Non c’è dubbio che la sterilità comporti un profondo riassestamento della relazione di coppia, soprattutto nell’espressione della sessualità tra eroicità e procreazione. Può accadere che si verifichi una collusione di coppia per cui il legame si annoda attorno alla frustrazione generativa. Di conseguenza tutta la sfera della sessualità viene strumentalizzata alla fecondazione. Nella relazione l’elemento romantico perde di importanza; si “devono” avere rapporti nei giorni stabiliti, anche se ammalati, stanchi o arrabbiati. Quando il sesso non è più spontaneo e nemmeno un piacere, ma viene fatto solo con l’obiettivo di ottenere una gravidanza, il livello di ansia cresce inevitabilmente. Spesso lo stress emotivo nella relazione nasce proprio dall’idea di non fare più l’amore, ma di fare un bambino. Si osserva, infatti, nell’uomo un frequente calo del desiderio sessuale con  conseguente deficit erettivo e ansia da prestazione proprio a “metà ciclo”, quando la donna, supposta fertile, percepisce il massimo del suo desiderio;  nella donna, di contro, può non esserci manifestazione di desiderio verso il partner nei periodi cosiddetti “infertili” e possono comparire problemi di lubrificazione, dolore duranti i rapporti sessuali e alterazioni del vissuto orgasmico.

Insorgono pertanto dei problemi sessuali secondari di coppia che possono complicare ulteriormente il quadro e non devono essere sottovalutati perché possono condurre la coppia fino alla richiesta di una fecondazione assistita, intesa come un concepimento senza sesso, non supportata cioè da reali problemi di natura organica.  D’altro canto si calcola che il 10% dei problemi di infertilità sia causato proprio da patologie psicosessuali, quali il vaginismo, le disfunzioni erettili, i disturbi dell’eiaculazione. Tutte difficoltà probabilmente compensate dalla coppia fino al momento in cui scatta il desiderio di avere un figlio.  Anche la fecondazione assistita sembra influenzare negativamente il vissuto sessuale di coppia, poiché la ridefinizione del nesso sessualità-procreazione viene affidata completamente all’istituzione medica. Comunque si proceda, permane un’aurea di artificiosità e di strumentalità che si estende all’intero processo fecondativo rendendolo “freddo” rispetto al desiderio sessuale e al piacere dell’intimità condivisa. Alcuni studi hanno però dimostrato un miglioramento del livello di comunicazione e intimità nella coppia con un maggior investimento sul partner; come se la difficoltà e, in alcuni casi, l’impossibilità di diventare genitori, stimoli la ricerca di risorse interiori capaci di creare una complicità che aiuti entrambi a superare la frustrazione di entrambi.

Bibliografia

C. Flamini, P. Mulinelli – Curare la sterilità – Roma - Carocci – 2001
J. Baldaro Verde, R.E. Nappi – Diagnostica Sessuologica: la sessuologia per la riproduzione – Aggiornamento Permanente in Ostetricia e Ginecologia – Aprile 2004 – Volume 8 – Pacini ed.
S. Veggetti Finzi – Il bambino della notte – Milano – Mondadori 1990.
S. Veggetti Finzi – Volere un figlio. La nuova maternità fra natura e scienza–  Milano - Oscar Saggi Mondatori -1997

L’immunoinfertilità o infertilità immunologica dovuta alla presenza degli anticorpi antisperma è, come dimostrano i dati statistici disponibili, una causa importante di infertilità negli esseri umani-

Sistema immunitario e infertilità
Sul concetto che una risposta immunitaria avversa a certi tessuti nel sistema riproduttivo possa causare l’infertilità vi è ormai sufficiente consenso in ambito scientifico, per cui l’attenzione è oggi diretta a scoprire l’origine degli squilibri immunitari e le loro conseguenze sulla funzione riproduttiva. Gli anticorpi antisperma (ASA) sono solo uno dei molti marcatori (markers) immunologici che si possono considerare nella valutazione dell’infertilità immunologica. La ricerca medica ha dimostrato inoltre che entrambi i sessi possono produrre anticorpi che reagiscono con lo sperma umano.

L’infertilità immunologica di coppia può avere luogo anche quando il muco cervicale femminile si costituisce come un ambiente ostile allo sperma perché produce anticorpi diretti contro gli spermatozoi del partner.

Nell’infertilità immunologica maschile, invece, gli anticorpi antisperma si attaccano a diverse parti dello spermatozoo e interferiscono con la fertilità in diversi modi: gli anticorpi presenti sulla coda (flagello) degli spermatozoi tendono a immobilizzarli e a farli agglutinare (aderire) tra di loro, mentre gli anticorpi antisperma che aderiscono alla testa degli spermatozoi possono impedire l’attraversamento efficiente del muco cervicale femminile, e anche quando l’ovocita venga infine raggiunto, possono rendere critica o impossibile la fecondazione.

Gli anticorpi antisperma circolanti, ovvero presenti nel sangue, sono invece rilevabili nella maggior parte (70%) degli uomini che si sono sottoposti a vasovasostomia, l’intervento di ricostruzione delle vie seminali successivo alla vasectomia (resezione dei dotti deferenti che trasportano gli spermatozoi), i quali mostrano la presenza di anticorpi antisperma anche nel plasma seminale.

Anticorpi antisperma nel sangue
Il ruolo degli anticorpi antisperma nell’inibire la penetrazione degli spermatozoi nel muco cervicale è stato definito con molta chiarezza da svariati autori, per esempio Moghissi ha rilevato la presenza di anticorpi antisperma nel muco cervicale nel 25% delle donne facenti parte di 172 coppie infertili, mentre il 13% delle donne dello stesso gruppo presentava anticorpi antisperma nel sangue. In un altro studio, il 64% di 66 coppie che non presentavano quantità significative di anticorpi antisperma sulla superficie degli spermatozoi mostrava un’adeguata motilità degli spermatozoi all’interno del muco cervicale, contro il 26% di 122 coppie con anticorpi antisperma associati agli spermatozoi (American Obstretics & Gynecology). La presenza di anticorpi antisperma nel sangue della donna non è strettamente correlata con la presenza di anticorpi antisperma nel muco cervicale, e in generale il significato clinico della presenza degli anticorpi antisperma nel sangue degli uomini e delle donne è controversa.

Meccanismo della reazione immunitaria
Gli spermatozoi sono “estranei” all’organismo perché, diversamente da tutte le altre cellule, contengono solo la metà del corredo cromosomico (23 cromosomi contro i  46 del corredo cromosomico normale), ovvero sono aploidi anziché diploidi. Quando lo sperma entra in contatto con il sangue è perciò in grado di scatenare una reazione immunitaria che consiste nella produzione di anticorpi antisperma. Proprio per questa ragione la spermatogenesi (la produzione degli spermatozoi) ha luogo dietro la “barriera immunitaria” rappresentata dai testicoli.

In condizioni normali i testicoli contengono una membrana basale, la barriera testicoli-sangue, che agendo come uno strato protettivo previene il contatto, all’interno del tratto riproduttivo maschile, tra lcellule immunitarie e spermatozoi. Questa barriera può rompersi a causa di eventi traumatici del tratto riproduttivo, cosicché le cellule immunitarie entrano in contatto con gli spermatozoi, attaccandoli e distruggendoli.

L’infertilità immunologica
I disturbi del sistema immunitario possono portare a fallimento riproduttivo in diversi stadi del processo di riproduzione: infertilità inspiegata, fallimento ripetuto della Fecondazione in Vitro (FIV) o della microiniezione di spermatozoi (ICSI), aborto spontaneo ripetuto. Il sistema immunitario è composto da cellule immunitarie e da prodotti cellulari (citochine) e tra le molte cellule immunitarie, due in particolare sono associate all’infertilità, al fallimento ricorrente dell’impianto dell’embrione e all’aborto spontaneo: le cellule CD56 (cellule Natural Killer), che producono citochine tossiche quali il Fattore di Necrosi Tumorale (αTNF) alfa e le cellule CD19, che producono anticorpi contro ormoni quali la gonadotropina corionica umana (hCG), il progesterone, e così via. Gli anticorpi sono proteine prodotte dai linfociti B, un tipo di cellula immunitaria, che circolano nel sangue e nei tessuti e che in condizioni normali proteggono l’organismo dall’invasione di entità estranee quali virus e batteri; in alcuni casi, tuttavia, l’organismo può sviluppare anticorpi contro le sue stesse cellule.

Al microscopio è possibile osservare in questi casi come gli anticorpi antisperma causino l’agglutinazione degli spermatozoi, compromettendone seriamente la motilità e in definitiva provocando l’infertilità. Alcuni autori ritengono che la prevalenza degli Anticorpi Antisperma aumenti con l’età del soggetto.

L’agglutinazione degli spermatozoi
”Agglutinazione” significa che gli spermatozoi mobili aderiscono gli uni agli altri testa a testa, corpo a corpo, coda a coda, o in forma mista, per esempio il corpo alla testa. L’aderenza degli spermatozoi mobili e non mobili al muco, a cellule diverse dagli spermatozoi o a scorie non può invece essere considerata una forma di agglutinazione. La presenza di agglutinazione suggerisce l’esistenza di un fattore immunologico di infertilità, ma non è sufficiente a dimostrarlo. In caso di agglutinazione è indispensabile procedere a una spermiocoltura per escludere la presenza di infezioni, per esempio da Escherichia coli. L’agglutinazione degli spermatozoi osservata durante un normale spermiogramma deve essere usata come indicazione per il MAR Test negli uomini infertili.

Purtroppo, una volta che il sistema immunitario è stato sensibilizzato agli spermatozoi è molto difficile invertire il processo, se non a prezzo dell’assunzione di elevate dosi di corticosteroidi che riducono temporaneamente la quantità di anticorpi (e quindi l’infertilità), e che oggi non vengono più impiegati a causa dei pesanti effetti collaterali.

 Le cause degli Anticorpi Antisperma
Alcune tra le più comuni cause di rottura della barriera testicoli-sangue e della conseguente formazione degli anticorpi antisperma comprendono:

• infezione
• criptorchidismo (testicolo ritenuto)
• torsione del testicolo
• trauma accidentale dei testicoli
• biopsia dei testicoli
• cancro dei testicoli
• varicocele
• assenza congenita del canale deferente
• malattie autommuni.

Il trattamento dell’infertilità immunologica
Le tecniche di Fecondazione Assistita si sono dimostrate le più utili per trattare le coppie che presentano un’infertilità di origine immunologica. In particolare, tra le tecniche più adatte segnaliamo sia la Fecondazione in Vitro (FIV), eventualmente associata ad ICSI (microiniezione di spermatozoi), sia la IUI o Inseminazione IntraUterina, nella quale si supera la presenza degli anticorpi antisperma presenti nel muco cervicale della donna depositando gli spermatozoi direttamente nell’utero. La IUI è la tecnica migliore soprattutto quando le difficoltà di fecondazione derivano dal muco cervicale. Il lavaggio degli spermatozoi prima della procedura consente inoltre di liberare lo sperma dalla maggior parte degli anticorpi.

Il sistema vascolare è costituito da una rete complessa di vasi sanguigni – arterie, vene, e capillari. Le arterie veicolano il sangue ricco di ossigeno ai tessuti dell’organismo, mentre le vene trasportano al cuore il sangue carico di anidride carbonica, una scoria del metabolismo. I capillari, i più piccoli vasi sanguigni del corpo, collegano le vene e le arterie e consentono il trasferimento di fluidi e nutrienti da- e verso- i tessuti circostanti.

Nella vasculite i vasi sanguigni si infiammano e si ispessiscono, restringendosi e riducendo la quantità di sangue, ossigeno e nutrienti vitali che raggiungono organi e tessuti. L’infiammazione può essere di breve durata (acuta) oppure a lungo termine (cronica). In alcuni casi nei vasi malati si assiste alla formazione di un coagulo (trombo) che ostruisce il flusso sanguigno. In altri casi, invece di restringersi i vasi malati si indeboliscono e si dilatano, dando luogo a uno sfiancamento detto aneurisma. Per molte delle sue forme, la causa della vasculite è sconosciuta (vasculitidi primarie), per alcuni tipi la causa è invece infettiva. Le forme di vasculite provocate da una patologia sottostante sono chiamate vasculitidi secondarie. Per esempio, nella maggior parte dei casi la crioglobulinemia è secondaria all’infezione da epatite C, mentre il virus dell’epatite B è responsabile di alcuni casi di poliarterite nodosa. Le vasculiti possono anche insorgere in conseguenza di una malattia del sistema immunitario come l’artrite reumatoide o il lupus, e infine quale reazione allergica a un farmaco antibiotico o diuretico.

La patologia dei testicoli come sintomo di vasculite è da considerarsi un’eccezione, in quanto nella maggior parte dei casi la vasculite testicolare insorge come parte di una malattia sistemica, quasi sempre la poliarterite nodosa (PAN), una rara forma di vasculite che colpisce soprattutto il sesso maschile (0.7 persone ogni 100.000). Nella sua forma classica riguarda le arterie piccole e medie di un organo; il testicolo è coinvolto in circa il 38-86% dei casi, dei quali è sintomatico solo il 18%. Per quanto comune, il coinvolgimento testicolare è di rado la prima manifestazione, e viene quasi sempre preceduto da sintomi sistemici quali febbre, malessere, perdita peso e talvolta da rash cutaneo e neuropatia periferica, i cui sintomi sono la sensazione di bruciore e prurito oppure debolezza e insensibilità della mano o del piede.

La diagnosi della vasculite testicolare autoimmune
L’impegno diagnostico maggiore è rappresentato dal distinguere ed escludere, in un paziente con sospetta vasculite, le cause secondarie o le condizioni che possono mimare una vasculite testicolare, per esempio il tumore dei testicoli. Poiché i segni e sintomi della vasculite sono simili a quelli di molte altre condizioni, la diagnosi si fa per esclusione. I test di laboratorio sono in parte non-specifici in quanto riflettono la natura infiammatoria sistemica della malattia:

• velocità di eritrosedimentazione (ESR) e formula leucocitaria: valori elevati suggeriscono la presenza di un’infiammazione
• colture di sangue per rilevare la presenza di eventuali infezioni
• sierologia Epatite B e C
• proteina C-reattiva (CRP): valori elevati suggeriscono la presenza di un’infiammazione
• Anticorpi Citoplasmici Anti-Neutrofili (C-ANCA) e Anticorpi Citoplasmici Anti-Neutrofili Perinucleari (P-ANCA): i primi sono specifici della granulomatosi di Wegener, gli altri sono presenti in altre forme di vasculite
• Fattore Reumatoide (RF): valori molto elevati sono presenti nell’artrite reumatoide, la sindrome di Sjögren e la vasculite associata a crioglobulinemia
• Complementi C3, C4, CH50. Sono normali o elevati in alcuni tipi di vasculite, ma tendono a essere bassi nella vasculite associata a lupus eritematoso sistemico, crioglobulinemia e vasculite associata a epatite B e C
• Anticorpi Anti-Nucleo (ANA)
• Crioglobuline: valori bassi suggeriscono il consumo da parte dei complessi immunitari, spesso ritrovati in alcune malattie autoimmuni. Devono essere presenti per diagnosticare la crioglobulinemia mista essenziale ma possono essere presenti anche in altre vasculiti primarie o secondarie.

In genere nei pazienti affetti sono presenti trombocitosi (piastrinosi), valori elevati della (ESR) e anemia normocromatica.

Si considerano nella diagnosi differenziale la vasculite o la poliartrite nodosa (PAN) quando il paziente presenta una massa dolente nel testicolo in assenza di trauma o epididimite, e quando la risonanza magnetica o l’ecodoppler scrotale (ecodoppler dei testicoli) evidenziano un sospetto tumore. La diagnosi di PAN si fa sulla base dei segni clinici sistemici e sui risultati delle analisi. L’ecodoppler dei testicoli consente di visualizzare la struttura intrascrotale e di decifrare molte patologie del contenuto scrotale. La terapia iniziale della maggior parte delle vasculiti consiste nella somministrazione di corticosteroidi.

La poliarterite nodosa è la causa più comune di vasculite sistemica necrotizzante dei testicoli (il termine “vasculite sistemica necrotizzante” descrive il processo sistemico nel quale l’architettura dei vasi sanguigni viene distrutta dalle cellule infiammatorie), tuttavia le vasculiti testicolari sono osservabili anche in altre malattie sistemiche associate alla vasculite e in alcuni casi possono insorgere anche in modo isolato, senza cioè essere necessariamente la manifestazione di una sottostante condizione sistemica.

La vasculite localizzata limitata a uno specifico sito anatomico o organo è spesso istologicamente indistinguibile dalle forme più gravi e sistemiche della vasculite. Per definizione, la vasculite localizzata coinvolge i vasi di una regione vascolare confinata o un singolo organo senza evidenza clinica di infiammazione generalizzata. Il riconoscimento della natura localizzata o sistemica del processo vasculitico è fondamentale per porre una diagnosi corretta e prescrivere la terapia adeguata.

Le malattie a trasmissione sessuale possono essere dolorose, debilitanti, fastidiose, pericolose. In proposito, è bene ricordare che:

• le malattie sessualmente trasmissibili si diffondono prevalentemente attraverso il contatto sessuale
• sono spesso provocate da un batterio o da un virus
• il rischio di contrarre una malattia a trasmissione sessuale si riduce (ma non si azzera) praticando il sesso sicuro, cioè usando il preservativo.

Le MST sono più frequenti negli adolescenti sessualmente attivi e nei giovani adulti, soprattutto quelli che hanno più partner sessuali. Secondo le stime dell’Organizzazione Mondiale della Sanità, nel mondo sarebbero circa 400 milioni le persone colpite da questo genere di patologie (escludendo il contagio da HIV). Nei soli Stati Uniti, ogni anno vengono infettate più di 13 milioni di persone, e più di 65 milioni hanno una MST incurabile.

Nella maggior parte dei casi, le MST sono malattie relativamente non pericolose, che producono pochi o nessun sintomo. Tuttavia, alcune MST come la clamidia sono asintomatiche o minimamente sintomatiche: alcune persone saranno affette per giorni o settimane, mentre altre lo saranno per periodi più lunghi, a volte anche a vita. Naturalmente, durante i periodi in cui la persona è malata, in quanto soggetto infetto o portatore può diffondere la malattia.

Nell’infezione persistente i patogeni sfuggono alla sorveglianza del sistema immunitario e sono parzialmente inattivi; questa inattività è detta latenza. Tuttavia, alcuni eventi scatenanti quali lo stress, l’immunosoppressione o un trauma fisico possono riattivare i patogeni latenti. In alcuni casi, la malattia riattivata è asintomatica, è per esempio il caso della clamidia, mentre in altri la malattia è conclamata, come nel caso dell’herpes. In altre situazioni, infine, la malattia può essere grave o addirittura fatale, per esempio nel caso dell’HIV/AIDS o dell’epatite. Le persone che hanno contratto una malattia sessualmente trasmessa sono a maggior rischio di contrarre altre malattie quali l’HIV o l’epatite.

Complicazioni
Le complicazioni delle malattie sessualmente trasmissibili comprendono la Malattia Infiammatoria Pelvica e la Cervicite (infiammazione della cervice) nelle donne, l’Uretrite (infiammazione dell’uretra) e la Prostatite (infiammazione della prostata) negli uomini. In entrambi i sessi, la presenza di una MST compromette la fertilità. Le possibili conseguenze sul nascituro che viene infettato durante la gestazione o il parto comprendono la natimortalità, la cecità e danni neurologici permanenti.

Quando rivolgersi al medico
Uomini e donne devono rivolgersi al medico e sottoporsi allo screening per le MST se sviluppano ferite, pustole, ulcerazioni, abrasioni o irritazioni genitali, o in presenza di una anomala perdita di fluidi dal pene o dalla vagina. Nella donna, l’associazione di perdite patologiche e di dolori addominali o febbre possono indicare la presenza della malattia infiammatoria pelvica, una condizione, provocata da una malattia sessualmente trasmessa, che causa infertilità.]]> http://www.fertilita.org/index.asp?ItemID=249 Claudio Manna, ginecologo specialista in fecondazione assistita lunedì, 14 Apr 2008 8:5:40 +01:00 di Alfredo Damiani, specialista in Ginecologia e Ostetricia (vai al curriculum), Luigi Melgrati, specialista in Ginecologia e Ostetricia (vai al curriculum) e Francesco Capobianco, specialista in Ginecologia e Ostetricia (vai al curriculum)

La laparoscopia è una moderna tecnica chirurgica mininvasiva che, avvalendosi di una specifica strumentazione introdotta nella cavità addominale attraverso piccole incisioni cutanee, permette di visualizzare in modo ottimale gli organi in essa contenuti e, se necessario, di intervenire chirurgicamente con il minimo trauma per gli organi ed i tessuti  da trattare.

Questi, infatti, non vengono né “manipolati” né “esteriorizzati”, ma restano nella loro sede naturale per tutta la durata dell’intervento. Attraverso una telecamera, l’immagine delle strutture anatomiche viene ingrandita e trasferita su uno o più schermi televisivi: ciò rende più agevole e preciso il lavoro del chirurgo, consentendo l’ottimizzazione della diagnosi e del risultato dell’intervento stesso. L’operatore, infatti, riesce a vedere quei particolari che ad occhio nudo non sarebbero visibili.

Ne consegue pertanto, rispetto alla chirurgia tradizionale (Laparotomia, cioè l’apertura dell’addome), una serie di vantaggi legati alla minore “invasività”, come:

• riduzione

-    del sanguinamento: anche i vasi sanguigni di minor calibro, non altrimenti visibili, vengono chiusi prima di essere sezionati

-    del dolore post operatorio: con minor necessità di ricorso a farmaci antidolorifici;

-    delle complicazioni infettive: l’uso degli antibiotici è limitato a pochi interventi;

-    degli esiti aderenziali post-chirurgici: dopo un intervento chirurgico addominale può verificarsi che le anse intestinali e gli organi coinvolti nell’intervento stesso “aderiscano” tra di loro come se ci fosse un adesivo. Le aderenze possono a volte ritardare o bloccare la funzione intestinale al punto tale da richiedere un successivo intervento chirurgico e spesso possono essere causa di sintomatologia dolorosa, persistente e ingravescente

• più rapido recupero post-operatorio:

nella maggior parte dei casi, ci si può alzare ed alimentare dopo poche ore dall’intervento

• miglior risultato estetico:

assenza di grosse cicatrici; delle piccole incisioni cutanee, inoltre, quella intraombelicale risulta praticamente invisibile.

• Breve degenza: 24-72 ore (salvo complicazioni).
• Breve convalescenza: rapida ripresa e ritorno alle proprie attività.
• Minor traumatismo, in caso di ripetitività dell’atto chirurgico.

Per ottenere una buona visione degli organi pelvici è necessaria, tuttavia, la distensione della parete addominale. Questa può avvenire con l’introduzione di Anidride Carbonica (CO2) nella cavità addominale tramite un sottile ago, o con un apposito strumento che, agganciando il tessuto sottocutaneo, solleva meccanicamente la parete addominale.  La scelta fra le due metodiche dipende dal tipo d’intervento e dalle eventuali controindicazioni all’utilizzo di CO2.

I sintomi
Nell’insorgenza prepuberale del deficit di testerone, lo sviluppo sessuale è assente o incompleto: assenza di crescita dei genitali, di peli  pubici, ascellari e facciali (barba), insufficiente sviluppo muscolare, debole o assente interesse sessuale e assenza del cambio del tono di voce. Poiché nei soggetti con ipogonadismo non inizia la produzione di spermatozoi (spermatogenesi), l’infertilità è la norma.

Nell’insorgenza postpuberale del deficit di testosterone, i caratteri sessuali secondari elencati sopra sono debolmente espressi. I sintomi comprendono stanchezza, libido attenuata e scarsa funzionalità sessuale, infertilità e sensazione generale di malessere, non di rado associata a depressione. In entrambi i casi prospettati, il deficit di testosterone è associato a una ridotta massa ossea, a un maggior rischio di fratture osteoporotiche e a lieve anemia.

Classificazione dell’Ipogonadismo

(1) Ipogonadismo primario
Il termine ipogonadismo primario o ipergonadotrofico caratterizza la carenza di testosterone associata a patologia dei testicoli. Il termine “ipergonadotrofico” è associato agli elevati livelli di LH (ormone luteinizzante) e FSH (ormone follicolostimolante) rilasciati dalla ghiandola pituitaria, che rendono vano qualunque tentativo di stimolare le gonadi assenti o scarsamente funzionanti a secernere più testosterone.

Cause dell’ipogonadismo primario:
- sindrome di Klinefelter (47XXY)
- criptorchidismo bilaterale (testicoli ritenuti)
- anorchia bilaterale (assenza di tessuto testicolare)
- torsione del testicolo, orchite, tumore del testicolo
- orchiectomia
- chemioterapia o radioterapia.

(2) Ipogonadismo secondario
Il termine ipogonadismo secondario connota una carenza di testosterone dovuta a una patologia dell’asse pituitario ipotalamico. È noto come ipogonadismo ipogonadotrofico a causa dei bassi livelli di LH e FSH. Si distingue infine l’ipogonadismo ipogonadotrofico isolato, dovuto a un deficit ipotalamico congenito dell’ormone rilasciante gonadotropina (GnRH).

Cause dell’ipogonadismo secondario:
- tumore della ghiandola pituitaria
- craniofaringioma, un tumore cerebrale benigno
- ipogonadismo ipogonadotrofico isolato
- sindrome di Kallmann
- sovraccarico di ferro (emocromatosi o frequenti trasfusioni di sangue)
- malattia sistemica acuta e cronica
- trattamento con glucocorticoidi
- AIDS
- obesità severa.
Il tumore della ghiandola pituitaria e la Sindrome di Klinefelter sono, nell’ordine, la prima e la seconda causa più comune dell’ipogonadismo.

Le analisi
Servono a confermare l’anomala concentrazione di testosterone. Una sola misurazione del testosterone totale è in genere sufficiente. La verifica dei valori degli ormoni LH e FSH consente di distinguere tra ipogonadismo primario e ipogonadismo secondario. Per identificare le cause dell’ipogonadismo e valutare la gravità della carenza di testosterone sono indicate queste analisi:

- prolattina e funzione tiroidea per valutare più approfonditamente la funzionalità pituitaria
- risonanza magnetica della ghiandola pituitaria se è confermata la diagnosi di ipogonadismo
   ipogonadotrofico
- cariotipo (Sindrome di Klinefelter nell’80% dei casi, mosaicismi, 48XXXY, ecc.)
- emoglobina
- densità ossea
- ecografia testicolare

Il trattamento
La terapia ormonale sostitutiva a base di testosterone deve essere iniziata solo dopo aver risolto le cause curabili dell’ipogonadismo.

Perché si fa
Per ottenere l’ovulazione generalmente di un solo follicolo.

Come si fa
Si somministrano idonee quantità di ormoni ( in genere FSH) per un numero di giorni variabile secondo la risposta individuale della paziente che viene controllata con una serie di ecografie (monitoraggio follicolare) ed eventualmente misurazioni degli ormoni nel sangue (monitoraggio ormonale) nel corso della terapia. Quando il follicolo ha raggiunto dimensioni mature (intorno ai 20 mm) si consigliano i rapporti sessuali e si somministra un farmaco (HCG) per provocare l’apertura del follicolo e la fuoriuscita dell’ovocita (ovulazione) che potrà essere fecondato.

Risultati
Le percentuali di gravidanza, nell'arco di sei mesi, con questa terapia, possono giungere al 55% . Una delle situazioni trattabili con questa terapia è la Sindrome dell'ovaio policistico(5).

Rischi
Se si sviluppano ed ovulano più di un follicolo sono probabili gravidanze gemellari e raramente l’”iperstimolazione ovarica”

Impegno della coppia
modesto.

Gli spermatozoi furono descritti per la prima da Leeuwenhoek, l’inventore del microscopio, nel XVII secolo, ma solo nel 1928 il loro numero nell’eiaculato venne associato al potenziale riproduttivo. Da allora sono stati sviluppati molti tipi di analisi del liquido seminale, e molti parametri del seme sono stati via via messi a punto nella speranza di chiarire se un uomo sia o meno in grado di fecondare la propria partner.

Nel 1677, Leeuwenhoek scopre l’esistenza degli spermatozoi, e in questi termini ne dà notizia alla Royal Society of London, la più autorevole istituzione scientifica del tempo: “Ciò che qui descrivo non è frutto di una mia peccaminosa invenzione. L’osservazione fu compiuta a seguito dell’eccesso del quale la Natura mi ha dotato nei miei rapporti coniugali”. Dopo aver chiarito di non essere un masturbatore compulsivo, Leeuwenhoek descrive ciò che aveva visto osservando il suo sperma al microscopio: “Animalucoli… Ritengo che un milione di loro non raggiungerebbe la dimensione di un granello di sabbia. I loro corpi sono sferici, smussati in cima e dotati di una lunga coda sottile. Muovevano la coda come serpenti, come le anguille quando nuotano nell’acqua”. Più tardi, Leeuwenhoek affinò la sua indagine sugli “animalucoli”, e analizzando la parte più spessa degli spermatozoi scoprì “un intrico di piccoli e grandi vasi, così variati e numerosi che non dubito che possiedano nervi, arterie e vene. Quando li vidi, mi convinsi che non esiste corpo adulto nel quale non vi siano vasi identici a quelli presenti nel seme”.

(1) Anomalie del liquido seminale
L’eiaculato normale è di almeno 2 ml e contiene più di 20 milioni di spermatozoi/ml, più del 50% mobili e il 20% o più di forma normale. Alcune condizioni come l’ipospadia, la fimosi, il cancro dei testicoli o il varicocele possono essere all’origine di uno sperma di qualità inadeguata alla fecondazione. Quando vi è evidenza di una grave anomalia del liquido seminale e il concepimento naturale è considerato improbabile, si può ricorrere a una tecnica di Fecondazione Assistita nota come ICSI, o microiniezione di spermatozoi. Questa forma di micromanipolazione consiste nell’iniettare al microscopio uno spermatozoo, accuratamente scelto per le sue caratteristiche, direttamente nell’ovocita. La ICSI viene effettuata solo all’interno delle Tecniche di Fecondazione Assistita, delle quali fa parte la Fecondazione in Vitro (IVF o FIV).

L’analisi del seme
Il seme maschile è un fluido rilasciato dal pene durante l’eiaculazione. É composto dal liquido seminale e dagli spermatozoi. Gli spermatozoi sono le cellule riproduttive maschili che fecondano l’uovo femminile. I parametri più importanti per determinare la qualità dello sperma sono il numero totale degli spermatozoi, la loro motilità e la loro forma (morfologia).

Tabella I. Valori normali delle variabili seminali secondo l’Organizzazione Mondiale della Sanità (1992)

Analisi standard

volume	2.0 ml o più
pH	7.2-8.0
concentrazione degli spermatozoi	20x106 spermatozoi/ml o più
conteggio totale degli spermatozoi	40x106 spermatozoi/eiaculato o più
motilità	50% o più con progressione di andata (categorie a e b) o 25% o più con rapida progressione (categoria a) a 60 minuti dall’eiaculazione
morfologia	30% o più con forma normale
vitalità	75% o più vivi
globuli bianchi	< 1x106/ml
immunobead test	< 20% degli spermatozoi con particelle adese
MAR test	< 10% degli spermatozoi con particelle adese

Analisi aggiuntive

a-glucosidasi neutra	20 mU o più/eiaculato
zinco (totale)	2.4 m-mol o più/eiaculato
acido citrico (totale)	52 m-mol o più/eiaculato
fosfatasi acida (totale)	200 U o più/eiaculato
fruttosio (totale)	13 m-mol o più/eiaculato

Tabella II. Nomenclatura delle variabili seminali secondo l’Organizzazione Mondiale della Sanità (1992)

normozoospermia	eiaculato normale come definito nella Tabella I
oligoazoospermia	concentrazione di spermatozoi inferiore a 20x106/ml
astenoazoospermia	meno del 50% di spermatozoi con progressione di andata (categorie a e b) o meno del 25% degli spermatozoi con movimento come da categoria a
teratoazoospermia	meno del 30% degli spermatozoi con morfologia normale
oligoastenoteratozoospermia	indica la presenza del disturbo che connota tutte e tre le variabili (è possibile usare la combinazione di due soli prefissi)
azoospermia	assenza di spermatozoi nell’eiaculato
aspermia	assenza completa di sperma

(2) Assenza di spermatozoi (azoospermia)
L’assenza di spermatozoi nell’eiaculato (azoospermia) rappresenta una grave diagnosi di infertilità perché rende sterile la coppia. L’azoospermia può essere di origine ostruttiva o non ostruttiva.

(2a) Nell’azoospermia ostruttiva lo sperma viene prodotto ma non può essere rilasciato dai testicoli a causa dell’assenza congenita dei vasi deferenti, come nei soggetti con Fibrosi Cistica, a causa di un’infezione che blocca i vasi deferenti come una malattia sessualmente trasmissibile, o più raramente a causa di un ingrossamento (iperplasia) della prostata. In questi casi il paziente deve essere in primo luogo affidato a un andrologo.

(2b) Nell’azoospermia non-ostruttiva i testicoli non producono spermatozoi oppure li producono in quantità estremamente esigua e in quest’ultimo caso essi non sono vitali e quindi non hanno capacità fecondante. Alcune tra le più frequenti cause di azoospermia non-ostruttiva sono:

• eiaculazione retrograda; lo sperma viene eiaculato nella vescica invece che all’esterno del corpo attraverso il pene
• azoospermia indotta dall’assunzione di testosterone, di agenti chemioterapici o dalla radioterapia
• fallimento testicolare. In alcuni casi i testicoli interrompono la produzione di spermatozoi per ragioni inspiegate. La produzione diminuisce gradualmente fino a cessare del tutto. Questa condizione può essere rilevata attraverso alcuni semplici dosaggi ormonali. Sfortunatamente non esistono trattamenti in grado di ripristinare la normale spermatogenesi, a meno che non sia diagnosticata una causa ormonale che può essere convenientemente curata
• vasectomia. È l’intervento che consiste nella resezione, dopo legatura, dei vasi deferenti che trasportano gli spermatozoi. Solo in rari casi è possibile ripristinare la fertilità con un intervento chirurgico di ricostruzione delle vie seminali chiamato vasovasostomia.

(3) Cause genetiche
Alcune malattie genetiche sono più comuni tra gli uomini con anomalie spermatiche:

• cariotipo anomalo. Gli uomini con azoospermia o con una quantità estremamente ridotta di spermatozoi nell’eiaculato hanno un maggior rischio di avere un’anomalia genetica. In questo caso le tecniche di Fecondazione Assistita non sono raccomandate
• microdelezione del cromosoma Y. L’assenza di alcuni geni dal cromosoma Y (il cromosoma maschile) è più frequente negli uomini con azoospermia. Al momento non è disponibile alcuna cura. L’uso della ICSI è sconsigliato in quanto i figli erediterebbero lo stesso difetto e quindi sarebbero sterili come il padre
• fibrosi cistica. In circa il 96% dei casi gli uomini affetti da fibrosi cistica non hanno spermatozoi nell’eiaculato, soprattutto a causa dell’assenza (agenesia) congenita bilaterale dei canali deferenti. La diagnosi di questa agenesia deve essere posta il più presto possibile all’interno del quadro diagnostico di un uomo infertile, in quanto la fibrosi cistica è una malattia ereditaria con il 25% di probabilità di essere trasmessa ai figli se entrambi i genitori sono portatori. Se un solo membro della coppia è portatore di fibrosi cistica è possibile ricorrere alla ICSI in quanto le probabilità di trasmissione della malattia sono basse; se entrambi i membri della coppia sono portatori, la Diagnosi Genetica Pre-Impianto consente di identificare gli zigoti anomali e di evitarne il transfer. Infine, quando risulta evidente una causa genetica di infertilità, la consulenza genetica prima della Fecondazione Assistita è la norma.

(4) Immobilità degli spermatozoi
Quando l’eiaculato contiene una quantità adeguata di spermatozoi ma questi non sono sufficientemente mobili o non hanno alcuna motilità, la fecondazione naturale non può avvenire per impossibilità degli spermatozoi di raggiungere l’ovocita nelle tube della donna. Alcune condizioni mediche, per esempio la sindrome di Kartagener, provocano l’immobilità degli spermatozoi, per la quale non esiste cura. Il ricorso alla ICSI è raro in quanto è difficile distinguere gli spermatozoi non vitali da quelli vitali ma immobili.

(5) Anticorpi antisperma
In questa condizione di infertilità immunologica, generalmente provocata da un trauma accidentale o chirurgico del tratto riproduttivo maschile, l’organismo produce piccole cellule, gli anticorpi antisperma, che aderiscono agli spermatozoi e ne impediscono l’azione. Maggiore è la percentuale degli anticorpi antisperma all’interno del liquido seminale, più severa è l’infertilità. Per ovviare a questa situazione si ricorre alla Fecondazione Assistita: Inseminazione Intrauterina, ICSI.

Some  anglo-saxon researches, in the prestigious English and American universities (Oxford and Harvard),  have developed a biological test that identifies a particular anti-embryonal activity of the immune system of women who present with poly-abortivity or absence of implantation.

The embryo toxicity test is performed using the 4 day old embryos of mice (blastocysts) cultivated for three days in the presence of the serum of the woman affected by poly-abortivity. The number of embryos that show “hatching” and “outgrowth”, that is the number of embryos that hatch out of the pellucid and implant on the Petri capsule. The use of a definitely fertile woman’s serum allows us to decide if the serum of the patient is embryo toxic.

This test seemingly identifies the presence of a hyper-production  of type Th1 (interleuchina and interferon –y in particular)  linfochine and interferons with cytotoxic effects, that damage the embryo.  The serum concentration of this peptide does not vary according to the menstrual cycle, consequently it is possible to analyse the possible presence of the embryo-toxic factor using a blood test performed on any day of the cycle.

 This clinical exam was invented by J. Sargeant  at Oxford University in England and successively modified by J. Hill of Harvard University in the United States.  The information regarding the clinical results has been published in international scientific journals these being JAMA (Journal of American Medical Association) American Journal of Obstetrics and Gynaecology, Fertility and Sterility American Journal of reproductive Immunology.

From these studies it is evidenced that 30-40% of women with recurring abortion result positive for the embryo toxic factor without any correlation with the possible presence of auto antibodies or other possible causes of abortion.  This test has been accepted by the American Food and Drug Administration (FDA), the highest authority in the United States for the control of  drugs and diagnostic exams, as a clinical test to perform on patients with recurrent abortions and lacking implantation.  The test is performed in a way that allows for the use of embryos obtained from 5 different mice, and at least 20 blastocysts per patient.  This is done in order to avoid that the test depends on the animal used and in order to have a statistically significant number of embryos to evaluate the sample tested and for control.

This test allows for the identification of a group of patients who show an immune response to abnormal T cells that can cause the elimination of the embryo, that, otherwise, would  not be identified using the clinical examinations generally used for the diagnosis of recurrent abortion.  The patients who test positive for the embryo toxicity factor do not generally test positive for other immunological tests, and are often helped by cortisone therapy.

About one third of patients who test negative for all the other exams result positive for the embryo toxic factor.  The execution of the test in these women allows for specific treatment.  Even though the test is not easy to perform, and has a significant cost, it could provide essential information towards the treatment of these patients.  To perform the test 5ml of blood has to be drawn and  serum obtained that has to be refrigerated and delivered the same day or frozen.

• The risk is calculated singularly for each embryo

The results of the biochemical test and of the ultrasound are combined to formulate the specific risk for chromosomal pathology. The Duotest is capable of identifying a large number of cases of Downs Syndrome, Trisomia 18 and Trisomia 13.  This exam is capable of identifying about 65% of the pathological cases with a 5% false positive margin.

If the tests show increased risk, this does not necessarily mean the  foetus has problems, but it may be opportune to deepen the investigation with an amniocentesis. In the case of a negative test one cannot completely exclude the possibility of foetal problems, because, even though it is reliable, this investigation remains probabilistic and gives an idea of the risk percentage, but does not give a diagnosis.  It should be remembered that the exam is not an alternative to an amniocentesis, in the case of  a high risk pregnancy because of advanced age or because of family history.

Disclaimer: the information provided on this site is designed to support, not replace, the relationship that exists between a patient/site visitor and his/her existing physician.

Before ovulation, however, entrance is easy.

If the hormonal secretions of the woman are normal and the cervix works well, the mucus changes in the days that precede ovulation to allow the spermatozoa to enter.  If the neck of the uterus has problems (e.g. cervicitis) or the hormonal secretions are not adequate the mucus is scanty, viscous and remains impermeable for the spermatozoa ,therefore, the meeting of the ova and the spermatozoon are not very likely to occur.  These abnormalities can cause infertility, this is why it is essential to verify the quality of the cervical mucus and the mobility of the spermatozoa in its presence.

The post-coital test, or Hunher test, is a laboratory examination that facilitates the study of the properties of the cervical mucus in the pre-ovulatory period, and allows us to upraise the mobility of the spermatozoa of the partner within the mucus. It is a painless exam, which is part of the initial routine of the infertility diagnosis. Since the test is interpretable, it is necessary to adhere scrupulously to all the conditions of its realisation: the test should be effected during the pre-ovulatory period( that is one or two days before the expected date of ovulation). To ascertain the exact moment in which to carry out the test, various methods can be used. Compile a basal body temperature curve, perform follicular monitoring or measure the hormonal dosages or perform a urine ovulation test. Often several systems are combined.  Anyhow,  even the woman herself is generally aware of the presence of cervical mucus and informs the gynaecologist who then performs the necessary  tests one of these being a quality and quantity test of the cervical mucus (“cervical score”).

In every case, the date of the last menstruation is noted, counting from the from the first day of blood loss.  For the man, 4 or 5 days of sexual abstinence are necessary in order for the quality of the sperm to be optimum.  Sexual intercourse has to take place 6 – 12 hours before the collection of the mucus, which take place in the laboratory where the number and the mobility of the spermatozoa in the cervical mucus will be tested.  Intercourse has to be followed by a rest period where the woman remains lying down for 20-30 minutes, and it is necessary not to wash the genitals before the collection of the mucus.

The collection of the mucus is painless and risk free and does not require admission into hospital or anaesthetic.  The woman is in a gynaecological position, and after the insertion of the speculum the mucus is drawn, especially endo-cervical mucus, from the cervical channel.  The mucus collected is immediately taken to the biologist, who examines it with a microscope to check the quantity and the viscosity, the transparency, cristalisation pattern  and of course the pH.  Any signs of infection are also checked for (the presence of germs and leucocytes , white blood cells)  Naturally the spermatozoa are counted especially the mobile ones taking note of the type of motility.

The results

Positive test: everything is normal because the mucus is abundant, it has normal viscosity, it is slimy, transparent and the cristalization results are normal ( under the microscope it presents with the typical fern form).  The pH is between 6.5 and 8.5, there are no germs or leucocytes and there are normally 5 spermatozoa with normal mobility (straight and fast) within the visual range.

Negative test: poor quality mucus.  Scanty mucus, with an acidic pH, opaque with poor cristalization. The live mobile spermatozoa are few.  In this case it has to be verified whether the test was really performed in the pre-ovulatory period, and if it is not so, the test is repeated two or three days later or in the following cycle.  If the quality of the mucus does not improve after two consecutive  post-coital tests, hormonal stimulation is prescribed in order to improve the quality.  In the presence of a bacterial infection antibiotic or antiseptic treatment is prescribed before another test is performed.  A reason for the negativity of the test could be that the cycle was not ovulatory and hormonal stimulation of the ovaries can normalise everything.

A negative test with good quality mucus: All the physical and chemical qualities of the mucus are normal and there are no signs of infection, live mobile sperm are absent or few or the mobility of the spermatozoa present is abnormal ( fixed with an oscillating movement).  In this case it has to be verified if sexual intercourse occurred in normal conditions and verify if the spermiogram is normal.  In the case of a normal spermiogram , the mucus or the mucus/spermatozoa interaction is the likely cause of the negative test results.  At this point we proceed to perform a  cross penetration test to find out if the abnormality is from the spermatozoa or the mucus.  The behaviour of the spermatozoa for instance can be verified in bovine mucus.  This last test could raise doubts as to the presence of  anti-spermatozoa immunisation in the mucus or the sperm itself, that is the presence of anti-spermatozoa antibodies.  The presence of antibodies is however are rare occurance.

If hormonal stimulation has not produced positive effects we then move on to intrauterine insemination.

Disclaimer: the information provided on this site is designed to support, not replace, the relationship that exists between a patient/site visitor and his/her existing physician.

This information is however not sufficient to evaluate and give information on the spermatozoa’s capacity to fertilise which, seemingly, does not depend only on the above mentioned parameters.  Recently, attention is being paid to other measurable characteristics of the spermatozoa.  New tests have been put in place that are capable of  evaluating the genetic inheritance of the spermatozoon  - a quality which is closely related to the capacity, more or less, to fertilise.

Test of spermatic maturity (Sperm-Hyaluronan Binding  Assay)
This test is based on the capacity of mature spermatozoa to bind themselves to hyaluronic acid,  the opposite of immature spermatozoa which are not capable of doing this.  This capacity is acquired after the process of spermatogenesis is completed, therefore the chromosomal load has become aploid and the male gametes have undergone a series of physiological changes, these being, the elimination of the cytoplasm and the remodelling of the plasmatic membrane, making them capable of binding themselves to hyaluronic acid when they meet the receptors. This test serves to evaluate the percentage of physiologically normal and mature spermatozoa in the sample being tested.  If 80% of the spermatozoa are bound this indicates the normality of the sample:  below 80% of the spermatozoa bound indicates diminished maturity.

Test of spermatic DNA fragmentation
The normal structure of the chromatin  of the spermatozoa is an indispensable characteristic for the correct transmission of paternal genetic information and for the correct functioning of the spermatozoon.  The increase of DNA fragmentation of spermatozoa is an important cause of male infertility in that it diminishes the percentage of fertilisation, naturally and in vitro.  It is estimated that in the presence of a  DNA fragmentation index (DFI) higher than 30% it is wise to join an assisted reproduction program, choosing the ICSI technique which in these cases seems to give best results.

Spermatic Aneuploid
This test, which is also effected on the seminal liquid, serves to evaluate if the chromosomes present in the spermatozoa are present in their normal numbers, or if some of them are missing or over numbered.  It is requested mostly in the presence of poly-abortivity in the couple,  since spermatozoa that are carriers of chromosomal abnormalities can, if they can achieve fertilisation, cause abortion  problems.

Disclaimer: the information provided on this site is designed to support, not replace, the relationship that exists between a patient/site visitor and his/her existing physician.

To test the quality of the seminal liquid the biologist uses two principal tests, the most important being a spermiogram.

A spermiogram allows the biologist to study the consistency of the sperm using a sperm count and observing therir mobility, the duration and the morphology.  The results of a spermiogram can show:

• Azoospermia: the complete absence of spermatozoa in the ejaculate
• Oligospermia: less that 30million spermatozoa per ml
• Asthenospermia: insufficient mobility of the spermatozoa
• Terathospermia: a very high number of abnormal spermatozoa

When these last three causes accumulate, this is referred to as oligo-astheno-terathospermia. The fertilising capacity becomes very poor, even if you cannot exclude accidental pregnancy. Whatever the result of the first examination may be, a spermiogram should show similar results after several tests (2 to 3 after an interval of one month): This is the condition that leads to the diagnosis of a pathology.  The analysis of normal seminal liquid is characterised by the definition of these parameters: volume, viscosity, number of spermatozoa per millimetre, mobility one hour and three hours after ejaculation and a morphological analysis of the spermatozoa.

Spermatozoa are mature reproductive cells, resulting from the maturation stage of the process of spermatogenesis.  Spermatozoa unite themselves with the secretions of the accessory glands to make sperm which is emitted during ejaculation. The spermatozoon fertilises the ovum in the moment of reproduction.  Produced in the seminal canal of the testicle, spermatozoa are directed towards the abdomen through different channels, where they mix with other secretions from the prostate to form sperm  During sexual intercourse, the spermatozoa are deposited into the woman’s vagina, from where they will continue their path till the fallopian tubes.  When they meet the ovule in the moment of fertilisation, only one spermatozoon can penetrate the membrane in that moment, the head enters but the tail remains outside.

A spermiogram is an analysis of the sperm, which is collected via masturbation (more rarely via coitus interruptus) into a sterile container (never a condom which may contain disactivating chemical agents) after three days of sexual abstinence.  A spermiogram is a simple, economic, quick, painless and absolutely fundamental examination.  The characteristics of the sperm should be observed immediately after withdrawal.  A spermiogram is generally repeated a month after the ferst withdrawal to confirm the diagnosis of infertility because the production of sperm can fluctuate in time.  Normal sperm contains between 20 – 200 million spermatozoa per cubic millimetre, of which 80% mobile, and the volume of the ejaculate between 2 and 5ml.

Spermioculture
This exam checks for bacteria in the sperm and is effected when there is a suspicion that an infection of the sperm could be the cause of  male infertility or when the presence of an infection could affect the result of FIV or ICSI.  The exam involves the  withdrawal of sperm via masturbation (like in a spermiogram) which is then put in culture in order to search for bacteria.
If the analysis identifies the presence of germs the doctor immediately prescribes therapy not only for the man, but often for his companion as well, who could be a carrier of an identical germ.

Male fertility depends on:
An adequate production of spermatozoa by the testicles (spermatogenesis), free circulation of the seminal liquid within the male genital tract, and lastly an adequate deposit of spermatozoa in the vagina of the woman.  Normal seminal liquid has the following characteristics;

• volume: 2-5ml
• number: 50-180 million spermatozoa/ml
• mobility: 80% on emission, 60% after 4 hours
• morphology: 60-80%  with normal form
• pH: 7.6-8.2
• fructose: >1g/l

When these parameters are altered the following conditions are present:

• Oligospermia : reduction of the total number of spermatozoa,
• Oligoasthenospermia : reducton of the number and the mobility of the spermatozoa
• Oligoasthenoterathospermia : reduction of the number, mobility and the presence of  abnormally shaped spermatozoa
• Azoospermia : total absence of spermatozoa
• Necrozoospermia: the sample does not contain live spermatozoa
• Haemospermia and piospermia: respectively presence of blood and pus in the ejaculate
• Hyperspermia and hypospermia: respectively a higher volume than 6ml and lower than 2ml

Abnormalities regarding the deposit of the sperm in the vagina can be traced back to: surgery of the bladder, of the neck of the bladder or of the prostate (retrograde ejaculation), prostatectomy (surgical removal of the prostate), ipospadia, premature ejaculation, impotence, anatomic abnormality of the female genitalia

The factors of male infertility are:

• Varicocele , damage to the veins of the spermatic funiculi that causes the reduction of spermatozoa production.
• Hormonal deficit : because of the hypophysis, resulting in alteration of spermatogenesis
• Infections : of the prostate, the testicles (orchitis) caused by differing pathogens, especially of the sexually transmitted kind.
• Immunologic : auto immune response
• Genetic : damage of the chromosomes (micro deletion of the Y), syndromes of genetic origin (Klinefelter syndrome) cystic fibrosis.
• Obstructive: from acquired or congenital pathologies

The list shows the normal values of the parameters of a spermiogram

• Normal volume : higher than or equal to 2.0ml
• pH : between 7.2 and 8.0
• concentration of spermatozoa, number : between 50 – 180mil/ml
• concentration of spermatozoa : higher than 20 x 106/ml
• mobility (1 hour after ejaculation) : higher than or equal to 50% progressive mobility
• morphology : higher than or equal to 50% normal form
• vitality : higher than or equal to 55% live spermatozoa

Another exam that facilitates the analysis of sperm is the Hunher test, or post coital test. This analysis facilitates the study of the behaviour of the spermatozoa in female mucus after sexual intercourse during the female ovulatory period, over and above the analysis of the sperm, it allows for the verification of the consistency of the female mucus during ovulation.  In this case, however, the problem could be because of the mucus and not of the spermatozoa.  Other tests are available for the analysis of the sperm which specifically measure the survival rate of the spermatozoa by measuring the dosages of certain components of the sperm and through bacteriologic research.  In case of abnormality, complementary exams are:

• karyotype
• hormonal dosages
• immunologic research
• testicular biopsy

Disclaimer: the information provided on this site is designed to support, not replace, the relationship that exists between a patient/site visitor and his/her existing physician.

Failed attempts, above all, often have economic implications.  In fact not everyone can  afford to spend money on interventions that are very costly; for this reason it is necessary to try and reduce the costs by keeping the therapy levels as high as possible.

Finally, the attempts involve a notable wastage of time (monitoring, therapy, rest after transfer)  For this reason all energy needs to be concentrated (for both the couple and the medical team) to the maximum for every single attempt.

Here we would like to explain to you why attempts can fail and what we do when this happens.  Naturally, this is a generic description and cannot substitute advice given in specific cases.

We, in fact, believe that the secret to success is the personalisation of the therapy, in all the phases of the cycle and particularly during stimulation.

Causes of failure
First of all, it is necessary to specify that the results  of  assisted reproductive cycles generally depend on 2 or 3 factors: the quality of the centre (there are centres that have less than 10% pregnancies and centres that have more than 50%), the age of the woman (the higher the age the lower the results especially after 50 years), ovarian response to stimulation (which is generally linked to the age of the woman).    Therefore, the principal causes of failure are because of:

• Poor quality centre to which you resort
• Advanced age of the woman
• Poor  response to ovarian stimulation

The embryo
These factors negatively affect the quality of the embryo, on which the failure of the cycle principally depends.  In fact it is known that implantation is linked also to the uterus but to a much lower degree than the embryo.

The quality of the embryo depends principally on the quality of the ovum (to a much lower degree that of the spermatozoon).  Bad ova generally result from bad stimulation.  Good embryos have 4 to 6 cells that are equal, 48 hours after fertilisation.  Even a reduced number of  embryos transferred is often a cause of failure.  It is noted that especially in women of advanced age there is the need to transfer many embryos in order to have good chances.

Transfer: the transfer of embryos is a very delicate procedure, often difficult, in every instance it is critical because one wrong move that lasts a few seconds creates the risk of destroying all the work that was done before!  Wrong transfers are much more than you would believe.

Uterus: sometimes the uterus presents with myoma, polyps or other formations that can impede implantation of the  embryo and favour abortion.  This can happen if the uterus is not studied well before and these defects are not recognised and eliminated.

Immunological factors: numerous studies have identified the presence of circulating antibodies of different kinds that could impede implantation and favour abortion.  A study of these antibodies should be performed in the case of failure of Assisted reproduction.

Psychological factors: whether anxiety or other psychological factors can play a role in missed embryo engagement is often discussed.  It seems that excessive and un-coordinated contractions of the uterus can impede implantation.  Maybe adverse  psychological conditions can influence actual uterine contraction but this is not well documented.  Certainly, relaxed conditions are beneficial for
the normal progress of cycles of FIVET or ICSI.

What do we do in the case of FIVET or ICSI failure
The most important thing is to personalise every phase of the process to the maximum because every patient is different from the next and it is necessary to adapt all the phases of the Assisted Reproductive cycle to the organism on which it is being undertaken at that moment to maximise the results obtained.

This requires lots of effort from the team but we believe that it is worthwhile effort!
This way we can list our programme in the cases of previous failures.

Tests that precede the attempt
We perform a very profound hormonal test before we begin stimulation.  This allows us to apply the most ideal type of stimulation for the patient (type of drugs, quantity and the method of administration).  In the same test cycle we perform the so called “test of transfer” which allows for a simulation of real transfer in order to choose the type of catheter to use, know exactly where to position the embryos (because not everyone has the same size uterus), know in advance the exact path the catheter should follow  (especially in the uterus) before you reach one cm from the bottom.  If we find any big obstacles that make transfer difficult these are removed.  In fact real transfer should be a quick and painless manoeuvre.

A certain amount of ability and sensitivity is necessary in order to perform embryo transfer which is a very delicate and critical procedure. The trial of transfer is part of an accurate study of the uterus that includes a hysteroscopy.

Any polyps and submucal fibroids should be removed and any conditions of  endometriosis (inflammation of the emdometrium) that have been diagnosed with the hysteroscopy, that if present can impede embryo implantation  should be treated.  Serious investigation is undertaken to find antibodies and pathologies that could be an obstacle for the implantation of the embryo.  In the case that these antibodies are found appropriate therapy is performed.

What do we do during the execution of an ICSI or FIVET cycle
Stimulation includes the use of various drugs that need to be adapted to the “type of endocrine system” of the patient we have in our care. Special  attention is given to patients who tend to develop few follicles (“low responder”) using particular preparations that precede stimulation itself.

Even those who tend to respond with an excessive number of follicles are treated with a particular therapy protocol, not so much for the prevention of hyper-stimulation, but, mainly in order to improve the quality of the ovules that are harvested, which in this case are immature or dismature thus giving way to poor quality embryos.

The heart of stimulation, because this allows for maximum efficacy, is monitoring   is and undertaken with extreme care and attention. In fact the dosage of at least 3 hormones is measured and an ultrasound  is performed, in order to adapt and modify the types and the quality of the drugs used to obtain optimal stimulation of the follicles which give the highest possible quality of ovules.

This program allows us to better evaluate if something isn’t working and therefore interrupt stimulation without reaching the harvest of ova and transfer of embryos that would have little or no possibility of implantation.  The monitoring that we perform is also put under computerised analysis using particular programmes that help in the decisions that need to be taken regarding the  drugs to be used from day to day.

What do we do in the laboratory to improve
Above all we keep very tight control of the conditions of the cellular culture for both bacterial pollution and for substances which are potentially toxic for the  ova and the embryo and also use special filters for the ambiental air circulation.

To improve the quality of the embryos we can use a certain number of special techniques. Hatching which involves the making an incision in the outer shell of the ovum called the “Zona Pellucida” by means of particular substances and ideal micro-utensils.  This is done to improve the exit of the embryo when in it should implant in the endometrium.

Culture is a laboratory technique: it involves maintaining the embryo immerged in an ideal    liquid, not alone, but with other cells that perform the function of absorbing toxic substances produced by the embryo itself or from the environment and produce growth factors that help the embryo to develop well.  Since the quality of the ova represents the most critical element for the success of the ICSI or FIVET attempt if the ova produced are bad regardless of all the effort made with stimulation, the chances of obtaining good embryos are almost inexistent.

Since the cytoplasm of the ova, that is the part that surrounds the nucleus with the chromosomes is often, in most of these cases, defective many  vacuole  (dark spots) are evident the only possibility might be that of transferring a certain quantity of cytoplasm that comes from a good ovum into the cavity of the poor quality ovum; this involves the transfer of cytoplasm which is a complicated technique that can render good results in certain cases.

Since the genetic material of the chromosomes from other peoples ova is neither touched nor transferred, this procedure is bio-ethically valid: it regards giving nutritive substances that come from the ovule of another more fertile patient (generally younger).  It is possible to perform culture of the embryos for  5 days till the blastocyst stage, this way they have a better chance of implantation.  Notwithstanding, if the embryo  was of good quality to start of with, it transforms into blastocysts even in the uterus after transfer.  If , however, it was of poor quality from the beginning it will not transform to blastocysts be it in culture outside the body nor inside the body.

From transfer and thereafter
The number of embryos that are transferred into the uterus greatly influences the chances of pregnancy.  Undoubtedly  the increase of embryos transferred the probability of twin or triplet pregnancies is higher.  Nevertheless, when many attempts fail especially in advanced age, a higher than average number of embryos are transferred.

In fact we believe that you cannot set a limit to the number of  embryos (lets say 3) to transfer because after a certain age (from 40 on) the quality of the ovules is not very good, it is therefore necessary to transfer many embryos to have higher possibility that at least one implants.

Transfer is a very delicate moment and can also be difficult because it is a manoeuvre that is generally undertaken “blindly”.  In fact once the catheter enters the uterus nothing can be seen and everything is linked to sensation or an indirect point of reference.

To be sure that the catheter is effectively inside the uterus and in the right place we follow its progress using ultrasound.  It is even possible to see the drop of liquid that contains the embryo coming out of the catheter.  After transfer, apart from the progesterone that is prescribed, a variable pharmacological  therapy is undertaken in order to make the endometrium more receptive to the embryo.

Disclaimer: the information provided on this site is designed to support, not replace, the relationship that exists between a patient/site visitor and his/her existing physician.

For a couple, but also for the medical team, the only result that really counts is obtaining a healthy baby.  Nevertheless, it is not enough to furnish the results of an assisted fertility activity only in terms of children born..

Understanding and interpreting the results of medically assisted fertilisation
In effect, the global results are nothing other than average statistics that can be very different from individual probability, every birth is the result of a complete chain of events that represent as many obstacles to overcome, each stage has its own difficulties, and not all couples are the same.  Therefore, for every method of assisted fertilisation we have to evaluate the results of every stage, the global results, the success factors that determine individual probability and lastly the short and long term risks.

Intrauterine insemination (IUI)
IUI is the first in line technique used in infertility cases where the tubes are permeable and  the quality of the sperm is good. If  it is combined with a small and controlled amount of ovarian stimulation, IUI offers pregnancy percentages in the region of 13% per cycle , with a risk of multiple pregnancies of 10%, essentially of twins.  In cases of multiple pregnancies, triplets or more are very rare, less than 1 in 1000.  Since the procedure is not very difficult, IUI can be repeated for several cycles.  The statistics demonstrate that 80% pregnancies occur in within the first four  attempts and 50% of the couples who  arrive at the sixth attempt become pregnant.

The elective reason for intrauterine insemination is cervical sterility caused by  the absence of mucus or caused by hostile mucus, because the treatment surpasses the obstacle represented by the uterine neck.  The circumstances are rare and they represent a very low portion of the innumerable number of IUI currently performed. The other reasons are female infertility, male infertility or infertility without a cause. In this case, the general idea is to guarantee the presence of the maximum number of  spermatozoa possible at the precise moment of ovulation, in order to optimise the probabilities of fertilisation.  500.000 spermatozoa need to be injected into the uterus in order to have good chances of pregnancy. The results of intrauterine insemination depend on many factors: the reasons, the age of the woman, the number of attempts, the type of ovarian stimulation if effected, the tracking of the cycle and the time of insemination in relation with ovulation, the sperm preparation method, the quality of the sperm before and after the preparation, the number of spermatozoa injected and so on. Because of many variables, the results demonstrate an extreme diversity. In controlled series, for all the reasons, the percentage of pregnancies varies between 0 and 23% per cycle with an average of about 8% per cycle.

The best results are obtained in cervical sterility (15%) and in unexplainable sterility (13%). The results are less satisfying in male reasons (5%).  These figures represent  the average obtained from available literature, and have a purely indicative value because, the techniques, the stimulation and criteria that determine the reasons, especially male, are extremely diversified.  With polyovulant stimulation, the percentage of pregnancies are often in the region of 15-18% per cycle, with 20% twin pregnancies and an undetermined number of triplet pregnancies, up to 6% according to some statistics.  With monoovulant stimulation it is possible to obtain pregnancy percentages of 12% per cycle, avoiding complications : without stimulation, less than 5% of twin pregnancies, triplet pregnancies rare.  It is important to realise that almost the total number of pregnancies is reached in the first 4 – 6 cycles of IUI; in the event of failure, the advise is to carry on with treatment.  The superiority of IUI in relation with intra-cervical insemination, even in cases where there are no abnormalities of the mucus, it has been demonstrated in the model represented by donor sperm with pregnancy percentages of 19.4% after IUI against 6.7% after intra-cervical insemination.

Stimulation with IUI tries to reproduce a normal cycle, that is to obtain the emission of only one or two ovules to the end of reducing the risks of multiple pregnancies.  The global success rate  of 11% may seem modest, but does not reflect the real degree of the method: what characterises IUI in relation to the  other medically assisted techniques is that  it is simple and can easily be repeated. The probabilities increase in proportion to the number of attempts. The elective use and therefore the use in series, that is repeating IUI in successive cycles, with intervals depending on the  couples chances. The results of a series of cycles, therefore, count more than those of a single cycle.  About 30% of couples become pregnant at the end of the third IUI, and more than 40% after the fourth attempt.

These figures can be compared to those of  IVF: a series of three cycles of  IUI gives better chances of pregnancy than a cycle of IVF, with less effort and at a lower cost.  This is the reason why IUI is proposed as the first line of fire to all couples who could benefit from it. The chances depend largely on three factors:  indication, the type of stimulation and the age of the woman. The indication is the reason why you have resorted to insemination.  In most cases infertility really isn’t present, but hypo-fertility, that is a spontaneous pregnancy is possible but the chances are diminished because of the presence of male or female abnormalities: permeable but slightly altered tubes, imperfect ovulation, lessening of the number and mobility of the spermatozoa, alteration of their form.  In reality IUI cannot be considered a real treatment, because once it has ended everything remains the same as it was originally.

Its objective is not therapeutic but substantial: IUI aims at optimising the chances of pregnancy by guaranteeing as perfect an ovulation as possible, and bringing close to the tube a slightly higher number of spermatozoa than what would be present in simple sexual intercourse.  In this context, it is impossible to precisely evaluate the influence of the different factors of infertility because in the majority of cases these are related.  Pure cases, in which a single factor is present, are too rare to allow statistical calculation except in the case of donor sperm, because in this case the sperm has proven fertility and the results are higher than average: 15.6% universally, but 20.3% for women less than 35 years old 9.1% between ages 35 and 39 and 6.4% after forty years.

Disclaimer: the information provided on this site is designed to support, not replace, the relationship that exists between a patient/site visitor and his/her existing physician.

For a couple, but also for the medical team, only the result really counts and obtaining a child in good health.  It is, therefore, not enough to furnish the results of  assisted fertilisation activity in only in terms of the number of children born.

Understanding and interpreting the results of assisted fertilisation
In effect, the global results are nothing other than average statistics that can be very different from the individual probabilities, each birth is a result of a complete chain of events that represent just as many obstacles to get over, each stage presents with its own difficulties, and not all couples are the same.  Therefore, with every method of assisted fertilisation, the results of every stage have to be evaluated, the global results, the factors that regulate individual probability, and finally the short and long term risks.

IVF (In vitro fertilisation) with micro-injection (ICSI)
ICSI is almost exclusively indicated for male infertility: the injection of only one spermatozoon into the ovule allows fertility to be achieved even in the case of  extreme spermatic insufficiency.  The cases of female infertility treatable with ICSI are exceptionally few, and always regard an abnormality where the ovule impedes the spermatozoon from penetrating. The systematic use of ICSI in place of  classic IVF does not improve the probability of obtaining a pregnancy.

Fertilisation failures were numerous before the advent of ICSI.  The situation has improved greatly and classical IVF is no longer used in serious cases of spermatic insufficiency.  The failures of ICSI are rare, about 6%, and they are essentially failures of female origin, concerning the woman’s age and the harvest of a scanty number of mature ova. The results of ICSI are better than those of  classical IVF, but this does not mean that ICSI is a better technique.  In effect, the difference is not because of the technique itself but rather the fact that the cases that are treated are not identical. Many controlled studies have shown that resorting to ICSI for patients who have tried IVF does not improve their results.  Global statistics correspond with average statistics, and their value is for the entire number of people treated.  With reference to couples, the probability of success depends principally on three factors: the diagnosis, the number of embryos transferred and the woman’s age.

Artificial insemination
Artificial insemination comprises of the introduction of spermatozoa into the female genital apparatus at the level of the uterine neck or further into the uterine cavity or the tubes, that is into the peritoneal cavity.  During intracervical insemination the sperm is simply deposited into the cervical mucus with a cannula , prolonging the contact and protecting the spermatozoa from vaginal acidity.  Insemination has to occur immediately before ovulation: when cycles are regular, the approximate favourable moment can be determined using a temperature curve and from an examination of the mucus. This moment represents the nadir, that is the day with the lowest point on the curve before the temperature increases.  The mucus is abundant, limpid and slimy.  If, however,  the cycle is irregular it is necessary to resort to ultrasound monitoring and doses of hormones, and often the stimulation of ovulation.  In this case the favourable moment comes 36 hours after the beginning of ovulation.

Intra-cervical insemination is indicated when the post-coital test (Huhner test) is negative while the mucus penetration test in vitro is positive.  This can come about as a result of many causes Ejaculation disturbances, retrograde ejaculation, low volume of ejaculation and poor quality sperm. The statistics regarding cervical insemination are dated because since 1985, this technique has been fundamentally abandoned in favour of IUI, intrauterine insemination which guarantees better results.  Nevertheless, this technique can be very efficient when the aim is to simply correct a defect concerning the meeting of the ovum and the spermatozoon in the presence of mucus, normal sperm and normal ovulation.  The percentages of pregnancy are about  15-20% per cycle in this rare instance but go down to 4% for reasons of spermatic insufficiency.  Intra cervical insemination is used today only for one principal reason: for insemination with donor sperm, it is the least medicalised method because it can be performed during a spontaneous cycle, without hormonal treatment (that is without the stimulation of ovulation) on condition that spontaneous ovulation is normal.  Nevertheless, if  ovulation is abnormal, stimulation is therefore made necessary and this then leads the way to intrauterine insemination which guarantees normal results.

Intrauterine insemination involves the introduction of spermatozoa directly into the uterus at the time of ovulation.  In spontaneous cycles the results are poor.  The treatment is always combined with ovarian stimulation and the percentage of pregnancy depends largely on the type of stimulation used and also on whether the attempt is to form only one or more ovules.

Disclaimer: the information provided on this site is designed to support, not replace, the relationship that exists between a patient/site visitor and his/her existing physician.

Abnormalities of the female genital tract can be found among the causes of  infertility. About a quarter of fertility disturbances can be blamed on problems of permeability of the tubes. Normally when the ovule is expelled from the ovaries, during ovulation, it is collected in the tubes where it is then reached by the spermatozoa that have crossed the uterus and travelled down the tube.  An obstacle, however, can impede the normal development of these events.  Let us distinguish between an obstruction of the uterine cavity, on the side of the ovaries : the ovule cannot be released into this space. The obstacle, however, can also be found at the entrance of the tubes, on the side near the uterus, and in this instance it’s the spermatozoa that cannot advance and reach the ovule.

Other causes
In most cases, the obstructions are caused by genital infections, of the tubes (salpingitis), almost always caused by sexually transmitted diseases (STD), for example chlamydia, which can go unobserved but are sufficient to cause an obstruction.  This is why it is important for all women to prevent the risks of STD’s, adequately protecting themselves during intercourse with occasional partners and regularly visiting the gynaecologist.  Other than infections, among the causes of obstructions, there are also adhesions that cause the sticking together of the walls of the tubes, and also problems associated with endometriosis.   

Discover the problem
In order to identify a tubal patency problem, the following exams are recommended:

• A fertiloscope, which is a new, mini-invasive, method of exploring the posterior pelvis which allows for a complete valuation of the mechanical factors of female infertility.
• A hysterosalpingogram, which is an x-ray of the pelvis which is conducted after the injection of a radio-opaque product into the uterus, through the vagina.  The exam is generally conducted by a radiologist and a gynaecologist, it entails the insertion of a catheter attached to a syringe containing the contrast liquid.  The product is gradually injected and the x-rays are made. Normally the tubes become opaque gradually and carries on till the radio-opaque product passes into the peritoneal cavity.

Presently the actual use of this method is relegated almost exclusively to the evaluation of  tubal patency and for the identification of possible congenital abnormalities of the uterus (e.g. uterus with a septum, uterus bicornis etc).  Sometimes, the hysterosalpingogram , which is a diagnostic operation, becomes therapeutic. It is not uncommon that the pressure used for injecting the contrast agent resolves the tubal narrowing.  The exam can be relatively painful but does not require anaesthesia. Sometimes anti-allergic pre-medication or prophylactic antibiotic-therapy is suggested.  This method has risks but they are rare : allergic reactions, infections (salpingitis, endometritis, reactivation of chronic salpingitis).

• Hysteroscopy : the objective is to examine the uterine cavity using an endoscope passed through natural passages.  It can be divided into diagnostic hysteroscopy and operative hysteroscopy.  The first is effected in a completely pain free way without the use of anaesthesia using a fine hysteroscope with a hydraulic mechanism.  With this approach it is sometimes possible to perform small surgical operations (e.g. the removal of polyps on a stalk).  The second is effected under general anaesthetic and allows for serious surgery for example the removal of fibroids and uterine sects, etc. It is important to remember that in some facilities, a diagnostic hysteroscopy  is undertaken with old generation hysteroscopes and requires either local anaesthetic or total anaesthetic.
• Hysterosonosalpingograph: consists of injecting  physiological solution into the uterus and evaluating the tubal patency with an ultrasound and colour doppler.  The reliability is almost overshadows that of a hysterosalpingograph (used very frequently in the USA) and is less fastidious. On the down side it is less reproducible in  respect to the hysterosalpingograph.
• A celioscopy , is an exam that requires anaesthetic.  The surgeon makes a small incision at the level of the navel and inserts a fibre optic scope in order to examine the tubes from the inside with or without the use of a special dye.
• An ultrasound indispensable for an accurate evaluation of the pelvis (uterus, ovaries, etc).  It can be used , especially the 3D – 4D methods, to find and correctly measure the size of uterine sects that can often cause problems if they are ample.  It can identify potential pelvic adhesions suspected in a high number of cases of endometriosis (the diagnosis of which sometimes requires a celioscopy).  Obviously an ultrasound is indispensable for the diagnosis of endometrial polyps, submucal fibroids, ovarian masses and some tubal pathologies.  Unfortunately the one real handicap of  an ultrasound is that it is often used superficially and often as a brief epilogue to a consultation. As is often highlighted, even at the beginning of congresses and courses: with ultrasound you only see what you have looked for carefully.  Most of the failures attributed to this method are in reality failures of the ultrasound operator.

Getting around the obstacle
The tubes can be re-canalised to render them functional again, this however, requires a direct action.  Generally, this means a surgical operation : the obstructed part of the tube is eliminated and the pieces are “glued” back together, the obstructed cavity is reopened.  The percentage of success in this sort of surgery is extremely variable and also increases the risk of extra-uterine pregnancies.  For some years now an interesting alternative exists, selective hysterography. A probe is placed at the entrance of the obstructed tube and a product is injected using progressive pressure. This allows for the “unblocking” of the tube without surgery.

Disclaimer: the information provided on this site is designed to support, not replace, the relationship that exists between a patient/site visitor and his/her existing physician.

The last born of the assisted procreation techniques, the intracytoplasmic sperm injection has rapidly demonstrated its stupefying efficacy.  The benefits of assisted reproductive techniques do not have to be demonstrated because they are responsible for tens of thousands of births worldwide each year. Nevertheless, some recent methods are attacked because of their potential dangers.  This is the case of ICSI.  Lets see why.

ICSI is the result of a biologists error. Researchers were trying to evaluate the benefits of the direct nearing of the spermatozoa to the membrane of the ova within a not very efficient technique called SUZY (sub-zonal insemination), which should have allowed fertilisation with originally non fertilising sperm.  During one of the manoeuvres one of the biologists made a sperm to penetrate into the cytoplasm of the ovum, and from this accidental manoeuvre a child was born in 1992.  This method has had increasing success in the last few years and it alone represents more than 35% of all the methods of assisted fertilisation in the world.  ICSI allows couples who are infertile for male reasons to become pregnant, conditions for which no solution existed apart from using donor sperm, and above all the success rate of ICSI is higher than that of a traditional FIVET which generally has a 25% success rate.  According to studies at the University of Brussels the success rate of ICSI is 33% higher if the woman is less than 37 years old allowing 80% of infertile couples affected by male sterility to become pregnant.  Even though thousands of children have been born as a result of  it, some governments have contested that abuse has occurred by the proposal of ICSI to patients who could have resorted to classical FIVET or simple surgical treatments.  To combat this, some states have established that ICSI can only be adopted by couples whose probabilities of success with traditional FIVET are considered very low.

Violation of the ovule or a helping hand to destiny?
ICSI involves injecting the spermatozoon directly into the ovule, and is used in instances of grave abnormalities of the sperm.  Some scientists are asking themselves about the possible consequences of this technique.  On one hand, the biologist himself chooses the spermatozoon to directly inject into the ova, this could however have defects and were fertilisation to take place “naturally” this would be rejected; on the other hand, the consequences of his manipulation, that is the eventual trauma suffered by the ovule, are mainly unknown.  An American study should, however, lessen the anxiety of the detractors of ICSI: the study, published by the prestigious magazine The Lancet, demonstrates that children born through ICSI develop completely normally.  Statistically speaking, after ICSI, only caesarean and premature births increase, nevertheless the numbers are not significantly different from the rest of the population.

Some months later (February 2002) the same magazine published a study by a group of  Swedish researchers who, however, reached completely different conclusions.  Even though you cannot isolate children born as a result of ICSI from those born as a result of other assisted fertilisation techniques, the researchers estimate that children born from ICSI run higher risks of cerebral diseases than children born as a result of spontaneous pregnancies.  To reach this conclusion the experts compared the frequency of neurological problems of 5.680 children born as a result of in vitro fertilisation will 11.360 conceived naturally and these are the results: the children born from this technique run the risk of developing  neurological problems, in particular cerebral palsy.  These risks are above all caused by the complications of multiple pregnancies and relative premature births of children born as a result of FIVET and not because of the technique itself.  To reduce these risks it is recommended that only one embryo is implanted during every cycle of in vitro fertilisation.  The number of embryos transferred, however, influences success as we have seen.  Assisted procreation centres, therefore, have for some years now limited themselves to the transfer of  2 or maximum 3 embryos.

Disclaimer: the information provided on this site is designed to support, not replace, the relationship that exists between a patient/site visitor and his/her existing physician.

As indicated by the name, FIVET makes it possible for ovules and the spermatozoa meet outside the uterus and control fertilisation. The woman undergoes hormonal treatment that favours the maturation of  many ovules simultaneously, and the man supplies the spermatozoa.  The ovules are harvested and put in a container of culture with the spermatozoa and the fertilisation of many ovules is observed with a microscope.  Three days after harvesting, the embryos’ are re-emitted into the uterus, normally in quantities of about 2-3 to increase the probability that at least one will result in pregnancy.  This method is successful about 25% of the time.

FIVET: why and for whom?
The first birth by in vitro fertilisation was by  English, Louise Brown in 1978, since then about 50.000 children have been born from FIVET.  In human beings natural fertilisation takes place inside the fallopian tubes after sexual intercourse during the ovulatory period; however for fertilisation to take place a large number of mobile spermatozoa capable of travelling from the uterus to the tubes is required, and these have to be perfectly functional and open in order to capture the ova when ovulation takes place.  The inside of the fallopian tube is made of tissue that makes small movements that allow the ova to move along its surface until they meet the spermatozoa, in fact, unlike the latter, the ova is not capable of moving on its own.  After fertilisation, movements of the tubes move the young embryo towards the uterine cavity where it will be permanently implanted after about a week.

A complicated process
The complicated and sophisticated reproductive mechanisms can be damaged by many pathologies.  Initially FIVET was put in place to allow women without tubes to conceive.  The idea was simple, organise the ova-spermatozoa meeting in the laboratory (in vitro) and support fertilisation this way, then transfer the embryo into the uterus.  From 1978, the year of the birth of the first test tube baby, the reasons for FIVET have continued to grow and they are no longer limited to tubal abnormalities.  The women who resort to classical FIVET, that is  without the micro-injection of the spermatozoa (ICSI), present with tubal abnormalities only 50% of the time.  The causes of these abnormalities are diverse: previous genital infections, post surgical adhesions, extra-uterine pregnancies…. in one third of these cases an alteration of the mans sperm is involved.  In fact abnormalities of the spermiogram alone are sufficient to direct towards classical FIVET in 20% of the cases, even when the tubes are perfectly healthy.  Other reasons for FIVET are endometriosis – a disease characterised by the presence of abnormal mucus in the peritoneo and in the ovaries – and unexplainable cases of infertility.  In this last case the resorting to FIVET happens after many fruitless attempts at simple ovarian stimulation and intra uterine insemination.

Methods and results
Generally simple ovarian stimulation can have 10-20% success rate per cycle, intrauterine insemination about 10-15%.  FIVET and ICSI yield an average of about 25% pregnancy rate per attempt.

How many spermatozoa?
Artificial insemination: 500.000 mobile spermatozoa
In vitro fertilisation: 2-300.000 mobile spermatozoa
Micro-injection (ICSI): 1 spermatozoon

FIVET: how does it work
Complicated to explain, FIVET seems easy because it “simply” consists of, recreating in a laboratory, in a test tube with special cultures, what happens during fertilisation in the woman’s tubes. The three stages of FIVET are: the harvesting of  the male and female sex cells (gametes), fertilisation and transfer of the embryo.

The gametes: ova, the female sex cells      
Found in the follicles, the ova are stored in the ovaries of  the future mother from birth, their development is blocked until puberty.  Starting from this moment in women of child bearing age only sex cell matures per menstrual cycle.  Every month an ovum completes its cellular maturation inside the follicle and is expelled by the ovary, mean while the growth of other follicles, which will have recommenced their development at the same time is arrested and they die.  The greater part of FIVET is realised starting with a stimulated cycle in order to obtain as many ova as possible and therefore increase the possibility of pregnancy.  Now, lets speak about multi-follicular stimulation.  This type of stimulation.  This type of stimulation entails the use of hormones that guarantee that one side of the ovaries is “put to rest”. Their desensitisation  can this way increase the number of follicles recruited, and the stimulation of their growth. Apart from the daily injections for a period varying from 2-3 weeks, this sort of stimulation requires very strict monitoring based on  the results of constant ovarian ultrasounds and of the hormonal dosages.  Referred to  as “monitoring” this allows that as many follicles as possible be brought to maturity and also helps to prevent over stimulation or hyper-stimulation which could have very serious consequences for the woman.  When the follicles have reached the right dimension an injection of human chorionic gonadotropine triggers ovulation allowing the ova contained in each follicle to reach maturity.  Thirty six hours after the injection the ovarian follicles, which now have a dimension of about 15-20mm are retrieved, an operation that generally takes place under local anaesthetic and consists in the aspiration of the liquid in the follicle via a needle guided by an ultrasound probe situated in the vagina.  The biologist can therefore look for mature ova necessary for fertilisation.                          

The gametes: spermatozoa, the male sex cells
To obtain spermatozoa from a man generally poses less problems because their production is constant, commencing from the age of puberty and there are millions in every ejaculation.  Practically, the man is required to abstain from sex for three days before FIVET, in order to obtain good quality sperm.  The harvest of the sperm generally happens on the same day as FIVET, through masturbation undertaken in the medical centre.  In particular cases, if the spermatozoa cannot be emitted because of an obstruction of one of the tubes, they have to extract the spermatozoa by way of a testicular biopsy on the same day as FIVET or some time before in which case they are frozen.

Insemination and fertilisation
The biologist prepares the gametes in the laboratory: the seminal liquid is collected and washed and the biologist selects the most mobile spermatozoa and allows the champions to warm up in a special place; the ova are extracted from the follicular liquid and isolated.  Each ovum is then placed in a culture  together  with the most mobile spermatozoa, between 10.000 and 100.000 per ovum, depending on the technique to be used.  This is the stage which is different in ICSI.  The containers of culture are placed in an incubator at 37° C and already after 24 hours it is possible to see the number of ova that have been fertilised.  In the following 24 hours, that is 48 hours after the extraction of the ova the number of embryos obtained is known.

Transfer of the embryos
Two days after the extraction of the ova the embryos are made up of an average of about four cells called blastomere. At this point they can be transferred into the uterine cavity.  They can also remain in culture for an additional four days, this allowing for a better selection of the embryos to take place and indirectly increasing the probability of pregnancy.  In special situations it is necessary to leave the embryos for longer in order to conduct pre-implant diagnosis.  These days in a large number of cases two embryos are transferred, painlessly, using a very fine plastic tube inserted into the neck of the uterus the embryos are pushed into the uterine cavity with an ordinary syringe and a small quantity of follicular liquid.  After about 12 days a pregnancy test is performed.  Any  extra embryos produced can be frozen, this decision is, however, left to the couple.

The results of FIVET
The recourse to the intracytoplasmic micro-injection of one spermatozoon (ICSI) is more and more frequent.  The percentage of pregnancies per transfer, identical in the case of FIVET to ICSI,  reaches about 25%.  If a woman undergoes embryo transfer, statistically she has one in four chances of  falling pregnant, even though it is important to say that this varies a lot depending on different factors.  In the case of ICSI the probability of success is higher if the abnormality involves only the sperm and not endometriosis.  One of the principal prognostic elements is the age of the woman at the moment of FIVET, given that the percentage of pregnancies by aspiration remains relatively stable until the age of  37 (>25%) but then rapidly decreases to 17% at age 40 and only 10% at age 42.  The number of embryos transferred also influences the success rate, because the probabilities of pregnancy are about 10% after the transfer of one embryo but more than 30% after the transfer of three embryos, even though this increases the risk of multiple pregnancies.  The probability of twin pregnancies is about 20% with the transfer of two embryos and more than 30% with the transfer of three embryos even though the probability of success does not increase by transferring more than three embryos, the percentage of multiple pregnancies decreases (15% of triplet pregnancies with the transfer of 6 embryos).  These statistics explain why FIVET centres limit transfer to a maximum of 2 or 3 embryos and the transfer of four or more embryos regards only 10% of the cases.

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In the case of normal ovulation no stimulation is effected but the natural cycle is followed, otherwise, in the same way as in other assisted fertilisation techniques the stimulation of the ovaries allows for the improvement and control of ovulation if necessary. The seminal liquid is prepared in the laboratory: specially selected spermatozoa (the most mobile) are injected directly into the uterus using a small plastic tube (catheter). This technique is totally painless and allows to get beyond the barriers that cervical mucus could create (cervical sterility) and to bring the spermatozoa near the ova.       

Ovarian stimulation
Ovarian stimulation begins between the 3rd and 5th day of the cycle (1st day of the cycle = 1st day of menstruation) and consists of daily intra-muscular or subcutaneous injections of follicle stimulating hormone (FSH). Tracking of the cycle begins on about the 8th day of the cycle (depending on the woman’s cycle) and ultrasound is used to count and measure the follicles and evaluate the thickness of the endometrium, and the hormonal dosage to measure the levels of the hormone estradiol (E2). Continuous monitoring (every 24 to 48 hours) is indispensable in order to adapt the treatment to the observed quality of the stimulation.  Once sufficient stimulation is achieved and follicular maturation ovulation can be induced, which means interruption of all the other treatment.  The stimulation is induced using drugs based on  human chorionic gonadotropine (HCG), that mimes a luteinising hormone peak, nevertheless, this all takes place only if the parameters are satisfactory. In rare cases the ovarian response is very high (hyperstimulation) and the treatment has to be interrupted because of the risk of multiple-pregnancies, in other cases the interruption can be motivated by a poor ovarian response (hypostimulation) therefore the therapeutic protocol has to be modified before another attempt.

Harvest and treatment of sperm
The harvest takes place on the day of insemination, via masturbation. It is effected after a 3-5 day period of abstinence and it is indispensable that the man urinates before the harvest to clean the urethra of bacterial contamination and for the same reason men are asked to carefully wash their hands and penis before the harvest. After the harvest, the sperm is prepared in the laboratory to reproduce the changes that occur during sexual intercourse when the spermatozoa traverse the cervical mucus.  Using a method “capacitation” where the seminal plasma