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Individualized Prolonged Luteal Support After Fresh Embryo Transfer in Women With Low Progesterone (ProLIS)

29 mei 2026 bijgewerkt door: University Hospital, Montpellier

Interest of Individualized Prolongation of Subcutaneous Luteal Phase Support up to 8 Weeks for Patients Pregnant After a Fresh Embryo Transfer and With Low Serum Progesterone Level at Pregnancy Test - a Multicentric Randomized Double Blinded Controlled Trial

The goal of this clinical trial is to compare live birth rate in a control group versus an interventional group in subjects aged 18 to 37, pregnant after a fresh embryo transfer and with a serum progesterone level below 17 ng/mL on the day of pregnancy test while using vaginal progesterone as a luteal support. .

This is the first randomized controlled trial to assess the benefit of prolonged subcutaneous progesterone administration in patients with a positive pregnancy test (Bêta chorionique gonadotropic hormone: β-hCG >100 IU/L) after fresh transfer and low progesterone level (<17 ng/mL).

Half the participants will be offered a an extension of luteal phase support , by subcutaneous progesterone supplementation for 6 weeks, the other half will have placebo injections. A double-blind, placebo-controlled, randomized design was chosen to prevent selection bias and ensure the comparability of both study arms.

Studie Overzicht

Toestand

Nog niet aan het werven

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

Introduction:

Progesterone is essential for implantation and early pregnancy maintenance. After ovarian stimulation for In vitro fertilization (IVF), luteal phase insufficiency may occur, requiring luteal phase support (LPS) with exogenous progesterone. Recent data suggest that patients with low serum progesterone levels (<17 ng/mL) at positive pregnancy test after fresh embryo transfer have lower live birth rates and higher miscarriage rates despite standard vaginal LPS.

Aim:

The primary objective of the study is to compare live birth rates between:

  • a control group receiving standard luteal phase support with vaginal progesterone until pregnancy test and placebo subcutaneous injections until 8 weeks of gestation, and
  • an intervention group receiving prolonged luteal phase support with subcutaneous progesterone until 8 weeks of gestation.

Secondary objectives include comparison of clinical pregnancy rate, ongoing pregnancy rate, miscarriage rate, treatment-related adverse events, obstetrical and neonatal outcomes, gestational age at delivery, birth weight, and cost-effectiveness of the individualized prolonged luteal support strategy.

An ancillary biological sub-study conducted at Montpellier University Hospital will assess serum 17-hydroxyprogesterone and estradiol levels at inclusion.

Methods:

This study is a phase III, multicenter, randomized, double-blind, placebo-controlled trial.

Women aged 18-37 years with positive pregnancy test (Bêta chorionique gonadotropic hormone: β-hCG >100 IU/L) and serum progesterone <17 ng/mL after fresh embryo transfer will be randomized (1:1) to receive either:

  • subcutaneous progesterone (PROGIRON®) for 6 weeks, or
  • matching placebo for 6 weeks. To ensure adequate progesterone exposure during treatment initiation, vaginal progesterone (PROGESTAN®) will be continued for the first 4 days after randomization in both groups.

Participants will be followed until delivery. A total of 214 participants will be enrolled across multiple In vitro fertilization (IVF) centers.

Studietype

Ingrijpend

Inschrijving (Geschat)

214

Fase

  • Fase 3

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studiecontact

Studie Contact Back-up

Studie Locaties

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

  • Volwassen

Accepteert gezonde vrijwilligers

Nee

Beschrijving

Inclusion Criteria:

  • Patient aged 18 to 37 year-old;
  • Patients with a BMI below 34 kg/m2;
  • After a fresh embryo transfer following an ovarian hyperstimulation for an IVF with a luteal phase support based on micronized vaginal progesterone;
  • With a positive pregnancy test (β-hCG > 100 UI/L);
  • With a serum progesterone level below 17 ng/mL on the day of pregnancy test;
  • Patient able to self-administer subcutaneous progesterone injections, either alone or with the help of her partner.

Exclusion Criteria:

  • Patient undertaking an additional source of progesterone (oral or injected) or a treatment stimulating endogenous progesterone secretion (such as Gonadotropin-Releasing Hormone: GnRH agonist, or chorionique gonadotropic hormone: hCG injections);
  • Patients with intolerance or contraindication to subcutaneous progesterone administration;
  • Patients with a known 21-hydroxylase deficiency;
  • Patients with uterine pathology or untreated hydrosalpinx;
  • Patients with a history of recurrent miscarriages (3 or more);
  • Patient undergoing pre-implantation genetic testing;
  • Patient unavailable or unwilling to participate in future visits or is unable to comply with trial protocol;
  • Subjects unable to read or/and write French;
  • Failure to obtain the consent;
  • Subjects non-beneficiary of the French social security (Government medical aid (AME) excluded);
  • Subjects placed under legal protection, under guardianship or under curatorship;
  • Patient in an exclusion period determined by a previous study;
  • Subjects participating in another interventional research.

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: Gerandomiseerd
  • Interventioneel model: Parallelle opdracht
  • Masker: Dubbele

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Placebo-vergelijker: Control group

Discontinuation of luteal phase support with a subcutaneous placebo daily until 8 weeks of gestation (for 6 weeks).

Vaginal progesterone will be continued for 4 days after placebo initiation. Apart from these 4 days of transition treatment, the patient will not receive any additional treatment for luteal phase support (discontinuation of progesterone soft capsule administration according to the center's standard practice).
Geneesmiddel: Placebo
One injection of PLACEBO (identical in appearance to the PROGIRON® pre-filled syringe) per day will be administered until 8 weeks of gestation (Day 1 to Day 42).
Andere namen:
  • PLACEBO, injectable solution
Geneesmiddel: Progesterone Vaginal Suppository
Vaginal progesterone treatment with PROGESTAN® (200 mg 3 times daily) will be continued for 4 days after initiation of the investigational medicinal product (Day 1 to Day 4), pending achievement of stable progesterone serum concentrations with injectable progesterone.
Andere namen:
  • PROGESTAN 200 mg, vaginal soft capsule
Experimenteel: Experimental group

Prolonged luteal phase support, switched to subcutaneous progesterone 25 mg daily until 8 weeks of gestation (for 6 weeks).

Vaginal progesterone will be continued for 4 days after subcutaneous progesterone initiation to ensure adequate serum levels while awaiting steady-state concentration of subcutaneous progesterone.

Apart from these 4 days of transition treatment, the patient will not receive any additional treatment for luteal phase support (discontinuation of progesterone soft capsule administration according to the center's standard practice).
Geneesmiddel: Progesterone Vaginal Suppository
Vaginal progesterone treatment with PROGESTAN® (200 mg 3 times daily) will be continued for 4 days after initiation of the investigational medicinal product (Day 1 to Day 4), pending achievement of stable progesterone serum concentrations with injectable progesterone.
Andere namen:
  • PROGESTAN 200 mg, vaginal soft capsule
Geneesmiddel: Progesterone Injectable
One injection of PROGIRON® (25 mg pre-filled syringe) per day will be administered until 8 weeks of gestation (Day 1 to Day 42).
Andere namen:
  • PROGIRON 25 mg, injectable solution

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Live birth rate
Tijdsspanne: At postpartum follow-up (Visit 4: Month 9 ±1 month)
Defined as a birth of at least one live born baby, weighing 500 g or more or 20 weeks or more of gestation, with the birth of twins counted as one live birth.
At postpartum follow-up (Visit 4: Month 9 ±1 month)

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Clinical pregnancy rate
Tijdsspanne: At first trimester follow-up (Visit 3: Week 12-14 of gestation)

Defined as ultrasound visualization of a gestational sac, excluding ectopic pregnancy.

Multiple gestational sacs in one participant will be counted as one clinical pregnancy
At first trimester follow-up (Visit 3: Week 12-14 of gestation)
Ongoing pregnancy rate
Tijdsspanne: At first trimester follow-up (Visit 3: Week 12-14 of gestation)
Defined as a viable intrauterine pregnancy at ≥12 weeks of gestation.
At first trimester follow-up (Visit 3: Week 12-14 of gestation)
Miscarriage rate
Tijdsspanne: From inclusion (Visit 1: positive pregnancy test or the following day) to 20 weeks of gestation
Defined as spontaneous pregnancy loss before 20 weeks of gestation, including early pregnancy loss (<12 weeks) and late pregnancy loss (12-20 weeks).
From inclusion (Visit 1: positive pregnancy test or the following day) to 20 weeks of gestation
Incidence of treatment-related adverse events
Tijdsspanne: From inclusion (Visit 1: positive pregnancy test or the following day) to follow-up (Visit 2: Week 6-7 after test +)
Incidence of adverse events reported during the intervention period.
From inclusion (Visit 1: positive pregnancy test or the following day) to follow-up (Visit 2: Week 6-7 after test +)
Incidence of obstetrical and neonatal complications
Tijdsspanne: At postpartum follow-up (Visit 4: Month 9 ±1 month)
Including premature rupture of membranes, preterm labor or delivery, fetal growth restriction, hypertensive disorders, pre-eclampsia, gestational diabetes, macrosomia, placental abnormalities, birth defects, stillbirth, perinatal death, and neonatal hospitalization.
At postpartum follow-up (Visit 4: Month 9 ±1 month)
Birth weight
Tijdsspanne: At postpartum follow-up (Visit 4: Month 9 ±1 month)
Weight of the newborn at delivery.
At postpartum follow-up (Visit 4: Month 9 ±1 month)
Gestational age at delivery
Tijdsspanne: At postpartum follow-up (Visit 4: Month 9 ±1 month)
Gestational age in weeks at the time of delivery.
At postpartum follow-up (Visit 4: Month 9 ±1 month)
Incremental cost-effectiveness ratio (ICER)
Tijdsspanne: From inclusion (Visit 1: Positive pregnancy test or the following day) to postpartum follow-up (Visit 4: Month 9 ±1 month)
Cost-effectiveness analysis comparing prolonged subcutaneous progesterone versus placebo, with effectiveness defined by live birth rate.
From inclusion (Visit 1: Positive pregnancy test or the following day) to postpartum follow-up (Visit 4: Month 9 ±1 month)

Andere uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Serum 17-hydroxyprogesterone level
Tijdsspanne: At inclusion (Visit 1: positive pregnancy test or the following day)
Sub-study objectives, only for participants from Montpellier University Hospital the serum levels of 17-hydroxy-progesterone (ng/mL) will be investigated on the day of inclusion.
At inclusion (Visit 1: positive pregnancy test or the following day)
Serum estradiol level
Tijdsspanne: At inclusion (Visit 1: positive pregnancy test or the following day)
Sub-study objectives, only for participants from Montpellier University Hospital the serum levels of estradiol (pg/mL) will be investigated on the day of inclusion.
At inclusion (Visit 1: positive pregnancy test or the following day)

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

University Hospital, Montpellier

Medewerkers

Hospices Civils de Lyon
Direction Générale de l'Offre de Soins
IBSA Institut Biochimique SA

Onderzoekers

  • Hoofdonderzoeker: Noémie RANISAVLJEVIC, MD, PhD, University Hospital, Montpellier
  • Studie stoel: Tal ANAHORY, MD, University Hospital, Montpellier

Publicaties en nuttige links

De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.

Algemene publicaties

Nuttige links

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Geschat)

1 maart 2027

Primaire voltooiing (Geschat)

1 september 2029

Studie voltooiing (Geschat)

1 september 2030

Studieregistratiedata

Eerst ingediend

21 mei 2026

Eerst ingediend dat voldeed aan de QC-criteria

21 mei 2026

Eerst geplaatst (Werkelijk)

29 mei 2026

Updates van studierecords

Laatste update geplaatst (Werkelijk)

2 juni 2026

Laatste update ingediend die voldeed aan QC-criteria

29 mei 2026

Laatst geverifieerd

1 mei 2026

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Andere studie-ID-nummers

  • RECHMPL_25_0581
  • 2026-525452-28-00 (Ctis)

Plan Individuele Deelnemersgegevens (IPD)

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NEE

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Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Nee

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Nee

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