I-pioglitazone ehlanganiswe ne-clomiphene citrate ngokumelene ne-clomiphene citrate yodwa kwabesifazane abangabatholi abantwana abane-polycystic ovary syndrome

I-Anovulation ingenye yezimbangela ezivamile zokungazali.I-Polycystic ovary syndrome (PCOS) isifo esivame kakhulu esivame kakhulu esingelapheki.Ngokwazi kwethu, ukumelana ne-insulin kuhlotshaniswa kakhulu ne-PCOS.Ngakho-ke, ezigulini ezine-PCO, izidakamizwa ezizwela i-insulin njenge-pioglitazone ingasetshenziswa ukuvuselela i-ovulation.
Iziguli ezingamashumi ayisithupha nanye ezine-PCOS zifakwe ocwaningweni ngokwemibandela yokufakwa/yokukhishwa ngemuva kokuthola imvume eKomidini Lokuziphatha le-Medical University of Mashhad.Iziguli zahlukaniswa ngamaqembu amabili.Iqembu lokuqala lathatha ama-milligrams (mg) angu-30 i-pioglitazone nsuku zonke kusukela osukwini lwesibili lokuya esikhathini.Owesibili wathola i-placebo.150 mgclomiphene citrateyayilawulwa kusukela osukwini lwe-3 kuya osukwini lwe-7 lokuya esikhathini.I-Ultrasonography ye-Vaginal yenziwa kubo bonke abesifazane, futhi ezimweni ze-follicle ezivuthiwe, ukufakwa kwe-intrauterine kwenziwa ngemva kokujova i-gonadotropin ye-chorionic yomuntu.Ukukhuthazwa kwe-Ovarian namazinga okukhulelwa aqhathaniswa eqenjini ngalinye.
Kwakungekho mehluko phakathi kwamaqembu ngokwezici zezibalo kanye nezinhlobo zokungazali.Inkomba yesisindo somzimba yayiphezulu eqenjini le-pioglitazone (28.3 ± 3.8 vs 26.2 ± 3.5, P value = 0.047).Usayizi we-follicle awuzange uhluke kakhulu phakathi kwamaqembu (2.2) ± 1.4 vs 1.3 ± 1.1, P value = 0.742).Amazinga okukhulelwa [4 (12.9%) vs 4 (13.3%), P value = 1] awazange ahluke phakathi kwamaqembu.

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Naphezu kwenani eliphakeme lama-follicle eqenjini le-pioglitazone, ucwaningo lwethu aluzange lubonise mehluko ekuvuselelweni kwe-ovarian namazinga okukhulelwa.
Ukungazali kuthinta cishe u-10-15% wemibhangqwana.30% yokungazali kwabesifazane kungenxa yokwehluleka kwe-ovulation [1].I-Polycystic ovary syndrome (PCOS) yisifo esisobala kakhulu nesivamile esihambisana nokuphazamiseka kwe-ovulatory okungapheli [2].Uma usebenzisa i-European I-Society for Human Reproduction and Embryology kanye ne-American Society for Reproductive Medicine (ESHRE/ASRM) indlela yokuxilonga, ukusabalala kwe-PCOS cishe ku-15-20% [3].
Amazinga e-lipoprotein angavamile ajwayelekile ezigulini ze-PCOS, ezine-cholesterol ephelele (Chol), i-triglycerides (TG), i-low-density lipoprotein (LDL), i-high-density lipoprotein (HDL), ne-apoptotic AI [4], 5,6]. Ushintsho olubaluleke kakhulu ku-lipids olubikiwe kwaba ukwehla kwe-HDL.I-Hyperinsulinemia kanye nokumelana ne-insulin (IR) kuvamile ku-PCOS.Mustafa et al.Cishe i-46% yabesifazane baseGibhithe abane-PCOS batholakala bene-IR [4, 7].I-insulin iphazamisa i-steroidogenesis ku-ovary ezimele ye-gonadotropin secretion I-PCOS [1].I-insulin receptors kanye ne-insulin-like growth factor-1 (IGF-I) ikhona kumangqamuzana e-ovarian stromal [5].Ukuncipha kwe-autophosphorylation, ukuphazamiseka okuthile okuhlotshaniswa ne-insulin receptor- ukusayinda okuphakathi, kutholwa ku-50% yabesifazane abane-PCOS [3].
I-glucose metabolism engavamile ithuthukisa kakhulu ukulahlekelwa isisindo;ukuncipha kwesisindo kungase kunciphise i-hyperandrogenism futhi kubuyisele umsebenzi we-ovulatory [7] .Abesifazane abakhuluphele abanokumelana ne-insulin, ukuvinjelwa kwekhalori, nokuncipha kwesisindo kunciphisa ukuqina kokumelana ne-insulin.Ngakolunye uhlangothi, ukuncipha kokugxila kwe-insulin kunciphisa ukukhiqizwa kwe-androgen [8].

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Namuhla,clomiphene citrateiyindlela yokwelapha enconywayo yokungeniswa kwe-ovulation kwabesifazane abane-PCOS.Ukumelana ne-insulin kuhlotshaniswa kakhulu ne-polycystic ovary syndrome, ngakho izidakamizwa ezandisa ukuzwela kwe-insulin receptor, njenge-metformin ne-beta-thiazolidinediones, ziyabhekwa ekwelapheni kwalezi ziguli.Ukwelashwa kwe-insulin ukumelana kungase kubangele i-ovulation, ikakhulukazi kwabesifazane abakhuluphele abanezinga eliphakeme lokumelana ne-insulin [9].
Ukumelana ne-insulin kusho ukusabela okuncishisiwe kwe-glucose ku-insulin, okulandelwa yi-hyperinsulinemia, okuholela ekukhuphukeni kwe-triglycerides, ukunciphisa i-HDL-cholesterol, ukungabekezelelani kwe-glucose, nobungozi benhliziyo nemithambo yegazi [10].I-Pioglitazone, esetshenziselwa ukwelapha uhlobo lwe-2 yesifo sikashukela, ithinta ngokuqondile ukuzwela kwe-insulin ye-peripheral. Kolunye ucwaningo lwakamuva, i-pioglitazone ikhonjiswe ukuthi yehlisa ukugeleza kwegazi kwe-intra-ovarian stromal.Ingase isize ukuthuthukisa imiphumela ye-ovarian kanye ne-in vitro fertilization (IVF) ezigulini ze-PCOS. .
Kuze kube manje, alukho ucwaningo oluhlole umphumela we-pioglitazone ekuvundeni ezigulini zethu.Ngakho-ke, sicabange ukuthi i-pioglitazone njengesibulala-magciwane se-insulin ingase ithuthukise ukuvuthwa kwamaqanda kanye namazinga okukhulelwa ezigulini ze-PCOS. ukukhulelwa emtholampilo, kanye nenani lama-follicles amakhulu kwabesifazane abangazalanga abane-PCOS.
I-Mashhad Medical University yengamele lolu cwaningo lokuhlolwa komtholampilo okungahleliwe kusukela ngo-2014 kuya ku-2017 futhi yasebenzisa indlela yokuthatha amasampula okungewona amathuba ukuze iqashe iziguli ze-PCOS ezingu-61 ezithunyelwe e-Milad Infertility Centre ukuze ziyolashwa inzalo. “NgoMashi 15, 2014” kanye nemvume ebhaliwe enolwazi yatholwa kubo bonke ababambiqhaza.
Izindlela zokufakwa kwakungabesifazane abangabatholi abantwana abaneminyaka engu-18-38 ubudala abane-hysterosalpingography evamile kanye ne-spermogram.Ukuxilongwa kwe-polycystic ovary syndrome kusekelwe ku-AES criteria (i-Androgen Excess Society 2006) ngokusekelwe kulezi zindlela ezingenhla: (1) i-hirsutism noma izimpawu ze-hyperandrogenic.(2) ) Ukungasebenzi kahle kwe-ovarian i-oligomenorrhea, noma i-polycystic ovary itholakala njengokubukeka kwe-lace yomlomo wesibeletho nge-ultrasound;(3) Ukugqugquzelwa kwezimbangela zesibili njengezimila zesibeletho nezindlala ze-adrenal kanye ne-pituitary adenomas.I-Polycystic ovary syndrome itholwa uma umjikelezo wokuya esikhathini kuyi-oligomenorrhoea, noma uma inani lama-peripheral follicle ku-ovary lingaphezu kuka-2-9 mm ngaphezu kuka-9 Isikali se-Ferriman-Gallway.
Iziguli ezinomlando wesifo senhliziyo esingapheli, isifo sezinso esingamahlalakhona, isifo sikashukela, isifo se-thyroid, nesifo samaphaphu asizange sifakwe.

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Ngemva kokukhetha iziguli ezifanelekayo, zahlukaniswa zaba ngamaqembu amabili ngokusampula okungahleliwe okulula kusetshenziswa isofthiwe yekhompyutha.Indlela yemvilophu yasetshenziselwa ukunikeza iziguli ngokungahleliwe emaqenjini okufunda.Ngale ndlela, inombolo engahleliwe izofakwa emvilophini evaliwe.Okuqukethwe imvilophu ayikwazi ukubonakala ngaphandle.Iqembu A lalinamaphilisi angu-30 e-pioglitazone, 30 mg, namaphilisi angu-15 e-clomiphene, kuyilapho iqembu B lafakwa namaphilisi angu-30 e-placebo kanye namaphilisi angu-15 e-clomiphene. Iziguli zazingaboni ukwelashwa ezazinikiwe.
Zonke iziguli zenza i-transvaginal ultrasonography ngosuku lwesibili lokuya esikhathini futhi zafakwa ocwaningweni uma kungekho ama-ovarian cysts angaphezu kuka-20 mm.
Inani le-follicles eliphakathi nendawo elikhulu kanye nokuqina kwe-endometrial kwahlolwa ngosuku lweshumi noma lweshumi nanye lokuya esikhathini.Amazinga okukhulelwa amakhemikhali kanye nomtholampilo ahlolwe.
Iqembu lokuqala lathola ama-30 mg we-pioglitazone nsuku zonke;iqembu lesibili lathola i-placebo kusukela ngosuku lwesibili lokuya esikhathini.Phakathi kwezinsuku ezi-3 nezingu-7 zomjikelezo wokuya esikhathini, womabili amaqembu anikezwa i-150 mgclomiphene citrate.I-Transvaginal ultrasonography ngosuku lwe-10 noma lwe-11.Cabangela i-chorionic gonadotropin (HCG) elandelwa yi-intrauterine insemination (IUI) kwabesifazane abanogqinsi lwe-endometrial engaphezu kuka-7 mm kanye nama-follicle angaphezu kuka-16 mm.
Endabeni yokubambezeleka kwezinsuku ezingu-5 ukuya esikhathini, amasampula egazi athathwa ukuze kuhlolwe amazinga e-βHCG.Imiphumela emibi ehlobene ne-Pioglitazone kanye nezinombolo ze-follicle ezingaphezu kuka-16 mm kanye nokuqina kwe-endometrial kwahlolwa ngesikhathi socwaningo.Ekugcineni, ukukhuthazwa kwe-ovarian kanye namazinga okukhulelwa ahlolwe. kuqhathaniswa kuwo wonke amaqembu.
Usayizi wesampula ubalwa kusetshenziswa isofthiwe ye-PASS 11 kanye nenani elimaphakathi lama-follicle eqenjini ngalinye laqhathaniswa.Ngokuzenzakalelayo, amaphutha ohlobo loku-1 angu-5% futhi amaphutha ohlobo lwe-2 angu-20%.Silinganise iziguli ezingu-22 iqembu ngalinye, kodwa ngenxa yamandla angenzeka. ukwehla, abahlanganyeli be-30 iqembu ngalinye bacatshangelwa.
Idatha yafakwa enguqulweni ye-SPSS 16.Ekuqaleni, izici zeqembu ngalinye zazichazwe ngezindlela zezibalo ezichazayo, okuhlanganisa izindlela nokuchezuka okujwayelekile kokuguquguquka okuqhubekayo kanye namaza ezinombolo kanye nenani lokuguquguquka kwezigaba.Bese, ukuqhathanisa ukuguquguquka kobuningi emaqenjini amabili ocwaningo, Ukuhlolwa kwe-t okuzimele noma ukuhlolwa kwe-Mann-Whitney-U kusetshenziswe ngemva kokuhlola ukujwayelekile kusetshenziswa ukuhlolwa kwe-Kolmogorov-Smirnov. Okuguquguqukayo kwekhwalithi kwaqhathaniswa kusetshenziswa ukuhlolwa kwe-chi-square. Kuzo zonke izibalo, amanani e-P angaphansi kuka-0.05 ayebhekwa njengamazinga abalulekile .
Ngokuphathelene nenqubo yokufakwa, abesifazane abangu-93 babambe iqhaza ocwaningweni, abangu-19 babenemibandela yokungabandakanyi kwathi abangu-13 bayeka. Iziguli ezingamashumi amathathu zahlukaniswa eqenjini le-placebo kanye ne-31 eqenjini lokungenelela. kuboniswe kuThebula 1.Kwakungekho mehluko phakathi kwamaqembu ngokwezici zezibalo kanye nohlobo lokungazali.Isilinganiso seminyaka yeqembu lokungenelela sasingu-28.20±5.46 kanye neqembu elilawulayo lalingu-27.07±4.18, futhi umehluko wawungabalulekile ngokwezibalo. .Nokho, inkomba yesisindo somzimba (BMI) yayiphezulu eqenjini le-pioglitazone.
Ithebula lesi-2 lifingqa okutholwe yi-sonographic yesiguli, njengenani lama-follicles anosayizi omaphakathi, inani lama-follicle amakhulu, ubukhulu be-follicle ubukhulu, nokuqina kwe-endometrial.Njengoba kubonisiwe kuThebula 2, usayizi we-follicle wawuseqenjini ngaphandle follicles medium-sized.
Ulwazi ngemiphumela yokwelashwa kokungeniswa kwe-ovulation, njengevolumu ye-ovulation, amakhemikhali, namazinga okukhulelwa emtholampilo ngomjikelezo ngamunye, kuvezwe kuThebula 3.Ukukhuthazwa kwe-Ovarian kanye namazinga okukhulelwa awazange ahluke phakathi kwamaqembu.
Imiphumela yalolu cwaningo ibonise ukuthi kunomehluko omkhulu enanini le-ovulation stimulations phakathi kweziguli eziphathwa nge-pioglitazone.I-Ultrasonography, eyenziwa ngosuku lwe-10 lokuya esikhathini, ibonise ukwanda okuphawulekayo kwenani elilinganiselwe lama-follicle eqenjini lokungenelela.Okutholakele kwethu qinisekisa okutholwe ocwaningweni lwango-2012 ngendima ye-pioglitazone ekungenweni kwe-ovulation ezigulini ze-hyperinsulinemic ezine-PCOS [12].Morley et al.Ukwenyuka kwe-ovulation kuye kwabikwa futhi ezigulini ze-PCOS ezithatha i-pioglitazone [13].
Kwakungekho mehluko ekuvuthweni kweqanda kanye namazinga okukhulelwa phakathi kwamaqembu amabili ocwaningo. Lokhu kungase kube ngenxa yesikhathi se-pioglitazone esetshenziswe ngaphambi kokuqala kwe-clomiphene.I-Ota yabonisa ukuthi imiphumela ka-2008 yabonisa ukuthi iziguli ezingu-7 kweziyi-9 ezathatha i-pioglitazone amasonto angu-12-30 ngaphambili. i-clomiphene yakhulelwa [14].Ucwaningo lukaKim lwango-2010 lwabonisa ukwehla okukhulu kwenani lama-follicle ngemva kokunikezwa kwe-pioglitazone.Ngaphezu kwalokho, ocwaningweni lwakhe, iqembu le-pioglitazone lalinezinga eliphezulu lokukhulelwa emtholampilo, kodwa lo mehluko wawungabalulekile ngokwezibalo. ihluke emiphumeleni yethu, kodwa ingachazwa ngemibandela yokukhetha isiguli, kuhlanganise neziguli ezimelana ne-clomiphene [15].
I-Ota yabonisa ukuthi i-pioglitazone ingathuthukisa amazinga okukhulelwa ezigulini ze-PCOS ezimelana ne-clomiphene ne-dexamethasone [14].Kubonakala sengathi izimo ze-PCOS ezine-hyperandrogenemia kufanele zikhethwe ngokucophelela.Iziguli ohlelweni lwe-Ota zinamazinga ahlukene amahomoni, angathinta umphumela Ukwelashwa kwe-pioglitazone.Ocwaningweni lwethu, amazinga e-hormone awazange ahluke kakhulu ngaphambi nangemva kokungenelela.
Esifundweni sethu, kwakungekho umehluko ophawulekayo ngenani lama-follicles amakhulu kanye nokuqina kwe-endometrial phakathi kwamaqembu okungenelela nokulawula.Nokho, kwakukhona ukwanda okuphawulekayo kwenani lama-follicles aphakathi eqenjini lokungenelela.
Ocwaningweni lwamanje, iqembu lokungenelela libe ne-BMI ephakeme, okusho ukuthi leli qembu lingase libe namathuba amaningi okuthuthukisa i-hyperinsulinemia futhi lithinte umphumela, nakuba lo mehluko wawungekho ngokwezibalo phakathi kwamaqembu amabili.
Azikho iziguli zethu ezaba nemiphumela engemihle.Azikho izinguquko ezibalulekile ngokwezibalo ekuhlolweni kokusebenza kwesibindi phakathi nenkathi yocwaningo.
Umkhawulo omkhulu wocwaningo lwethu kwakuwukuthi ucwaningo lwaklanywa njengephrojekthi yokulawula icala, okwaholela ekuhlukeni kwe-BMI phakathi kwamaqembu amabili.Ngakho-ke, imiphumela ingase ithinteke kulo mehluko.Nokho, azikho izifundo ezifanayo zalezi ezimbili- uhlobo lwezidakamizwa lwenziwe ezigulini esifundeni sethu.Nokho, ngenxa yomphumela we-pioglitazone ekumelaneni ne-insulin, kubonakala sengathi izinga lempumelelo liyakhula uma iziguli zithola i-pioglitazone isikhathi eside ngaphambi kokuqala ukudla kwe-clomiphene.Ngakho-ke, ucwaningo olwengeziwe luyanconywa thola isikhathi esingcono kakhulu sokusebenzisa i-pioglitazone.
Naphezu kwenani eliphakeme lama-follicle eqenjini le-pioglitazone, ucwaningo lwethu aluzange lubonise mehluko ekuvuselelweni kwe-ovarian kanye namazinga okukhulelwa phakathi kwamaqembu amabili.
Eqinisweni, siye saphatha ngempumelelo izinkinga ezithile ezinjengokungatholi abantwana, ukopha ngenxa yokungasebenzi kahle kwesibeletho kanye ne-hirsutism esikhathini esidlule.Manje sesinethuba (futhi ngempela sinesibopho) sokuhlinzeka ngokungenelela ukuvimbela noma ukulungisa ezinye zezinkinga ze-metabolic zokungazali (okuyinto ingaba nomthelela omkhulu empilweni jikelele kanye nekhwalithi kanye nenani lempilo).


Isikhathi sokuthumela: Mar-30-2022