INFERTILITYINFERTILITYINFERTILITYINFERTILITYPatricia M. DillonPatricia M. Dillon

Updated Spring 2009Updated Spring 2009ByBy

Professor Unn HidleProfessor Unn Hidle

Infertility affects about 5.3 million Americans, or Infertility affects about 5.3 million Americans, or 9 percent of the reproductive age population, 9 percent of the reproductive age population, according to the American Society for according to the American Society for Reproductive Medicine. Reproductive Medicine.

Usually 70-80% of couples that do not use any Usually 70-80% of couples that do not use any birth control conceive within a year and 80-90% birth control conceive within a year and 80-90% conceive within 2 years. conceive within 2 years.

2002 Statistics from the CDC2002 Statistics from the CDC

Number/Percent of women ages 15-44 with Number/Percent of women ages 15-44 with impaired fecundity (impaired ability to have impaired fecundity (impaired ability to have children): 7.3 million or 11.8%children): 7.3 million or 11.8%Number of married women ages 15-44 that are Number of married women ages 15-44 that are infertile (unable to get pregnant for infertile (unable to get pregnant for at least 12 at least 12 consecutive monthsconsecutive months): 2.1 million): 2.1 millionPercent of married women ages 15-44 that are Percent of married women ages 15-44 that are infertile: 7.4%infertile: 7.4%Number of women ages 15-44 who have ever Number of women ages 15-44 who have ever used infertility services: 7.3 millionused infertility services: 7.3 million

DefinitionDefinition Unprotected coital exposure for 12 months Unprotected coital exposure for 12 months

without conception. without conception. (15% - 20% of U.S. Couples)(15% - 20% of U.S. Couples)

A physician will generally initiate a medical A physician will generally initiate a medical evaluation only if a couple has not conceived after evaluation only if a couple has not conceived after one year of trying, or, if the woman is over 35, one year of trying, or, if the woman is over 35, after six months.after six months.

Of note, with the increase in infertility Of note, with the increase in infertility services/clinics in the later years, many services/clinics in the later years, many physicians will initiate infertility treatments sooner. physicians will initiate infertility treatments sooner.

Age Factor in InfertilityAge Factor in InfertilityIf the woman and man are approximately 25

years old, there is a 50% chance that the couple will conceive within 5 months. After age 35, the ability to become pregnant in the woman decreases noticeably. After menopause the ability to conceive disappears completely

Pregnancy rates for men decrease considerably after age 45. However, unlike women, a man’s sperm can fertilize an egg into senescence (old age).

Infertility ManagementInfertility Management

Assess and treat causes of infertilityAssess and treat causes of infertility

Provide Provide accurate informationaccurate information and dispel myths and dispel myths http://www.ihr.com/infertility/http://www.ihr.com/infertility/

Identify expectations and stressIdentify expectations and stress

Counsel couples and provide emotional supportCounsel couples and provide emotional support

Etiologic Factors in InfertilityEtiologic Factors in Infertility

Male FactorMale Factor 40%40%

Tubal FactorTubal Factor 40%40%

Ovulation ProblemOvulation Problem 10%10%

UnexplainedUnexplained 10%10%

Male Factors in Male Factors in InfertilityInfertility

Male infertility most commonly occurs because of: Anatomical inadequacies Poor sperm motility Short lifespan (a normal sperm has a lifespan

of about 4 days) Delivery issue Inadequate sperm production No sperm at all.

Male Factors in Male Factors in InfertilityInfertility

Etiological reasons for problems or lack of sperm include:

Endocrine dysfunction Cryptorchidism, varicocele, hypospadius, and

epispadius Exposure to toxic chemicals or radiation

(envirnomental) Genetic disorders, such as Klinefelter’s syndrome Testicular exposure to high temperatures such as

taking frequent, long, hot tub baths, occupations that increase heat to the testes (i.e. cab driver) and wearing constrictive clothing (i.e. tight jeans)

alcohol, tobacco, or drug abuse A severe mumps infection as an adolescent or adult.

VARICOCELEVARICOCELE

Courtesy of: Netter, F.H., The CIBA Collection & Miguel F. da Cunha, Ph.D., The University of Texas – Houston Health Science Center

Courtesy of www.andrologia.lazio.it/varicocele.jpg

(incompetent veins along the spermatic cord)

CRYPTORCHIDISCRYPTORCHIDISMM

Courtesy of UCLA Media book from: www.crump.ucla.edu:8801/NM-Mediabook/figures/REPRODUCTIVE/cryptorchidism.gif

From: Netter, F.H., The CIBA Collection

Courtesy: http://www.hypospadias.net/

HYPOSPADIAHYPOSPADIASS

http://www.rnweb.com/be_core/content/journals/k/data/2001/0202/screen/k2a089f01.jpg

Courtesy: Contemporary Pediatrics® Archive

Infants Curtesy of: http://cai.md.chula.ac.th

/lesson/atlas

Un-repaired Adult Male

Courtesy of: http://www.epispadias

-info.com/photos.html

FEMALFEMALE infantE infant

MALEMALEinfantinfant

From: Netter, F.H., The CIBA Collection

EPISPADIAEPISPADIASS

MALE FACTORSMALE FACTORS

Retrograde ejaculation (semen reflux into the bladder) due to Spinal Cord Damage resulting in paralysis

Beta blockers

Diabetic neuropathy

Early ejaculation

Inability to maintain an erection due to Blood pressure medications

Diseases such as Diabetes, Peyronie’s Disease

Anti-sperm antibody production

Damage to genitalia from infections of accessory glands or

radiation therapy

Male Factors Male Factors PhysiologicalPhysiological AbnormalitiesAbnormalities

Male Male Clinical EvaluationClinical Evaluation

Basic Assessment Procedures:Basic Assessment Procedures: Physical examination

A semen analysis to check for the number and quality of sperm

Blood tests to check for infections from sexually transmitted

diseases and for a hormone imbalance (endocrine profile: T, LH,

FSH, PRL)

Cultures of fluid from the penis to check for infections.

Semen Analysis ValuesSemen Analysis Values

1) Volume2) pH3) Sperm concentration4) Morphology5) Viability6) Forward motility7) Forward progression rate8) WBC

>2 ml 7.2-7.8>20x10(6)/ml>30% Normal>60% @ 1hr>50% are motile>3+ (Scale: 0-4)<1x10(6)/ml

Adjunctive Procedures:Adjunctive Procedures:

Postcoital test

Optimized Sperm Penetration Assay

Testicular biopsy

Antisperm antibody test

Male ClMale Clinical Evaluationinical Evaluation

FEMALE FACTORSFEMALE FACTORS

I.I. Anovulation / AmenorrheaAnovulation / AmenorrheaCauses:

Psychological dysfunction

Emotional stress

Genetic abnormalities

A menstrual cycle that is too brief

Nutritional deficiencies (anorexia, bulimia, etc.)

Endocrine problems (hormone imbalance) or CNS disease

Decreased progesterone production

Excessive body weight

Excessive exercise

Abuse of alcohol, drugs, tobacco, coffee, tea, or other

products containing caffeine.

Disorders of OvulationDisorders of Ovulation

II.II. Cervical mucus dysfunctionCervical mucus dysfunctionIII.III. Damaged fallopian tube or uterusDamaged fallopian tube or uterus

psychological dysfunction previous infection (pelvic inflammatory disease

or STDs) birth defects previous uterine/adenexa surgery (adhesions

and scar tissue) other conditions such as endometriosis,

fibroids, or an abnormally-shaped or tipped uterus.

IV.IV. Rare antigen-antibody reaction to Rare antigen-antibody reaction to spermsperm

V.V. Natural decline with ageNatural decline with age

Other Female Other Female Factors Factors

Female Factors:Female Factors:Clinical EvaluationClinical Evaluation

Postcoital test: evidence of:Quality, quantity and mobility of semen and quality of cervical mucus

adequacy of coital technique and anatomy

http://www.universityobgyn.com/postcoit.htm

BBT recording: evidence of ovulation http://www.early-pregnancy-tests.com/bbt-basal-body-

temperature.html

Endometrial biopsy and profile for

progesterone

Female Factors:Female Factors:Clinical EvaluationClinical Evaluation

Tests on a sample of cervical mucus and a sample of

tissue from the lining of your uterus to determine if

ovulation is occurring

Urine and blood tests on both to check for sexually

transmitted infections and hormonal imbalance

Assays on female to check the evidence of

sperm antibodies for semen allergy (http://www.

womenshealth.org/a/semen_allergy.htm)

Basal Body TemperatureBasal Body Temperature After ovulation every month, the ovary produces a large amount of

natural progesterone, which acts to increase a woman’s body temperature .

The basis of checking basal body temperature (BBT) =The increase can be very subtle, only one to two degrees

Fahrenheit; taken immediately upon awakening in the morning, since

any activity can also raise the BBT.

Since the BBT can be affected so easily:the use of over-the-counter ovulation predictor kits tend to

be more accurate and easier to perform. They measure the Leutinizing Hormone, which is made in the pituitary gland and spikes 24 to 48 hours prior to ovulation.

Female Factors:Female Factors:Clinical EvaluationClinical Evaluation

Tubal/peritoneal/uterine diagnostic tests:HysterosalpingographyHysterosalpingography

http://www.radiologyinfo.org/en/info.cfm?PG=hysterosalp

LaparoscopyLaparoscopy http://www.ivf.com/laprscpy.htmlhttp://www.ivf.com/laprscpy.html http://www.nhs.uk/conditions/Laparoscopy/Pages/http://www.nhs.uk/conditions/Laparoscopy/Pages/

Introduction.aspx?url=Pages/What-is-it.aspxIntroduction.aspx?url=Pages/What-is-it.aspx

HysteroscopyHysteroscopy http://www.gynalternatives.com/hsc.htm

Tubal/peritoneal/uterine diagnostic tests:

Adjunctive Procedures:

Follicular ultrasound

Thyroid panel

Prolactin

FSH

Summary of Diagnostic Summary of Diagnostic TestsTests

TESTSTESTS ADJUNCTIVE TESTSADJUNCTIVE TESTS

Male:Male: Semen analysis

FemaleFemale:: Ovulation history Progesterone BBT Endometrial biopsy

HysterosalpingographyHysterosalpingography LaparoscopyLaparoscopy HysteroscopyHysteroscopy

Postcoital testAntisperm antibodiesSperm penetration

Follicular ultrasoundProlactinThyroid panelFSH

EndometriosisEndometriosishttp://www.ivf.com/endohtml.html

Definition:

““Growth of endometrial ectopic tissue”Growth of endometrial ectopic tissue” Transformation of intra-abdominal tissue into Transformation of intra-abdominal tissue into

endometrial-like tissue endometrial-like tissue

Distant sitesDistant sites

Abdominal cavityAbdominal cavity

Myths: OnlyOnly affects women over 30 affects women over 30

OnlyOnly affects white women affects white women

Does not occur before menarcheDoes not occur before menarche

Confined to nulliparous womenConfined to nulliparous women

EndometriosisEndometriosis

Manifestations: DysmenorrheaDysmenorrhea

Diffuse pain (bladder, rectum areas)Diffuse pain (bladder, rectum areas)

Low back painLow back pain

Premenstrual spottingPremenstrual spotting

Dyspareuria (pain with intercourse)Dyspareuria (pain with intercourse)

EndometriosisEndometriosis

WithWith ovarian problems as a result of adhesions ovarian problems as a result of adhesions

WithoutWithout ovarian involvement from: ovarian involvement from:

Increased prostaglandins =Increased prostaglandins =Decreased tubal motility, Decreased tubal motility, oror

Impaired follicular maturation, Impaired follicular maturation, oror

Impaired corpus luteum functionImpaired corpus luteum function

Endometriosis and Endometriosis and InfertilityInfertility

Principle: estrogen stimulates growthPrinciple: estrogen stimulates growthApproach: anti-estrogenic agentsApproach: anti-estrogenic agentsUntil late 70s: oral contraceptivesUntil late 70s: oral contraceptivesModern approach: DanazolModern approach: DanazolResults (Danazol):Results (Danazol):

Hypoestrenism --> stops growth of implantsHypoestrenism --> stops growth of implants Amenorrhea --> stops new bleedingAmenorrhea --> stops new bleeding

Treatment of Treatment of Endometriosis: Endometriosis: Hormonal ApproachHormonal Approach

http://www.mayoclinic.com/health/endometriosis/DS00289/DSECThttp://www.mayoclinic.com/health/endometriosis/DS00289/DSECTION=treatments-and-drugsION=treatments-and-drugs

Weight gainWeight gain FatigueFatigue Decreased breast sizeDecreased breast size Acne and oily skinAcne and oily skin Deepening of voiceDeepening of voice Hot flushesHot flushes Muscle crampsMuscle cramps Emotional labilityEmotional lability Liver damageLiver damage

Treatment of Endometriosis:Treatment of Endometriosis:Adverse Events (Danazol)Adverse Events (Danazol)

Occur in 80% ofwomen, but only

10% consider them significantenough to stop

treatment

Other hormonal treatment Other hormonal treatment approachesapproaches

Hormonal contraceptives:Hormonal contraceptives: Birth control pills, patches and the vaginal ring Control the hormones responsible for the buildup of endometrial

tissue Using hormonal contraceptives can reduce or eliminate the pain

of mild to moderate endometriosis.

Gonadotropin-releasing hormone (Gn-RH) agonists Gonadotropin-releasing hormone (Gn-RH) agonists and antagonists:and antagonists:

Block the production of ovarian-stimulating hormones Prevents menstruation and dramatically lowers estrogen levels Causes endometrial implants to shrink Gn-RH agonists and antagonists can force endometriosis into These drugs create an artificial menopause that can sometimes

lead to troublesome side effects, such as hot flashes and vaginal dryness.

Other hormonal treatment Other hormonal treatment approachesapproaches

Medroxyprogesterone (Depo-Provera):Medroxyprogesterone (Depo-Provera): Injectable drug effective in halting menstruation and the growth

of endometrial implants Relieves the signs and symptoms of endometriosis

Aromatase inhibitors:Aromatase inhibitors: Known for their effectiveness in treating breast cancer May be useful for endometriosis Work by blocking the conversion of hormones such as

androstenedione and testosterone into estrogen and by blocking the production of estrogen from endometrial implants

This deprives endometriosis of the estrogen it needs to grow. Early studies suggest that aromatase inhibitors are at least as

good as other hormonal approaches and may be better tolerated.

Recommended if > 1cmRecommended if > 1cmGoal is to restore anatomy & destroy Goal is to restore anatomy & destroy

growthsgrowthsConservative & Radical ApproachesConservative & Radical ApproachesDanger is still developing adhesions!Danger is still developing adhesions!

Treatment of Endometriosis:Treatment of Endometriosis:Surgical ApproachSurgical Approach

TREATMENT SUCESS AFTER SURGICAL TREATMENT SUCESS AFTER SURGICAL REPAIRREPAIR

SSTATISTICS COURTESY OF : TATISTICS COURTESY OF : Miguel F. daMiguel F. da Cunha, Ph.D.Cunha, Ph.D.

The University of Texas - HoustonThe University of Texas - HoustonHealth Science CenterHealth Science Center

Varicocele repairVaricocele repair

50-70%50-70%

Probability of pregnancy: Probability of Probability of pregnancy: Probability of

semen improvement 25-50%semen improvement 25-50%

VasoepididymostomyVasoepididymostomy

Patency rates: 60-70%Patency rates: 60-70%

Probability of pregnancy: >30%Probability of pregnancy: >30%

VasovasostomyVasovasostomy

Overall pregnancy rate: 50-60%Overall pregnancy rate: 50-60%

Ejaculatory disorders:Ejaculatory disorders: Sympathomimetic drugs: 20-30%

Retrograde ejaculation:Retrograde ejaculation: Sperm rescue from urine: variable success rate

Antisperm antibody:Antisperm antibody: Immunosuppressive drugs: variable success

TREATMENT OUTCOMESTREATMENT OUTCOMESwith ejaculatory problemswith ejaculatory problemsTREATMENT OUTCOMESTREATMENT OUTCOMES

with ejaculatory problemswith ejaculatory problems

ASSISTED REPRODUCTIVE ASSISTED REPRODUCTIVE TECHNIQUESTECHNIQUES

http://www.nlm.nih.gov/medlineplus/infertility.html

IUI (intrauterine insemination) http://www.mayoclinic.com/print/intrauterine-insemination/

MY00104/METHOD=print&DSECTION=all IVF (in vitro fertilization)

http://www.ivf.com/ivffaq.html ZIFT (zygote intrafallopian transfer)

http://www.monlezun.com/art-5.htm GIFT (gamete intrafallopian transfer)

http://www.monlezun.com/art-4.htm ICSI (intracytoplasmic sperm injection)

http://www.asrm.org/Patients/FactSheets/ICSI-Fact.pdf Of note, ZIFT, GIFT and ICSI are very rarely used

Food For Thought……Food For Thought……

Ethical issuesEthical issues““Designer Babies”Designer Babies”Sperm donationSperm donationPreserving ovumPreserving ovum““Wombs For Hire”Wombs For Hire”Surrogacy Surrogacy Insurance issuesInsurance issuesAnd more……….And more……….

THE ENDTHE END