Endocrine 2 Exam 2: Koerner Fertility

Infertility: Failure to achieve a successful pregnancy after __ months or more of appropriate, timed unprotected intercourse or therapeutic donor insemination

12

If over the age of ___, early evaluation and treatment for infertility may be considered after only 6 months

35

Treatment for infertility is directed at the ___

cause

Primary Infertility Causes include (7):

primary ovarian insufficiency, PCOS, obesity, weight changes, excessive exercise, thyroid dsyfunction, hyperprolactinemia

Follicular Phase

- ____ _____ stimulate _____ _____

-increasing ______ levels with growing _____

-__mm follicle causes ____ in ___ and triggers ___ of _____

pituitary gonadotropins, follicle growth, estradiol, follicle, 20, increase, LH, release, ovum

Luteal Phase

-remainder of the follicle transforms to ____ ____which produces ____

-progesterone changes the ______ and prepares it for _____ ______

-if no pregnancy, ____ _____ dissolves, ___ in ______ level and _____ occurs

corpus luteum, progesterone, endometrium, embryo implementation, corpus luteum, drop, progesterone, menstruation

where do medications works?

gonadotropin releasing hormone

the gonadotropin releasing hormone regulates what and what tells them to do what?

pituitary, hypothalamus, release or stop FSH and LH

FSH

-produced by the __ ___ and stimulates early ____ of _____ and ____ secretion

anterior pituitary, maturation, follicles, estrogen

LH

-produced by the __ ___ and stimulates _____; maintains the ____ _____

anterior pituitary, ovulation, corpus luteum

GnRH

-produced by the _____ and stimulates _____ of ____ and ___

hypothalamus, secretion, FSH, LH

Estrogen

-produced by the ____ and stimulates growth of ___

ovaries, follicles

Progesterone

-produced by the __ ___/____ ____ and prepares for _____

ovarian follicle, corpus lutem, implantation

hCG

-produced by the ___/___ and maintains ____ _____ during ____ _____

trophoblast/placenta, hormone synthesis, early pregnancy

Fertilization occurs in ___ ___

fallopian tube

Fertilization occurs in fallopian tube and if it implants there, this is an ___ _____ (medical emergency)

ectopic pregnancy

Normal menstrual cycle ranges from 25-35 days (day 0 is first day of __)

menses

Ovulation is typically __ days before the next cycle

14

T/F Ovulation can be monitored with kits

True

After ovulation, the egg is viable for fertilization for __ ___ (differs from sperm, which is __-__ ___)

24 hours, 5-7 days

Male Infertility Common Problems include:

low sperm count, poor sperm motility, malformed sperm, blocked sperm ducts

Female Infertility

1. Tubal/pritoneal causes, including ___ and ___ ____ ___

endometriosis, pelvic inflammatory disease

Treatment for infertility caused by tubal/pritoneal is ___

surgical

Female Infertility

2. Ovulation dysfunction, including _____ ____ ____ ____, ___, and ___

Hypothalamus pituitary ovary axis abnormalities, hyperprolactinemia, PCOS

Treatment for infertility caused by ovarian dysfunction is ___

medications

Note that ___ accounts for up to 40% of infertility and commonly presents as menstrual disturbances, either ____ or ____

PCOS, oligomenorrhea, amenorrhea

Female Infertility

3. Pelvic/Uterine causes including ___ or ___, and ____/___ abnormalities

fibroids, polyps, congenital/structural

Treatment for infertility caused by pelvic/uterine causes is ___

surgical

Female Infertility

4. ___

5. ___ (_____, _____, ____)

6. unknown

immune, infectious, chlamydia, ureaplasma, mycoplasma

Medications that ____ ____ levels can lead to ____ in _____

increase prolactin, infertility, women

Medications that increase prolactin (12):

chlorpromazine, cimetidine, estrogen, haloperidol, medroxyprogesterone acetate, methyldopa, prenothiazine, pimozide, resperpine, TCAs, verapamil

Medications that decrease __ ___ can lead to infertility in ___

sperm activity, men

Medications that decrease sperm count (13):

alcohol (excess), allopurinol, anabolic/androgenic steroids, caffeine, CCBs, chemo, cocaine, colchicine, marijuana, nitrogurantoin, spironolactone, sulfasalazine, tetracycline

Evaluation-female

1. duration

2. ___ history

3. ___ history (eg history ectopic pregnancy?)

menstrual, pregnancy

Evaluation-female

4. PMH (including abnormal pap smears, PID, and STDs)

5. ___ history

6. ___ history (recent weight/exercise changes)

family, social

Evaluation-female

7. ___ and exposure to environmental hazards

8. History of alcohol, tobacco, and recreational or __ drug use

9. ___ function tests should be performed

occupation, illicit, thyroid

Infertility Testing

1. First patient we test is the ___ (less invasive, less expensive)

male

Infertility Testing

2. __ detection (ovulation prediction kits that show surge occurring 1-2 days before ovulation)

LH

Infertility Testing

3. serum ___ (timed to show if ovulation is occurring about 1 week prior to next menses, cycle day 21)

progesterone

Infertility Testing

4. ____

5. ___

6. ___

prolactin, FSH, estradiol

Infertility Testing

7. serum ___ hormone (predicts how successful assisted reproductive technology will be)

antimullerian

Infertility Testing

8. Trans-vaginal ____

9. Endometrial biopsy

10, Laparoscopy

11. Hysterosalingography (___)- puts dye into uterus to evaluate if tubes are patent (ie open)

ultrasound, HSG

Infertility Non-Pharm Treatment

-____ contributing medications/agents (eg nicotine, alcohol, illicit drugs)

avoid

Infertility Non-Pharm Treatment

-___ adjustments (remember BMI that is too low or too high can cause infertility)

weight

Infertility Non-Pharm Treatment

-multivitamin with ___ ___

folic acid

A ___ ___ containing folic acid should be started immediately in patients who are trying to conceive or experiencing difficulty becoming pregnant.

prenatal vitamin

Considerations for Ovulation Induction/Ferility Procedures

1. ___ (most insurances don't pay for this)

2. adverse effects of meds

3. risks of __ births (twins, triplets)

4. Invasive nature of intervention

cost, multiple

Goal of infertility treatment: Induce ____ to achieve development of at least one ovarian follicle and therefore enable conception

ovulation

Remember

-Some patients use just ___ or just ___ ___ __ (ART)

meds, artificial reproductive technology

Remember

-Dosing is ____ driven and therefore may not be the same as on drug monographs

-Varying ___ of medications may be used

-Multiple gestations depends on med combo and procedure

-ADR rates will vary on dosing and combinations

protocol, combinations

To treat infertility caused by hyperprolactinemia:

1. ____

2. ___

bromocriptine, cabergoline

What is 1st line for infertility?

Clomiphene Citrate

Clomiphene Citrate (Clomid)

-estrogen ___

-inhibits negative feedback on HPA axis to increase release of gonadotropin ___

antagonist, FSH

Clomiphene Citrate (Clomid)

-enhances normal follicular maturation process and ovulation without __ stimulating the ovary

directly

Clomiphene Citrate (Clomid)

-given ___ on days 5-9 (so that by day 14, ovulation will hopefully occur)

orally

Clomiphene Citrate (Clomid)

-titrate dose up each cycle; after __ cycles with no pregnancy, consider another therapy

6

Clomiphene Citrate (Clomid)

-we do not give this med for >12 months because it can increase for __ ___

ovarian cancer

Clomiphene Citrate (Clomid) ADRs

-vaginal dryness and moodiness

-abdominal discomfort

-___ disturbances ("floaters")

-thickening cervical mucus

visual

Clomiphene Citrate (Clomid)

-increases risk for multiple births

-80-85% of patients will ovulate; 40-50% will become ___ in 6 months

pregnant

Clomiphene Citrate Positive Predictors

-age <___

-history of ___ (vs oligomenorrhea)

30, amenorrhea

What is the brand name of letrozole?

Femara

What is the brand name of anastrozole?

Arimidex

Anastrozole and Letrozole

-aromatase inhibitors; prevent conversion of androgen to estrogen (antiestrogen)

-therefore, similar to clomid, this will decrease negative feedback and cause hypothalamus to release ___ and ___

FSH, LH

Anastrozole and Letrozole

-given ___ on cycle days 3-7

-ADRs= vasomotor symptoms, headache, breast tenderness

orally

Anastrozole and Letrozole

-44-90% will ovulate with PCOS; 9.7-40% will become __ with PCOS

pregnant

Anastrozole and Letrozole Problems

-optimal dose

-question of increase risk of spontaneous loss of pregnancy

-may cause ___ abnormalities

congenital

Anastrozole and Letrozole

-can be combined with ___

gonadotropins

There is data that shows individuals with PCOS have some insulin ____ which affects there ovulatory function through hyperinsulinemia

resistance

Metformin

-given for insulin resistance in PCOS

-MOA is insulin-sensitizing agent

-given orally

-success rate is 90% when given with ___

clomiphene

Metformin

-ADR= ___ symptoms (important counseling point)

abdominal

Metformin

-not considered 1st line over clomiphene

-BMI may be predictor of ___

-some studies show improvement in ovulation rates and clinical pregnancy rates, but no improvement in live births

success

Metformin

-Consider as 1st line IN COMBINATION with clomiphene for clomiphene ___ patients

resistant

Metformin

-potential advantage is no endometrial ADR, no increase in multiple birth rates, and no known long term ovarian risk

-disadvantage = takes up to __ months to show effect (so not the best choice for older patient)

6

Treatment Algorithm

1. give clomiphene, potentially give aromatase inhibitor, potentially metformin

2. if non-responder, give ___ ___

exogenous gonadotropins

We can consider starting with ___ with exogenous gonadotropins, the only disadvantages are higher ADE risk and potential for multiple follicles

combination

Exogenous Gonadotropins

-either ___ alone or in combination with __ that directly works on the ovaries to induce follicular development

FSH, LH

Exogenous Gonadotropins

-many products available

-doses are customized to patient

-no advantage of one agent over another; main considerations are if it is on ___, route of ____, and delivery ___

formulary, administration, device

What are the 3 gonadotropins?

1. ___ ___ (Reponex)

2. ___ (Brevelle)

3. ___ ___ (Gonal-F) and ___ ___ (Follistim)

human menotropins, urofollitropin, follitropin alfa, follitropin beta

Urofollitropin, follitropin alfa, and follitropin beta are FSH. Human menotropins (Reponex) contains FSH and __ (but the amount is so small it doesn't do anything)

LH

human menotropins (Reponex) and urofollitropin (Brevelle) are purified FSH extracted from __ of post-menopausal women

urine

follitropin alfa (Gonal-F) and follitropin beta (Follistim) is ____ FSH

recombinant

follitropin alfa (Gonal-F) and follitropin beta (Follistim) come in a ___, and therefore is easier for patients

pen

Gonadotropins

-increase follicular recruitment and development in conjunction with __ (may get more than 1 follicle)

hCG

Gonadotropins ADRs

-hot flashes, breast tenderness, abdominal pain, nausea, diarrhea

-___ site reactions

-dry skin, rash, alopecia, hives

-____

injection, OHSS

OHSS = ___ ___ ___

ovarian hyperstimulation syndrome

OHSS

-rare but has __ threatening complications (eg kidney failure, thrombosis, stroke)

life

OHSS

-excessive response to ovulation therapy (__ estradiol and follicle number)

high

OHSS

-monitored for with serial ultrasounds and estradiol concentrations every day or 2 (goal is __-__pg/mL per follicle with no more than __ mature follicles)

150-300, 2

OHSS Risk Factors

-__ and repeated doses of exogenous gonadotropins

-___

high, PCOS

OHSS Treatment

-withhold ___ (ie stop the cycle; this is bad because it could have cost up to $10k)

hCG

OHSS Symptoms

Mild → abdominal discomfort, N/V/D

Severe → hemodynamic ___, ascites, severe ___, dyspnea and ____

instability, pain, tachypnea

When dosing a gonadotropin, you can either step ___ (less ADEs) or step ____ (patient won't have to be on med for as long)

up, down

Gonadotropins Step-up Protocols

-increase dose until _____ ____

-increase is based on _____ _____

-dose is then maintained until ___ ___ is administered (___-____)

desired response, follicular development, ovulation inducer, 16-18mm

Gonadotropins Step-up Protocols

-Start with a ___ dose of gonadotropins, then can ____ the ____ ____

low, adjust, second round

Advantage of starting with low dose of gonadotropins = ____ ____ ___ effects (eg OHSS) and ___ __ ____ risk

less excessive adverse, less multiple pregnancy

low dose gonadotropins = ___-___ IU daily for ___ ___then increase by ____ ___ ___to max ___ __ ____

37.5-75, 14 days, 37.5 IU weekly, 225 IU daily

Gonadotropins Step-down Protocols

-advantage = ____ __ of medications

-disadvantage = ____ ___, including ___ and __ ___

shorter duration, more ADEs, OHSS, multiple births

Important to know that patients receiving ____ can still _____ through ____, so gonadotropin therapy is not automatically combined with ___ (but it often is)

gonadotropin, conceive, intercourse, ART

2 STEPS for gonadotropin therapy

First= give ______ (___) to stimulate _____ ____

Next= give ____ ___ (mimics ___) to trigger ___.

gonadotropins, FSH, follicle development, chorionic gonadotropins, LH, ovulation

Chorionic Gonadotropins (hCG) = ___, ___, ___

Novarel, Ovidrel, Pregnyl