Clinical trial NCT04725864: Progesterone as Luteal Support in Frozen IVF Natural Cycles
Official title: Vaginal Progesterone as Luteal Support for Improvement of Live Birth in Frozen/Thawed In-vitro Fertilization Natural Cycles; a Multicenter, Open, Randomized Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Infertility
Embryo Transfer
Keywords: progesterone
luteal phase support
frozen embryo transfer
natural cycles
live birth
Lead sponsor: Vastra Gotaland Region
Sponsor class: OTHER_GOV
Collaborators: name: Göteborg University
First posted: 2021-01-27
Enrollment: 1800
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 43
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Two main arms, of which the experimental arm is split in two arms with different duration of treatment
Primary purpose: TREATMENT

Brief summary: The ProFET study aims to investigate if luteal phase support by vaginal progesterone, is superior to no luteal phase support, in terms of live birth rate per woman after a frozen embryo transfer (FET), in a natural cycle (NC) after in-vitro fertilization (IVF), and if 7 weeks of treatment is superior to 3 weeks duration.

Detailed description: Vaginal progesterone supplementation is routine treatment after IVF with fresh embryo transfer, but it is uncertain whether vaginal progesterone after frozen embryo transfer in natural cycles is efficacious in terms of increasing the chance of a live birth.

The ProFET study is a multicenter, open randomized, controlled trial planning to include 1800 women, intended to undergo a FET in a natural cycle.

Primary objectives are to investigate if luteal phase support by vaginal progesterone, is superior to no luteal phase support, in terms of live birth rate per woman after a frozen embryo transfer, in a natural cycle and if 7 weeks of treatment is superior to 3 weeks duration.

Secondary objectives are to compare groups regarding pregnancy outcomes including biochemical pregnancy, clinical, ongoing and term pregnancy rates, as well as rates of miscarriage, termination of pregnancy, and ectopic pregnancy.

Secondary objectives are also perinatal and obstetrics outcomes, self-reported side effects, adverse events and cost effectiveness.

The investigators will also analyze the effect of S-Progesterone level before FET on the chance of achieving live birth and secondary pregnancy outcomes.

Eligibility criteria: Inclusion Criteria:

* Planned for a FET-NC with a blastocyst
* BMI \>18.5 \<35
* Regular menstrual cycles 24-35 days
* Given informed consent
* Understand written and spoken Swedish, English or Arabic

Exclusion Criteria:

* Oocyte donor cycles, preimplantation genetic testing (PGT) cycles. Uterine malformation, submucous myoma and endometrial polyps.
* Hypersensitivity against study medication. Other contraindications according to www.fass.se
* Development of serious disease contraindicating ART or pregnancy.
* Participation or recent participation in a clinical study with an investigational product (past 30 days). Previous participation in this study.

Primary outcomes:
measure: Number of participants with live birth
timeFrame: Up to 41 weeks after embryo transfer.
Secondary outcomes:
measure: Number of participants with biochemical pregnancy
timeFrame: 2-3 weeks after embryo transfer.
measure: Number of participants with clinical pregnancy
timeFrame: 4-8 weeks after embryo transfer.
measure: Number of participants with ongoing pregnancy
timeFrame: 5-7 weeks after embryo transfer.
measure: Number of participants with miscarriage
timeFrame: Up to 20 weeks after embryo transfer.
measure: Number of participants with ectopic pregnancy
timeFrame: Up to 20 weeks after embryo transfer.
measure: Number of participants with termination of pregnancy
timeFrame: Up to 20 weeks after embryo transfer.
measure: Birth weight
timeFrame: Up to 41 weeks after embryo transfer.
measure: Gestational age at delivery
timeFrame: Up to 41 weeks after embryo transfer.
measure: Preterm birth
timeFrame: Up to 35 weeks after embryo transfer.
measure: Very preterm birth
timeFrame: Up to 30 weeks after embryo transfer.
measure: Low birth weight
timeFrame: Up to 41 weeks after embryo transfer.
measure: Very low birth weight
timeFrame: Up to 41 weeks after embryo transfer.
measure: Stillbirth
timeFrame: Up to 41 weeks after embryo transfer.
measure: Perinatal death
timeFrame: Up to 41 weeks after embryo transfer and 7 days after birth.
measure: Number of children with birth defects
timeFrame: Up to 41 weeks after embryo transfer.
measure: Number of children admitted to Neonatal Intensive Care Unit (NICU)
timeFrame: Up to 41 weeks after embryo transfer and 7 days after birth.
measure: Number of participants with hypertensive disorders of pregnancy
timeFrame: Up to 41 weeks after embryo transfer including the postpartum period before discharge of mother.
measure: Number of participants with placenta previa
timeFrame: Up to 41 weeks after embryo transfer.
measure: Number of participants with placenta abruption
timeFrame: Up to 41 weeks after embryo transfer.
measure: Number of participants with postpartum hemorrhage
timeFrame: Up to 41 weeks after embryo transfer.
measure: Number of participants with Cesarean section
timeFrame: Up to 41 weeks after embryo transfer.
measure: Number of participants with thromboembolic events
timeFrame: Up to 41 weeks after embryo transfer including the postpartum period before discharge of mother.
measure: Maternal mortality
timeFrame: Up to 41 weeks after embryo transfer including the postpartum period before discharge of mother.
measure: Number of participants with treatment related side effects
timeFrame: Up to 8 weeks after embryo transfer.
measure: Number of participants with adverse events
timeFrame: Up to 8 weeks after embryo transfer.
measure: Cost effectiveness
timeFrame: After study completion, an average of 1 year.
Other outcomes:
Locations:
city: Gothenburg
country: Sweden
facility: Department of Reproductive Medicine
Study officials:
affiliation: Vastra Gotaland
name: Åsa Magnusson, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Duffy JMN, AlAhwany H, Bhattacharya S, Collura B, Curtis C, Evers JLH, Farquharson RG, Franik S, Giudice LC, Khalaf Y, Knijnenburg JML, Leeners B, Legro RS, Lensen S, Vazquez-Niebla JC, Mavrelos D, Mol BWJ, Niederberger C, Ng EHY, Otter AS, Puscasiu L, Rautakallio-Hokkanen S, Repping S, Sarris I, Simpson JL, Strandell A, Strawbridge C, Torrance HL, Vail A, van Wely M, Vercoe MA, Vuong NL, Wang AY, Wang R, Wilkinson J, Youssef MA, Farquhar CM; Core Outcome Measure for Infertility Trials (COMMIT) initiative. Developing a core outcome set for future infertility research: an international consensus development studydagger double dagger. Hum Reprod. 2020 Dec 1;35(12):2725-2734. doi: 10.1093/humrep/deaa241.
citation: Stadelmann C, Bergh C, Brannstrom M, Olsen KH, Khatibi A, Kitlinski M, Liffner S, Lundborg E, Rodriguez-Wallberg KA, Strandell A, Westlander G, Widlund G, Magnusson A. Vaginal progesterone as luteal phase support in natural cycle frozen-thawed embryo transfer (ProFET): protocol for a multicentre, open-label, randomised controlled trial. BMJ Open. 2022 Jul 8;12(7):e062400. doi: 10.1136/bmjopen-2022-062400.