NCT05899010

Brief Summary

This randomized trial was designed as non-inferiority trial aiming to compare ongoing pregnancy rates following LPS with 600 mg/day vs 800 mg/day vaginal VMP. All patients will undergo an artificial cycle frozen embryo transfer (AC-FET) with transdermal estradiol 6mg/day Patients undergoing an artificial cycle FET will start estrogen priming with transdermal estradiol 6mg/day (Estrogel®) on cycle D1-D3. Following 10-12 days of estrogen priming, patients will be randomized to luteal phase support with a standard formulation (200mg tid, Utrogestan®) or a new formulation (400mg bid) VMP. All patients will undergo a serum P measurement on the day before embryo transfer (ET). Patients with P\<10 ng/ml will receive a supplement of oral micronized progesterone 300mg, while patients with P≥10ng/ml will maintain the previous luteal phase support (LPS) protocol

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1,020

participants targeted

Target at P75+ for phase_3

Timeline
23mo left

Started Jul 2023

Longer than P75 for phase_3

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress60%
Jul 2023Apr 2028

First Submitted

Initial submission to the registry

June 1, 2023

Completed
11 days until next milestone

First Posted

Study publicly available on registry

June 12, 2023

Completed
23 days until next milestone

Study Start

First participant enrolled

July 5, 2023

Completed
3.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2027

Expected
10 months until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2028

Last Updated

March 30, 2026

Status Verified

March 1, 2026

Enrollment Period

3.9 years

First QC Date

June 1, 2023

Last Update Submit

March 25, 2026

Conditions

Infertility

Outcome Measures

Primary Outcomes (1)

  • Ongoing pregnancy rate

    A positive heart beat at ultrasound after 11-13 weeks of gestation

    7-9 weeks after embryo transfer

Secondary Outcomes (5)

  • Implantation rate

    3-4 weeks after embryo transfer

  • Biochemical pregnancy rate

    10 to 12 days after embryo transfer

  • Clinical pregnancy rate

    3-4 weeks after embryo transfer

  • Miscarriage rate

    before completion of 12 weeks of gestation

  • Frequency of adverse events

    Until 15 days after the end of treatment with progesterone

Study Arms (2)

Vaginal progesterone 600mg

ACTIVE COMPARATOR

Vaginal progesterone 600mg daily (200mg tid) will be started and maintained until 10 weeks of pregnancy or either up to menses or up to negative pregnancy test performed 10 days after ET

Drug: Vaginal progesterone 600mg daily

Vaginal progesterone 800mg

EXPERIMENTAL

Vaginal progesterone 800mg daily (400mg bid) will be started and maintained until 10 weeks of pregnancy or either up to menses or up to negative pregnancy test performed 10 days after ET.

Drug: Vaginal progesterone 800mg daily

Interventions

Vaginal progesterone 600mg dailyDRUG

If endometrial thickness (ETH) ≥7 mm and follicle dominance/ultrasound (US) signs of ovulation P levels are measured: if P ≤1.5 patients start LPS, else cycle is cancelled. If ETH \<7mm and no follicle dominance: estradiol dose is increased to 9mg/day and new US is performed up to 4 days after. If persistent thin endometrium after dose increase, cycle is cancelled. 24-48h pre ET, E2 and P are measured. in the morning, pre VMP dose, or at least 6h after last progesterone dose. If progesterone \<10ng/ml, additional 300mg daily oral micronized progesterone is administered on the day of the ET and maintained until 10 weeks pregnancy or up to menses or up to negative pregnancy test 10 days after ET. ET will be performed with available blastocysts 6 days after start of LPS. 3-5 days, after ET, a blood test for P measurement will be performed in the morning, before VMP dose, or at least 6h after last progesterone dose. 10 days after ET, the last P test will be done with pregnancy test.

Vaginal progesterone 600mg
Vaginal progesterone 800mg dailyDRUG

If endometrial thickness (ETH) ≥7 mm and follicle dominance/ultrasound (US) signs of ovulation P levels are measured: if P ≤1.5 patients start LPS, else cycle is cancelled. If ETH \<7mm and no follicle dominance: estradiol dose is increased to 9mg/day and new US is performed up to 4 days after. If persistent thin endometrium after dose increase, cycle is cancelled. 24-48h pre ET, E2 and P are measured. in the morning, pre VMP dose, or at least 6h after last progesterone dose. If progesterone \<10ng/ml, additional 300mg daily oral micronized progesterone is administered on the day of the ET and maintained until 10 weeks pregnancy or up to menses or up to negative pregnancy test 10 days after ET. ET will be performed with available blastocysts 6 days after start of LPS. 3-5 days, after ET, a blood test for P measurement will be performed in the morning, before VMP dose, or at least 6h after last progesterone dose. 10 days after ET, the last P test will be done with pregnancy test.

Vaginal progesterone 800mg

Eligibility Criteria

Age18 Years - 50 Years
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • Endometrial preparation with hormone replacement therapy
  • Age 18-43 years following an autologous IVF cycle (with or without preimplantation genetic testing for aneuploidy)
  • Age \< 50 years following an egg donation cycle
  • BMI \> 18 and \< 30 kg/m2
  • blastocyst embryo transfer
  • Willing to participate in the study
  • Able to come to the Center to comply with the procedures of the study: blood tests, appointments and drug dispensation.
  • Exlusion Criteria:
  • Uterine diseases (e.g. submucosal fibroids, polyps, previously diagnosed Müllerian abnormalities)
  • Hydrosalpinx
  • Recurrent pregnancy loss (≥ 3 previous miscarriages)
  • Recurrent implantation failure (≥ 3 previously failed embryo transfers of good-quality blastocysts)
  • Allergy to study medication
  • Pregnancy or lactation
  • Contraindication for hormonal treatment
  • +2 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Hospital Universitario Quiron Dexeus

Barcelona, 08028, Spain

RECRUITING

Related Publications (12)

  • De Geyter C, Calhaz-Jorge C, Kupka MS, Wyns C, Mocanu E, Motrenko T, Scaravelli G, Smeenk J, Vidakovic S, Goossens V; European IVF-monitoring Consortium (EIM) for the European Society of Human Reproduction and Embryology (ESHRE). ART in Europe, 2015: results generated from European registries by ESHRE. Hum Reprod Open. 2020 Feb 24;2020(1):hoz038. doi: 10.1093/hropen/hoz038. eCollection 2020.

    PMID: 32123753BACKGROUND

  • Devroey P, Polyzos NP, Blockeel C. An OHSS-Free Clinic by segmentation of IVF treatment. Hum Reprod. 2011 Oct;26(10):2593-7. doi: 10.1093/humrep/der251. Epub 2011 Aug 9.

    PMID: 21828116BACKGROUND

  • Rienzi L, Gracia C, Maggiulli R, LaBarbera AR, Kaser DJ, Ubaldi FM, Vanderpoel S, Racowsky C. Oocyte, embryo and blastocyst cryopreservation in ART: systematic review and meta-analysis comparing slow-freezing versus vitrification to produce evidence for the development of global guidance. Hum Reprod Update. 2017 Mar 1;23(2):139-155. doi: 10.1093/humupd/dmw038.

    PMID: 27827818BACKGROUND

  • Shi Y, Sun Y, Hao C, Zhang H, Wei D, Zhang Y, Zhu Y, Deng X, Qi X, Li H, Ma X, Ren H, Wang Y, Zhang D, Wang B, Liu F, Wu Q, Wang Z, Bai H, Li Y, Zhou Y, Sun M, Liu H, Li J, Zhang L, Chen X, Zhang S, Sun X, Legro RS, Chen ZJ. Transfer of Fresh versus Frozen Embryos in Ovulatory Women. N Engl J Med. 2018 Jan 11;378(2):126-136. doi: 10.1056/NEJMoa1705334.

    PMID: 29320646BACKGROUND

  • Wei D, Liu JY, Sun Y, Shi Y, Zhang B, Liu JQ, Tan J, Liang X, Cao Y, Wang Z, Qin Y, Zhao H, Zhou Y, Ren H, Hao G, Ling X, Zhao J, Zhang Y, Qi X, Zhang L, Deng X, Chen X, Zhu Y, Wang X, Tian LF, Lv Q, Ma X, Zhang H, Legro RS, Chen ZJ. Frozen versus fresh single blastocyst transfer in ovulatory women: a multicentre, randomised controlled trial. Lancet. 2019 Mar 30;393(10178):1310-1318. doi: 10.1016/S0140-6736(18)32843-5. Epub 2019 Feb 28.

    PMID: 30827784BACKGROUND

  • Roque M, Haahr T, Geber S, Esteves SC, Humaidan P. Fresh versus elective frozen embryo transfer in IVF/ICSI cycles: a systematic review and meta-analysis of reproductive outcomes. Hum Reprod Update. 2019 Jan 1;25(1):2-14. doi: 10.1093/humupd/dmy033.

    PMID: 30388233BACKGROUND

  • Groenewoud ER, Cohlen BJ, Al-Oraiby A, Brinkhuis EA, Broekmans FJ, de Bruin JP, van den Dool G, Fleisher K, Friederich J, Goddijn M, Hoek A, Hoozemans DA, Kaaijk EM, Koks CA, Laven JS, van der Linden PJ, Manger AP, Slappendel E, Spinder T, Kollen BJ, Macklon NS. A randomized controlled, non-inferiority trial of modified natural versus artificial cycle for cryo-thawed embryo transfer. Hum Reprod. 2016 Jul;31(7):1483-92. doi: 10.1093/humrep/dew120. Epub 2016 May 13.

    PMID: 27179265BACKGROUND

  • Ghobara T, Gelbaya TA, Ayeleke RO. Cycle regimens for frozen-thawed embryo transfer. Cochrane Database Syst Rev. 2017 Jul 5;7(7):CD003414. doi: 10.1002/14651858.CD003414.pub3.

    PMID: 28675921BACKGROUND

  • Groenewoud ER, Cohlen BJ, Macklon NS. Programming the endometrium for deferred transfer of cryopreserved embryos: hormone replacement versus modified natural cycles. Fertil Steril. 2018 May;109(5):768-774. doi: 10.1016/j.fertnstert.2018.02.135.

    PMID: 29778369BACKGROUND

  • Vaisbuch E, de Ziegler D, Leong M, Weissman A, Shoham Z. Luteal-phase support in assisted reproduction treatment: real-life practices reported worldwide by an updated website-based survey. Reprod Biomed Online. 2014 Mar;28(3):330-5. doi: 10.1016/j.rbmo.2013.10.022. Epub 2013 Nov 14.

    PMID: 24447959BACKGROUND

  • Nawroth F, Ludwig M. What is the 'ideal' duration of progesterone supplementation before the transfer of cryopreserved-thawed embryos in estrogen/progesterone replacement protocols? Hum Reprod. 2005 May;20(5):1127-34. doi: 10.1093/humrep/deh762. Epub 2005 Feb 3.

    PMID: 15695314BACKGROUND

  • Griesinger G, Blockeel C, Sukhikh GT, Patki A, Dhorepatil B, Yang DZ, Chen ZJ, Kahler E, Pexman-Fieth C, Tournaye H. Oral dydrogesterone versus intravaginal micronized progesterone gel for luteal phase support in IVF: a randomized clinical trial. Hum Reprod. 2018 Dec 1;33(12):2212-2221. doi: 10.1093/humrep/dey306.

    PMID: 30304457BACKGROUND

Related Links

MeSH Terms

Conditions

Infertility

Condition Hierarchy (Ancestors)

Genital DiseasesUrogenital Diseases

Study Officials

  • Nikolaos P Polyzos, MD, PhD

    Service of Reproductive Medicine Dexeus University Hospital

    STUDY CHAIR

  • Noemie Sachs-Guedj, MD

    Service of Reproductive Medicine Dexeus University Hospital

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Nikolaos P Polyzos, MD, PhD

CONTACT

0034932274700nikpol@dexeus.com

Ignacio Rodríguez, MSc

CONTACT

0034932274700nacrod@dexeus.com

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 1, 2023

First Posted

June 12, 2023

Study Start

July 5, 2023

Primary Completion (Estimated)

June 1, 2027

Study Completion (Estimated)

April 1, 2028

Last Updated

March 30, 2026

Record last verified: 2026-03

Locations

ES(1)