What is the normal length of the female menstural cycle?
28 days + or - 7
What is the duration of flow during menses for most women
4 +/- 2 days
Excessive bleeding in the menstrual cycle occurs when the cycle lenght is less than ____, the duration of flow is more than ___ or the blood lost per cycle is more than ___
less than 21 days
more than 7 days
more than 80ml per cycle
What is the treatment for women with dysfunctional/anovulatory bleeding?
Horomone control of the cycle
If they want to get pregnant: give medication to ovulate either clomiphene or gonadotropins
If they want contraception: give birth control (cycllic control but no ovulation will also benifit PCOS) or if have contraindications to the pill (just give progesterone Provera (bad lipid profile), aygestin or Mirena
What are some "organic" causes of abnormal uterine bleeding
Benign pelvic lesions (Fibroids, Endometrial and endocervical polyps, adenomyosis)
If the endometrial thickness is < ___ mm on ultrasound then there is a 3% chance of cancer
5mm
___ is the type of fibroid that causes the majority of abnormal uterine bleeds
Sumbucous myomata
___ is a rare form of uterin fibroid that dose not usually cause bleeds
Intramural myomata
__ is a fibroid type that is the cause of pain and pressure but never bleeding
Subserosal
Do endometrial and endocervical polyps typically cause
A. Midcycle spotting
What are some changes in mensturation that a pt may complain of that will tip you off that she is having an abnormal uterine bleed?
If the pt complains that it disrupts thier life
if they have an increase by 2 sanitary pads/day
If the duration is 3 days longer than usual
if there is intermenstrual bleeding
if the cycle is 2 days shorter than usual
Blood clots and socially embarassing bleeding
What are some questions you should ask while taking a history from a pt with abnormal uterine bleeding?
Past medical history
medications
contraceptive use
age of AUB onset
LMP to r/o pregnancy
sexually active?
cycle regularity
abnormal bleeding from other sites
What are some diagnostic studies you should perform if you determine a pt to be anovulatory?
Hormone levels: hypothalamus makes GnRH every 90 mins pulse which stimustes pitutitary and FSH and LH ovary and then to estrogen and progesterone
Hypothalamic amenorrhea
Prolactin
TSH
If FSH is high and estrogen is low during a hormone level test for an anovulatory pt then it means
the ovary is not responding.
Ovarian failure
Either premature or premenopausal
If FSH is low and estrogen is low during a horomone level test for an anovulatory pt then it means
Hypothalamic problem
THe brain is not responding to the low estrogen
anorexic pts and pts who are heavy exercisers (runners more than 35 miles/wk)
Or a Brain lesion that compress the hormone stalk between the hypothalamus ans the pituitary gland - HA
What is the treatment for Anovulatory abnormal uterine bleeding?
Progestins,
E2/P4
OCPs
Thyroid replacement
parlodel
Mirena IUD
Von willebrand type I, II and III as well as platelet abnromalities, and abnormal vessel wall components lead to (primary or secondary) hemostasis
Primary
Stabilization of platelet plug with fibrin deposition abnormalities such as factor deficencies, oral anticoagulants and aquired factor deficencies are disorders of (primary or secondary) hemostasis
secondary
22 y.o. F presents for her yearly pap. When questioned about her menstruation she states "yes, it is very heavy and lasts 7 days on average". Before leaving she also says "I know you are not a dermatologist but I have been getting this rash on my legs since I started running recently," she pulls up her pant leg to reveal diffuse petechial rash along her calfs and several bruises near her knees and shins. What is her abnormal uterine due to?
Primary Hemostatsis problem it could be a platelet abnormality, vessel wall malformation or Von willibrands disease
15 y.o. presents with abnormally heavy bleeding. She reached menarche about a year ago and has noted that it has been getting heavier since the onset. She has gained 4 pounds since the onset of puberty but is still thin for her height. She also has noticed large ecchymosis and when questioned about it she says "I bruise easily, mom says I have to go to a special dentist because when the pull teeth those bleed more than normal too" What do you suspect is causing her abnormal uterine bleeding? What diagnostic studies do you want to order?
Secondary hemostasis A factor deficiency of some sort
CBC and platelet count
PT factors 2,5,7,10 and fibrinogen
APTT factors 8,9,12,5,10,2
Bleeding time- platelet function platelet number, von willibrand factor and vascular integrity
Platelet function test- replace bleeding time
vWF screen - vWAg
What evaluations of the reproductive tract should you perform for a pt with abnormal uterine bleeding?
Endometrial biopsy especially if over 35y.o.
Vaginal US if post menopausal
Pap smear +/- colposcopy
Guiac
r/o infection: cervical cultures, EB to rule out chronic endometritis
R/o adenmyosis: MRI, US, hysteroscopy
What are the 4 indications for uterine cavity evaluation in a pt with abnormal uterine bleeding
premenopausal and ovulatory
premenopausal and anovulatory but fails hormone therapy
postmenopausal bleeding HRT
unexpected peost menopausal bleeding on HRT
What are 4 diagnostic techniques for Uterine cavity evaluation
D and C
Hysterosalpingogram
Vaginal probe ultrasound
Sonohysterography
Office hysteroscopy
D and C for abnormal uterine bleed
Misses 40% of focal lesions (polyps and fibroids)
equal to pipelle office biopsy for detecting diffuse endometrial carcinoma
Shouldent be done only indicated when office biopsy cannot be obtained
Histerosalpingogram
is a radiologic procedure to investigate the shape of the uterine cavity and the shape and patency of the fallopian tubes. It entails the injection of a radio-opaque material into the cervical canal and usually fluoroscopy
with image intensification. A normal result shows the filling of the uterine cavity and the bilateral filling of the fallopian tube with the injection material. To demonstrate tubal rupture spillage of the
material into the peritoneal cavity needs to be observed.
T or F vaginal ultrasound is sensitive for endometiral lesions like polyps, myomas and focal cancers
False
It can evaluate intramural and subserosal fibroids
Useful for post menopausal bleeding >6mm endometrium = bad
What is a sonohysterography?
When the inject 20 cc of fluid into the uterus
much more accurate than US alone
if the uterus is pointed to the left the uterus is anteroflexed
if the uterus is pointed the right the uterus is retroflexed
What is the diagnostic test of choice for abnormal uterine bleeding
Office hysteroscopy
During what part of the cycle should a office hysterography be performed?
Early follicular phase
Most common cause of mid cycle spotting
polyp
"string of pearls' seen on vaginal ultrasound of ovaries
PCOS
how many cysts on the ovaries are diagnostic of PCOS
10
30 y.o. F presents with abnormal hair growth, obesity, abnormal uterine bleeding and anovulation. On an examination of her hormone levels you find that LH is 3x higher than FSH. What is her diagnosis
Poly cystic Ovarian Syndrome
Infertility is __ yr with unprotected intercourse without producing a child
1
If conception occurs then the corpus luteum is maintained by __ secretion by the trophoblast and continues to produce progesterone until ___ development occurs at 9-10 wks
maintained by hCG secretion
placenta takes over a 10 wks
In men LH stimulates ___ cells to secrete testosterone
Leydig
Testosterone provides negative feedback to the hypothalamus by stimulating __ cells to secrete inhibin which decreases __ secretion
Sertoli cells
FSH
Sertoli cells secrete __ and __
testosterone and inhibin
What is premature ovarian insuficency?
Premature Ovarian Failure (POF), also known as premature ovarian insufficiency, primary ovarian insufficiency (this is the most accurate term as some women may still conceive), premature menopause, hypergonadotropic hypogonadism, is the loss of function of the ovaries before age 40. A commonly cited triad for the diagnosis is amenorrhea, hypergonadotropinism, and hypoestrogenism. If it has a genetic cause, it may be called gonadal dysgenesis
What are some genetic causes of premature ovarian insufficency?
X chromosome disorders (turner's syndrome)
Deletion of the distal arm of X
FMR1 gene mutation
What are 5 iatrogenic causes of premature ovairian insufficency? (hint: includes surgical causes)
Pelvic radiation
Chemotherapy
Autoimmune disorders (not really iaterogenic but maybe...)
Surgical: hysterectomy
UAE
___ is characterized by at least 4 months of abnormal uterine bleeding in conjunction with more than one elevated FSH level. Especially the triad of Disordered uterine bleeding, oligomenorrhea, amenorrhea (in that order)
Premature ovarian insufficency
___ is a dysfunction of GnRH pulsatility from the hypothalamus causing decreased levels of FSH, LH and estradiol
Hypogonadotrophic hypogonadism
What are some causes of hypogonadotrophic gonadism
eating disorders: anorexia bulemia
extreme exercise
Stress
Hyperprolactinemia
Primary hypothyroidism
CNS lesion
Genetic: kallermanns Syndrome
Idiopathic
What are two negative long term effects of hypogonadotropic hypogonadism in women
osteopenia, osteoporosis
2 sx of hypoganadotrophic hypogonadism
amehorrhea
vaginal dryness
What diagnostic test do you do for hypogonadotrophic hypogonadism
Progesterone Challenge test
an assessment of estrogen production
negative withdrawl bleed is diagnostic
Perscribe provera 10mg PO for 5-7 days if HCG is negative and P4 level is consistent with anovulation
WHat is the treatment for hypogonadotrophic hypogonadism
Gonadotrophin therapy to replace deficient FSH and LH
hCG to trigger ovulation
Clomiphene citrate does not induce ovulation in pts with this disorder
To help a woman with hypogonadotrophic hypogonadism achieve pregnancy which should you not! prescribe?
A. Gonadotrophin therapy
B. hCG
C. Clomiphene
D. all of these are effective
Clomiphene citrate does not induce ovulation in pts with this disorder
__ is a complex endocrine disorder associated with hyperandrogenism and chronic anovulation in cases where secondary causes have been excluded. It is characterized by multiple cysts that form on the ovaries from partially ruptured follicles.
Polycystic Ovarian Syndrome
Which of the following is NOT true about the pathophysiology of PCOS?
B. Adrenal androgen remains constant is FALSE there is alos an abnormal adrenal androgen production
What are some of the effects of excess insulin associated with PCOS? (there are alot basically it F's you up)
Increased ovarian androgen production
Excess growth of basal cells of the skin
Increased vascular and endothelial activity
Abnormal hepatic and peripheral lipid metabolism
Sodium retention
Vascular remodling
Increased response to angiotensin II
Increased production of triglycerides
Decreased production of protective HDL
Increased LDL especially the more atherogenic small partical LDL that can invade the vascular endothelium
Increased platelet adhesion
Increased inflammation as seen in elevated c-reactive protein
Increased production of fibrinogen
Reduced amounts of nitric oxide
Incresed uric acid
Increased infiltration of fatty acids in the liver which can cause inflammation and lead to fibrosis as evidence by elevated LFTs and abnormal ultrasounds of the liver
Fatty streaks on liver
Decreased hepatic production of binding proteins such as SHBG and IGF
Increased tissue growth in the throat area, leading to obstructive sleep apnea
Shunting of fat dispostion to the abdominal cavity
Hyperpigmentation of the kin in the flexor surfaces clinicaly known as acanthosis nigricans
What is the new diagnostic criteria for PCOS? (the Rotterdam criteria)
At least 2 of the 3 criteria must be present:
Oligoovulation or anovulation
Clinical or biochemical signs of hyperandrogenism (elevated hormone levels, total testosterone, Androstenedione, DHEAS, Insulin)
Testosterone and insuline both inhibit SHBG synthesis from the liver which results in further elevated testosterone levels
polycystic ovaries
Must also exlcude other eitiologies:
nonclassic adrenal hyperplasia
androgen secreting tumors
hyperprolactinemia or hyperthyroidism
What are the 4 treatment goals for a pt with PCOS?
Reversing the signs and symptoms of androgen excess
instituting cyclic menstruation
restoring fertility
ameliorating metabolic disturbances such as insulin resistance with weight reduction and exercise
What are some lifestyle modifications that a pt with PCOS to help ameliorate their condition?
Obesity reduction: increases peripheral aromatization of androgens to estrogens, decreases levels of SHBG and increases insulin levels pregnancy safer; accomplished with change in foods and exercise
What drugs should be given to a pt with PCOS to induce ovulation?
Clomid
Clomid metforman (in pts with anovulatory infertility that is not prevously treated the combo is not nessicarily better)
Gonadotropins with IUI
If a pt with PCOS is clomiphene resistant with a high insulin resistance what would be your next line drug of choice to try?
Metforman
increases rate of spontaneous ovulation
What are some health risks associated with PCOS?
Lipid abnormalities
Hypertension
Clot formation
Heart diasease stroke and type 2 diabetes
endometrial cancer
pregnancy loss
Elevated serum prolactin levels above __ ng/mL surpress GnRH secretion from the hypothalamus
20
What are some causes of hyperprolactinemia?
Prolactin secreting tumors
Tumors that block the action of PIF to the pituitary
Medications that inhibit the release of PIF (antipsychotics, antidepressants, GI drugs lik tagament and reglan, antihypertensives like aldomet)
Hypothyroidism
What are the Sx or clinical findings of hyperprolactinemia
galactorrhea
causes ovulatory dysfunction ranging from oligomenorrhea to ammenorrhea
What is the treatment for a pt with hyperprolactinema who wishes to become pregnant?
Discontinue medicatiosn that inhibit the release of PIF
treat underlying medical condition (hypothyroidism)
surgically resect large macroadenomas
suppress prolactin release using dopamine agonists like Bromocriptidne and Cabergoline
2 drugs that are used to suppress prolactin release (hint: they are dopamine agonists)
Cabergoline
Bromocryptidine
__ is when there is damage or blockage of the fallopian tube caused by endometriosis, PID or STDs. It results in proximal tubal occlusion, distal tubal occlusion or adenexal adhesions. Impedes migration of sperm and egg decreasing fertility and increasing risk of ectopic pregnancy
Tubal Factor
What are the two treatment modalities for Tubal factor in infertility?
Surgical repair: success is related to the severity of disease, there is an increased ectopic rate
IVF: pts wth hydrosalpinges have a 50% lower pregnancy rate compared to those without hydrosalpinges.
Recommendations prior to IVF Laparoscopic salpingectomy or proximal tubal occlusion
__ is the presence of endometrial glands and stroma outside the uterus
endometriosis
What is the effect of endometriosis on fertility
distorted pelvic anatomy from tubal scarring and pelvic adhesions
peritoneal factors increased macrophages and prostaglandins in peritoneal fluid
Impaired implantation
28 y.o. F presents after a 2 yr period of trying unsuccessfully with her new husband to become pregnant. She has normal periods that are regular but are painful and associated with pelvic pain. She also reports dyspareunia. On PE she has some nodularity of the uterosacral ligament.. you think. What would you do to further investigate? What do you think she has? for your suspected diagnosis what is the gold standard diagnostic proceedure?
Pelvic ultrasound for further eval
She may have endometriosis
Laparoscopy is the gold standard
What is the gold standard diagnostic proceedure for endometriosis
Laparoscopy
What is treatment for endometriosis
surgical treatment
ovulation induction with IUI: clomid and gonadotropins
IVF
Uterine factors in infertility acount for 10% of cases, they intervere with the ability to implant or develop. There are two types Anatomic and ____. name some anatomic eitiologies
Endometiral insufficency is the other category it is hormonal in eitiology
What is the hormonal therapy for male factor infertility
testosterone and clomid
What are the three most likely proceedures that will occur to overcome male factor infertility?
IUI
IVF and
ICSI
__ refer's to a womans reproductive potential with respect to ovarian follicle number and oocyte quality and quantity
Ovarian reserve
What are some reasons for diminished ovarian reserve?
Genetic
Pelvic surgery
Iatrogenic
Smoking
T or F cycles may remain regular even with markedly decreased ovarian reserve
True
Anyone trying to concieve who's BMI is over 36 needs to have a __ consult before attempting IVF. They also require more meds to stimulate ovulation, and if they become pregnant they have a higher risk for these conditions during their pregnancy....
Anesthesia consult
HIGH risk pregnancy with diabetes, HTN preeclampsia
What is the first line evaluation for ovarian reserve?
Cycle day 3 FSH/Estradiol
Normal: FSH less than 10 and E2 less than 80
If their value of FSH is over 15 then are in menopause and rejected for Infertility treatment
Inhibin B: also drawn on day 3, secreted by the granulosa cells. Inhibits FSH secretion. expect a high value
What is a clomiphene challenge test?
Reserved for women over 40
100 mg daily on cycle days 5-9 return on cycle day 10 to retest FSH
Clomid binds to estrogen receptors in the brain. It stimulates the ovaries to produce estrogen. FSH then decreases. Day 10 FSH should be either lower ro the same as the day 3 value. If it is higher then there is a compromised ovarian reserve
An FSH less than 15 on both 3 and 10 is an adequate ovarin reserve
What is an antral follicle count
looking at the number of small follicles on the ovary on day 3. US of the ovary on days 2-3. if there are between 2-10 follicles = normal
___ is a fertility test used for older pts. it is produced by the primordial folicle and is an indicator of ovarian follicular core
Anti-mullerian hormone
___ is the gold standard test for evaluation of the uterine cavity and falloian tube. It is done with flouroscopy/x-ray
Hysterosalpingogram
A hysterosapingogram must be done before day __ in the cycle
12
what must you ask pts to do prior to a hysterosalpingogram?
abstain from sexual intercourse or use protection you don't want ne chance of pregnancy b/c this will kill it
ALWAYS ask when was your last menstrual period and was it normal b/c they could have had spotting due to implantation and thought it was a light period
A sperm specimin for analysis must be analyzed within __ hrs of ejaculation and must be kept at what temperature during that time
1 hr
body temp
less then 10 million motile sperm the therapy of choice for infertility is __
insemination
greater than 15 million motile sperm the infertility treatment of choice is __
intercourse
50-100,000 per oocyte are needed for this treatment for infertility
IVF
___ is the most precise tx for male infertility and requires only one viable sperm
ICIS
__ is the DOC for anovulatory pts with an intact hypothalamic pituitary axis
Clomid
__ is a drug that binds to the estrogen receptors in the anterior pituitary and hypothalamus thereby blocking negative feedback to the pituitary
clomid
Ovulation causes a (increase? or decrease?) in basal body temperature
Decrease
After ovulation there is a (increase? or decrease?) in body temperature?
increase the corpus luteum has a stimulatory effect this is when the egg is already ovulated and traveling in the tube prime for fertilization!
Using a urinary LH surge kit, the kit detects a surge, then the pt will ovulate ___ hrs later
Concern for birth defects possible increase with cardiac, locomotor malformations
MOA of aromatase inhitibors
Letrozole
blocks peripheral conversion of androgens to estrogens
releases HPO axis from negative feedback and increases the release of FSH
No antiestrogenic effects
Name an aromatase inhibitor
Letrozole
Indications for the use of gonadotropins as therapy for infertility
Ovulation inductino in women who do not respond to oral agents
Controlled ovarian stimulation with IUI or IVF
What are the two types of gonadotropins?
Urinary: menopur and repronex (FSH with very small amnts of LH
Recombinant: gonal-f and follistim act as FSH
What is the MOA of gonadotropins
bind to FSH receptors and promote follicular development and E2 prodution from granulosa cells
gonadotropins are administered __
SC
What are the SEs of gonadotropin use
local reaction at injection site
multiple gestation
OHSS
Ectopic pregnancy
Adnexal torsion
Ovarian cancer
Explain ovulation induction monitoring
baseline ultrasound on cycle day 3 to ensure there are not residual cysts on the ovaries
if everything is normal then start the gonadotropin injections
Cycle day 11 do an US
monitor the follicles that responded and the estradiol levels
if everything is ready to go administer hCG
36 hrs later insemination!
on specific day roughtly 2 wks later come in for pregnancy test
What are the indications for using hCG in infertility
trigger ovulation/final follicle maturation
LH support during folliculogenesis
What is the MOA of hCG?
similar in structure to LH and functions like LH to binding to LH receptors
mode of administration of hCG is __
SC
ovulation occurs ___ hrs after injection of hCG
36-44hrs
GnRH agonists (name one, what does it do?, why do we use it? method of delivery?)
Lupron
chemically similar to GnRH causes an initial increase in the circulating levels of FSH and LH from the pituitary. Continued administration results in down regulatin and supression of the pituitary FSH and LH secretion within 2-4 wks. This suppresion means the provider has entire control over when the FSH/LH spike (thus ovulation) occurs and allows for the havesting of eggs
Method of admin: SC inject
GnRH antagonists (name 2, what do they do?, why do we use them? method of delivery)
Antagon
Cetrotide
Competitively blocks GnRH receptors
Induces a rapid reversible suppression of LH and FSH secretion by the pituitary (occurs 2 hrs after SC dose)
No initial flare
givent when lead follicle reaches 12-14mm
What are some medications for luteal support? how do they help conception?
