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PregnancyPhase 3ProLISNCT07613528

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

A Phase 3 study testing Progesterone Injectable and Progesterone Vaginal Suppository in people with Pregnancy and Progesterone Supplementation, run by University Hospital, Montpellier at 1 site in France.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
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Trial summary

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. . Read more about this study

Who is it for?
Ages 18 to 37 years, women only
What is being tested?
Progesterone Injectable and Progesterone Vaginal Suppository
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
214 participants
Where
1 siteFrance
Study dates
Mar 2027to Sep 2030
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 37 years
  • Women only
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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.

Who cannot join

  • 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;
Show all 13Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Noémie RANISAVLJEVIC, MD, PhD contact

+33467336481

n-ranisavljevic@chu-montpellier.fr

Tal ANAHORY, MD contact

+33467335955

t-anahory@chu-montpellier.fr

France1 site

  • CHU de Montpellier

    Montpellier, 34295

    Noémie RANISAVLJEVIC, MD, PhD, +33467336481, n-ranisavljevic@chu-montpellier.fr

Other trials in France

About this study

Official title: 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.

Read the detailed description

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.

Being tested
Progesterone Injectable, Placebo, Progesterone Vaginal Suppository
Keywords
luteal phase support, Serum progesterone level, individualized treatment, fresh embryo transfer, live birth rate

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Progesterone InjectableDrug

    Also called PROGIRON 25 mg, injectable solution

    One injection of PROGIRON® (25 mg pre-filled syringe) per day will be administered until 8 weeks of gestation (Day 1 to Day 42).

  • PlaceboDrug

    Also called PLACEBO, injectable solution

    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).

  • Progesterone Vaginal SuppositoryDrug

    Also called PROGESTAN 200 mg, vaginal soft capsule

    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.

Study groups in NCT07613528
Study groupRoleWhat they receive
Control groupPlacebo comparatorDiscontinuation 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).
Receives: Drug: Placebo; Drug: Progesterone Vaginal Suppository
Experimental groupExperimentalProlonged 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).
Receives: Drug: Progesterone Injectable; Drug: Progesterone Vaginal Suppository

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Live birth rate

    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.

    Measured: At postpartum follow-up (Visit 4: Month 9 ±1 month)

Secondary outcomes (8)

  1. Clinical pregnancy rate

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

    Multiple gestational sacs in one participant will be counted as one clinical pregnancy

    Measured: At first trimester follow-up (Visit 3: Week 12-14 of gestation)

  2. Ongoing pregnancy rate

    Defined as a viable intrauterine pregnancy at ≥12 weeks of gestation.

    Measured: At first trimester follow-up (Visit 3: Week 12-14 of gestation)

  3. Miscarriage rate

    Defined as spontaneous pregnancy loss before 20 weeks of gestation, including early pregnancy loss (<12 weeks) and late pregnancy loss (12-20 weeks).

    Measured: From inclusion (Visit 1: positive pregnancy test or the following day) to 20 weeks of gestation

  4. Incidence of treatment-related adverse events

    Incidence of adverse events reported during the intervention period.

    Measured: From inclusion (Visit 1: positive pregnancy test or the following day) to follow-up (Visit 2: Week 6-7 after test +)

  5. Incidence of obstetrical and neonatal complications

    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.

    Measured: At postpartum follow-up (Visit 4: Month 9 ±1 month)

  6. Birth weight

    Weight of the newborn at delivery.

    Measured: At postpartum follow-up (Visit 4: Month 9 ±1 month)

  7. Gestational age at delivery

    Gestational age in weeks at the time of delivery.

    Measured: At postpartum follow-up (Visit 4: Month 9 ±1 month)

  8. Incremental cost-effectiveness ratio (ICER)

    Cost-effectiveness analysis comparing prolonged subcutaneous progesterone versus placebo, with effectiveness defined by live birth rate.

    Measured: From inclusion (Visit 1: Positive pregnancy test or the following day) to postpartum follow-up (Visit 4: Month 9 ±1 month)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 May 2026
  2. Study startMar 2027 (estimated)
  3. Primary completionSep 2029 (estimated)
  4. Study completionSep 2030 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Multicentric, prospective, controlled, double-blinded, superiority, randomized trial in 2 parallel groups: injections of a placebo or injections of subcutaneous progesterone.
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
214 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07613528
Sponsor's protocol ID
RECHMPL_25_0581
Other IDs
2026-525452-28-00
Acronym
ProLIS
Status last verified
May 2026
First submitted
21 May 2026
Last updated
2 Jun 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Eijkemans MJC, Kersten FAM, Lintsen AME, Hunault CC, Bouwmans CAM, Roijen LH, Habbema JDF, Braat DDM. Cost-effectiveness of 'immediate IVF' versus 'delayed IVF': a prospective study. Hum Reprod. 2017 May 1;32(5):999-1008. doi: 10.1093/humrep/dex018.

    PubMed 28204519

  • Aslih N, Ellenbogen A, Shavit T, Michaeli M, Yakobi D, Shalom-Paz E. Can we alter pregnancy outcome by adjusting progesterone treatment at mid-luteal phase: a randomized controlled trial. Gynecol Endocrinol. 2017 Aug;33(8):602-606. doi: 10.1080/09513590.2017.1298742. Epub 2017 Mar 9.

    PubMed 28277886

  • Cedrin-Durnerin I, Bstandig B, Herve F, Wolf J, Uzan M, Hugues J. A comparative study of high fixed-dose and decremental-dose regimens of gonadotropins in a minidose gonadotropin-releasing hormone agonist flare protocol for poor responders. Fertil Steril. 2000 May;73(5):1055-6. doi: 10.1016/s0015-0282(00)00471-4. No abstract available.

    PubMed 10785239

  • Cozzolino M, Hervas I, Ergun Y, Massaro MG, Pellicer N, de Angelis F, Labarta E, Galliano D. Higher serum progesterone level has no negative impact on live birth rate in frozen embryo transfer. Eur J Obstet Gynecol Reprod Biol. 2024 Dec;303:15-21. doi: 10.1016/j.ejogrb.2024.10.011. Epub 2024 Oct 9.

    PubMed 39395245

  • Duport Percier M, Brouillet S, Mollevi C, Duraes M, Anahory T, Ranisavljevic N. Serum progesterone concentration on pregnancy test day might predict ongoing pregnancy after controlled ovarian stimulation and fresh embryo transfer. Front Endocrinol (Lausanne). 2023 Jun 26;14:1191648. doi: 10.3389/fendo.2023.1191648. eCollection 2023.

    PubMed 37455896

  • Griesinger G. Editorial commentary: is it time to abandon progesterone supplementation of early pregnancy after IVF? Hum Reprod. 2011 May;26(5):1017-9. doi: 10.1093/humrep/der013. Epub 2011 Feb 4. No abstract available.

    PubMed 21296804

  • Ioannidis G, Sacks G, Reddy N, Seyani L, Margara R, Lavery S, Trew G. Day 14 maternal serum progesterone levels predict pregnancy outcome in IVF/ICSI treatment cycles: a prospective study. Hum Reprod. 2005 Mar;20(3):741-6. doi: 10.1093/humrep/deh644. Epub 2004 Dec 9.

    PubMed 15591085

  • Kawachiya S, Bodri D, Hirosawa T, Yao Serna J, Kuwahara A, Irahara M. Endogenous progesterone levels could predict reproductive outcome in frozen embryo replacement cycles supplemented with synthetic progestogens: A retrospective cohort study. Reprod Med Biol. 2018 Nov 1;18(1):91-96. doi: 10.1002/rmb2.12254. eCollection 2019 Jan.

    PubMed 30655726

  • Kawwass JF, Kulkarni AD, Hipp HS, Crawford S, Kissin DM, Jamieson DJ. Extremities of body mass index and their association with pregnancy outcomes in women undergoing in vitro fertilization in the United States. Fertil Steril. 2016 Dec;106(7):1742-1750. doi: 10.1016/j.fertnstert.2016.08.028. Epub 2016 Sep 22.

    PubMed 27666564

  • Levy T, Yairi Y, Bar-Hava I, Shalev J, Orvieto R, Ben-Rafael Z. Pharmacokinetics of the progesterone-containing vaginal tablet and its use in assisted reproduction. Steroids. 2000 Oct-Nov;65(10-11):645-9. doi: 10.1016/s0039-128x(00)00121-5.

    PubMed 11108871

  • Melo P, Chung Y, Pickering O, Price MJ, Fishel S, Khairy M, Kingsland C, Lowe P, Petsas G, Rajkhowa M, Sephton V, Tozer A, Wood S, Labarta E, Wilcox M, Devall A, Gallos I, Coomarasamy A. Serum luteal phase progesterone in women undergoing frozen embryo transfer in assisted conception: a systematic review and meta-analysis. Fertil Steril. 2021 Dec;116(6):1534-1556. doi: 10.1016/j.fertnstert.2021.07.002. Epub 2021 Aug 10.

    PubMed 34384594

  • Petersen JF, Andersen AN, Klein BM, Helmgaard L, Arce JC. Luteal phase progesterone and oestradiol after ovarian stimulation: relation to response and prediction of pregnancy. Reprod Biomed Online. 2018 Apr;36(4):427-434. doi: 10.1016/j.rbmo.2017.12.019. Epub 2018 Jan 17.

    PubMed 29398418

  • Sator M, Radicioni M, Cometti B, Loprete L, Leuratti C, Schmidl D, Garhofer G. Pharmacokinetics and safety profile of a novel progesterone aqueous formulation administered by the s.c. route. Gynecol Endocrinol. 2013 Mar;29(3):205-8. doi: 10.3109/09513590.2012.736560. Epub 2012 Nov 6.

    PubMed 23127204

  • Segal L, Breyzman T, Kol S. Luteal phase support post IVF: individualized early stop. Reprod Biomed Online. 2015 Nov;31(5):633-7. doi: 10.1016/j.rbmo.2015.07.011. Epub 2015 Aug 10.

    PubMed 26371712

  • van der Linden M, Buckingham K, Farquhar C, Kremer JA, Metwally M. Luteal phase support for assisted reproduction cycles. Cochrane Database Syst Rev. 2015 Jul 7;2015(7):CD009154. doi: 10.1002/14651858.CD009154.pub3.

    PubMed 26148507

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Progesterone Injectable and Progesterone Vaginal Suppository in people with Pregnancy and Progesterone Supplementation, run by University Hospital, Montpellier at 1 site in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 2 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Noémie RANISAVLJEVIC, MD, PhD (+33467336481, n-ranisavljevic@chu-montpellier.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Live birth rate (time frame: At postpartum follow-up (Visit 4: Month 9 ±1 month)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07613528, which also lists 15 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jun 2026.

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