Columbus: Infertility and ovulation induction Flashcards
Define infertility, fecundity, fecundability
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
Who is at increased risk of ovarian insufficiency and should have ovarian reserve testing?
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
What factors have led to a decreased the general fertility rate since 1950?
Later marriage
Use of improved contraception
Career before conception
Decreasing family size
How does increasing age decrease fertility?
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
How can ovarian reserve be tested?
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
What are causes of male infertility?
Abnormalities in spermatogenesis
Obstruction of outflow tract
Abnormalities of hormone support of sperm production (such as increased prolactin which decreases testosterone)
Coital problems
What are causes and rates of infertility for couples?
Tubal and pelvic disease 35% Male factors 35% Ovulatory dysfunction 15% Unexplained 10% Unusual problems 5%
What are the causes and rates of female infertility?
Ovulatory dysfunction 40%
Tubal and pelvic disease 40%
Unexplained 10%
Unusual problems 10%
When is fertility evaluation recommended?
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
What is the effect of smoking on fertility?
Higher prevalence of infertility
Accelerated follicular loss
Gamete or embryo mutagenesis
Menstrual cycle abnormalities
What are the key components of the history for infertility evaluation?
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
What is the relative risk of an ovulation with BMI greater than 27?
Less than 17?
RR 3.1
RR 1.6
How does marijuana affect fertility?
Cocaine?
Inhibits GnRH pulsatility
Impairs spermatogenesis
What features of the physical exam are important for fertility evaluation?
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
What preconceptual genetic screening is recommended for which ethnic groups?
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)
What laboratory testing is recommended for preconceptual screening?
Rubella immunity Varicella immunity Type and screen Pap STI screening Genetic screening by ethnicity
How can ovulatory status be determined?
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
What lab testing should be done to look for hormonal causes of anovulation?
TSH
Prolactin
Total testosterone
17 hydroxyprogesterone
What is the gold standard for evaluation of tubal status for infertility?
What secondary options can be considered?
HSG
Sonohysterogram, laparoscopy, ultrasound
Which women benefit from ovulation induction?
Hypoestrogenic and normal estrogen with anovulation
What therapy should be recommended for obese women with PCOS before clomiphene?
Weight loss. In one study, average weight loss of 10 kg was associated with a 90% chance of spontaneous ovulation and a 67% fecundity
What causes hypoestrogenism?
Exercise-induced amenorrhea
Eating disorder amenorrhea
Isolated gonadotropin deficiency
Kallmann syndrome (GnRH deficiency with anosmia)
What is the mechanism of clomiphene citrate?
What happens to fertility as a higher doses are administered?
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
What are the side effects of Clomid?
Hot flashes Visual disturbances Breast tenderness Nausea Pelvic pain
What is the rate of ovulation on Clomid?
Pregnancy rate?
Multiple rate?
60 to 80%
22%
7 to 10%
How would you counsel patient about the effectiveness of clomiphene?
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
What is the mechanism of metformin?
What does ASRM say about ovulation induction using metformin?
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
How is Letrozole dosed?
What are common side effects?
2.5-5 mg for five days
Hot flashes, leg cramps, headaches
What are the advantages of aromatase inhibitors?
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
What is the mechanism of action of aromatase inhibitors such as Letrozole?
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
What are the concerns over aromatase inhibitor use?
Animal models showed teratogenic effect. Subsequent human studies have shown no difference in miscarriage, ectopic or or malformations
Not FDA approved
When should dexamethasone use be considered for the treatment of infertility?
In patients with elevated DHEAS
What is the purpose of laparoscopic ovarian drilling?
What is the theoretical concern?
Which patients are especially good candidates for ovarian drilling?
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)
For which patients is gonadotropin therapy indicated for infertility?
WHO class I such as Kallmans syndrome and WHO class II who have failed oral therapy
What are the disadvantages to gonadotropin therapy?
High rate of cycle cancellation due to multi-follicular development
Increased concern for multiple gestation
Increased risk of ovarian hyperstimulation syndrome
How is gonadotropin therapy monitored?
What additional medications are need for conception? Pregnancy support?
Serial ultrasound
Serum estradiol to adjust dose
Exogenous hCG given to stimulate ovulation
Luteal phase support with exogenous progesterone
What medicines are associated with ovarian hyperstimulation syndrome?
What are risk factors for OHSS?
Gonadotropins, followed by clomiphene
Low bodyweight, young age, PCOS