Post on 26-Dec-2015
OverviewDefinitions and NumbersIndications for evaluationCauses of infertility
Ovulatory dysfunctionTubal and pelvicMale factor
Laboratory evaluationTreatment with ClomidWhen to refer
DefinitionsInfertility – 1 year of unprotected intercourse without
conception (10-15% of couples)Fecundability – probability that a single cycle will result
in pregnancy (20-25% if normal)
Lies, Damn Lies and StatisticsTime required for conception in couples who will attain
pregnancy Exposure % Pregnant
3 mo 576 mo 721 yr 852 yr 93
Indications for EvaluationEducation should be offered to any couple who seeks it –
even without trying firstAny couple who is infertileAny woman older than 35yo with irregular or infrequent
mensesWomen with a history of PIDMen with known or suspected poor quality semen
Causes of InfertilityOvulatory dysfunction – 15-20%
PCOS, ovarian failureTubal and peritoneal pathology – 30-40%
Congenital malformations, fibroids, tubal scarring, intrauterine adhesions (Asherman’s)
Male factors – 30-40%Unexplained – 10-15%
Ovulatory Dysfunction20% of infertile women have ovulatory disordersThe cause of anovulation will guide treatmentSymptoms
polymenorrhea, oligomenorrhea, amenorrheaRegular menstrual cycles (22-35d) with presence of
premenstrual symptoms is highly suggestive of ovulation (~95%)
Ovulatory DysfunctionDifferential diagnosis
PCOS (70%)Hypothalamic amenorrhea (10%)
aka hypogonadotropi c hypogonadism Low GnRH, LH, FSH, Estrogen
Hyperprolactinemia (10%) Can be caused by hypothyroid (TRH acts as PRF)
Premature ovarian failure/insufficiency (10%) aka hypergonadotropic hypoestrogenic anovulation
PCOSMust have 2 of 3 diagnostic criteria
“polycystic ovaries” on sonoClinical or lab evidence of increased testosteroneOligo- or amenorrhea
Diagnosis of exclusionthyroid/prolactin disordersTestosterone secreting tumor, non-typical congenital
adrenal hyperplasia (CAH), Cushing’s syndrome
Other Ovulatory DysfunctionHypothalamic amenorrhea
aka hypogonadotropic hypogonadismLow GnRH, LH, FSH, EstrogenFrequently found in athletes and women with very low BMI
– consider eating disordersHyperprolactinemia
Can be caused by hypothyroid (TRH acts as PRF)MRI to look for prolactinoma of pituitary
Other Ovulatory DysfunctionPremature ovarian failure/insufficiency
aka hypergonadotropic hypoestrogenic anovulationPremature if less than 35 to 40yoUsually not complete “failure”High FSH and LH but low estrogen levels
Signs that the ovaries are not respondingRule out chromosomal abnormalities
Y chromosome, Turner’s syndrome, Fragile X
Ovulatory Dysfunction EvalPhysical exam (after a very thorough history)
Galactorrhea, thyroid evalAcanthosis nigricans, hirsutism, acneBMI (>30 or <20)
Laboratory evaluation for ovulationBasal body temperatureUrine testing for LH surge (seen after ovulation)Pelvic sono
Tubal and Peritoneal PathologyCervical factor – post-coital test not commonUterine factor
Fibroids: size, symptoms, sonoIntrauterine adhesions – Asherman’s syndrome
Painful, short menses Classically after a D&C, may also be after infection
Tubal and Peritoneal PathologyTubal factor
History of PID (or untreated STI)Abdominal/pelvic surgeryEndometriosis – painful menses
Tubal and Peritoneal PathologyEvaluation
Pelvic sonoHysterosalpingography (HSG)Sonohysterography (SHG)HysteroscopyLaparoscopy with tubal dye instillation
Male FactorSemen analysis
Volume 1.5 – 5mlpH > 7.2Concentration > 20 mil/mlTotal number > 40 milPercent motile >50%Normal morphology – lab: 14%, 30%, or 50%
If abnormal, repeat then refer if still abnormal
Laboratory EvaluationFor ovulatory dysfunction
Basal body temperature, urinary LHTSHProlactin (ideal conditions if first test abnormal)Cycle day 3 labs
FSH, Estradiol
Consider other screeningPap, Rubella, STI, genetics
Clomiphene CitrateClomid – estrogen agonist and antagonist
Binds to nuclear estrogen receptorsCirculating estrogen levels perceived as lowStimulates increased pituitary gonadotropinsIncreases ovarian follicular development
Side effectsAntiestrogenicMultiples: 7% twins, 1% triplets
Clomiphene CitrateWho to give
Anovulatory woman with normal TSH, PRL Normal estradiol or menstrual response to progesterone
challengeUnexplained fertility
How to give50mg PO qday on cycle days 3-7 (or 5-9)
New prescription every monthScheduled intercourse QOD days 10-18
Clomiphene CitrateWhen it fails (no menses and not pregnant)
Double check a pregnancy test (usually CD 33-35)Induce menses with progesterone challenge
Provera 5mg PO qday x 5 daysIncrease dose of CC by 50 mg
Max dose 150 mg – 250 mg
How long to give3 to 6 to 9 months – patient and provider specific
Other optionsInsulin sensitizers
Metformin 500 – 875 mg, BID to TIDLetrozole (Femara)
Aromatase inhibitor2.5 mg PO on cycle days 3-7
Laparoscopic ovarian drillingInjectible gonadotropins
When to referRight away
Advanced agePrevious treatmentUpon patient request
Non-ovulatory dysfunctionTubal or peritoneal factory, male factor
When Clomid doesn’t work3 to 6 to 9 months