NCT03795220

Brief Summary

The increasing use of FET emphasizes the importance of preparing and timing the endometrium in FET cycles, however there is no consensus on luteal phase progesterone supplementation in mNC-FET and the optimal day of blastocyst warming and transfer. The aim of this multicenter RCT is to assess the effect of progesterone supplementation in hCG-triggered mNC-FET and the effect of embryo thawing and transfer at hCG+6 or hCG+7 days, respectively. In total 604 patients will be included with n=151 in each of the four study arms. The primary outcome is live birth rate per transfer (LBR) and the goal is to show a 10% increase in LBR after progesterone supplementation and to assess whether blastocyst warming+transfer 6 days after hCG trigger is superior to 7 days after hCG trigger in mNC-FET.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
679

participants targeted

Target at P75+ for phase_4

Timeline
Completed

Started Jan 2019

Longer than P75 for phase_4

Geographic Reach
1 country

1 active site

Status
completed

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

First Submitted

Initial submission to the registry

December 4, 2018

Completed
1 month until next milestone

Study Start

First participant enrolled

January 6, 2019

Completed
1 day until next milestone

First Posted

Study publicly available on registry

January 7, 2019

Completed
6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2024

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2024

Completed
Last Updated

May 15, 2025

Status Verified

February 1, 2024

Enrollment Period

6 years

First QC Date

December 4, 2018

Last Update Submit

May 12, 2025

Conditions

Infertility

Outcome Measures

Primary Outcomes (1)

  • Live birth rates per transfer

    Comparison of live birth rates between patients receiving and not receiving Lutinus, with blastocyst warming and transfer day 6 or 7 after hCG trigger.

    Registered at the one-year follow-up after a positive pregnancy test.

Secondary Outcomes (17)

  • Chemical pregnancy rates per transfer

    Measured 16 days after ovulation trigger (hCG+16).

  • Clinical pregnancy rates per transfer

    Ultrasound performed at 7-8 weeks of gestation.

  • Abortion rates per transfer

    Registered at the one-year follow-up after a positive pregnancy test.

  • ASAT (U/L)

    Measured at baseline.

  • ALAT (U/L)

    Measured at baseline.

  • +12 more secondary outcomes

Study Arms (4)

Vaginal progesterone + transfer 6. day

ACTIVE COMPARATOR

Lutinus + blastocyst warming and transfer 6 days after hCG trigger

Drug: Lutinus + transfer day 6

Vaginal progesterone + transfer 7. day

ACTIVE COMPARATOR

Lutinus + blastocyst warming and transfer 7 days after hCG trigger

Drug: Lutinus + transfer day 7

No progesterone + transfer 6. day

ACTIVE COMPARATOR

No Lutinus + blastocyst warming and transfer 6 days after hCG trigger

Drug: No Lutinus + transfer day 6

No progesterone + transfer 7. day

ACTIVE COMPARATOR

No Lutinus + blastocyst warming and transfer 7 days after hCG trigger

Drug: No Lutinus + transfer day 7

Interventions

Lutinus + transfer day 6DRUG

Four parallel groups of patients undergoing fertility treatment (modified natural cycle frozen embryo transfer) will be compared using/not using vaginal progesterone (Lutinus) and subject to blastocyst warming and transfer 6/7 days after hCG trigger.

Also known as: Lutinus
Vaginal progesterone + transfer 6. day
Lutinus + transfer day 7DRUG

Four parallel groups of patients undergoing fertility treatment (modified natural cycle frozen embryo transfer) will be compared using/not using vaginal progesterone (Lutinus) and subject to blastocyst warming and transfer 6/7 days after hCG trigger.

Also known as: Lutinus
Vaginal progesterone + transfer 7. day
No Lutinus + transfer day 6DRUG

Four parallel groups of patients undergoing fertility treatment (modified natural cycle frozen embryo transfer) will be compared using/not using vaginal progesterone (Lutinus) and subject to blastocyst warming and transfer 6/7 days after hCG trigger.

No progesterone + transfer 6. day
No Lutinus + transfer day 7DRUG

Four parallel groups of patients undergoing fertility treatment (modified natural cycle frozen embryo transfer) will be compared using/not using vaginal progesterone (Lutinus) and subject to blastocyst warming and transfer 6/7 days after hCG trigger.

No progesterone + transfer 7. day

Eligibility Criteria

Age18 Years - 41 Years
Sexfemale(Gender-based eligibility)
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • Female age 18-41 years, regular menstrual cycle (23-35 days), vitrified blastocysts derived from 1.-3. IVF/ICSI cycle in a public hospital and undergoing single blastocyst transfer.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Fertility Clinic, Rigshospitalet, Copenhagen University Hospital

Copenhagen, 2100, Denmark

Location

Related Publications (3)

  • Saupstad M, Colombo C, Bergenheim SJ, Pistoljevic-Kristiansen N, Dam TV, Bogstad JW, Praetorius L, Freiesleben NC, Klajnbard A, Oxlund-Mariegaard B, Humaidan P, Lokkegaard ECL, Husth M, Knudsen UB, Gabrielsen A, Forman JL, Petersen MR, Lossl K, Pinborg A. Optimizing the protocol for modified natural cycle frozen embryo transfer (mNC-FET): a multicentre, single-blinded randomized controlled trial. Hum Reprod Open. 2026 Jan 13;2026(1):hoag003. doi: 10.1093/hropen/hoag003. eCollection 2026.

    PMID: 41640422DERIVED

  • Colombo C, Pistoljevic-Kristiansen N, Saupstad M, Bergenheim SJ, Spangmose AL, Klajnbard A, la Cour Freiesleben N, Lokkegaard EC, Englund AL, Husth M, Breth Knudsen U, Alsbjerg B, Praetorius L, Lossl K, Schmidt L, Pinborg A. Does luteal phase progesterone supplementation affect physical and psychosocial well-being among women undergoing modified natural cycle-FET? A sub-study of a randomized controlled trial. Hum Reprod. 2023 Oct 3;38(10):1970-1980. doi: 10.1093/humrep/dead171.

    PMID: 37634089DERIVED

  • Saupstad M, Freiesleben NC, Skouby SO, Andersen LF, Knudsen UB, Petersen KB, Husth M, Egeberg A, Petersen MR, Ziebe S, Andersen AN, Lossl K, Pinborg A. Preparation of the endometrium and timing of blastocyst transfer in modified natural cycle frozen-thawed embryo transfers (mNC-FET): a study protocol for a randomised controlled multicentre trial. BMJ Open. 2019 Dec 15;9(12):e031811. doi: 10.1136/bmjopen-2019-031811.

    PMID: 31843833DERIVED

MeSH Terms

Conditions

Infertility

Condition Hierarchy (Ancestors)

Genital DiseasesUrogenital Diseases

Study Officials

  • Anja B. Pinborg, Prof., DMSC

    Rigshospitalet, Denmark

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
INVESTIGATOR
Masking Details
The study is a single blinded study; therefore, the study medication will be blinded for the treating doctors, but not for the patients, the non-treating doctors or the study nurses. Patients will only be seen by a treating doctor at the day of blastocyst transfer and at the day of the pregnancy scan. The participants will not take progesterone the morning of the blastocyst transfer, but immediately after to keep the treating doctors blinded. Patients will be instructed in not disclosing their study group to the treating doctor.
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: Randomized, controlled multicenter trial with inclusion of 604 mNC-FET cycles. We will include 604 patients divided 1:1 (302:302) in each arm +/- progesterone supplementation and these will further be divided 1:1 in blastocyst warming and transfer +6 and +7 days after hCG injection. Patients randomised to progesterone supplementation will start administering medicine four days after the ovulation trigger up til the day of the pregnancy test. If the pregnancy test is positive, medication will continue for 30 days more.
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Professor, chief consultant, DMSC

Study Record Dates

First Submitted

December 4, 2018

First Posted

January 7, 2019

Study Start

January 6, 2019

Primary Completion

December 31, 2024

Study Completion

December 31, 2024

Last Updated

May 15, 2025

Record last verified: 2024-02

Data Sharing

IPD Sharing
Will share

On request the study protocol and deidentified individual study data collected during the trial, including stored biobank samples, can be shared with research groups with relevant aims and a methodologically sound proposal. Approvals by necessary ethic committees and the Danish Data Protection Agency will be needed before sharing of data. All costs for data sharing will be covered by the party requesting the data. Data cannot be shared with groups working on research projects with the same aims, secondary aims or purposes. Further no data can be shared until 3 months after publication of first papers on the primary and secondary outcomes in this study. Biobank samples cannot be shared with research groups outside Denmark. Proposals of data sharing should be directed to anja.bisgaard.pinborg@regionh.dk. To gain access, data requestors will need to sign a data sharing agreement.

Shared Documents
STUDY PROTOCOL
Time Frame
Data will be available from 3 months after publication of first papers on the primary and secondary outcomes in this study.
Access Criteria
Approvals by necessary relevant ethic committees and the Danish Data Protection Agency will be needed before sharing of data. All costs for data sharing will be covered by the party requesting the data. Data cannot be shared with groups working on research projects with the same aims, secondary aims or purposes. Biobank samples cannot be shared with research groups outside Denmark.

Locations

DK(1)