Day 3 Versus Day 5 Embryo Transfer in IVF Patients With Few Embryos
Trial Snapshot
- Phase
- Phase 3
- Status
- Recruiting
- Enrollment
- 1,126
- Locations
- 1
- Primary Endpoint
- cumulative live birth per IVF cycle
Study Overview
Brief Summary
Infertility affects more than 6 million women the United States and is a major life event that results in a wide range of socio-cultural, emotional, physical and financial problems. The most successful treatment for infertility, in-vitro fertilization (IVF), fertilizes a woman's eggs with her partner's sperm in a culture dish and transfers the resulting embryos into the uterus. Most of the time, prior to being transferred, embryos are grown in the dish for 5-7 days after which some of them reach an advanced stage (blastocyst stage). This has several advantages such as a lower chance of a multiple pregnancies (twins, triplets etc.) after transfer and fewer transfer procedures. However, it is possible that embryos would survive better if transferred into the uterus at the 8-cell stage after growing them for only 3 days. Thus, when patients only have a small number of embryos they and their physicians face the difficult choice when to transfer because there are currently no studies available to guide this decision.
This randomized controlled trial is comparing pregnancy outcomes and patient satisfaction of poor prognosis patients with 5 or fewer embryos undergoing either transfer of an advanced (blastocyst) or an 8-cell embryo.
This study will provide the data for the development of guidelines for IVF providers to make evidence-based decisions when to transfer embryos in poor prognosis IVF patients, reduce patients' anxiety regarding cycle cancellation and improve patient counseling, which will increase patients' ability to participate in the development of their treatment plan.
Detailed Description
Background and Significance:
It is a major unanswered question for many IVF patients and their providers whether embryos which did not develop into a blastocyst after in vitro culture to day 5-7 of development may have resulted in a pregnancy when transferred into the uterus on day 3, at the cleavage (8-cell) stage. For patients with few (<=5) embryos there is a lack of studies analyzing pregnancy outcomes with either type of embryo transfer (ET). As a result of this uncertainty, these patients and their providers face the difficult clinical decision when to transfer their embryos. This decision is often based on 'expert opinion' and driven by patient anxiety about embryo survival in vitro but not high-quality evidence. Thus, patients with few embryos often receive cleavage-stage transfers forgoing the advantages of blastocyst transfer such as the possibility to transfer a single embryo (SET) which reduces the incidence of multiple pregnancies without reducing the live birth rate per ET.
The investigators are working with nine IVF centers across the US to enroll 1126 patients age 18-44 who are treated for infertility with IVF for the first time and have 5 or fewer embryos. The investigators will assign an equal number of patients by chance to either the 8-cell embryo or the blastocyst transfer group. If there are any surplus embryos that meet freezing criteria they will be frozen and then thawed and transferred in a subsequent cycle. The investigators will monitor patients for 6 months or until all embryos are transferred and, if pregnancy is achieved, until delivery (9 months). For each group the investigators will measure the chance to have a live birth per cycle (primary outcome) and the risk of miscarriage, multiple pregnancy, cycle cancellation (secondary) outcomes based on clinical assessments.
The investigators are working with patients, advocacy groups (RESOLVE, Fertility within Reach), professional societies in reproductive medicine (ASRM, NEFS), clinicians, embryologists, nurses, implementation experts, and a health psychologist, as well as payer (Optum, Winfertility) and policymaker (ASRM, NEFS) representatives to design, and conduct this study and implement the results.
Study Aims:
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 44 Years (Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •First autologous IVF cycle
- •≤5 zygotes on day 1 of development
- •Fresh embryo transfer
Exclusion Criteria
- •Planned preimplantation genetic testing (PGT)
- •History of recurrent pregnancy loss (≥3)
- •Body mass index >40
- •Presence of uterine factor infertility
- •Planned gestational carrier
- •Endometrial lining <6mm measured on the day of trigger
- •Lupron-only trigger, elevated progesterone in the fresh cycle (≥1.5ng/ml)
- •Delayed fertilization (>18 hours)
- •Rescue intracytoplasmic sperm injection (following failed regular fertilization)
- •Use of non-ejaculated sperm (testicular sperm extraction)
- •Embryo transfer number outside American Society of Reproductive Medicine (ASRM) guidelines
- •Cycle is converted to a cycle in which all embryos are frozen
Arms & Interventions
cleavage-stage embryo transfer
embryo(s) will be transferred on day 3 of embryo development (cleavage-stage embryo)
Intervention: embryo transfer (Procedure)
blastocyst embryo transfer
embryo(s) will be transferred on day 5-7 of embryo development (blastocyst-stage embryo)
Intervention: embryo transfer (Procedure)
Outcomes
Primary Outcomes
cumulative live birth per IVF cycle
Time Frame: month 9 after embryo transfer
the number of live births resulting from transfer of all embryos obtained from one egg retrieval
Secondary Outcomes
- multiple pregnancy(month 9 after embryo transfer)
- number of involved procedures(month 9 after embryo transfer)
- live birth rate/fresh embryo transfer(month 9 after embryo transfer)
- adverse perinatal outcomes (stillbirth, preterm birth)(month 9 after embryo transfer)
- financial burden(month 9 after embryo transfer)
- ectopic pregnancy(month 9 after embryo transfer)
- Incidence of patient satisfaction/psychological distress(month 9 after embryo transfer)
- Incidence of facilitators and barriers for patient involvement(month 9 after embryo transfer)
Investigators
Werner Neuhausser
Principal Investigator
Beth Israel Deaconess Medical Center