Block 3: Fertility Control

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How many pregnancies in the US are unintended?: 50%
What % of couples are using: OC Sterilization Nothing Condom Withdrawal Periodic Abstinence Everything else: O-26
S-24
N-20
C-19
W-6
P-3
E-2
Pregnancy/100 women-years IUD Norplant Depo OC Male Condom/Female Condom No method: I-0.1
N-0.3
D-0.3
O-3.0
M/F-12/21
N-85
How long does a levonorgestrel-releasing IUD provide protection: 5 years
How does lev-IUD work?: Prevents fertilization via sterile inflammation and sperm destruction, inhibits ovulation
Benefits of Lev-IUD: No systemic exposure to hormones
Ease of use
Can be used during lactation
Lower menstrual blood loss
May decrease risk of endometrial cancer
Highly effective
Problems with Lev-IUD (5): Acne
Changes in menstrual flow
Need to check for string
Risk of uterine perf
Risk of pelvic infection during first 20 days after insertion
Norplant is effective for how many years? What's it look like: Five years
Six rods implanted into the arm
How does Norplant work?: Suppresses ovulation (80% of cycles), thickens cervical mucous, thins endometrial lining
Benefits of Norplant (7): Ease
During lactation
Highly effective
Decreases anemia
Decreases PID
Decreases ectopic pregnancy
Decreases endo cancer
Problems with Norplant: Irregular menses
Wt. gain
Headaches
Acne
Mood changes
Mastalgia (pain in breasts)
Requires minor surgery
Depo-Provera administration: 150 mg every 3 months
Depo MA: Same as Norplant

Suppresses ovulation (80% of cycles), thickens cervical mucous, thins endometrial lining
Benefits of Depo: Same as Norplant

Ease
During lactation
Highly effective
Decreases anemia
Decreases PID
Decreases ectopic pregnancy
Decreases endo cancer
Problems of Depo: Irregular menses
Amenorrhea (80% by 3 years)
Difficulty determining pregnancy b.c. of amenorrhea
Wt. gain
Acne
Mood changes
Headache
How many combinations of OCs are there: over 30, and 2 progestin only forms
Current regimens of OCs contain how much hormone: ~20-35 micrograms
NNNNDEDG OCs: Norethindrone
Norethynodrel
Norgestrel
Norgestimate
Desogestrel
Ethynodiol
Diacetate
Gestodene
How do OCs work: Inhibits midcycle surge of LH (supresses ovulation 90-95%) also alter uterine and tubal motility
Do progestin only pills consistently inhibit ovulation: no
Why are women on OCs at greater risk for clot?: Increased fibrinogen, Factor V, VII, and X
Does the risk of DVT increase as concentration of estrogen increases: Yes
What is the risk of DVT in women who take OCs and also have an activated protein C resistance?: 30/10,000 as compared with 6/10,000
Old progesin pills lead to an increase in what?: Glucose and insulin
Taking OCs decrease your risk for which cancers?: Endometrial (40%)
Ovarian (50%)
Other conditions that are decreased with OC use: Ectopic pregnancy
Benign breast dz
PID
Acne
RA
Osteoporosis
Problems with OC use: Increased risk for cervical dysplasia and cancer
Increased risk of Thromboembolism
Breast tenderness
Nausea
Fluid retention
3 types of emergency contraception: Plan B
Preven
LoOvral
What is in Plan B pills: 0.75 mg levonorgestrel only
What is in Preven: Each contains .25 mg levonorgestrel and 50 mics ethinyl estradiol
What is in LoOvral: 35 mics ethinyl estradiol and .3 mg Norgestrel

Take 4 tablets split by 12 hours

*Plan B is 0.75 mg BID of levonorgestrel
What is a must in EOC: Must be taken within 72 hours of intercourse, will not work if implantation has already occurred
Infertility stats: 40% male
25% female
25% female b.c. of tubal/peritoneal issue
10% unexplained
Unexplained must fail which 3 tests.: Hysterosalpingography- documents patent fallopian tubes

Serum progesterone test
Semen analysis
What is Clomiphene Citrate: A SERM similar to DES
MA of Clomiphene Citrate: Binding of hypothalamic intra nuclear estrogen receptors--retard receptor replenishment
Consequence of Clomiphene Citrate: Decreases negative estrogen feedback tone on GnRH release, in anovulatory women it restores appropriate GnRH discharge
Where does GnRH come from: Arcuate nucleus
Net effect of Clomiphene Citrate: Favor FSH release over LH
What category drug is Clomiphene Citrate: Category Xm-- contraindicated during pregnancy
What was seen in experimental animals that were pregnant and given Clomiphene Citrate: Dose dependent increase in fetal malformations when CC was given during organogenesis
1/2 life of Clomiphene Citrate: extremely long (51% fecal excretion at 5 days
SE of CC: Vasomotor flushing, blurry vision, scotomata (visual spots or flashes), headache
According to PDR (prescription drug reference) what is the twinning rate and triplet rate of CC: 10% twinning
<1% triplets
Clinical use of CC in anovulatory women: 50 mg days 5-9, intercourse days 10-20, Walk up 50 mg per cycle till ovulatory

do a day 21-24 serum progesterone
What do you have to screen for before CC use?: Insulin resistance
21-hydroxylase def.
Hypothyroidism
Hyperprolactinemia
What differs about CC in unexplained fertility: Start CC earlier in the cycle (day 3-7) and add gonadotropins on day 9

*Goal is more than one egg, whereas for anovulatory women it is not (that's why they can have sex at home ;) )
Where do we get exogenous gonadotropins?: Urine of menopausal women
Recombinant gonadotropins
What are the gonadotropins? Structure?: LH and FSH
Two hydrophobic non-covalently associated alpha and beta subunits
What do all gonadotropin hormones share, including hCG and TSH. What gives them their specificity: A common alpha unit, the beta subunit gives the hormone specificity.
What are the gonadotropins used for: Inducton of ovulation in pts who have failed to ovulate with CC
Frequency of ovulation for CC 50mg 100mg 150mg 200mg 250mg: 52%
22%
12%
7%
5%
Controlled ovarian hyperstimulation: Use of gonadotropins and intrauterine insemination for cases of unexplained infertility
Choice agent for ART (Assisted Reproductive Technologies, like IVF): Gonadotropins
Do gonadotropins induce the large numbers of oocytes seen in ART: No, they rescue those oocytes that would otherwise have become atretic
Ovulation induction in hypothalamic anovulatory patients: LH and FSH a must!
Monitor patients with serial estradiol levels and US
What happens when the follicle reaches 18-20 mm diameter in hypothalmic anovulaory patients? What then: Admin 10,000 units of hCG i.m.(surrogate for LH surge)

Patients have intercouse or insemination 36-40 hours later
What is the difference when inducing a euestrogenic woman with a functional hypothalmic-pituitary axis? What is the goal?: Same but LH may not be necessary

2-3 follicles
Avg. number of hormone ampules used in ART per cycle: 34
ART side effects: 26% twins
5% triplets
Native gonadotropin structure, breakdown, and 1/2 life: 10 a.a. w/cleavage sites at 5-6, 6-7, 9-10. Cleavage by endopeptidases
t1/2 = 2-3 minutes
GnRH agonists: Altered structure increasing the half life
MA of GnRH agonists: Initial flare of activities last 7-10 days--then down regulation of pituitary gonadotrophs--then desensitization
Net effect of GnRH agonists: Reduced pituitary gonadotropin secretion
Clinical use of the flare caused by GnRH agonists: ART harnesses the flare by using it early in the stimulation cycle--need fewer ampules to achieve ovarian hyperstimulation
Clinical use of the hypogonadal state following GnRH agonist admin.: ART uses both the flare and the hypogonadal state, the HG state prevents premature luteinization (ovulation)
How does the hypogonadal state from GnRH agonists work in endometriosis?: Useful in reducing the stimulation to endometrial implants
GnRH and uterine myomas (estrogen sensitive tumors): Reduce symptoms/growth
May stabilize Hct before surgery
SE of GnRH agonists: Persistant hypogonadal state can lead to hypoestrogenism-- decreased bone mineral density, adverse lipid profile

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