Progesteronska potpora žutom tijelu u stimuliranim ciklusima izvantjelesne oplodnje

Tomić, Vlatka (2018) Progesteronska potpora žutom tijelu u stimuliranim ciklusima izvantjelesne oplodnje. PhD thesis, Sveučilište u Zagrebu.

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Abstract

Objectives: To compare efficacy (on-going pregnancy rate and early abortion rate), satisfaction and tolerability of different route of progesterone supplementation i.e. oral dydrogesterone, vaginal progesterone gel, micronized vaginal capsules and combined therapy of oral micronized progesterone capsules plus vaginal progesterone gel used in luteal support of stimulated cycles. Study design: Meta-analysis of three own prospective clinical studies. Study population consisted of a total of 1508 infertile women undergoing IVF/ICSI treatment in University Hospital Center ‘‘Sisters of Mercy’’ and IVF Polyclinic, Zagreb, Croatia. Luteal support was provided as: a) Crinone 8% vaginal progesterone gel (1x90 mg) administered daily, or Utrogestan vaginal capsules (2x100 mg) administered three times daily; b) Comibined therapy of Crinone 8% vaginal gel, 1x90 mg daily dose and Utrogestan oral capsules 3x100 mg, or Crinone 8% vaginal gel, 1x90 mg daily; c) Crinone 8% vaginal progesterone gel (1x90 mg) administered daily, or oral dydrogesterone Duphaston (2x10 mg) administered two times daily. Progesterone was administered from the day of oocyte retrieval (day 0) to menses or, in a case of pregnancy, until week 10. Results: The primary outcome aims were on-going pregnancy rate and early abortion rate. The on-going pregnancy rates were comparable between different routes of progesterone supplementation in luteal support i.e. in the case of combined oral-vaginal route 39.5% vrs. Crinone 8% vaginal gel 33.5%; Crinone 8% vaginal gel vrs. Utrogestan vaginal capsules 30.9%; oral progesterone tablets (Duphaston) 30.5% vrs Crinone vaginal progesterone gel 32.9% per ET (RR 0.93-1.18; p= 0.78). Early abortion rate was almost equal between different routes of progesterone supplementation with the exception of comparison between combined progesterone therapy 6.4% and vaginal progesterone gel 15.6%, which presented lower abortion rate with the use of combined progesterone therapy (RR 0.41; 95%CI 0.22-0.79; p <0.01). Early abortion rate in other comparison arms was as following: Crinone 8% vaginal gel 10.8% vrs. Utrogestan vaginal capsules 14.7%; Crinone 8% vaginal gel 6.8% vrs. Duphaston oral progesterone tablets 10.1% that give a meta-analysis RR 0.59; 95%CI 0.43-0.82 and p=0.44. Overall tolerability showed similar rates but vaginal bleeding was significantly more present with the use of Crinone 8% vaginal gel when compared with the combined therapy (RR 0.21; 95%CI 0.07-0.61; p<0.01) and oral progesterone tablets. Interference with coitus and local adverse side effects such as perineal irritation (RR 0.06; 95%CI 0.01-0.47; p<0.01) and vaginal discharge (RR 0.08; 95%CI 0.02-0.32; p<0.001) occurred significantly more with the use of vaginal progesterone (capsules and vaginal gel) than with the use of oral dydrogesterone. Satisfaction assessment showed significantly more absolutely satisfied patients with the used of oral progesterone tablets (Duphaston) in comparison with vaginal progesterone gel. Almost the same result was noticed with the use of vaginal gel vrs vaginal capsules. Overall the patients were significantly more satisfied with the use of vaginal progesterone gel, combined oral-vaginal progesterone therapy and oral vaginal tablets then with the use of vaginal progesterone capsules. Users of oral progesterone tablets showed significantly more absolute satisfaction and significantly less absolute dissatisfaction when compared with all other routes of progesterone supplementation. Conclusions: All routes of progesterone supplementation in luteal phase support of induced cycles showed almost equall efficacy considering rate of on-going pregnancy and early abortion rate. Oral tablets of dydrogesterone are effective drug, well tolerated with less adverse side effects such as perineal irritation and vaginal discharge and more overall satisfaction among patients when compared with combined therapy and vaginal route of progesterone use and can be considered for routine luteal support.

Abstract in Croatian

Ciljevi: Usporediti učinkovitost (stopa nastavljajućih kliničkih trudnoća i stope ranih pobačaja), zadovoljstvo i podnošljivost različitih puteva primjene progesterone: oralni didrogesteron, vaginalni progesteronski gel, mikronizirane vaginalne kapsule i kombinirana terapija oralnim mikroniziranim progesteronskim kapsulama i vaginalnim progesteronskim gel u luteinskoj potpori stimuliranih ciklusa. Metode: Meta-analiza triju vlastitih prospektivnih kliničkih istraživanja. Ispitivanu populaciju činilo je ukupno 1508 neplodnih žena koje su bile podvrgnute IVF / ICSI postupku u Sveučilišnom bolničkom centru "Sestara milosrdnica" i IVF poliklinici, Zagreb, Hrvatska. Luteinska potpora osigurana je kao: a) Crinone 8% vaginalni progesteronski gel (1x90 mg) koji se primjenjuju dnevno, ili utrogestanske vaginalne kapsule (2x100 mg) primijenjene tri puta dnevno; b) Kombinirana terapija 8% vaginalnog gela Crinone, 1x90 mg dnevno i Utrogestan oralne kapsule 3 x 100 mg, ili Crinone 8% vaginalni gel, 1x90 mg dnevno; c) Crinone 8% vaginalni progesteronski gel (1x90 mg) primijenjen jednom dnevno ili oralni didrogesteron Duphaston (2x10 mg) koji se primjenjuje dva puta dnevno. Progesteron se primjenjuje od dana aspiracije oocita (dan 0) do menstruacije ili, u slučaju trudnoće, do 10. tjedna. Rezultati: Stope trudnoće bile su usporedive između različitih putova progesteronske lueinske potpore, tj. u slučaju kombiniranog oralnog-vaginalnog puta 39,5% vrs. Crinone 8% vaginalni gel 33,5%; Crinone 8% vaginalni gel vrs. Utrogestanske vaginalne kapsule 30,9%; oralne progesteronske tablete (Duphaston) 30,5% vrs Crinone vaginalni progesteronski gel 32,9% po ET (RR 0,93-1,18; p = 0,78). Stope ranih pobačaja bile su gotovo jednake između različitih načina progesteronske dopunjavanja, s izuzetkom usporedbe kombinirane progesteronske terapije od 6,4% i vaginalnog progesteronskog gela 15,6% (RR 0,41, 95% CI 0,22-0,79, p <0,01). Ukupna podnošljivost pokazala je slične rezultate, ali je vaginalno krvarenje bilo znatno više prisutno uz korištenje 8% vaginalnog gela Crinone u usporedbi s kombiniranom terapijom (RR 0,21, 95% CI 0,07-0,61, p <0,01). Interferencija s koitusom i lokalnim nuspojavama kao što su perinealna iritacija (RR 0,06, 95% CI 0,01-0,47, p <0,01) i vaginalni iscjedak (RR 0,08, 95% CI 0,02 -0,32; p <0,001) pojavljuje se značajno više kod uporabe vaginalnog progesterona (kapsula i vaginalnog gela) nego kod primjene oralnog didrogesterona. Korisnice oralnih tableta progesterona pokazale su značajno apsolutno zadovoljstvo i značajno manje apsolutno nezadovoljstvo u usporedbi sa svim ostalim putovima progesteronske potpore. Zaključci: Svi načini progesteronske primjene u luteinskoj fazi potpore induciranim ciklusima pokazali su skoro jednaku učinkovitost s obzirom na stopu nastavljajuće trudnoće i stopu ranih pobačaja. Oralne tablete didrogesterona su učinkovite, dobro se podnosnoe s manje nuspojavama kao što su perinealna iritacija i vaginalni iscjedak uz više opće zadovoljstvo pacijenata u usporedbi s kombiniranom terapijom i vaginalnim putem primjene progesterona i mogu se uzeti u obzir za rutinsku lutealnu potporu.

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