Infertility Flashcards
What is infertility?
the inability to conceive after 1 year of unprotected intercourse
Differentiate primary and secondary infertility.
primary infertility:
-couple has never conceived a child
secondary infertility:
-couple previously successful in conceiving but unable to achieve a subsequent pregnancy
What are the impacts of infertility?
emotionally and psychologically difficult
-feelings of anger, sadness, jealously, guilt
impacts relationships
When should infertility be assessed?
women is < 35 yo: after 12 months of unprotected intercourse
earlier: investigation ( 6 mo) may be appropriate in some
-age > 35
-menstrual abnormality
-previous abd/pelvic/urogenital surgery
-hx of pelvic disease
-hx of STIs
-abnormal genital exam
What are the risk factors for infertility?
risk factors depend on reason for infertility
as an example, some risk factors for ovulation disorders:
-smoking (1st and 2nd hand)
-weight (over or underweight)
What are the potential causes of infertility in women?
increasing age
ovulatory dysfunction
-anovulation
-PCOS
-luteal phase defect
anatomical factors
-tubal dysfunction
-cervical factors
At what age does fertility begin to decline?
declines after 30 yo; marked decline after 40 yo
-1/3 of women who delay pregnancy until mid-late 30s (and 1/2 of women > 40 yo) will be unable to conceive w/o assistance
What is ovulatory dysfunction?
ovaries fail to produce a mature egg on a regular basis
What causes anovulation?
occurs as a result of disruption in the HPO axis
can be due to a variety of causes
-physical injury to hypothalamus or pituitary gland
-obesity, anorexia, bulimia
-excessive exercise
-stress
-exposure to chemotherapy/radiation
-endocrine disorders
What is PCOS?
a syndrome of ovarian dysfunction which is characterized by:
-hyperandrogenism
-ovulatory dysfunction
-polycystic ovaries
What is the leading cause of anovulatory infertility?
PCOS
What causes PCOS?
unknown
-thought that peripheral insulin resistance can lead to hyperinsulinemia & stimulation of excess ovarian androgen production
-there is a genetic link
What are the signs and symptoms of PCOS?
menstrual irregularities - amenorrhea or oligomenorrhea
hyperandrogenism
-hirsutism, acne, seborrhea, alopecia
overweight/obesity
infertility
20% may be asymptomatic
What are the comorbidities often associated with PCOS?
reproductive challenges
-infertility, pregnancy complications
endometrial hyperplasia or cancer
metabolic issues
-diabetes, CVD, metabolic syndrome
obstructive sleep apnea
depression
What might the goals of therapy look like for PCOS?
decrease/get rid of hyperandrogenic features
manage underlying cardio metabolic abnormalities
prevent endometrial hyperplasia as a result of chronic anovulation
contraception for those not wanting pregnancy
ovulation induction for pregnancy
What are the 1st, 2nd, and 3rd line options for PCOS?
1st line for overweight/obese women: weight loss
-through lifestyle
-help improve fertility, hirsutism, BP/BG/lipids
2nd line: pharmacotherapy
3rd line: bariatric surgery
What is 1st line for menstrual cycle irregularities caused by PCOS?
CHC
-oral preferred but can use patch or ring
What are the benefits of CHC in menstrual irregularities caused by PCOS?
regulate menstruation in those with oligomenorrhea
protects from endometrial hyperplasia
-chronic anovulation associated with increased risk
helps androgenic symptoms
How should CHCs be dosed for menstrual irregularities caused by PCOS?
low dose of EE and a progestin with low androgenicitiy
What are some alternatives to CHCs for menstrual cycle irregularities caused by PCOS?
progestin-only therapy
metformin
Which symptoms of PCOS are not helped with progestin-only therapy?
androgenic
What are the benefits of using metformin in PCOS?
improves glucose tolerance
reduced androgen production in ovaries
may help restore ovulatory cycles in up to 50% of women
its ability to provide endometrial protection is less well established
What is 1st line for hirsutism that is a result of PCOS?
CHC
-oral preferred, can use patch or ring
How do CHC work for hirustism?
suppress androgen
How should CHCs be dosed for hirsutism caused by PCOS?
typically start with 20 mcg EE and progestin with lower androgenicity
How long should CHCs be trialed for hirsutism before moving on?
try for 6 months before moving on to correlate with growth cycle of terminal hair
What is 2nd line for hirsutism that is a result of PCOS?
antiandrogen - if suboptimal response at 6 months
-spironolactone
-finasteride
How do spironolactone and finasteride work for hirsutism?
spironolactone:
-antagonizes the androgenic effect of DHT on the hair follicle
finasteride:
-reduces 5a-DHT concentrations
How long does it take to see improvement in hirsutism with spironolactone?
6-9 months
What is required with spironolactone and finasteride in females?
contraception
What is a topical option that can be tried for hirsutism that is a result of PCOS?
eflornithine HCl cream
How does eflornithine work for hirsutism?
topical agent that inhibits hair growth
-slows hair growth, does not remove
must be used indefinitely to prevent regrowth
What can be tried for acne that is a result of PCOS?
1st line: CHC
-particularly low androgen progestins
topical acne medications
consider spironolactone
What are some metabolic abnormalities seen in PCOS?
obesity
insulin resistance
dyslipidemia
OSA
depression/anxiety
What is the 1st line option for fertility in PCOS?
lifestyle modification
-goal is to optimize health before starting drug therapy
-wt loss of 5-10% can help restore ovulatory cycles
-also helps insulin resistance, CV risk, hirsutism
What are the medications used for ovulation induction?
letrozole
clomiphene
metformin
gonadotropins
What is an off-label use of letrozole?
anovulation
What is the MOA of letrozole for infertility?
as aromatase is suppressed, so is estrogen levels, and the hypothalamus & pituitary increase FSH output which stimulates ovarian follicles to develop and mature in the ovary so ovulation can occur
How effective is letrozole for infertility?
70-80% will ovulate and a cumulative pregnancy rate of ~ 30%
How many cycles is letrozole used for?
on average - 3 cycles
What are the adverse effects of letrozole?
hot flashes or night sweats
fatigue
nausea
multiple births
What is a contraindication of letrozole?
pregnancy
Where would you find clomiphene?
only available at compounding pharmacies
What is the MOA of clomiphene?
SERM
-blocks estradiol receptors in hypothalamus which increased FSH release
-this results in growth of the ovarian follicle and in turn ovulation
How should clomiphene be taken?
day 5 of the menstrual cycle after a spontaneous or progestin-induced menstruation OR at any time if amenorrheic and no recent bleeding
What are the adverse effects of clomiphene?
multiple gestations
hot flashes
abdominal discomfort
vision disturbances
What is a contraindication of clomiphene?
pregnancy
When is ovulation expected with letrozole and clomiphene?
5-10 days after the last dose
How do letrozole and clomiphene differ in efficacy?
letrozole appears more effective than clomiphene for achieving live birth in pts with ovulatory disorders
for unexplained fertility they appear equally effective
-less effective then gonadotropin-based treatments
Describe the frequency and timing of intercourse when using clomiphene or letrozole.
around ovulation (4-5 days prior to ovulation) every 24-48h
-replenishment of ejaculate volume requires 24-48h
-egg survives for up to 24h after ovulation; sperm can survive for up to 5 days in the female reproductive tract
How does metformin work for improving fertility?
decreasing hepatic glucose output and improving peripheral insulin sensitivity
results in lower insulin levels and decrease androgen production
How is metformin typically used for infertility?
as an add-on to clomiphene
When should metformin be discontinued when being used for fertility?
with pregnancy
What is the luteal phase defect?
insufficient progesterone levels do not allow for preparation of the endometrium for implantation
-failure to implant
the uterine lining doesnt grow properly, hence there may be difficulty with achieving or maintaining pregnancy
What is the treatment for luteal phase defect?
progesterone
-luteal phase support to improve pregnancy rates when used with ovulation stimulators, gonadotropins
How is progesterone administered for luteal phase defect?
depends on the protocol for ovarian stimulation
optimal timing and dose (and route) not entirely known
What are some anatomical factors that can contribute to infertility?
blocked fallopian tubes
endometriosis
PID
What might contribute to male factor infertility?
obstructive/physical/genetic factors
sexual intercourse factors
endocrine factors
gonadotoxic (sperm) factors
What might cause obstructive/physical/genetic factors that lead to male infertility?
trauma
surgery
STI
cystic fibrosis
Kleinfelter syndrome
What might contribute to the sexual intercourse factors that lead to male infertility?
decreased libido
erectile dysfunction
impaired ejaculation
What are some endocrine factors that lead to male infertility?
obesity
hypothalamic or pituitary dysfunction alters the secretion of LH, FSH, and testosterone
What are some factors that affect spermatogenesis?
environmental and lifestyle:
-alcohol, smoking
-excessive heat to scrotal area
-radiation, toxin exposure
drug-induced:
-marijuana, cocaine
-chemotherapy
-anabolic steroids
-cimetidine
-finasteride
-spironolactone
-sulfasalazine
-nitrofurantoin
What are the treatment options for male factor infertility?
correct the modifiable risk factors
surgical repair –> varioceles; obstructive lesions
hormone therapy –> hypogonadtrophic hypogonadism
-decreased T, LH, and FSH
-tx with hormone therapy: gonadotropins, GnRH infusion
sperm cryopreservation
ART
What is basal body temperature?
temperature that occurs prior to rising in the AM
What happens to basal body temperature with ovulation?
with ovulation, corpus luteum releases progesterone causing an increase in temp of approx 0.28 C or 0.5 F
-progesterone is thermogenic
-temp rises occurs over a period of up to 3 days and is usually maintained until day 1 of menses
What are some counselling tips for BBT charting?
take 1st measurement on 1st day of menstrual period
take temp for at least 5 mins each morning upon awakening, before any activity or getting out of bed
record info for 1-3 cycles in order to identify a pattern
chart temp on graph daily
What do ovulation prediction kits do?
detect the LH surge that precedes ovulation by measuring its concentration in urine
How accurate are ovulation prediction kits?
98.3% accurate if performed correctly
How do you use ovulation prediction kits?
chart menstrual cycle ahead of time so that ovulation may be predicted; it is also helpful to know that the most fertile period is 14 days before next menses
test 2-4 days before anticipated ovulation at same time of day (usually AM)
