Christopher R. Graber, MDSalina Women’s Clinic

10 Dec 2010

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

Questions?