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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
- Implantation bleeding
- Systemic diseases (coagulopathies, hypothyroidism, liver disease)
- 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
___ is the type of fibroid that causes the majority of abnormal uterine bleeds
___ is a rare form of uterin fibroid that dose not usually cause bleeds
__ is a fibroid type that is the cause of pain and pressure but never bleeding
Do endometrial and endocervical polyps typically cause
A. Midcycle spotting
B. Heavy menstruation
C. Heaving bleeding
D. None of the above
A. Midcycle spotting
(this multiple choice question has been scrambled)
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
- 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
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?
- Thyroid replacement
- 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
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
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
- 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
- Vaginal probe ultrasound
- 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
- 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
- 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
During what part of the cycle should a office hysterography be performed?
Early follicular phase
Most common cause of mid cycle spotting
"string of pearls' seen on vaginal ultrasound of ovaries
how many cysts on the ovaries are diagnostic of PCOS
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
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
Testosterone provides negative feedback to the hypothalamus by stimulating __ cells to secrete inhibin which decreases __ secretion
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
- Autoimmune disorders (not really iaterogenic but maybe...)
- Surgical: hysterectomy
___ 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
What are some causes of hypogonadotrophic gonadism
- eating disorders: anorexia bulemia
- extreme exercise
- Primary hypothyroidism
- CNS lesion
- Genetic: kallermanns Syndrome
What are two negative long term effects of hypogonadotropic hypogonadism in women
2 sx of hypoganadotrophic hypogonadism
- 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
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?
A. Insulin resistance can develop
B. Adrenal androgen remains constant
C. Elevated ovarian androgen production is present
D. GnRH pulses increase in frequency and amplitude leading to altered LH/FSH ratios
B. Adrenal androgen remains constant is FALSE there is alos an abnormal adrenal androgen production
(this multiple choice question has been scrambled)
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 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?
- increases rate of spontaneous ovulation
What are some health risks associated with PCOS?
- Lipid abnormalities
- 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
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)
What are the Sx or clinical findings of hyperprolactinemia
- 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)
__ 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
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
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
What is treatment for endometriosis
- surgical treatment
- ovulation induction with IUI: clomid and gonadotropins
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
- Anatomic eitiologies include: Asherman's syndrome, Fibroids, Mullerian anomalies (septate or bicornuate uterus)
What diagnostic evaluations would you do if you supected uterine factor infertility
- 3D pelvic ultrasound
- Endometrial biopsy
What is the treatment for Uterine factor infertility?
- Surgery: Hysteroscopic lysis of adhesions, hysteroscopic metroplasty, myomectomy
- Hormonal supplementaion: correct endometrial insufficency
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?
__ refer's to a womans reproductive potential with respect to ovarian follicle number and oocyte quality and quantity
What are some reasons for diminished ovarian reserve?
- Pelvic surgery
T or F cycles may remain regular even with markedly decreased ovarian reserve
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
___ is the gold standard test for evaluation of the uterine cavity and falloian tube. It is done with flouroscopy/x-ray
A hysterosapingogram must be done before day __ in the cycle
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
less then 10 million motile sperm the therapy of choice for infertility is __
greater than 15 million motile sperm the infertility treatment of choice is __
50-100,000 per oocyte are needed for this treatment for infertility
___ is the most precise tx for male infertility and requires only one viable sperm
__ is the DOC for anovulatory pts with an intact hypothalamic pituitary axis
__ is a drug that binds to the estrogen receptors in the anterior pituitary and hypothalamus thereby blocking negative feedback to the pituitary
Ovulation causes a (increase? or decrease?) in basal body temperature
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
What are the SEs associated with clomid?
- Anti-estrogen side effects: vasomotor symptoms, mood swings, thin EM, scant cervical mucous
- Visual symptoms: blurred or double vision
- Risk of ectopic preg
- Risk of multiple gestation
- Risk or OHSS
- Risk of adenexal torsion
- risk of ovarian cancer
SEs of aromatase inhibitors
- hot flashes
- GI upset
- Concern for birth defects possible increase with cardiac, locomotor malformations
MOA of aromatase inhitibors
- 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
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 __
What are the SEs of gonadotropin use
- local reaction at injection site
- multiple gestation
- 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 __
ovulation occurs ___ hrs after injection of hCG
GnRH agonists (name one, what does it do?, why do we use it? method of delivery?)
- 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)
- 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?
- Systemic: progesterone oil 50mg IM daily
- Local: progesterone vaginal suppositiories, crinone, prometrium
- Normal luteal function requires optimal preovulatory follicular development
- Luteal phase adequacy may be compromised with IVF cycles due to ovulation-induction of medications and follicular aspiration
- Therapy is discontinued with a negative hCG level or at 12 wks of pregnancy
- In-vitro fertilization
- ovarian suppression
- ovarian stimulation and ultrasound and monitoring
- ultrasound guided oocyte retreival
- Laboratory process: identification of mature oocytes, sperm preparation, fertilization, embryo culture, embryo selection
- Embryo transfer usually done 3 days later
- Cryopreservation of excess embryos
Explain the process of ICSI
- Ajunct therapy to IVF in cases of male factor infertility
- Single sperm injected directly into the cytoplasm of the egg
- Sperm obtained from ejaculation, electroejaculation, epidiymal aspiration or testicular biopsy
- treatment for male factor infertility
- only one sperm per egg needed
- sperm from ejaculate or biopsy aspiration
What is assisted hatching?
- Recommended for women who are older or have poor ovarian reserve
- the embryo is surrounded by the zona a protective layering
- normally at a certain stage the embryo breaks out of the zona and is then able to implant into the uterine wall
- This process can be assisted by using a TINY probe with acid to poke a hole through the zona
- the embryo is then transferred and implanted
What is pre-implantation genetic diagnosis
- a procedure that allows for genetic testing of the embryo prior to transfer
- a single cell is removed from the blastocyst and placed in culture
- genes of the embryo are examined for the presence of chromosomal defects
What are some indications for pre-implantation genetic diagnosis
- previous family history of genetic d/o
- Known genetically linked miscarriages
- known sex linked genetic disorders
- aneuploidy screening in pts with advanced maternal age
What is embryo cryopreservation? why is it done?
- cryo preservation of viable fertilized embryos
- Enhances the opportunities for conception beyond the initial IVF cycle without having to repeat harvesting
- Avoids waste of viable embryos
- Limits the risk of multiple gestation
- Lowers the risk of ovarian hyperstimulation syndrome