Progesterone Supplementation After Letrozole-stimulated Insemination (LIFT)

Luteal Phase Support Following Letrozole Treatment in Women Undergoing Intrauterine Insemination: a Multicenter Randomized Trial

This trial aims to investigate whether luteal phase support improves the chance of pregnancy in women undergoing intrauterine insemination (IUI) following ovarian stimulation with letrozole.

In this randomized clinical trial, 690 women undergoing letrozole-stimulated IUI at four public fertility clinics in Denmark will be randomly allocated to one of two groups:

• Vaginal progesterone from the day after insemination (Cyclogest 400 mg twice daily)
• No luteal phase support, reflecting current clinical practice

All participants will undergo a standard letrozole-stimulated IUI treatment, including ultrasound monitoring, ovulation triggering, and insemination. Blood samples will be collected on the day of insemination and 7-9 days after insemination to measure hormone levels.

The results of this trial will provide further insight into the role of progesterone support in letrozole-stimulated IUI cycles.

Study Overview

• Status: Not yet recruiting
• Conditions: Infertility
• Intervention / Treatment: Drug: Progesterone

• Study Type: Interventional
• Enrollment (Estimated): 690
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Kirstine Kirkegaard, Clinical Associate Professor; Phone Number: +4578426562; Email: fertilitet@horsens.rm.dk

Study Locations

• Denmark
  • Copenhagen, Denmark, 2100
    • Copenhagen University Hospital - Rigshospitalet. Department of Gynecology, Fertility and Obstetrics
    • Contact: Kristine Løssl, Clinical Associate Professor; Phone Number: +4535451077; Email: fertilitet.rigshospitalet@regionh.dk
    • Principal Investigator: Kristine Løssl, Clinical Associate Professor
  • Herlev, Denmark, 2730
    • The Fertility Clinic, Herlev Hospital
    • Contact: Maria Birkvad Rasmussen, Clinical Associate Professor; Phone Number: +4538683868; Email: HEH-gynaekologisk-obstetrisk.afdeling.g@regionh.dk
    • Principal Investigator: Maria Birkvad Rasmussen, Clinical Associate Professor
  • Horsens, Denmark, 8700
    • University Clinic for Fertility, Horsens Regional Hospital, Central Denmark Region
    • Contact: Kirstine Kirkegaard, Clinical Associate Professor; Phone Number: +4578426562; Email: fertilitet@horsens.rm.dk
    • Principal Investigator: Kirstine Kirkegaard, Clinical Associate Professor
  • Hvidovre, Denmark, 2650
    • The Fertility Clinic, Hvidovre Hospital
    • Contact: Nina la Cour Freiesleben, Clinical Associate Professor; Phone Number: +4538622744; Email: fertilitetsklinikken.amager-og-hvidovre-hospital@regionh.dk
    • Principal Investigator: Nina la Cour Freiesleben, Clinical Associate Professor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 18-37 years
• Scheduled for IUI with homologous or donor sperm
• Undergoing mild ovarian stimulation with letrozole
• Ability to provide written informed consent

Exclusion Criteria:

• Age > 37 years
• Anovulation due to hypogonadotropic hypogonadism
• Known hypersensitivity to progesterone or hard fat listed as an excipient in the Summary of Product Characteristics (SmPC) for Cyclogest.
• Known or suspected progesterone-sensitive malignant tumours
• Porphyria
• Known missed abortion or ectopic pregnancy
• Active arterial or venous thromboembolism, severe thrombophlebitis, or a history of these conditions
• Severe hepatic dysfunction or liver disease
• Inability to speak or understand Danish sufficiently to comprehend oral and written study information

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; Vaginal progesterone luteal phase support. Progesterone is administered as Cyclogest 400 mg twice daily form the day after insemination. Treatment is continued until gestational age 10 weeks in the event of clinical pregnancy, or until pregnancy is ruled out in women who do not achieve a clinical pregnancy.	Drug: Progesterone; Vaginal progesterone (Cyclogest) 400 mg administered twice daily starting the day after insemination. Treatment is continued until gestational age 10 weeks in the event of clinical pregnancy or until clinical pregnancy is ruled out.; Other Names: Cyclogest
No Intervention: Comparison; No luteal phase support will be administered after insemination, reflecting current standard treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Pregnancy Rate	Defined as an ultrasonographically visible foetal heartbeat at 7-9 weeks of gestation	Gestational age 7-9 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Live Birth Rate	Defined as the birth of one or more living infants after a pregnancy of GA ≥ 22 weeks	At the time of delivery
Biochemical Pregnancy Rate	Defined as a positive serum or urine β-hCG test 14-17 days after intrauterine insemination	14-17 days after intrauterine insemination
Early Pregnancy Loss	Defined as intrauterine pregnancy loss before 10 weeks of gestational age	Up to 10 weeks of gestation
Fetal miscarriage	Defined as pregnancy loss ≥ 10 weeks size with a fetus (≥ 33 mm) on ultrasound	From 10 weeks of gestation to delivery
Obstetric outcomes	Obstetric complications including hypertensive disorders of pregnancy, gestational diabetes, postpartum hemorrhage and cesarean section	At time of delivery
Perinatal outcomes	Preterm birth, birth weight, congenital malformations, and perinatal mortality (defined as foetal or neonatal death from GA 22+0 to 7 days after birth).	At time of delivery
Hormone levels	Serum hormone levels measured on the day of insemination, in the mid-luteal phase and on the day of ovulation trigger (optional), including progesterone, estradiol, LH and FSH.	Time of insemination and mid-luteal phase (approximately 7-9 days after insemination).

Collaborators and Investigators

• Sponsor: Kirstine Kirkegaard
• Investigators: Principal Investigator: Kirstine Kirkegaard, Clinical Associate Professor, University Clinic for Fertility, Horsens Regional Hospital, Central Denmark Region

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): January 1, 2030

Study Registration Dates

• First Submitted: March 27, 2026
• First Submitted That Met QC Criteria: March 27, 2026
• First Posted (Actual): April 2, 2026

Study Record Updates

• Last Update Posted (Actual): April 2, 2026
• Last Update Submitted That Met QC Criteria: March 27, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Randomized clinical trial; Ovulation induction; Letrozole; Intrauterine insemination; Luteal phase support; Vaginal progesterone
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Infertility; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Polycyclic Compounds; Pregnanes; Steroids; Fused-Ring Compounds; Gonadal Steroid Hormones; Gonadal Hormones; Pregnenediones; Pregnenes; Corpus Luteum Hormones; Progesterone Congeners; Progesterone
• Other Study ID Numbers: 05112025; 2025-524327-53-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be made avaliable.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No