Impact of Esmya on Fertility to Infertile Women With Fibroids Managed With Assisted Reproduction Techniques (NACRE)

A Retrospective, National, Multicenter Study Evaluating the Impact of Ulipristal Acetate (Esmya®) on Infertility to Infertile Women With Fibroids Managed With Assisted Reproduction Techniques (ART)

Fibroid is a frequent pathology of infertile women. Its deleterious effect on the infertility would be due to the mechanical way.

The interest of the resection of intramural fibroids is discussed. It is necessary to measure the indication of a myomectomy, whatever the surgical procedure. On the one hand, it may cause important potential complications, and on the other hand, the surgery does not improve the parameters of the fertility.

Thus, it is a major stake to avoid the surgical operation. A decrease of the size of these fibroids by medical treatment is then a good option.

When the surgical treatment is necessary, a medical pre-surgical treatment is often proposed in order to decrease the symptomatology and to reduce the size of the fibroid to facilitate the surgery.

Acetate Ulipristal (UPA) has been marketed in this indication. Following the Pearl I-II studies, the first indication in France was a pre-surgical treatment for 3 months at a dose of 5 mg per day.

The Pearl III and IV studies evaluated the Esmya® administration as a long-term intermittent repeated treatment, giving to it a prominent position for the long-term management of symptomatic fibroids.

Furthermore, cases of pregnancy before surgery are frequently described in women with fibroids treated by UPA for a pre-IVF surgery.

5 to 10 % of women who are managed for infertility have fibroids and only 2% to 3% have this unique cause of infertility.

Then, some of patients followed in ART centers have been treated by UPA to reduce the fibroids size and/or to decrease the associate symptoms.

The aim of this study is to evaluate in the different French ART centers, the impact on fertilization of UPA administration for infertile women with fibroids and to describe the modalities of its prescriptions and to collect information regarding safety tolerance profile of Esmya® in this patient population.

Study Overview

• Status: Completed
• Conditions: Infertility, Female; Fibroid Uterus
• Intervention / Treatment: Drug: ULIPRISTAL ACETATE

Detailed Description

A retrospective, national, multicenter study

• Study Type: Observational
• Enrollment (Actual): 127

Contacts and Locations

Study Locations

• France
  • Angers, France
    • CHU Angers
  • Besançon, France
    • CHU Besançon
  • Bordeaux, France
    • CHU Pellegrin
  • Bruges, France
    • Polyclinique Jean Villar
  • Créteil, France
    • Centre Hospitalier Intercommunal Créteil
  • Dijon, France
    • CHU Dijon
  • Ecully, France
    • Clinique Val D'Ouest
  • Lille, France
    • CHRU Lille
  • Marseille, France
    • Cpma Marseille
  • Marseille, France
    • Imr Rocca
  • Montpellier, France
    • Chevalier
  • Montpellier, France
    • POUGET
  • Nice, France
    • CHU NICE
  • Nîmes, France
    • CHU Nimes
  • Paris, France
    • Ch Antoine Beclere
  • Paris, France
    • CH Tenon
  • Paris, France
    • Maternite Bichat
  • Paris, France
    • MENARD
  • Paris, France
    • Port Royal - Chirurgie
  • Rennes, France
    • CHU Rennes
  • Schiltigheim, France
    • Cmco - University Hospitals of Strasbourg
  • Toulouse, France
    • Chu Toulouse
• New Caledonia
  • Nouméa, New Caledonia
    • Centre Hospitalier Territorial Gaston Bourret

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 43 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Probability Sample

Study Population

Infertile women with fibroids managed with assisted reproduction techniques (ART)

Description

Inclusion Criteria:

1. Age between 18 to 43 years 'old at the time of the beginning of ulipristal acetate intake
2. Women with fibroid at the time of ulipristal acetate prescription
3. Women with desire to have children and managed for infertility in an ART center (whatever the type of infertility treatment)
4. Women having received a treatment by ulipristal acetate
5. Data collected between 2013/12/01 and 2018/06/30 ; data collected between ulipristal acetate prescription until the term of pregnancy or embryo transfer failure (up to 4) or death/lost to follow up or ART treatment discontinuation

Exclusion Criteria:

none

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical pregnancy	Clinical pregnancy rate after maximum 4 embryos transferred by IVF/ICSI procedures ; pregnancy is defined by beta-hCG> 1000 or presence of a gestation sac	15 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Spontaneous pregnancy	Spontaneous pregnancy rate before first embryo transferred by IVF/ICSI procedures; pregnancy is defined by beta-hCG > 1000 or presence of a gestation sac	at least 2 months
Live birth / miscarriage	Live birth rate / miscarriage rate	9 months
Fibroids size	Fibroids size reduction	Baseline (before ulipristal acetate administration) and 20 months
Surgery rate	Rate of surgery	3 months
Surgery description	Description of the surgery type and surgery indication	3 months
Description of ulipristal acetate prescription	Reasons of the prescription, type of fibroids concerned, number of cycles of treatment, treatment duration	20 months
Safety impact on ulipristal acetate administration	Review of adverse drug reactions resulting in ulipristal acetate treatment modification or discontinuation	20 months
Ulipristal acetate safety analysis in infertile women with fibroids	Review of all serious adverse reactions (expected or unexpected) in this population	20 months

Collaborators and Investigators

• Sponsor: ASSOCIATION POUR LE DEVELOPPEMENT EN FECONDATION IN VITRO
• Collaborators: Gedeon Richter Plc.
• Investigators: Principal Investigator: Catherine RONGIERES, MD, ADEFIV & University Hospitals of Strasbourg

Study record dates

Study Major Dates

• Study Start (Actual): December 29, 2017
• Primary Completion (Actual): June 30, 2018
• Study Completion (Actual): January 8, 2019

Study Registration Dates

• First Submitted: November 10, 2017
• First Submitted That Met QC Criteria: November 16, 2017
• First Posted (Actual): November 21, 2017

Study Record Updates

• Last Update Posted (Actual): January 9, 2019
• Last Update Submitted That Met QC Criteria: January 8, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Connective Tissue Diseases; Neoplasms, Connective Tissue; Neoplasms, Muscle Tissue; Infertility; Infertility, Female; Leiomyoma; Myofibroma; Physiological Effects of Drugs; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Ulipristal acetate
• Other Study ID Numbers: 0001 (Cancer Research Institute)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No