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Problem analysis of multiple pregnancies conceived by in vitro fertilization

dc.contributor.advisorBjelica, Artur
dc.contributor.otherVejnović, Tihomir
dc.contributor.otherJovanović, Ana
dc.contributor.otherTrninić-Pjević, Aleksandra
dc.contributor.otherKapamadžija, Aleksandra
dc.contributor.otherPetrović, Đorđe
dc.creatorIlić, Đorđe
dc.date.accessioned2020-07-03T13:26:34Z
dc.date.available2020-07-03T13:26:34Z
dc.date.issued2015-02-18
dc.identifier.urihttp://www.cris.uns.ac.rs/DownloadFileServlet/Disertacija141234027434121.pdf?controlNumber=(BISIS)90376&fileName=141234027434121.pdf&id=2776&source=NaRDuS&language=srsr
dc.identifier.urihttp://nardus.mpn.gov.rs/handle/123456789/4708
dc.identifier.urihttp://www.cris.uns.ac.rs/record.jsf?recordId=90376&source=NaRDuS&language=srsr
dc.identifier.urihttp://www.cris.uns.ac.rs/DownloadFileServlet/IzvestajKomisije141234027993470.pdf?controlNumber=(BISIS)90376&fileName=141234027993470.pdf&id=2777&source=NaRDuS&language=srsr
dc.description.abstractUvod: Višeplodne trudnoće se javljaju u 1,5% svih trudnoća nakon spontane koncepcije, dok nakon postupaka vantelesne oplodnje ovaj postotak u Evropi iznosi preko 20% uz velike varijacije među zemljama. U našoj sredini, stopa višeplodnih trudnoća nakon postupaka vantelesne oplodnje iznosi daleko iznad 30%. Pojava hipertenzivnog sindroma u trudnoći, gestacijskog dijabetesa, operativnog završavanja trudnoće, prevremenog porođaja, male porođajne telesne mase, neuroloških sekvela kod rođene dece i gotovo svih drugih komplikacija po majku i plod, kao i celokupno opterećenje zdravstvenog sistema višestruko su veći kod višeplodnih u odnosu na jednoplodne trudnoće i udeo navednih komplikacija raste sa brojem plodova. Sa druge strane deca iz postupaka vantelesne oplodnje čine i do 4,5% sve živorođene dece u pojedinim zemljama, što uz činjenicu da infertilitet pogađa 16-18% parova u našoj sredini daje ovoj pojavi posebnu dimenziju i činije i društvenim problemom. Perinatalni ishodi trudnoća iz postupaka vantelesne oplodnje su u velikoj meri kompromitovani visokom stopom multiplih trudnoća, koje se danas smatraju komplikacijom, a ne uspehom postupaka vantelesne oplodnje. Jednoplodne trudnoće iz postupaka vantelesne oplodnje u većim studijama pokazuju diskretno slabije perinatalne ishode u odnosu na one spontano začete, dok kod višeplodnih trudnoća ova korelacija nije jasno izražena i dokumentovana, uz prisutnu dilemu da li je višeplodnost sama po sebi ili način koncepcije glavni problem u zapaženoj pojavi. Cilj rada: Uporediti perinatalne ishode višeplodnih trudnoća nastalih postupcima vantelesne oplodnje i spontano začetih kao i perinatalne ishode jednoplodnih i višeplodnih trudnoća iz postupaka vantelesne oplodnje. Pored navdenog cilj rada je i ukazati sveobuhvatnost navedenog problema i na moguća rešenja za smanjenje njihove učestalosti. Materijal i metode: Kombinacijom retrospektivne opservacione studije i prospektivne longitudinalne kohortne studije u periodu analizom perinatalnih ishoda pacijentkinja porođenih na Klinici za ginekologiju i akušerstvo Kliničkog centra Vojvodine u periodu od od 01.01.2008. do 31.12.2010. godine, studija je analizirala i poredila perinatalne ishode kod 174 spontano začete višeplodne trudnoće, 163 višeplodne trudnoće nastale postupkom vantelesne oplodnje, kao i 155 jednoplodnih trudnoća začete postupkom vantelesne oplodnje. Analizirani parametric bili su telesna masa novorođenčeta, dostignuta gestacijska starost, vrednosti Apgar skora, učestalost hipertenzivnog sindroma kod majke i brojni drugi parametri perinatalnog ishoda. Uzeti od strane obučenih kliničara i unošeni u posebno dizajniranu bazu podataka, rezultati su statistički analizirani u program JMP ver 9.0 (SAS publisher) uz korišćenje ANOVA analize za testiranje statističke značajnosti između srednjih vrednosti kontinuiranih varijabli, dok je statistička značajnost razlike učestalosti kategorijskih varijabli je određivana Pearsonovim χ2 testom. Rezultati: Jednoplodne ART trudnoće uz prosečnu starost od 33,5 godine, prosečnu gestacijsku starost na porođaju od 38,26 gn, udeo prevremenih porođaja od 12,9%, prosečnu telesnu masu od 3258 g, AS u prvom minutu od 8,35 i u petom minutu od 9,2, stopu carskog reza od 65,81%, udeo GDM-a od 7,1%, anemije od 41,94% i preeklampsije od 4,52%, ima sve relevantne parametre perinatalnog ishoda statistički značajno (p<0.0001) superiornije od kako ART tako i non ART blizanačkih trudnoća. ART blizanačke trudnoće pokazale su prosečnu starost majke od 32,9 godina, prosečnu gestacijsku starost na porođaju od 35,6 gn, udeo prevremenih porođaja od 58,27%, prosečnu telesnu masu od 2374 g, AS u prvom minutu od 7,45 i u petom minutu od 8,65, stopu carskog reza od 83,7%, udeo GDM-a od 15,11%, anemije od 78,42% i preeklampsije od 12,23%, dok su non ART blizanačke trudnoće pokazale prosečnu starost majke od 28,8 godina, prosečnu gestacijsku starost na porođaju od 36,08 gn, udeo prevremenih porođaja od 49,71%, prosečnu telesnu masu od 2433 g, AS u prvom minutu od 7,75 i u petom minutu od 8,75, stopu carskog reza od 58,33%, udeo GDM-a od 7,02%, anemije od 67,84% i preeklampsije od 11,11%. Pored godina majke i udela carskog reza koji su bili viši u ART blizanačkim trudnoćama (<0.0001), kao i blago veće pojavi poremećaja količine plodove vode (p=0,033), gotovo svi ostali pokazatelji toka i ishoda trudnoće bili su komparabilni u navedenim grupama. Diskusija i zaključak: Studija je pokazala da su tok i ishod višeplodnih trudnoća nastalih spontano i postupcima vantelesne oplodnje ekvivalentni u gotovo svim pokazateljima uz sličnu prosečnu telesnu masu i gestacijsku starost novorođenčadi, kao i da su svi navedeni parametri ovih višeplodnih trudnoća bez obzira na način koncepcije upadljivo i podjednako lošiji u poređenju sa jednoplodnim trudnoćama iz postupka vantelesne oplodnje. Izuzimajući višeplodnost kao factor rizika deca iz postupaka vantelesne oplodnje su generalno zdrava. Sama višeplodnost, a ne način koncepcije predstavljaju problem, koje se sa pravom smatra najvećom komplikacijom vantelesne oplodnje. Dodatna analiza iskustava drugih zdravstvenih sistema ukazuje da jedino široka i sveobuhvatna implementacija strategije vraćanja samo jednog embriona (Single embryo transfer – SET) može da dovede do smanjivanje stope multiplih trudnoća nakon postupaka vantelesne oplodnje, i sledstvenih komplikacija, a bez ugrožavanja samog uspeha vantelesne oplodnje. Iskustva drugih zdravstvenih sistema ukazuju da je uspešna implementacija SET-a jedino moguća uz angažovanje celog društva, zajedno sa brojnim legislativnim merama iz domena nadzora, kontrole i finansiranja postupaka vantelesne oplodnje. Obim i način finansiranja postupaka vantelesne oplodnje od strane države (uz više besplatnih pokušaja za infertilne parove) uz obaveznu upotrebu SET-a, i sistema krioprezervacije na osnovu primera iz prakse predstavlja ključ u borbi za smanjenje problema višeplodnih trudnoća nakon postupaka vantelesne oplodnje.sr
dc.description.abstractIntroduction: Multiple pregnancies occur in 1.5% of all pregnancies after spontaneous conception and in more than 20 % of all pregnancies concieved after assisted reproductive technologies in Europe, with large variations between countries. In our setting, the rate of multiple pregnancies after the ART is well above 30%. The occurrence of hypertensive syndrome in pregnancy, gestational diabetes, operative delivery, premature birth, low birth weight, neurological and developmental impairment in children, and almost all the other complications for the mother and fetus, as well as the entire burden of the health system are several times higher in multiple pregnancies compared with singleton pregnancies. Incidence of  forementioned complications rises with number of fetuses. On the other hand, children from in vitro fertilization procedures make up 4.5% of all live births in some countries, which together with the fact that infertility affects aproximately 16-18% of couples in our country gives an extra dimension to this phenomenon and makes it not just medical but wider social problem. Perinatal outcomes of pregnancies after assisted reproductive technologies (ART) are greatly compromised by the high rate of multiple pregnancies, which are now considered to be a complication rather than success of ART procedures. ART Singleton pregnancies have, in larger studies, show discretely lower perinatal outcomes compared with those conceived spontaneously, while for the multiple pregnancies, this correlation is not clearly expressed and documented. There remains dilemma whether multiplicity itself or the way of conception (ART vs. non ART) constitutes a major problem in the observed differences regarding perinatal outcome of ART pregnancies. Objective: To compare the perinatal outcomes of multiple pregnancies conceived by In vitro fertilization (IVF) and spontaneously and perinatal outcomes of IVF conceived singleton and multiple pregnancies. Additional aim of this thesis is to point out the complexity of this problem and offer possible solutions. Materials and Methods: Design of a study was a combination of retrospective and prospective observational longitudinal cohort study. Analysis included pregnancies which had delivery at the Department of Gynecology and Obstetrics, Clinical Center of Vojvodina in the period from 1.01.2008. to 31.12.2010. The study analyzed and compared the perinatal outcomes in 174 spontaneous conceived multiple pregnancies, 163 multiple pregnancies resulting from IVF procedures, and 155 singleton pregnancies conceived by IVF procedure. Analyzed parameters were newborns birth weight, gestational age at delivery, the value of the Apgar score, occurrence of hypertensive syndrome in pregnancy, gestational diabetes, as well as numerous parameters of perinatal outcome. Taken by trained clinicians and were entered into a specially designed database, the results were statistically analyzed in JMP ver 9.0 software (SAS publisher) using ANOVA analysis to test the statistical significance between the mean values of continuous variables, while the statistical significance of the difference in frequency of categorical variables was assessed by Pearsons χ2 test. Results: ART singleton pregnancies had an average mothers age of 33.5 years, the average gestational age at birth of 38.26 gestational weeks (gw), preterm delivery rate of 12.9%, average birth weight 3258 g, Apgar score (AS) in the first minute 8.35, and in the fifth minute 9.2, cesarean section rate 65.81%, Gestational diabetes (GDM) in 7.1% pregnancies, anemia occurred in 41.94% of pregnancies, while preeclampsia was observed in 4.52% of all pregnancies. All relevant parameters of perinatal outcome were significantly (p<0.0001) superior to both ART and non-ART twin pregnancies. ART twin pregnancy showed the average mothers age of 32.9 years, the average gestational age at birth of 35.6 gw, the preterm delivery rate 58.27%, the average body weight newborns 2374 g, AS in the first minute of 7.45, and in the fifth minute of 8.65, the cesarean section rate of 83.7%, GDM in 15.11% of all pregnancies, anemia occurred in 78.42% and preeclampsia in 12.23% of pregnancies, while the non-ART twin pregnancy showed an average mothers age of 28.8 years, the average gestational age at birth of 36.08 gw, the preterm delivery rate of 49.71%, the average body weight of 2433 g, AS in the first minute of 7.75 in the fifth minute 8.75, the caesarian section rate of 58.33%, GDM-a occurred in 7.02%, anemia in 67.84% and preeclampsia in 11.11% of pregnancies. Except for maternal age and the caesarean section rate, which were significantly higher in ART twin pregnancies (p<0.0001), as well as small increase in proportion of amniotic fluid volume disorders (p = 0.033), almost all other parameters of perinatal outcome of were comparable in these groups. Discussion and Conclusion: The study showed that the course and outcome of multiple pregnancies conceived spontaneous and after IVF procedures are equivalent in almost all parameters with similar average body weight and gestational age at birth, and that all these parameters of multiple pregnancies regardless of the conception mode are equally worse compared with singleton pregnancies from IVF procedures. With the exception of multiplicity as a risk factor children from in vitro fertilization procedures are generally healthy. Multiplicity itself and not the mode of conception presented a problem, which is rightly considered the major complication of IVF today. Additional analysis of the experiences of other health system indicates that only a broad and comprehensive implementation of strategy to return only one embryo (SET–single embryo transfer) can lead to a reduction of the rate of multiple pregnancies after IVF procedures, and the accompanying complications, without compromising IVF success. The experience of other health systems indicate that a successful implementation of SET is only possible with the involvement of the whole society, along with a number of legislative measures in the field of monitoring, control and reimbursement of assisted reproduction procedures. The scope and funding of an IVF procedures (with more free attempts for infertile couples, reimbursed by public health) with mandatory use of SET, and good cryopreservation programs are, based on examples in other countries who had successfully dealt with his problem, is the key in reducing the problem of multiple pregnancies after IVF procedures.en
dc.languagesr (latin script)
dc.publisherУниверзитет у Новом Саду, Медицински факултетsr
dc.rightsopenAccessen
dc.sourceУниверзитет у Новом Садуsr
dc.subjectVantelesna oplodnjasr
dc.subjectIn vitro fertilizationen
dc.subjectIVFsr
dc.subjectICSIsr
dc.subjectVišeplodne trudnoćesr
dc.subjectBlizanačke trudnoćesr
dc.subjectTroplodne trudnoćesr
dc.subjectVišeplodne trudnoće iz postupka VTOsr
dc.subjectTrudnoće iz postupaka VTOsr
dc.subjectPerinatalni ishodsr
dc.subjectPrevremeni porođajsr
dc.subjectHipertenzivni sindrom u trudnoćisr
dc.subjectGestacijski dijabetessr
dc.subjectSingle embryo transfer – SETsr
dc.subjectDouble embryo transfer – DETsr
dc.subjectFetalna redukcijasr
dc.subjectNadzor postupaka vantelesne oplodnjesr
dc.subjectLegislativa postupaka vantelesne oplodnjesr
dc.subjectFinansiranje postupaka vantelesne oplodnjesr
dc.subjectIVFen
dc.subjectICSIen
dc.subjectMultiple pregnanciesen
dc.subjectTwin pregnanciesen
dc.subjectTriplet pregnanciesen
dc.subjectMultiple pregnancy after assisted reproductionen
dc.subjectPerinatal outcomeen
dc.subjectPreterm deliveryen
dc.subjectHypertensive syndrome in pregnancyen
dc.subjectGestational diabetesen
dc.subjectSingle embryo transfer - SETen
dc.subjectDouble embryo transfer - DETen
dc.subjectFetal reductionen
dc.subjectMonitoring of assisted reproductionen
dc.subjectLegislation of assisted reproductionen
dc.subjectReimbursement of assisted reproductionen
dc.titleAnaliza problema višeplodnih trudnoća nastalih vantelesnom oplodnjomsr
dc.titleProblem analysis of multiple pregnancies conceived by in vitro fertilizationen
dc.typedoctoralThesissr
dc.rights.licenseBY-NC
dcterms.abstractБјелица Aртур; Вејновић Тихомир; Јовановић Aна; Трнинић-Пјевић Aлександра; Капамаджија Aлександра; Петровић Ђорђе; Илић Ђорђе; Aнализа проблема вишеплодних трудноћа насталих вантелесном оплодњом; Aнализа проблема вишеплодних трудноћа насталих вантелесном оплодњом;
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/34807/IzvestajKomisije282.pdf
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/34806/Disertacija282.pdf


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