Infertility

InfertilityJohannes SoedjonoSub Department Andrlogy Indonesian Naval Hospital Dr RamelanCentre for the Study of Mens Health, Reproduction, Sex and AgingSchool of Medicine Hang Tuah UniversitySurabayaObjectivesDefine primary and secondary infertility

Describe the causes of infertility

Diagnosis and management of infertility

Requirements for Conception Production of healthy egg and spermUnblocked tubes that allow sperm to reach the eggThe sperms ability to penetrate and fertilize the eggImplantation of the embryo into the uterusFinally a healthy pregnancyInfertilityThe inability to conceive following unprotected sexual intercourse 1 year (age < 35) or 6 months (age >35)Affects 15% of reproductive couples6.1 million couples Men and women equally affected

InfertilityReproductive age for womenGenerally 15-44 years of ageFertility is approximately halved between 37th and 45th year due to alterations in ovulation20% of women have their first child after age 301/3 of couples over 35 have fertility problemsOvulation decreasesHealth of the egg declinesWith the proper treatment 85% of infertile couples can expect to have a child

Health problems developSABInfertilityPrimary infertilitya couple that has never conceived

Secondary infertilityinfertility that occurs after previous pregnancy regardless of outcome

Conception rates for fertile couples

Age and Pregnancy

PregnancyRates %Cycle numberAge and related miscarriage

Causes for infertilityMaleETOHDrugsTobaccoHealth problemsRadiation/ChemotherapyAgeEnviromental factorsPesticidesLead

FemaleAge StressPoor dietAthletic trainingOver/underweightTobaccoETOHSTDsHealth problems

Causes of InfertilityAnovulation (10-20%)Anatomic defects of the female genital tract (30%)Abnormal spermatogenesis (40%)Unexplained (10%-20%)Evaluation of the Infertile coupleHistory and Physical examSemen analysisThyroid and prolactin evaluationDetermination of ovulationBasal body temperature recordSerum progesteroneOvarian reserve testingHysterosalpingogram

Abnormalities of SpermatogenesisMale Factor40% of the cause for infertilitySperm is constantly produced by the germinal epithelium of the testicleSperm generation time 73 daysSperm production is thermoregulated1 F less than body temperatureBoth men and women can produce anti-sperm antibodies which interfere with the penetration of the cervical mucusSemen Analysis (SA)Obtained by masturbationProvides immediate informationQuantityQualityDensity of the spermAbstain from coitus 2 to 3 days Collect all the ejaculateAnalyze within 1 hourA normal semen analysis excludes male factor 90% of the timeMorphologyMotility

Normal Values for SAVolumeSperm ConcentrationMotility

ViscosityMorphologypHWBC 2.0 ml or more20 million/ml or more50% forward progression 25% rapid progressionLiquification in 30-60 min30% or more normal forms7.2-7.8Fewer than 1 million/mlCauses for male infertility42% varicocelerepair if there is a low count or decreased motility22% idiopathic14% obstruction20% other (genetic abnormalities)Abnormal Semen AnalysisAzospermiaKlinefelters (1 in 500)Hypogonadotropic-hypogonadismDuctal obstruction (absence of the Vas deferens)

OligospermiaAnatomic defectsEndocrinopathiesGenetic factorsExogenous (e.g. heat)Abnormal volumeRetrograde ejaculationInfectionEjaculatory failure

Evaluation of Abnormal SARepeat semen analysis in 30 daysPhysical examinationTesticular sizeVaricoceleLaboratory testsTestosterone levelFSH (spermatogenesis- Sertoli cells)LH (testosterone- Leydig cells)Referral to urologyAnatomic Disorders of the Female Genital Tract

Sperm transport, Fertilization, & ImplantationThe female genital tract is not just a conduitfacilitates sperm transportcervical mucus traps the coagulated ejaculatethe fallopian tube picks up the eggFertilization must occur in the proximal portion of the tubethe fertilized oocyte cleaves and forms a zygoteenters the endometrial cavity at 3 to 5 daysImplants into the secretory endometrium for growth and developmentAcquired DisordersAcute salpingitisAlters the functional integrity of the fallopian tubeN. gonorrhea and C. trachomatisIntrauterine scarring Can be caused by curettageEndometriosis, scarring from surgery, tumors of the uterus and ovaryFibroids, endometriomasTrauma

Congenital Anatomic Abnormalities

HysterosalpingogramAn X-ray that evaluates the internal female genital tractarchitecture and integrity of the systemPerformed between the 7th and 11th day of the cycleDiagnostic accuracy of 70%

HysterosalpingogramThe endometrial cavitySmoothSymmetricalFallopian tubesProximal 2/3 slenderAmpulla is dilated Dye should spill promptly

Unexplained infertility10% of infertile couples will have a completely normal workup

Pregnancy rates in unexplained infertilityno treatment 1.3-4.1%clomid and intrauterine insemination 8.3%gonadotropins and intrauterine insemination 17.1%

Treatment of the Infertile CoupleInadequate SpermatogenesisEliminate alterations of thermoregulationClomiphene citrate is occasionally used for induction of spermatogenesis20% successIn vitro fertilization may facilitate fertilizationArtificial insemination with donor sperm is often successful

AnovulationRestore ovulationAdminister ovulation inducing agents Clomiphene citrateAntiestrogenCombines and blocks estrogen receptors at the hypothalamus and pituitary causing a negative feedbackIncreases FSH production stimulates the ovary to make folliclesClomidGiven for 5 days in the early part of the cycleMaximum dose is usually 150mg50mg dose - 50% ovulate100mg -25% more ovulate150mg lower numbers of ovulationNo changes in birth defects If no pregnancy in 6 months refer for advanced therapies7% risk of twins 0.3% tripletsSAB rate 15%

Superovulatory MedicationsIf no response with clomid then gonadotropins- FSH (e.g. pergonal) can be administered intramuscularlyThis is usually given under the guidance of someone who specializes in infertility This therapy is expensive and patients need to be followed closelyAdverse effectsHyperstimulation of the ovariesMultiple gestationFetal wastageAnatomic AbnormalitiesSurgical treatmentsLysis of adhesionsSeptoplastyTuboplastyMyomectomySurgery may be performed laparoscopicallyhysteroscopicallyIf the fallopian tubes are beyond repair one must consider in vitro fertilizationAssisted Reproductive Technologies (ART)Explosion of ART has occurred in the last decade.Theses technologies help provide infertile couples with tools to bypass the normal mechanisms of gamete transportation.Probability of pregnancy in healthy couples is 30-40% per cycle, live birth rate 25%.this varies depending on age

Emotional ImpactInfertility places a great emotional burden on the infertile couple.The quest for having a child becomes the driving force of the couples relationship.The mental anguish that arises from infertility is nearly as incapacitating as the pain of other diseases.It is important to address the emotional needs of these patients.

ConclusionInfertility should be evaluated after one year of unprotected intercourse.History and Physical examination usually will help to identify the etiology.If patients fail the initial therapies then the proper referral should be made to a reproductive specialist.Test Question Case 1

A couple in their late 20s with primary infertility for 18 months. The women has regular monthly cycles. The husband has never fathered a child. Neither partner has a history of STDs or major illness. No difficulties with erection or ejaculation. Which is the most likely cause of their infertility?A. AnovulationB. Abnormality of SpermatogenesisC. Female Anatomic disorderD. Immunologic disorderCase 1 Spermatogenesis- causes 40% infertility, anovulation-10-20% and anatomic defects- 30-40%-the majority of which being from salpingititis. Given the history of regular menstrual cycles and no infections, anovulation and anatomic defects is unlikely.Which study would not be indicated as part of the initial evaluation?A. Basal Body temperature recordB. Semen AnalysisC. HysterosalpingogramD. Diagnostic Laparoscopy

Case 1Diagnostic Laparoscopy- This should be reserved until the initial tests are completed. All the other tests are used in the initial workup.

Anovulation is found in the female partner, despite her regular cycles. The next step is?A. Induce ovulation with clomidB. Perform artificial inseminationC. Induce ovulation with gonadotropins (pergonal)D. Perform diagnostic laparoscopy to rule out other causes

Case 1Induce ovulation with clomid- Gonadotropins would be used if the patient failed clomid. Artificial insemination and laparoscopy are not indicated yet.Case 2A 37 yo women with a history of gonococcal salpingitis presents with her spouse for evaluation of infertility.What study is most indicated on the initial evaluation?A. Basal body temperature recordB. Semen analysisC. HysterosalpingogramD. Endometrial BiopsyCase 2Without evidence of anovulation the endometrial bx is not indicated. The couple should have A, B, and C.The HSG reveals bilateral tubal obstruction. A consultant recommends she not have surgery because of the poor prognosis of pregnancy. What should be recommended next?A. Intrauterine inseminationB. In vitro fertilizationC. No therapy at allD. Adoption Case 2Because of the obstruction in the tubes the only appropriate therapy would be in vitro fertilization. Insemination would not get the sperm past the obstruction. Adoption is also and option.Questions?

Causes for Abnormal SANo spermKlinefelters syndromeSertoli only syndromeDuctal obstructionHypogonadotropic-hypogonadismFew spermGenetic disorderEndocrinopathiesVaricoceleExogenous (e.g., Heat)

Abnormal CountCont. causes for abnormal SAAbnormal MorphologyVaricoceleStressInfection (mumps)Abnormal MotilityImmunologic factorsInfectionDefect in sperm structurePoor liquefactionVaricoceleAbnormal VolumeNo ejaculateDuctal obstructionRetrograde ejaculationEjaculatory failureHypogonadismLow VolumeObstruction of ductsAbsence of vas deferensAbsence of seminal vesiclePartial retrograde ejaculationInfection