Ovulation induction and luteal phase support with GnRH agonists in in vitro fertilization

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Patients

Age range

18-64 years

Gender

Female

Therapeutic area

Phenomena and Processes [G] - Biological Phenomena [G16]

Trial duration

27 Jun 2024 → ongoing

Decision date (initial)

2023-10-17

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

French Health Ministry

External identifiers

EU CT number

2023-505126-34-00

ClinicalTrials.gov

NCT06150703

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

Demonstrate an increase in the rate of live births after 22 weeks' amenorrhea (SA) per cycle with GnRH agonist induction and support compared with the reference protocol combining hCG induction and luteal support with exogenous vaginal progesterone.

Secondary objectives 11

1. Demonstrate improved embryo implantation rate with GnRH agonist induction and support versus hCG induction and luteal support with exogenous vaginal progesterone
2. Demonstrate an improvement in the rate of early pregnancy between induction and GnRH agonist support versus induction with hCG and luteal support with vaginal exogenous progesterone
3. Demonstrate improvement in clinical pregnancy rate between induction and GnRH agonist support versus hCG induction and luteal support with exogenous vaginal progesterone
4. Demonstrate a decrease in the rate of miscarriage per incipient pregnancy between induction and GnRH agonist support versus induction with hCG and luteal support with vaginal exogenous progesterone
5. Demonstrate an increase in the rate of progressive pregnancy at 12 weeks' amenorrhea (12 SA) per cycle with GnRH agonist induction and support compared with the reference protocol combining hCG induction and luteal support with exogenous vaginal progesterone
6. Compare the impact on obstetrical data of induction and support with GnRH agonist versus induction with hCG and luteal support with exogenous vaginal progesterone
7. Demonstrate a decrease in the rate of moderate to severe ovarian hyperstimulation syndrome, both early and late, with GnRH agonist induction and support versus hCG induction and luteal support with vaginal exogenous progesterone
8. To compare the evolution of corpora lutea in the luteal phase between initiation and support by GnRH agonist versus initiation by hCG and luteal support by exogenous vaginal progesterone
9. Evaluate the association of progesterone, estradiol, LH and hCG levels with pregnancies and miscarriages throughout follow-up between induction and GnRH agonist support, and induction by hCG and luteal support by vaginal exogenous progesterone
10. Evaluate side effects between induction and GnRH agonist support versus induction with hCG and luteal support with vaginal exogenous progesterone
11. Compare embryonic development between triggering and support by GnRH agonist versus triggering by hCG and luteal support by exogenous vaginal progesterone.

Conditions and MedDRA coding

IVF (In vitro fertilization) or ICSI (intracytoplasmic sperm injection) protocol with embryo transfer planned on the same cycle.

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Patients requiring conventional IVF or IVF with sperm injection (ICSI) from a partner or donor under the conditions defined by French law, after agreement by a multidisciplinary consultation meeting
2. Patients aged 18 to 39 included
3. First, second or third attempt at IVF or ICSI for a pregnancy
4. BMI < 35 kg/m2
5. AMH > 1 ng/ml (= 7 pmol/L) and/or antral follicle count ≥ 8 in the assessment in the year before inclusion
6. AMH <5 ng/ml and/or antral follicle count <40 in the year before inclusion
7. Antagonist protocol (programmed or not)
8. Treatment with daily recombinant FSH
9. Initial dose of daily recombinant FSH between 75 and 450 IU or 5 à 30 µg
10. Signed informed consent
11. Social security affiliation (excluding AME)

Exclusion criteria 22

1. Patient with HIV
2. Current participation in another therapeutic interventional trial on the day of inclusion
3. Patients who do not speak or understand French
4. ICSI with sperm from testicular biopsy
5. Pre-implantation diagnosis
6. Hypogonadotropic hypogonadism (amenorrhea or spaniomenorrhea with basal LH <1.2 IU/L)
7. History of severe ovarian hyperstimulation syndrome (OHSS)
8. Unoperated hydrosalpinx
9. Intracavitary polyps or myomas deforming the cavity
10. Known hypersensitivity to the investigational drugs and/or their excipients (human chorionic gonadotropin, progesterone, nafarelin acetate, GnRH, GnRH analogues, mannitol, sodium chloride, water for injection, glacial acetic acid, sodium hydroxide and/or hydrochloric acid, sorbitol, purified water, benzalkonium chloride, sunflower oil, soy lecithin, gelatin, glycerol, titanium dioxide (E171), methionine, poloxamer 18, phosphoric acid)
11. Gynaecological bleeding or genital haemorrhage
12. Tumors of the hypothalamus or pituitary gland
13. Impaired renal function
14. Major characterized depressive episode in progress
15. Ovarian hypertrophy or cysts unrelated to polycystic ovary syndrome
16. Severe adenomyosis requiring a long protocol
17. Carcinoma of the ovary, uterus or breast
18. Progressive thromboembolic events
19. Severe impairment of liver function
20. Breast-feeding women
21. Patients under safeguard of justice, guardianship or curatorship
22. History of epilepsy and/or intracranial tumors potentially causing epilepsy

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Live birth, defined as the presence of a live birth after 22 weeks. Twin pregnancies will be counted as one birth.

Secondary endpoints 11

1. 1. Embryo implantation defined by the presence of a gestational sac visible on the first ultrasound (5-8 weeks)
2. 2. Early pregnancy defined by the presence of an hCG level > 10 IU/ml 14 days after oocyte retrieval.
3. 3. Clinical pregnancy, defined by the presence of an intrauterine gestational sac with embryo showing cardiac activity on ultrasound for 5-10 SA
4. 4. Miscarriage before 12 weeks, defined by the cessation of development of an early pregnancy before 12 weeks. An early pregnancy is defined as having an hCG level > 10 IU/ml 14 days after oocyte retrieval.
5. 5. Ongoing pregnancy, defined as the presence of an intrauterine sac with an embryo with cardiac activity visible on ultrasound between 11 WA and 13 WA + 6 days (first trimester ultrasound of pregnancy).
6. 6. Pregnancy hypertension and its term of onset, pre-eclampsia and its term of onset, gestational diabetes and its term of onset, term and mode of delivery, medical termination of pregnancy, late miscarriage (between 12 and 22 SA), fetal death in utero
7. 7. Ovarian hyperstimulation syndrome defined as the presence of a moderate to severe syndrome, early and late. Early defined as the period before D10 post puncture and late defined as OHSS linked to pregnancy, according to the ABM reference system.
8. 8. Level of progesterone, estradiol, LH and hCG on the day of the puncture and on D7 post puncture
9. 9. Progesterone, estradiol, LH and hCG levels during follow-up, presence of pregnancy and presence of miscarriage
10. 10. All adverse events up to delivery
11. Number of oocytes collected, number of mature oocytes, number of fertilized oocytes, number of embryos on the second day of development, number of blastocysts obtained, number of blastocysts transferred, number of blastocysts frozen

Investigational products

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

Test 2

Comparator 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Dr Maëliss PEIGNÉ

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Dr Maëliss PEIGNÉ

Locations

1 EU/EEA country · 8 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 21 files

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

Application history

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