Repro Part 9

Front 1

bleeding during reproductive years ~~

Back 1

Complications of pregnancy

Organic lesions:
-Endometritis
- Leiomyomas
-Polyps
-Hyperplasia
-Carcinoma

DUB

Front 2

penny-nickel-dime -quarter wrt malignant pot. of hyperplasia:

Back 2

1% if simple and w/o atypia

5% if complex w/o atypia
(over 10-15 years)

25% if complex and atypia

Front 3

most important prognostic factor for surface epithelium carcinomas =

Back 3

stage - whether it's confined to the ovary (stage I) or not

- serous and clear cell = poor prognosis epithelial types

- endometrioid and mucinous types = good

Front 4

histo of endometrioma:

Back 4

hemosiderin-laden mP's within the stroma

Front 5

Endometriosis can cause obstruction of the:

Back 5

appendix, resulting in acute appendicitis

Front 6

cul-de-sac =

Back 6

pouch of Douglas

Front 7

adnexal =

Back 7

appendage of an organ

Front 8

"immature" teratoma =

Back 8

not a distinct, mature tissue like bone or skin

- embryonal

Front 9

teratomas are:

Back 9

GERM-cell tumors

Front 10

ovarian torsion can occur with:

Back 10

ANY ovarian mass

Front 11

Call-Exner bodies (areas of degeneration) ~~

Back 11

coffee beans on histo

~~ sex-cord tumors

Front 12

sex-cord tumors are:

Back 12

low-grade malignant

Front 13

Infertility =

Back 13

>1 yr unprotected intercourse w/o conception

Front 14

Fecundability =

Back 14

probability of achieving pregnancy in a single menstrual cycle

-20-25% in young couples

Fecundity = probability of achieving a live birth after attempting conception for a single menstrual cycle

Front 15

fertile window:

Back 15

- sperm can only survive in the female genital tract for about 5-6 days
- eggs, once ovulated have about a 2 day window to be fertilized

=> there’s only about a 6-7 day window in which conception could even occur that cycle

- highest probability of conception ~~ day 14 (ovulation)

Front 16

the sperm have to be waiting when:

Back 16

the egg is released

Front 17

methods of predicting ovulation:

(3)

Back 17

1. ovulation prediction kits

2. basal body temp

3. cervical mucus monitoring

Front 18

ovulation prediction kits measure:

Back 18

LH,

which increases a day or so before ovulation

- m. b/w 11 am and 3 pm

Front 19

what's the deal with m'g basal body temp?

Back 19

basal body temp increases after ovulation starts

- m. every morning before you get out of bed

=> add to your diary in order to plan for intercourse your next cycle

Front 20

rationale behind cervical mucus memb:

Back 20

cervical mucus changes as you approach ovulation

- check toilet paper
- type 1 is least fertile
- type 4 is most (raw egg whites)
=> intercourse on day with type 4 mucus results in higher rates of conception

Front 21

fertilization occurs in the:

Back 21

Fallopian tube

Front 22

2 m.c. causes of infertility:

Back 22

1. male factor

2. tubal/peritoneal issue

Front 23

"male factor" =

(3)

Back 23

1. ED

2. ejaculatory dysfunction

3. abnl sperm quality or quantity

Front 24

Oligospermia =

Back 24

low number of sperm

Front 25

Azoospermia =

Back 25

no sperm

Front 26

Asthenospermia =

Back 26

poor motility of sperm

Front 27

Teratospermia =

Back 27

abnl morphology

Front 28

causes of abnl sperm:

(3)

Back 28

1. Genetic
- Klinefelters
- CFTR mut.– CBAVD
- Microdeletion of the Y chromosome

2. Hormonal
- Hypothlamic/pituitary dysfunction => lack of stimulation of testis => dec. TEST => dec. production of sperm

3. Environmental toxins
- Smoking, radiation, heat (via varicocele)

Front 29

Klinefelters syndrome =

Back 29

extra X chromosome (46,XXY)

Front 30

4 features of Klinefelters:

Back 30

1. c.c. of testicular failure

2. tall

3. small firm testes

4. under-virilized
(which means that they don’t have as much male pattern hair or male traits)
- due to low TEST due to testicular failure

Front 31

vas deferens connects:

Back 31

testis to penis

Front 32

varicocele =

Back 32

abnly enlarged spermatic vein

=> inc. heat of testis

Front 33

order of evaluating male infertility:

(3)

Back 33

1. semen analysis

2. hormone analysis
(including thyroid)

3. genetic workup

Front 34

male hormone therapy wrt infertility is:

Back 34

unreliable

- exogenous TEST actually decreases sperm count

Front 35

If the issue is one where sperm is made but not present in the ejaculate (such as CBAVD) then they can undergo:

Back 35

testicular biopsy or aspiration to obtain sperm directly from the teste.

Front 36

evaluating ovarian factor in infertility:

(4)

Back 36

1. HPO axis
- FSH/LH, estradiol
- drawn between cycle day 2-4

2. Thyroid
- TSH, Free T4

3. Hyperprolactinemia
- Prolactin

4. Genetic
- Karyotype, FMR1 (fragile X)

Front 37

Thyroid disorders and hyperprolactinemia are underlying conditions that when treated:

Back 37

frequently result in resumption of ovulation without further intervention.

Front 38

med to induce ovulation:

Back 38

Clomiphene

Front 39

4 features of Clomiphene:

Back 39

1. SERM - binds ER'

2. acts as agonist OR antagonist
- primarily an antagonist in pre-menopausal women
- gives the brain a false perception of low EST

3. tissue specific - acts at hypothalamus

4. **req's functional HPO axis**

Front 40

Clomiphene blocks ER's in hypothalamus; reduced negative feedback from EST leads to:

Back 40

increased GnRH secretion

=> increased FSH/LH from pituitary

=> ovarian stimulation

This stimulation eventually results in an LH surge and ovulation

Front 41

If the HPO axis is not functioning, then EST is:

Back 41

ALREADY LOW and therefore clomiphene will not work

Front 42

aromatase converts:

Back 42

androgens to estrogens

Front 43

aromatase inhibitors help infertility b/c:

Back 43

they dec. amount of estrogen that's made

=> stimulates GnRH to release FSH/LH => ovaries => LH surge => ovulation

Front 44

aromatase inhibitors ALSO require:

Back 44

an intact HPO axis

Front 45

2 aromatase inhibitors:

Back 45

1. Letrozole

2. Anastrozole

Front 46

difference b/w Clomiphene therapy and aromatase inhibitor therapy:

Back 46

in Clomiphene therapy, EST levels are *perceived* as low, while with Letrozole they are ACTUALLY low

Front 47

tubal factors wrt infertility:

(2)

Back 47

1. Tubal damage
- Chlamydia inf. - c.c. of obstruction
- Gonorrhea
- Salpingitis isthmica nodosa (SIN)

2. Adhesions => tubal blockage
- Endometriosis
- ruptured appendicitis

Front 48

to dx tubal blockage:

(2)

Back 48

1. hysterosalpingogram (HSG)

HSG = fluoroscopic procedure that is done by placing a catheter into the uterus through the cervix and injecting dye. X-rays are then taken and the dye shows up white. The dye goes into the uterus and out the tubes. If you see the dye spill out the end of the tube you know the fallopian tubes are patent (which is good)

2. Chromopertubation during laparoscopy
- watch dye come out during surgery

Front 49

tx of tubal factor:

(2)

Back 49

1. surgery

2. IVF (much more successful)

Front 50

uterine factors wrt infertility:

(4)

Back 50

1. septate uterus (developmental)

2. fibroids

3. polyp(s)

4. intrauterine adhesions

Front 51

dx of uterine factor:

(2)

Back 51

1. Hysterosalpingogram (HSG)

2. hydrosonogram/saline infusion sonogram - SIS)
(water and U/S instead of dye and x-ray)

Front 52

tx of uterine factor:

Back 52

surgical, often via hysteroscopy

Front 53

tx for unexplained infertility =

(2)

Back 53

1. more eggs (superovulation or IVF)

AND

2. more sperm (insemination or IVF)

Front 54

Superovulation =

Back 54

Increased number of oocytes PER CYCLE

Front 55

how is superovulation achieved?

(2)

Back 55

1. higher doses of Clomiphene and Letrozole
(oral)

2. FSH
(if HPO axis not intact and those two drugs^ useless)

Front 56

risk of superovulation =

Back 56

higher chance of multiples

Front 57

IVF is a tx for:

(3)

Back 57

1. male,

2. tubal, and

3. unexplained infertility

Front 58

IVF involves stimulation of the ovaries with:

Back 58

gonadotropins.

- Just like superovulation requires a higher dose than ovulation induction, IVF requires an even higher dose than superovulation

Front 59

in IVF, we don't want the LH surge/ovulation to happen too early (before the oocytes mature i.e. are able to be fertilized); 2 ways to prevent LH surge/ovulation:

Back 59

1. GnRH antagonist
- administer when the EST approaches a level that might lead to the LH surge

2. non-pulsatile GnRH *agonist*
- initially stimulates FSH/LH, then pit. becomes desensitized => FSH/LH desensitized

Front 60

In order to achieve downregulation at the desired time, (non-pulsatile) GnRH agonists must be administered:

Back 60

PRIOR to starting stimulation with exogenous gonadotropins

Front 61

Although we do not want a natural LH surge to occur, mostly because we want to be in control of the timing, we do need to simulate an LH surge so that the oocytes are able to complete maturation and be released from the wall of the follicle so that they are floating freely in the follicular fluid and can be aspirated. Therefore we create a *pharmacologic* LH surge.

Back 61

use hCG (trigger shot)

- longer half-life than LH (24 hours vs. 20 min)

=> resumption of oocyte maturation.

- egg retrieval is usually performed approximately 35 hours after the trigger shot

Front 62

Intracytoplasmic Sperm Injection IVF =

Back 62

injecting one sperm into each egg

Front 63

Ganerelix =

Back 63

GnRH antagonist

Front 64

Leuprolide =

Back 64

GnRH *agonist*

Front 65

Premature ovarian failure =

Back 65

as cessation of menses due to ovarian failure prior to 40 y.o.

- phenotype and morbidity will vary depending on timing of process and etiology

Front 66

etiology of premature ovarian failure:

Back 66

largely unknown, but genetic with increased rate of follicle disappearance/atresia

- m.c.ly 45X, 47XXY

- more common in families with Fragile X

Front 67

climacteric = perimenopause =

Back 67

gradual regression of ovarian function

Front 68

features of climacteric:

(4)

Back 68

1. initially have shortened follicular phase (short cycle)

2. followed by episodic ovulation (lengthening of cycle).

3. metrorrhagia is NEVER nl

4. increasing symptoms

Front 69

symptoms of perimenopause:

(4)

Back 69

1. *vasomotor instability* (85%)
(referring to the constriction/dilation of blood vessles)

2. => sleep disturbances

3. => mood disturbances.

4. Somatic symps
(fatigue, palpitations, HA/migraine, breast pain and enlargement)

Front 70

perimenopause follows:

Back 70

decreasing fertility

Front 71

menopause =

Back 71

*permanent* cessation of menstruation caused by failure of ovarian follicular development in the presence of high gonadotrophin levels

~~51-52

- a clinical dx - no menses for 12 months

Front 72

menopause is genetically determined but definitely influenced by environment;

Back 72

smoking ~~ earlier menopause

Front 73

***hormone levels in menopause:***

(4)

Back 73

high FSH,

low EST,

low inhibin (no follicles)

NO Prog (since there's no ovulation)

Front 74

5 key physical signs of menopause:

Back 74

1. vasomotor instability => hot flashes

2. Metabolic Changes

3. CAD

4. bone loss

5. Urogenital atrophy
(includes bladder)

Front 75

4 post-menopausal health risks:

Back 75

Osteoporosis

CV dz

Breast/Endometrial/Ovarian/Colon Cancer

Incontinence and pelvic organ prolapse

Front 76

greatest bone loss occurs:

Back 76

immediate 10 years after menopause

Front 77

risk factors for osteoporosis:

Back 77

White or Asian
Smoking
Alcohol
Caffeine
Sedentary
Low BMI
Chronic steroid use
Premature menopause
Calcium and Vitamin D deficiency.

Front 78

consequences of osteoporosis:

(4)

Back 78

1. Spinal (vertebral) compression fractures
- Back pain
- Loss of height and mobility
- Postural deformities

2. Colles’ (forearm) fractures

3. Hip Fractures

4. Tooth loss

Front 79

EST *cannot* increase bone mass; instead, it:

(1 => 4)

Back 79

**reduces bone resorption**

1. blocks action of parathyroid hormone
2. inc.'s calcitonin
3. stimulates osteoblasts
4. inc's Ca2+ absorption

Front 80

best screening for osteoporosis =

Back 80

DEXA

- evaluate spine and femoral neck
- indicated for all women > 65 or,
<65 with 1 risk factor for osteoporosis

Front 81

tx to offset osteoporosis:

(6)

Back 81

1. HRT
- start within 5 years of menopause, continue for 10 years

2. Bisphosphonates
(-dronates)

3. PTH

4. Denosumba
- blocks RANKL

5. Ca2+/Vit. D

6. SERM's
(Raloxifene, Tamoxifen)

Front 82

Raloxifene interactions with EST:

(2)

Back 82

1. EST agonist on bone,

2. EST *antagonist* on breast, endometrium, vagina

Front 83

Tamoxifen interactions with EST:

(2)

Back 83

1. EST agonist on bone, endometrium

2. EST antagonist on breast

Front 84

primary mechanism of Bisphosphonates =

Back 84

inhibition of osteoclast bone resorption

Front 85

at >65 y.o., male to female ratio of MI's =

Back 85

1:1

- heart dz kills many more women than BC

Front 86

4 functions of PROG:

Back 86

1. inhibits LH/FSH

2. thickens cervical mucus

3. thins endometrium

4. decreases tubal motility

Front 87

reproductive aging ~~

Back 87

hormonal changes

Front 88

menopause can be induced by:

Back 88

removing both ovaries

Front 89

best therapy for hot flashes:

Back 89

EST

Front 90

hot flashes/night sweats =>

Back 90

sleep and mood disturbances

- women w/ hx of depression may => recurrence

Front 91

urogenitary symps during menopause:

(7)

Back 91

1. Dysuria

2. Urgency

3. Frequency

4. Recurrent UTIs

5. Dysparunia

6. Pruritus

7. stenosis of vagina

Front 92

tx for urogenitary symps:

(2)

Back 92

1. vaginal EST

2. HRT

Front 93

metabolic syndrome of menopause:

(3)

Back 93

1. lipid triad
(inc. TG's, Inc. LDL, dec. HDL)

2. insulin R

3. endothelial dysfunction, others

Front 94

first-line tx's of osteoporosis:

(2)

Back 94

1. Bisphosphonates

2. Raloxifene

Front 95

other reasons why EST must be the solution to menopause:

Back 95

Lowers LDL
Increases HDL
Increases triglycerides
Increases venous and arterial thromboembolism
Improves vascular function
Reduces atherosclerosis formation
Improves insulin sensitivity (reduction in type 2 DM)

Front 96

HRT of just EST is ONLY for:

Back 96

women w/o a uterus

- if you have a uterus, need progestin to oppose EST's affect at the uterus

Front 97

current recommendations for HRT:

Back 97

take the lowest dose and for the shortest amount of time while you're going through menopause

Front 98

early menopause =

Back 98

ages 40-44

Front 99

premature menopause =

Back 99

<40

- caused by premature ovarian failure OR surgical removal of ovaries

Front 100

premature ovarian failure =

(4)

Back 100

1. sex chromosome abnormalities
(usually involving the X Chromosome)

2. Fragile X premutation

3. AI

4. Chemotherapy/Irradiation

Front 101

to evaluate premature ovarian failure:

(3)

Back 101

1. karyotype (<30 years of age)

2. assessment for Fragile X (number of CGG repeats)

3. Survey for other AI dz's (such as hypothyroidism, adrenal insufficiency)

Front 102

menopause results from failure of:

Back 102

ovarian follicular development

Front 103

what is responsible for the rise of FSH in menopause?

Back 103

low inhibin

Front 104

ALL osteoporosis therapies work by:

Back 104

reducing bone resorption

Front 105

what's the biggest killer of post-menopausal women?

Back 105

CHD

Front 106

in women with a uterus, EST must ALWAYS be:

Back 106

accompanied by PROG

Front 107

HRT is associated with increased rates of:

(4)

Back 107

CHD, BC, PE, and stroke