| Sažetak | 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. |
| Sažetak (engleski) | 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. |
