obg01 infertility
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InfertilityInfertility
Edward A. Rose, M.D., M.S.A.Edward A. Rose, M.D., M.S.A.
North Oakland Medical North Oakland Medical CentersCenters
Pontiac, MIPontiac, MI
Description of CaseDescription of Case
29 y o G29 y o G00 concerned about not concerned about not getting pregnantgetting pregnant
Unprotected sex X 1 ½ yearsUnprotected sex X 1 ½ years PMHx negativePMHx negative No other complaintsNo other complaints
Further History?Further History?
Frequency of intercourse, use of Frequency of intercourse, use of lubricants (e.g., K-Y gel) that could be lubricants (e.g., K-Y gel) that could be spermicidal, use of vaginal douches after spermicidal, use of vaginal douches after intercourse, or presence of any sexual intercourse, or presence of any sexual dysfunction such as anorgasmia or dysfunction such as anorgasmia or dyspareuniadyspareunia
Menstrual history, frequency, and Menstrual history, frequency, and patterns since menarche; weight patterns since menarche; weight changes, hirsutism, frontal balding, acnechanges, hirsutism, frontal balding, acne
History (continued)History (continued) Male partners: previous spermogram Male partners: previous spermogram
results, history of impotence, premature results, history of impotence, premature ejaculation, change in libido, history of ejaculation, change in libido, history of testicular trauma, previous relationships, testicular trauma, previous relationships, history of any previous pregnancy, history of any previous pregnancy, existence of offspring from previous existence of offspring from previous partnerspartners
History of sexually transmitted diseases; History of sexually transmitted diseases; surgical contraception (e.g. vasectomy, surgical contraception (e.g. vasectomy, tubal ligation); lifestyle; consumption of tubal ligation); lifestyle; consumption of alcohol, tobacco, and recreational drugs; alcohol, tobacco, and recreational drugs; occupation; physical activitiesoccupation; physical activities
History (continued)History (continued)
Either partner currently under Either partner currently under medical treatment, the reason, and medical treatment, the reason, and whether they have a history of whether they have a history of allergiesallergies
Complete review of systems may be Complete review of systems may be helpful to identify any helpful to identify any endocrinological or immunological endocrinological or immunological problemproblem
Your PatientYour Patient
History of weight gain, acne, facial History of weight gain, acne, facial hair, irregular menseshair, irregular menses
ROS + for an elevated glucose and ROS + for an elevated glucose and elevated BP a few months agoelevated BP a few months ago
Exam shows android body habitus, Exam shows android body habitus, weight 205#, acne on face and back, weight 205#, acne on face and back, some facial hairsome facial hair
Diagnosis, first years?Diagnosis, first years?
DefinitionDefinition
Inability to Inability to conceive after one conceive after one year of intercourse year of intercourse without without contraceptioncontraception
Counsel patience!Counsel patience!
Percent Who Conceive Within:
50%
22%
13%
5%
10%
3 Months
6 Months
12 Months
24 Months
Never
Causes of InfertilityCauses of Infertility
23%
18%
14%9%
5%
3%
28%
Male Factor
OvulatoryDysfunction
Tubal Damage
Endometriosis
Coital problems
Cervical factor
Unexplained
Male FactorMale Factor
Male partner should be evaluated Male partner should be evaluated simultaneously with female partnersimultaneously with female partner
Causes of male infertility:Causes of male infertility:– Reversible conditions (varicocele, obstructive Reversible conditions (varicocele, obstructive
azoospermia)azoospermia)– Not reversible, but viable sperm available Not reversible, but viable sperm available
(ejaculatory dysfunction, inoperative obstructive (ejaculatory dysfunction, inoperative obstructive azoospermia)azoospermia)
– Not reversible, no viable sperm (hypogonadism)Not reversible, no viable sperm (hypogonadism)– Genetic abnormalitiesGenetic abnormalities– Testicular or pituitary cancerTesticular or pituitary cancer
Ovulatory DysfunctionOvulatory Dysfunction
Causes 18% of infertilityCauses 18% of infertility Diagnosed byDiagnosed by
– Menstrual irregularitiesMenstrual irregularities– Basal body temperaturesBasal body temperatures– Ovulation prediction kitsOvulation prediction kits– Serum progesterone levels (18-24 days Serum progesterone levels (18-24 days
after onset of menses; level > 3 ng/ml is after onset of menses; level > 3 ng/ml is diagnostic of ovulation) diagnostic of ovulation)
BBT KitBBT Kit
Completed Sample BBT Completed Sample BBT ChartChart
Evaluation of Ovarian Evaluation of Ovarian ReserveReserve
Assessed in women > 35 or younger women Assessed in women > 35 or younger women with risk factors for premature ovarian failurewith risk factors for premature ovarian failure
Day 3 FSH and CCCT (clomiphene citrate Day 3 FSH and CCCT (clomiphene citrate challenge test)challenge test)– Administer 100 mg clomiphene on cycle days 5-9Administer 100 mg clomiphene on cycle days 5-9– Measure FSH on days 3 and 10; maybe estradiol Measure FSH on days 3 and 10; maybe estradiol
on day 3 (conflicting data)on day 3 (conflicting data)– Normal test not useful, but abnormal test virtually Normal test not useful, but abnormal test virtually
assures that pregnancy will not occur even with assures that pregnancy will not occur even with treatmenttreatment
Ultrasound may also be usedUltrasound may also be used
Causes of Ovulatory Causes of Ovulatory DysfunctionDysfunction
Polycystic ovary syndromePolycystic ovary syndrome Hypothalamic anovulationHypothalamic anovulation HyperprolactinemiaHyperprolactinemia Premature and age-related ovarian failurePremature and age-related ovarian failure Luteal phase defectLuteal phase defect
– Abnormalities of corpus luteum resulting in Abnormalities of corpus luteum resulting in inadequate production of progesteroneinadequate production of progesterone
– Based on finding of 2 consecutive endometrial Based on finding of 2 consecutive endometrial biopsy specimens showing histology > 2 days biopsy specimens showing histology > 2 days out-of-phase with actual biopsy dateout-of-phase with actual biopsy date
– Relevance is controversialRelevance is controversial
Polycystic Ovarian Polycystic Ovarian SyndromeSyndrome
Oligomenorrhea/amenorrhea and Oligomenorrhea/amenorrhea and hyperandrogenismhyperandrogenism
Prevalence: 5%Prevalence: 5% Among women with ovulatory dysfunction, Among women with ovulatory dysfunction,
70% have PCOS70% have PCOS Clinical evidence: hirsutism, acne, obesityClinical evidence: hirsutism, acne, obesity Lab evidence: elevated testosterone, Lab evidence: elevated testosterone,
elevated DHEA-Selevated DHEA-S ““Polycystic ovaries” supportive, not Polycystic ovaries” supportive, not
diagnosticdiagnostic
PCOS Treatment ApproachPCOS Treatment Approach
Weight loss if BMI > 30Weight loss if BMI > 30 Clomiphene to induce ovulationClomiphene to induce ovulation If DHEA-S > 2, clomiphene + If DHEA-S > 2, clomiphene +
glucocorticoid (dexamethasone)glucocorticoid (dexamethasone) If clomiphene alone unsuccessful, try If clomiphene alone unsuccessful, try
metformin + clomiphenemetformin + clomiphene
Hypothalamic AnovulationHypothalamic Anovulation
Low levels of GnRH, low or normal Low levels of GnRH, low or normal levels of FSH/LH, low levels of levels of FSH/LH, low levels of endogenous estrogenendogenous estrogen
Associated factors: low BMI (< 20), Associated factors: low BMI (< 20), high-intensity exercise, extreme high-intensity exercise, extreme diets, stressdiets, stress
Treatment: lifestyle modificationTreatment: lifestyle modification
HyperprolactinemiaHyperprolactinemia
Causes: pituitary adenoma, psych medsCauses: pituitary adenoma, psych meds Test for pregnancy, thyroid diseaseTest for pregnancy, thyroid disease Imaging: MRI for macro vs. Imaging: MRI for macro vs.
microadenomamicroadenoma Treatment: Bromocriptine (dopamine Treatment: Bromocriptine (dopamine
agonist)agonist) After treatment, 80% of women will After treatment, 80% of women will
ovulate, 80% will get pregnantovulate, 80% will get pregnant Discontinue treatment once pregnancy Discontinue treatment once pregnancy
establishedestablished
What Can I Do?What Can I Do?
History and Physical - History and Physical - FemaleFemale
HistoryHistory– Menarche, pubertyMenarche, puberty– Menstrual historyMenstrual history– Pregnancies, abortions, Pregnancies, abortions,
birth controlbirth control– Dyspareunia, Dyspareunia,
dysmenorrheadysmenorrhea– STDs, abdominal STDs, abdominal
surgery, galactorrheasurgery, galactorrhea– Weight loss/gainWeight loss/gain– Stress, exercise, drugs, Stress, exercise, drugs,
alcohol, psychologicalalcohol, psychological
PhysicalPhysical– Weight/BMIWeight/BMI– ThyroidThyroid– Skin (striae, Skin (striae,
acanthosis acanthosis nigricans)nigricans)
– Pelvic (vaginal Pelvic (vaginal mucosa, masses, mucosa, masses, pain)pain)
– Rectal (uterosacral Rectal (uterosacral nodularity)nodularity)
History and Physical - MaleHistory and Physical - Male
HistoryHistory– Prior fertilityPrior fertility– MedicationsMedications– History of diabetes, History of diabetes,
mumps, undescended mumps, undescended testestestes
– Genital surgery, Genital surgery, trauma, infectionstrauma, infections
– EDED– Drug/alcohol use, stressDrug/alcohol use, stress– Underwear, hot tubs, Underwear, hot tubs,
frequent coitusfrequent coitus
PhysicalPhysical– Habitus, Habitus,
gynecomastiagynecomastia– Sexual Sexual
developmentdevelopment– Testicular volume Testicular volume
(5x3 cm)(5x3 cm)– Epididymis, vas, Epididymis, vas,
prostate by prostate by palpationpalpation
– Check for varicoceleCheck for varicocele
How Long To Wait Before How Long To Wait Before Work-upWork-up
For young patients, wait a yearFor young patients, wait a year Don’t wait a year if:Don’t wait a year if:
– Irregular menses; intermenstrual bleedingIrregular menses; intermenstrual bleeding– History of PIDHistory of PID– History of appendicitis with ruptureHistory of appendicitis with rupture– History of abdominal surgeryHistory of abdominal surgery– DyspareuniaDyspareunia– Age > 35Age > 35– Male factorsMale factors
On The First VisitOn The First Visit
Semen analysis Semen analysis Confirm ovulationConfirm ovulation
– Basal body temperatureBasal body temperaturechartingcharting
– Ovulation predictor kitsOvulation predictor kits(detect LH surge)(detect LH surge)
– Consider serum progesterone on day 21Consider serum progesterone on day 21
Labs: Labs: – TSH and prolactinTSH and prolactin– DHEA-S if concern for PCOSDHEA-S if concern for PCOS– FSH and estradiol on cycle day 3 and 10 if >35yFSH and estradiol on cycle day 3 and 10 if >35y– Cervical cultures prnCervical cultures prn
Three Months LaterThree Months Later
HysterosalpingogramHysterosalpingogram– Evaluates tubal patency and uterine Evaluates tubal patency and uterine
cavity shapecavity shape– Noninvasive but involves a tenaculumNoninvasive but involves a tenaculum– NotNot a painless test a painless test– Performed by radiology with gynecology Performed by radiology with gynecology
supervisionsupervision– Diagnostic and therapeuticDiagnostic and therapeutic
HysterosalpingogramHysterosalpingogram
Limited Clinical UtilityLimited Clinical Utility Postcoital testPostcoital test
– Limited diagnostic potential, poor predictive valueLimited diagnostic potential, poor predictive value Endometrial biopsy (luteal phase defect)Endometrial biopsy (luteal phase defect) BBTsBBTs
– Very inexpensive but interpretation difficultVery inexpensive but interpretation difficult– Temperature changes too late to be useful for timing Temperature changes too late to be useful for timing
intercourseintercourse Zona-free hamster oocyte penetration testZona-free hamster oocyte penetration test
– Not sure if hamster oocytes predict human oocytesNot sure if hamster oocytes predict human oocytes Immune testing for antiphospholipid, antisperm, Immune testing for antiphospholipid, antisperm,
antinuclear, antithyroid antibodiesantinuclear, antithyroid antibodies Routine cervical culturesRoutine cervical cultures
– Mycoplasma hominisMycoplasma hominis or or Ureaplasma urealyticumUreaplasma urealyticum KaryotypeKaryotype
Clomiphene CitrateClomiphene Citrate
Effective for anovulatory patientsEffective for anovulatory patients– Also used in unexplained fertility, but no Also used in unexplained fertility, but no
data to supportdata to support– Most effective for women with normal FSH Most effective for women with normal FSH
and estrogen, least effective in and estrogen, least effective in hypothalamic amenorrhea or elevated FSHhypothalamic amenorrhea or elevated FSH
Induces ovulation by unknown mechanismInduces ovulation by unknown mechanism Most pregnancies occur in first 3 cyclesMost pregnancies occur in first 3 cycles 80% will ovulate, 40% will become pregnant in 80% will ovulate, 40% will become pregnant in
3 cycles3 cycles
Clomiphene - ComplicationsClomiphene - Complications
7% twin gestations, 0.3% triplet 7% twin gestations, 0.3% triplet gestationsgestations
Miscarriage rate = 15%Miscarriage rate = 15% Birth defect rate unchanged from controlsBirth defect rate unchanged from controls Side effects: hot flashes, adnexal Side effects: hot flashes, adnexal
tenderness, nausea, headache, blurry tenderness, nausea, headache, blurry visionvision
Contraindications: pregnancy, ovarian Contraindications: pregnancy, ovarian cystscysts
Clomiphene - AdministrationClomiphene - Administration
50 mg daily, cycle day 3 through 750 mg daily, cycle day 3 through 7– Induce bleeding first with progesterone Induce bleeding first with progesterone
if amenorrheicif amenorrheic Intercourse QOD cycle days 12 - 17Intercourse QOD cycle days 12 - 17 Track ovulation with BBT or ovulation Track ovulation with BBT or ovulation
detection kitsdetection kits Increase dose to 100 mg daily, then Increase dose to 100 mg daily, then
150, if no ovulation occurs150, if no ovulation occurs
Thank You!Thank You!
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