Chapter 26 Infertility and Assisted Reproductive Technologies

Question 1

fecundity rate in normal couple with unprotected intercourse is 20-25% for first 3 months, followed by 15% during the next 9 months. 80-90% of couples are able to spontaneously conceive within 12 months

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Question 2

45-55% of infertility is attributed to female factors

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Question 3

35% of infertility attributed to male factors

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Question 4

after evaluation, 10% of couple will have no identifiable cause for their infertility

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Question 5

most common identifiable female factors were: ovulatory (32%)
fallopian tube abnormalities including pelvic adhesion 34%
endometriosis 15%

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Question 6

most common ovulatory disorders that lead to infertility are PCOS and advanced maternal age

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Question 7

oocyte aging is important factor affecting female fertility. 1-2 million oocyte at birth, and 300,000 at onset of puberty. the # of viable follicles continues to decline throughout the reproductive years and the rate of loss accelerates after the mid 30s. at time of menopause, ovary contains fewer than 1,000 follicles.

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Question 8

age related decrease in fecundability is due to both decline of quantity and quality of the oocytes.
oocyte age is the single most important factor affecting probability of success with ART.

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Question 9

age related decrease in fertility may be due to corresponding increase in the rate of aneuploidy

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Question 10

PCOS is most common cause of oligo-ovulation and anovulation among all women and those presenting with infertility. diagnostic criteria of this syndrome have been avidly debated ever since it was first described by STEIN AND LEVENTHAL.

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Question 11

stein and leventhal described criteria to diagnose PCOS as
menstrual irregularity due to oligo-ovulation or anovulation
cliical / biochemical evidence of hyperandrogenism (hirsutism, acne, male pattern baling, or elevated serum androgen concetrations)
and exclusion of other causes of hyperandrogenism and menstrual irregularity.

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Question 12

endometriosis can interfere with tubal mobility, cause tubal obstruction, or result in tubal / ovarian adhesions that contribute to infertility by holding the fallopian tube away from the ovary, obstructin gthe tube, or by trapping the relased oocyte.

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Question 13

luteal phase defect - inadequate production of progesterone by the corpus luteum and subsequent delay in endometrial maturation. this results in impaired implantation following fertilization

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Question 14

most common aneuploidy associated with female infertility is 45X ___

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turner syndrome

Question 15

diagnostic evalution of ovulatory factor in infertility involve looking for evidence of ovulation by tracking menstrual cycle.
measuring mid luteal progesterone (day 21-23)

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Question 16

measurement of a day 3 FSH is based on the notion that women with good ovarian reserve will make enough ovarian hormone early in the menstrual cycle to provide inhibition of FSH, thus keeping it at a low level

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Question 17

measurement of the day 3 ESTRADIOL level may also be used to assess ovarian reserve by looking for elevated basal rates of estradiol. this may be indicative of premature follicle recruitment that can occur in women with poor ovarian reserve. thus a higher day 3 estradiol level (>80pg/mL) is suggestive of diminished reserve, whereas a lower level <80 is suggestive of adequate ovarian capacity.

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Question 18

measurement of ANTRAL FOLLICLE COUNT. ultrasound test measures # of antral follicles (2-10mm in diameter present between days 2 and 4 of the menstrual cycle. in general, the presence of 4-10 antral follicles is a sign of good ovarian reserve, whereas lower follicle numbers suggest poor reserve.

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Question 19

measurement of ANTI-MULLERIAN HORMONE has been used in predicting ovarian reserve. based on measurement of AMH from the primordial follicle pool. when the pool is robust, a high level of AMH is detected. as women age and the pool declines, a lower amount is found. a level of AMH greater than 0.5ng/mL is considered adequate vs AMH < 0.15ng/mL are suggestive of reduced follicle pool and decreased pregnancy rates

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Question 20

metformin 500mg once daily, then increase to bid after one week (total 1000mg) then increas to 500mg tid after another week total (1500mg).

most effective dose for PCOS is 500mg TID.
take with meals

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Question 21

vellus hair - nonpigmented and soft, covers the entire body
___ hair is pigmented and thick, and covers the scalp, axilla, and pubic area. androgens are responsible for the conversion of vellus to terminal hair at puberty, resulting in pubic and axillary hair.

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terminal

Question 22

____ refers to increase in terminal hair on the face, chest, bac, lower abdomen, and inner thighs in a woman.

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hirsutism

Question 23

virilization refers to

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development of male features, such as deepening of the voice, frontal balding, increased muscle mass, clitoromegaly, breast atrophy, and male body habitus

Question 24

because DHEAS is derived almost entirely from the adrenal glands, its elevation is used as amarker for adrenal androgen production

in the ovary, any increase in LH or in the LH:FSH ratio appears to lead to excess androgen production. furthe, tumors of both adrenal gland and the ovary can lead to excess androgens. regardless of the source, elevated androgens lead to hirsutism and possibly virilism

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Question 25

because DHEAS is derived almost entirely from the adrenal glands, its elevation is used as amarker for adrenal androgen production

in the ovary, any increase in LH or in the LH:FSH ratio appears to lead to excess androgen production. furthe, tumors of both adrenal gland and the ovary can lead to excess androgens. regardless of the source, elevated androgens lead to hirsutism and possibly virilism

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Question 26

primary causes of hirsutism and virilization include PCOS, ovarian tumors, adrenal tumors, CAH, and cushing syndrome

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Question 27

diagnosis of hirsutism and virilization includes history, and physical, serum assays for testosterone, DHEAS, and 17-ohp and imaging studies

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Question 28

when cushing syndrome is suspected, it can be diagnosed with overnight dexamethasone suppression kit. a plasma cortisol level greater than 10ug/dL is diagnostic, whereas a value between 5and 10 is indeterminate. dx acn be confirmed by collecting 24 hr urine specimen and checking free cortisone levels

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Question 29

CONGENITAL ADRENAL HYPERPLASIA. common disrder is 21alphahydroxylase deficiency. will lead to accumulation of 17alpha hydroxyprogesterone (17-OHP) which is then shunted to androgen pathway.

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Question 30

patients with Congenital adrenal hyperplasia do not synthesize cortisol / mineralocorticoids and thus present with salt wasting and adrenal insufficiency at birth. female infants will have ambiguous genitalia due to androgen excess. other types of congential adrenal hyperplasia accumulate DHEA because they are unable to convert pregnenolone to progesterone or DHEA down the androgen synthesis pathway. DHEA and its sulfate, DHEAS oth have mild androgenic effects.
wHEN CAH is suspcected, 17-OHP level should be checked. if elevated >200 the diagnosis can be confirmed with ACTH stimulation test in which cortrosyn (acth) is given IV and a 17-ohp level is checked after 1 hour. marked increase in 17-ohp is consistent with CAH with lower elevated values being seen in late-onset CAH and heterozygote carriers for the 21alpha hydroxylase deficiency.

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Question 31

polycystic ovarian syndrome (pcos) previously known as

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stein-leventhal syndrome 1935

Question 32

pcos affects up to 10% of reproductive age women. synmptoms

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1. hirsutism
2. virilization
3. anovulation
4. amenorrhea
5. obesity
6. increased incidence of hyperinsulinemia, diminished insulin sensitivity, and type 2 diabetes mellitus

cause of androgen excess appears to be related to excess LH stimulation leading to cystic changes in the ovaries and increased ovarian androgen secretion. incrased LH levels are thought to be caused by an increase in the pulsatile frequency of GnRH, but what causes this increased frequency is unclear.

Question 33

patients with CAH do not synthesize CORTISOL or MINERALOCORTICOIDS and thus present with salt wasting and adrenal insufficiency at birth. female infants will have ambiguous genitalia due to ANDROGEN EXCESS.

in milder or adult-onset forms, the degree of deficiency can vary, and often the only presenting sign is mild virilization and menstrual irregularities.

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Question 34

theca lutein cysts.
theca cells of the ovary are stimulated by LH to produce androstenedione and testosterone. these androgens ar enormally shunted to the granulosa cells for aromatization to estrone and estradiol. theca lutein cysts produce an excess amt of ANDROGENS that are secreted into the circulation. these cysts may be present in either normal or molar pregnancy. more common with elevated levels of BETA HCG (MOLAR PREGNANCY, MULTIPLE PREGNANCIES, AND DURING GONADOTROPIN STIMULATION WITH INFERTILITY)

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Question 35

sex hormone binding globulin is one of the major proteins that bind circulating testosterone, leaving a small proportion of free testosterone to interact at the cellular level. androgens and corticotsteroids decrease SHBG, leaving a greater % free testosterone circiulating.

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Question 36

physical exam: inspection of escutcheon - pattern of pubic hair, clitoromegaly, palpation for ovarian masses. acanthosis nigrican (velvety, thickened hyperpigmentation in axilla, nape of neck. this dermatologic finding often associated with polycystic ovarian syndrome

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Question 37

physical exam: inspection of escutcheon - pattern of pubic hair, clitoromegaly, palpation for ovarian masses. acanthosis nigrican (velvety, thickened hyperpigmentation in axilla, nape of neck. this dermatologic finding often associated with polycystic ovarian syndrome

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Question 38

laboratory evaluation: free testostrone, 17-hydroxyprogesterone, DHEAS (EXCLUSIVE TO ADRENAL GLAND).

elevated testosterone confirms androgen excess
elevated dheas suggests adrenal source
elevated 17-OHP is suggestive of congenital adrena hyperplasia

if adrenal source is suspected, an abdominal CT should be performed to r/o an adrenal tumor, a well as further tests to diagnose cushing syndrome or CAH

if DHEAS normal or minimally elevated, ovarian source should be considered pelvic ultrasound or CT should be performed to r/o ovarian neoplasm

if LH:FSH ratio >3, suggestive of PCOS. however, most obgyn do not diagnose pcos with LH:FSH ny longer. rather, polycystic ovarian syndrome is a diagnosis of exclusion when two out of three Rotterdam criteria are met: secondary amenorrhea/oligomenorrhea, evidence of hyperandrogenism, or evidence of polycystic ovaries as assessed by ultrasound.

rapid onset of virilization and testosterone levels >200 ng/dL may indicate an ovarian neoplasm. source of androgen excess is not readily evident and further diagnostic tests such as abdominal MRI and selective venous sampling need to be done for localiation.

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