Generations Final
Terms
undefined, object
copy deck
- define INFERTILITY
- 1 year of unprotected intercourse without conception
- Primary infertility = ?
- infertility with NO PRIOR CONCEPTION
- Secondary infertility = ?
- infertility WITH a prior conception
- how long can sperm survive in reproductive tract?
- 3-5 days
- When can an oocyte be successfully fertilized?
- 12-24 hours after ovulation
- When is "timed coitus" most likely to be successful?
- 5 days before ovulation up to the day of ovulation
- What are some of the reasons (6) that birth rates have gone from 55/1000 pop to 14.1/1000 pop, from 1790 to 2001 (and fert rates from 106.2/1000 women 15-44 in 1950 to 65.3/1000 women 15-44 in 2001)?
-
>advanced education and careers for women; childbearing delayed
>Marriage issues - later marriage & more frequent divorce
>family planning-desire for smaller families and better contraception - What challenges do older women face in becoming pregnant?
- pregnancy rate decreases, while spontaneous abortion increases
- What are some changes in the menstrual cycle as women age?
-
1) follicular phase is SHORTER
2) DOMINANT FOLLICLE is selected earlier
3) There are FEWER follicles SO: LESS ESTROGEN is produced, LESS Inhibin A and B produced, HIGHER levels of FSH - Why does oocyte aneuploidy increase with age?
-
1) premature separation of sister chromatids in meiosis I (d/t changes in cohesins, preventing alignment of sister chromosomes on meiotic spindle, before they separate)
2) Whole chromosome nondisjunction in meiosis II
3) - oocytes present at 1) 16-20 wks gestation _____ 2) at birth ____ 3) at puberty onset ____ 4) ages 37-38 ___ 5) at menopause
-
1) 6-7 million
2) 1 million
3) 300-500K
4) 25K
5) 1K - What are some (3) GENERAL causes of male infertility (after correcting for woman's age)?
-
1) sperm volume goes down
2) sperm motility goes down
3) sperm morphology aberrations - What are some (5) of the physiology changes in male reproductive system as men age?
-
1) seminiferous tubule sclerosis
2) germ cell & Leydig cell # decrease
3) decreased testosterone
4) increased FSH
5) more sperm chromosomal damage - What history components (6) are important for evaluating a woman with fertility probs?
-
Prior pregnancy outcomes
Cycle length, dysmenorrhea
Prior infertility testing?
PM/SH
Tobacco? Alcohol?
Family hx of early menopause
Coital frequency, lubrication - What history components (8) are important for evaluating a man with fertility probs?
-
Prior pregnancies?
Coital frequency?
Previous testing?
Childhood illness (mumps)
Previous surgery
Environmental toxins?
Medications?
Smoking? Alcohol? - What important physical exam components (8) should be done when evaluating a woman w/fert probs?
-
Weight, BMI
Thyroid enlargement?
Breast discharge?
Hirsutism?
Normal pelvic exam? Tenderness in cul de sac? Uterine tenderness?
Cervical discharge? - What important physical exam components (5) should be done when evaluating a man w/fert probs?
-
Location of urethral meatus
Testicular size
Presence of vas deferens, epididymis
Varicocele?
Body habitus, hair distribution - What are some basic tests to determine why couple is infertile (5)?
-
1) ovulatory function
2) ovarian reserve
3) semenalysis
4) tubal patency (hysterosalpingogram)
5) laparoscopy - When determining why a couple is infertile, what do you assess with ovarian function testing (4)?
-
1) regular menses?
2) luteal phase progesterone (marker for ovulation)
3) basal body temp (progesterone effect on hypothalamus)
4) use an ovulation predictor - When determining why a couple is infertile, what is assessed when examining ovarian reserve?
- FSH is measured on cycle day 3
- When determining why a couple is infertile, why is a hysterosalpingogram done?
- To make sure there is adequate Fallopian tube diameter. Should see no spill of dye into abdomen.
- How do you induce ovulation in women with PCOS?
-
1) Clomiphene citrate (antiestrogen)
2) injectable gonadotropins if clomiphene doesn't work - How do you induce ovulation in women with hyperprolactinemia?
- Parlodel
- What else can you use injectable gonadotropins for (aside from clomiphene resistant PCOS)?
- inducing ovulation in hypothalamic amenorrhea
- What conditions lead to anovulation that can be treated?
-
1) PCOS 2) hyperprolactinemia
3) hypothalamic amenorrhea - What is easiest type of infertility to treat? (1 glaring exception)
- ovulation disorders (except (premature) ovarian failure)
- What are some (3) TX options for infertility caused by a tubal factor?
-
1) IVF 2) tubal surgery
3) tx Endometriosis - What are some (3) TX options for infertility caused by Ovulatory dysfunction?
- 1) Clomiphene 2) parlodel, 3) injectable gonadotropins
- What are some (3) TX options for infertility caused by a factor in the Male partner?
- 1) Intrauterine insemination (IUI),2) IVF, 3) donor sperm
- What are some (3) TX options for Unexplained infertility?
-
Clomiphene or gonadotropins with hCG & IUI,
or IVF
Clom combo-25-30% preg in 4 mos
IG combo - 40% preg in 4 mos - What are some (6) of the clinical features of endometriosis?
-
Reproductive Aged Women
Pelvic Pain, Infertility
Early Menache, Short Cycles
Incidence 6 – 7 X In 1st Degree Relatives - Surg management = Med management for pain management in endometriosis, T or F
- True
- What is easiest infertility cause to tx?
- Ovulation disorders (except if there's ovarian failure)
- What fert probs (3) can the clomiphene citrate/hCG/IUI?
-
1) unexplained
2) male factor
3) minimal endometriosis - Why does endometriosis cause infertility (4)?
-
Anatomic Distortion
Abnormal Eutopic Endometrium
Disorders of Ovulation
Abnormal Peritoneal Fluid - What are 5 goals in surg tx of endometriosis?
-
Restore Normal Anat & Mobility
Remove All Visible Disease
Know Atypical Appearance
Excise Deep Disease and Endometriomas
Prep Bowel & UT Disease - What are the 3 qualities about Embryonic stem cells (ES cells)?
-
1) immortal
2) pluripotent
3) undifferentiated - Where do you get ES cells from?
- inner cell mass (of epiblast) from pre-implantation blastocyst (less than 1 wk old)
- What are biggest risks of using injectable gonadotropins for tx'ing fert probs?
- ovarian hyperstimulation and multiple gestations (less of prob w/IVF)
- What is the fate of ES cells?
-
1) divide w/o differentiating (long term self-renewal)
2) differentiation into germ or somatic cells - Clonogenic means = ?
- a single ES cell can give rise to colony of gen identical cells (clones) - same properties as the original cell
- factors for self-renewal (4):
-
1) basic FGF
2) Wnts
3) Noggin
4) Oct 3/4 (extrinsic) - What are some of the major challenges of ES cells (biomedical standpoint)? (3)
-
1) efficacious?
2) safe?
3) will they be rejected? - somatic cell nuclear transplant = ?
- removal of oocyte nucleus which is replaced by pt's somatic cell nucleus
- therapeutic cloning steps
-
1) somatic cell nuclear transplant
2) cell division stimulation up to blastocyst stage
3) harvest inner cell mass for ES cells - therapeutic cloning goals
- these cells would be matched to pt's immune system - so no immunosuppressants would be needed
- Monthly chance of conception?
- 10%
- Chance for multiples in pregnancy?
- 1%
- there is an epidemic of infertility? T or F
- False
- What steps does IVF involve?
-
-->Harvest of multiple mature ovulatory human oocytes
-->Extracorporeal fertilization (outside the body)
-->Subsequent replacement of a limited number of day 3 post fertilization embryos into the recipient’s uterus - fecundability = ?
- probability that 1 cycle will result in pregnancy
- fecundity = ?
- probability that 1 cycle will result in live birth
- What is the Wyden bill of 1992 for?
- TO make fert clinic success rates known to public (CDC and SART publish auditable info)
- IVF is a last resort tx - T or F?
- False
- Intracytoplasmic Sperm Injection (ICSI) tx's
- male factor infertility
- Intracytoplasmic Sperm Injection (ICSI) involves what procedure?
- injecting single sperm directly into egg
- Gestational carrier = ?
- intended father's sperm; surrogate egg
- Gestational surrogacy = ?
- intended father's sperm; intended mother's egg
- 6 reasons for a poor sperm count
- smoking, alcohol, trauma, drugs, toxins, genetic (CF, Y microdeletions)
- ICSI makes 4 processes possible:
-
1) Sperm freezing before or during chemotherapy
2) Sperm freezing at vasectomy reversal
3) Microsurgical epididymal sperm aspiration (MESA)
4) Testicular sperm extraction (TESE, ROSNI) - risk of ICSI seems to be ___?
- No increase in miscarriage, slight increase in birth defects
- In semenalysis, what are the criteria for normal, healthy male fertility?
-
Volume : >1 Ml
Count: 20 million/ml
Motility: >50% moving
Morphology:
>30% normal (WHO)
>4% normal forms (Kruger’s strict) - Why do sperm counts seem to be declining?
-
1) 2% decline/yr of birth
2) Enviromental endocrine disruptors
3) Urban Vs rural
4) Increasing incidence of testicular cancer and undescended testicles - what are the success rates of various tubal reconstructive surgeries and how do they compare to IVF?
-
Removing pelvic adhesions: 50-70% (better)
Repairing partially blocked tube: 40-60% (better)
Opening damaged tube: 15-25%
Salvage operative laparoscopy: 5-15%
IVF: 30-40% - What are some disadvantages of tubal reconstructive surgery?
-
1) Long time to pregnancy
2)High incidence of ectopic pregnancy (>5 % Vs 0.3 to 3% at IVF)
3) Major morbidities
4) High cost - 5 IVF complications
-
Cost
Multiple pregnancy
Ovarian hyperstimulat'n synd
Risks of retrieval- Bleeding
& Infection
Birth defects - IVF reduces multiple pregnancies - T or F?
- True
- Implanting more embryos increases chances of successfully becoming pregnant - T or F?
- False - just increases chances of mult pregnancies
- What are 5 reasons repro surg is done in the IVF era?
-
1) remove hydrosalpinges
2) remove ov cysts
3) remove endometriomas
4) ensure vaginal ovarian access
5) normalize the uterine cavity - What's so great about removing hydrosalpinges?
-
1) improves pregnancy rates
2) decreases aspiration complications
3) improves transvaginal ovarian access - What kinds of birth defects do you see w/ART?
-
1) small for gestational age
2) sex chrom disorders w/ICSI
3) congen anomalies (2x risk)
4) ?Imprinting disorders (Beckwith-Wiedeman, Angelman) - What are the indications (3) for doing donor oocyte IVF?
-
Indications:
1) Diminished ovarian reserve
2) Multiple miscarriage
3) Maternal chromosomal anomaly - What factors (5) diminish ovarian reserve?
-
Smoking
Age
Ovarian surgery
High altitude
Chemotherapy/radiation therapy - What is "assisted hatching" IVF?
- Slit zona pellucida of embryos prior to transfer
- What phenomenon does "assisted hatching" increase?
- Chances for monozygotic twins
- "assisted hatching" is used to improve
- implantation rate in >38 yo, previous failed IVF w/good embryos, thick zona
- drawback of cytoplasmic donation (donor oocyte cytoplasm into old oocyte - improves chances of preg):
- mitochondrial DNA transfer from donor
- What's good (1) and what's bad (3) about new BLASTOCYST TRANSFER technique?
-
good- 50-70% preg rate BUT
difficult culture technique
freq failure of blast dev
appreciable multiple rate - What is preimplantation genetic dx (PGD)?
- Single cell biopsy and amplification or staining of DNA
- What is PGD used for?
-
1) dx- gen dz (1 gene-CF,HD)
2)ID chrom abnorm embryos (DS)
3) sex selection
4) select favorable chars
5) gen engineering - WHat's the difference between reproductive cloning and therapeutic cloning?
-
Nuclear transfer blastocyst - tx'ic - harvest ES cells...
repro - implant into female uterus - MENOPAUSE definition
- Last menstrual cycle; no menses for 1 yr
- age of menopause
-
median - 51;
range - 40-57 - best predictor of menopause?
- age of menopause of female relatives (genetic)
- earlier (but not premature) menopause is related to... (3)?
-
1) Gyn surg (uterus, ovaries)
2) smoking
3) chronic malnutrition - premature ovarian failure is caused by...(5)?
-
1) idiopathic
2) chrom abnorms - Turner, Fragile X
3) radiation tx (>800 rads)
4) chemo (esp alkylating agents, cyclophosphamide - 60%)
5) autoimmune endocrinopathies (parathyroid, thyroid, adrenal) - PERIMENOPAUSE definition
- defined by onset of irregular menses - time between regular menses (pre) and final menses
- age of perimenopause
- av - 46; range 39-51
- early, mid, late menopause defined by cycle length...
- early <25 d, mid up to 90 d, late >90 d
- climacteric sx of menopause are caused by:
- loss of ovarian hormones
- climacteric sx of menopause include (4)
-
1) vasomotor sx
2) vaginal/vulvar sx
3) mood changes
4) sexual changes - estrogen loss in perimenopause causes (4 and a possible)
-
1) vasomotor sx
2) vag/vulvar/bladder changes
3) loss of bone/osteoporosis
4) decreased breast tissue
?cognitive fnx, ?sexuality - progesterone loss in perimenopause causes
- irregular menses
- testosterone loss in perimenopause may cause...
-
1)vasomotor sx
2)muscle mass
3)sexuality - at menopause/perimenopause vasomotor sx = ?
-
hot flashes/night sweats - sudden onset head, neck, chest skin reddening, intense body heat, rapid HR, perspiration and chilling;
(might be caused by loss of estrogen effect on hypothalamus) - Who is affected by vasomotor sx at menopause/perimen?
- 85% women after menopause; 50% perimenopause; decreases 2 yrs after menopause
- what are the vaginal/vulvar changes of menopause/peri?
-
vag dryness, thinning, dyspareunia, postcoital bleeding, vaginitis
(vag higher pH, loss of collagen, adipose, thin epith and subcut tissue) - 50% of women - bladder/pelvic changes during menopause
- weakness of vag (caused by loss of m and collagen) - can prolapse w/uterus, bladder (cystocele), rectum (rectocele) or intestine (enterocele)
- Bone loss in menopause (type)
- trabecular bone
- Bone loss in menopause (rate)
- 5%/yr early in menopause w/50% loss in 20 yrs
- factors affecting bone loss (6)
- genetics, dietary, meds, smoking, exercise, weight
- dx of osteoporosis
- DEXA hip and spine - greater than -2.5 SD on T score (osteopenia - -1 to -2.5); normal (0- (-1))
- estrogen effect on cardiovascular system (3)
-
1) increases HDL
2) lowers LDL
3) endothelium pos effects - vasodilatation and lowers plaque - risks (3) of exogenous estrogen
-
1) thromboembolic events
2) CRP up
3) triglyceride levels up - breast changes w/menopause
- decrease in glandular tissue density (adipose main tissue present allows easier mammo detection)
- estrogen loss (menopausal) effects on cognition
- unclear but may decrease verbal and ST memory (E may help prevent Alz, but stroke risk)
- what were the results of the WHI?
-
HRT decreases: osteopor risk and colon ca risk
BUT increases: heart dz, breast ca, stroke, blood clots - FDA recommendations re: HRT
- lowest dose for shortest time possible
- 5 ways to managem menopausal sx:
-
1) avoid stress
2) avoid heat
3) avoid EtOH
4) layered clothing
5) relaxation techniques - 4 drug classes for menopausal sx management:
-
1) antidepressants (Effexor, Zoloft, Paxil)
2) nerve blockage - neurontin
3) sleep agents - Z class - ambien, lunesta
4) tachycardia - catapres patch - The story on soy...
- no help w/menopausal sx. but lowers tot cholesterol, LDL, triglycerides (AHA, FDA)
- the only herb to help w/menopausal sx...
- black cohosh (Remifemin)
- in order what reduces CV dz risk most
-
1) quit smoking
2) lose weight to <20% above IBW
3) exercise - 2 things to prevent bone loss
- weight bearing exercise, 1500 mg/d Calcium supplement
- tx of T score <-2 SD or osteoporosis
-
1) SERM - Evista
2) bisphosphonate - Fosamax or Actonel- daily/weekly
3) Boniva - monthly - when would estrogen alone HRT be acceptable?
- if woman has had hysterectomy (no risk of endometrial ca)
- tx of vag sx of menopause
- lube, topical vag estrogen tx, corticosteroids for vulvar/vag fissures, vaginitis tx if nec, keep having sex
- urinary incontinence tx - post-men (4)
-
1) Kegel exercises
2) biofeedback/PT
3) pessary (also for uterine prolapse)
4) surg - collagen, bladder elevation - when is HRT indicated?
- when sx affect QOL (sleep, daily activities, sex)
- at menopause, how often is bone density screening indicated?
- initial screen at menopause, and every 2 yrs if osteopenia present
- at menopause, how often is Pap test screening indicated?
- every 2 yrs if normal for 10 yrs
- at menopause, how often is mammo screening indicated?
- every yr
- what happens to FSH w/menopausal changes?
- increases
- what happens to follicular phase length w/perimenopausal changes?
- they get shorter d/t less FSH
- what happens to menstrual cycle length w/perimenopausal changes?
- they get shorter d/t shorter folicular phases
- What happens to luteal phase length w/perimenopausal changes?
- no change
- Why is estradiol lower in peri/menopause?
- b/c ovary not as responsive to FSH (even though increased!)
- in perimenopause, why are there more anovulatory cycles?
- b/c lower estradiol levels --> no LH surge
- anovulation causes ___ cycles w/___menses:
- longer cycles w/ normal/heavy menses - b/c low progesterone pdtn
- anovulation with lowered estradiol (perimenopause) leads to ___ cycles
- lighter cycles
- perimenopause - gonadotropins, ____ increase/decrease
- FSH, LH; increase
- perimenopause - ovarian hormones, ___ , increase/decrease
- estradiol, progesterone; decrease markedly
- perimenopause - adrenal hormones ____, increase/decrease
- dehydroepiandrosterone, testosterone; decrease
- 6 barriers to MDs and pts (5) discussing sexual health
-
1) cultural silence
2) personal discomfort
3) environ shift/role transformation (pt expectations)
4) inadequate/no sexual history training
5) what should I do w/info?
6) conflict between personal values and pt cntrd care - 6 ways on how to better facilitate open, trusting environment re: sexual history
-
1) anti-discrim sign
2) waiting room materials - heteronorm/GLBT
3) unisex restrooms
4) more options to select on intake forms
5) well-trained staff (gender)
6) updated list of resources/referrals - when is sex/repro history assessed? (5)
-
1) routine health maint (primary care)
2) repro health visits
3) acute visits - sexual issues may be contrib to cause of CC
4) sexual assault/abuse concerns
5) whenever pt wishes - 6 ways on how do you create a pos atmosphere for sexual history taking?
- privacy, limited interruptions, pt dressed, eye level w/pt, culturally approp language, anat models/drawings
- exceptions to confidentiality re: sexual history info gathering
- reporting of STIs, sexual abuse of minor
- High risk behaviors not sexual orientation put someone at risk, T or F?
- True
- What are 4 sx of poss prostate health probs?
-
1) pain w/ BMs
2) diff/pain w/urination
3) pain w/ejaculation
4) lower ab pain - chancroid is caused by _____
- Hemophilus ducreyi
- Hemophilus ducreyi is a Gram __ ____ (shape)
- negative rod
- HSV presentation:
- multiple vesicles and ulcers
- HSV painful/painless
- Painful
- syphilis presentation
- indurated smooth borders w/clean base (chancre)
- H. ducreyi presentation
- tender papule --> painful ulcer w/sharp or ragged edges w/purulent base (opposite of what's seen in syphilis)
- syphilis - painful/painless
- painless
- H.ducreyi painful/painless
- VERY PAINFUL
- LGV is caused by ___
- C. trachomatis L1-L3
- LGV painful/painless
- painless
- good test for H. ducreyi
- PCR - sens and spec (hard to grow in culture, requires enriched media)
- Tx for H ducreyi
-
oral Z-pack or IM ceftriaxone
erythromycin - How to prevent H ducreyi
- abstinence/barrier
- reservoir for herpes
- humans are the only natural reservoir
- sx of trichomonas
- variable amt of poss malodorous, frothy, yellow-green discharge w/ or w/o itching; dysuria and dyspareunia; cervicitis poss - if cervix red and inflamed - strawberry cervic; asx'ic? 20-50% women; most men
- if men show sx of H ducreyi, what will they be?
- dysuria and clear discharge
- Clinical signs of trichomonas
- frothy discharge, vag wall redness, elevated vag pH (5-6 vs. 4.5)
- how to dx trichomonas
- vag discharge wet mount - darting motility
- How to tx trichomonas - specific med and in general
-
med - metronidazole (Flagyl)
general - tx male partner - Candida vulvovaginitis caused by ______
- OVERGROWTH of C. albicans (normal flora in 50% of women)
- C. albicans overgrowth in Candida vulvovaginitis caused by (5) _____
-
1) ABX
2) poorly controlled diabetes
3) pregnancy
4) HIV
5) steroids - Candida can cause ____ in men
- balanitis (but not very common)
- sx of Candida vulvovaginitis
- ITCHY!!!! white thick cottage cheese discharge (not so smelly) adheres to vag wall, vulvar/vag wall redness, scale/fissure of vulvar tissue, dyspareunia, dysuria
- tx for Candida vulvovaginitis
- azole anti-fungals (oral, topical, suppositories); male partner tx - unnecessary unless balanitis
- most common form of vaginitis
- bacterial vaginosis
- spp causing bacterial vaginosis (3)
-
1) gardnerella vaginalis
2) mycoplasma spp
3) anaerobes - sx of bact vaginosis
- if there are sx (many are asx'ic); thin gray-white SMELLY discharge, NOT ITCHY, less vag redness compared to yeasty/trich
- dx of Candida vulvovaginitis
- round Gram + yeast, 10% KOH - yeast w/hyphal elements - 70-90% sens; rapid latex agglutination - good sens
- clinical signs of Candida vulvovaginitis
- itchiness, vaginal/vulvar redness, cottage cheese; normal vag pH
- the best dx'ic indicator of bacterial vaginosis
- CLUE cells (sq cells w/adherent coccobacilli)
- another way to dx bact vaginosis
- Whiff test - 10% KOH - smells like fish!
- how is bact vaginosis like trichomonas but unlike candida?
- BV and Trich pH > the normal 4.5
- painful ulcer, neg herpes test
- H ducreyi
- tx of bacterial vaginosis
- 7 days of metronidazole/Clindamycin; tx of partner DOES NOT prevent re-infection
- Causes of prostatitis
- bacterial (E coli, pseudomonas), unknown for non-bacterial and prostadynia
- sx of acute bacterial prostatitis
- SUDDEN perineal, sacral, suprapubic pain w/common chills/fever and irritative voiding sx (may need hosp)
- sx of chronic bacterial prostatitis
- like UTI sx, irritative voiding sx, mild perineal/suprapubic discomfort may or may be there...(similar for non-bact and prostadynia)
- dx of bacterial prostatis
- both acute and chronic - UA - pyuria & bacteriuria; urine cultures --> pathogenic bacteria
- dx non-bacterial prostatitis
- WBCs - prostatic fluid and urine; no bact growth in culture
- dx of prostadynia
- no bacteria/no WBCs on UA/prostatic secretions
- tx of prostatitis/prostadynia
-
bact: acute:1-2 wks ABX,
chronic:4-12 wks ABX
non-bact and prostadynia - hot baths - HSV age groups
- 1- all; 2 - after puberty (unless sexual abuse)
- % of adults seropositive for HSV-2
- 25
- most common genital ulcer dz worldwide
- 80%
- spread of HSV
- by direct contact w/infected secretions; condoms - 40-50% effective at prevention; daily medication effective at preventing spread
- primary HSV infections sx
-
painful ulcers at point of contact 5-7 d after sexual contact;
1/3 pts -systemic - fever, malaise, myalgia, adenopathy, 8% aseptic viral meningitis - recurrent genital herpes characteristics
- shorter duration of outbreak,milder sx, localized to genitals,no systemic; ASX'ic shedding very common
- difference in dz course between HSV-1 and HSV-2
- HSV-2 much more likely to lead to reactivation (80% w/in 12 mos)
- 5 ways to dx HSV
-
1) Tzanck prep - giemsa/wright stain - multinucleation, molding, margination
2) ELISA
3) Pap smear
4) PCR
5) gold std - cell culture - tx of HSV
- acyclovir, valacyclovir, famcyclovir - decrease duration and intensity of acute infections, prevents both sx'ic and asx'ic reactivation
- HPV prevention - 4 ways
-
1) abstinence
2) barrier
3) Pap smear
4) vaccine - HPV vaccines
- gardisil, cervarix; gardisil - quadrivalent (6/11/16/18)-virus like particle (VLP) vaccine; 3 doses, women between 9-26 yo; not rec for men yet
- HPV tx
- never 100% effective; exophytic warts resolve on own; cryotx, laser/surg/trichloroacetic acid removal
- HPV dx (3)
-
1) Pap smear
2) HPV nucleic acid probe
3) colposcopy (after abnormal Pap)- acetowhitening - Sx of HPV
- Often asx'ic esp in women (flat on cervix); types 6&11 - exophytic warts (condyloma acuminata)
- Most common viral STD in USA
- Condyloma acuminata (HPV 6/11)
- HPV #'s assoc w/benign warts
- 6 and 11
- HPV #'s assoc w/warty, flat lesions which can progress to malignancy
- 16, 18, 31, 45
- __ and __ are the principle transforming genes of HPV
- E6, E7
- HPV E6 binds to ____ ; degrading it --> so cells are allowed to progress from ___ to ___ in the cell cycle and chromosomal damage doesn't stop cell growth
- p53, G0/G1, S
- HPV E7 binds to ___ . As a result ____ cannot be inactivated; w/this TF unchecked, DNA synth (S phase) of cell cycle promoted
- Rb, E2F
- HPV induces hyperplasia of ____ layer of epithelium
- basal
- HPV viral DNA does what?
- Integrates into cell genome -disrupts reg actions of host genes
- what anchors the breast to the dermis?
- Suspensory ligaments of Cooper (fibrous septa)
- division of breast starting from nipple
-
nipple-->lactiferous sinus-->lacterifous duct which bifurcates successively
until terminal bifurcation-->lobule; each breast has 5-10 radially arranged lobes (each lobe has 1 lact duct and many lobules) - Acini are referred to as _____ when not pregnant, and ___ when one is.
- rudimentary, true
- functional unit of the breast
- terminal ductal lobular unit (TDLU) = ductules, rudimentary acini, surrounding a terminal duct
- intralobular CT can be found _____
- surrounding each lobule
- interlobular CT can be found ____
- between each lobule
- intralobular vs. interlobular CT
- loose, myxomatous (intralobular) vs. dense, fibrous (interlobular)
- Name 2 lesions of LOBULAR stroma
-
1) Fibroadenoma
2) Phyllodes tumor - the deep dorsal limit of the breast
- anterior pectoral fascia
- estrogen acts on the _____ of the breast to promote ______
- duct epithelium; growth
- progesterone acts on the _____ of the breast to produce _____/____
- TDLU epithelium, secretory change/stromal edema
- follicular phase - breast is _____
- quiescent (epith undergoes apoptosis, lobules atrophy, edema decreases)
- luteal phase - breast cells _____
- actively proliferate, lobular hyperplasia, stromal edema
- swelling and discomfort in breasts before menses is caused by this
- stromal edema
- Why is it recommended to do Breast self-exam 1 wk after menses?
- b/c no stromal edema, breast nodularity at its lowest
- hallmark of perinatal breast development
- lactiferous ducts only
- at 6 wks gestation, breast development
- primary bud (epidermis into dermis)
- at 12 wks gestation, breast development
- secondary bud
- breast development from 12 wks to birth
- development of mammary pit in secondary bud (w/areola and depressed nipple), lactiferous ducts develop
- breast development in infant and childhood
- more branching ducts (male breast arrests at pre-pubertal phase)
- pubertal breast development
- complex branching ducts, terminal ducts/saccules, stromal proliferation
- menarche breast development
- saccules --> terminal ductules, rudimentary acini, TDLU
- gestational/lactating breast
- true secretory gland, fully developed breast
- post lactation breast
- epith atrophy, some fatty replacement of stroma
- postmenopausal breast
- stromal and glandular atrophy, fatty replacement
- what is commonly seen on the milk line?
- accessory breast tissue (also common in axilla) or supernumerary nipple (esp below breast)
- atypical ductal hyperplasia (ADH) = ?
- some but not all the features of DCIS (can't differentiate ADH from well diff DCIS)
- histopath features of atypical ductal hyperplasia (high grade)
- monotonous nuclei, fried egg appearance of cells, prominent intracytoplasmic vacuoles, a few signet ring cell forms
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Sx: varying sized irregular masses in both breasts, painful mass in one breast (needed excision), told "no cancer"
Name the breast condition: - fibrocystic changes
-
Sx: intermittent brownish nipple discharge for 5 wks, small palpable mass below nipple
DDx for breast dz: -
1) Papilloma
2) Papillary Carcinoma (inv vs. non-inv)
3) Pagets (poss but usually no mass) - T or F? Pagets dz of nipple is often associated w/ a mass
- False
- Papilloma vs. Papillary carcinoma differences (breast)
- malignant dz - lacks myoepithelial layer, has delicate vascular stroma and solid/cribiform areas w/high mitoses); benign - fibrovascular cores; 2 layer epith
- most common part of breast to have carcinoma found
- UOQ
-
Sx: freely movable mass in 1 breast (young woman)
Name of Breast condition: - fibroadenoma
- Histopath features of fibroadenoma
- biphasic (epith/glandular and stromal) neoplasm; ducts - small and round (pericanalicular pattern) or long and C-shaped (intra-canalicular pattern); no atypia; mitoses absent/few
- histopath features of phyllodes tumor
- gland architecture complex, stroma very cellular - some stellate (atypical) w/mitoses present; higher risk for recurrence and malignant potential;
- What alarming feature can be seen in fibrocystic change?
- sclerosing adenosis (nests of hyperplastic cells - proliferation of small ducts)
- What proportion of women who get breast ca have known RFs?
- 3/10
- BRCA1
- 17q mutation of tumor suppressor gene; 85% lifetime risk of breast ca, 20-50% ov ca;
- Carriers of BRCA1 (similar BRCA2)
- 50% of breast ca families, 90% breast/ov ca families, 3% Jewish women (25% if Jewish women who get breast ca before 42 have it)