26: Infertility and ART Flashcards
Female factor infertility is purely responsible for ?% of all infertility cases. These can be divided into ? factors.
45% to 55%
ovulatory, tubal, uterine, and cervical factors
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 ?
PCOS, primary ovarian insufficiency, hyperprolactinemia, and thyroid diseases
PCOS and advanced maternal age.
Ovulatory factors are diagnosed by confirming ovulation through ?
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).
PCOS-related infertility can be treated with ?
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.
The most common causes of tubal factor infertility are ?
These factors are diagnosed by ? and treated ?
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.
Female infertility may be due to uterine factors such as ? Uterine factors are diagnosed by ?
uterine synechiae (Asherman’s syndrome), polyps, submucosal fibroids, congenital malformations, or endometritis.
diagnosed by pelvic US, HSG, saline sonohysterogram, hysteroscopy, and laparoscopy.
treatment of Uterine infertility factors: Synechiae, fibroids, and polyps can be ? endometritis is treated with ?
resected
antibiotics
Female infertility may also be due to cervical factors such as ? These factors are diagnosed ? and treated how ?
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.
Male factor infertility is purely responsible for ?% of all infertility cases.
35%
Male infertility may be idiopathic or due to ?
improper coital practices, sexual dysfunction, endocrine disorders, or abnormalities in spermatogenesis, sperm volume, density, or mobility
Male factor infertility is diagnosed by ? The treatment of male factor infertility depends on the causal agent and includes ?
semen analysis and endocrine evaluation if indicated
-improved coital practices, repair of anatomic defects, ICSI (Intracytoplasmic sperm injection) and the use of donor sperm.
?% of couples find no explanation for infertility after their initial assessment. further assessment and treatment?
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.
Couples with unexplained infertility who choose no treatment will conceive up to ?% of the time over 3 to 5 year.
60%
-Most therapies for unexplained infertility have not been shown to have higher success rates than no treatment.
Clomiphene citrate MOA
an antiestrogen that binds to estrogen receptors in the hypothalamus to cause increased FSH and LH production, thereby promoting follicular maturation and ovulation
Letrozole MOA
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
Clomiphene citrate is best used for OI in women with ? after specific causes of ? have been ruled out.
chronic anovulation or mild hypothalamic insufficiency
hypothalamic dysfunction
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 ?
follicular maturation in patients for whom Clomid has failed, or those with hypothalamic or pituitary failure or unexplained infertility
The primary complications of fertility drugs include ?
ovarian hyperstimulation and multiple gestation pregnancy.
IVF and ICSI may be used to bypass the normal mechanisms of ? with deliveries in about ?% of cases.
gamete transport and fertilization
30%
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
12 months
6 months
fecundity rate in a normal couple who has had unprotected intercourse
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
Average Conception Rates for All Couples
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
WHO classifications
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
Causes of Ovulatory Factor Infertility
-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)
2/3 criteria to diagnose PCOS are ?
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.
2/3 criteria to diagnose PCOS are ?
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.
clomiphene citrate challenge test (CCCT)
largely replaced by ?
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.
Day 3 FSH level 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
-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
Metformin (Glucophage) in PCOS
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
Drugs That Decrease Semen Quality and Quantity
Cimetidine, Metoclopramide, Anabolic steroids, Sulfasalazine, Chemotherapeutic agents, Marijuana, Spironolactone, Beta blockers, Alcohol abuse, Antidepressants, Nitrofurans, Heroin/cocaine abuse
Semen Analysis Normal Parameters
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
endocrine evaluation in case of abnormal semen analysis
TFTs, prolactin, LH, and FSH (to assess for parenchymal damage to testes and hypogonadism).
Preimplantation genetic diagnosis (PGD)
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
