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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
1,800
The study drug is progesterone 100 mg administrated as a vaginal tablet three times daily.
Department of Reproductive Medicine
Gothenburg, Sweden
RECRUITINGNumber of participants with live birth
A child born alive. Also, the outcome will be reported according to Core Outcome Measure for Infertility Trials (Duffy et al., 2020) in a separate appendix.
Time frame: Up to 41 weeks after embryo transfer.
Number of participants with biochemical pregnancy
A pregnancy diagnosed only by the detection of beta hCG in serum or urine.
Time frame: 2-3 weeks after embryo transfer.
Number of participants with clinical pregnancy
A pregnancy diagnosed by ultrasonographic visualization of one or more gestational sacs.
Time frame: 4-8 weeks after embryo transfer.
Number of participants with ongoing pregnancy
An intrauterine pregnancy with one or more fetuses with heartbeats measured in gestational week 7+5 to 9+0 with vaginal ultrasound.
Time frame: 5-7 weeks after embryo transfer.
Number of participants with miscarriage
The spontaneous loss of an intra-uterine pregnancy prior to 22 completed weeks of gestational age. Also, the outcome will be reported according to Core Outcome Measure for Infertility Trials (Duffy et al., 2020) in a separate appendix.
Time frame: Up to 20 weeks after embryo transfer.
Number of participants with ectopic pregnancy
A pregnancy outside the uterine cavity, diagnosed by ultrasound, surgical visualization, or histopathology.
Time frame: Up to 20 weeks after embryo transfer.
Number of participants with termination of pregnancy
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Defined as the termination of a clinical pregnancy, by deliberate interference that takes place before 22 completed weeks of gestational age. Also, the outcome will be reported according to Core Outcome Measure for Infertility Trials (Duffy et al., 2020) in a separate appendix.
Time frame: Up to 20 weeks after embryo transfer.
Birth weight
Defined as weight in grams at birth.
Time frame: Up to 41 weeks after embryo transfer.
Gestational age at delivery
The gestational age at FET is calculated by adding the number of culture days to ovulation (ovulation=day 14). Gestational age at delivery is then calculated by adding the number of days since FET.
Time frame: Up to 41 weeks after embryo transfer.
Preterm birth
Defined as a child born alive before 37 completed weeks of pregnancy.
Time frame: Up to 35 weeks after embryo transfer.
Very preterm birth
Defined as a child born alive before 32 completed weeks of pregnancy.
Time frame: Up to 30 weeks after embryo transfer.
Low birth weight
Birth weight less than 2500 g.
Time frame: Up to 41 weeks after embryo transfer.
Very low birth weight
Birth weight less than 1500 g.
Time frame: Up to 41 weeks after embryo transfer.
Stillbirth
The death of a fetus prior to the complete expulsion or extraction from its mother, after and including 22 completed weeks of gestational age. Also, the outcome will be reported according to Core Outcome Measure for Infertility Trials (Duffy et al., 2020) in a separate appendix.
Time frame: Up to 41 weeks after embryo transfer.
Perinatal death
Fetal or neonatal death occurring during late pregnancy (at 22 completed weeks of gestational age and later), during childbirth, or up to seven days after birth. Also, the outcome will be reported according to Core Outcome Measure for Infertility Trials (Duffy et al., 2020) in a separate appendix.
Time frame: Up to 41 weeks after embryo transfer and 7 days after birth.
Number of children with birth defects
Congenital birth defects were defined according the International Statistical Classification of Diseases and Related Health Problems (ICD-10). And further defined according to the EUROCAT classification system.
Time frame: Up to 41 weeks after embryo transfer.
Number of children admitted to Neonatal Intensive Care Unit (NICU)
Defined as children that were admitted to NICU after birth.
Time frame: Up to 41 weeks after embryo transfer and 7 days after birth.
Number of participants with hypertensive disorders of pregnancy
Hypertensive disorders of pregnancy defined as high blood pressure disorders including preeclampsia, gestational hypertension and chronic hypertension.
Time frame: Up to 41 weeks after embryo transfer including the postpartum period before discharge of mother.
Number of participants with placenta previa
Defined as a placenta covering the internal os of the cervix, at time of delivery.
Time frame: Up to 41 weeks after embryo transfer.
Number of participants with placenta abruption
Defined as the premature separation of a normally located placenta from the uterine wall that occurs before delivery of the fetus.
Time frame: Up to 41 weeks after embryo transfer.
Number of participants with postpartum hemorrhage
Defined as a cumulative blood loss of greater than 1,000 mL or blood loss accompanied by signs or symptoms of hypovolemia within 24 hours after the birth process.
Time frame: Up to 41 weeks after embryo transfer.
Number of participants with Cesarean section
Defined as a surgical procedure used to deliver a baby through incisions in the abdomen and uterus.
Time frame: Up to 41 weeks after embryo transfer.
Number of participants with thromboembolic events
Defined as formation in a blood vessel of a clot (thrombus) that breaks loose and is carried by the blood stream to plug another vessel.
Time frame: Up to 41 weeks after embryo transfer including the postpartum period before discharge of mother.
Maternal mortality
Defined as female deaths from any cause related to or aggravated by pregnancy or its management (excluding accidental or incidental causes) during pregnancy and childbirth.
Time frame: Up to 41 weeks after embryo transfer including the postpartum period before discharge of mother.
Number of participants with treatment related side effects
Side effects reported according to study specific questionnaire. Questions are answered with yes or no. If yes, symptoms are described, but not by using a scale.
Time frame: Up to 8 weeks after embryo transfer.
Number of participants with adverse events
Any untoward medical occurrence in symptom or disease temporally associated with the use of the medicinal (investigational) product, whether or not related to the medicinal product.
Time frame: Up to 8 weeks after embryo transfer.
Cost effectiveness
Comparison between groups regarding the total costs for the intervention divided by treatment efficacy (live birth).
Time frame: After study completion, an average of 1 year.