NCT03940807

Impact of Ultra-long Versus Long Down-regulation Protocol on IVF/ICSI in Adenomyosis

Phase III Trial to Assess Impact of Ultra-long Versus Long Down-regulation Protocol on IVF/ICSI Outcomes in Infertile Women Presenting With Adenomyosis.

• Status: Withdrawn
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: University Hospital, Toulouse · Academic / Other
• Sex: Female
• Age: 18 Years – 40 Years
• Healthy volunteers: Not accepted

Summary

Adenomyosis is a benign condition defined as the invasion of ectopic endometrium into the myometrium, resulting in smooth muscle hyperplasia and endometrial inflammation, commonly associated with endometriosis and uterine fibroids. Heterogeneity among studies regarding diagnostic criteria and therapeutic management has fed the debate surrounding the impact of adenomyosis on assisted reproductive therapy outcomes. Nevertheless, recent data support that adenomyosis impairs reproductive outcomes associated with in vitro fertilization (IVF). According to several experimental data, prolonged exposure to gonadotropin releasing hormone (GnRH) agonists may overcome part of the detrimental impact of adenomyosis on fertility outcome. Overall, GnRH agonist treatment resulted in decreased local production of cytochrome P450 aromatase, decreased intrauterine concentration of free radicals and reduced inflammatory response and angiogenesis in endometrium, myometrium and adenomyosis lesions. At the same time, GnRH agonists affect neither endometrial capacity to support invasion nor invasive potential of the blastocyst in the early stages of implantation. For IVF, 2 main protocols based on GnRH agonist pituitary down-regulation are available: * the long protocol involving a 15 days pituitary down-regulation; * the ultra-long protocol involving a 3 months pituitary down-regulation. Most studies using ultra-long protocol reported similar IVF outcomes in adenomyosis patients and control groups. Conversely, studies involving long or GnRH antagonist protocols demonstrated a significant reduction in clinical and ongoing pregnancy rates in adenomyosis patients compared to control subjects. Thus supporting that ultra-long protocol may be beneficial to improve IVF outcomes in the setting of adenomyosis.This is what investigators would like to demonstrate in this study

Conditions

• Adenomyosis

Interventions

Type	Name	Description
DRUG	11.25mg GnRH agonist	Ultra-long protocol group women will receive one intra-muscular administration of 11.25 mg GnRH agonist (triptorelin acetate) on the luteal phase of their menstrual cycle. Ovarian stimulation will be started after 90 days desensitization. After the desensitization period, all patients will undergo standardized ovarian stimulation, follicular aspiration, fertilization of all oocytes using either standard insemination or ICSI according to the features of sperm examination, fresh embryo transfer and luteal phase support.
DRUG	0.1 mg GnRH agonist	Long protocol group women will receive a 15-days pituitary down-regulation protocol that consists of daily subcutaneous injection of 0.1mg of GnRH agonist (triptorelin acetate) started on the luteal phase of their menstrual cycle. Ovarian stimulation will begin after 15 days desensitization. After the desensitization period, all patients will undergo standardized ovarian stimulation, follicular aspiration, fertilization of all oocytes using either standard insemination or ICSI according to the features of sperm examination, fresh embryo transfer and luteal phase support.
DRUG	25 µg transdermal oestradiol	Add back therapy (transdermal estradiol, 25μg twice a week) will be administrated throughout down-regulation period.

Timeline

• Start date: 2022-04-29
• Primary completion: 2025-01-01
• Completion: 2025-01-01
• First posted: 2019-05-07
• Last updated: 2022-11-18

Locations

14 sites across 1 country: France