Columbus: Infertility and ovulation induction

Question 1

Define infertility, fecundity, fecundability

Answer 1

One year of unprotected intercourse without conception

The probability the single cycle will lead to a life birth

The probability that a single cycle will result in a pregnancy

Question 2

Who is at increased risk of ovarian insufficiency and should have ovarian reserve testing?

Answer 2

Greater than 35 years of age
Anyone with unexplained infertility
Prior ovarian surgery
Anyone with poor response to gonadotropin stimulation
Smokers
Family history of premature menopause

Question 2

What factors have led to a decreased the general fertility rate since 1950?

Answer 2

Later marriage
Use of improved contraception
Career before conception
Decreasing family size

Question 3

How does increasing age decrease fertility?

Answer 3

Limited number of oocytes
Follicular hormone changes such as increased FSH, decreased inhibin and shorter follicular phase
Disordered meiotic spindle formation and function leading to increased aneuploidy

Question 5

How can ovarian reserve be tested?

Answer 5

Day 3 FSH and estradiol
Clomiphene citrate challenge test (collect D3 FSH and estradiol, then repeat after completing Clomid cycle. Total FSH for both should be less than 26)
Ovarian volume
Antral follicle count (3-10 follicles less than 10 mm is low)
Anti-mullerian hormone

Question 6

What are causes of male infertility?

Answer 6

Abnormalities in spermatogenesis
Obstruction of outflow tract
Abnormalities of hormone support of sperm production (such as increased prolactin which decreases testosterone)
Coital problems

Question 6

What are causes and rates of infertility for couples?

Answer 6

Tubal and pelvic disease 35%
Male factors 35%
Ovulatory dysfunction 15%
Unexplained 10%
Unusual problems 5%

Question 7

What are the causes and rates of female infertility?

Answer 7

Ovulatory dysfunction 40%
Tubal and pelvic disease 40%
Unexplained 10%
Unusual problems 10%

Question 8

When is fertility evaluation recommended?

Answer 8

Those who have not conceived in 1 year
Women 35 years old or older who is not conceived at 6 months or earlier
Women with irregular periods or amenorrhea
Women with a history of pelvic inflammatory disease, endometriosis, or prior pelvic or abdominal surgeries

Question 9

What is the effect of smoking on fertility?

Answer 9

Higher prevalence of infertility
Accelerated follicular loss
Gamete or embryo mutagenesis
Menstrual cycle abnormalities

Question 11

What are the key components of the history for infertility evaluation?

Answer 11

Prior pregnancy outcomes
Medical history including PCOS, thyroid or pituitary disease
Surgical history including pelvic surgery and ovarian surgery
Gyn history including menstrual history and STI
Medications including NSAIDs and Aldactone
Substance abuse such as smoking, marijuana, cocaine, alcohol, caffeine
Environmental exposures such as toluene, herbicides, and fungicides
Family history including early menopause, birth defects and genetic abnormalities

Question 12

What is the relative risk of an ovulation with BMI greater than 27?

Less than 17?

Answer 12

RR 3.1

RR 1.6

Question 12

How does marijuana affect fertility?

Cocaine?

Answer 12

Inhibits GnRH pulsatility

Impairs spermatogenesis

Question 13

What features of the physical exam are important for fertility evaluation?

Answer 13

BMI
Hirsutism and acne
Thyroid
Breast discharge
Pelvic exam including size of uterus and ovaries, cervical infection, tenderness or nodularity in the cul-de-sac

Question 14

What preconceptual genetic screening is recommended for which ethnic groups?

Answer 14

Ashkenazi Jews: Hexosaminidase A (Tay Sachs, lysosomal storage disease)
African-American: hemoglobin electrophoresis (Sickle cell)
Mediterranean: MCV less than 80 then hemoglobin electrophoresis
European whites: CFTR gene mutation (cystic fibrosis)

Question 15

What laboratory testing is recommended for preconceptual screening?

Answer 15

Rubella immunity
Varicella immunity
Type and screen
Pap
STI screening
Genetic screening by ethnicity

Question 16

How can ovulatory status be determined?

Answer 16

Basal body temperature: nadir is the day prior or day of LH surge
Serum progesterone: Peak 7-8 days after LH surge, greater than 3 ng/mL confirms
Urine LH kit: predicts ovulation within 24-48 hours, 90% accurate

Question 17

What lab testing should be done to look for hormonal causes of anovulation?

Answer 17

TSH
Prolactin
Total testosterone
17 hydroxyprogesterone

Question 18

What is the gold standard for evaluation of tubal status for infertility?

What secondary options can be considered?

Answer 18

HSG

Sonohysterogram, laparoscopy, ultrasound

Question 19

Which women benefit from ovulation induction?

Answer 19

Hypoestrogenic and normal estrogen with anovulation

Question 20

What therapy should be recommended for obese women with PCOS before clomiphene?

Answer 20

Weight loss. In one study, average weight loss of 10 kg was associated with a 90% chance of spontaneous ovulation and a 67% fecundity

Question 21

What causes hypoestrogenism?

Answer 21

Exercise-induced amenorrhea
Eating disorder amenorrhea
Isolated gonadotropin deficiency
Kallmann syndrome (GnRH deficiency with anosmia)

Question 23

What is the mechanism of clomiphene citrate?

What happens to fertility as a higher doses are administered?

Answer 23

Estrogen receptor antagonist blocks negative feedback of estrogen at hypothalamus which increases GnRH and thus LH and FSH

Higher doses are anti-estrogenic to the uterine lining and decrease fertility

Question 23

What are the side effects of Clomid?

Answer 23

Hot flashes
Visual disturbances
Breast tenderness
Nausea
Pelvic pain

Question 24

What is the rate of ovulation on Clomid? Pregnancy rate? Multiple rate?

Answer 24

60 to 80% 22% 7 to 10%

Question 25

How would you counsel patient about the effectiveness of clomiphene?

Answer 25

Conception rate is approximately 40% Live birthrate approximately 22% Rates are highest during the first three cycles and drop to less than 10% after the sixth cycle

Question 26

What is the mechanism of metformin? What does ASRM say about ovulation induction using metformin?

Answer 26

Insulin sensitizing agent, decreases androgen environment Clomid is superior to metformin for conception, and slightly better when used in combination. Combination use may be considered for women who fail to ovulate on clomiphene alone. The use of metformin solely to induce ovulation is unwarranted, November 2008

Question 27

How is Letrozole dosed? What are common side effects?

Answer 27

2.5-5 mg for five days Hot flashes, leg cramps, headaches

Question 28

What are the advantages of aromatase inhibitors?

Answer 28

``` High ovulation rate 70–88% High pregnancy rate 20–27% per cycle High safety due to short half-life Decreased multiple gestation Lower-cost then gonadotropins ```

Question 29

What is the mechanism of action of aromatase inhibitors such as Letrozole?

Answer 29

Blocks estrogen production (prevents aromatization of androgens to estrogen) and removes estrogen's negative feedback on hypothalamus Leads to increased FSH and LH More commonly results in monofollicular development

Question 30

What are the concerns over aromatase inhibitor use?

Answer 30

Animal models showed teratogenic effect. Subsequent human studies have shown no difference in miscarriage, ectopic or or malformations Not FDA approved

Question 31

When should dexamethasone use be considered for the treatment of infertility?

Answer 31

In patients with elevated DHEAS

Question 32

What is the purpose of laparoscopic ovarian drilling? What is the theoretical concern? Which patients are especially good candidates for ovarian drilling?

Answer 32

Reduces ovarian theca cells which reduces androgen production Potential for postoperative adhesions but this is not been verified Those with high LH (due to excessive theca cells)

Question 33

For which patients is gonadotropin therapy indicated for infertility?

Answer 33

WHO class I such as Kallmans syndrome and WHO class II who have failed oral therapy

Question 34

What are the disadvantages to gonadotropin therapy?

Answer 34

High rate of cycle cancellation due to multi-follicular development Increased concern for multiple gestation Increased risk of ovarian hyperstimulation syndrome

Question 35

How is gonadotropin therapy monitored? What additional medications are need for conception? Pregnancy support?

Answer 35

Serial ultrasound Serum estradiol to adjust dose Exogenous hCG given to stimulate ovulation Luteal phase support with exogenous progesterone

Question 37

What medicines are associated with ovarian hyperstimulation syndrome? What are risk factors for OHSS?

Answer 37

Gonadotropins, followed by clomiphene Low bodyweight, young age, PCOS