estradiol feedback at menopause.Loss of estradiol feedback in menopause → excess LH and FSH metabolites in urine and loss of menstrual/ovulatory cycles
FSH effect in MALES (testes)germ cell maturation and spermatogenesis; LH stimulates steroidogenesis
FSH effect in femalesrecruits next cycle’s follicle; LH stimulates ovulation and steroidogenesis
Give three indications of hMG.Ovulation induction; INFERTILITY- hypogonadotropic hypogonadism (Men and Women); In Vitro Fertilization
Explain the MOA of hCG.LH Receptor Agonist (Stimulates ovulation mimicking the physiological ‘LH surge’)
Explain the mechanism and action of LH/hCG on the testes.Responsible for steroidogenesis (Testosterone Production needed for complete spermatogenesis)
Give three non-gonadal causes of infertility.Thyroid Dysfunction; Hyperprolactinemia; Polycystic Ovary Syndrome (PCOS)
Explain what type of drug clomiphene isclomiphene is a Selective Estrogen Receptor Modulator (SERM)
What effect does clomiphene have on gonadotropic hormone levels.Induces ovulation by INCREASING GnRH, FSH and LH secretion; Estrogen receptor partial agonist preventing endogenous estrogen’s negative feedback on the hypothalamus
Explain why dopamine agonists treat hyperprolactinemia.Prolactin is regulated by dopamine, as dopamine inhibits prolactin. Therefore, a dopamine agonist would enhance that inhibition of prolactin by activating dopamine receptors, which would oppose the effects of the prolactinemia.
3 phases of ovarian stimulation for IVFcontrolled ovarian hyperstimulation, ovulation induction, luteal phase support
Step 1 of ovarian stimulation for IVFControlled ovarian hyperstimulation
Drugs for step 1 of ovarian stimulation for IVFOral contraceptives (optional) up to 28 days; GnRH analogs; FSH-gonadotropins
Step 2 of ovarian stimulation for IVF and drug associatedOvulation induction; hCG
Step 3 of ovarian stimulation for IVF and drug associatedLuteal Phase Support; Progesterone
Conventionally used drugs used for secondary hypogonadism in maleshCG 8-12 weeks followed by hMG (Total Tx: 4-6 mos)
Alternative protocols for for secondary hypogonadism in malesUrofollitropin; r-FSH; Clomiphene

Handout Objectives


Question Answer
Describe the effect of LH stimulation of the ovary to stimulate steroid production.LH stimulates the enzyme that converts cholesterol into pregnenolone (the precursor of all steroid hormones) which increases production of sex hormones estrogen or testosterone
Source and action of Inhibinproduced by the gonads in response to FSH and exerts negative feedback on gonadotrophs to inhibit further release of FSH.
Source and action of Activinproduced in pituitary and acts in a paracrine fashion to stimulate FSH secretion.
GnRH agonists timing for IVFtakes 7-10 days to suppress gonadotropin release
GnRH antagonists timing for IVFrapid onset
Give which gonadotropic formulations can result in ovarian hyperstimulation syndrome (OHSS).Follitropin; Choriogonadotropin alfa
Sx of severe OHSSfullness/bloating above waist, lower abdominal pain, SOB, pleural effusion, urination darker or has ceased, calf pain, chest pain.
Timing of severe OHSS Sxcan occur early < 9 days after oocyte retrieval or late > 10 days after oocyte retrieval.
Describe when aromatase inhibitors should be used for infertility cases.Use for infertility after failure to multiple clomiphene treatments or intolerant to clomiphene
Progesterone Indicationsfemale infertility adjunct
Progesterone MOAtransforms proliferative endometrium into secretory and quiet endometrium, suppresses secretion of gonadotropins, prevents menstruation and uterine contractility (“Quiets the uterus down to allow for implantation”)
Progesterone route of administration and when it is givenIM or vaginally (Gel = 1-2 x/d; Insert = 2-3 x/d)

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