Embryo Transfer, Infertility
Conditions
Keywords
progesterone, luteal phase support, frozen embryo transfer, natural cycles, live birth
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.
Interventions
DRUGProgesterone vaginal tablet
The study drug is progesterone 100 mg administrated as a vaginal tablet three times daily.
Sponsors
Göteborg University
Vastra Gotaland Region
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Two main arms, of which the experimental arm is split in two arms with different duration of treatment
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 43 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with live birth | Up to 41 weeks after embryo transfer. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with biochemical pregnancy | 2-3 weeks after embryo transfer. | A pregnancy diagnosed only by the detection of beta hCG in serum or urine. |
| Number of participants with ongoing pregnancy | 5-7 weeks after embryo transfer. | An intrauterine pregnancy with one or more fetuses with heartbeats measured in gestational week 7+5 to 9+0 with vaginal ultrasound. |
| Number of participants with miscarriage | Up to 20 weeks after embryo transfer. | 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. |
| Number of participants with ectopic pregnancy | Up to 20 weeks after embryo transfer. | A pregnancy outside the uterine cavity, diagnosed by ultrasound, surgical visualization, or histopathology. |
| Number of children admitted to Neonatal Intensive Care Unit (NICU) | Up to 41 weeks after embryo transfer and 7 days after birth. | Defined as children that were admitted to NICU after birth. |
| Number of participants with termination of pregnancy | Up to 20 weeks after embryo transfer. | 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. |
| Birth weight | Up to 41 weeks after embryo transfer. | Defined as weight in grams at birth. |
| Gestational age at delivery | Up to 41 weeks after embryo transfer. | 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. |
| Preterm birth | Up to 35 weeks after embryo transfer. | Defined as a child born alive before 37 completed weeks of pregnancy. |
| Very preterm birth | Up to 30 weeks after embryo transfer. | Defined as a child born alive before 32 completed weeks of pregnancy. |
| Low birth weight | Up to 41 weeks after embryo transfer. | Birth weight less than 2500 g. |
| Very low birth weight | Up to 41 weeks after embryo transfer. | Birth weight less than 1500 g. |
| Number of participants with clinical pregnancy | 4-8 weeks after embryo transfer. | A pregnancy diagnosed by ultrasonographic visualization of one or more gestational sacs. |
| Perinatal death | Up to 41 weeks after embryo transfer and 7 days after birth. | 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. |
| Number of children with birth defects | Up to 41 weeks after embryo transfer. | 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. |
| Number of participants with hypertensive disorders of pregnancy | Up to 41 weeks after embryo transfer including the postpartum period before discharge of mother. | Hypertensive disorders of pregnancy defined as high blood pressure disorders including preeclampsia, gestational hypertension and chronic hypertension. |
| Number of participants with placenta previa | Up to 41 weeks after embryo transfer. | Defined as a placenta covering the internal os of the cervix, at time of delivery. |
| Number of participants with placenta abruption | Up to 41 weeks after embryo transfer. | Defined as the premature separation of a normally located placenta from the uterine wall that occurs before delivery of the fetus. |
| Number of participants with postpartum hemorrhage | Up to 41 weeks after embryo transfer. | 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. |
| Number of participants with Cesarean section | Up to 41 weeks after embryo transfer. | Defined as a surgical procedure used to deliver a baby through incisions in the abdomen and uterus. |
| Number of participants with thromboembolic events | Up to 41 weeks after embryo transfer including the postpartum period before discharge of mother. | 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. |
| Maternal mortality | Up to 41 weeks after embryo transfer including the postpartum period before discharge of mother. | 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. |
| Number of participants with treatment related side effects | Up to 8 weeks after embryo transfer. | 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. |
| Number of participants with adverse events | Up to 8 weeks after embryo transfer. | 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. |
| Cost effectiveness | After study completion, an average of 1 year. | Comparison between groups regarding the total costs for the intervention divided by treatment efficacy (live birth). |
| Stillbirth | Up to 41 weeks after embryo transfer. | 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. |
Countries
Sweden
Contacts
Primary ContactÅsa Magnusson, MD, PhD
Backup ContactCaroline Stadelmann, MD
Outcome results
None listed