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Infertility Infertility Petrenko N., M.D. PhD
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Infertility Petrenko N., M.D. PhD Definitions Infertility –Inability to conceive after one year of unprotected intercourse (6 months for women over 35?)

Dec 14, 2015

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Page 1: Infertility Petrenko N., M.D. PhD Definitions Infertility –Inability to conceive after one year of unprotected intercourse (6 months for women over 35?)

InfertilityInfertility

Petrenko N., M.D. PhD

Page 2: Infertility Petrenko N., M.D. PhD Definitions Infertility –Inability to conceive after one year of unprotected intercourse (6 months for women over 35?)

DefinitionsDefinitions

• Infertility– Inability to conceive after one year of

unprotected intercourse (6 months for women over 35?)

• Fertility– Ability to conceive

• Fecundity– Ability to carry to delivery

Page 3: Infertility Petrenko N., M.D. PhD Definitions Infertility –Inability to conceive after one year of unprotected intercourse (6 months for women over 35?)

StatisticsStatistics• 80% of couples will conceive within 1 year of

unprotected intercourse

• ~86% will conceive within 2 years

• ~14-20% of US couples are infertile by definition (~3 million couples)

• Origin:– Female factor ~40%– Male factor ~30%– Combined ~30%

Page 4: Infertility Petrenko N., M.D. PhD Definitions Infertility –Inability to conceive after one year of unprotected intercourse (6 months for women over 35?)

EtiologiesEtiologies

• Sperm disorders 30.6%

• Anovulation/oligoovulation 30%

• Tubal disease 16%

• Unexplained 13.4%

• Cx factors 5.2%

• Peritoneal factors 4.8%

Page 5: Infertility Petrenko N., M.D. PhD Definitions Infertility –Inability to conceive after one year of unprotected intercourse (6 months for women over 35?)

Associated FactorsAssociated Factors• PID• Endometriosis • Ovarian aging• Spermatic varicocoele• Toxins • Previous abdominal surgery (adhesions)• Cervical/uterine abnormalities• Cervical/uterine surgery• Fibroids

Page 6: Infertility Petrenko N., M.D. PhD Definitions Infertility –Inability to conceive after one year of unprotected intercourse (6 months for women over 35?)

Emotional and Educational Emotional and Educational NeedsNeeds

• Disease of couples, not individuals

• Feelings of guilt

• Where to go for information?

• Options

• Feelings of frustration and anger

• Support groups (e.g. Resolve)

Page 7: Infertility Petrenko N., M.D. PhD Definitions Infertility –Inability to conceive after one year of unprotected intercourse (6 months for women over 35?)

Overview of EvaluationOverview of Evaluation• Female

– Ovary– Tube – Corpus– Cervix– Peritoneum

• Male– Sperm count and function– Ejaculate characteristics, immunology– Anatomic anomalies

Page 8: Infertility Petrenko N., M.D. PhD Definitions Infertility –Inability to conceive after one year of unprotected intercourse (6 months for women over 35?)

The Most Important Factor in The Most Important Factor in the Evaluation of the Infertile the Evaluation of the Infertile

Couple Is:Couple Is:

Page 9: Infertility Petrenko N., M.D. PhD Definitions Infertility –Inability to conceive after one year of unprotected intercourse (6 months for women over 35?)

HISTORYHISTORY

Page 10: Infertility Petrenko N., M.D. PhD Definitions Infertility –Inability to conceive after one year of unprotected intercourse (6 months for women over 35?)

History-GeneralHistory-General

• Both couples should be present• Age• Previous pregnancies by each partner• Length of time without pregnancy• Sexual history

– Frequency and timing of intercourse– Use of lubricants– Impotence, anorgasmia, dyspareunia– Contraceptive history

Page 11: Infertility Petrenko N., M.D. PhD Definitions Infertility –Inability to conceive after one year of unprotected intercourse (6 months for women over 35?)

History-MaleHistory-Male

• History of pelvic infection

• Radiation, toxic exposures (include drugs)

• Mumps

• Testicular surgery/injury

• Excessive heat exposure (spermicidal)

Page 12: Infertility Petrenko N., M.D. PhD Definitions Infertility –Inability to conceive after one year of unprotected intercourse (6 months for women over 35?)

History-FemaleHistory-Female

• Previous female pelvic surgery

• PID

• Appendicitis

• IUD use

• Ectopic pregnancy history

• DES (?relation to infertility)

• Endometriosis

Page 13: Infertility Petrenko N., M.D. PhD Definitions Infertility –Inability to conceive after one year of unprotected intercourse (6 months for women over 35?)

History-FemaleHistory-Female

• Irregular menses, amenorrhea, detailed menstrual history

• Vasomotor symptoms • Stress• Weight changes• Exercise• Cervical and uterine surgery

Page 14: Infertility Petrenko N., M.D. PhD Definitions Infertility –Inability to conceive after one year of unprotected intercourse (6 months for women over 35?)

When Not to Pursue an When Not to Pursue an Infertility EvaluationInfertility Evaluation

• Patient not sexually-active

• Patient not in long-term relationship?

• Patient declines treatment at this time

• Couple does not meet the definition of an infertile couple

Page 15: Infertility Petrenko N., M.D. PhD Definitions Infertility –Inability to conceive after one year of unprotected intercourse (6 months for women over 35?)

Physical Exam-MalePhysical Exam-Male

• Size of testicles

• Testicular descent

• Varicocoele

• Outflow abnormalities (hypospadias, etc)

Page 16: Infertility Petrenko N., M.D. PhD Definitions Infertility –Inability to conceive after one year of unprotected intercourse (6 months for women over 35?)

Physical Exam-FemalePhysical Exam-Female

• Pelvic masses

• Uterosacral nodularity

• Abdominopelvic tenderness

• Uterine enlargement

• Thyroid exam

• Uterine mobility

• Cervical abnormalities

Page 17: Infertility Petrenko N., M.D. PhD Definitions Infertility –Inability to conceive after one year of unprotected intercourse (6 months for women over 35?)

Overall Guidelines for Work-Overall Guidelines for Work-up up

• Timeliness of testing-w/u can usually be accomplished in 1-2 cycles

• Timing of tests

• Don’t over test

• Cut to the chase, i.e. proceed with laparoscopy if adhesive disease is likely

Page 18: Infertility Petrenko N., M.D. PhD Definitions Infertility –Inability to conceive after one year of unprotected intercourse (6 months for women over 35?)

Ovarian FunctionOvarian Function

• Document ovulation:– BBT– Luteal phase progesterone – LH surge– EMBx

• If POF suspected, perform FSH

• TSH, PRL, adrenal functions if indicated

• The only convincing proof of ovulation is pregnancy

Page 19: Infertility Petrenko N., M.D. PhD Definitions Infertility –Inability to conceive after one year of unprotected intercourse (6 months for women over 35?)

Ovarian FunctionOvarian Function

• Three main types of dysfunction– Hypogonadotrophic, hypoestrogenic (central)– Normogonadotrophic, normoestrogenic (e.g.

PCOS)– Hypergonadotrophic, hypoestrogenic (POF)

Page 20: Infertility Petrenko N., M.D. PhD Definitions Infertility –Inability to conceive after one year of unprotected intercourse (6 months for women over 35?)

BBTBBT

• Cheap and easy, but…– Inconsistent results– Provides evidence after the fact (like the old story

about the barn door and the horse)– May delay timely diagnosis and treatment– 98% of women will ovulate within 3 days of the

nadir– Biphasic profiles can also be seen with LUF

syndrome

Page 21: Infertility Petrenko N., M.D. PhD Definitions Infertility –Inability to conceive after one year of unprotected intercourse (6 months for women over 35?)

Luteal Phase ProgesteroneLuteal Phase Progesterone

• Pulsatile release, thus single level may not be useful unless elevated

• Performed 7 days after presumptive ovulation

• Done properly, >15 ng/ml consistent with ovulation

Page 22: Infertility Petrenko N., M.D. PhD Definitions Infertility –Inability to conceive after one year of unprotected intercourse (6 months for women over 35?)

Urinary LH KitsUrinary LH Kits

• Very sensitive and accurate

• Positive test precedes ovulation by ~24 hours, so useful for timing intercourse

• Downside: price, obsession with timing of intercourse

Page 23: Infertility Petrenko N., M.D. PhD Definitions Infertility –Inability to conceive after one year of unprotected intercourse (6 months for women over 35?)

Endometrial Biopsy Endometrial Biopsy • Invasive, but the only reliable way to diagnose LPD• ??Is LPD a genuine disorder???• Pregnancy loss rate <1%• Perform around 2 days before expected

menstruation (= day 28 by definition)• Lag of >2 days is consistent with LPD• Must be done in two different cycles to confirm

diagnosis of LPD

Page 24: Infertility Petrenko N., M.D. PhD Definitions Infertility –Inability to conceive after one year of unprotected intercourse (6 months for women over 35?)

Tubal FunctionTubal Function

• Evaluate tubal patency whenever there is a history of PID, endometriosis or other adhesiogenic condition

• Kartagener’s syndrome can be associated with decreased tubal motility

• Tests– HSG

– Laparoscopy

– Falloposcopy (not widely available)

Page 25: Infertility Petrenko N., M.D. PhD Definitions Infertility –Inability to conceive after one year of unprotected intercourse (6 months for women over 35?)

Hysterosalpingography (HSG)Hysterosalpingography (HSG)

• Radiologic procedure requiring contrast• Performed optimally in early proliferative phase

(avoids pregnancy)• Low risk of PID except if previous history of PID

(give prophylactic doxycycline or consider laparoscopy)

• Oil-based contrast– Higher risk of anaphylaxis than H2O-based

– May be associated with fertility rates

Page 26: Infertility Petrenko N., M.D. PhD Definitions Infertility –Inability to conceive after one year of unprotected intercourse (6 months for women over 35?)

Hysterosalpingography (HSG)Hysterosalpingography (HSG)

• Can be uncomfortable

• Pregnancy test is advisable

• Can detect intrauterine and tubal disorders but not always definitive

Page 27: Infertility Petrenko N., M.D. PhD Definitions Infertility –Inability to conceive after one year of unprotected intercourse (6 months for women over 35?)

Laparoscopy Laparoscopy

• Invasive; requires OR or office setting

• Can offer diagnosis and treatment in one sitting

• Not necessary in all patients

• Uses (examples):– Lysis of adhesions– Diagnosis and excision of endometriosis– Myomectomy – Tubal reconstructive surgery

Page 28: Infertility Petrenko N., M.D. PhD Definitions Infertility –Inability to conceive after one year of unprotected intercourse (6 months for women over 35?)

FalloposcopyFalloposcopy

• Hysteroscopic procedure with cannulation of the Fallopian tubes

• Can be useful for diagnosis of intraluminal pathology

• Promising technique but not yet widespread

Page 29: Infertility Petrenko N., M.D. PhD Definitions Infertility –Inability to conceive after one year of unprotected intercourse (6 months for women over 35?)

CorpusCorpus• Asherman Syndrome

– Diagnosis by HSG or hysteroscopy– Usually s/p D+C, myomectomy, other intrauterine

surgery– Associated with hypo/amenorrhea, recurrent miscarriage

• Fibroids, Uterine Anomalies– Rarely associated with infertility– Work-up:

• Ultrasound • Hysteroscopy• Laparoscopy

Page 30: Infertility Petrenko N., M.D. PhD Definitions Infertility –Inability to conceive after one year of unprotected intercourse (6 months for women over 35?)

Cervical FunctionCervical Function

• Infection– Ureaplasma suspected

• Stenosis– S/P LEEP, Cryosurgery, Cone biopsy (probably

overstated)

• Immunologic Factors– Sperm-mucus interaction

Page 31: Infertility Petrenko N., M.D. PhD Definitions Infertility –Inability to conceive after one year of unprotected intercourse (6 months for women over 35?)

Cervical FunctionCervical Function

• Tests:– Culture for suspected pathogens – Postcoital test (PK tests)

• Scheduled around 1-2d before ovulation (increased estrogen effect)

• 480 of male abstinence before test

• No lubricants

• Evaluate 8-12h after coitus (overnight is ok!)

• Remove mucus from cervix (forceps, syringe)

Page 32: Infertility Petrenko N., M.D. PhD Definitions Infertility –Inability to conceive after one year of unprotected intercourse (6 months for women over 35?)

Cervical FunctionCervical Function

• PK, continued (normal values in yellow)– Quantity (very subjective)– Quality (spinnbarkeit) (>8 cm)– Clarity (clear)– Ferning (branched)– Viscosity (thin)– WBC’s (~0)

– # progressively motile sperm/hpf (5-10/hpf)– Gross sperm morphology (WNL)

Male factorsMale factors

Page 33: Infertility Petrenko N., M.D. PhD Definitions Infertility –Inability to conceive after one year of unprotected intercourse (6 months for women over 35?)

Problems with the PK testProblems with the PK test

• Subjective

• Timing varies; may need to be repeated

• In some studies, “infertile” couples with an abnormal PK conceived successfully during that same cycle

Page 34: Infertility Petrenko N., M.D. PhD Definitions Infertility –Inability to conceive after one year of unprotected intercourse (6 months for women over 35?)

Peritoneal FactorsPeritoneal Factors

• Endometriosis – 2x relative risk of infertility– Diagnosis (and best treatment) by laparoscopy – Can be familial; can occur in adolescents– Etiology unknown but likely multiple ones

• Retrograde menstruation• Immunologic factors• Genetics• Bad karma

– Medical options remain suboptimal

Page 35: Infertility Petrenko N., M.D. PhD Definitions Infertility –Inability to conceive after one year of unprotected intercourse (6 months for women over 35?)

Male FactorsMale Factors

• Serum T, FSH, PRL levels

• Semen analysis

• Testicular biopsy

• Sperm penetration assay (SPA)

Page 36: Infertility Petrenko N., M.D. PhD Definitions Infertility –Inability to conceive after one year of unprotected intercourse (6 months for women over 35?)

Male Factors-Semen AnalysisMale Factors-Semen Analysis

• Collected after 480 of abstinence

• Evaluated within one hour of ejaculation

• If abnormal parameters, repeat twice, 2 weeks apart

Page 37: Infertility Petrenko N., M.D. PhD Definitions Infertility –Inability to conceive after one year of unprotected intercourse (6 months for women over 35?)

Normal Semen AnalysisNormal Semen Analysis

Quality Normal Value

Volume >1 cc

Concentration >2 x 106/cc

Initial ForwardMotility

>50%

Normal Morphology >60%

Page 38: Infertility Petrenko N., M.D. PhD Definitions Infertility –Inability to conceive after one year of unprotected intercourse (6 months for women over 35?)

Sperm Penetration AssaySperm Penetration Assay

• aka “zona-free hamster ova assay”

• Dynamic test of fertilization capacity of sperm

• Failure to penetrate at least 10% of zona-free ova consistent with male factor

• False positives and negatives exist

Page 39: Infertility Petrenko N., M.D. PhD Definitions Infertility –Inability to conceive after one year of unprotected intercourse (6 months for women over 35?)

Ovarian DisordersOvarian Disorders

• Anovulation– Clomiphene Citrate ± hCG– hMG– Induction + IUI (often done but unjustified)

• PRL– Bromocriptine– TSS if macroadenoma

• POF– ?high-dose hMG (not very effective)

Page 40: Infertility Petrenko N., M.D. PhD Definitions Infertility –Inability to conceive after one year of unprotected intercourse (6 months for women over 35?)

Ovarian DisordersOvarian Disorders

• Central amenorrhea– CC first, then hMG– Pulsatile GnRH

• LPD– Progesterone suppositories during luteal phase– CC ± hCG

Page 41: Infertility Petrenko N., M.D. PhD Definitions Infertility –Inability to conceive after one year of unprotected intercourse (6 months for women over 35?)

Ovulation InductionOvulation Induction

• CC– 70% induction rate, ~40% pregnancy rate– Patients should typically be normoestrogenic– Induce menses and start on day 5– With dosages, antiestrogen effects dominate– Multifetal rates 5-10%– Monitor effects with PK, pelvic exam

Page 42: Infertility Petrenko N., M.D. PhD Definitions Infertility –Inability to conceive after one year of unprotected intercourse (6 months for women over 35?)

hMG (Pergonal)hMG (Pergonal)

• LH +FSH (also FSH alone = Metrodin)

• For patients with hypogonadotrophic hypoestrogenism or normal FSH and E2 levels

• Close monitoring essential, including estradiol levels

• 60-80% pregnancy rates overall, lower for PCOS patients

• 10-15% multifetal pregnancy rate

Page 43: Infertility Petrenko N., M.D. PhD Definitions Infertility –Inability to conceive after one year of unprotected intercourse (6 months for women over 35?)

Risks Risks

CC• Vasomotor symptoms • H/A• Ovarian enlargement• Multiple gestation• NO risk of SAb or

malformations

hMG• Multiple gestation• OHSS (~1%)

– Can often be managed as outpatient

– Diuresis

– Severe cases fatal if untreated in ICU setting

Page 44: Infertility Petrenko N., M.D. PhD Definitions Infertility –Inability to conceive after one year of unprotected intercourse (6 months for women over 35?)

Fallopian TubesFallopian Tubes

• Tuboplasty

• IVF

• GIFT, ZIFT not options

Page 45: Infertility Petrenko N., M.D. PhD Definitions Infertility –Inability to conceive after one year of unprotected intercourse (6 months for women over 35?)

CorpusCorpus

• Asherman syndrome– Hysteroscopic lysis of adhesions (scissor)

– Postop Abx, E2

• Fibroids (rarely need treatment)– Myomectomy(hysteroscopic, laparoscopic, open)– ??UAE

• Uterine anomalies (rarely need treatment)– metroplasty

Page 46: Infertility Petrenko N., M.D. PhD Definitions Infertility –Inability to conceive after one year of unprotected intercourse (6 months for women over 35?)

CervixCervix

• Repeat PK test to rule out inaccurate timing of test

• If cervicitis Abx

• If scant mucus low-dose estrogen

• Sperm motility issues (? Antisperm AB’s)– Steroids?– IUI

Page 47: Infertility Petrenko N., M.D. PhD Definitions Infertility –Inability to conceive after one year of unprotected intercourse (6 months for women over 35?)

Peritoneum (Endometriosis)Peritoneum (Endometriosis)• From a fertility standpoint, excision beats medical

management• Lysis of adhesions • GnRH-a (not a cure and has side effects,

expense)• Danazol (side effects, cost)• Continuous OCP’s (poor fertility rates)• Chances of pregnancy highest within 6 mos-1 year

after treatment

Page 48: Infertility Petrenko N., M.D. PhD Definitions Infertility –Inability to conceive after one year of unprotected intercourse (6 months for women over 35?)

Male FactorMale Factor

• Hypogonadotrophism– hMG– GnRH– CC, hCG results poor

• Varicocoele– Ligation? (no definitive data yet)

• Retrograde ejaculation– Ephedrine, imipramine– AIH with recovered sperm

Page 49: Infertility Petrenko N., M.D. PhD Definitions Infertility –Inability to conceive after one year of unprotected intercourse (6 months for women over 35?)

Male FactorMale Factor

• Idiopathic oligospermia– No effective treatment – ?IVF– donor insemination

Page 50: Infertility Petrenko N., M.D. PhD Definitions Infertility –Inability to conceive after one year of unprotected intercourse (6 months for women over 35?)

Unexplained InfertilityUnexplained Infertility• 5-10% of couples• Consider PRL, laparoscopy, other hormonal tests,

cultures, ASA testing, SPA if not done• Review previous tests for validity• Empiric treatment:

– Ovulation induction– Abx– IUI– Consider IVF and its variants

• Adoption

Page 51: Infertility Petrenko N., M.D. PhD Definitions Infertility –Inability to conceive after one year of unprotected intercourse (6 months for women over 35?)

SummarySummary

• Infertility is a common problem• Infertility is a disease of couples• Evaluation must be thorough, but individualized• Treatment is available, including IVF, but can

be expensive, invasive, and of limited efficacy in some cases

• Consultation with a BC/BE reproductive endocrinologist is advisable

Page 52: Infertility Petrenko N., M.D. PhD Definitions Infertility –Inability to conceive after one year of unprotected intercourse (6 months for women over 35?)

Thank you!