A Phase 4 interventional study of Enantone and Dienogest 2 MG (milligram) in Adenomyosis, sponsored by Azienda Ospedaliero-Universitaria di Modena. Recruiting at 1 site in Italy. Open to female participants aged 18 Years to 42 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2023-07-10.
Sponsored by Azienda Ospedaliero-Universitaria di Modena · Phase 4, Interventional, and Treatment
The goal of this clinical trial is to:
Adenomyosis (internal endometriosis) may negatively influence fertility and perinatal outcomes. Inflammation, immune modulation, oxidative stress, extracellular matrix remodelling, aberrant angiogenesis have been implicated in altered oocyte development, uterine receptivity, implantation, successful maintenance of pregnancy. An improvement for infertile women could be a longer GnRH(gonadotropin-releasing hormone) agonist protocol with the addition of a preventive high-dose progestin treatment during controlled ovarian hyperstimulation (COH) Infertile women with transvaginal ultrasound (TV-US) based diagnosis of adenomyosis treated will be randomized into 3 different protocols of COH. Study group 1: Long COH, Study group 2: Long COH + high-dose dienogest (DNG), Study Group 3: Ultra-long COH. COH in controls without adenomyosis will be performed using a long GnRH agonist protocol as previous described or using a flexible GnRH antagonist protocol, according to clinical practice. Our aim is to include a total of n=250 women with adenomyosis and n=250 healthy women of a similar age and basal features at the first ART attempt. The primary outcome will be the number of live birth defined as delivery of one or more live-born infant at > 22 weeks of gestation. Many secondary outcomes will be evaluated as well.
Subsequent eventual ongoing pregnancies will be followed as in normal clinical practice, in particular for the risk of preterm delivery, pre-eclampsia, Caesarean section, fetal malpresentation,small for gestational age, low birth weight and postpartum hemorrhage. In a subgroup of randomized women, the role of endometrial decidualization and its mechanisms will be evaluated in endometrial cells in vitro looking at the response to progesterone and DNG stimulated decidualization markers (in particular osteopontin and prolactin). The different responses will be related to the outcome of ARt and pregnancy related outcomes (preterm delivery, pre-eclampsia, Caesarean section, fetal malpresentation, small for gestational age, low birth weight and postpartum hemorrhage).
Another in vitro study will evaluate the immune system contribution in the implantation period and its changes in the different trimesters of pregnancies after ART conception in women with and without adenomyosis. Blood samples will be obtained - Baseline: prior to ovarian stimulation - Post ovarian stimulation (day of HCG, human chorionic gonadotropin, administration) - Post implantation (2 weeks after embryo transfer, the day of first beta HCG measurement -Second (18-24 gestational weeks) and -Third trimester (28-32 gestational week) of eventual subsequent pregnancies).
The aim of this study will be to identify immunological markers such as cellular component and related cytokines in healthy women and women with adenomyosis that undergo ART. In particular the immune system cells population and relative cytokines, the frequency of immune system cells, the interleukins profile, T cells activity and of specific receptors of pregnancy hormone involved in T cell activity will be studied. These results will be linked with estradiol, progesterone and nitric oxide in vivo levels: this will be very important in order to prevent birth losses and to propose new therapies and targets to improve early stages of blastocyst implantation in women with adenomyosis. Forty women with adenomyosis vs. 40 healthy controls will be included in this last part of the study.
135 studies on the registry are indexed under Adenomyosis; 50 are open to participants now.
This study's planned enrollment of 500 is above the median of 100 across 73 interventional studies indexed under Adenomyosis.
Browse Adenomyosis studies →Azienda Ospedaliero-Universitaria di Modena is the lead sponsor of 46 studies on the registry; 19 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
COH will be performed using a long GnRH agonist protocol(administration of depot leuprorelin 3.75 mg on day 21 of the previous luteal phase of the stimulation cycle). COH will be commenced when pituitary desensitization was achieved(\~14 days after the initiation of GnRH agonists) as evidenced by the absence of ovarian follicles \>10 mm and endometrial thickness \<4 mm on TV-US examination.
Drug: Enantone
Before COH, patients will be treated with DNG at high dose (2 mg+2 mg/day) for 28 days, from the first day of previous menstrual cycle. COH will be performed using a long GnRH agonist protocol (administration of depot leuprorelin 3.75 mg on day 21 of the previous luteal phase of the stimulation cycle). COH will be commenced when pituitary desensitization was achieved (\~14 days after the initiation of GnRH agonists), as defined above.
Drug: Dienogest 2 MG (milligram) · Drug: Enantone
COH will be performed using a ultra-long GnRH agonist protocol (administration of the first depot leuprorelin 3.75 mg on day 21 of menstrual cycle, repeated after 28 days for other two times). COH will be commenced when pituitary desensitization was achieved (\~14 days after the initiation of GnRH agonists), as described above.
Drug: Enantone
COH will be performed by using a long GnRH agonist protocol as previous described or using a flexible GnRH antagonist protocol. During TV-US monitoring, when at least one follicle reached 14 mm in diameter, to achieve LH (luteinizing hormone) suppression avoiding spontaneous ovulation, GnRH antagonist 0.25 mg/day will be added subcutaneously until the day of HCG administration.
Drug: long GnRH agonist or flexible GnRH antagonist protocol.
administration of depot leuprorelin 3.75 mg on day 21 of the previous luteal phase of the stimulation cycle.
Before COH, patients will be treated with DNG at high dose (2 mg+2 mg/day) for 28 days, from the first day of previous menstrual cycle. COH will be performed using a long GnRH agonist protocol (administration of depot leuprorelin 3.75 mg on day 21 of the previous luteal phase of the stimulation cycle).
Also known as: Enantone
COH will be performed using a ultra-long GnRH agonist protocol (administration of the first depot leuprorelin 3.75 mg on day 21 of menstrual cycle, repeated after 28 days for other two times).
During TV-US monitoring, when at least one follicle reached 14 mm in diameter, to achieve LH suppression avoiding spontaneous ovulation, GnRH antagonist 0.25 mg/day will be added subcutaneously until the day of HCG administration.
live birth after ART
Primary Outcome:Number of live birth after ART attempt defined as delivery of one or more live-born infant at \>22 weeks of gestation.
Time frame: Through study completion, an average of 2 year
Other ART and pregnancy outcomes
Uterine volume reduction between TV-US measurements at baseline and at time of COH onset
Time frame: Through study completion, an average of 2 year
Other ART and pregnancy outcomes
Occurrence of poor responders
Time frame: Through study completion, an average of 2 year
Other ART and pregnancy outcomes
Implantation rate
Time frame: Through study completion, an average of 2 year
Other ART and pregnancy outcomes
Number of participants with ongoing pregnancy
Time frame: Through study completion, an average of 2 year
Other ART and pregnancy outcomes
Preterm delivery rate
Time frame: Immediately after the childbirth
Other ART and pregnancy outcomes
Pre-eclampsia occurrence
Time frame: Immediately after the childbirth
Other ART and pregnancy outcomes
Caesarean section rate
Time frame: Immediately after the childbirth
Other ART and pregnancy outcomes
Fetal malpresentation rate
Time frame: Immediately after the childbirth
Other ART and pregnancy outcomes
Small for gestational age rate
Time frame: Immediately after the childbirth
Other ART and pregnancy outcomes
Low birth weight (\<5 centile) rate
Time frame: Immediately after the childbirth
Other ART and pregnancy outcomes
Postpartum hemorrhage(\>500 ml) rate
Time frame: Immediately after the childbirth
Plan to share: No
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Azienda Ospedaliero-Universitaria di Modena