Raspa Infertility Final(Optimized)

7/30/2019 Raspa Infertility Final(Optimized)

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Objectives:

List the common causes of male and female

infertility

Begin an infertility evaluation, ordering initialtests

Prescribe simple treatments for infertile

couples Facilitate appropriate referral to infertility

specialists


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Infertility:

Inability to conceive after 12 months of

frequent, unprotected intercourse

Some however begin initial work-up after 6months as the fecundability (ability to

conceive) decreases as times passes,

particularly if history suggests infertility or if

female partner older than 35 (decreased

ovarian function)


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Is infertility common?

10-15% of couples in the US

1.2 million women visited their primary caredoctor for infertility in 2002


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Risk Factors

Smokingdecreased conception

Alcoholincreased infertility

Stress (acupuncture helps)

IUD removaltakes longer to conceive

Increased agefathers over 40

Gulf war vets

Inflammatory bowel disease


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Other Factors

No increased risk with male underwear type

or

Ruptured appendix Unknown effects of environmental

estrogensPCBs

Nifedipine may decrease male fertility?


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Timing Factors

Sperm live 48-72 hours

Eggs live 12 hours

Fertility Focused Intercourse is important


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Etiology:

Male: 20%

Female: 38%

Mixed: 27%

Unexplained: 15%

Importance of evaluation of both partners

WHO 1982-1985 multi-center study


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Causes of Female Infertility

Ovulation disorders-25%

Endometriosis-25%

Pelvic Adhesions-12%

Tubal Blockage-11%

Other Tubal Factors-11%

Hyperprolactinemia-7%WHO Technical Report Series 1992


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Female Causes:

Cervical factorsbad mucus, antibodies, infection

Uterine Factorssubmucosal fibroids, bicornuate

uterus, Ashermans syndrome

Tubal factorsPID, endometriosis, post-op

adhesions

Ovary Factorsanovulation, luteal phase defect,

toxins (chemotherapy) Bad eggschromosomal (Turners Syndrome)


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Female H&P:

Gs and Ps

PMH including STD Hx

Medications

Substance Use Menstrual Hx

Age at onset? Regular? Duration? Premenstral Sx?

Endometriosis Sx: dysmenorrhea, dyspareunia,

Endocrine Sx: galactorrhea, hirsuitism, fatigue,constipation, weight gain, etc

Exercise


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Female H&P:

Physical Exam:

Vitals, BMI

Skin: Acne, hirsuitism

Thyroid: enlargement

Breast: galactorrhea, development

Pelvic: uterine size, tenderness, discharge,

masses, development


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Initial Counseling:

Frequency and timing of intercourse

Fertile Interval: 5 days preceding ovulation and day of

ovulation

Smoking Alcohol

Caffeine

Stress Body weight (Ideal BMI is 20-25)

Prenatal vitamins


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Initial Female Work-Up:

Ovulation???:

Regular Menses with Premenstrual Sx:

Some confirm ovulation by history/chartingalone

Irregular Menses or desire confirmation:

Charting

Progesterone on cycle day 21

LH surge (home urinary kits)


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Charting:


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Menstrual Cycle:


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Ovulation Disorders:

WHO Classification:

1: Hypogonadotropic Hypogonadal

5-10%

2: Normogonadotropic Normoestrogenic

70-85%

Includes PCOS

3: Hypergonadotropic Hypoestrogenic 10-30%

Hyperprolactinemia


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Anovulation:

Determination of cause/class:

FSH/LH

Estradiol (E2)

Progesterone

Prolactin/TSH

Comprehensive Metabolic Panelliver, renal

Testosterone, Androstenedione, DHEA-S,

17-OH Progesterone


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Class 1 Anovulation:

Hypogonadotropic Hypogonadal Low FSH and low estradiol

Due to either decreased hypothalamic secretion

of GnRH (Kallmans) or pituitary insensitivity toGnRH

Results in decreased pituitary release of FSH

FSH stimulates follicular maturation and thus

estradiol secretion


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Class 1 Treatment:

Gonadotropins (FSH/LH)

Indications:

Class 1 anovulatory pts Class 2 anovulatory pts who have failed initial tx

Risks:

Multiple gestations Ovarian hyperstimulation


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Class 1 Treatment:

Gonadotropins (FSH/LH)

Dose:

Step-up vs Step-down protocols Monitoring:

Transvaginal US q2-3 days to monitor follicles

and timing of hCG dose to induce ovulation of

dominant follicle

Given by Reproductive Endocrinologists


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Normogonadotropic Normoestrogenic:

Normal levels of FSH and estrodiol

FSH secretion during follicular phase is sub-

normal

May ovulate intermittently, particularly if have

oligomenorrhea

Causes: PCOS, Hyperthyroidism, Androgenichormones from tumors, liver or renal disease,

Cushings (work-up is here)


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Treatment of Class 2 Anovulation:

Check lab results from anovulatory work upand treat as appropriate

PCOS: increased BMI, hirsuitism, anovulation,

2:1 LH:FSH ratio Best treatment is achieve ideal body weight

or at least a 10% reduction in wt.

Best BMI 20-25 Low body wt or high stress decreases

GnRH, can be like WHO 1 .


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Class 2 Treatment: Metformin

Improves insulin insensitiviy

Restores ovulation in 50% of PCOS

Titrate dose to minimize side effects

Minimal effect on hirsuitism Trial for 6 months with continued charting to eval

for ovulation

Not FDA approved for combo with Clomiphene butsome trials have shown benefit of combo whileothers show similar success rates as Clomiphenealonecombined effect 60% preg rate in PCOS


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Class 2 Treatment: Clomiphene

Induces ovulation by increased gonadotropinrelease

Dose: 50mg days 5-9; up to 100mg daily if needed

Intercourse timing and frequency; +/- urine LH kit +/- Metformin (PCOS)

+/- Intrauterine Insemination (cervical factors)

6 cycles max

Letrazole is alternative with similar efficacy to

Clomiphene


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Class 2 Treatment: Aromatase

Inhibitors Block final step of estrogen synthesis

Letrozol 2.5 - 5mg daily on days 3-7

(anastazol) or 25mg once day 3.

Intercourse timing and frequency; +/- urineLH kit

Similar efficacy to clomiphene

Minimal side effects

Lower incidence of multiple gestations


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Hypergonadotropic Hypoestrogenic:

High FSH and low estradiol

FSH is inappropriately high due to lack of

negative feedback from estradiol

Causes: Premature ovarian failure or Ovarian

resistance

Resistant to treatment


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Rare

Poor Prognosis--best test is Antimullerian

Hormonehigh is good, less than 2.5 is bad Clue given with Clomiphene Challenge Test

Test FSH on Day 3

Clomiphene Day 5-9 Test FSH on Day 10

If either FSH greater than 10, reduced ovarian

function.


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Anovulatory Treatment Overview:

WHO Class 1: GnRH problemtreat with

GnRH pump and support (Not available in

US) or Gonadotropins (Refer)

WHO Class 2: Most patients herewe can

treat

WHO Class 3: Ovarian failurelittle hope

with any therapy (Refer)

Hyperprolactinemia: RxDrugs or Surgery


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Regular Menses:

Ovulatory cycles confirmed by:

Charting x 3 months

Cycle day 21 Progesterone

LH surge

Fertility focused intercourse


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Ovulation confirmed:

Lifestyle changes

Chlamydia/GC test

Male partner testing

Good Cervical Mucus Mucus enhancermucinex, vit B6

Increase mucus with antibiotics day 9-14

Prolactin, TSH

Luteal phase defect? < 10 days

Fertility focused intercourse x 3 months


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Further work-up:

Check Hysterosalpingogram (HSG)

Tubal factors: patency

Uterine factors: anatomy, submucosal fibroids

Oil based contrast has a good track record ofpregnancy after HSG

If 3 more months go by will need laparoscopy to

check for endometriosis, adhesions, ovarianproblems (hydrosalpinges)

Key to treatment is find the problem and treat


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Male Infertility

Male factor infertility 20% of couples

Contributes to 30-40%

Azoospermiano sperm

Aspermiano semen

Oligospermiadecreased normal sperm

Need 2 sperm samples after 48-72 hourabstinence say experts

AUA and ASRM Practice Committee Reports2001


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Male Infertility

Pre-testicularendocrinetreatablerare

Testicularspermatogenesisuntreatableexcept varicoceles

Post-testicular40% obstruction

History

Mumps, Trauma, Infection, Chemo, Radiation,

HeatUnderwear doesnt matter Family History?

Prior Fertility?


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Male Workup

Exam

Male secondary sex characteristics

Assure vas deferens bilaterally

Testis size

Varicocele


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Sperm Count

FertileOver 48 million, Over 63% motile,

Over 12% normal morphology

Likely Not FertileLess than 13.5

million,Less than 32% motile, Less than 9%

normal morphology

In the middleindeterminateNew England J Med 2001:345:1388


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Lab Workup

Abnormal semen--


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Male Causes

Absense of vas deferens

Renal agenesis in 10-20%

Cystic Fibrosismost will have congenital

bilateral absence of vas deferens

CFTR mutationif positive, check female

Bilateral testicular atrophy

Low FSH and TKallman or Pituitary tumor

Check prolactin and MRI


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Duct Obstruction

May be treatable

If normal volumeeither disordered

spermatogenesis or near testicular

obstruction

If FSH upspermatogenesis problem

If FSH is normal, biopsy testis

Low sperm volumeejaculatory dysfunction

Consider TRUS


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Azoospermia

Check chromosome7% abnormal

2/3 Klinefelters XXY

Microdeletions on Y chromosome seen with

PCR, not on karyotype

Assay when non-obstructive oligospermia with

sperm less than 5 million


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Unexplained Infertility

Most likely combined male and female

factors

Treatments are multiple but many

unsatisfying

Time alone may be treatment or

Refer


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Advanced Reproductive

Technologies (ART)

Most deliver normal infants

BUT: Infertility treatment associated with

increased risk of adverse pregnancy

outcomes

Placental abruption, fetal loss 2nd trimester,

preeclampsia, previa, C/S, ovarian torsion


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Advanced Reproductive

Technologies (ART)

Multiple births and birth defects, preterm

and low birth weight, cerebral palsey

Insufficient evidence regarding risks and

benefits for IVF for unexplained infertility

18-22% success per cycle


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Other Drugs

Metformin may induce ovulation inanovulatory women withouthyperandrogenism

ASA doesnt help Testosterone doesnt help for males

Ginseng may help increase sperm count

and motility Chasteberry associated with increased

pregnancy ratelevel 2 evidence


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Other considerations

Intrauterine insemination (IUI) better if

antibodies or if subfertile male

As effective, cheaper, and safer than IVF for

idiopathic infertilityLancet 2000

Varicocele repair probably doesnt help

FSH (HCG) therapy for subfertilitymixedresults


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Pregnancy Support:

After conception progesterone

supplementation has been shown to be

effective in reducing miscarriage,

preeclampsia and preterm birthin IVF andwithout

Can use HCG as wellstimulates estrogen

and progesterone


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Pregnancy Support:

Counselinggroupimproved pregnancy

rate

Accupuncture works for IVFlikely works

for normal conception if stress is an issue


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Summary:

Consider causes of infertility

Do systematic workupovulatory vs non-

ovulatory

If ovulatory, consider tubal and male factors

Find the cause and treat.

Refer when unable to find cause or if unableto perform treatment


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Questions?

Documents

Raspa Infertility Final(Optimized)