E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Women with transvaginal ultrasound (TV-US)-based diagnosis of adenomyosis and women without adenomyosis but with similar baseline reproductive risks |
Donne con diagnosi di adenomiosi basata sull'ecografia transvaginale (TV-US) e donne senza adenomiosi ma con rischi riproduttivi di base simili |
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E.1.1.1 | Medical condition in easily understood language |
Women with and without a diagnosis of adenomyosis with reproductive risks |
Donne con e senza diagnosi di adenomiosi con rischi riproduttivi |
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E.1.1.2 | Therapeutic area | Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10014778 |
E.1.2 | Term | Endometriosis |
E.1.2 | System Organ Class | 10038604 - Reproductive system and breast disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To prospectively investigate the association of Adenomyosis with fertility outcomes in relation to COH protocols for ART (long or ultra-long protocol) with a preventive high-dose anti-inflammatory progestin such as dienogest (DNG). |
Indagare in modo prospettico l'associazione di Adenomiosi con gli esiti di fertilità in relazione ai protocolli COH (Iperstimolazione Ovarica Controllata) per ART (protocollo lungo o ultra-lungo) con un progestinico anti-infiammatorio preventivo ad alte dosi come il DNG. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the association of COH (Controlled Ovarian Hyperstimulation) protocols for ART (long or ultra-long protocol) with a high-dose preventive anti-inflammatory progestogen such as DNG with pregnancy and neonatal outcomes (preterm delivery, pre-eclampsia, cesarean section, fetal malformation, SGA, low birth weight and postpartum haemorrhage). |
Valutare l'associazione dei protocolli COH (Iperstimolazione Ovarica Controllata) per ART (protocollo lungo o ultra-lungo) con un progestinico anti-infiammatorio preventivo ad alte dosi come il DNG con gli esiti della gravidanza e neonatali (parto pretermine, pre-eclampsia, taglio cesareo, malformazione fetale, SGA, basso peso alla nascita ed emorragia del post-partum). |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Other types of substudies Specify title, date and version of each substudy with relative objectives: 1) In-vitro study of endometrial decidualization. Objective: to evaluate the endometrial interface by studying the response of progesterone and DNG stimulated decidualization markers, correlating them with the success of COH protocol stimulation and to pregnancy specific outcomes.
2) In-vitro study of immunological features. Objective: o study the immune changes during the implantation period and in the different trimesters of the pregnancies after ART conception. Immunological markers will be identify such as cellular component and related cytokines in relation to the presence of adenomyosis.
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Altre tipologie di sottostudi specificare il titolo, la data e la versione di ogni sottostudio con i relativi obiettivi: 1) Studio in vitro della decidualizzazione dell'endometrio. Obiettivo: valutare l'interfaccia endometriale studiando la risposta dei marker di decidualizzazione stimolati da progesterone e DNG, correlandoli con il successo della stimolazione del protocollo COH e con gli esiti specifici della gravidanza.
2) Studio in vitro delle caratteristiche immunologiche. Obiettivo: studiare i cambiamenti immunitari durante il periodo di impianto e nei diversi trimestri delle gravidanze dopo il concepimento dell'ART. Verranno identificati marker immunologici quali la componente cellulare e le relative citochine in relazione alla presenza di adenomiosi.
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E.3 | Principal inclusion criteria |
Adenomyosis of the uterus defined with at least one of the following features: (1) heterogeneous myometrium; (2) hypoechoic striation in the myometrium; (3) myometrial anechoic lacunae or cysts; (4) asymmetrical myometrial thickening of the uterine walls. Couples who are undergoing a cycle of IVF/ICSI, where a cycle is defined as egg collection following ovarian stimulation. First or second IVF or ICSI attempt. Absence of severe premature ovarian insufficiency defined by antral follicle count < 8 and AMH < 1ng/ml Meet the criteria from the Italian law to be included in a ART program. The female partner is =18 and < 42 years of age. The female partner has a BMI <30. Both partners are willing and able to provide written informed consent. |
Adenomiosi dell'utero definita con almeno una delle seguenti caratteristiche: (1) miometrio eterogeneo; (2) striatura ipoecogena nel miometrio; (3) lacune o cisti anecoiche miometriali; (4) ispessimento miometriale asimmetrico delle pareti uterine. Coppie che stanno effettuando un ciclo di FIV/ICSI, dove per ciclo si intende la raccolta degli ovuli a seguito di stimolazione ovarica. Primo o secondo tentativo di fecondazione in vitro o ICSI. Assenza di insufficienza ovarica prematura grave definita da conta follicolare antrale < 8 e AMH < 1 ng/ml Soddisfare i criteri della legge italiana per essere inclusi in un programma ART. La compagna ha =18 anni e < 42 anni. La compagna ha un BMI <30. Entrambi i partner sono disposti e in grado di fornire un consenso informato scritto. |
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E.4 | Principal exclusion criteria |
Concurrent and/or recent involvement in other research that is likely to interfere with the intervention within the previous 3 months of study enrolment. Other potential causes of implantation failure: in situ leiomyoma, hydrosalpinx, malformed uterus (unicornis, bicornis, septate, duplex), antiphospholipid syndrome Uterine fibroids (untreated FIGO Type 0-I-II and type III-IV fibroids > 3 cm) Use of GnRH analogues within previous 3 months. Extremely severe male factor infertility (sperm count < 1x 106/ml, use o surgically retrieved spermatozoa) Positive plasma viral load for human immunodeficiency virus(HIV), hepatitis C virus (HCV) or hepatitis B virus (HBV) for one (or both) in the couple during the year before inclusion Couples unable to give fully informed consent to the study. |
Coinvolgimento concomitante e/o recente in altre ricerche che potrebbero interferire con l'intervento entro i 3 mesi precedenti l'iscrizione allo studio. Altre potenziali cause di fallimento dell'impianto: leiomioma in situ, idrosalpinge, utero malformato (unicornis, bicornis, settato, duplex), sindrome antifosfolipidica Fibromi uterini (fibromi FIGO di tipo 0-I-II e di tipo III-IV non trattati > 3 cm) Uso di analoghi del GnRH nei 3 mesi precedenti. Infertilità da fattore maschile estremamente grave (conta spermatica < 1 x 106/ml, utilizzare spermatozoi prelevati chirurgicamente) Carica virale plasmatica positiva per virus dell'immunodeficienza umana (HIV), virus dell'epatite C (HCV) o virus dell'epatite B (HBV) per uno (o entrambi) nella coppia durante l'anno prima dell'inclusione Coppie incapaci di dare un consenso pienamente informato allo studio. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Number of live births after ART (delivery of one or more live-born infant at >22 weeks of gestation). |
Numero di nati vivi dopo ART (parto di uno o più neonati vivi a >22 settimane di gestazione). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
>22 weeks of gestation |
>22 settimane di gestazione |
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E.5.2 | Secondary end point(s) |
Uterine volume changes by TV-US measurements at baseline and at time of COH onset, occurrence of poor responders, implantation and clinical pregnancy rate. Moreover, the rate of preterm delivery, pre-eclampsia, small for gestational age (<5th centile), low birth weight, Caesarean section, fetal mal-presentation and postpartum hemorrage (>500 ml) will be calculated. |
Variazioni del volume uterino mediante misurazioni TV-US al basale e al momento dell'insorgenza di COH, insorgenza di scarsa risposta, impianto e tasso di gravidanza clinica. Inoltre, sarà calcolato il tasso di parto pretermine, pre-eclampsia, piccoli per età gestazionale (<5° centile), basso peso alla nascita, taglio cesareo, malformazione fetale ed emorragia postpartum (>500 ml). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The study will last 24 months and will end at the end of the in vitro analyzes. |
Lo studio durerà 24 mesi e si concluderà al termine delle analisi in vitro. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |