Assisted reproductive technology (ART) and pregnancy outcomes in women with adenomyosis (internal endometriosis) according to stimulation protocol in relation to immunological and endometrial features: a prospective, randomized study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Azienda Ospedaliero Universitaria Di Modena

Participant type

Patients

Age range

18-64 years

Gender

Female

Therapeutic area

Diseases [C] - Female Urogenital Diseases and Pregnancy Complications [C13]

Trial duration

12 Aug 2024 → ongoing

Decision date (initial)

2024-08-12

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Ministero della Salute

External identifiers

EU CT number

2024-516089-12-00

EudraCT number

2021-005005-28

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

Number of live birth after ART attempt defined as delivery of one or more live-born infant at >22 weeks of gestation in infertile women with adenomyosis vs. infertile women without adenomyosis.

Secondary objectives 2

1. Uterine volume changes by TV-US measurements at baseline and at time of COH onset, occurrence of poor responders (defined as ≤3 oocytes with a conventional stimulation protocol), number of follicles (total and by size category) at end-of-stimulation, number of oocytes retrieved, number of fertilized oocytes and fertilization rate, 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. These values will be compared between 1) women with adenomyosis vs. women without adenomyosis and 2) in women with adenomyosis according to the different COH protocol used.
2. Secondary in-vitro sub-studies: Stimulated (P and DNG) markers of decidualization (osteopontin, prolactin) in relation to ART success in women with and without A. Immune system cell population and relative cytokines, the frequency of immune system cells, the interleukin profile, cell activity, specific receptors of pregnancy hormone involved in T cell activity in women with A in comparison to healthy subjects.

Conditions and MedDRA coding

women with transvaginal ultrasound (TV-US)-based diagnosis of adenomyosis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. - Uterine adenomyosis diagnosed on ultrasound scan defined when at least ne of the following features is recognized: (1) heterogeneous myometrium; (2) hypoechoic striation in the myometrium; (3) myometrial anechoic lacunae or cysts; (4) asymmetrical myometrial thickening of the uterine walls. - Couples requiring a cycle of IVF/ICSI meeting the criteria of the Italian law to be included in an ART program. - Good physical and mental health (e.g. no contraindication to the therapeutic regimen for IVF/ICSI, like moderate or severe impairment of renal or hepatic function etc.). - First or second IVF/ICSI attempt. - Absence of severe premature ovarian insufficiency defined by antral follicle count < 8 and AMH < 1ng/ml. - 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.

Exclusion criteria 1

1. - Concurrent and/or recent involvement in other studies likely to interfere with the intervention within the previous 3 months of study enrolment. - Other potential causes of implantation failure: leiomyoma, actual hydrosalpinx, malformed uterus (unicornis, bicornis, septate, duplex), antiphospholipid syndrome - A prior history of endometrial ablation, endometrial polyps, hydrosalpinx, smocking habits, known endometriosis stage III-IV, abnormal uterine bleeding of unknown cause. - Uterine fibroids (untreated FIGO Type 0-I-II and type III-IV fibroids > 3 cm) - Use of GnRH analogues within previous 3 months. - Extreme severe male factor infertility (sperm count < 1 x 106/ml, use or 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 who in the opinion of the researcher would be unable to give fully informed consent to the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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).

Secondary endpoints 2

1. 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, preeclampsia, cesarean section, fetal malformation, SGA, low birth weight and postpartum haemorrhage).
2. Secondary in-vitro sub-studies: Stimulated (P and DNG) markers of decidualization (osteopontin, prolactin) in relation to ART success in women with and without A. Immune system cell population and relative cytokines, the frequency of immune system cells, the interleukin profile, cell activity, specific receptors of pregnancy hormone involved in T cell activity in women with A in comparison to healthy subjects.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Azienda Ospedaliero Universitaria Di Modena

Sponsor organisation

Azienda Ospedaliero Universitaria Di Modena

Address

Largo Del Pozzo 71

City

Modena

Postcode

41124

Country

Italy

Scientific contact point

Organisation

Azienda Ospedaliero Universitaria Di Modena

Contact name

Giovanni Grandi

Public contact point

Organisation

Azienda Ospedaliero Universitaria Di Modena

Contact name

Giovanni Grandi

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications