26: Infertility and ART

Question 1

Female factor infertility is purely responsible for ?% of all infertility cases. These can be divided into ? factors.

Answer 1

45% to 55%

ovulatory, tubal, uterine, and cervical factors

Question 2

Female factor infertility may be due to ovulatory factors that interrupt the hypothalamic-pituitary-ovarian axis such as ? The most common causes of ovulatory factor infertility are ?

Answer 2

PCOS, primary ovarian insufficiency, hyperprolactinemia, and thyroid diseases

PCOS and advanced maternal age.

Question 3

Ovulatory factors are diagnosed by confirming ovulation through ?

Answer 3

menstrual history, ovulation detection kits, midluteal progesterone level, along with endocrine evaluation (TSH, prolactin, FSH, and LH) and assessment of ovarian reserve (Day 3 FSH and estradiol levels, AMH levels, and AFC).

Question 4

PCOS-related infertility can be treated with ?

Answer 4

weight loss, metformin, and OI with Clomid or letrozole. When refractory to treatment, OI with human gonadotropins can be used along with along with IUI or IVF.

Question 5

The most common causes of tubal factor infertility are ?

These factors are diagnosed by ? and treated ?

Answer 5

endometriosis, pelvic adhesions, PID and tubal ligation

• diagnosed by history and laparoscopy or laparotomy
• treated surgically to improve fertility rates. Tubal occlusion may be repaired with microsurgical tuboplasty, but most couples opt for IVF.

Question 6

Female infertility may be due to uterine factors such as ? Uterine factors are diagnosed by ?

Answer 6

uterine synechiae (Asherman’s syndrome), polyps, submucosal fibroids, congenital malformations, or endometritis.

diagnosed by pelvic US, HSG, saline sonohysterogram, hysteroscopy, and laparoscopy.

Question 7

treatment of Uterine infertility factors: Synechiae, fibroids, and polyps can be ? endometritis is treated with ?

Answer 7

resected

antibiotics

Question 8

Female infertility may also be due to cervical factors such as ? These factors are diagnosed ? and treated how ?

Answer 8

cervical stenosis from surgical or mechanical dilation. also Müllerian duct and Cervicitis or chronic inflammation

diagnosed on PE and treated with surgical or mechanical dilation of the endocervical canal or IUI to bypass the cervix.

Question 9

Male factor infertility is purely responsible for ?% of all infertility cases.

Answer 9

35%

Question 10

Male infertility may be idiopathic or due to ?

Answer 10

improper coital practices, sexual dysfunction, endocrine disorders, or abnormalities in spermatogenesis, sperm volume, density, or mobility

Question 11

Male factor infertility is diagnosed by ? The treatment of male factor infertility depends on the causal agent and includes ?

Answer 11

semen analysis and endocrine evaluation if indicated
-improved coital practices, repair of anatomic defects, ICSI (Intracytoplasmic sperm injection) and the use of donor sperm.

Question 12

?% of couples find no explanation for infertility after their initial assessment. further assessment and treatment?

Answer 12

10%
search for problems with sperm transport, ability to penetrate and fertilize the egg, and antisperm antibodies. IVF/ICSI can be used to treat these patients.

Question 13

Couples with unexplained infertility who choose no treatment will conceive up to ?% of the time over 3 to 5 year.

Answer 13

60%

-Most therapies for unexplained infertility have not been shown to have higher success rates than no treatment.

Question 14

Clomiphene citrate MOA

Answer 14

an antiestrogen that binds to estrogen receptors in the hypothalamus to cause increased FSH and LH production, thereby promoting follicular maturation and ovulation

Question 15

Letrozole MOA

Answer 15

an aromatase inhibitor that decreases the conversion of androgens into estrogens, thereby lowering estrogen levels and increasing FSH and follicular development. Its use for OI is off-label in the US

Question 16

Clomiphene citrate is best used for OI in women with ? after specific causes of ? have been ruled out.

Answer 16

chronic anovulation or mild hypothalamic insufficiency

hypothalamic dysfunction

Question 17

Human menopausal gonadotropins are forms of FSH, or combinations of FSH and LH that directly stimulate ? in patients for whom ? has failed, or those with ?

Answer 17

follicular maturation in patients for whom Clomid has failed, or those with hypothalamic or pituitary failure or unexplained infertility

Question 18

The primary complications of fertility drugs include ?

Answer 18

ovarian hyperstimulation and multiple gestation pregnancy.

Question 19

IVF and ICSI may be used to bypass the normal mechanisms of ? with deliveries in about ?% of cases.

Answer 19

gamete transport and fertilization

30%

Question 20

Infertility is defined as the failure of a couple to conceive after ? of unprotected sexual intercourse. If the female partner is 35 year of age or older, evaluation should be initiated after ? of unprotected intercourse

Answer 20

12 months

6 months

Question 21

fecundity rate in a normal couple who has had unprotected intercourse

Answer 21

20% to 25% for the first 3 months, followed by 15% during the next 9 months
80% to 90% of couples are able to spontaneously conceive within 12 months

Question 22

Average Conception Rates for All Couples

Answer 22

20%	Conceive within 1 month
60%	Conceive within 6 months
75%	Conceive within 9 months
80%	Conceive within 12 months
90%	Conceive within 18 months

Question 23

WHO classifications

Answer 23

WHO group 1: hypogonadotropic hypogonadal anovulation (hypothalamic amenorrhea)
WHO group 2: normogonadotropic normoestrogenic anovulation (polycystic ovarian syndrome [PCOS])
WHO group 3: hypergonadotropic hypoestrogenic anovulation (premature ovarian failure, advanced maternal age)
WHO group 4: hyperprolactinemic anovulation

Question 24

Causes of Ovulatory Factor Infertility

Answer 24

-Central: Pituitary insufficiency (trauma, tumor, congenital), Hypothalamic insufficiency, Hyperprolactinemia (drug, tumor, empty sella), Luteal phase defects
-Peripheral defects: Gonadal dysgenesis, POF, Ovarian tumor, Ovarian resistance
-Metabolic disease:
PCOS (chronic hyperandrogenemic an ovulation), Thyroid disease, Liver disease, Obesity, Androgen excess (adrenal, neoplastic)

Question 25

2/3 criteria to diagnose PCOS are ?

Answer 25

menstrual irregularity due to oligo-ovulation or anovulation, clinical or biochemical evidence of hyperandrogenism (hirsutism, acne, male pattern balding, or elevated serum androgen concentrations)
-also exclusion of other causes of hyperandrogenism and menstrual irregularity.

Question 26

2/3 criteria to diagnose PCOS are ?

Answer 26

menstrual irregularity due to oligo-ovulation or anovulation, clinical or biochemical evidence of hyperandrogenism (hirsutism, acne, male pattern balding, or elevated serum androgen concentrations)
-also exclusion of other causes of hyperandrogenism and menstrual irregularity.

Question 27

clomiphene citrate challenge test (CCCT)

largely replaced by ?

Answer 27

used to assess for decreased ovarian reserve
-100 mg of clomiphene citrate (Clomid) on days 5-9 of the menstrual cycle.
(FSH) level is measured on days 3 and 10. Even small elevations in FSH levels correlate with decreased fecundity
-replaced by the use of basal FSH/estradiol testing, the antral follicle count (AFC), and the anti-Mullërian hormone (AMH) assay.

Question 28

Day 3 FSH level is based on the notion that ?

Answer 28

women with good ovarian reserve will make enough ovarian hormone early in the menstrual cycle to provide inhibition of FSH
-less than 10 mIU/mL is indicative of adequate ovarian reserve; 10 to 15 mIU/mL of borderline, and greater than 20 mIU/mL is indicative of poor ovarian reserve

Question 29

Metformin (Glucophage) in PCOS

Answer 29

insulin sensitizer results in inhibition of gluconeogenesis and increased peripheral glucose uptake. PCOS patients using metformin experience a decrease in fasting insulin levels and testosterone levels; helps promote the reestablishment of spontaneous ovulation

Question 30

Drugs That Decrease Semen Quality and Quantity

Answer 30

Cimetidine, Metoclopramide, Anabolic steroids, Sulfasalazine, Chemotherapeutic agents, Marijuana, Spironolactone, Beta blockers, Alcohol abuse, Antidepressants, Nitrofurans, Heroin/cocaine abuse

Question 31

Semen Analysis Normal Parameters

Answer 31

Volume greater than 2.0 mL
pH	7.2–7.8
Concentration greater than 20 million/mL
Morphology greater than 30% normal forms
Motility more than 50% with forward progression
WBC more than 1 million/mL

Question 32

endocrine evaluation in case of abnormal semen analysis

Answer 32

TFTs, prolactin, LH, and FSH (to assess for parenchymal damage to testes and hypogonadism).

Question 33

Preimplantation genetic diagnosis (PGD)

Answer 33

evaluation of the embryo for genetic abnormalities prior to transfer during an IVF cycle.
i.e. sickle cell anemia, Tay-Sachs disease, cystic fibrosis, Down syndrome, hemophilia A, and fragile X syndrome