Clinical trial NCT03152643: Cumulative Live Birth Rates After Cleavage-stage Versus Blastocyst-stage Embryo Transfer
Official title: Cumulative Live Birth Rates After Cleavage-stage Versus Blastocyst-stage Embryo Transfer: A Multicenter, Prospective, Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Infertility
Keywords: Cumulative live birth rates
cleavage-stage embryo transfer
blastocyst transfer
Lead sponsor: The First Affiliated Hospital with Nanjing Medical University
Sponsor class: OTHER
Collaborators: name: Shandong Provincial Hospital
name: RenJi Hospital
name: Guangxi Maternal and Child Health Hospital
name: Third Affiliated Hospital of Zhengzhou University
name: Shengjing Hospital
name: The Third Affiliated Hospital of Guangzhou Medical University
name: General Hospital of Ningxia Medical University
name: Suzhou Municipal Hospital
name: Henan Provincial People's Hospital
name: The First Affiliated Hospital of Anhui Medical University
First posted: 2017-05-15
Enrollment: 992
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of this RCT is to compare differences in the efficacy and safety between cleavage-stage embryo transfer and blastocyst-stage embryo transfer in IVF/ICSI treatment cycle, taking into account of subsequent vitrified embryo transfers. Subjects with 3 or more transferrable cleavage embryos will be randomized to the cleavage-stage or blastocyst-stage embryos transfer group. The primary outcome is cumulative live birth rate (CLBR) per patient until the first live birth from one initiated oocyte retrieval cycle, calculated using outcomes from the first three embryo transfers within 1 year after randomization.

Detailed description: This is a multicenter, randomized clinical trial comparing the efficacy and safety between cleavage-stage embryo transfer and blastocyst-stage embryo transfer in IVF/ICSI treatment cycle, taking into account of subsequent vitrified embryo transfers.Randomization will be performed on day 2/3 after oocyte retrieval, when at least 3 embryos are achieved. Patients in group A will have 1 cleavage-stage embryo transferred. Patients in group B will have 1 blastocyst-stage embryo transferred. The outcomes from all the embryo transfers within 1 year after randomization will be followed up. If a pregnancy/live birth is not achieved, single embryo transfer is required for the first 3 embryo transfers within 1 year after randomization. For embryo transfers beyond the third within the 1 year, patient's treatment must follow their randomized allocation, and SET is no longer mandatory. The follow-up period is 2 years from the day of randomization.Due to the COVID-19 pandemic, the participants who were unable to undergo the embryo transfers in 1 year of randomization will have 3 months extension for frozen embryo transfer. The follow-up for these participants will be extended for 3 months as well.

Eligibility criteria: Inclusion criteria:

1. Women aged ≥20 and ≤40 years.
2. Women with the number of transferrable cleavage embryos ≥ 3;
3. Women undergoing their first or second cycle of IVF or ICSI.

Exclusion criteria

1. Women who have been diagnosed with uterine abnormalities (confirmed by three-dimensional ultrasonography or hysteroscopy), including malformed uterus (uterus unicornis, septate uterus or duplex uterus), submucous myoma, or intrauterine adhesion
2. Women who plan to undergo In Vitro Maturation (IVM);
3. Women who plan to undergo Preimplantation Genetic Diagnosis (PGD) /Preimplantation Genetic Screening (PGS).
4. Women who have Women who have hydrosalpinx visible on ultrasound.
5. Women who have experienced recurrent spontaneous abortions, defined as 2 or more previous pregnancy losses.
6. Women who have been developed a "freeze-all" treatment plan for purpose of subsequent surgery, such as salpingectomy due to hydrosalpinx after oocytes retrieval.
7. Women with contraindications to assisted reproductive technology and/or pregnancy, such as uncontrolled hypertension, symptomatic heart diseases, uncontrolled diabetes, undiagnosed liver disease or dysfunction (based on serum liver enzyme test results), undiagnosed renal disease or abnormal renal function, severe anemia, history of deep venous thrombosis, pulmonary embolus or cerebrovascular accident, history of or suspicious for cancer, undiagnosed vaginal bleeding.

Primary outcomes:
measure: cumulative live birth rate
timeFrame: 30 months
Secondary outcomes:
measure: biochemical pregnancy rate
timeFrame: 30 months
measure: clinical pregnancy rate
timeFrame: 30 months
measure: ongoing pregnancy rate
timeFrame: 30 months
measure: Pregnancy loss rate
timeFrame: 30 months
measure: moderate or severe OHSS rate
timeFrame: 12 months
measure: ectopic pregnancy
timeFrame: 24 months
measure: sex ratio
timeFrame: 30 months
measure: multiple pregnancy
timeFrame: 30 months
measure: incidence of obstetric and perinatal complications
timeFrame: 30 months
measure: congenital anomalies
timeFrame: 30 months
measure: implantation rate
timeFrame: 30 months
measure: Birth weight
timeFrame: 30 months
Other outcomes:
Locations:
city: Hefei
country: China
facility: The First Affiliated Hospital of Anhui Medical University
state: Anhui
city: Shenyang
country: China
facility: Shengjing Hospital of China Medical University
state: Dongbei
city: Guangzhou
country: China
facility: The Third Affiliated Hospital of Guangzhou Medical University
state: Guangdong
city: Nanning
country: China
facility: Guangxi Maternal and Child Health Hospital
state: Guangxi
city: Zhengzhou
country: China
facility: Henan Provincial People's Hospital
state: Henan
city: Zhengzhou
country: China
facility: The Third Affiliated Hospital of Zhengzhou University
state: Henan
city: Nanjing
country: China
facility: Clinical Center of Reproductive Medicine at the First Affiliated Hospital of Nanjing Medical University
state: Jiangsu
city: Yinchuan
country: China
facility: General Hospital of Ningxia Medical University
state: Ningxia
city: Jinan
country: China
facility: Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University
state: Shandong
city: Shanghai
country: China
facility: Renji Hospital affiliated to Shanghai Jiaotong University School of Medicine
state: Shanghai
city: Suzhou
country: China
facility: Suzhou Municipal Hospital
state: Suzhou
Study officials:
affiliation: The First Affiliated Hospital with Nanjing Medical University
name: Jiayin Liu, MD &PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Center for Reproductive Medicine, affiliated to Shandong University
name: Zi-Jiang Chen, MD &PhD
role: PRINCIPAL_INVESTIGATOR
References: