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Title:Povezava genov odgovornih za delovanje hormonov in hormonskih receptorjev, z odzivom na hormonsko uravnavanje folikulogeneze
Authors:ID Čuš, Maruška (Author)
ID Potočnik, Uroš (Comentor)
ID Kovačič, Borut (Mentor) More about this mentor... New window
Files:.pdf DR_Cus_Maruska_2019.pdf (1,61 MB)
MD5: B5B4A0279B38B127F53FC1A81BF9B087
PID: 20.500.12556/dkum/849347a5-d470-4fee-9ea1-e681afd64b75
 
Language:Slovenian
Work type:Doctoral dissertation
Typology:2.08 - Doctoral Dissertation
Organization:MF - Faculty of Medicine
Abstract:Cilj študije je bil raziskati, ali so posamezni polimorfizmi (SNP) v izbranih genih, ki so odgovorni za hormonsko uravnavanje folikulogeneze, povezani z odzivom na nadzorovano prekomerno spodbujanje ovulacije in kliničnimi značilnostmi žensk, vključenih v postopek oploditve z biomedicinsko pomočjo (OBMP). V raziskavo smo vključili šestdeset preiskovank, ki so bile vključene v postopek zdravljenja neplodnosti s postopkoma IVF (zunajtelesna oploditev) ter ICSI (neposredni vnos semenčice v citoplazmo jajčne celice). Pred postopkom OBMP smo preiskovankam določili serumske vrednosti hormonov FSH, LH in AMH. Kri za določitev vrednosti serumskega LH in FSH je bila odvzeta drugi oziroma tretji dan menstruacijskega ciklusa. Vrednosti E2 smo določali na dan aplikacije hCG. Preiskovanke smo razvrstili v tri skupine glede na odziv hormonskega spodbujanja ovulacije; slabo odzivne (glede na bolonjska merila), normalno odzivne (≤ 15 jajčnih celic) in prekomerno odzivne preiskovanke (> 15 jajčnih celic). Gensko izražanje smo izmerili genom FSHR, AMH, LHCGR, AR in BMP6. Genotipizacijo smo izvedli za polimorfizme rs10407022 v genu AMH; rs1394205 in rs6166 v genu FSHR; rs3741664 v genu AMH in rs2234693 v genu ESR1. Bazalni FSH (bFSH), estradiol (E2) in anti-Müllerjev hormon (AMH) so bili izmerjeni z encimsko povezanim imunosorbentnim testom (ELISA). Preiskovanke z genotipom GG polimorfizma rs1394205 so imele značilno nižjo raven AMH (P = 0,016) in so tako zahtevale višji odmerek rFSH v jajčni celici v primerjavi s preiskovankami z AA- ali AG-genotipom (P = 0,036). Ugotovili smo tudi večjo pogostnost genotipa GG rs1394205 pri preiskovankah s slabim odzivom (76,5 %) v primerjavi s tistimi, ki so se odzvale prekomerno (37,5 %; P = 0,002). Preiskovanke z genotipom AA polimorfizma rs6166 so imele višjo raven izmerjenega bFSH v primerjavi s tistimi z genotipi AG ali GG (P = 0,043). Preiskovanke z genotipom GG polimorfizma rs3741664 so potrebovale višji odmerek rFSH v primerjavi s preiskovankami, ki so imele genotip AA ali AG (P = 0,028). Genotip GG polimorfizma rs1394205 je povezan z napovedano vrednostjo za slabo odzivnost jajčnikov na KOH. Pacientke s tem genotipom potrebujejo višje odmerke rFSH za indukcijo ovulacije.
Keywords:hormonsko spodbujanje ovulacije, polimorfizem posameznega nukleotida, FSHR, AMHR, genotipizacija
Place of publishing:Maribor
Year of publishing:2019
PID:20.500.12556/DKUM-73566 New window
COBISS.SI-ID:300264704 New window
NUK URN:URN:SI:UM:DK:KTL86U7O
Publication date in DKUM:07.06.2019
Views:1828
Downloads:131
Metadata:XML DC-XML DC-RDF
Categories:MF
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Secondary language

Language:English
Title:ASSOCIATION OF GENES, RESPONSIBLE FOR THE ACTION OF HORMONES IN HORMONAL RECEPTORS, WITH RESPONSE TO HORMONAL REGULATION OF FOLLICULOGENESIS
Abstract:The aim of this study was to investigate if single nucleotide polymorphisms (SNPs) in selected genes, responsible for hormonal regulation of folliculogenesis, are associated with response to controlled ovarian hyperstimulation (COH) and clinical characteristics of women enrolled in in vitro fertilization (IVF) program. In a cross-sectional study 60 (IVF) patients underwent COH by using gonadotrophin – releasing hormone (GnRH) antagonist and recombinant follicle-stimulating hormone (rFSH) protocol. Patients were classified into three groups: poor-responders (according to Bologna criteria), normo-responders (≤ 15 oocytes), and hyper-responders (> 15 oocytes). Genotyping of SNPs AMH rs10407022, AMHR rs3741664, FSHR rs1394205 and rs6166 and ESR1 rs2234693 was performed using high resolution melting analysis (HRMA). Basal FSH (bFSH), estradiol (E2) and anti-Müllerian hormone (AMH) were measured by enzymelinked immunosorbent assay (ELISA). Patients with GG genotype of FSHR rs1394205 had significantly lower AMH level (P = 0,016) and required higher rFSH dose per oocyte compared to women with AA or AG genotype (P = 0,036). We also found higher frequency of GG genotype of FSHR rs1394205 in poor- (76.5 %) than in hyper-responders (37.5 %, P = 0,002). Patients with AA genotype of FSHR rs6166 had higher level of measured bFSH compared to those with AG or GG genotypes (P = 0,043). Women with GG genotype of AMHR rs3741664 required higher rFSH dose in comparison with patients carrying genotypes AA or AG (P = 0,028). The GG genotype at position rs1394205 is associated with poor ovarian response to COH. The patients with this genotype may require higher doses of rFSH for ovulation induction
Keywords:Controlled ovarian hyperstimulation, single nucleotide polymorphisms, FSHR, AMHR, genotyping


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