Progesterone Supplementation After Letrozole-stimulated Insemination

NCT07508657 — Phase 4, Recruiting, 690 participants, Kirstine Kirkegaard

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

Registry	NCT07508657, acronym LIFT
Status	Recruiting
Phase	Phase 4
Study type	Interventional; randomized, parallel, masking: single, treatment
Enrollment	690 (Estimated)
Sponsor	Kirstine Kirkegaard (Other)
Conditions	Infertility
Interventions	Progesterone (Drug)
Dates	start 2026-08-28, primary completion 2029-06-01 (estimated), completion 2030-01-01 (estimated), first posted 2026-04-02, last updated 2026-09-09
Locations	4 sites in Denmark

-Summary

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.

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+Arms and interventions

Arm	Type	Interventions	Description
Intervention	Experimental	Drug: Progesterone	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.
Comparison	No intervention		No luteal phase support will be administered after insemination, reflecting current standard treatment.

Progesterone (Drug), also known as Cyclogest: 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.

+Outcome measures

Primary outcomes

Clinical Pregnancy Rate [Gestational age 7-9 weeks]: Defined as an ultrasonographically visible foetal heartbeat at 7-9 weeks of gestation

Secondary outcomes

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

+Eligibility

Sex: Female, ages: 18 Years to 37 Years

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

+Locations (4)

Facility	City	Country	Status
Copenhagen University Hospital - Rigshospitalet. Department of Gynecology, Fertility and Obstetrics	Copenhagen	Denmark	Not yet recruiting
The Fertility Clinic, Herlev Hospital	Herlev	Denmark	Not yet recruiting
University Clinic for Fertility, Horsens Regional Hospital, Central Denmark Region	Horsens	Denmark	Recruiting
The Fertility Clinic, Hvidovre Hospital	Hvidovre	Denmark	Not yet recruiting

+Investigators

Kirstine Kirkegaard, Clinical Associate Professor, Principal investigator, University Clinic for Fertility, Horsens Regional Hospital, Central Denmark Region

+Funding

NIH grants: 2025