Niepłodność – Patofizjologia i mechanizm

Niepłodność
Patofizjologia i mechanizm

Niepłodność definiowana jest jako brak ciąży po roku regularnego, niezabezpieczonego współżycia i dotyczy 10-15% par w wieku reprodukcyjnym. Etiologia jest wieloczynnikowa, obejmując zaburzenia owulacji (25% przypadków), endometriozę (10-15% kobiet), czynniki jajowodowe, maciczne oraz męskie (40-50% przypadków). Zaburzenia owulacji klasyfikuje WHO na trzy grupy: niewydolność przysadki (10%), dysfunkcję osi podwzgórze-przysadka-jajniki (85%) i niewydolność jajników (5%), z poziomem FSH powyżej 30-40 mIU/ml i niskim estradiolem wskazującym na niewydolność jajników. W patogenezie istotną rolę odgrywa stres oksydacyjny, prowadzący do uszkodzeń DNA, peroksydacji lipidów i dysfunkcji mitochondriów, co pogłębia stan zapalny i zaburza funkcje rozrodcze. U mężczyzn niepłodność często wiąże się z zaburzeniami spermatogenezy, genetycznymi mutacjami, zaburzeniami endokrynologicznymi, niedrożnością nasieniowodów, żylakami powrózka nasiennego oraz infekcjami przenoszonymi drogą płciową. Nowe badania wskazują na rolę mutacji de novo w genach związanych ze spermatogenezą oraz na immunologiczne przyczyny niepłodności, w tym autoimmunologiczne zapalenie prostaty. Diagnostyka obejmuje ocenę hormonalną, badania genetyczne (np. zespół Klinefeltera, delecje AZF), a także analizę fragmentacji DNA plemników (SDF), która koreluje z obniżoną płodnością i gorszymi wynikami ART.

Patogeneza niepłodności

Ogólne mechanizmy zaburzające płodność
Patogeneza niepłodności kobiecej
Patogeneza niepłodności męskiej
Niepłodność niewyjaśniona
Czynniki immunologiczne w niepłodności

Molekularne mechanizmy niepłodności

Mechanizmy genetyczne
Mechanizmy hormonalne
Mechanizmy epigenetyczne
Mechanizmy mikrobiologiczne
Mechanizmy środowiskowe
Stres oksydacyjny

Leczenie niepłodności

Leczenie niepłodności u kobiet
Leczenie niepłodności u mężczyzn
Techniki wspomaganego rozrodu

Przyszłe kierunki badań nad niepłodnością

Kolejne rozdziały

Patogeneza niepłodności

Niepłodność to złożona wieloczynnikowa choroba, która może powodować negatywne skutki psychologiczne, fizyczne, duchowe i medyczne u pacjenta. Jest definiowana jako niezdolność do osiągnięcia ciąży po roku regularnego, niezabezpieczonego współżycia seksualnego. Dotyczy około 10-15% par w wieku reprodukcyjnym, stanowiąc istotny problem zdrowotny na całym świecie¹²³.

Według badań Światowej Organizacji Zdrowia (WHO) dotyczących rozkładu płci i etiologii niepłodności, u 37% niepłodnych par przyczyną jest czynnik żeński, u 35% par zidentyfikowano zarówno przyczyny męskie, jak i żeńskie, a u 8% stwierdzono czynnik męski. Warto zauważyć, że w około 10-17% przypadków niepłodności nie można zidentyfikować jednoznacznej przyczyny (niepłodność idiopatyczna)⁴⁵.

Ogólne mechanizmy zaburzające płodność

Aby zrozumieć patogenezę niepłodności, należy zrozumieć normalną zdolność do zapłodnienia, czyli prawdopodobieństwo osiągnięcia ciąży w jednym cyklu menstruacyjnym. Proces reprodukcji wymaga interakcji i integralności żeńskiego i męskiego układu rozrodczego, co obejmuje: (1) uwolnienie prawidłowego przedowulacyjnego oocytu, (2) wytworzenie odpowiednich plemników, (3) prawidłowy transport gamet do części bańkowej jajowodu (gdzie dochodzi do zapłodnienia) oraz (4) późniejszy transport dzielącego się zarodka do jamy macicy w celu implantacji i rozwoju⁶⁷.

Niepłodność może być spowodowana zaburzeniami w rozwoju układu moczowo-płciowego i jego funkcjonowaniu, defektami genetycznymi układu endokrynnego, w tym osi podwzgórze-przysadka-gonady, a także defektami gametogenezy, erekcji, ejakulacji, funkcji gamet, zapłodnienia lub wczesnego rozwoju zarodkowego⁸.

Istotną rolę w patogenezie niepłodności odgrywa stres oksydacyjny, czyli brak równowagi między reaktywnymi formami tlenu (ROS) a przeciwutleniaczami. Stan ten zaburza procesy reprodukcyjne i powoduje ogólne zakłócenia poprzez stan zapalny, uszkodzenie DNA, peroksydację lipidów, zmiany białkowe oraz dysfunkcję mitochondriów⁹¹⁰¹¹.

Między stanem zapalnym a stresem oksydacyjnym istnieje ścisły związek, który ma poważne implikacje dla niepłodności. Relację tę przedstawia się jako samonapędzający się cykl, w którym procesy zapalne wywołują stres oksydacyjny, który z kolei wzmacnia odpowiedź zapalną¹².

Patogeneza niepłodności kobiecej

Zaburzenia owulacji stanowią co najmniej 25% przypadków niepłodności na całym świecie i są najczęstszą przyczyną niepłodności u kobiet¹³¹⁴¹⁵. Brak owulacji lub rzadka owulacja powoduje niepłodność, ponieważ komórki jajowe nie są uwalniane co miesiąc, co uniemożliwia zapłodnienie i ciążę¹⁶.

WHO kategoryzuje zaburzenia owulacji na trzy grupy:

Grupa I – spowodowana niewydolnością przysadki mózgowej (10%)
Grupa II – wynika z dysfunkcji osi podwzgórze-przysadka-jajniki (85%)
Grupa III – spowodowana niewydolnością jajników (5%)¹⁷

Wysoki poziom FSH w surowicy (powyżej 30-40 mIU/ml) z niskim poziomem estradiolu może odróżnić niewydolność jajników od niewydolności przysadki mózgowej, która zwykle wykazuje niski lub normalny poziom FSH (poniżej 10 mIU/ml) i niski poziom estradiolu¹⁸.

Przyczyny zaburzeń owulacji obejmują:

Zespół policystycznych jajników (PCOS) – najczęstszy typ normogonadalnej normoestrogenicznej anuowulacji, który stanowi 80-85% wszystkich pacjentek z zaburzeniami owulacji i dotyczy 8% wszystkich kobiet w wieku reprodukcyjnym¹⁹²⁰
Niewydolność podwzgórza lub czynnościową niewydolność podwzgórza (FHA) – związaną z zaburzeniami odżywiania i nadmiernym wysiłkiem fizycznym, co prowadzi do zmniejszenia wydzielania GnRH przez podwzgórze²¹²²
Zaburzenia endokrynologiczne – hiperprolaktynemia, niedoczynność tarczycy, cukrzyca²³²⁴
Przedwczesną niewydolność jajników – wywołaną niewyjaśnionymi przyczynami, chemioterapią, radioterapią, autoimmunologicznym zniszczeniem jajników czy zespołami genetycznymi (np. zespół Turnera)²⁵

Endometrioza – definiowana jako obecność tkanki endometrium poza jamą macicy – wpływa na 10-15% kobiet w wieku reprodukcyjnym, przy czym do 50% tych kobiet zmaga się z problemami z płodnością. Patogeneza niepłodności związanej z endometriozą jest złożona i obejmuje wiele czynników, w tym ból i dyspareunia, czynniki mechaniczne, zmniejszoną rezerwę jajnikową, stres oksydacyjny, zmiany w jakości zarodków i oocytów, zaburzoną owulację oraz zmniejszoną receptywność endometrium²⁶²⁷.

Ektopowe komórki endometrium implantują się, wywołując lokalną odpowiedź zapalną, co dalej zmniejsza mobilność jajeczka/plemnika²⁸. Niepłodność związana z endometriozą może być leczona chirurgicznie, indukcją owulacji z inseminacją wewnątrzmaciczną lub zapłodnieniem in vitro²⁹.

Przyczyny jajowodowe obejmują infekcje przenoszone drogą płciową (STI), powikłania po niebezpiecznej aborcji, sepsy poporodowej lub operacji jamy brzusznej/miednicy³⁰. Nieprawidłowości lub uszkodzenia jajowodu zaburzają płodność i są odpowiedzialne za nieprawidłową implantację (np. ciążę ektopową)³¹.

Choroby zapalne miednicy mniejszej (PID) są główną przyczyną zachorowalności i trudności reprodukcyjnych u kobiet w wieku rozrodczym. Ascensja drobnoustrojów do górnego układu rozrodczego następuje w wyniku zakłócenia normalnych barier ochronnych dolnego układu rozrodczego przez patogeny przyczynowe³².

Konsekwencje PID są główną przyczyną zachorowalności reprodukcyjnej u kobiet w wieku rozrodczym, powodując przewlekły ból miednicy, ciążę ektopową i niepłodność. Ryzyko niepłodności wzrasta w korelacji ze stopniem uszkodzenia jajowodów widocznym podczas laparoskopii i może wynosić nawet 30% u kobiet z poważnymi uszkodzeniami jajowodów³³.

Czynniki maciczne w niepłodności są związane z zajmującymi przestrzeń zmianami lub zmniejszoną receptywnością endometrium³⁴. Złotym standardem oceny jamy macicy jest histeroskopia, która umożliwia bezpośrednią wizualizację patologii wewnątrzmacicznej i stwarza możliwość natychmiastowej korekty chirurgicznej³⁵.

Przyczynami niepłodności macicznej są anomalie macicy, takie jak nieprawidłowy kształt macicy i przegroda wewnątrzmaciczna, polipy, mięśniaki macicy i zespół Ashermana³⁶. Duże mięśniaki mogą powodować niepłodność poprzez uszkodzenie błony śluzowej macicy, blokowanie jajowodu, zniekształcenie kształtu jamy macicy lub zmianę położenia szyjki macicy³⁷.

Gruczolakowatość macicy (adenomyosis) odnosi się do patologicznych zmian polegających na wrastaniu endometrium (łącznie z gruczołami i podścieliskiem) do mięśniówki macicy. Coraz więcej dowodów wskazuje, że adenomyoza jest ściśle związana z defektami strukturalnymi i funkcjonalnymi endometrium właściwego i strefy łączenia mięśniówki (MJZ), co może prowadzić do niepowodzenia implantacji zarodka i niepłodności³⁸.

Adenomyoza może wpływać na funkcje reprodukcyjne pacjenta poprzez wpływ na transport plemników, implantację zarodka, zmianę perystaltyki macicy, wpływ na strukturę i funkcję endometrium oraz zmianę środowiska wewnątrzmacicznego³⁹.

Patogeneza niepłodności męskiej

Niepłodność męska odnosi się do niezdolności mężczyzny do zapłodnienia płodnej kobiety. Czynniki męskie stanowią 40-50% przypadków niepłodności u ludzi⁴⁰. W 30-40% przypadków niepłodności męskiej nie można znaleźć przyczyny (idiopatyczna niepłodność męska)⁴¹.

Niepłodność u mężczyzn może wynikać z niedoborów w tworzeniu plemników, ich koncentracji lub transporcie. Ten ogólny podział pozwala na odpowiednie zbadanie potencjalnych przyczyn niepłodności i pomaga określić sposób postępowania terapeutycznego⁴².

Funkcje gonadalne i seksualne są kontrolowane przez oś podwzgórze-przysadka-gonady, zamknięty układ z kontrolą zwrotną z jąder. Podwzgórze, główny ośrodek integracyjny, reaguje na różne sygnały z centralnego układu nerwowego (CNS), przysadki mózgowej i jąder, wydzielając hormon uwalniający gonadotropinę (GnRH) w pulsacyjnym wzorcu co około 70-90 minut⁴³.

Uwolnienie GnRH jest stymulowane przez melatoninę z szyszynki i hamowane przez testosteron, inhibinę, hormon uwalniający kortykotropinę, opiaty, choroby i stres. Pulsacyjny charakter GnRH jest niezbędny do normalnego wydzielania gonadotropin; ciągła stymulacja hamuje ich wydzielanie⁴⁴.

Podwzgórze produkuje również hormon uwalniający tyreotropinę (TRH) i wazoaktywny peptyd jelitowy (VIP), które stymulują uwalnianie prolaktyny z przedniego płata przysadki, oraz dopaminę, która hamuje uwalnianie prolaktyny. Prolaktyna hamuje produkcję GnRH z podwzgórza oraz LH i FSH z przysadki⁴⁵.

Główne przyczyny niepłodności męskiej obejmują:

Zaburzenia spermatogenezy – niskie liczby plemników (oligozoospermia), nieprawidłowa morfologia plemników (teratozoospermia) i niska ruchliwość plemników (asthenozoospermia) są stanami, które zwykle nie dają objawów u większości mężczyzn, ale mają duże znaczenie etiologiczne⁴⁶
Zaburzenia genetyczne – mężczyźni z oligozoospermią z 10 milionami plemników mają wyższe ryzyko wystąpienia nieprawidłowości autosomalnych niż mężczyźni z azoospermią⁴⁷
Zaburzenia endokrynologiczne – wtórny hipogonadyzm (hipogonadyzm hipogonadotropowy) wynika z niewydolności osi podwzgórze-przysadka do stymulacji normalnej funkcji gonad⁴⁸
Niedrożność nasieniowodu i przewodu wytryskowego – może być ważną przyczyną niepłodności, ponieważ wpływa na ejakulację. Azoospermia obstrukcyjna może wynikać z wcześniejszej wazektomii, patologii najądrza lub przewodu wytryskowego⁴⁹
Wsteczna ejakulacja – przepływ nasienia do pęcherza moczowego z powodu niecałkowicie zamkniętej szyi pęcherza moczowego. Różne mechaniczne, neurologiczne i farmakologiczne etiologie są odpowiedzialne za wsteczną ejakulację⁵⁰
Żylaki powrózka nasiennego – mogą prowadzić do upośledzenia spermatogenezy jądrowej i steroidogenezy, potencjalnie z powodu zwiększonej temperatury wewnątrzjądrowej, refluksu toksycznych metabolitów i/lub hipoksji komórek rozrodczych⁵¹
Czynniki środowiskowe – toksyny takie jak kleje, lotne rozpuszczalniki organiczne, silikony, czynniki fizyczne, pyły chemiczne i pestycydy wywołują uszkadzające działanie w jądrach i wpływają na jakość i ilość plemników⁵²
Palenie tytoniu i spożywanie alkoholu – zaobserwowano, że palenie tytoniu uszkadza DNA plemników⁵³
Infekcje – choroby przenoszone drogą płciową (STD) są chorobami przenoszonymi poprzez aktywność seksualną z zakażonym partnerem, powodowanymi przez wirusy, bakterie lub pasożytnicze mikroorganizmy. STD są główną przyczyną niepłodności⁵⁴
Stres oksydacyjny – badania ze Stanów Zjednoczonych wykazały, że główną przyczyną niepłodności męskiej są ROS. W 30-40% osoczu nasienia niepłodnych mężczyzn występuje wzrost poziomu ROS⁵⁵

Ostatnie badania wykazały, że białko plemników, zwane fosfolipazą C zeta (PLCζ), jest niezbędne do zapłodnienia jajeczka. PLCζ jest podstawowym wyzwalaczem pierwszego etapu „aktywacji jajeczka” zapłodnienia⁵⁶.

Naukowcy z Uniwersytetu Newcastle zidentyfikowali nowy mechanizm genetyczny, który może powodować ciężkie formy niepłodności męskiej. Badania wykazały, że nowe mutacje, które nie są dziedziczone od ojca ani matki, odgrywają ważną rolę w tym stanie medycznym. Eksperci odkryli, że mutacje występujące podczas procesu reprodukcji, gdy DNA obu rodziców jest replikowane, mogą prowadzić do niepłodności u mężczyzn w późniejszym życiu⁵⁷.

Naukowcy zebrali i przebadali DNA od globalnej kohorty 185 niepłodnych mężczyzn i ich rodziców. Zidentyfikowali 145 rzadkich mutacji zmieniających białka, które prawdopodobnie negatywnie wpływają na płodność męską. Aż 29 mutacji wpływa na geny bezpośrednio zaangażowane w procesy związane ze spermatogenezą – proces rozwoju komórek plemnikowych – lub inne procesy komórkowe związane z reprodukcją⁵⁸.

Niepłodność niewyjaśniona

U wielu niepłodnych par nadal stawiana jest diagnoza niepłodności idiopatycznej lub opisowe diagnozy, które nie wskazują przyczyny ich defektu. Gdy te wysoce regulowane procesy szwankują, może wystąpić niepłodność⁵⁹.

Niepłodność idiopatyczna męska (IMI) dotyka prawie 10-15% mężczyzn w ich podstawowym wieku reprodukcyjnym. Ponad 500 genów docelowych zostało postulowanych jako związanych z tym stanem chorobowym poprzez różne badania genomiczne. Wyzwaniem jest określenie funkcjonalnej roli tych genów i białek, które stanowią część większej sieci prowadzącej do patogenezy fenotypu IMI u ludzi⁶⁰.

Każda nierównowaga w tych genach poprzez mutację, polimorfizmy pojedynczego nukleotydu (SNP) lub inne formy może prowadzić do nieprawidłowej regulacji genów prowadzącej do niepłodności⁶¹.

Wzbogacone funkcje biologiczne w SNP, a także analiza funkcjonalna genów IMI, doprowadziły do identyfikacji nowych par genów, na podstawie których zaproponowano nowe modele opisujące podstawową patogenezę tego stanu chorobowego⁶².

Wynik tego badania dostarczy nowego zestawu genów i białek, które mogłyby pomóc wyjaśnić chorobę z globalnej perspektywy, która wcześniej nie była poruszana przy użyciu standardowych podejść⁶³.

Czynniki immunologiczne w niepłodności

Złożone mechanizmy leżące u podstaw immunologicznych przyczyn niepłodności męskiej stopniowo zyskują znaczenie w medycynie reprodukcyjnej. Obecny rozdział wyjaśnia komponenty immunologiczne jąder, tolerancję i odpowiedź immunologiczną, a także aspekty etiologiczne tych elementów immunologicznych, podkreślając potencjalną rolę podatności genetycznej, infekcji lub urazu męskiego układu rozrodczego oraz ekspozycji na toksyny środowiskowe jako czynników przyczyniających się do niepłodności męskiej⁶⁴.

Nowe szwedzkie badanie łączy niepłodność męską z autoimmunologicznym zapaleniem prostaty. W obecnym badaniu naukowcy odkryli przyczynę zmniejszonej płodności u osób z autoimmunologicznym zespołem wielogruczołowym typu 1 (APS1), który zwiększa ryzyko rozwoju chorób autoimmunologicznych⁶⁵.

Podczas gdy niepłodność u kobiet z APS1 jest spowodowana autoimmunologicznym działaniem przeciwko jajnikom, to, co powoduje odpowiednią niepłodność u mężczyzn, nigdy nie zostało stwierdzone. Naukowcy odkryli, że układ odpornościowy w dużej grupie pacjentów reagował na białko tworzące się tylko w prostacie, a mianowicie enzym transglutaminazę 4⁶⁶.

Co ciekawe, wcześniejsze badania na myszach wykazały, że transglutaminaza 4 odgrywa ważną rolę w płodności męskiej⁶⁷.

Przeciwciała przeciwplemnikowe powstają, gdy bariera krew-jądro zostaje zakłócona, zwykle z powodu infekcji lub urazu męskiego układu płciowego, i mogą prowadzić do unieruchomienia i aglutynacji plemników lub mieć działanie spermatotoksyczne⁶⁸.

Molekularne mechanizmy niepłodności

Mechanizmy genetyczne

Niepłodność może wynikać z zaburzeń w rozwoju dróg płciowych i narządów płciowych wtórnych, zależnych od występowania jądra lub jajnika oraz obecności lub braku genu determinującego płeć Y (SRY) znajdującego się na chromosomie Y⁶⁹.

Prenatalna produkcja testowego hormonu anty-Müllerowskiego (AMH), działającego poprzez swój receptor AMHR2, indukuje regresję przewodu Müllera, podczas gdy testosteron napędza rozwój tych pochodnych przewodu Wolffa⁷⁰.

Głównym genem związanym z przypadkami odwrócenia płci u ludzi jest SRY, gen determinujący męskość na chromosomie Y. Nieprawidłowe określenie płci odgrywa ważną rolę w etiologii interseksu, począwszy od prawidłowego rozwoju jądra lub jajnika z grzebienia płciowego⁷¹.

Badania genetyczne są wskazane u pacjentów z ciężką oligospermią (<5 milionów/ml), ponieważ częstość występowania nieprawidłowości kariotypu jest odwrotnie proporcjonalna do liczby plemników. Najczęstszą nieprawidłowością jest zespół Klinefeltera (47, XXY), który stanowi około dwie trzecie nieprawidłowości u niepłodnych mężczyzn⁷².

Określony region, nazwany AZF (czynnik azoospermii), w długim ramieniu chromosomu Y ma kluczowe znaczenie dla prawidłowej spermatogenezy⁷³.

Badacze z Uniwersytetu Kumamoto w Japonii rozpoczęli ocenę białek zaangażowanych w mejozę, aby wyjaśnić jej rozwój. Używając spektrometrii masowej, grupa była w stanie zidentyfikować gen, który działa jako przełącznik mejozy, nazywając go „Meiosin” (inicjator mejozy). Gen Meiosin ma niezwykle rzadką właściwość aktywowania się tylko w określonym czasie – tuż przed rozpoczęciem mejozy w gonadach⁷⁴.

W eksperymentach na zwierzętach badacze stwierdzili, że zarówno samce, jak i samice myszy stały się niepłodne, jeśli gen Meiosin został sztucznie zahamowany. Dalsza analiza męskich i żeńskich gonad myszy wyjaśniła, że gen odgrywa kluczową rolę w aktywacji mejozy. Gen Meiosin działa jak wieża kontrolna, która jednocześnie włącza setki genów do tworzenia komórek rozrodczych i wydaje się być związany z niepłodnością⁷⁵.

Mechanizmy hormonalne

Oś podwzgórze-przysadka-gonady to główny ewolucyjnie zachowany pozytywny i negatywny system sprzężenia zwrotnego endokrynnego, który reguluje produkcję dojrzałych gamet⁷⁶.

Przełomowe odkrycia genetyczne w zrozumieniu dodatkowych regulatorów tej osi i przyczyn niepłodności u ludzi obejmowały badania sygnalizacji między czynnikiem wzrostu peptydowym, kisspeptyna (kodowanym przez KISS1) i receptorem KISS1 (KISS1R, znanym również jako GPR54)⁷⁷.

Podobnie jak w przypadku sygnalizacji krzyżowej tkanek w obrębie osi podwzgórze-przysadka-gonady, istnieją ważne dwukierunkowe interakcje parakrynne i jukstakrynne między oocytem a otaczającymi go komórkami somatycznymi jajnika, które rozpoczynają się po wejściu pierwotnych komórek rozrodczych do grzebienia płciowego i trwają przez owulację⁷⁸.

Zakłócenie tych intymnych szlaków komunikacyjnych blokuje rozwój żeńskich gamet zdolnych do zapłodnienia⁷⁹.

Proces spermatogenezy obejmuje odnowę i różnicowanie spermatogonialnych komórek macierzystych w szybko proliferujące spermatogonie, komórki mejotyczne (spermatocyty) i komórki haploidalne (okrągłe, wydłużające się i wydłużone spermatydy) przed uwolnieniem plemnika do światła kanalika⁸⁰.

Jądro zawiera komórki Leydiga i komórki Sertoliego i jest pokryte tunica albuginea, która również zapewnia przegrody, które dzielą ją na około 200-350 piramid. Komórki Sertoliego wydzielają również inhibinę, która zapewnia negatywne sprzężenie zwrotne na podwzgórze, oraz białko wiążące androgeny, które pomaga modulować aktywność androgenów w kanalikach nasiennych⁸¹.

W odpowiedzi na stymulację FSH w okresie dojrzewania, komórki rozrodcze stają się spermatogoniami i przechodzą uporządkowane dojrzewanie, aby stać się plemnikami. Cały proces rozwoju od spermatogonium do spermatydy trwa 74 dni i jest opisany w 14 krokach; w miarę dojrzewania, rozwijające się spermatydy przesuwają się bliżej światła kanalika nasiennego⁸².

Akrosom, pochodna procesu Golgiego, otacza jądro od przodu i zawiera enzymy niezbędne do penetracji komórki jajowej⁸³.

Najądrze dodatkowo wydziela substancje do odżywiania i ochrony plemników, takie jak glicerofosforylcholina, karnityna i kwas sialowy⁸⁴.

Mechanizmy epigenetyczne

Obecność długo żyjącego RNA w transkrypcyjnie nieaktywnym plemniku była znana, dopiero jednak prace Krawetza i jego współpracowników ukazały potencjał diagnostyczny tego RNA⁸⁵.

Kilka badań wykazało, że niedobór protamin w plemniku jest związany z niską jakością plemników i niepłodnością. Kilka badań wykazało, że istnieje znaczący odwrotny związek między niedoborem protamin w plemniku a wskaźnikiem zapłodnienia i ciąży po technikach wspomaganego rozrodu, a główną przyczyną niedoboru protamin w plemniku jest wzrost stresu oksydacyjnego, który w konsekwencji powoduje uszkodzenie DNA⁸⁶.

Fragmentacja DNA plemników lub akumulacja pojedynczych i podwójnych pęknięć DNA występuje w plemnikach, a wzrost poziomu SDF (fragmentacji DNA plemników) zmniejszył szanse na naturalne poczęcie. Chociaż żadne badania jednoznacznie i bezpośrednio nie przetestowały wpływu SDF na kliniczne postępowanie z niepłodnymi parami, SDF jest częstszy u niepłodnych mężczyzn i został zidentyfikowany jako główny czynnik przyczyniający się do niepłodności męskiej, a także gorszych wyników po ART, w tym upośledzonego rozwoju zarodka, poronienia, nawracającej utraty ciąży i wad wrodzonych⁸⁷.

Mechanizmy mikrobiologiczne

Niepłodność jest wieloczynnikową chorobą, a różne czynniki etiologiczne, takie jak infekcja, są znane jako rozwijające to zaburzenie. Ostatnio opublikowane badania wykazały, że różne bakterie, takie jak Chlamydia trachomatis, Mycoplasma spp, Ureaplasma urealyticum, Escherichia coli, Staphylococcus aureus i Pseudomonas aeruginosa, mogą prowadzić do niepłodności poprzez efekty immunopatologiczne, stres oksydacyjny i niekorzystne efekty na koncentrację plemników, ruchliwość, morfologię i kondensację DNA⁸⁸.

Interakcje pomiędzy bakteriami a płodnością są złożone. Badania wykazały, że mechanizmy prowadzące do tworzenia przeciwciał przeciwplemnikowych u mężczyzn po zakażeniu układu płciowego Chlamydia trachomatis pozostają do wyjaśnienia⁸⁹.

Infekcje są również głównym czynnikiem niepłodności męskiej, drugim po oligospermii. Najlepszą nadzieją na zmniejszenie częstości występowania niepłodności związanej z infekcją jest profilaktyka oraz wczesne wykrywanie i leczenie nowo nabytych bezobjawowych lub łagodnie objawowych infekcji⁹⁰.

Pomimo obecnego skupienia się na chorobach przenoszonych drogą płciową (STD), niepłodność może również wynikać z infekcji przenoszonych przez krew, takich jak gruźlica, mieszanych infekcji tlenowych i beztlenowych innych miejsc miednicy, powikłań zapalnych urazu chirurgicznego, poaborcyjnej i poporodowej sepsy oraz pęknięcia wyrostka robaczkowego⁹¹.

Wirus opryszczki jest znany jako przyczyna opryszczki, choroby z objawami bolesnych lub swędzących małych pęcherzy wokół warg i na narządach płciowych. Ostatnio wirus ten wzbudził zainteresowanie ze względu na trwające badania mające na celu sprawdzenie, czy wirus ten powoduje również niepłodność⁹².

Eksperyment na szczurach ujawnił, że kinaza tymidynowa pochodzenia wirusa opryszczki zakłóca spermiogenezę i wywołuje niepłodność u mężczyzn. Gdy pewne czynniki powodują ekspresję genu wirusa opryszczki w jądrze, spermiogeneza staje się nieprawidłowa⁹³.

Mechanizmy środowiskowe

Czynniki środowiskowe i zawodowe wiązano ze zwiększonym ryzykiem niepłodności. Palenie tytoniu wiązało się z niepłodnością zarówno u mężczyzn, jak i kobiet⁹⁴.

Otyłość może być związana z brakiem owulacji i oligomenorrhoea. U mężczyzn otyłość wiązała się z obniżoną jakością nasienia⁹⁵.

Zaawansowany wiek ojcowski (APA) pojawił się jako jeden z dodatkowych czynników ryzyka związanych z postępującym wzrostem częstości występowania niepłodności czynnika męskiego⁹⁶.

Czynniki stylu życia, takie jak palenie, nadmierne spożycie alkoholu i otyłość, mogą wpływać na płodność. Ponadto ekspozycja na zanieczyszczenia środowiska i toksyny może być bezpośrednio toksyczna dla gamet (jajeczek i plemników), powodując zmniejszenie ich liczby i niską jakość⁹⁷.

Stres oksydacyjny

Stres oksydacyjny (OS) to termin używany do opisania nierównowagi oksydacyjnej faworyzującej homeostazę między tworzeniem reaktywnych form tlenu (ROS) lub innych związków powodujących stres oksydacyjny a przeciwdziałającymi aktywnościami/poziomami enzymatycznych lub nieenzymatycznych przeciwutleniaczy⁹⁸.

Stres oksydacyjny jest uważany za kluczowy w niepłodności męskiej poprzez wpływ na jakość plemników, funkcję, a także integralność plemników. Stres oksydacyjny może prowadzić do uszkodzenia DNA plemników i gorszej integralności DNA, co jest związane ze słabym rozwojem zarodka, poronieniem i niepłodnością⁹⁹.

Stres oksydacyjny spowodowany w wyniku wolnych rodników ma znaczący wpływ na produkcję, a także zwiększenie nieprawidłowych plemników, zmniejszenie liczby plemników oraz promowanie transformacji i fragmentacji DNA plemników¹⁰⁰.

Stres oksydacyjny może również powodować niedrożność tętnic, a następnie poważne uszkodzenie komórek układu rozrodczego, w wyniku czego występują wady spermatogenezy¹⁰¹.

Aby wyjaśnić rolę stresu oksydacyjnego w steroidogenezie, przeprowadzono szereg badań na modelach zwierzęcych poprzez wprowadzenie egzogennych źródeł utleniaczy. W innym badaniu na zwierzętach steroidogeneza, wyrażona poziomem FSH, LH i testosteronu, okazała się zmniejszona u zwierząt karmionych dietą z niedoborem selenu w porównaniu ze zwierzętami karmionymi selenem¹⁰².

Zaobserwowano, że wzrost poziomu ROS wiąże się ze zmniejszeniem zdolności reprodukcyjnej u kobiet i niepłodnością. ROS wytwarzane w komórkach ziarnistych mogą mieć negatywny wpływ na zapłodnienie oocytu, a także na tempo i jakość implantacji zarodka¹⁰³.

Stres oksydacyjny spowodowany stanem zapalnym endometriozy również powoduje niepłodność poprzez uszkodzenie DNA. Stan zapalny powoduje produkcję reaktywnych form tlenu (ROS), które następnie gromadzą się w płynie otrzewnowym i jajowodach. Ta kolekcja uszkadza DNA oocytów, plemników i zarodków, co przejawia się niepłodnością u dotkniętych osób¹⁰⁴.

Leczenie niepłodności

Leczenie niepłodności zależy głównie od przyczyny i celów pacjenta. W 85% do 90% przypadków, modyfikacja stylu życia, leki, techniki wspomaganego rozrodu (ART) lub chirurgia mogą leczyć niepłodność i umożliwić kobiecie zajście w ciążę¹⁰⁵.

Znacząca poprawa w leczeniu niepłodności umożliwiła wielu pacjentom poczęcie przy pomocy medycznej. Kobiety z patologią jajowodów lub po wcześniejszym podwiązaniu jajowodów mogą zajść w ciążę dzięki zapłodnieniu in vitro (IVF)¹⁰⁶.

Leczenie niepłodności u kobiet

Cel indukcji owulacji polega na stymulowaniu rozwoju pojedynczego dominującego pęcherzyka u pacjentów z brakiem owulacji. Indukcja owulacji zwiększa ryzyko ciąży mnogiej, a indukcja owulacji egzogennymi gonadotropinami zwiększa ryzyko zespołu hiperstymulacji jajników¹⁰⁷.

Zespół hiperstymulacji jajników (OHSS) to potencjalnie zagrażające życiu powikłanie indukcji owulacji lub stymulacji jajników egzogenną gonadotropiną kosmówkową (hCG). Egzogenny hCG jest uważany za odpowiedzialny za masową luteinizację komórek ziarnistych jajnika¹⁰⁸.

Zespół hiperstymulacji jajników (OHSS) to jatrogenne powikłanie kontrolowanej hiperstymulacji jajników, które skutkuje szerokim zakresem oznak i objawów, od rozdęcia brzucha, nudności, wymiotów, powiększonych jajników, pęcznienia płynów w przestrzeni trzeciej, niewydolności nerek i zakrzepicy żylnej, zespołu ostrej niewydolności oddechowej, zaburzeń elektrolitowych, arytmii serca i sepsy¹⁰⁹.

W przypadku niepłodności związanej z PCOS, inhibitory aromatazy okazały się skuteczne w indukcji owulacji u kobiet z PCOS z problemami owulacyjnymi. Inhibitory aromatazy wraz z supresorem gonadotropiny również wykazały potencjał poprzez zmniejszenie przewlekłego bólu miednicy związanego z endometriozą¹¹⁰.

Badanie prowadzone przez zespół z Uniwersytetu Kumamoto odkryło nowy mechanizm, który może zrewolucjonizować opiekę nad niepłodnością poprzez promowanie implantacji zarodka. Odkrycie koncentruje się na receptorach prostaglandyny (PG) w macicy, które wzmacniają krytyczny proces decydualizacji, niezbędny dla pomyślnej ciąży¹¹¹.

Zespół badawczy odkrył, że dwa rodzaje prostaglandyn – PGD2 i PGE2 – wytwarzane w macicy na wczesnych etapach ciąży, aktywują określone receptory, DP i EP4, aby promować tworzenie tkanki doczesnej, która wspiera implantację zarodka¹¹².

Zespół odkrył, że gdy stymulowany jest receptor DP lub EP4, decydualizacja jest wzmacniana, umożliwiając bardziej efektywną implantację zarodka, co dodatkowo sugeruje, że zarówno ścieżki receptorów PGD2-DP, jak i PGE2-EP4 kompensują funkcje nawzajem. To przełomowe odkrycie sugeruje, że wzmocnienie tych ścieżek za pomocą specjalistycznych leków, zwanych agonistami DP/EP4, mogłoby pomóc kobietom zmagającym się z niepłodnością z powodu problemów z implantacją¹¹³.

Leczenie niepłodności u mężczyzn

Korekcja żylaków powrózka nasiennego jest wskazana u pacjentów z klinicznie wykrywalnym żylakowatością i nieprawidłowym wynikiem badania nasienia, ponieważ poprawia wskaźniki ciąży¹¹⁴.

Wielu pacjentów z azoospermią obstrukcyjną może poddać się operacji rekonstrukcyjnej w celu przywrócenia ciągłości transportu plemników¹¹⁵.

Mikrochirurgiczna ekstrakcja plemników z jąder (microTESE) umożliwia identyfikację i selektywne wycięcie większych kanalików nasiennych, które z większym prawdopodobieństwem dostarczą plemniki¹¹⁶.

Procedury wspomaganej ejakulacji są stosowane do pozyskiwania plemników do wspomaganego rozrodu u mężczyzn anorgazmicznych i anejakulacyjnych. Dwie najczęściej stosowane techniki to stymulacja wibracyjna prącia (PVS) i elektroejakulacja (EEJ)¹¹⁷.

Badania pokazują, że plemniki można pozyskać za pomocą PVS lub EEJ u 97% mężczyzn z urazem rdzenia kręgowego. Jeśli wysiłki mające na celu przywrócenie przepływu antegrade lub PVS zawiodą, można zastosować elektrostymulację z sondą doodbytniczą lub EEJ¹¹⁸.

Techniki wspomaganego rozrodu

In vitro fertilization (IVF) to złożona seria procedur, które mogą prowadzić do ciąży. Jest to leczenie niepłodności, stanu, w którym nie można zajść w ciążę po co najmniej roku prób w przypadku większości par. IVF może być również stosowany w celu zapobiegania przekazywaniu problemów genetycznych dziecku¹¹⁹.

Podczas zapłodnienia in vitro jajeczka są pobierane z pęcherzyków zwanych pęcherzykami w obrębie jajnika. Jajeczko jest zapładniane przez wstrzyknięcie pojedynczego plemnika do jajeczka lub zmieszanie jajeczka z plemnikami w probówce. Zapłodnione jajeczko, zwane zarodkiem, jest przenoszone do macicy¹²⁰.

In vitro fertilization jest najbardziej efektywnym rodzajem leczenia niepłodności, który obejmuje manipulację jajeczkami lub zarodkami i plemnikami. Razem ta grupa zabiegów nosi nazwę technik wspomaganego rozrodu¹²¹.

IVF może być opcją, jeśli ty lub twój partner ma uszkodzenie lub zablokowanie jajowodów. Jajeczka przemieszczają się z jajników do macicy przez jajowody. Jeśli oba jajowody zostaną uszkodzone lub zablokowane, utrudnia to zapłodnienie jajeczka lub przemieszczenie się zarodka do macicy¹²².

IVF może być opcją, jeśli ty lub twój partner ma zaburzenia owulacji. Jeśli owulacja nie występuje lub nie występuje często, do zapłodnienia przez plemniki dostępnych jest mniej jajeczek¹²³.

IVF może być opcją, jeśli ty lub twój partner ma endometriozę. Ten stan występuje, gdy tkanka podobna do błony śluzowej macicy rośnie poza macicą. Endometrioza często wpływa na jajniki, macicę i jajowody¹²⁴.

IVF może być opcją, jeśli ty lub twój partner ma mięśniaki macicy. Mięśniaki to guzy w macicy. Najczęściej nie są to nowotwory. Są powszechne u osób w wieku 30 i 40 lat. Mięśniaki mogą powodować trudności z przytwierdzeniem się zapłodnionego jajeczka do błony śluzowej macicy¹²⁵.

IVF może być opcją, jeśli ty lub twój partner ma problemy z plemnikami. Niska liczba plemników lub nietypowe zmiany w ich ruchu, rozmiarze lub kształcie mogą utrudniać plemnikom zapłodnienie jajeczka¹²⁶.

IVF może być opcją, jeśli ty lub twój partner ma niewyjaśnioną niepłodność. Jest to sytuacja, gdy badania nie mogą znaleźć przyczyny niepłodności kogoś¹²⁷.

Przyszłe kierunki badań nad niepłodnością

Przyszłość trzyma wielką obietnicę istotnych postępów badawczych w dziedzinie biologii i medycyny reprodukcyjnej¹²⁸.

Naukowcy z Newcastle University kontynuują swoje badania, przeprowadzając dalsze badania nad rolą nowo zidentyfikowanych zmutowanych genów w spermatogenezie i ogólnej płodności u ludzi¹²⁹.

Jeśli udałoby się udowodnić, że infekcja wirusem opryszczki jest jedną z etiologii niepłodności męskiej, a podstawowy mechanizm zostałby odkryty w przyszłości, to badanie mogłoby przejść do opracowania metod diagnostycznych i terapeutycznych oraz leków¹³⁰.

Grupa badawcza z Uniwersytetu Azabu ujawniła poprzez badania na myszach, że niedobór cynku może prowadzić do niepłodności, uniemożliwiając zapłodnionym jajeczkom implantację w macicy. Wyniki wykazały, że w grupie, w której ZIP10 funkcjonował normalnie, część nabłonka błony śluzowej macicy uległa rozpadowi, pozwalając zapłodnionemu jajeczku na zagnieżdżenie się z czasem, z widocznymi płodami w macicy do 10 dnia ciąży¹³¹.

Badanie wykazało również, że w grupie, w której ZIP10 nie funkcjonował, efekt progesteronu – żeńskiego hormonu niezbędnego do ustanowienia i utrzymania ciąży – został osłabiony, co wyjaśnia niepowodzenie implantacji. Ponadto te same wyniki uzyskano przy użyciu hodowanych komórek pochodzących z ludzkiej błony śluzowej macicy, co sugeruje, że podobne sytuacje występują w przypadkach niepłodności u ludzi¹³².

Leczenie przeciwutleniaczami może zmniejszyć stres oksydacyjny u niepłodnych mężczyzn i poprawić parametry plemników, zawartość protamin w plemnikach i integralność DNA¹³³.

Wyjaśnienie mechanizmu glikozylacji może doprowadzić do nowych metod leczenia plemników z zaburzeniami ruchliwości i niepłodności męskiej¹³⁴.

Razem, projekt badania mechanizmów adenomyozy i endometriozy zapewni głęboki wgląd w to, co dzieje się nie tak w endometriozie i jej niepłodności, z perspektywami odkrycia nowych celów terapeutycznych¹³⁵.

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Materiały źródłowe

#1 Infertility: Practice Essentials, Overview, Etiology of Infertility
https://emedicine.medscape.com/article/274143-overview
Infertility is the failure to conceive (regardless of cause) after 12 months or more of regular, unprotected sexual intercourse. This condition affects approximately 10-15% of reproductive-aged couples. […] Infertility is caused by male and/or female factors. Male and female factors each account for approximately 35% of cases. Often, there is more than one factor, with male and female factors combined causing 20% of infertility. In the remaining 10% of cases, the etiology is unknown. […] Reproduction requires the interaction and integrity of the female and male reproductive tracts, which involves (1) the release of a normal preovulatory oocyte, (2) the production of adequate spermatozoa, (3) the normal transport of the gametes to the ampullary portion of the fallopian tube (where fertilization occurs), and (4) the subsequent transport of the cleaving embryo into the endometrial cavity for implantation and development.
#2 Female Infertility – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK556033/
Infertility is a medical condition that can cause psychological, physical, mental, spiritual, and medical detriments to the patient. […] To understand infertility, one must understand normal fecundability, the probability of achieving pregnancy in one menstrual cycle. […] The research community has established a fecundability rate multiple times, which has helped establish normal pregnancy rates to assist in diagnosing infertility. […] The World Health Organization (WHO) performed a large multinational study to determine gender distribution and infertility etiologies. In 37% of infertile couples, female infertility was the cause; in 35% of couples, both male and female causes were identified; in 8%, there was male factor infertility. […] Ovulatory disorders make up 25% of the known causes of female infertility. Oligo-ovulation or anovulation results in infertility because no oocyte are released monthly. Without an oocyte, there is no opportunity for fertilization and pregnancy.
#3
https://link.springer.com/article/10.1007/s00203-024-04231-w
Infertility can harm a patient in physical, psychological, spiritual, and medical ways. […] Infertility is a multifactorial disease, and various etiological factors like infection are known to develop this disorder. Recently published studies reported that different bacteria, such as Chlamydia trachomatis, Mycoplasma spp, Ureaplasma urealyticum, Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa, can lead to infertility by immunopathological effects, oxidative stress, and adverse effects on sperm concentration, motility, morphology, and DNA condensation. […] Noteworthy, oxidative stress could have a role in many pathological changes in the reproductive system. Recent findings show that microorganisms can increase reactive oxygen species concentration inside the host cells, leading to oxidative stress and sperm distress and dysfunction. Therefore, this article explores the potential significance of critical bacteria linked to infertility and their pathogenic mechanisms that can affect sperm function and the female reproductive system.
#4 Female Infertility – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK556033/
Infertility is a medical condition that can cause psychological, physical, mental, spiritual, and medical detriments to the patient. […] To understand infertility, one must understand normal fecundability, the probability of achieving pregnancy in one menstrual cycle. […] The research community has established a fecundability rate multiple times, which has helped establish normal pregnancy rates to assist in diagnosing infertility. […] The World Health Organization (WHO) performed a large multinational study to determine gender distribution and infertility etiologies. In 37% of infertile couples, female infertility was the cause; in 35% of couples, both male and female causes were identified; in 8%, there was male factor infertility. […] Ovulatory disorders make up 25% of the known causes of female infertility. Oligo-ovulation or anovulation results in infertility because no oocyte are released monthly. Without an oocyte, there is no opportunity for fertilization and pregnancy.
#5 Molecular Mechanism of Resveratrol and Its Therapeutic Potential on Female Infertility
https://www.mdpi.com/1422-0067/25/7/3613
Infertility is a global healthcare problem, affecting around 8â12% of couples. It is estimated that the female factor contributes to around 50% of couplesâ infertility and can be classified as primary (no previously achieved pregnancy) or secondary (previously achieved pregnancies) infertility. The leading cause of female infertility was reported to be due to polycystic ovarian syndrome (PCOS). Other causes include endometriosis, tubal obstruction due to sexually transmitted infections, uterine fibroids, and endocrine and uterine anatomical abnormalities. However, in 10â17% of females, no cause is identified (idiopathic infertility). Despite that, some studies have reported that idiopathic infertility could be a consequence of imbalanced adaptive immunity or genetic abnormalities. […] Treatment options depend on the cause. Numerous animal and human studies have reported that some supplements could aid in ovulation, fertilization, embryo development, and improve infertility-related pathologies. Until now, beneficial effects were reported for dietary antioxidants (vitamin C and E), L-arginine, multivitamin and mineral supplementation, inositol, calcium and vitamin D, melatonin, coenzyme Q10, l-carnitine, selenium with vitamin E, Î±-lipoic acid and myoinositol, folate or rather 5-methyltetrahydrofolate and vitamin B12, and omega-3 fatty acid. Of the potential supplements, polyphenols, including curcumin, quercetin, and rutin, were also associated with improved reproduction. One of the polyphenols is resveratrol, whose research has also greatly increased in recent years.
#6 Infertility: Practice Essentials, Overview, Etiology of Infertility
https://emedicine.medscape.com/article/274143-overview
Infertility is the failure to conceive (regardless of cause) after 12 months or more of regular, unprotected sexual intercourse. This condition affects approximately 10-15% of reproductive-aged couples. […] Infertility is caused by male and/or female factors. Male and female factors each account for approximately 35% of cases. Often, there is more than one factor, with male and female factors combined causing 20% of infertility. In the remaining 10% of cases, the etiology is unknown. […] Reproduction requires the interaction and integrity of the female and male reproductive tracts, which involves (1) the release of a normal preovulatory oocyte, (2) the production of adequate spermatozoa, (3) the normal transport of the gametes to the ampullary portion of the fallopian tube (where fertilization occurs), and (4) the subsequent transport of the cleaving embryo into the endometrial cavity for implantation and development.
#7 The biology of infertility: research advances and clinical challenges
https://pmc.ncbi.nlm.nih.gov/articles/PMC3786590/
Disruption of these intimate communication pathways blocks the development of fertilizable female gametes. […] The process of spermatogenesis involves the renewal and differentiation of spermatogonial stem cells into rapidly proliferating spermatogonia, meiotic cells (spermatocytes) and haploid cells (round, elongating and elongated spermatids) before release of a spermatozoon into the tubule lumen. […] It is likely that this complexity contributes to the large number of unresolved idiopathic infertility cases in male humans. […] Infertility can be caused by defects in the development of the urogenital system and in its function, by genetic defects of the endocrine system, including the hypothalamic-pituitary-gonadal axis, and by defects in gametogenesis, erection, ejaculation, gamete function, fertilization or early embryonic development.
#8 The biology of infertility: research advances and clinical challenges
https://pmc.ncbi.nlm.nih.gov/articles/PMC3786590/
Disruption of these intimate communication pathways blocks the development of fertilizable female gametes. […] The process of spermatogenesis involves the renewal and differentiation of spermatogonial stem cells into rapidly proliferating spermatogonia, meiotic cells (spermatocytes) and haploid cells (round, elongating and elongated spermatids) before release of a spermatozoon into the tubule lumen. […] It is likely that this complexity contributes to the large number of unresolved idiopathic infertility cases in male humans. […] Infertility can be caused by defects in the development of the urogenital system and in its function, by genetic defects of the endocrine system, including the hypothalamic-pituitary-gonadal axis, and by defects in gametogenesis, erection, ejaculation, gamete function, fertilization or early embryonic development.
#9 Importance of Oxidative Stress Mechanism in Reproductive Functions and Infertility | IntechOpen
https://www.intechopen.com/chapters/83976
Oxidative stress (OS) is a term used to describe the homeostatic oxidation-favoring imbalance between the formation of reactive oxygen species (ROS) or other compounds causing oxidative stress and the countering activities/levels of enzymatic or non-enzymatic antioxidants. […] Through available evidence, it appears that oxidative state impairs reproductive processes and causes general disruptions through inflammation, DNA damage, lipid peroxidation, protein alterations and mitochondrial dysfunction. […] Previous investigations have implicated OS and its mechanisms in a number of diseases, including infertility. […] In men, free radical elevation in the ejaculate is mainly sponsored by high leukocyte counts as well as immature spermatozoa, which cause low fertility owing to lipid peroxidation, apoptosis and damage to the DNA of sperm cells.
#10
https://benthamscience.com/public/ebook_volume/3854
Male infertility is a significant global health concern, necessitating an understanding of its molecular basis to develop effective diagnostics and treatments. […] Male infertility can result from disruptions in these processes due to factors such as genetic mutations, impaired sperm motility, hormonal imbalances, and oxidative stress (OS). […] Genetic alterations can affect genes crucial for spermatogenesis, sperm function, or hormonal regulation. […] OS, arising from an imbalance between reactive oxygen species (ROS) and antioxidants, can cause sperm DNA damage. […] The intricate mechanisms underlying immunological causes of male infertility are progressively gaining prominence within the field of reproductive medicine. […] The present chapter explains the testicular immune components, immune tolerance and response, and also the etiological aspects of these immunological elements, emphasizing the potential role of genetic susceptibility, infection or trauma to the male reproductive tract, and environmental toxin exposure as contributory factors to male infertility.
#11 Importance of Oxidative Stress Mechanism in Reproductive Functions and Infertility | IntechOpen
https://www.intechopen.com/chapters/83976
Hence, elevation in the ROS level is detrimental to the growth of the embryo and Sperm-oocyte interaction. […] Oxidative stress plays a notable role along the several processes involved in male and female reproduction. […] This oxidative stress state impairs the reproductive processes and causes general disruption through inflammation, DNA damage, lipid peroxidation, protein alterations and mitochondrial dysfunction.
#12
https://benthamscience.com/public/ebook_volume/3854
An intricate relationship exists between inflammation and oxidative stress, a connection that has profound implications for male infertility. […] This relationship is depicted as a self-perpetuating cycle in which inflammatory processes induce OS, which in turn amplifies the inflammatory response. […] The chapter also emphasizes the need for tailored therapeutic approaches, balancing the advantages of antibiotics, antivirals, and supplementary treatments against potential risks to male fertility.
#13 Female Infertility – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK556033/
Infertility is a medical condition that can cause psychological, physical, mental, spiritual, and medical detriments to the patient. […] To understand infertility, one must understand normal fecundability, the probability of achieving pregnancy in one menstrual cycle. […] The research community has established a fecundability rate multiple times, which has helped establish normal pregnancy rates to assist in diagnosing infertility. […] The World Health Organization (WHO) performed a large multinational study to determine gender distribution and infertility etiologies. In 37% of infertile couples, female infertility was the cause; in 35% of couples, both male and female causes were identified; in 8%, there was male factor infertility. […] Ovulatory disorders make up 25% of the known causes of female infertility. Oligo-ovulation or anovulation results in infertility because no oocyte are released monthly. Without an oocyte, there is no opportunity for fertilization and pregnancy.
#14 Infertility pathophysiology – wikidoc
https://www.wikidoc.org/index.php/Infertility_pathophysiology
Disorders of ovulation make up at least 25% of the cases of infertility worldwide, according to a study done by WHO. Other pathologies such as genital tract infections, pelvic inflammatory disease, endometriosis make up the bulk of female infertility cases. […] A decrease in sperm count. […] A fertilized egg or embryo does not survive once it sticks to the lining of the womb (uterus). […] Hormonal imbalance such as hyperprolactinemia, hypothyroidism, diabetes mellitus, PCOS which interfere with fertility.
#15 Female infertility: Causes – UpToDate
https://www.uptodate.com/contents/female-infertility-causes
Infertility is a complex disorder with significant medical, psychosocial, and economic aspects. The etiologies of female infertility will be reviewed here. […] In a World Health Organization (WHO) study of 8500 infertile couples, female factor infertility was reported in 37 percent of infertile couples in developed countries, male factor infertility in 8 percent, and both male and female factor infertility in 35 percent. The most common identifiable female factors, which accounted for 81 percent of female infertility, were: […] Ovulatory disorders (25 percent).
#16 Female Infertility – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK556033/
Infertility is a medical condition that can cause psychological, physical, mental, spiritual, and medical detriments to the patient. […] To understand infertility, one must understand normal fecundability, the probability of achieving pregnancy in one menstrual cycle. […] The research community has established a fecundability rate multiple times, which has helped establish normal pregnancy rates to assist in diagnosing infertility. […] The World Health Organization (WHO) performed a large multinational study to determine gender distribution and infertility etiologies. In 37% of infertile couples, female infertility was the cause; in 35% of couples, both male and female causes were identified; in 8%, there was male factor infertility. […] Ovulatory disorders make up 25% of the known causes of female infertility. Oligo-ovulation or anovulation results in infertility because no oocyte are released monthly. Without an oocyte, there is no opportunity for fertilization and pregnancy.
#17 Evaluation and Treatment of Infertility | AAFP
https://www.aafp.org/pubs/afp/issues/2015/0301/p308.html
Infertility is defined as the inability to achieve pregnancy after one year of regular, unprotected intercourse. […] Causes of infertility include male factors, ovulatory dysfunction, uterine abnormalities, tubal obstruction, peritoneal factors, or cervical factors. […] Infertility may arise from male factors, female factors, or a combination of these. […] The etiology of female infertility can be broken down into ovulation disorders, uterine abnormalities, tubal obstruction, and peritoneal factors. […] Evaluation of cervical mucus is unreliable; therefore, investigation is not helpful with the management of infertility. […] WHO categorizes ovulatory disorders into three groups: group I is caused by hypothalamic pituitary failure (10%), group II results from dysfunction of hypothalamic-pituitary-ovarian axis (85%), and group III is caused by ovarian failure (5%).
#18 Evaluation and Treatment of Infertility | AAFP
https://www.aafp.org/pubs/afp/issues/2015/0301/p308.html
A high serum FSH level (greater than 30 to 40 mIU per mL [30 to 40 IU per L]) with a low estradiol level can distinguish ovarian failure from hypothalamic pituitary failure, which typically reveals a low or normal FSH level (less than 10 mIU per mL [10 IU per L]) and a low estradiol level. […] Women with no clear risk of tubal obstruction should be offered hysterosalpingography to screen for tubal occlusion and structural uterine abnormalities. […] Treatment of tubal obstruction generally requires referral for subspecialty care. […] Couples who have no identified cause of infertility should be counseled on timing of intercourse for the most fertile period (i.e., the six days preceding ovulation). […] Intrauterine insemination and ovulation induction do not result in increased pregnancy rates in women with unexplained infertility.
#19 Female Infertility – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK556033/
Hypothalamic amenorrhea or functional hypothalamic amenorrhea (FHA) is associated with eating disorders and excessive exercise, which results in a decrease in hypothalamic GnRH secretion. […] The most common type of Normogonadotropic normoestrogenic anovulation is PCOS. PCOS accounts for 80% to 85% of all anovulatory patients and affects 8% of all reproductive-aged females. […] Endometriosis is defined as endometrial tissue outside the uterine cavity. The diagnosis is based on the histological identification of endometrial glands or stroma outside the uterus. […] Pelvic and tubal adhesions, along with uterine and tubal abnormalities, account for a large portion of female infertility. […] Uterine causes of infertility are associated with either space-occupying lesions or reduced endometrial receptivity.
#20
https://www.nhs.uk/conditions/infertility/causes/
Infertility is commonly caused by problems with ovulation (the monthly release of an egg from the ovaries). […] Ovulation problems can be a result of: polycystic ovary syndrome (PCOS), thyroid problems both an overactive thyroid gland and an underactive thyroid gland can prevent ovulation, premature ovarian failure where the ovaries stop working before the age of 40. […] Endometriosis is a condition where tissue, similar to the lining of the womb (the endometrium), grows in other places outside of the womb. This can damage the ovaries or fallopian tubes and cause fertility problems. […] Pelvic inflammatory disease (PID) is an infection of the upper female genital tract, which includes the womb, fallopian tubes and ovaries. PID can damage and scar the fallopian tubes, making it virtually impossible for an egg to travel down into the womb.
#21 Female Infertility – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK556033/
Hypothalamic amenorrhea or functional hypothalamic amenorrhea (FHA) is associated with eating disorders and excessive exercise, which results in a decrease in hypothalamic GnRH secretion. […] The most common type of Normogonadotropic normoestrogenic anovulation is PCOS. PCOS accounts for 80% to 85% of all anovulatory patients and affects 8% of all reproductive-aged females. […] Endometriosis is defined as endometrial tissue outside the uterine cavity. The diagnosis is based on the histological identification of endometrial glands or stroma outside the uterus. […] Pelvic and tubal adhesions, along with uterine and tubal abnormalities, account for a large portion of female infertility. […] Uterine causes of infertility are associated with either space-occupying lesions or reduced endometrial receptivity.
#22 Pathogenesis-of-Female-Infertility | Calgary Guide
https://calgaryguide.ucalgary.ca/pathogenesis-of-female-infertility/pathogenesis-of-female-infertility/
Pathogenesis of female infertility […] Extreme stress, eating disorder, excessive exercise, intracranial tumor, or hyperprolactinemia […] Gonadotropin releasing hormone (GnRN) from hypothalamus release of Luteinizing hormone (LH) Follicle stimulating hormone (FSH) by pituitary release of estrogen by ovaries Anovulation (oocyte is not released) Fewer follicles available to ovulate […] Causes of Hyperprolactinemia include: prolactinoma (prolactin-producing tumor), hypothalamic infiltrate or mass, chest wall irritation, hypothyroidism, renal or liver disease ( prolactin clearance), dopamine antagonists that prolactin secretion (antipsychotics, anti- depressants, anti-emetics) […] Polycystic ovary syndrome (see PCOS: Pathogenesis and Clinical findings) androgen production estrogen earlier in the menstrual cycle FSH follicle growth rate of follicle depletion Oocyte not available every month for fertilization
#23 Infertility pathophysiology – wikidoc
https://www.wikidoc.org/index.php/Infertility_pathophysiology
Disorders of ovulation make up at least 25% of the cases of infertility worldwide, according to a study done by WHO. Other pathologies such as genital tract infections, pelvic inflammatory disease, endometriosis make up the bulk of female infertility cases. […] A decrease in sperm count. […] A fertilized egg or embryo does not survive once it sticks to the lining of the womb (uterus). […] Hormonal imbalance such as hyperprolactinemia, hypothyroidism, diabetes mellitus, PCOS which interfere with fertility.
#24 Pathogenesis-of-Female-Infertility | Calgary Guide
https://calgaryguide.ucalgary.ca/pathogenesis-of-female-infertility/pathogenesis-of-female-infertility/
Pathogenesis of female infertility […] Extreme stress, eating disorder, excessive exercise, intracranial tumor, or hyperprolactinemia […] Gonadotropin releasing hormone (GnRN) from hypothalamus release of Luteinizing hormone (LH) Follicle stimulating hormone (FSH) by pituitary release of estrogen by ovaries Anovulation (oocyte is not released) Fewer follicles available to ovulate […] Causes of Hyperprolactinemia include: prolactinoma (prolactin-producing tumor), hypothalamic infiltrate or mass, chest wall irritation, hypothyroidism, renal or liver disease ( prolactin clearance), dopamine antagonists that prolactin secretion (antipsychotics, anti- depressants, anti-emetics) […] Polycystic ovary syndrome (see PCOS: Pathogenesis and Clinical findings) androgen production estrogen earlier in the menstrual cycle FSH follicle growth rate of follicle depletion Oocyte not available every month for fertilization
#25 Pathogenesis-of-Female-Infertility | Calgary Guide
https://calgaryguide.ucalgary.ca/pathogenesis-of-female-infertility/pathogenesis-of-female-infertility/
Premature ovarian insufficiency due to unexplained causes, chemotherapy, radiation, autoimmune ovarian destruction, Turners Fragile X Syndromes […] Damage in germ cells that accumulates over a womans lifetime Age-related changes in quality of granulosa cells surrounding oocyte Genetic damage accumulates, such as rates of meiotic nondisjunction (failure of chromosomes to separate during gamete cell division) […] Tubal occlusion or transport of oocyte tubal cilia dysfunction through fallopian tube quality of oocytes Normal transport of oocyte sperm through fallopian tube is impaired facilitation of sperm transportation Inhibits normal zygote implantation […] Chlamydial or gonorrhoeal pathogens Previous tubal surgery or ectopic pregnancy surgery tissue removal transport of oocyte through fallopian tube
#26 Female Infertility – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK556033/
Hypothalamic amenorrhea or functional hypothalamic amenorrhea (FHA) is associated with eating disorders and excessive exercise, which results in a decrease in hypothalamic GnRH secretion. […] The most common type of Normogonadotropic normoestrogenic anovulation is PCOS. PCOS accounts for 80% to 85% of all anovulatory patients and affects 8% of all reproductive-aged females. […] Endometriosis is defined as endometrial tissue outside the uterine cavity. The diagnosis is based on the histological identification of endometrial glands or stroma outside the uterus. […] Pelvic and tubal adhesions, along with uterine and tubal abnormalities, account for a large portion of female infertility. […] Uterine causes of infertility are associated with either space-occupying lesions or reduced endometrial receptivity.
#27
https://apcz.umk.pl/QS/article/view/55644
Endometriosis is a complex systemic condition characterized by the growth of functional endometrial tissue outside the uterine cavity, affecting 10-15% of women of reproductive age. Up to 50% of these women face infertility challenges. […] Although there is a scientifically established connection between endometriosis and infertility, the underlying mechanisms remain not fully understood. […] The pathogenesis of infertility associated with endometriosis is complex and involves multiple factors. The most frequently cited contributors in the scientific literature include pain and dyspareunia, mechanical factors, reduced ovarian reserve, oxidative stress, changes in embryo and oocyte quality, impaired ovulation, and compromised endometrial receptivity. […] Endometriosis affects a growing number of women worldwide, with nearly half experiencing infertility. The complexity and involvement of multiple organ systems make it difficult to pinpoint a single cause, posing a challenge for clinicians. Addressing these diverse factors is essential for improving fertility management in women with endometriosis.
#28 Pathogenesis-of-Female-Infertility | Calgary Guide
https://calgaryguide.ucalgary.ca/pathogenesis-of-female-infertility/pathogenesis-of-female-infertility/
Female Infertility Previous abdominal infection or surgery Endometriosis Congenital malformations or trauma / surgery to cervix Uterine leiomyomata (benign smooth muscle monoclonal tumor) or polyp Intrauterine procedures Pelvic adhesions (scar-like tissue that tether together abdominal organs) may distort the shape and normal anatomy of the fallopian tube […] Ectopic endometrial cells implant Local inflammatory response grow along pathway of egg/sperm further egg/sperm mobility […] Inability of cervix to produce normal mucus, and/or sperm physically unable to enter the cervix Submucosal or intracavitary component disrupts uterine lining Trauma to basalis layer of endometrium Intrauterine scarring or synechiae (adhesions) vascularization endometrial regrowth.
#29 Infertility | AAFP
https://www.aafp.org/pubs/afp/issues/2007/0315/p849.html
Women with poor ovarian reserve have more success with oocyte donation. […] In certain cases, tubal disease may be treatable by surgical repair or by in vitro fertilization. […] Infertility attributed to endometriosis may be amenable to surgery, induction of ovulation with intrauterine insemination, or in vitro fertilization. […] Unexplained infertility may be managed with ovulation induction, intrauterine insemination, or both. […] The overall likelihood of successful pregnancy with treatment is nearly 50 percent. […] The overall likelihood of successful treatment for infertility is nearly 50 percent, but this varies by cause, age of the female partner, history of previous fertility, and duration of infertility. […] Of the various etiologies, infertility attributed to ovulatory dysfunction has the best prognosis, with treatment success rates approaching 50 percent overall. […] Infertility caused by tubal factors or severe endometriosis has the least likelihood for success (i.e., 21 and 17 percent, respectively).
#30
https://www.who.int/news-room/fact-sheets/detail/infertility
Infertility may occur due to male, female or unexplained factors. Some causes of infertility are preventable. Treatment of infertility often involves in-vitro fertilization (IVF) and other types of medically assisted reproduction. […] In the female reproductive system, infertility may be caused by tubal disorders such as blocked fallopian tubes, which are in turn caused by untreated sexually transmitted infections (STIs) or complications of unsafe abortion, postpartum sepsis or abdominal/pelvic surgery; uterine disorders which could be inflammatory in nature (such as such endometriosis), congenital in nature (such as septate uterus), or benign in nature (such as fibroids); disorders of the ovaries, such as polycystic ovarian syndrome and other follicular disorders; disorders of the endocrine system causing imbalances of reproductive hormones.
#31 Infertility: Practice Essentials, Overview, Etiology of Infertility
https://emedicine.medscape.com/article/274143-overview
Abnormalities or damage to the fallopian tube interferes with fertility and is responsible for abnormal implantation (eg, ectopic pregnancy). […] Anatomical defects or physiologic dysfunctions of the peritoneal cavity, including infection, adhesions, and adnexal masses, may cause infertility. […] Endometriosis remains an enigmatic disease that affects women during their reproductive years. […] Male factor infertility can be divided into pretesticular, testicular, and posttesticular etiologies. […] Environmental and occupational factors have been associated with an increased risk of infertility. […] Smoking has been associated with infertility in both males and females. […] Obesity may be associated with anovulation and oligomenorrhea. In men, obesity has been associated with decreased sperm quality. […] The American Society of Reproductive Medicine (ASRM) has several patient education guides and physician practice guidelines regarding infertility.
#32 Pelvic inflammatory disease and infertility
https://www1.racgp.org.au/ajgp/2023/april/pelvic-inflammatory-disease-and-infertility
Pelvic inflammatory disease (PID) is a major cause of morbidity and reproductive difficulty in women of childbearing age. […] This article outlines the pathogenesis, clinical evaluation and management of PID with a focus on the management of long-term fertility-related sequelae. […] Pelvic inflammatory disease (PID) refers to the inflammatory pathology of the female upper reproductive tract that occurs in response to infection with microbial pathogens. […] The ascension of microbes to the upper reproductive tract occurs as a result of disruption of the normal protective barriers of the lower reproductive tract by the causative pathogens. […] After initial infection, it is common for a polymicrobial infection to develop from the transposition of vaginal facultative organisms, including those associated with bacterial vaginosis, and respiratory and gastrointestinal organisms that have colonised the lower genital tract.
#33 Pelvic inflammatory disease and infertility
https://www1.racgp.org.au/ajgp/2023/april/pelvic-inflammatory-disease-and-infertility
The sequelae of PID are a major cause of reproductive morbidity in women of childbearing age, resulting in chronic pelvic pain, ectopic pregnancy and infertility. […] The risk of infertility increases in correlation with the degree of fallopian tube damage seen at laparoscopy, and may be as high as 30% in women with severe tubal damage. […] Recurrent infections are associated with a marked increase in the risk of infertility. […] Tubal factors account for 25-35% of cases of female infertility, with PID being the causative factor in more than half. […] The risk of tubal infertility increases with recurrent PID and, after three episodes, more than 50% of women will have tubal dysfunction. […] PID may result in proximal and/or distal disease of the fallopian tube. […] Although surgery for distal tubal disease offers a reasonable prospect for re-establishing tubal patency, it cannot reverse the ciliary damage of the tubal epithelium and architecture that results from the causative disease process. […] Tubal infertility is a not uncommon sequela of PID.
#34 Female Infertility – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK556033/
Hypothalamic amenorrhea or functional hypothalamic amenorrhea (FHA) is associated with eating disorders and excessive exercise, which results in a decrease in hypothalamic GnRH secretion. […] The most common type of Normogonadotropic normoestrogenic anovulation is PCOS. PCOS accounts for 80% to 85% of all anovulatory patients and affects 8% of all reproductive-aged females. […] Endometriosis is defined as endometrial tissue outside the uterine cavity. The diagnosis is based on the histological identification of endometrial glands or stroma outside the uterus. […] Pelvic and tubal adhesions, along with uterine and tubal abnormalities, account for a large portion of female infertility. […] Uterine causes of infertility are associated with either space-occupying lesions or reduced endometrial receptivity.
#35 Female Infertility – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK556033/
The gold standard for assessing the uterine cavity is hysteroscopy, which allows direct visualization of the intrauterine pathology and provides an opportunity for immediate surgical correction. […] Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic complication of controlled ovarian hyperstimulation that results in a broad range of signs and symptoms, ranging from abdominal distention, nausea, vomiting, enlarged ovaries, third-spacing of fluids, renal failure, and venous thrombosis, acute respiratory distress syndrome, electrolyte derangements, cardiac arrhythmias, and sepsis.
#36 Pathophysiology of Infertility | PPT
https://www.slideshare.net/slideshow/pathophysiology-of-infertility/231838678
Tubal factors in infertility include endometriosis, pelvic adhesions, pelvic inflammatory diseases, tubal occlusion and tubal dysfunction. Endometriosis is a noncancerous condition and may cause adhesions between the uterus, ovaries, and fallopian tubes, thereby preventing the transfer of the egg to the tube and thus infertility […] Notable amongst uterine factors are uterine malformation such as abnormal uterine shape and intrauterine septum polyps, leiomyoma, and Asherman’s syndrome. Benign fibroid in the uterus are extremely common in women in their 30s. Large fibroids may cause infertility by impairing the uterine lining, blocking the fallopian tube, distorting the shape of the uterine cavity or altering the position of the cervix […] The hypothalamus, through the release of gonadotrophin releasing hormones, controls the pituitary gland which directly or indirectly controls most other hormonal glands in the human body. Thus, alterations in the chemical signals from the hypothalamus can affect the pituitary gland, ovaries, thyroid, mammary gland and hence, hormonal abnormalities. Women with hormonal imbalance will not produce enough follicles to ensure the development of an ovule.
#37 Pathophysiology of Infertility | PPT
https://www.slideshare.net/slideshow/pathophysiology-of-infertility/231838678
Tubal factors in infertility include endometriosis, pelvic adhesions, pelvic inflammatory diseases, tubal occlusion and tubal dysfunction. Endometriosis is a noncancerous condition and may cause adhesions between the uterus, ovaries, and fallopian tubes, thereby preventing the transfer of the egg to the tube and thus infertility […] Notable amongst uterine factors are uterine malformation such as abnormal uterine shape and intrauterine septum polyps, leiomyoma, and Asherman’s syndrome. Benign fibroid in the uterus are extremely common in women in their 30s. Large fibroids may cause infertility by impairing the uterine lining, blocking the fallopian tube, distorting the shape of the uterine cavity or altering the position of the cervix […] The hypothalamus, through the release of gonadotrophin releasing hormones, controls the pituitary gland which directly or indirectly controls most other hormonal glands in the human body. Thus, alterations in the chemical signals from the hypothalamus can affect the pituitary gland, ovaries, thyroid, mammary gland and hence, hormonal abnormalities. Women with hormonal imbalance will not produce enough follicles to ensure the development of an ovule.
#38
https://www.alliedacademies.org/articles/pathogenesis-and-treatment-status-of-adenomyosis-complicated-with-infertility-10060.html
Adenomyosis (AD) refers to the endometrium (including glands and stroma) into myometrium growth of pathological changes, with the delay of women’s childbearing age, the patients with Adenomyosis -associated infertility increased significantly. […] more and more evidence showed that Adenomyosis was closely related to the structural and functional defects of the eutopic endometrium and myometrial junctional zone (MJZ), which may lead to embryo implantation failure and infertility. […] Adenomyosis may influence the patient?s reproductive function by affecting sperm transport, embryo implantation, altering uterine peristalsis, influencing the structure and function of endometrium, and changing the intrauterine environment. […] The clinical and experimental studies of Adenomyosis complicated with infertility and its possible pathogenesis and treatment in recent years are reviewed in this article.
#39
https://www.alliedacademies.org/articles/pathogenesis-and-treatment-status-of-adenomyosis-complicated-with-infertility-10060.html
Adenomyosis (AD) refers to the endometrium (including glands and stroma) into myometrium growth of pathological changes, with the delay of women’s childbearing age, the patients with Adenomyosis -associated infertility increased significantly. […] more and more evidence showed that Adenomyosis was closely related to the structural and functional defects of the eutopic endometrium and myometrial junctional zone (MJZ), which may lead to embryo implantation failure and infertility. […] Adenomyosis may influence the patient?s reproductive function by affecting sperm transport, embryo implantation, altering uterine peristalsis, influencing the structure and function of endometrium, and changing the intrauterine environment. […] The clinical and experimental studies of Adenomyosis complicated with infertility and its possible pathogenesis and treatment in recent years are reviewed in this article.
#40 Pathophysiology of Infertility | PPT
https://www.slideshare.net/slideshow/pathophysiology-of-infertility/231838678
Infertility is the inability of a couple to achieve pregnancy over an average period of one year despite adequate, regular (3-4 times per week), unprotected sexual intercourse. Infertility may also be referred to as the inability to carry a pregnancy to the delivery of a live baby. The couple conceived and delivered a live baby in 1st pregnancy but unable to conceive for the 2nd time is also termed as infertility […] Infertility can be due to the Woman (60-70%) Man (40-50%) Both […] Male infertility refers to the inability of a male to achieve pregnancy in a fertile female. Male factors accounts for 40-50% of infertility in human […] Low sperm counts, abnormal spermatozoa morphology (shape) and low sperm motility are conditions that are usually asymptomatic to most males but of great etiological importance. The quality of the spermatozoa (count, vitality, motility and morphology) and the composition of seminal fluid are also important index of sperm function. Improper sperm function can lead to infertility
#41 Male infertility â The other side of the equation
https://www.racgp.org.au/afp/2017/september/male-infertility
Male infertility can result from anatomical or genetic abnormalities, systemic or neurological diseases, infections, trauma, iatrogenic injury, gonadotoxins and development of sperm antibodies. […] Male infertility is associated with poorer overall health, increased cancer risk and decreased life expectancy. […] Male infertility can be caused by a wide range of conditions, encompassing anatomical or genetic abnormalities, systemic or neurological diseases, infections, trauma, iatrogenic injury, gonadotoxins and development of sperm antibodies. […] In 30-40% of male infertility cases, no cause is identified (idiopathic male infertility). […] The minimal assessment includes measurement of serum follicle stimulating hormone (FSH) and morning testosterone levels. […] Hypogonadotropic hypogonadism, also known as secondary hypogonadism, results from failure of the hypothalamic-pituitary axis to stimulate normal gonadal function.
#42 Male Infertility: Practice Essentials, Background, Pathophysiology
https://emedicine.medscape.com/article/436829-overview
Infertility in men can result from deficiencies in sperm formation, concentration, or transportation. This general division allows an appropriate workup of potential underlying causes of infertility and helps define a course of action for treatment. […] Infertile men may have deficiencies in sperm formation, concentration (eg, oligospermia [too few sperm], azoospermia [no sperm in the ejaculate]), or transportation. The causes can be categorized as obstructive or nonobstructive. This general division allows an appropriate workup of potential underlying causes of infertility and helps define a course of action for treatment. […] Gonadal and sexual functions are mediated by the hypothalamic-pituitary-gonadal axis, a closed-loop system with feedback control from the testicles. The hypothalamus, the primary integration center, responds to various signals from the central nervous system (CNS), pituitary gland, and testicles to secrete gonadotropin-releasing hormone (GnRH) in a pulsatile pattern approximately every 70-90 minutes.
#43 Male Infertility: Practice Essentials, Background, Pathophysiology
https://emedicine.medscape.com/article/436829-overview
Infertility in men can result from deficiencies in sperm formation, concentration, or transportation. This general division allows an appropriate workup of potential underlying causes of infertility and helps define a course of action for treatment. […] Infertile men may have deficiencies in sperm formation, concentration (eg, oligospermia [too few sperm], azoospermia [no sperm in the ejaculate]), or transportation. The causes can be categorized as obstructive or nonobstructive. This general division allows an appropriate workup of potential underlying causes of infertility and helps define a course of action for treatment. […] Gonadal and sexual functions are mediated by the hypothalamic-pituitary-gonadal axis, a closed-loop system with feedback control from the testicles. The hypothalamus, the primary integration center, responds to various signals from the central nervous system (CNS), pituitary gland, and testicles to secrete gonadotropin-releasing hormone (GnRH) in a pulsatile pattern approximately every 70-90 minutes.
#44 Male Infertility: Practice Essentials, Background, Pathophysiology
https://emedicine.medscape.com/article/436829-overview
Release of GnRH is stimulated by melatonin from the pineal gland and inhibited by testosterone, inhibin, corticotropin-releasing hormone, opiates, illness, and stress. […] The pulsatile nature of GnRH is essential to normal gonadotropin release; a continuous stimulation inhibits their secretion. […] The hypothalamus also produces thyrotropin-releasing hormone (TRH) and vasoactive intestinal peptide (VIP), both of which stimulate prolactin release from the anterior pituitary, and dopamine, which inhibits prolactin release. […] Prolactin inhibits the production of GnRH from the hypothalamus and LH and FSH from the pituitary. […] Testosterone is secreted in a diurnal pattern, peaking a few hours after the man awakens from sleep. […] Testosterone and estradiol function as feedback inhibitors of gonadotropin release.
#45 Male Infertility: Practice Essentials, Background, Pathophysiology
https://emedicine.medscape.com/article/436829-overview
Release of GnRH is stimulated by melatonin from the pineal gland and inhibited by testosterone, inhibin, corticotropin-releasing hormone, opiates, illness, and stress. […] The pulsatile nature of GnRH is essential to normal gonadotropin release; a continuous stimulation inhibits their secretion. […] The hypothalamus also produces thyrotropin-releasing hormone (TRH) and vasoactive intestinal peptide (VIP), both of which stimulate prolactin release from the anterior pituitary, and dopamine, which inhibits prolactin release. […] Prolactin inhibits the production of GnRH from the hypothalamus and LH and FSH from the pituitary. […] Testosterone is secreted in a diurnal pattern, peaking a few hours after the man awakens from sleep. […] Testosterone and estradiol function as feedback inhibitors of gonadotropin release.
#46 Pathophysiology of Infertility | PPT
https://www.slideshare.net/slideshow/pathophysiology-of-infertility/231838678
Infertility is the inability of a couple to achieve pregnancy over an average period of one year despite adequate, regular (3-4 times per week), unprotected sexual intercourse. Infertility may also be referred to as the inability to carry a pregnancy to the delivery of a live baby. The couple conceived and delivered a live baby in 1st pregnancy but unable to conceive for the 2nd time is also termed as infertility […] Infertility can be due to the Woman (60-70%) Man (40-50%) Both […] Male infertility refers to the inability of a male to achieve pregnancy in a fertile female. Male factors accounts for 40-50% of infertility in human […] Low sperm counts, abnormal spermatozoa morphology (shape) and low sperm motility are conditions that are usually asymptomatic to most males but of great etiological importance. The quality of the spermatozoa (count, vitality, motility and morphology) and the composition of seminal fluid are also important index of sperm function. Improper sperm function can lead to infertility
#47
https://typeset.io/papers/male-infertility-pathogenesis-and-clinical-diagnosis-1tixs2ibrb
The only available therapy for male factor infertility is assisted reproduction which allows conception also in severe male factor, including azoospermia following testicular sperm extraction. […] Oligozoospermic men with 10 million spermatozoa have a higher risk to have autosomal abnormalities than azoospermic men. […] The importance of the detection of these structural chromosomal anomalies is related to the increased risk of aneuploidy or unbalanced chromosomal complements in the fetus. […] Mutational analyses of a few spermatogenesis candidate gene have been performed mainly in research context and up to now translation of results into clinical practice is lacking. […] The interaction of genetic and environmental (mainly endocrine disrupters) factors acting on the fetal testis has been proposed as the major determinant of the progressive increase during the past 50 years of pathologies such as cryptorchidism, testis cancer, hypospadia and impaired spermatogenesis in Western countries. […] The presence of not one but three spermatogenesis loci in Yq11 is proposed and that each locus is active during a different phase of male germ cell development.
#48 Male infertility â The other side of the equation
https://www.racgp.org.au/afp/2017/september/male-infertility
Male infertility can result from anatomical or genetic abnormalities, systemic or neurological diseases, infections, trauma, iatrogenic injury, gonadotoxins and development of sperm antibodies. […] Male infertility is associated with poorer overall health, increased cancer risk and decreased life expectancy. […] Male infertility can be caused by a wide range of conditions, encompassing anatomical or genetic abnormalities, systemic or neurological diseases, infections, trauma, iatrogenic injury, gonadotoxins and development of sperm antibodies. […] In 30-40% of male infertility cases, no cause is identified (idiopathic male infertility). […] The minimal assessment includes measurement of serum follicle stimulating hormone (FSH) and morning testosterone levels. […] Hypogonadotropic hypogonadism, also known as secondary hypogonadism, results from failure of the hypothalamic-pituitary axis to stimulate normal gonadal function.
#49 Pathophysiology of Infertility | PPT
https://www.slideshare.net/slideshow/pathophysiology-of-infertility/231838678
Aspermia – complete lack of semen, Hypospermia – reduced seminal volume, Oligozoospermia – decreased number of spermatozoa in semen, Azoospermia – absence of sperm cells in semen, Teratospermia – increase in sperm with abnormal morphology, Asthenozoospermia – reduced sperm motility. These conditions can lead to infertility […] Vas deferens and ejaculatory duct obstruction could be an important cause of infertility as they affect ejaculation. Obstructive azoospermia may result from previous vasectomy; epididymal, or ejaculatory duct pathology […] It has been established that environmental factors can lead to infertility. Toxins such as glues, volatile organic solvents, silicones, physical agents, chemical dusts and pesticides are found to produce damaging effects in testis and affecting sperm quality and quantity. Radiations and excessive heat to the genitalia have damaging effect on the testicles. Hence individuals having direct contact with or exposure to such chemicals have high chances of having primary or secondary infertility
#50 Ejaculatory physiology and pathophysiology: assessment and treatment in male infertility – Revenig – Translational Andrology and Urology
https://tau.amegroups.org/article/view/3515/html
Azoospermia is a heterogeneous condition with multiple etiologies and a variety of treatments. […] Retrograde ejaculation and failure of emission are in a spectrum of ejaculatory disorders which impair male fertility. […] Retrograde ejaculation and failure of emission are the two disorders of ejaculatory function which result in anejaculation and infertility. […] While all three have a common pathway of anejaculation, the disorders leading to these conditions comprise a heterogeneous group of conditions with differing etiologies and therapies. […] Retrograde ejaculation is the flow of semen into the bladder due to an incompletely closed bladder neck. […] A variety of mechanical, neurologic, and pharmacologic etiologies are responsible for retrograde ejaculation. […] Surgical injury to the nerves influencing ejaculatory function also carry the risk of retrograde ejaculation with the most common being retroperitoneal surgeries, colorectal surgery, and spine surgery.
#51 Male Infertility: Practice Essentials, Background, Pathophysiology
https://emedicine.medscape.com/article/436829-overview
The epididymis additionally secretes substances for sperm nutrition and protection such as glycerophosphorylcholine, carnitine, and sialic acid. […] Varicoceles may lead to impaired testicular spermatogenesis and steroidogenesis, potentially due to an increased intratesticular temperature, reflux of toxic metabolites, and/or germ cell hypoxia; this appears to be progressive over time. […] Varicoceles lead to an increased incidence of sperm immaturity, apoptosis, and necrosis with severe disturbances in meiotic segregation compared with fertile men without varicoceles.
#52 Pathophysiology of Infertility | PPT
https://www.slideshare.net/slideshow/pathophysiology-of-infertility/231838678
Aspermia – complete lack of semen, Hypospermia – reduced seminal volume, Oligozoospermia – decreased number of spermatozoa in semen, Azoospermia – absence of sperm cells in semen, Teratospermia – increase in sperm with abnormal morphology, Asthenozoospermia – reduced sperm motility. These conditions can lead to infertility […] Vas deferens and ejaculatory duct obstruction could be an important cause of infertility as they affect ejaculation. Obstructive azoospermia may result from previous vasectomy; epididymal, or ejaculatory duct pathology […] It has been established that environmental factors can lead to infertility. Toxins such as glues, volatile organic solvents, silicones, physical agents, chemical dusts and pesticides are found to produce damaging effects in testis and affecting sperm quality and quantity. Radiations and excessive heat to the genitalia have damaging effect on the testicles. Hence individuals having direct contact with or exposure to such chemicals have high chances of having primary or secondary infertility
#53 Pathophysiology of Infertility | PPT
https://www.slideshare.net/slideshow/pathophysiology-of-infertility/231838678
The contribution of tobacco smoking and alcohol intake to infertility had been established. Tobacco smoking was observed to damage sperm DNA. Though some of the damage is irreversible, stopping smoking can prevent further damage. Smokers are 60% more likely to be infertile than non-smokers […] STDs are diseases transmitted through sexual activity with an infected partner caused by viruses, bacteria, or parasitic microorganisms. STDs are a leading cause of infertility. They are often asymptomatic but may display few symptoms, with the risk of failing to seek proper treatment in time to prevent decreased fertility […] A woman of reproductive age who has not conceived after 1 year of unprotected vaginal sexual intercourse is known as female infertility. It is estimated that female infertility accounts for 50-70%
#54 Pathophysiology of Infertility | PPT
https://www.slideshare.net/slideshow/pathophysiology-of-infertility/231838678
The contribution of tobacco smoking and alcohol intake to infertility had been established. Tobacco smoking was observed to damage sperm DNA. Though some of the damage is irreversible, stopping smoking can prevent further damage. Smokers are 60% more likely to be infertile than non-smokers […] STDs are diseases transmitted through sexual activity with an infected partner caused by viruses, bacteria, or parasitic microorganisms. STDs are a leading cause of infertility. They are often asymptomatic but may display few symptoms, with the risk of failing to seek proper treatment in time to prevent decreased fertility […] A woman of reproductive age who has not conceived after 1 year of unprotected vaginal sexual intercourse is known as female infertility. It is estimated that female infertility accounts for 50-70%
#55 Insights of Sperm Pathology and Its Association with Infertility | IntechOpen
https://www.intechopen.com/chapters/70916
It is broadly acquired that precious motility of sperm is the chief component of fertility of male. […] Statistics from United States depicted that the major cause of male infertility is ROS. […] In 30-40% of infertile mens seminal plasma, there is an increase in the level of ROS. […] The production of ROS at the level of mitochondria is the chief source. […] Quality of sperm and function is affected by the high concentration of ROS and is potentially toxic. […] Physiological level of ROS plays a significant task in the physiological process such as capacitation, hyperactivation, acrosomal reaction, fusion of sperm and oocyte in order to assure the proper fertilization. […] Sperm DNA of healthy males is protected from osmotic stress by two mechanisms; Tightly packed and coiled DNA so that the genetic material is less exposed to ROS and Production of ROS is minimized by natural antioxidant present in seminal plasma and spermatozoa. […] This augmented production of ROS has negative impact on spermatozoa quality and damage their capacity of fertilizing the egg.
#56 Infertility mechanism in males identified
https://medicalxpress.com/news/2018-04-infertility-mechanism-males.html
Infertility mechanism in males identified […] A sperm protein, called phospholipase C zeta (PLCÎ¶), has been found to be necessary for egg fertilization. […] The team was able to initiate the fertilization process in the lab by injecting eggs with a higher amount of the PLCÎ¶ protein than naturally found in the sperm of infertile men. […] Sperm PLCÎ¶ is an essential trigger of the first 'egg activation’ stage of fertilization. […] Recent clinical studies have reported that the sperm of some males fail to initiate fertilization despite having normal morphology and motility. […] The team investigated the effects of a mutation in the gene that codes for PLCÎ¶ on infertility. […] However, if they increased the amount of abnormal protein to higher levels than naturally present, the normal fertilization process began. […] We hope that this work will lead to a PLCÎ¶ therapy to help couples suffering from infertility to have the chance of a family.
#57 Azthena logo with the word Azthena
https://www.news-medical.net/news/20220110/New-genetic-mechanism-that-can-cause-severe-male-infertility-identified.aspx
Scientists at Newcastle University have identified a new genetic mechanism that can cause severe forms of male infertility. […] This breakthrough in understanding the underlying cause of male infertility offers hope of better treatment options for patients in the future. […] The study, published today in Nature Communications, shows that new mutations, not inherited from father or mother, play a major role in this medical condition. […] Experts have found that mutations occurring during the reproduction process, when the DNA of both parents is replicated, can result in infertility in men later in life. […] This is a real paradigm shift in our understanding of the causes of male infertility. […] However, our research has found that mutations which occur when the DNA is replicated during reproduction in parents plays a significant role in the infertility in their sons.
#58 Azthena logo with the word Azthena
https://www.news-medical.net/news/20220110/New-genetic-mechanism-that-can-cause-severe-male-infertility-identified.aspx
Scientists collected and studied DNA from a global cohort of 185 infertile men and their parents. They identified 145 rare protein-altering mutations that are likely to negatively impact male fertility. […] As many as 29 of the mutations affect genes directly involved in processes related to spermatogenesis the process of sperm cell development – or other cellular processes related to reproduction. […] Experts identified mutations in the gene RBM5 in multiple infertile men. […] Importantly, these mutations mostly cause a dominant form of infertility, where only one mutated gene is required. […] This research indicates a significant proportion of these children may inherit infertility from their father. […] Moving forwards, the scientists want to expand their work by studying thousands of patients and their parents in a large international consortium. […] They will follow-up their research by conducting further studies into the role these newly identified mutated genes have on the impact of spermatogenesis and on the overall fertility in humans.
#59 The biology of infertility: research advances and clinical challenges
https://pmc.ncbi.nlm.nih.gov/articles/PMC3786590/
Reproduction is required for the survival of all mammalian species, and thousands of essential sex genes are conserved through evolution. […] However, many infertile couples continue to be labeled with the diagnosis of idiopathic infertility or given descriptive diagnoses that do not provide a cause for their defect. […] When these highly regulated processes go awry, infertility can occur. […] This review focuses on the mechanisms directing the development of the reproductive tract and the regulatory controls of each process, from gametogenesis through genital tract transit to fertilization. […] The development of the genital tract and secondary sex organs depends upon the occurrence of a testis or an ovary and the presence or absence, respectively, of the sex determining region Y (SRY) gene carried on the Y chromosome.
#60 Pathogenic landscape of idiopathic male infertility: new insight towards its regulatory networks | npj Genomic Medicine
https://www.nature.com/articles/npjgenmed201623
Idiopathic male infertility (IMI) affects nearly 10-15% of men in their prime reproductive age. More than 500 target genes were postulated to be associated with this disease condition through various genomic studies. The challenge is to determine the functional role of these genes and proteins that form part of a larger network leading to pathogenesis of the IMI phenotype in humans. […] Any imbalance in these genes through mutation, single-nucleotide polymorphisms (SNPs) or other forms could result in abnormal regulation of genes leading to infertility. […] The enriched biological functions in SNPs, as well as functional analysis of IMI genes, resulted in the identification of novel gene pairs, from which we proposed new models to describe the underlying pathogenesis of this disease condition.
#61 Pathogenic landscape of idiopathic male infertility: new insight towards its regulatory networks | npj Genomic Medicine
https://www.nature.com/articles/npjgenmed201623
Idiopathic male infertility (IMI) affects nearly 10-15% of men in their prime reproductive age. More than 500 target genes were postulated to be associated with this disease condition through various genomic studies. The challenge is to determine the functional role of these genes and proteins that form part of a larger network leading to pathogenesis of the IMI phenotype in humans. […] Any imbalance in these genes through mutation, single-nucleotide polymorphisms (SNPs) or other forms could result in abnormal regulation of genes leading to infertility. […] The enriched biological functions in SNPs, as well as functional analysis of IMI genes, resulted in the identification of novel gene pairs, from which we proposed new models to describe the underlying pathogenesis of this disease condition.
#62 Pathogenic landscape of idiopathic male infertility: new insight towards its regulatory networks | npj Genomic Medicine
https://www.nature.com/articles/npjgenmed201623
Idiopathic male infertility (IMI) affects nearly 10-15% of men in their prime reproductive age. More than 500 target genes were postulated to be associated with this disease condition through various genomic studies. The challenge is to determine the functional role of these genes and proteins that form part of a larger network leading to pathogenesis of the IMI phenotype in humans. […] Any imbalance in these genes through mutation, single-nucleotide polymorphisms (SNPs) or other forms could result in abnormal regulation of genes leading to infertility. […] The enriched biological functions in SNPs, as well as functional analysis of IMI genes, resulted in the identification of novel gene pairs, from which we proposed new models to describe the underlying pathogenesis of this disease condition.
#63 Pathogenic landscape of idiopathic male infertility: new insight towards its regulatory networks | npj Genomic Medicine
https://www.nature.com/articles/npjgenmed201623
The outcome of this study will give a new set of genes and proteins that could help explain the disease from a global perspective previously not addressed using standard approaches. […] IMI is a much-debated terminology considering the different degrees of male infertility prevalent in the general population, with most severe forms manifested as azoospermia and asthenozoospermia. […] Current consensus on idiopathic infertility describes the condition as following an array of genetic testing to identify the disease condition the etiology remains unknown for about 40% of primary testicular failure cases. […] Based on investigations carried out using different platforms including biochemical, genetic and molecular studies it could be inferred that male infertility is a complex heterogeneous multifactorial disorder, which has met with limited success in identifying the real causes behind this condition.
#64
https://benthamscience.com/public/ebook_volume/3854
Male infertility is a significant global health concern, necessitating an understanding of its molecular basis to develop effective diagnostics and treatments. […] Male infertility can result from disruptions in these processes due to factors such as genetic mutations, impaired sperm motility, hormonal imbalances, and oxidative stress (OS). […] Genetic alterations can affect genes crucial for spermatogenesis, sperm function, or hormonal regulation. […] OS, arising from an imbalance between reactive oxygen species (ROS) and antioxidants, can cause sperm DNA damage. […] The intricate mechanisms underlying immunological causes of male infertility are progressively gaining prominence within the field of reproductive medicine. […] The present chapter explains the testicular immune components, immune tolerance and response, and also the etiological aspects of these immunological elements, emphasizing the potential role of genetic susceptibility, infection or trauma to the male reproductive tract, and environmental toxin exposure as contributory factors to male infertility.
#65 New mechanism for male infertility discovered | EurekAlert!
https://www.eurekalert.org/news-releases/898862
A new study led from Karolinska Institutet in Sweden links male infertility to autoimmune prostatic inflammation. […] In the present study, the researchers have discovered a reason for reduced fertility in people with autoimmune polyendocrine syndrome type 1 (APS1), which increases the risk of developing autoimmune disease (caused by the immune system attacking and damaging healthy cells) and which is often used as a model for autoimmune disease in general. […] While infertility in women with APS1 is caused by autoimmune action against the ovaries, what gives rise to the corresponding infertility in men has never been ascertained. […] „We found that the immune system in a large group of patients reacted to a protein formed only in the prostate, namely the enzyme transglutaminase 4,” says lead investigator Dr Nils Landegren at Karolinska Institutet’s Department of Medicine in Solna.
#66 New mechanism for male infertility discovered | EurekAlert!
https://www.eurekalert.org/news-releases/898862
A new study led from Karolinska Institutet in Sweden links male infertility to autoimmune prostatic inflammation. […] In the present study, the researchers have discovered a reason for reduced fertility in people with autoimmune polyendocrine syndrome type 1 (APS1), which increases the risk of developing autoimmune disease (caused by the immune system attacking and damaging healthy cells) and which is often used as a model for autoimmune disease in general. […] While infertility in women with APS1 is caused by autoimmune action against the ovaries, what gives rise to the corresponding infertility in men has never been ascertained. […] „We found that the immune system in a large group of patients reacted to a protein formed only in the prostate, namely the enzyme transglutaminase 4,” says lead investigator Dr Nils Landegren at Karolinska Institutet’s Department of Medicine in Solna.
#67 New mechanism for male infertility discovered | EurekAlert!
https://www.eurekalert.org/news-releases/898862
Interestingly, previous studies on mice have shown that transglutaminase 4 plays an important part in male fertility. […] „The finds are important as they point to a new disease mechanism for male infertility, but more work needs to be done to understand the significance of autoimmune prostatitis to infertility in the male population at large,” says Dr Landegren.
#68 Infertility – Knowledge @ AMBOSS
https://www.amboss.com/us/knowledge/infertility/
Infertility is the inability to achieve pregnancy after 12 months of regular unprotected sexual intercourse in female individuals of age and after 6 months in those 35 years of age, or the need for medically assisted reproduction to achieve pregnancy. […] Causes of female infertility include diminished ovarian reserve, ovulatory dysfunction, and tubal, pelvic, uterine, and cervical disorders. […] Causes of male infertility include male hypogonadism and sperm transport disorders. […] The cause of infertility remains unexplained in up to a third of affected couples. […] Antisperm antibodies form when the blood testis barrier is disrupted, usually due to infections or trauma of the male genital tract, and can lead to immobilization and agglutination of sperm or have a spermatoxic effect.
#69 The biology of infertility: research advances and clinical challenges
https://pmc.ncbi.nlm.nih.gov/articles/PMC3786590/
Reproduction is required for the survival of all mammalian species, and thousands of essential sex genes are conserved through evolution. […] However, many infertile couples continue to be labeled with the diagnosis of idiopathic infertility or given descriptive diagnoses that do not provide a cause for their defect. […] When these highly regulated processes go awry, infertility can occur. […] This review focuses on the mechanisms directing the development of the reproductive tract and the regulatory controls of each process, from gametogenesis through genital tract transit to fertilization. […] The development of the genital tract and secondary sex organs depends upon the occurrence of a testis or an ovary and the presence or absence, respectively, of the sex determining region Y (SRY) gene carried on the Y chromosome.
#70 The biology of infertility: research advances and clinical challenges
https://pmc.ncbi.nlm.nih.gov/articles/PMC3786590/
The prenatal production of testicular anti-Mullerian hormone (AMH), acting through its receptor AMHR2, induces the regression of the Mullerian duct, whereas testosterone drives the development of these Wolffian duct derivatives. […] The hypothalamic-pituitary-gonadal axis is the major evolutionarily conserved positive- and negative-endocrine feedback system that regulates the production of mature gametes. […] Genetic breakthroughs in understanding additional regulators of this axis and the causes of infertility in humans have involved studies of the signaling between the peptide growth factor, kisspeptin (encoded by KISS1) and KISS1 receptor (KISS1R, also known as GPR54). […] Similar to the tissue cross talk within the hypothalamic-pituitary-gonadal axis, there are important bidirectional paracrine and juxtracrine interactions between the oocyte and the surrounding somatic cells of the ovary that begin upon entry of primordial germ cells into the genital ridge and continue through ovulation.
#71 The biology of infertility: research advances and clinical challenges
https://pmc.ncbi.nlm.nih.gov/articles/PMC3786590/
The initial events ultimately required for later fertility are gonadal determination and differentiation of the sexual characteristics of the developing fetus. […] The major gene implicated in human sex reversal cases is SRY, the Y chromosome male-determining gene. […] Aberrant sex determination has an important role in the etiology of intersex, beginning with the proper development of the testis or ovary from the genital ridge. […] Hormonal, gonadal and end-organ defects can be associated with absent or incomplete virilization in males and masculinization in females. […] The presence of ectopic endometriotic tissue, or endometriosis, affects 10% of women and is hypothesized to originate from retrograde sloughing of the uterine lining during menses. […] The presence of long-lived RNA in the transcriptionally inactive sperm was known, it was not until the work of Krawetz and his colleagues that the diagnostic potential of this RNA became evident. […] The future holds great promise for substantial research advances in the field of reproductive biology and medicine.
#72 Male infertility â The other side of the equation
https://www.racgp.org.au/afp/2017/september/male-infertility
Even if hypogonadism is identified, exogenous testosterone use is contraindicated in patients seeking fertility treatment. […] Sperm DNA fragmentation tests may provide some prognostic information, its role in management of an infertile male is yet to be established. […] Genetic testing is indicated for patients with severe oligospermia (5 million/mL). […] A specific region, named AZF (azoospermia factor), in the long arm of the Y chromosome is critical to normal spermatogenesis. […] Karyotype testing is indicated in patients with severe oligospermia (5 million/mL), because the prevalence of karyotype abnormalities is inversely proportional to sperm count. […] The most common abnormality is Klinefelter syndrome (47, XXY), which accounts for approximately two-thirds of abnormalities in men who are infertile.
#73 Male infertility â The other side of the equation
https://www.racgp.org.au/afp/2017/september/male-infertility
Even if hypogonadism is identified, exogenous testosterone use is contraindicated in patients seeking fertility treatment. […] Sperm DNA fragmentation tests may provide some prognostic information, its role in management of an infertile male is yet to be established. […] Genetic testing is indicated for patients with severe oligospermia (5 million/mL). […] A specific region, named AZF (azoospermia factor), in the long arm of the Y chromosome is critical to normal spermatogenesis. […] Karyotype testing is indicated in patients with severe oligospermia (5 million/mL), because the prevalence of karyotype abnormalities is inversely proportional to sperm count. […] The most common abnormality is Klinefelter syndrome (47, XXY), which accounts for approximately two-thirds of abnormalities in men who are infertile.
#74 Discovery of genes involved in infertility mechanism
https://medicalxpress.com/news/2020-02-discovery-genes-involved-infertility-mechanism.html
Discovery of genes involved in infertility mechanism […] Researchers from Kumamoto University (Japan) performed genome editing experiments to verify that the Meiosin gene was indeed the trigger for meiosis. When they removed the gene in a murine experimental model, meiosis did not begin and germ cells were not produced rendering the animals infertile. […] Recently, a group of researchers from Kumamoto University in Japan set out to assess the proteins involved in meiosis to clarify its development. Using mass spectrometry, the group was able to identify a gene that acts as a meiosis on switch, labeling it „Meiosin” (for meiosis initiator). The Meiosin gene has the extremely rare property of becoming activated only at a specific timeâjust before the beginning of meiosis in the gonads. In animal experiments, the researchers found that both male and female mice became infertile if the Meiosin gene was artificially inhibited. Further analysis of the mouse male and female gonads clarified that the gene plays an essential role in meiosis activation. The Meiosin gene acts as a control tower that simultaneously switches on hundreds of genes for germ cell formation, and appears to be involved with infertility.
#75 Discovery of genes involved in infertility mechanism
https://medicalxpress.com/news/2020-02-discovery-genes-involved-infertility-mechanism.html
Discovery of genes involved in infertility mechanism […] Researchers from Kumamoto University (Japan) performed genome editing experiments to verify that the Meiosin gene was indeed the trigger for meiosis. When they removed the gene in a murine experimental model, meiosis did not begin and germ cells were not produced rendering the animals infertile. […] Recently, a group of researchers from Kumamoto University in Japan set out to assess the proteins involved in meiosis to clarify its development. Using mass spectrometry, the group was able to identify a gene that acts as a meiosis on switch, labeling it „Meiosin” (for meiosis initiator). The Meiosin gene has the extremely rare property of becoming activated only at a specific timeâjust before the beginning of meiosis in the gonads. In animal experiments, the researchers found that both male and female mice became infertile if the Meiosin gene was artificially inhibited. Further analysis of the mouse male and female gonads clarified that the gene plays an essential role in meiosis activation. The Meiosin gene acts as a control tower that simultaneously switches on hundreds of genes for germ cell formation, and appears to be involved with infertility.
#76 The biology of infertility: research advances and clinical challenges
https://pmc.ncbi.nlm.nih.gov/articles/PMC3786590/
The prenatal production of testicular anti-Mullerian hormone (AMH), acting through its receptor AMHR2, induces the regression of the Mullerian duct, whereas testosterone drives the development of these Wolffian duct derivatives. […] The hypothalamic-pituitary-gonadal axis is the major evolutionarily conserved positive- and negative-endocrine feedback system that regulates the production of mature gametes. […] Genetic breakthroughs in understanding additional regulators of this axis and the causes of infertility in humans have involved studies of the signaling between the peptide growth factor, kisspeptin (encoded by KISS1) and KISS1 receptor (KISS1R, also known as GPR54). […] Similar to the tissue cross talk within the hypothalamic-pituitary-gonadal axis, there are important bidirectional paracrine and juxtracrine interactions between the oocyte and the surrounding somatic cells of the ovary that begin upon entry of primordial germ cells into the genital ridge and continue through ovulation.
#77 The biology of infertility: research advances and clinical challenges
https://pmc.ncbi.nlm.nih.gov/articles/PMC3786590/
The prenatal production of testicular anti-Mullerian hormone (AMH), acting through its receptor AMHR2, induces the regression of the Mullerian duct, whereas testosterone drives the development of these Wolffian duct derivatives. […] The hypothalamic-pituitary-gonadal axis is the major evolutionarily conserved positive- and negative-endocrine feedback system that regulates the production of mature gametes. […] Genetic breakthroughs in understanding additional regulators of this axis and the causes of infertility in humans have involved studies of the signaling between the peptide growth factor, kisspeptin (encoded by KISS1) and KISS1 receptor (KISS1R, also known as GPR54). […] Similar to the tissue cross talk within the hypothalamic-pituitary-gonadal axis, there are important bidirectional paracrine and juxtracrine interactions between the oocyte and the surrounding somatic cells of the ovary that begin upon entry of primordial germ cells into the genital ridge and continue through ovulation.
#78 The biology of infertility: research advances and clinical challenges
https://pmc.ncbi.nlm.nih.gov/articles/PMC3786590/
The prenatal production of testicular anti-Mullerian hormone (AMH), acting through its receptor AMHR2, induces the regression of the Mullerian duct, whereas testosterone drives the development of these Wolffian duct derivatives. […] The hypothalamic-pituitary-gonadal axis is the major evolutionarily conserved positive- and negative-endocrine feedback system that regulates the production of mature gametes. […] Genetic breakthroughs in understanding additional regulators of this axis and the causes of infertility in humans have involved studies of the signaling between the peptide growth factor, kisspeptin (encoded by KISS1) and KISS1 receptor (KISS1R, also known as GPR54). […] Similar to the tissue cross talk within the hypothalamic-pituitary-gonadal axis, there are important bidirectional paracrine and juxtracrine interactions between the oocyte and the surrounding somatic cells of the ovary that begin upon entry of primordial germ cells into the genital ridge and continue through ovulation.
#79 The biology of infertility: research advances and clinical challenges
https://pmc.ncbi.nlm.nih.gov/articles/PMC3786590/
Disruption of these intimate communication pathways blocks the development of fertilizable female gametes. […] The process of spermatogenesis involves the renewal and differentiation of spermatogonial stem cells into rapidly proliferating spermatogonia, meiotic cells (spermatocytes) and haploid cells (round, elongating and elongated spermatids) before release of a spermatozoon into the tubule lumen. […] It is likely that this complexity contributes to the large number of unresolved idiopathic infertility cases in male humans. […] Infertility can be caused by defects in the development of the urogenital system and in its function, by genetic defects of the endocrine system, including the hypothalamic-pituitary-gonadal axis, and by defects in gametogenesis, erection, ejaculation, gamete function, fertilization or early embryonic development.
#80 The biology of infertility: research advances and clinical challenges
https://pmc.ncbi.nlm.nih.gov/articles/PMC3786590/
Disruption of these intimate communication pathways blocks the development of fertilizable female gametes. […] The process of spermatogenesis involves the renewal and differentiation of spermatogonial stem cells into rapidly proliferating spermatogonia, meiotic cells (spermatocytes) and haploid cells (round, elongating and elongated spermatids) before release of a spermatozoon into the tubule lumen. […] It is likely that this complexity contributes to the large number of unresolved idiopathic infertility cases in male humans. […] Infertility can be caused by defects in the development of the urogenital system and in its function, by genetic defects of the endocrine system, including the hypothalamic-pituitary-gonadal axis, and by defects in gametogenesis, erection, ejaculation, gamete function, fertilization or early embryonic development.
#81 Male Infertility: Practice Essentials, Background, Pathophysiology
https://emedicine.medscape.com/article/436829-overview
The testicle contains the Leydig cells and the Sertoli cells and is covered by the tunica albuginea, which also provides septae that divide it into approximately 200-350 pyramids. […] Sertoli cells also secrete inhibin, which provides negative feedback on the hypothalamus, and androgen-binding protein, which helps modulate androgen activity in the seminiferous tubules. […] In response to FSH stimulation at puberty, germ cells become spermatogonia and undergo an ordered maturation to become spermatozoa. […] The entire process of development from spermatogonium to spermatid takes 74 days and is described in 14 steps; as they mature, the developing spermatids progress closer to the lumen of the seminiferous tubule. […] The acrosome, a derivative of the Golgi process, surrounds the nucleus anteriorly and contains enzymes necessary to penetrate the ovum.
#82 Male Infertility: Practice Essentials, Background, Pathophysiology
https://emedicine.medscape.com/article/436829-overview
The testicle contains the Leydig cells and the Sertoli cells and is covered by the tunica albuginea, which also provides septae that divide it into approximately 200-350 pyramids. […] Sertoli cells also secrete inhibin, which provides negative feedback on the hypothalamus, and androgen-binding protein, which helps modulate androgen activity in the seminiferous tubules. […] In response to FSH stimulation at puberty, germ cells become spermatogonia and undergo an ordered maturation to become spermatozoa. […] The entire process of development from spermatogonium to spermatid takes 74 days and is described in 14 steps; as they mature, the developing spermatids progress closer to the lumen of the seminiferous tubule. […] The acrosome, a derivative of the Golgi process, surrounds the nucleus anteriorly and contains enzymes necessary to penetrate the ovum.
#83 Male Infertility: Practice Essentials, Background, Pathophysiology
https://emedicine.medscape.com/article/436829-overview
The testicle contains the Leydig cells and the Sertoli cells and is covered by the tunica albuginea, which also provides septae that divide it into approximately 200-350 pyramids. […] Sertoli cells also secrete inhibin, which provides negative feedback on the hypothalamus, and androgen-binding protein, which helps modulate androgen activity in the seminiferous tubules. […] In response to FSH stimulation at puberty, germ cells become spermatogonia and undergo an ordered maturation to become spermatozoa. […] The entire process of development from spermatogonium to spermatid takes 74 days and is described in 14 steps; as they mature, the developing spermatids progress closer to the lumen of the seminiferous tubule. […] The acrosome, a derivative of the Golgi process, surrounds the nucleus anteriorly and contains enzymes necessary to penetrate the ovum.
#84 Male Infertility: Practice Essentials, Background, Pathophysiology
https://emedicine.medscape.com/article/436829-overview
The epididymis additionally secretes substances for sperm nutrition and protection such as glycerophosphorylcholine, carnitine, and sialic acid. […] Varicoceles may lead to impaired testicular spermatogenesis and steroidogenesis, potentially due to an increased intratesticular temperature, reflux of toxic metabolites, and/or germ cell hypoxia; this appears to be progressive over time. […] Varicoceles lead to an increased incidence of sperm immaturity, apoptosis, and necrosis with severe disturbances in meiotic segregation compared with fertile men without varicoceles.
#85 The biology of infertility: research advances and clinical challenges
https://pmc.ncbi.nlm.nih.gov/articles/PMC3786590/
The initial events ultimately required for later fertility are gonadal determination and differentiation of the sexual characteristics of the developing fetus. […] The major gene implicated in human sex reversal cases is SRY, the Y chromosome male-determining gene. […] Aberrant sex determination has an important role in the etiology of intersex, beginning with the proper development of the testis or ovary from the genital ridge. […] Hormonal, gonadal and end-organ defects can be associated with absent or incomplete virilization in males and masculinization in females. […] The presence of ectopic endometriotic tissue, or endometriosis, affects 10% of women and is hypothesized to originate from retrograde sloughing of the uterine lining during menses. […] The presence of long-lived RNA in the transcriptionally inactive sperm was known, it was not until the work of Krawetz and his colleagues that the diagnostic potential of this RNA became evident. […] The future holds great promise for substantial research advances in the field of reproductive biology and medicine.
#86 Journal of Advanced Biomedical Sciences
https://journal.fums.ac.ir/browse.php?a_id=1578&sid=1&slc_lang=fa
Approximately 40-50% of infertility is due to male factor infertility that abnormal sperm chromatin structure as a major cause of infertility has been suggested. […] Several studies have shown that the protamine deficiency in sperm is associated with low sperm quality and infertility. […] Several studies have shown that there is a significant reverse relationship between protamine deficiency in sperm with fertilization and pregnancy rate following assisted reproduction techniques and central cause of protamine deficiency in sperm is due to the increase of oxidative stress which consequently causes to DNA damage. […] Treatment with antioxidants can reduce oxidative stress in infertile men, and improve sperm parameters, sperm protamine content, and DNA integrity.
#87 EAU Guidelines on Sexual and Reproductive Health – Uroweb
https://uroweb.org/guidelines/sexual-and-reproductive-health/chapter/male-infertility
Advanced paternal age (APA) has emerged as one of the additional risk factors associated with the progressive increase in the prevalence of male factor infertility. […] Oxidative stress is considered to be central in male infertility by affecting sperm quality, function, as well as the integrity of sperm. Oxidative stress may lead to sperm DNA damage and poorer DNA integrity, which are associated with poor embryo development, miscarriage and infertility. […] Sperm DNA fragmentation, or the accumulation of single- and double-strand DNA breaks occur in sperm, and an increase in the level of SDF has been shown to reduce the chances of natural conception. Although no studies have unequivocally and directly tested the impact of SDF on the clinical management of infertile couples, SDF is more common in infertile men and has been identified as a major contributor to male infertility, as well as poorer outcomes following ART, including impaired embryo development, miscarriage, recurrent pregnancy loss, and birth defects.
#88
https://link.springer.com/article/10.1007/s00203-024-04231-w
Infertility can harm a patient in physical, psychological, spiritual, and medical ways. […] Infertility is a multifactorial disease, and various etiological factors like infection are known to develop this disorder. Recently published studies reported that different bacteria, such as Chlamydia trachomatis, Mycoplasma spp, Ureaplasma urealyticum, Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa, can lead to infertility by immunopathological effects, oxidative stress, and adverse effects on sperm concentration, motility, morphology, and DNA condensation. […] Noteworthy, oxidative stress could have a role in many pathological changes in the reproductive system. Recent findings show that microorganisms can increase reactive oxygen species concentration inside the host cells, leading to oxidative stress and sperm distress and dysfunction. Therefore, this article explores the potential significance of critical bacteria linked to infertility and their pathogenic mechanisms that can affect sperm function and the female reproductive system.
#89 Infections as a Cause of Infertility | GLOWM
https://www.glowm.com/section-view/heading/Infections%20as%20a%20Cause%20of%20Infertility/item/327
The pathways of spread of genital tract infections are shown in Figure 2. In gonococcal and chlamydial salpingitis, the microorganisms ascend by surface extension from the lower genital tract through the cervical canal by way of the endometrium to the fallopian tubes. […] The sequelae of PID that are responsible for infertility include chronic interstitial salpingitis, hydrosalpinx, salpingitis isthmica nodosa, and periadnexal adhesions. […] Early recognition and proper treatment of upper genital tract infection are mandatory to prevent permanent damage to the female reproductive tract and subsequent infertility. […] The mechanisms leading to antisperm antibody formation in men after a Chlamydia trachomatis genital tract infection remains to be elucidated.
#90 Infections as a Cause of Infertility | GLOWM
https://www.glowm.com/section-view/heading/Infections%20as%20a%20Cause%20of%20Infertility/item/327
Approximately 35% of women with an infertility problem are afflicted with postinflammatory changes of the oviduct or surrounding peritoneum that interfere with tuboovarian function. Most of these alterations result from infection. […] Infection is also a major factor in male infertility, second only to oligospermia. […] The best hope for reducing the incidence of infertility related to infection lies in prevention and early detection and treatment of newly acquired asymptomatic or mildly symptomatic infections. […] Despite the current focus on sexually transmitted diseases (STDs), infertility may also follow bloodborne infections such as tuberculosis, mixed aerobic and anaerobic infections of other pelvic sites, inflammatory complications of surgical trauma, postabortal and puerperal sepsis, and appendiceal rupture.
#91 Infections as a Cause of Infertility | GLOWM
https://www.glowm.com/section-view/heading/Infections%20as%20a%20Cause%20of%20Infertility/item/327
Approximately 35% of women with an infertility problem are afflicted with postinflammatory changes of the oviduct or surrounding peritoneum that interfere with tuboovarian function. Most of these alterations result from infection. […] Infection is also a major factor in male infertility, second only to oligospermia. […] The best hope for reducing the incidence of infertility related to infection lies in prevention and early detection and treatment of newly acquired asymptomatic or mildly symptomatic infections. […] Despite the current focus on sexually transmitted diseases (STDs), infertility may also follow bloodborne infections such as tuberculosis, mixed aerobic and anaerobic infections of other pelvic sites, inflammatory complications of surgical trauma, postabortal and puerperal sepsis, and appendiceal rupture.
#92 July 8, 2016 | New Research to Uncover Infertility Mechanism | Meiji.net:Meiji University
https://english-meiji.net/articles/449/
Herpes virus is known as the cause of herpes, a disease with symptom of painful or itchy, small blisters around the lips and on the genitals. Recently, this virus has attracted attention due to on-going research to investigate if the virus also causes infertility. […] The rat experiments revealed that thymidine kinase of herpes virus origin disrupts spermiogenesis and triggers male infertility. […] When certain factors cause the herpes virus gene to be expressed in the testis, spermiogenesis becomes abnormal. […] If herpes virus infection was proved to be one etiology for male infertility, and the underlying mechanism is uncovered in the future, this research could advance into the development of diagnostic and therapeutic methods and medicines. […] Expression of thymidine kinase of herpes virus origin in round spermatid cells during spermiogenesis causes abnormality or disruption of spermiogenesis. […] Elucidation of this mechanism might also lead to development of a male contraceptive, which temporarily disturbs spermiogenesis only when administered, without permanently shutting down spermiogenesis.
#93 July 8, 2016 | New Research to Uncover Infertility Mechanism | Meiji.net:Meiji University
https://english-meiji.net/articles/449/
Herpes virus is known as the cause of herpes, a disease with symptom of painful or itchy, small blisters around the lips and on the genitals. Recently, this virus has attracted attention due to on-going research to investigate if the virus also causes infertility. […] The rat experiments revealed that thymidine kinase of herpes virus origin disrupts spermiogenesis and triggers male infertility. […] When certain factors cause the herpes virus gene to be expressed in the testis, spermiogenesis becomes abnormal. […] If herpes virus infection was proved to be one etiology for male infertility, and the underlying mechanism is uncovered in the future, this research could advance into the development of diagnostic and therapeutic methods and medicines. […] Expression of thymidine kinase of herpes virus origin in round spermatid cells during spermiogenesis causes abnormality or disruption of spermiogenesis. […] Elucidation of this mechanism might also lead to development of a male contraceptive, which temporarily disturbs spermiogenesis only when administered, without permanently shutting down spermiogenesis.
#94 Infertility: Practice Essentials, Overview, Etiology of Infertility
https://emedicine.medscape.com/article/274143-overview
Abnormalities or damage to the fallopian tube interferes with fertility and is responsible for abnormal implantation (eg, ectopic pregnancy). […] Anatomical defects or physiologic dysfunctions of the peritoneal cavity, including infection, adhesions, and adnexal masses, may cause infertility. […] Endometriosis remains an enigmatic disease that affects women during their reproductive years. […] Male factor infertility can be divided into pretesticular, testicular, and posttesticular etiologies. […] Environmental and occupational factors have been associated with an increased risk of infertility. […] Smoking has been associated with infertility in both males and females. […] Obesity may be associated with anovulation and oligomenorrhea. In men, obesity has been associated with decreased sperm quality. […] The American Society of Reproductive Medicine (ASRM) has several patient education guides and physician practice guidelines regarding infertility.
#95 Infertility: Practice Essentials, Overview, Etiology of Infertility
https://emedicine.medscape.com/article/274143-overview
Abnormalities or damage to the fallopian tube interferes with fertility and is responsible for abnormal implantation (eg, ectopic pregnancy). […] Anatomical defects or physiologic dysfunctions of the peritoneal cavity, including infection, adhesions, and adnexal masses, may cause infertility. […] Endometriosis remains an enigmatic disease that affects women during their reproductive years. […] Male factor infertility can be divided into pretesticular, testicular, and posttesticular etiologies. […] Environmental and occupational factors have been associated with an increased risk of infertility. […] Smoking has been associated with infertility in both males and females. […] Obesity may be associated with anovulation and oligomenorrhea. In men, obesity has been associated with decreased sperm quality. […] The American Society of Reproductive Medicine (ASRM) has several patient education guides and physician practice guidelines regarding infertility.
#96 EAU Guidelines on Sexual and Reproductive Health – Uroweb
https://uroweb.org/guidelines/sexual-and-reproductive-health/chapter/male-infertility
Advanced paternal age (APA) has emerged as one of the additional risk factors associated with the progressive increase in the prevalence of male factor infertility. […] Oxidative stress is considered to be central in male infertility by affecting sperm quality, function, as well as the integrity of sperm. Oxidative stress may lead to sperm DNA damage and poorer DNA integrity, which are associated with poor embryo development, miscarriage and infertility. […] Sperm DNA fragmentation, or the accumulation of single- and double-strand DNA breaks occur in sperm, and an increase in the level of SDF has been shown to reduce the chances of natural conception. Although no studies have unequivocally and directly tested the impact of SDF on the clinical management of infertile couples, SDF is more common in infertile men and has been identified as a major contributor to male infertility, as well as poorer outcomes following ART, including impaired embryo development, miscarriage, recurrent pregnancy loss, and birth defects.
#97
https://www.who.int/news-room/fact-sheets/detail/infertility
In the male reproductive system, infertility may be caused by obstruction of the reproductive tract causing dysfunctionalities in the ejection of semen. This blockage can occur in the tubes that carry semen (such as ejaculatory ducts and seminal vesicles). Blockages are commonly due to injuries or infections of the genital tract; hormonal disorders leading to abnormalities in hormones produced by the pituitary gland, hypothalamus and testicles hormones such as testosterone regulate sperm production. Example of disorders that result in hormonal imbalance include pituitary or testicular cancers; testicular failure to produce sperm, for example due to varicoceles or medical treatments that impair sperm-producing cells (such as chemotherapy); and abnormal sperm function and quality. Conditions or situations that cause abnormal shape (morphology) and movement (motility) of the sperm negatively affect fertility. […] Lifestyle factors such as smoking, excessive alcohol intake and obesity can affect fertility. In addition, exposure to environmental pollutants and toxins can be directly toxic to gametes (eggs and sperm), resulting in their decreased numbers and poor quality.
#98 Importance of Oxidative Stress Mechanism in Reproductive Functions and Infertility | IntechOpen
https://www.intechopen.com/chapters/83976
Oxidative stress (OS) is a term used to describe the homeostatic oxidation-favoring imbalance between the formation of reactive oxygen species (ROS) or other compounds causing oxidative stress and the countering activities/levels of enzymatic or non-enzymatic antioxidants. […] Through available evidence, it appears that oxidative state impairs reproductive processes and causes general disruptions through inflammation, DNA damage, lipid peroxidation, protein alterations and mitochondrial dysfunction. […] Previous investigations have implicated OS and its mechanisms in a number of diseases, including infertility. […] In men, free radical elevation in the ejaculate is mainly sponsored by high leukocyte counts as well as immature spermatozoa, which cause low fertility owing to lipid peroxidation, apoptosis and damage to the DNA of sperm cells.
#99 EAU Guidelines on Sexual and Reproductive Health – Uroweb
https://uroweb.org/guidelines/sexual-and-reproductive-health/chapter/male-infertility
Advanced paternal age (APA) has emerged as one of the additional risk factors associated with the progressive increase in the prevalence of male factor infertility. […] Oxidative stress is considered to be central in male infertility by affecting sperm quality, function, as well as the integrity of sperm. Oxidative stress may lead to sperm DNA damage and poorer DNA integrity, which are associated with poor embryo development, miscarriage and infertility. […] Sperm DNA fragmentation, or the accumulation of single- and double-strand DNA breaks occur in sperm, and an increase in the level of SDF has been shown to reduce the chances of natural conception. Although no studies have unequivocally and directly tested the impact of SDF on the clinical management of infertile couples, SDF is more common in infertile men and has been identified as a major contributor to male infertility, as well as poorer outcomes following ART, including impaired embryo development, miscarriage, recurrent pregnancy loss, and birth defects.
#100 Importance of Oxidative Stress Mechanism in Reproductive Functions and Infertility | IntechOpen
https://www.intechopen.com/chapters/83976
Furthermore, conditions like varicocele, testicular cancer, idiopathic male infertility and erectile dysfunction have been strongly associated with oxidative stress. […] In females, disproportionate levels of anti- and pro-oxidants have been associated with conditions like polycystic ovary syndrome (PCOS), endometriosis and unexplained infertility. […] One of the major ways in which oxidative stress impairs female fertility is its harmful effects on proteins and nucleic acids. […] Reports have shown OS to be a common denominator in the majority of infertility states in males and females. […] Approximately, ROS contributes to about 30-80 percent of male infertility and male gametes activities are altered by oxidative stress. […] The oxidative stress caused as a result of free radicals have a significant impact in the production as well as increasing abnormal spermatozoa, decreasing spermatozoa count and promoting sperm DNA transformation and fragmentation.
#101 Importance of Oxidative Stress Mechanism in Reproductive Functions and Infertility | IntechOpen
https://www.intechopen.com/chapters/83976
Oxidative stress can also result in arterial occlusion then severe damage to the cell of the reproductive system and as a result defects in spermatogenesis occurs. […] So as to elucidate the role of oxidative stress in steroidogenesis, a number of studies have been done on animal models through introduction of exogenous sources of oxidants. […] In another animal study, steroidogenesis, as implied by the level of FSH, LH and testosterone was seen to be reduced in animals fed with selenium-deficient diet when compared with selenium-fed animals. […] It has been reported that increase in the levels ROS is related with reduction in the reproductive capability in females and infertility. […] The ROS produced in granulosa cells may have a negative impact on oocyte fertilization as well as the rate and quality of implantation of the embryo.
#102 Importance of Oxidative Stress Mechanism in Reproductive Functions and Infertility | IntechOpen
https://www.intechopen.com/chapters/83976
Oxidative stress can also result in arterial occlusion then severe damage to the cell of the reproductive system and as a result defects in spermatogenesis occurs. […] So as to elucidate the role of oxidative stress in steroidogenesis, a number of studies have been done on animal models through introduction of exogenous sources of oxidants. […] In another animal study, steroidogenesis, as implied by the level of FSH, LH and testosterone was seen to be reduced in animals fed with selenium-deficient diet when compared with selenium-fed animals. […] It has been reported that increase in the levels ROS is related with reduction in the reproductive capability in females and infertility. […] The ROS produced in granulosa cells may have a negative impact on oocyte fertilization as well as the rate and quality of implantation of the embryo.
#103 Importance of Oxidative Stress Mechanism in Reproductive Functions and Infertility | IntechOpen
https://www.intechopen.com/chapters/83976
Oxidative stress can also result in arterial occlusion then severe damage to the cell of the reproductive system and as a result defects in spermatogenesis occurs. […] So as to elucidate the role of oxidative stress in steroidogenesis, a number of studies have been done on animal models through introduction of exogenous sources of oxidants. […] In another animal study, steroidogenesis, as implied by the level of FSH, LH and testosterone was seen to be reduced in animals fed with selenium-deficient diet when compared with selenium-fed animals. […] It has been reported that increase in the levels ROS is related with reduction in the reproductive capability in females and infertility. […] The ROS produced in granulosa cells may have a negative impact on oocyte fertilization as well as the rate and quality of implantation of the embryo.
#104 MicroRNAs in the pathogenesis of endometriosis and infertility | EndoNews
https://www.endonews.com/micrornas-in-the-pathogenesis-of-endometriosis-and-infertility
Several MicroRNAs are responsible for the pathogenesis in endometriosis and infertility study discusses […] MicroRNAs play a role in the pathogenesis of endometriosis through different pathways such as promoting inflammation, cell proliferation, angiogenesis, and tissue remodeling. […] MiRNAs are known to cause infertility by hormonal disturbance. […] Oxidative stress caused by the inflammatory state of endometriosis also causes infertility by damaging DNA. […] By causing hormonal imbalances miRNAs are also found to be involved in infertility pathogenesis in endometriotic patients. […] The role of oxidative stress in infertility in endometriosis patients is also discussed thoroughly. The inflammatory state causes the Reactive Oxygen Species (ROS) production which then accumulates in the peritoneal fluid and fallopian tubes. This collection damages the DNA of oocytes, sperm, and embryos which presents as infertility in affected individuals. […] The hormonal imbalance, particularly dysregulation of progesterone levels, caused by miRNAs in endometriotic patients was also found to be associated with infertility.
#105 Infertility: Types, Causes, Symptoms, Diagnosis & Treatment
https://my.clevelandclinic.org/health/diseases/16083-infertility
There are many causes of infertility, and sometimes, there isnt a simple answer as to why youre not getting pregnant. […] While causes of infertility vary, studies show that: 33% of infertility involves women. 33% of infertility involves men. 33% of infertility involves both partners or is unexplained. […] Some causes of infertility affect just one partner, while others affect both partners. Risk factors for infertility include: Age, particularly being in your late 30s or 40s. For men, age begins affecting fertility closer to 50. […] Ovulation disorders are the most common cause of infertility in women. Ovulation is the process in which your ovary releases an egg to meet sperm for fertilization. […] The most common cause of male infertility involves problems with the shape, movement (motility) or amount (low sperm count) of sperm. […] Treatment for infertility depends mostly on the cause and your goals. […] In 85% to 90% of cases, lifestyle modification, medication, ART or surgery can treat infertility and allow a woman to conceive.
#106 Infertility: Practice Essentials, Overview, Etiology of Infertility
https://emedicine.medscape.com/article/274143-overview
Significant improvements in fertility treatment have made it possible for many patients to conceive with medical assistance. Women with fallopian tube pathology or who have had a prior tubal ligation can conceive with in vitro fertilization (IVF). […] The ovulatory process is initiated once the hypothalamus-pituitary-ovarian axis matures and follicle-stimulating hormone (FSH) and luteinizing hormone (LH), under the regulation of gonadotropin-releasing hormone (GnRH), acquire their normal secretory patterns. […] Ovulatory dysfunction is defined as an alteration in the frequency and duration of the menstrual cycle. A normal menstrual cycle lasts 25-35 days, with an average of 28 days. Failure to ovulate is the most common infertility problem. […] The prevalence of infertility rises dramatically as age increases.
#107 Infertility – Knowledge @ AMBOSS
https://www.amboss.com/us/knowledge/infertility/
Although ovarian reserve testing can predict responsiveness to ovarian stimulation, it does not predict reproductive potential better than the patient’s age and should not be performed to evaluate reproductive potential in female individuals without infertility. […] The goal of ovulation induction is to stimulate development of a single dominant follicle in patients with anovulation. […] Ovulation induction increases the risk of multiple pregnancy, and ovulation induction with exogenous gonadotropins increases the risk of ovarian hyperstimulation syndrome. […] Ovarian hyperstimulation syndrome (OHSS) is a potentially life-threatening complication of ovulation induction or ovarian stimulation with exogenous human chorionic gonadotropin (hCG). […] Exogenous hCG is thought to be responsible for the massive luteinization of the ovarian granulosa cells.
#108 Infertility – Knowledge @ AMBOSS
https://www.amboss.com/us/knowledge/infertility/
Although ovarian reserve testing can predict responsiveness to ovarian stimulation, it does not predict reproductive potential better than the patient’s age and should not be performed to evaluate reproductive potential in female individuals without infertility. […] The goal of ovulation induction is to stimulate development of a single dominant follicle in patients with anovulation. […] Ovulation induction increases the risk of multiple pregnancy, and ovulation induction with exogenous gonadotropins increases the risk of ovarian hyperstimulation syndrome. […] Ovarian hyperstimulation syndrome (OHSS) is a potentially life-threatening complication of ovulation induction or ovarian stimulation with exogenous human chorionic gonadotropin (hCG). […] Exogenous hCG is thought to be responsible for the massive luteinization of the ovarian granulosa cells.
#109 Female Infertility – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK556033/
The gold standard for assessing the uterine cavity is hysteroscopy, which allows direct visualization of the intrauterine pathology and provides an opportunity for immediate surgical correction. […] Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic complication of controlled ovarian hyperstimulation that results in a broad range of signs and symptoms, ranging from abdominal distention, nausea, vomiting, enlarged ovaries, third-spacing of fluids, renal failure, and venous thrombosis, acute respiratory distress syndrome, electrolyte derangements, cardiac arrhythmias, and sepsis.
#110 Molecular Mechanism of Resveratrol and Its Therapeutic Potential on Female Infertility
https://www.mdpi.com/1422-0067/25/7/3613
Another molecule whose effect is mediated by resveratrol is aromatase. Aromatase is an enzyme that is involved with converting androgen to estrogens. In infertility management, aromatase inhibition has been observed to be effective for the induction of ovulation in PCOS women with ovulatory problems. Aromatase inhibitors, together with a gonadotropin suppressor, also showed potential by decreasing endometriosis-related chronic pelvic pain. Besides infertility-related conditions, aromatase is also involved in carcinogenesis as it favors breast cancer proliferation, therefore presenting as an interesting molecular target for endocrine-responsive breast cancer. Regarding resveratrol, studies observed that its administration was able to inhibit aromatase in breast cancer cells. […] As reported, resveratrol targets many different molecular factors. Due to its numerous beneficial effects on non-reproductive cells, supplementation of resveratrol has been studied in various other diseases, including reproductive-related disorders and infertility.
#111 Azthena logo with the word Azthena
https://www.news-medical.net/news/20240918/Newly-discovered-mechanism-could-revolutionize-infertility-care-by-promoting-embryo-implantation.aspx
A team from Kumamoto University has uncovered a new mechanism that could revolutionize infertility care by promoting embryo implantation. The discovery focuses on prostaglandin (PG) receptors in the uterus that enhance the critical process of decidualization, which is necessary for a successful pregnancy. […] A research team led by Professor Yukihiko Sugimoto and Assistant Professor Tomoaki Inazumi found that two types of prostaglandins – PGD2 and PGE2 – produced in the uterus during the early stages of pregnancy, activate specific receptors, DP and EP4, to promote the formation of the decidual tissue that supports embryo implantation. […] The team discovered that when either the DP or EP4 receptor is stimulated, decidualization is enhanced, allowing the embryo to implant more effectively, further implying that both PGD2-DP and PGE2-EP4 receptor pathways compensate for each other’s function. This groundbreaking discovery suggests that boosting these pathways with specialized drugs, called DP/EP4 agonists, could help women struggling with infertility due to implantation issues. […] This novel understanding of how prostaglandin receptors aid in implantation paves the way for innovative infertility therapies, potentially transforming reproductive medicine by improving the chances of pregnancy for many individuals.
#112 Azthena logo with the word Azthena
https://www.news-medical.net/news/20240918/Newly-discovered-mechanism-could-revolutionize-infertility-care-by-promoting-embryo-implantation.aspx
A team from Kumamoto University has uncovered a new mechanism that could revolutionize infertility care by promoting embryo implantation. The discovery focuses on prostaglandin (PG) receptors in the uterus that enhance the critical process of decidualization, which is necessary for a successful pregnancy. […] A research team led by Professor Yukihiko Sugimoto and Assistant Professor Tomoaki Inazumi found that two types of prostaglandins – PGD2 and PGE2 – produced in the uterus during the early stages of pregnancy, activate specific receptors, DP and EP4, to promote the formation of the decidual tissue that supports embryo implantation. […] The team discovered that when either the DP or EP4 receptor is stimulated, decidualization is enhanced, allowing the embryo to implant more effectively, further implying that both PGD2-DP and PGE2-EP4 receptor pathways compensate for each other’s function. This groundbreaking discovery suggests that boosting these pathways with specialized drugs, called DP/EP4 agonists, could help women struggling with infertility due to implantation issues. […] This novel understanding of how prostaglandin receptors aid in implantation paves the way for innovative infertility therapies, potentially transforming reproductive medicine by improving the chances of pregnancy for many individuals.
#113 Azthena logo with the word Azthena
https://www.news-medical.net/news/20240918/Newly-discovered-mechanism-could-revolutionize-infertility-care-by-promoting-embryo-implantation.aspx
A team from Kumamoto University has uncovered a new mechanism that could revolutionize infertility care by promoting embryo implantation. The discovery focuses on prostaglandin (PG) receptors in the uterus that enhance the critical process of decidualization, which is necessary for a successful pregnancy. […] A research team led by Professor Yukihiko Sugimoto and Assistant Professor Tomoaki Inazumi found that two types of prostaglandins – PGD2 and PGE2 – produced in the uterus during the early stages of pregnancy, activate specific receptors, DP and EP4, to promote the formation of the decidual tissue that supports embryo implantation. […] The team discovered that when either the DP or EP4 receptor is stimulated, decidualization is enhanced, allowing the embryo to implant more effectively, further implying that both PGD2-DP and PGE2-EP4 receptor pathways compensate for each other’s function. This groundbreaking discovery suggests that boosting these pathways with specialized drugs, called DP/EP4 agonists, could help women struggling with infertility due to implantation issues. […] This novel understanding of how prostaglandin receptors aid in implantation paves the way for innovative infertility therapies, potentially transforming reproductive medicine by improving the chances of pregnancy for many individuals.
#114 Male infertility â The other side of the equation
https://www.racgp.org.au/afp/2017/september/male-infertility
Correction of varicocele is indicated in patients with a clinically detectable varicocele and abnormal semen analysis as it improves pregnancy rates. […] Many patients with obstructive azoospermia can undergo reconstructive surgery to restore sperm transport continuity. […] Microsurgical testicular sperm extraction (microTESE) allows for identification and selective excision of larger seminiferous tubules, which are more likely to yield sperm.
#115 Male infertility â The other side of the equation
https://www.racgp.org.au/afp/2017/september/male-infertility
Correction of varicocele is indicated in patients with a clinically detectable varicocele and abnormal semen analysis as it improves pregnancy rates. […] Many patients with obstructive azoospermia can undergo reconstructive surgery to restore sperm transport continuity. […] Microsurgical testicular sperm extraction (microTESE) allows for identification and selective excision of larger seminiferous tubules, which are more likely to yield sperm.
#116 Male infertility â The other side of the equation
https://www.racgp.org.au/afp/2017/september/male-infertility
Correction of varicocele is indicated in patients with a clinically detectable varicocele and abnormal semen analysis as it improves pregnancy rates. […] Many patients with obstructive azoospermia can undergo reconstructive surgery to restore sperm transport continuity. […] Microsurgical testicular sperm extraction (microTESE) allows for identification and selective excision of larger seminiferous tubules, which are more likely to yield sperm.
#117 Ejaculatory physiology and pathophysiology: assessment and treatment in male infertility – Revenig – Translational Andrology and Urology
https://tau.amegroups.org/article/view/3515/html
Assisted ejaculation procedures are used to harvest sperm for assisted reproduction in anorgasmic and anejaculatory men. […] The two most commonly used techniques are penile vibratory stimulation (PVS) and electroejaculation (EEJ). […] Overall, studies show that sperm can be retrieved by PVS or EEJ in 97% of SCI men. […] If efforts to restore antegrade flow or PVS fail, then rectal probe electrostimulation or EEJ can be used. […] Ejaculatory dysfunction resulting in azoospermia can be due to retrograde ejaculation or failure of emission.
#118 Ejaculatory physiology and pathophysiology: assessment and treatment in male infertility – Revenig – Translational Andrology and Urology
https://tau.amegroups.org/article/view/3515/html
Assisted ejaculation procedures are used to harvest sperm for assisted reproduction in anorgasmic and anejaculatory men. […] The two most commonly used techniques are penile vibratory stimulation (PVS) and electroejaculation (EEJ). […] Overall, studies show that sperm can be retrieved by PVS or EEJ in 97% of SCI men. […] If efforts to restore antegrade flow or PVS fail, then rectal probe electrostimulation or EEJ can be used. […] Ejaculatory dysfunction resulting in azoospermia can be due to retrograde ejaculation or failure of emission.
#119 In vitro fertilization (IVF) – Mayo Clinic
https://www.mayoclinic.org/tests-procedures/in-vitro-fertilization/about/pac-20384716
During in vitro fertilization, eggs are removed from sacs called follicles within an ovary. An egg is fertilized by injecting a single sperm into the egg or mixing the egg with sperm in a petri dish. The fertilized egg, called an embryo, is transferred into the uterus. […] In vitro fertilization, also called IVF, is a complex series of procedures that can lead to a pregnancy. It’s a treatment for infertility, a condition in which you can’t get pregnant after at least a year of trying for most couples. IVF also can be used to prevent passing on genetic problems to a child. […] In vitro fertilization is the most effective type of fertility treatment that involves the handling of eggs or embryos and sperm. Together, this group of treatments is called assisted reproductive technology. […] In vitro fertilization is a treatment for infertility or genetic problems.
#120 In vitro fertilization (IVF) – Mayo Clinic
https://www.mayoclinic.org/tests-procedures/in-vitro-fertilization/about/pac-20384716
During in vitro fertilization, eggs are removed from sacs called follicles within an ovary. An egg is fertilized by injecting a single sperm into the egg or mixing the egg with sperm in a petri dish. The fertilized egg, called an embryo, is transferred into the uterus. […] In vitro fertilization, also called IVF, is a complex series of procedures that can lead to a pregnancy. It’s a treatment for infertility, a condition in which you can’t get pregnant after at least a year of trying for most couples. IVF also can be used to prevent passing on genetic problems to a child. […] In vitro fertilization is the most effective type of fertility treatment that involves the handling of eggs or embryos and sperm. Together, this group of treatments is called assisted reproductive technology. […] In vitro fertilization is a treatment for infertility or genetic problems.
#121 In vitro fertilization (IVF) – Mayo Clinic
https://www.mayoclinic.org/tests-procedures/in-vitro-fertilization/about/pac-20384716
During in vitro fertilization, eggs are removed from sacs called follicles within an ovary. An egg is fertilized by injecting a single sperm into the egg or mixing the egg with sperm in a petri dish. The fertilized egg, called an embryo, is transferred into the uterus. […] In vitro fertilization, also called IVF, is a complex series of procedures that can lead to a pregnancy. It’s a treatment for infertility, a condition in which you can’t get pregnant after at least a year of trying for most couples. IVF also can be used to prevent passing on genetic problems to a child. […] In vitro fertilization is the most effective type of fertility treatment that involves the handling of eggs or embryos and sperm. Together, this group of treatments is called assisted reproductive technology. […] In vitro fertilization is a treatment for infertility or genetic problems.
#122 In vitro fertilization (IVF) – Mayo Clinic
https://www.mayoclinic.org/tests-procedures/in-vitro-fertilization/about/pac-20384716
IVF may be an option if you or your partner has fallopian tube damage or blockage. Eggs move from the ovaries to the uterus through the fallopian tubes. If both tubes get damaged or blocked, that makes it hard for an egg to be fertilized or for an embryo to travel to the uterus. […] IVF may be an option if you or your partner has ovulation disorders. If ovulation doesn’t happen or doesn’t occur often, fewer eggs are available to be fertilized by sperm. […] IVF may be an option if you or your partner has endometriosis. This condition happens when tissue that’s like the lining of the uterus grows outside of the uterus. Endometriosis often affects the ovaries, uterus and fallopian tubes. […] IVF may be an option if you or your partner has uterine fibroids. Fibroids are tumors in the uterus. Most often, they’re not cancer. They’re common in people in their 30s and 40s. Fibroids can cause a fertilized egg to have trouble attaching to the lining of the uterus.
#123 In vitro fertilization (IVF) – Mayo Clinic
https://www.mayoclinic.org/tests-procedures/in-vitro-fertilization/about/pac-20384716
IVF may be an option if you or your partner has fallopian tube damage or blockage. Eggs move from the ovaries to the uterus through the fallopian tubes. If both tubes get damaged or blocked, that makes it hard for an egg to be fertilized or for an embryo to travel to the uterus. […] IVF may be an option if you or your partner has ovulation disorders. If ovulation doesn’t happen or doesn’t occur often, fewer eggs are available to be fertilized by sperm. […] IVF may be an option if you or your partner has endometriosis. This condition happens when tissue that’s like the lining of the uterus grows outside of the uterus. Endometriosis often affects the ovaries, uterus and fallopian tubes. […] IVF may be an option if you or your partner has uterine fibroids. Fibroids are tumors in the uterus. Most often, they’re not cancer. They’re common in people in their 30s and 40s. Fibroids can cause a fertilized egg to have trouble attaching to the lining of the uterus.
#124 In vitro fertilization (IVF) – Mayo Clinic
https://www.mayoclinic.org/tests-procedures/in-vitro-fertilization/about/pac-20384716
IVF may be an option if you or your partner has fallopian tube damage or blockage. Eggs move from the ovaries to the uterus through the fallopian tubes. If both tubes get damaged or blocked, that makes it hard for an egg to be fertilized or for an embryo to travel to the uterus. […] IVF may be an option if you or your partner has ovulation disorders. If ovulation doesn’t happen or doesn’t occur often, fewer eggs are available to be fertilized by sperm. […] IVF may be an option if you or your partner has endometriosis. This condition happens when tissue that’s like the lining of the uterus grows outside of the uterus. Endometriosis often affects the ovaries, uterus and fallopian tubes. […] IVF may be an option if you or your partner has uterine fibroids. Fibroids are tumors in the uterus. Most often, they’re not cancer. They’re common in people in their 30s and 40s. Fibroids can cause a fertilized egg to have trouble attaching to the lining of the uterus.
#125 In vitro fertilization (IVF) – Mayo Clinic
https://www.mayoclinic.org/tests-procedures/in-vitro-fertilization/about/pac-20384716
IVF may be an option if you or your partner has fallopian tube damage or blockage. Eggs move from the ovaries to the uterus through the fallopian tubes. If both tubes get damaged or blocked, that makes it hard for an egg to be fertilized or for an embryo to travel to the uterus. […] IVF may be an option if you or your partner has ovulation disorders. If ovulation doesn’t happen or doesn’t occur often, fewer eggs are available to be fertilized by sperm. […] IVF may be an option if you or your partner has endometriosis. This condition happens when tissue that’s like the lining of the uterus grows outside of the uterus. Endometriosis often affects the ovaries, uterus and fallopian tubes. […] IVF may be an option if you or your partner has uterine fibroids. Fibroids are tumors in the uterus. Most often, they’re not cancer. They’re common in people in their 30s and 40s. Fibroids can cause a fertilized egg to have trouble attaching to the lining of the uterus.
#126 In vitro fertilization (IVF) – Mayo Clinic
https://www.mayoclinic.org/tests-procedures/in-vitro-fertilization/about/pac-20384716
IVF may be an option if you or your partner has issues with sperm. A low number of sperm or unusual changes in their movement, size or shape can make it hard for sperm to fertilize an egg. […] IVF may be an option if you or your partner has unexplained infertility. This is when tests can’t find the reason for someone’s infertility. […] IVF may be an option if you or your partner has a genetic disorder. If you or your partner is at risk of passing on a genetic disorder to your child, your health care team might recommend getting a procedure that involves IVF. […] IVF raises the chances of certain health problems. […] Ovarian hyperstimulation syndrome is a condition in which the ovaries become swollen and painful. It can be caused by receiving shots of fertility medicines, such as human chorionic gonadotropin (HCG), to trigger ovulation.
#127 In vitro fertilization (IVF) – Mayo Clinic
https://www.mayoclinic.org/tests-procedures/in-vitro-fertilization/about/pac-20384716
IVF may be an option if you or your partner has issues with sperm. A low number of sperm or unusual changes in their movement, size or shape can make it hard for sperm to fertilize an egg. […] IVF may be an option if you or your partner has unexplained infertility. This is when tests can’t find the reason for someone’s infertility. […] IVF may be an option if you or your partner has a genetic disorder. If you or your partner is at risk of passing on a genetic disorder to your child, your health care team might recommend getting a procedure that involves IVF. […] IVF raises the chances of certain health problems. […] Ovarian hyperstimulation syndrome is a condition in which the ovaries become swollen and painful. It can be caused by receiving shots of fertility medicines, such as human chorionic gonadotropin (HCG), to trigger ovulation.
#128 The biology of infertility: research advances and clinical challenges
https://pmc.ncbi.nlm.nih.gov/articles/PMC3786590/
The initial events ultimately required for later fertility are gonadal determination and differentiation of the sexual characteristics of the developing fetus. […] The major gene implicated in human sex reversal cases is SRY, the Y chromosome male-determining gene. […] Aberrant sex determination has an important role in the etiology of intersex, beginning with the proper development of the testis or ovary from the genital ridge. […] Hormonal, gonadal and end-organ defects can be associated with absent or incomplete virilization in males and masculinization in females. […] The presence of ectopic endometriotic tissue, or endometriosis, affects 10% of women and is hypothesized to originate from retrograde sloughing of the uterine lining during menses. […] The presence of long-lived RNA in the transcriptionally inactive sperm was known, it was not until the work of Krawetz and his colleagues that the diagnostic potential of this RNA became evident. […] The future holds great promise for substantial research advances in the field of reproductive biology and medicine.
#129 New Genetic Mechanism Can Cause Severe Forms of Male Infertility | Technology Networks
https://www.technologynetworks.com/genomics/news/new-genetic-mechanism-can-cause-severe-forms-of-male-infertility-357377
As many as 29 of the mutations affect genes directly involved in processes related to spermatogenesis the process of sperm cell development – or other cellular processes related to reproduction. […] Experts identified mutations in the gene RBM5 in multiple infertile men. […] Importantly, these mutations mostly cause a dominant form of infertility, where only one mutated gene is required. […] This research indicates a significant proportion of these children may inherit infertility from their father. […] Professor Veltman said: If we are able to obtain a genetic diagnosis, then we can start understanding better male infertility problems and why some infertile men still produce sperm that can be used successfully for assisted reproduction. […] They will follow-up their research by conducting further studies into the role these newly identified mutated genes have on the impact of spermatogenesis and on the overall fertility in humans.
#130 July 8, 2016 | New Research to Uncover Infertility Mechanism | Meiji.net:Meiji University
https://english-meiji.net/articles/449/
Herpes virus is known as the cause of herpes, a disease with symptom of painful or itchy, small blisters around the lips and on the genitals. Recently, this virus has attracted attention due to on-going research to investigate if the virus also causes infertility. […] The rat experiments revealed that thymidine kinase of herpes virus origin disrupts spermiogenesis and triggers male infertility. […] When certain factors cause the herpes virus gene to be expressed in the testis, spermiogenesis becomes abnormal. […] If herpes virus infection was proved to be one etiology for male infertility, and the underlying mechanism is uncovered in the future, this research could advance into the development of diagnostic and therapeutic methods and medicines. […] Expression of thymidine kinase of herpes virus origin in round spermatid cells during spermiogenesis causes abnormality or disruption of spermiogenesis. […] Elucidation of this mechanism might also lead to development of a male contraceptive, which temporarily disturbs spermiogenesis only when administered, without permanently shutting down spermiogenesis.
#131 Azabu University discovers that zinc deficiency causes infertility | News | Science Japan
https://sj.jst.go.jp/news/202505/n0508-02p.html
A research group from Azabu University has revealed through studies with mice that zinc deficiency can lead to infertility by preventing fertilized eggs from implanting in the uterus. […] The results showed that in the group where ZIP10 functioned normally, part of the epithelium of the uterine lining broke down, allowing the fertilized egg to embed itself over time, with fetuses visible in the uterus by day 10 of pregnancy. However, in the group where ZIP10 did not function, the epithelium did not break down, preventing the fertilized egg from properly embedding in the endometrium, leading to implantation failure. This means that pregnancy cannot be established even when transferring high-quality fertilized eggs through in vitro fertilization. […] Additionally, the study revealed that in the group where ZIP10 did not function, the effect of progesteroneâa female hormone essential for establishing and maintaining pregnancyâwas weakened, explaining the failure to implant. Furthermore, the same results were obtained using cultured cells derived from human uterine lining, suggesting that similar situations occur in human infertility cases.
#132 Azabu University discovers that zinc deficiency causes infertility | News | Science Japan
https://sj.jst.go.jp/news/202505/n0508-02p.html
A research group from Azabu University has revealed through studies with mice that zinc deficiency can lead to infertility by preventing fertilized eggs from implanting in the uterus. […] The results showed that in the group where ZIP10 functioned normally, part of the epithelium of the uterine lining broke down, allowing the fertilized egg to embed itself over time, with fetuses visible in the uterus by day 10 of pregnancy. However, in the group where ZIP10 did not function, the epithelium did not break down, preventing the fertilized egg from properly embedding in the endometrium, leading to implantation failure. This means that pregnancy cannot be established even when transferring high-quality fertilized eggs through in vitro fertilization. […] Additionally, the study revealed that in the group where ZIP10 did not function, the effect of progesteroneâa female hormone essential for establishing and maintaining pregnancyâwas weakened, explaining the failure to implant. Furthermore, the same results were obtained using cultured cells derived from human uterine lining, suggesting that similar situations occur in human infertility cases.
#133 Journal of Advanced Biomedical Sciences
https://journal.fums.ac.ir/browse.php?a_id=1578&sid=1&slc_lang=fa
Approximately 40-50% of infertility is due to male factor infertility that abnormal sperm chromatin structure as a major cause of infertility has been suggested. […] Several studies have shown that the protamine deficiency in sperm is associated with low sperm quality and infertility. […] Several studies have shown that there is a significant reverse relationship between protamine deficiency in sperm with fertilization and pregnancy rate following assisted reproduction techniques and central cause of protamine deficiency in sperm is due to the increase of oxidative stress which consequently causes to DNA damage. […] Treatment with antioxidants can reduce oxidative stress in infertile men, and improve sperm parameters, sperm protamine content, and DNA integrity.
#134 New mechanism underlying male infertility | ScienceDaily
https://www.sciencedaily.com/releases/2021/01/210107164756.htm
In the absence of glycylation, they became uncoordinated, and as a result, we suddenly saw sperm swimming in circles. […] „We observed functional defects on sperm from mice lacking glycylation, which resulted in a reduction of fertility. Since mice as a model system are known to have robust fertility, a similar defect in humans, could lead to male sterility” says Carsten Janke. […] This study, which shows how important glycylation is for the control of the dynein motors of the flagellum, is a prime example of how microtubule modifications directly affects the function of other proteins in cells. Our findings provide direct evidence that microtubules have an active role in regulating fundamental biological processes via a code of tubulin modifications. Further, this study points to a new mechanism underlying male infertility.
#135 Deciphering pathogenesis of endometriosis and concomitant infertility using cutting-edge endometrium and implantation models
https://research.kuleuven.be/portal/en/project/3M220600
Endometriosis is a widespread and burdening gynecological disorder. To date, little is known on its pathogenesis, neither on the mechanisms behind its prominently associated infertility. […] These organoid models now allow to profoundly search for mechanisms underlying endometriosis pathogenesis and associated infertility. Here, we will focus on the HGF-PI3K/AKT and epithelial-mesenchymal transition pathways, both linked to the central inflammatory component of the disease, all together found upregulated in patients primary lesions and derived organoids. The same pathways will also be queried for involvement in deficient endometrial functioning in endometriosis, particularly regarding receptivity for, and interaction with, the embryo. […] Together, our project will provide deep insight into what goes awry in endometriosis and its infertility, with perspectives to discovering novel therapeutic targets.