InfertilityInfertilityVersionVersion 1 1

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Infertility: Infertility: IntroductionIntroduction

Significant social and medical problem affecting Significant social and medical problem affecting couples worldwidecouples worldwide Average incidence of infertility is about 15% globallyAverage incidence of infertility is about 15% globally

varies in different populationsvaries in different populations Some causes can be detected and treated, whereas Some causes can be detected and treated, whereas

others cannotothers cannot unexplained infertility constitutes about 10% of unexplained infertility constitutes about 10% of

all casesall cases

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Definition of InfertilityDefinition of Infertility

Inability to conceive after 12 months of having sexual Inability to conceive after 12 months of having sexual intercourse with average frequency (2 to 3 times per intercourse with average frequency (2 to 3 times per week), without the use of any form of birth control week), without the use of any form of birth control

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Types of InfertilityTypes of Infertility

Primary infertilityPrimary infertility couple has never produced a pregnancycouple has never produced a pregnancy

Secondary infertilitySecondary infertility woman has previously been pregnant, regardless of the woman has previously been pregnant, regardless of the

outcome, andoutcome, and now is unable to conceivenow is unable to conceive

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Conception and FertilityConception and Fertility

The chances of conceiving in any given menstrual The chances of conceiving in any given menstrual cycle is less than 20%cycle is less than 20%

Main events necessary for pregnancy to occur are:Main events necessary for pregnancy to occur are: ovulationovulation fertilizationfertilization implantationimplantation

Any condition that interferes with these events may Any condition that interferes with these events may result in infertility result in infertility

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17%

Factors Affecting Fertility:Factors Affecting Fertility:Frequency of IntercourseFrequency of Intercourse

Coital frequency is positively correlated with pregnancy Coital frequency is positively correlated with pregnancy ratesrates

Frequency of intercourse

Probability ofconception

(within 6 months)

1 timeper week

3 timesper week

50%

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Factors Affecting Fertility:Factors Affecting Fertility:Timing of IntercourseTiming of Intercourse

Intercourse just before ovulation maximizes the Intercourse just before ovulation maximizes the chance of pregnancychance of pregnancy Sperm survives as long as 5 days in the female Sperm survives as long as 5 days in the female

genital tractgenital tract Ovum life expectancy is about 1 day if not fertilizedOvum life expectancy is about 1 day if not fertilized Sperm should be available in the female genital Sperm should be available in the female genital

tract at or shortly before ovulationtract at or shortly before ovulation

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Factors Affecting Fertility:Factors Affecting Fertility:STIs and Other InfectionsSTIs and Other Infections

Gonorrhea and chlamydia can cause:Gonorrhea and chlamydia can cause: in women: pelvic inflammatory disease (major cause of in women: pelvic inflammatory disease (major cause of

tubal infertility) and cervicitistubal infertility) and cervicitis in men: urethritis, epididymitis, accessory gland infectionin men: urethritis, epididymitis, accessory gland infection

Mumps, leading to orchitis, may cause secondary Mumps, leading to orchitis, may cause secondary testicular atrophytesticular atrophy

Other infections that may affect fertility include Other infections that may affect fertility include tuberculosis, toxoplasmosis, malaria, schistosomiasis tuberculosis, toxoplasmosis, malaria, schistosomiasis and leprosyand leprosy

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Factors Affecting Fertility Factors Affecting Fertility (Continued)(Continued)

Age of the womanAge of the woman after 40 the fertility rate decreases by 50% while the risk after 40 the fertility rate decreases by 50% while the risk

of miscarriage increasesof miscarriage increases Age of the manAge of the man

increased age affects coital frequency and sexual increased age affects coital frequency and sexual functionfunction

NutritionNutrition for women, weight 10% to15% below normal or obesity for women, weight 10% to15% below normal or obesity

may lead to less frequent ovulation and reduced fertilitymay lead to less frequent ovulation and reduced fertility

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Factors Affecting FertilityFactors Affecting Fertility (Continued)(Continued)

Factors that can contribute to Factors that can contribute to fertility problems include:fertility problems include: toxic agents, such as lead, toxic toxic agents, such as lead, toxic

fumes and pesticidesfumes and pesticides smoking and alcoholsmoking and alcohol

All these factors may cause:All these factors may cause: in women: reduced conceptions and in women: reduced conceptions and

increased risk of fetal wastageincreased risk of fetal wastage in men: reduced sex drive and in men: reduced sex drive and

sperm countsperm count

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Infertility: Infertility: Female and Male FactorsFemale and Male Factors

Infertility may be a result of one or more male or Infertility may be a result of one or more male or female factorsfemale factors

Female and male factors are equally responsible Female and male factors are equally responsible for infertility (30% to 40% each)for infertility (30% to 40% each) in 20% of cases there is a combination of both factorsin 20% of cases there is a combination of both factors

Evaluating both partners is essentialEvaluating both partners is essential

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Requirements for Female FertilityRequirements for Female Fertility

Vagina capable of receiving spermVagina capable of receiving sperm Normal cervical mucus to allow sperm passageNormal cervical mucus to allow sperm passage Ovulatory cyclesOvulatory cycles Patent fallopian tubesPatent fallopian tubes Uterus capable of developing and sustaining Uterus capable of developing and sustaining

pregnancypregnancy Adequate hormonal status to maintain pregnancyAdequate hormonal status to maintain pregnancy

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Requirements for Female Fertility Requirements for Female Fertility (Continued)(Continued)

Adequate sexual drive and sexual functionAdequate sexual drive and sexual function Normal immunologic responses to accommodate Normal immunologic responses to accommodate

sperm and conceptussperm and conceptus Adequate nutritional and health status to maintain Adequate nutritional and health status to maintain

nutrition and oxygenation of placenta and fetusnutrition and oxygenation of placenta and fetus

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Requirements for Male FertilityRequirements for Male Fertility

Normal spermatogenesis in order to fertilize egg:Normal spermatogenesis in order to fertilize egg: sperm countsperm count motilitymotility biological structure and functionbiological structure and function

Normal ductal system to carry sperm from the Normal ductal system to carry sperm from the testicles to the penistesticles to the penis

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Requirements for Male Fertility Requirements for Male Fertility (Continued)(Continued)

Ability to transmit sperm to vagina achieved Ability to transmit sperm to vagina achieved throughthrough adequate sexual driveadequate sexual drive ability to maintain erectionability to maintain erection ability to achieve normal ejaculationability to achieve normal ejaculation placement of ejaculate in vaginal vaultplacement of ejaculate in vaginal vault

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Causes of Female InfertilityCauses of Female Infertility

Pelvic inflammatory disease (PID) leading to Pelvic inflammatory disease (PID) leading to blocked or damaged fallopian tubesblocked or damaged fallopian tubes may interfere with fertilization and transport of eggmay interfere with fertilization and transport of egg

Ovarian dysfunction resulting in absent or Ovarian dysfunction resulting in absent or diminished egg productiondiminished egg production

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Causes of Female InfertilityCauses of Female Infertility (Continued)(Continued)

Local factors in the uterus and cervixLocal factors in the uterus and cervix may interfere with implantation and woman’s ability to may interfere with implantation and woman’s ability to

carry pregnancy to termcarry pregnancy to term Luteal phase defectLuteal phase defect

results in low production of progesteroneresults in low production of progesterone may lead to early miscarriagemay lead to early miscarriage

Production of anti-sperm antibodiesProduction of anti-sperm antibodies can interfere with fertilizationcan interfere with fertilization

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Causes of Male InfertilityCauses of Male Infertility

Conditions that affect quality or quantity of sperm Conditions that affect quality or quantity of sperm may lead to infertilitymay lead to infertility

These conditions include:These conditions include: varicocelevaricocele primary testicular failureprimary testicular failure accessory gland infectionaccessory gland infection idiopathic low sperm motilityidiopathic low sperm motility

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Causes of Infertility AffectingCauses of Infertility AffectingBoth PartnersBoth Partners

PsychologicalPsychological sexual behavior may reflect couple’s desire sexual behavior may reflect couple’s desire notnot to to

have childrenhave children Immunological incompatibilityImmunological incompatibility

may cause sperm agglutinationmay cause sperm agglutination Unknown causesUnknown causes

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Basic Work-up for InfertilityBasic Work-up for Infertility

Evaluating both partners is essentialEvaluating both partners is essential Detailed history andDetailed history and physical examination for physical examination for

bothboth Semen analysisSemen analysis Evidence of ovulationEvidence of ovulation Evidence of fallopian tubes Evidence of fallopian tubes

patencypatency Postcoital testPostcoital test

still performed by some cliniciansstill performed by some clinicians not found valid by some studies not found valid by some studies

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Fertility Evaluation ProcedureFertility Evaluation Procedure

Couple should be informed about:Couple should be informed about: different causes of infertilitydifferent causes of infertility tests and procedures required to tests and procedures required to

make a diagnosismake a diagnosis various therapeutic possibilitiesvarious therapeutic possibilities

Couple’s interview is conducted Couple’s interview is conducted together as well as separately to together as well as separately to obtain confidential informationobtain confidential information R

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Fertility Evaluation:Fertility Evaluation:General and Sexual HistoryGeneral and Sexual History

General historyGeneral history occupation and backgroundoccupation and background use of tobacco, alcohol and drugsuse of tobacco, alcohol and drugs history of abdominal surgery and earlier history of abdominal surgery and earlier

diseases/infectionsdiseases/infections Sexual historySexual history

sexual disturbances or dysfunction such as vaginismus, sexual disturbances or dysfunction such as vaginismus, dyspareunia or erectile dysfunctiondyspareunia or erectile dysfunction

sexually transmitted infectionssexually transmitted infections

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Fertility Evaluation: Fertility Evaluation: Obstetric and Obstetric and Gynecological HistoryGynecological History

Reproductive historyReproductive history Gynecological historyGynecological history Age at menarcheAge at menarche Menstrual periods: duration and intervalsMenstrual periods: duration and intervals Previous contraceptive usePrevious contraceptive use Previous testing and treatment for infertilityPrevious testing and treatment for infertility

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Fertility Evaluation: Fertility Evaluation: General and General and Gynecological ExaminationGynecological Examination

Visual evaluation andpelvic exam for women

to rule out:

Visual evaluation andpelvic exam for women

to rule out:

Visual evaluation andpenile exam for men

to rule out:

Visual evaluation andpenile exam for men

to rule out:

EndocrinopathyEndocrinopathy

Congenital anomaliesCongenital anomalies

Uterine hypoplasiaUterine hypoplasia

Cervical lesionsCervical lesions

DyspareuniaDyspareunia

HypogonadismHypogonadism

TumorsTumors

Epididymal cystsEpididymal cysts

CryptorchidismCryptorchidism

HydroceleHydrocele

VaricoceleVaricocele

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Fertility Evaluation of Female Partner: Fertility Evaluation of Female Partner: Evidence of OvulationEvidence of Ovulation

Ovulation can be established based on:Ovulation can be established based on: Urine testUrine test

measures the LH in urine to detect if and when ovulation measures the LH in urine to detect if and when ovulation occurredoccurred

Basal body temperature chartBasal body temperature chart temperature is measured every morning, before woman temperature is measured every morning, before woman

gets out of bed gets out of bed elevation in temperature indicates ovulationelevation in temperature indicates ovulation

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Fertility Evaluation of Female Partner: Fertility Evaluation of Female Partner: Evidence of Ovulation Evidence of Ovulation (Continued)(Continued)

Progesterone testProgesterone test progesterone level in blood is measured on days 21 or 22 progesterone level in blood is measured on days 21 or 22

of 28-day cycleof 28-day cycle

Endometrial biopsyEndometrial biopsy done during premenstrual phasedone during premenstrual phase detects if endometrium undergoes expected changes detects if endometrium undergoes expected changes

(consistent with ovulation and production of progesterone)(consistent with ovulation and production of progesterone)

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Fertility Evaluation of Female Partner: Fertility Evaluation of Female Partner: Other TestsOther Tests

Hysterosalpinogram (HSG)Hysterosalpinogram (HSG) to determine whether fallopian tubes are blockedto determine whether fallopian tubes are blocked

LaparoscopyLaparoscopy to evaluate for pelvic disease, such as endometriosis, and to evaluate for pelvic disease, such as endometriosis, and

check patency of fallopian tubescheck patency of fallopian tubes HysteroscopyHysteroscopy

to evaluate condition of uterine cavity (polyps, fibroids)to evaluate condition of uterine cavity (polyps, fibroids)

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Fertility Evaluation of Male Partner: Fertility Evaluation of Male Partner: Semen AnalysisSemen Analysis

Semen is studied for a number of factors including:Semen is studied for a number of factors including: Volume (1.5 cc to 5.0 cc)Volume (1.5 cc to 5.0 cc) Number of sperm present (> 20 million/ml)Number of sperm present (> 20 million/ml) Sperm motility (> 60%) and forward progression Sperm motility (> 60%) and forward progression

(more than 2 on scale 1 to 4)(more than 2 on scale 1 to 4) Morphology (> 60% normal forms)Morphology (> 60% normal forms) Presence of any infectionPresence of any infection

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Fertility Evaluation of Male Partner: Fertility Evaluation of Male Partner: Other TestsOther Tests

Urine analysis: to rule out infectionUrine analysis: to rule out infection Endocrine tests: to measure concentrations of Endocrine tests: to measure concentrations of

hormones testosterone, FSH and LHhormones testosterone, FSH and LH Anti-sperm antibodiesAnti-sperm antibodies Sperm penetration assay: to establish ability of Sperm penetration assay: to establish ability of

sperm to penetrate eggsperm to penetrate egg Postcoital test (low validity): to establish ability of Postcoital test (low validity): to establish ability of

sperm to penetrate cervical mucussperm to penetrate cervical mucus

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Treatment Possibilities:Treatment Possibilities:Female InfertilityFemale Infertility

Ovulation disordersOvulation disorders Ovulation-inducing drugsOvulation-inducing drugs

HyperprolactinemiaHyperprolactinemia Prolactin-suppressing drugs

Prolactin-suppressing drugs

Uterine and tubal abnormalities

Uterine and tubal abnormalities Surgical proceduresSurgical procedures

Cervical mucus problemsCervical mucus problems Intrauterine inseminationIntrauterine insemination

EndometriosisEndometriosis Suppressing hormones or surgical procedure

Suppressing hormones or surgical procedure

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Treatment of Female Infertility:Treatment of Female Infertility:Induction of OvulationInduction of Ovulation

Involves the use of medication to stimulate Involves the use of medication to stimulate development of one or more mature folliclesdevelopment of one or more mature follicles

Success rates vary considerably and depend on Success rates vary considerably and depend on age of the woman, the type of medication used, age of the woman, the type of medication used, whether there are other infertility factors present in whether there are other infertility factors present in the couple and other reasonsthe couple and other reasons

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Treatment of Female Infertility:Treatment of Female Infertility:Ovulation Induction AgentsOvulation Induction Agents

induces release of gonadotropins

Gonadotropins

Clomiphene citrate

Gonadotropin releasing hormone analogs

similar in structure to natural GnRH, provoke a massive release of GnRH into the circulation

human menopausal gonadotropin (HMG), which contains equal quantities of FSH and LH

Bromocriptine suppresses production of prolactin

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Treatment of Female Infertility:Treatment of Female Infertility:Intrauterine InseminationIntrauterine Insemination

A fertility procedure in which sperm are washed, A fertility procedure in which sperm are washed, concentrated and injected directly into a woman’s concentrated and injected directly into a woman’s uterusuterus

Increases the number of sperm in the fallopian tubesIncreases the number of sperm in the fallopian tubes Not recommended in cases of tubal blockage, poor egg Not recommended in cases of tubal blockage, poor egg

quality, ovarian failure and severe male factor infertilityquality, ovarian failure and severe male factor infertility Most successful when coupled with drugs inducing Most successful when coupled with drugs inducing

ovulation (success rates of 5% to 20% per cycle) ovulation (success rates of 5% to 20% per cycle)

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Treatment of Female Infertility:Treatment of Female Infertility:Assisted Reproductive Technology (ART)Assisted Reproductive Technology (ART)

Noncoital methods of conception Noncoital methods of conception Includes all fertility treatments in which both eggs Includes all fertility treatments in which both eggs

and sperm are manipulatedand sperm are manipulated Types of ART include:Types of ART include:

In Vitro Fertilization (IVF)In Vitro Fertilization (IVF) Zygote Intrafallopian Transfer (ZIFT)Zygote Intrafallopian Transfer (ZIFT) Gamete Intrafallopian Transfer (GIFT)Gamete Intrafallopian Transfer (GIFT)

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ART: ART: In Vitro FertilizationIn Vitro Fertilization

Involves retrieving eggs and sperm from female Involves retrieving eggs and sperm from female and male partners and placing them in a lab dish to and male partners and placing them in a lab dish to enhance fertilizationenhance fertilization

Fertilized eggs are transferred several days later Fertilized eggs are transferred several days later into the uterusinto the uterus

Ovarian stimulation drugs are used prior to Ovarian stimulation drugs are used prior to procedure in order to retrieve several eggs and procedure in order to retrieve several eggs and maximize chances for successful fertilizationmaximize chances for successful fertilization

Success rates are about 20% per egg retrievalSuccess rates are about 20% per egg retrieval

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ART: ART: Gamete Intrafallopian Gamete Intrafallopian Transfer (GIFT)Transfer (GIFT)

GIFT is a procedure that involves:GIFT is a procedure that involves: ovarian stimulationovarian stimulation retrieval of eggsretrieval of eggs placing a mixture of sperm and eggs directly into the placing a mixture of sperm and eggs directly into the

woman’s fallopian tubewoman’s fallopian tube GIFT does not allow visual confirmation of GIFT does not allow visual confirmation of

fertilizationfertilization Success rates per egg retrieval are about 28% Success rates per egg retrieval are about 28%

(higher than for IVF)(higher than for IVF)

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ART: ART: Zygote Intrafallopian Zygote Intrafallopian Transfer (ZIFT)Transfer (ZIFT)

ZIFT, also called tubal embryo transfer, is another ZIFT, also called tubal embryo transfer, is another variation of IVFvariation of IVF

As with IVF, the actual fertilization takes place in a As with IVF, the actual fertilization takes place in a lab dishlab dish

Fertilized eggs are placed directly into a fallopian Fertilized eggs are placed directly into a fallopian tubetube

Success rate is about 29% per egg retrievalSuccess rate is about 29% per egg retrieval

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Treatment Possibilities: Treatment Possibilities: Male InfertilityMale Infertility

Surgical treatment in some cases (varicocele) Surgical treatment in some cases (varicocele) Intrauterine insemination can be performed either with Intrauterine insemination can be performed either with

patient’s or donor’s spermpatient’s or donor’s sperm ART procedures:ART procedures:

GIFTGIFT IVFIVF ICSIICSI

Donor semen should be free from STDs/HIVDonor semen should be free from STDs/HIV

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ART: ART: Intracytoplasmic Sperm Injection (ICSI)Intracytoplasmic Sperm Injection (ICSI)

Involves injection of single sperm into the eggInvolves injection of single sperm into the egg The woman is administered fertility drugs prior to The woman is administered fertility drugs prior to

the procedure to aid in the production of multiple the procedure to aid in the production of multiple eggseggs

Only active undamaged sperm are selected for Only active undamaged sperm are selected for injectionsinjections

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ART: ART: Intracytoplasmic Sperm Injection (ICSI)Intracytoplasmic Sperm Injection (ICSI)(Continued)(Continued)

Eggs are observed to see if fertilization takes placeEggs are observed to see if fertilization takes place average fertilization rate is 65%average fertilization rate is 65%

Implantation into the uterus takes place within 72 Implantation into the uterus takes place within 72 hours after ICSI hours after ICSI

Success rates range from 15% to 35% per egg Success rates range from 15% to 35% per egg retrievalretrieval

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Infertility: Infertility: SummarySummary

Infertility is a significant social and medical Infertility is a significant social and medical problem affecting couples worldwideproblem affecting couples worldwide

Female and male factors are equally responsible Female and male factors are equally responsible Evaluation of both partners is essentialEvaluation of both partners is essential Treatment depends on the cause of infertility and Treatment depends on the cause of infertility and

varies from ovulation-inducing drugs to surgery varies from ovulation-inducing drugs to surgery to ARTto ART