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CuplulCuplul infertilinfertil

DefinitiaDefinitia modernamoderna aa infertilitatiiinfertilitatii ± ± neobtinereaneobtinerea

uneiunei sarcinisarcini dupadupa 1212 luniluni dede viataviata sexualasexuala

regulataregulata sisi neprotejataneprotejata1010--1515%% dindin cupluricupluri

1.1. CauzeCauze masculinemasculine 3535%%

2.2. CauzeCauze femininefeminine 3535%%3.3. CauzeCauze mixtemixte 2020%%

4.4. CauzeCauze inexplicabileinexplicabile 1010%% ((cupluricupluri normalenormale

infertile)infertile)



DEFINITIIDEFINITII

FertilitateaFertilitatea ± ± capacitateacapacitatea dede aa sese reproduce,reproduce,

capacitateacapacitatea dede aa fifi fertilfertil

FecundabilitateaFecundabilitatea ± ± probabilitateaprobabilitatea dede aa obtineobtine oo sarcinasarcina

inin fiecarefiecare lunaluna

FecunditateaFecunditatea ± ± capacitateacapacitatea dede aa nastenaste raportatraportat pepe

ciclulciclul menstrualmenstrual (( ratarata fecunditatiifecunditatii esteeste dede 00,,1515--00,,1818

per per lunaluna,, aproxaprox 9090%%/an)/an) InfertilitateaInfertilitatea ± ± incapacitateaincapacitatea dede aa obtineobtine oo sarcinasarcina dupadupa

11 anan dede viataviata sexualasexuala neprotejataneprotejata ± ± 1010--1515%%dindin cupluricupluri



FertilitateaFertilitatea

ScadeScade cucu inaintareainaintarea inin varstavarsta aa femeiifemeii

ModificariModificari inin planificareaplanificarea familialafamiliala

ConditiiConditii::

a.a. EliberareEliberare ovocitovocit

b.b. ProductieProductie normalanormala dede spermatozoizispermatozoizi

c.c. TransportulTransportul gametilor gametilor inin portiuneaportiunea ampularaampulara tubaratubara;;

fertilizareafertilizaread.d. TransportulTransportul ouluioului fecundatfecundat inin fazelefazele salesale evolutiveevolutive

sprespre cavitateacavitatea endometrialaendometriala;; nidatianidatia





InfertilitateaInfertilitatea femininfeminin



FactoriiFactorii femininifeminini

OvarieniOvarieni ((axaaxa HTHT--HFHF--ovar ovar ± ± ovulatiaovulatia))

CervicaliCervicali ((stenozestenoze congenitalecongenitale sausau dobinditedobindite ± ±infectiiinfectii,,

iatrogeneiatrogene,, hipoestrogenismhipoestrogenism sausau anomaliianomalii alealeinteractiuniiinteractiunii spermatozoizispermatozoizi ± ±mucus)mucus)

UteriniUterini ((anomaliianomalii congenitalecongenitale,, endometriteendometrite,, polipipolipi,,

fibroamefibroame submucoasesubmucoase))

TubariTubari (BIP,(BIP, hidrosalpinxhidrosalpinx)) Altii Altii:: virstavirsta,, factoriifactorii peritonealiperitoneali (( BIP,BIP, endometriozaendometrioza,, sdsd

aderentialeaderentiale))



FactorulFactorul femininfeminin

OvulatiaOvulatia

TesteTeste hormonalehormonale

FactorulFactorul tubar tubar

FactorulFactorul uterinuterin

FactorulFactorul cervical (cervical (investigatiiinvestigatii

bacteriologicebacteriologice))

FactorulFactorul coitacoitall



FactorulFactorul cervicalcervical

StenozaStenoza

CalitateaCalitatea mucusuluimucusului

InteractiuneaInteractiunea mucusmucus-- spermatozoizispermatozoizi ((

activareaactivarea sisi capacitatiacapacitatia))

PotPot existaexista modificarimodificari datoratedatorate

tratamentelor tratamentelor ± ± CCCC scadescade cantitateacantitatea

mucusuluimucusului!!



FactorulFactorul uterinuterin

FactoriFactori congenitalicongenitali ((anomaliianomalii de tipde tip sdsd

RokitanskiRokitanski--Kuster Kuster--Hauser,Hauser, altealte anomaliianomalii

mullerienemulleriene ± ±uter uter unicorn,unicorn, septatseptat etcetc))

FactoriFactori dobanditidobanditi ± ± endometritaendometrita,, sdsd

aderentialeaderentiale intrauterine,intrauterine, polipiipolipii

endometrialiendometriali,, fibroamelefibroamele submucoasesubmucoase, cu, cudeformareadeformarea cavitatiicavitatii,, adenomiozaadenomioza



FactorulFactorul ovarianovarian

Amenoree Amenoree primaraprimara ± ± hipogonadismhipogonadism hipogonadotropichipogonadotropic

((insuficientainsuficienta hipotalamicahipotalamica,, defectedefecte dede tiptip

neurotransmitatorineurotransmitatori,, insuficienteinsuficiente gonadotropicegonadotropice izolateizolate,,

stressstress croniccronic,, malnutritiemalnutritie cronicacronica)) sausau

hipergonadotropichipergonadotropic ((sdsd Turner,Turner, chimioterapiechimioterapie cucu agentiagenti

alchilantialchilanti,, iradiereiradiere pelvinapelvina))



FactorulFactorul ovarianovarian

Amenoree Amenoree secundarasecundara ± ± absentaabsenta menstreimenstrei timptimp dede 66

luniluni ± ± afectiuniafectiuni tiroidienetiroidiene,, SR,SR, hipofizarehipofizare ((tumoritumori))

InsuficientaInsuficienta ovarianaovariana prematuraprematura

OligomenoreeaOligomenoreea ± ± SOP,SOP, obezitateobezitate etcetc

VarstaVarsta ± ± calitateacalitatea ovocitelor ovocitelor//anomaliianomalii

cromozomialecromozomiale//calitateacalitatea embrionilor embrionilor//calitateacalitateaendometruluiendometrului



FactorulFactorul tubar tubar

Anomalii Anomalii congenitalecongenitale

InfectiiInfectii tubaretubare

HidrosalpinxHidrosalpinx

FactorulFactorul peritonealperitoneal ± ± BIP,BIP, endometriozaendometrioza

(+/_deficit de(+/_deficit de fazafaza lutealaluteala))



FactorulFactorul masculinmasculin

ClasificareClasificare::

± ± FactoriFactori pretesticularipretesticulari ((axaaxa HTHT--HF)/HF)/

-- FactoriFactori testicularitesticulari ((geneticigenetici ± ± sdsd Klinefelter Klinefelter;; virstavirsta;; infectiiinfectii;;

varicocelvaricocel;; traumatismetraumatisme,, iradiereiradiere,, droguridroguri)/)/

-- FactoriFactori posttesticulariposttesticulari ((obstructiiobstructii ductaleductale congenitalecongenitale sausau postpostinfectiiinfectii,, chirurgicelchirurgicel sausau posttraumaticeposttraumatice))

SpermogramaSpermograma

Consult urologicConsult urologic ConsultConsult endocrinologicendocrinologic ((testosterontestosteron, FSH, LH,, FSH, LH,

prolactinaprolactina))

FactorulFactorul coitalcoital



ProtocolulProtocolul de diagnosticde diagnostic

IstoriculIstoricul cupluluicuplului

1.1. TipulTipul sisi duratadurata infertilitatiiinfertilitatii

2.2. Alte Alte sarcinisarcini

3.3. Anamneza Anamneza vietiivietii sexualesexuale

4.4. Anamneza Anamneza femeiifemeii ± ± menstramenstra, BTS , BTS etcetc

5.5. Anamneza Anamneza barbatuluibarbatului

6.6. TratamenteTratamente efectuateefectuate/in curs/in curs



SituatiaSituatia actualaactuala

ModificarileModificarile stiluluistilului dede viataviata//profesionaleprofesionale ± ±

consiliereconsiliere specificaspecifica ((subfertilitatesubfertilitate))

FactoriFactori dede mediumediu//comportamentalicomportamentali:: substantesubstantetoxicetoxice,, tutuntutun,, droguridroguri,, activitateactivitate fizicafizica intensaintensa,,

dietediete neadecvateneadecvate cucu fluctuatiifluctuatii marimari dede greutategreutate



InvestigatiiInvestigatii

DocumentareaDocumentarea ovulatieiovulatiei sisi aa rezerveirezervei

ovarieneovariene (Z3 estradiol, FSH, LH, DHEA(Z3 estradiol, FSH, LH, DHEA--

S,S, TestosteronTestosteron liber liber, AMH,, AMH, inhibinainhibina B; nr B; nr foliculilor foliculilor antraliantrali,, volumulvolumul ovarian; Z21ovarian; Z21--

Pro)Pro)

VerificareaVerificarea uteruluiuterului ± ± US, HSG, HSCUS, HSG, HSC

VerificareaVerificarea trompelor trompelor ± ± HSG, LSCHSG, LSC

VerificareaVerificarea Tyr (TSH,Tyr (TSH, prolactinaprolactina))



Curba termicaCurba termica





HSGHSG



HSGHSG



HSGHSG



HSGHSG



HSGHSG



HSGHSG



TRATAMENTTRATAMENT

FactorulFactorul cervicalcervical ± ± tratareatratarea infectiilor infectiilor,,

inseminareainseminarea intrauterinaintrauterina,, altealte procedeeprocedee

RUARUA FactorulFactorul uterinuterin ± ± rezectierezectie polipipolipi,, ablatieablatie

fibroamefibroame,, reconstructiireconstructii uterine,uterine, rezectiirezectii

septsept,, ablatieablatie sinechiisinechii FactorulFactorul tubaltubal sisi peritonealperitoneal -- LSCLSC



InseminareaInseminarea intrauterinaintrauterina

IndicatiiIndicatii (factor (factor femininfeminin cervical,cervical, oligospermieoligospermie,, anomaliianomalii

ejaculatoriiejaculatorii etc)etc)

SpermaSperma preparatapreparata ((centrifugarecentrifugare,, separareseparare,, mediimedii

nutritive)nutritive) homologahomologa sausau heterologaheterologa -- donator donator

CiclulCiclul naturalnatural sausau indusindus

La 30La 30--34 ore de la surge34 ore de la surge--ulul LHLH sausau la 36 ore de lala 36 ore de la

administrareaadministrarea a 10.000 UI HCGa 10.000 UI HCG

Cateter Cateter special, laspecial, la fundulfundul uteruluiuterului

1010--15 minute15 minute dupadupa proceduraprocedura -- repausrepaus inin decubitdecubit

RezultateRezultate: 8%/: 8%/ciclulciclul natural; 12%/natural; 12%/cicluciclu indusindus cu CC;cu CC;

15%15% stimularestimulare FSHr FSHr; 85%; 85% dupadupa 44 inseminariinseminari



TratamentulTratamentul anovulatieianovulatiei

ClomifenClomifen citratcitrat CCCC ± ± 5050 mgmg ««..250250 mg/mg/zizi ZZ 33--77//55--99;; ZZ1212

incepeincepe monitorizareamonitorizarea folicularafoliculara

InhibitoriiInhibitorii dede aromatazaaromataza-- letrozolletrozol 22,,55 mgmg ZZ 33--77

anastrozolanastrozol;; MetforminMetformin (SOMPC)(SOMPC)

FSH,FSH, LHLH recombinatrecombinat (³pen´(³pen´ FSHr FSHr 5050««150150UI,UI, dindin ZZ22--33,,

77 zilezile));; inainteinainte ± ±Menopur Menopur (FSH(FSH +LH+LH urinaurina menopauzamenopauza))

Analogii Analogii dede GnRHGnRH ± ± GonadorelinGonadorelin,, DipherelinDipherelin

Antagonistii Antagonistii dede GnRHGnRH -- CetrorelixCetrorelix

DeclansareaDeclansarea ovulatieiovulatiei ± ± foliculfolicul dede 1818--2020mmmm ± ± PregnylPregnyl

50005000 sausau 1000010000UIUI ((gonadotrofinagonadotrofina corionicacorionica umanaumana))



SindromulSindromul dede

hiperstimularehiperstimulare ovarianaovariana ExtravazareExtravazare masivamasiva extravascularaextravasculara ((scadereascaderea volumuluivolumului circulantcirculant,,

hemoconcentratiehemoconcentratie,, dezechibrudezechibru hidroelectolitichidroelectolitic))

MarireMarire dede volumvolum aa ovarelor ovarelor 55--12 cm,12 cm, ascitaascita,, cistigcistig poderalpoderal,, g+vg+v,,

hidrotoraxhidrotorax,, edemeedeme perifericeperiferice,, oligurieoligurie, IRA,, IRA, trombocitozatrombocitoza, soc,, soc,exitusexitus

CelCel maimai frecventfrecvent lala pacientepaciente tineretinere cu SOP,cu SOP, slabeslabe,, cece raspundraspund cucu

un nr mare deun nr mare de foliculuifolicului sisi valorivalori marimari de E2de E2

NuNu tbtb declansatadeclansata ovulatiaovulatia ± ± nu senu se maimai admadm hCGhCG!!!!!!!!

TratamentTratament ± ± internareinternare,, reechreech HE,HE, albuminaalbumina 25% 50 ml/h IV 4 ore,25% 50 ml/h IV 4 ore,

paracentezaparacenteza//toracentezatoracenteza,, heparinaheparina 5000 UIx2/5000 UIx2/zizi



ReproducereReproducere umanaumana

asistataasistata FIVFIV

ICSI (INTRACITOPLASMATIC SPERMICSI (INTRACITOPLASMATIC SPERM

INJECTION)INJECTION) ± ± ratarata fertlizariifertlizarii: 50: 50--75%/75%/ovocitovocit

AH (ASSISTED HATCHING) AH (ASSISTED HATCHING) ± ± subtieresubtiere aa

zoneizonei pellucidapellucida CrioprezervareaCrioprezervarea embrionilor embrionilor (din(din fazafaza dede

22 pronucleipronuclei ± ± blastochistblastochist))



FIVFIV

OvocitOvocit preovulator preovulator,, fertilizarefertilizare cucu

spermatozoid IV,spermatozoid IV, embriotransfer embriotransfer inin cavcav

endometrialaendometriala IndicatiiIndicatii:: absentaabsenta trompelor trompelor,, sdsd aderentialaderential

sever,sever, endometriozaendometrioza severasevera,, malformatiimalformatii

severe,severe, oligospermieoligospermie,, infertilitateinfertilitate dedeetiologieetiologie neprecizataneprecizata



FIV FIV --EtapeEtape

StimulareStimulare ovarianaovariana

Aspiratia Aspiratia folicularafoliculara

ClasificareaClasificarea ovocitelor ovocitelor

PreparareaPrepararea spermeispermei

InseminareaInseminarea ovocitelor ovocitelor

CultivareaCultivarea embrionilor embrionilor

EmbriotransferulEmbriotransferul



StimulareaStimularea ovarianaovariana

11.. CCCC ± ±rar rar

22.. CCCC sisi gonadotropinegonadotropine dede menopauzamenopauza (HMG)(HMG)

33.. HMG

HMG

± ± r FS

Hr FS

H,, rLHrLH 44..Agonistii Agonistii GnRHGnRH (protocol(protocol flareflare--upup;; flareflare--upup modificatmodificat;;

protocolprotocol dede fazafaza lutealaluteala))

55.. Antagonistii Antagonistii GnRHGnRH

SeS

e monitorizeazamonitorizeaza ecoeco ++ dozaredozare EE22FoliculFolicul dede 1717--1818 mm,mm, hCGhCG 1010..000000 UI,UI, lala 3535 oreore punctiapunctia

folicularafoliculara

SpermaSperma -- specimenspecimen recoltatrecoltat dupadupa 33--55 zilezile dede abstinentaabstinenta

SpermaS

perma preparatapreparata-- adaugataadaugata ovocitelor ovocitelor --



StimulareStimulare ovarianaovariana-- gonadotropinegonadotropine

FSHFSH purificatpurificat,, FSHrecombinatFSHrecombinat, LH, LH

recombinatrecombinat ((studiistudii cliniceclinice))

Administare Administare individualizataindividualizata,, monitorizindmonitorizind

raspunsulraspunsul ovarianovarian

Poor Poor-- respondererespondere: 2: 2--33 foliculifoliculi,, ovociteovocite dede

proastaproasta calitatecalitate



StimulareStimulare ovarianaovariana -- agonistiiagonistii GnRHGnRH

1.Protocol flare1.Protocol flare--up: z1up: z1--55 GnRHaGnRHa ((recrutarerecrutare folicularafoliculara,,

apoiapoi downdown--regulationregulation sisi sese blocheazablocheaza surgesurge--ulul de LH;)de LH;)

din Z5din Z5 FSHr FSHr

2. Flare2. Flare--up modificat:Z4up modificat:Z4--21 CM ACO; DIN z121 CM ACO; DIN z1 GnRHaGnRHa,,

din Z4din Z4 FSHr FSHr

3. Protocol de3. Protocol de fazafaza lutealaluteala:: GnRHaGnRHa din Z17din Z17 sausau Z21;Z21;

din Z2 a CMdin Z2 a CM urmator urmator ± ± FSHr FSHr

RiscuriRiscuri ± ± sdsd de HSS de HSS ovarianaovariana



StimulareStimulare ovarianaovariana ² ²antagonistiantagonisti GnRHGnRH

ScopScop:: blocareblocare LHLH farafara efectefect flareflare--upup

Scheme:Scheme: dozadoza unicaunica Z8; cdZ8; cd celcel maimai maremare

foliculfolicul areare diamdiam de 14mm;cd LHde 14mm;cd LH ser ser pestepeste 10mUI/ml10mUI/ml

Avantaj Avantaj: doze: doze maimai micimici dede goandotropinegoandotropine;;

nu se producenu se produce efectefect de HSS de HSS ovarianaovariana



AlternativeAlternative

OvociteOvocite donatedonate

SpermaSperma donatadonata

EmbrioniEmbrioni donatidonati

MamaMama purtatoarepurtatoare//surogatsurogat



InfertilitateaInfertilitatea masculinamasculina



FiziopatologieFiziopatologie

1.1. InfertilitateaInfertilitatea dede cauzacauza mecanicamecanica (0,3(0,3--7%)7%)

CoitusulCoitusul esteeste ineficientineficient,, datoritadatorita fiefie uneiunei nesincr onizarinesincr onizari inin timptimp,,

uneiunei imposibilitatiimposibilitati fizicefizice,, anomaliianomalii anatomiceanatomice,, disfunctiidisfunctii erectileerectile

sausau ejaculatoriiejaculatorii2.2. AzoospermiaAzoospermia (0,9(0,9--16%)16%)

NuNu existaexista S laS la nivelulnivelul spermeispermei -- insuficientainsuficienta gonadicagonadica primaraprimara sausau

secundarasecundara sausau obstructiiobstructii de tract genitalde tract genital

3.3. InfertilitateaInfertilitatea imunologicaimunologica (3,4(3,4--25%)25%)

Antico

rpiAntico

rpi antispermaticiantispermatici lala nivelulnivelul spermeispermei4.4. AnomaliiAnomalii aleale calitatiicalitatii spermeispermei (23(23--48%)48%)

SpermatozoiziiSpermatozoizii suntsunt disfunctionalidisfunctionali lala analizaanaliza spermeispermei,, dar dar existaexista sisi

cazuricazuri in care S auin care S au functiefunctie normalanormala

5.5. DisfunctiiDisfunctii aleale spermeispermei (0(0--25%)25%)

AnalizaAnaliza spermeispermei esteeste normalanormala dar dar existaexista disfunctiidisfunctii oculteoculte



Analiza spermeiAnaliza spermei

Type of assays

1. Descriptive assay: spermogram

2. Functional assays: penetration of cervical mucus (postcoital test, in vitro penetration

assay)

binding of spz to the zona pellucida

fusion of spz with zona-free hamster oocytehypoosmotic swelling of the flagella

3. Immunological assay: mixed agglutination test

immunobead test

sperm immobilization in cervical mucus




Definitions of semen classificationsDefinitions of semen classifications

Normozoospermia When all the spermatozoal parameters areNormozoospermia When all the spermatozoal parameters arenormal together with normal seminal plasma ,WBCs and there isnormal together with normal seminal plasma ,WBCs and there isno agglutination.no agglutination.

Oligozoospermia When sperm concentration is < 20 million/ml.Oligozoospermia When sperm concentration is < 20 million/ml. Asthenozoospermia Fewer than 50% spermatozoa with forward Asthenozoospermia Fewer than 50% spermatozoa with forward

progression(categories (a) and (b) or fewer than 25%progression(categories (a) and (b) or fewer than 25%spermatozoa with category (a) movement.spermatozoa with category (a) movement.

Teratozoospermia Fewer than 50% spermatozoa with normalTeratozoospermia Fewer than 50% spermatozoa with normalmorphology.morphology.

OligoasthenoteratozoospermiaSignifies disturbance of all theOligoasthenoteratozoospermiaSignifies disturbance of all thethree variables (combination of only two prefixes may also bethree variables (combination of only two prefixes may also beused).used).

Azoospermia No spermatozoa in the ejaculate. Azoospermia No spermatozoa in the ejaculate.

Aspermia No ejaculate. Aspermia No ejaculate.




Standard tests Normal valuesStandard tests Normal values

Volume 2.0 ml or moreVolume 2.0 ml or more

pH7. 2pH7. 2--7.87.8

Sperm concentration 20x106 spermatozoa/ml or moreSperm concentration 20x106 spermatozoa/ml or more

Total sperm count 40x106 spermatozoa or moreTotal sperm count 40x106 spermatozoa or more

Motility 50% or more with forward progression or 25%Motility 50% or more with forward progression or 25%or more with rapid progression within 60 min after or more with rapid progression within 60 min after

collectioncollection Morphology 30% or more with normal morphologybMorphology 30% or more with normal morphologyb

Vitality 75% or more liveVitality 75% or more live

White blood cells Fewer than 1x106/mlWhite blood cells Fewer than 1x106/ml



Spermograma normalaSpermograma normala



Immunological testsImmunological tests

Immunobead test Fewer than 20% spermatozoa with adherentImmunobead test Fewer than 20% spermatozoa with adherentparticlesparticles

MAR test Fewer than 10% spermatozoa with adherent particlesMAR test Fewer than 10% spermatozoa with adherent particles

Seminal plasma biochemical analysisSeminal plasma biochemical analysis Epididymal markers aEpididymal markers a--glucosidase (neutral) 20 mU or more per glucosidase (neutral) 20 mU or more per

ejaculateejaculate

Carnitine 0.8Carnitine 0.8--2.9 mmole per ejaculate2.9 mmole per ejaculate

Prostate markers Zinc (total) 2.4 mmole or more per ejaculateProstate markers Zinc (total) 2.4 mmole or more per ejaculate

Citric acid (total) 52 mmole or more per ejaculateCitric acid (total) 52 mmole or more per ejaculate

Acid phosphatase (total) 200 U or more per ejaculate Acid phosphatase (total) 200 U or more per ejaculate

Seminal vesicle marker Fructose (total) 13 mmole or more per Seminal vesicle marker Fructose (total) 13 mmole or more per ejaculateejaculate

WHOmanual, 3rd edition, 1992.WHOmanual, 3rd edition, 1992.

