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Infertility Infertility
Infertility
Infertility
Infertility Infertility David Toub, M.D. Medical Director Newton Interactive Microsoft are needed QuickTimeª Video to Utility

David Toub, M.D. Medical Director Newton Interactive

Microsoft are needed QuickTimeª Video to Utility see and this dec a p

Definitions

Definitions

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

Statistics

Statistics

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%

Etiologies

Etiologies

Sperm disorders 30.6% Anovulation/oligoovulation 30% Tubal disease 16% Unexplained 13.4% Cx factors 5.2% Peritoneal factors 4.8%

Associated

Associated Factors

Factors

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

Emotional

Emotional and

and Educational

Educational

Needs

Needs

Disease of couples, not individuals Feelings of guilt Where to go for information? Options Feelings of frustration and anger Support groups (e.g. Resolve)

Overview ofof Evaluation

Overview

Evaluation

Female

Ovary – Tube Corpus Cervix Peritoneum

Male

Sperm count and function Ejaculate characteristics, immunology Anatomic anomalies

The Most

The

Most Important

Important Factor

Factor inin

the Evaluation

the

Evaluation ofof the

the Infertile

Infertile

Couple

Couple Is:

Is:

HISTORY

HISTORY

History-General

History-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

History-Male

History-Male

History of pelvic infection Radiation, toxic exposures (include drugs) Mumps Testicular surgery/injury Excessive heat exposure (spermicidal)

History-Female

History-Female

Previous female pelvic surgery PID Appendicitis IUD use Ectopic pregnancy history DES (?relation to infertility) Endometriosis

History-Female

History-Female

Irregular menses, amenorrhea, detailed menstrual history Vasomotor symptoms Stress Weight changes Exercise Cervical and uterine surgery

When Not

When

Not toto Pursue

Pursue anan

Infertility Evaluation

Infertility

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

Physical

Physical Exam-Male

Exam-Male

Size of testicles Testicular descent Varicocoele Outflow abnormalities (hypospadias, etc)

Physical

Physical Exam-Female

Exam-Female

Pelvic masses Uterosacral nodularity Abdominopelvic tenderness Uterine enlargement Thyroid exam Uterine mobility Cervical abnormalities

Overall Guidelines

Overall

Guidelines for

for Work-

Work-

upup

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

Work-up byby Organ

Work-up

Organ Unit

Unit

Ovary

Ovary

Ovarian Function

Ovarian

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

Ovarian Function

Ovarian

Function

Three main types of dysfunction

– Hypogonadotrophic, hypoestrogenic (central) – Normogonadotrophic, normoestrogenic (e.g. PCOS) – Hypergonadotrophic, hypoestrogenic (POF)

BBT

BBT

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

Luteal Phase

Luteal

Phase Progesterone

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

Urinary LHLH Kits

Urinary

Kits

Very sensitive and accurate

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

Downside: price, obsession with timing of intercourse

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

Fallopian

Fallopian Tubes

Tubes

Tubal Function

Tubal

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)

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 H 2 O-based May be associated with fertility rates

Hysterosalpingography (HSG)

Hysterosalpingography

(HSG)

Can be uncomfortable Pregnancy test is advisable

Can detect intrauterine and tubal disorders but not always definitive

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

Falloposcopy

Falloposcopy

Hysteroscopic procedure with cannulation of the Fallopian tubes

Can be useful for diagnosis of intraluminal pathology

Promising technique but not yet widespread

Uterine

Uterine Corpus

Corpus

Corpus

Corpus

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

Cervix

Cervix

Cervical Function

Cervical

Function

Infection

– Ureaplasma suspected

Stenosis

– S/P LEEP, Cryosurgery, Cone biopsy (probably overstated)

Immunologic Factors

– Sperm-mucus interaction

Cervical Function

Cervical

Function

Tests:

Culture for suspected pathogens Postcoital test (PK tests)

Scheduled around 1-2d before ovulation (increased estrogen effect) 48 0 of male abstinence before test No lubricants Evaluate 8-12h after coitus (overnight is ok!) Remove mucus from cervix (forceps, syringe)

Cervical Function

Cervical

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

Male factors

factors

Problems with

Problems

with the

the PKPK test

test

Subjective Timing varies; may need to be repeated In some studies, “infertile” couples with an abnormal PK conceived successfully during that same cycle

Peritoneum

Peritoneum

Peritoneal

Peritoneal Factors

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

Male Factors

Male

Factors

Male Factors Male Factors

Male Factors

Male

Factors

Serum T, FSH, PRL levels Semen analysis Testicular biopsy Sperm penetration assay (SPA)

Male Factors-Semen

Male

Factors-Semen Analysis

Analysis

Collected after 48 0 of abstinence Evaluated within one hour of ejaculation If abnormal parameters, repeat twice, 2 weeks apart

Normal Semen

Normal

Semen Analysis

Analysis

Quality

Normal Value

Volume

 

Concentration

>1 cc >2 x 10 6 /cc

Initial Forward

>50%

Motility Normal Morphology

>60%

Sperm Penetration

Sperm

Penetration Assay

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

Treatment Options

Treatment

Options

Ovarian Disorders

Ovarian

Disorders

Anovulation

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

Ovarian Disorders Ovarian Disorders Anovulation Clomiphene Citrate ± hCG hMG Induction + IUI (often done but

PRL

Bromocriptine TSS if macroadenoma

POF

?high-dose hMG (not very effective)

Ovarian Disorders

Ovarian

Disorders

Central amenorrhea

– CC first, then hMG – Pulsatile GnRH

LPD

– Progesterone suppositories during luteal phase – CC ± hCG

Ovarian Matrix

Ovarian

Matrix

Gonadotropins

E 2

Treatment

 
     

High

Low

??high-dose hMG, r/o autoimmune diseases

WNL

WNL

  • CC ± hCG

Low

Low

  • CC first, then hMG

Ovulation Induction

Ovulation

Induction

CC

– 70% induction rate, ~40% pregnancy rate

– Patients should typically be normoestrogenic – Induce menses and start on day 5

Ovulation Induction Ovulation Induction • CC – 70% induction rate, ~40% pregnancy rate – Patients should

– With

dosages, antiestrogen effects dominate

– Multifetal rates 5-10% – Monitor effects with PK, pelvic exam

hMG

hMG (Pergonal)

(Pergonal)

LH +FSH (also FSH alone = Metrodin) For patients with hypogonadotrophic hypoestrogenism or normal FSH and E 2 levels

Close monitoring essential, including estradiol levels 60-80% pregnancy rates overall, lower for PCOS patients 10-15% multifetal pregnancy rate

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

Fallopian

Fallopian Tubes

Tubes

Tuboplasty IVF GIFT, ZIFT not options

Corpus

Corpus

Asherman syndrome

Hysteroscopic lysis of adhesions (scissor) Postop Abx, E 2

Fibroids (rarely need treatment)

Myomectomy(hysteroscopic, laparoscopic, open) ??UAE

Uterine anomalies (rarely need treatment)

metroplasty

Cervix

Cervix

Repeat PK test to rule out inaccurate timing of test

If cervicitis

Abx

Cervix Cervix Repeat PK test to rule out inaccurate timing of test If cervicitis Abx If

If scant mucuslow-dose estrogen Sperm motility issues (? Antisperm AB’s)

Steroids? IUI

Cervix Cervix Repeat PK test to rule out inaccurate timing of test If cervicitis Abx If

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

Male Factor

Male

Factor

Hypogonadotrophism

hMG GnRH CC, hCG results poor

Varicocoele

Ligation? (no definitive data yet)

Retrograde ejaculation

Ephedrine, imipramine AIH with recovered sperm

Male Factor

Male

Factor

Idiopathic oligospermia

– No effective treatment – ?IVF – donor insemination

Unexplained Infertility

Unexplained

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

Summary

Summary

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

Thank you!

Thank you!