Back to resultsCumulative Live Birth Rates After Cleavage-stage Versus Blastocyst-stage Embryo Transfer (CLBR-CBSET)
Primary Purpose
Infertility
Status
Completed
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
blastocyst-stage embryo transfer
cleavage-stage embryo transfer
Sponsored by
About this trial
This is an interventional treatment trial for Infertility focused on measuring Cumulative live birth rates, cleavage-stage embryo transfer, blastocyst transfer
Eligibility Criteria
Inclusion criteria:
- Women aged ≥20 and ≤40 years.
- Women with the number of transferrable cleavage embryos ≥ 3;
- Women undergoing their first or second cycle of IVF or ICSI.
Exclusion criteria
- 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
- Women who plan to undergo In Vitro Maturation (IVM);
- Women who plan to undergo Preimplantation Genetic Diagnosis (PGD) /Preimplantation Genetic Screening (PGS).
- Women who have Women who have hydrosalpinx visible on ultrasound.
- Women who have experienced recurrent spontaneous abortions, defined as 2 or more previous pregnancy losses.
- Women who have been developed a "freeze-all" treatment plan for purpose of subsequent surgery, such as salpingectomy due to hydrosalpinx after oocytes retrieval.
- 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.
Sites / Locations
- The First Affiliated Hospital of Anhui Medical University
- Shengjing Hospital of China Medical University
- The Third Affiliated Hospital of Guangzhou Medical University
- Guangxi Maternal and Child Health Hospital
- Henan Provincial People's Hospital
- The Third Affiliated Hospital of Zhengzhou University
- Clinical Center of Reproductive Medicine at the First Affiliated Hospital of Nanjing Medical University
- General Hospital of Ningxia Medical University
- Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University
- Renji Hospital affiliated to Shanghai Jiaotong University School of Medicine
- Suzhou Municipal Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
blastocyst-stage embryo transfer group
cleavage-stage embryo transfer group
Arm Description
For subjects assigned to blastocyst-stage (D5/D6) embryo transfer group, all embryos will be cultured to D5 or D6. 1 blastocysts of the best quality will be transferred in fresh cycle on D5 or D6 after oocyte retrieval (D5 embryo will be the prior choice). The surplus embryos, if any, will be vitrified for future FET in case the fresh cycle does not result in a live birth. If a patient is at a high risk of OHSS, all embryos on D5 or D6 can be cryopreserved with vitrification for patient's safety. The FET cycle will be initiated on the second menstrual cycle after oocyte retrieval.
For subjects assigned to the cleavage-stage (D2/3) embryo transfer group, 1 cleavage embryos of the best quality will be transferred in fresh cycle on Day 2/3 after oocyte retrieval. The surplus embryos, if any, will be vitrified for future FET if the fresh cycle does not result in a live birth. If a patient is at a high risk of OHSS, all embryos on Day 2/3 are allowed to be cryopreserved with vitrification for patient's safety. The FET cycle will be initiated on the second menstrual cycle after oocyte retrieval.
Outcomes
Primary Outcome Measures
cumulative live birth rate
Cumulative live birth rate (CLBR) is defined the first live birth per patient from one initiated oocyte retrieval cycle(Calculated using outcomes from the first three embryo transfers within 1 year after randomization). Live birth is defined as delivery of any neonate ≥24 weeks gestation with heart beat and breath.
Secondary Outcome Measures
biochemical pregnancy rate
Biochemical pregnancy is defined as a serum β-HCG level of at least 25 IU/L 14 days after embryo transfer.
clinical pregnancy rate
Clinical pregnancy is defined by the presence of intrauterine gestation sacs at 30-35 days after embryo transfer.
ongoing pregnancy rate
Ongoing pregnancy is defined as a viable pregnancy at 12 weeks gestation.
Pregnancy loss rate
Pregnancy loss is defined as a pregnancy that results in a spontaneous abortion or therapeutic abortion that occurred throughout pregnancy.
moderate or severe OHSS rate
Number of patients with moderate or severe OHSS/ number of COS cycles.
ectopic pregnancy
diagnosed by ultrasound examination or laparoscopic surgery visualizing more than or equal to 1 gestational sacs outside the uterus or by abnormally increasing serum hCG level without sonographic visualization and the absence of chorionic villi inside the uterus after uterine curettage, which was treated by methotrexate.
sex ratio
the ratio of males to females in the newborns
multiple pregnancy
Number of multiple pregnancies / number of clinical pregnancies.
incidence of obstetric and perinatal complications
Number of pregnancies with complications / number of pregnancies; ;number of live births with neonatal complications / number of live births
congenital anomalies
structural or functional anomalies that occur during intrauterine life and can be identified prenatally, at birth or later in life.
implantation rate
the number of gestational sacs detected with sonography at 6 weeks of pregnancy/the number of embryos transferred
Birth weight
Weight of newborns at delivery
Full Information
NCT ID
NCT03152643
First Posted
May 9, 2017
Last Updated
June 8, 2022
Sponsor
The First Affiliated Hospital with Nanjing Medical University
Collaborators
Shandong Provincial Hospital, RenJi Hospital, Guangxi Maternal and Child Health Hospital, Third Affiliated Hospital of Zhengzhou University, Shengjing Hospital, The Third Affiliated Hospital of Guangzhou Medical University, General Hospital of Ningxia Medical University, Suzhou Municipal Hospital, Henan Provincial People's Hospital, The First Affiliated Hospital of Anhui Medical University
1. Study Identification
Unique Protocol Identification Number
NCT03152643
Brief Title
Cumulative Live Birth Rates After Cleavage-stage Versus Blastocyst-stage Embryo Transfer
Acronym
CLBR-CBSET
Official Title
Cumulative Live Birth Rates After Cleavage-stage Versus Blastocyst-stage Embryo Transfer: A Multicenter, Prospective, Randomized Controlled Trial
Study Type
Interventional
2. Study Status
Record Verification Date
June 2022
Overall Recruitment Status
Completed
Study Start Date
September 29, 2018 (Actual)
Primary Completion Date
September 6, 2021 (Actual)
Study Completion Date
February 18, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The First Affiliated Hospital with Nanjing Medical University
Collaborators
Shandong Provincial Hospital, RenJi Hospital, Guangxi Maternal and Child Health Hospital, Third Affiliated Hospital of Zhengzhou University, Shengjing Hospital, The Third Affiliated Hospital of Guangzhou Medical University, General Hospital of Ningxia Medical University, Suzhou Municipal Hospital, Henan Provincial People's Hospital, The First Affiliated Hospital of Anhui Medical University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Infertility
Keywords
Cumulative live birth rates, cleavage-stage embryo transfer, blastocyst transfer
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
992 (Actual)
8. Arms, Groups, and Interventions
Arm Title
blastocyst-stage embryo transfer group
Arm Type
Experimental
Arm Description
For subjects assigned to blastocyst-stage (D5/D6) embryo transfer group, all embryos will be cultured to D5 or D6. 1 blastocysts of the best quality will be transferred in fresh cycle on D5 or D6 after oocyte retrieval (D5 embryo will be the prior choice). The surplus embryos, if any, will be vitrified for future FET in case the fresh cycle does not result in a live birth. If a patient is at a high risk of OHSS, all embryos on D5 or D6 can be cryopreserved with vitrification for patient's safety. The FET cycle will be initiated on the second menstrual cycle after oocyte retrieval.
Arm Title
cleavage-stage embryo transfer group
Arm Type
Experimental
Arm Description
For subjects assigned to the cleavage-stage (D2/3) embryo transfer group, 1 cleavage embryos of the best quality will be transferred in fresh cycle on Day 2/3 after oocyte retrieval. The surplus embryos, if any, will be vitrified for future FET if the fresh cycle does not result in a live birth. If a patient is at a high risk of OHSS, all embryos on Day 2/3 are allowed to be cryopreserved with vitrification for patient's safety. The FET cycle will be initiated on the second menstrual cycle after oocyte retrieval.
Intervention Type
Procedure
Intervention Name(s)
blastocyst-stage embryo transfer
Intervention Description
All the participants will receive a long GnRH-agonist, ultra-long GnRH-agonist, short GnRH-agonist or GnRH antagonist protocol in combination with recombinant FSH. HCG will be administered for final oocyte maturation. Patients will have a single blastocyst-stage embryos transferred. The outcomes of all the embryo transfers within 1 year after randomization will be followed up. Single embryo transfer (SET) is required for the first 3 embryo transfers within 1 year after randomization. For embryo transfers beyond the third within the 1 year, patients' treatment must follow their randomized allocation, and SET is no longer mandatory. Luteal phase support will be administered before embryo transfer. If pregnancy is confirmed, luteal phase support will be continued until 10 weeks of gestation. The follow up will be continued until 6 weeks after delivery.
Intervention Type
Procedure
Intervention Name(s)
cleavage-stage embryo transfer
Intervention Description
All the participants will receive a long GnRH-agonist, ultra-long GnRH-agonist, short GnRH-agonist or GnRH antagonist protocol in combination with recombinant FSH. HCG will be administered for final oocyte maturation. Patients will have a single cleavage-stage embryos transferred. The outcomes of all the embryo transfers within 1 year after randomization will be followed up. Single embryo transfer (SET) is required for the first 3 embryo transfers within 1 year after randomization. For embryo transfers beyond the third within the 1 year, patients' treatment must follow their randomized allocation, and SET is no longer mandatory. Luteal phase support will be administered before embryo transfer. If pregnancy is confirmed, luteal phase support will be continued until 10 weeks of gestation. The follow up will be continued until 6 weeks after delivery.
Primary Outcome Measure Information:
Title
cumulative live birth rate
Description
Cumulative live birth rate (CLBR) is defined the first live birth per patient from one initiated oocyte retrieval cycle(Calculated using outcomes from the first three embryo transfers within 1 year after randomization). Live birth is defined as delivery of any neonate ≥24 weeks gestation with heart beat and breath.
Time Frame
30 months
Secondary Outcome Measure Information:
Title
biochemical pregnancy rate
Description
Biochemical pregnancy is defined as a serum β-HCG level of at least 25 IU/L 14 days after embryo transfer.
Time Frame
30 months
Title
clinical pregnancy rate
Description
Clinical pregnancy is defined by the presence of intrauterine gestation sacs at 30-35 days after embryo transfer.
Time Frame
30 months
Title
ongoing pregnancy rate
Description
Ongoing pregnancy is defined as a viable pregnancy at 12 weeks gestation.
Time Frame
30 months
Title
Pregnancy loss rate
Description
Pregnancy loss is defined as a pregnancy that results in a spontaneous abortion or therapeutic abortion that occurred throughout pregnancy.
Time Frame
30 months
Title
moderate or severe OHSS rate
Description
Number of patients with moderate or severe OHSS/ number of COS cycles.
Time Frame
12 months
Title
ectopic pregnancy
Description
diagnosed by ultrasound examination or laparoscopic surgery visualizing more than or equal to 1 gestational sacs outside the uterus or by abnormally increasing serum hCG level without sonographic visualization and the absence of chorionic villi inside the uterus after uterine curettage, which was treated by methotrexate.
Time Frame
24 months
Title
sex ratio
Description
the ratio of males to females in the newborns
Time Frame
30 months
Title
multiple pregnancy
Description
Number of multiple pregnancies / number of clinical pregnancies.
Time Frame
30 months
Title
incidence of obstetric and perinatal complications
Description
Number of pregnancies with complications / number of pregnancies; ;number of live births with neonatal complications / number of live births
Time Frame
30 months
Title
congenital anomalies
Description
structural or functional anomalies that occur during intrauterine life and can be identified prenatally, at birth or later in life.
Time Frame
30 months
Title
implantation rate
Description
the number of gestational sacs detected with sonography at 6 weeks of pregnancy/the number of embryos transferred
Time Frame
30 months
Title
Birth weight
Description
Weight of newborns at delivery
Time Frame
30 months
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion criteria:
Women aged ≥20 and ≤40 years.
Women with the number of transferrable cleavage embryos ≥ 3;
Women undergoing their first or second cycle of IVF or ICSI.
Exclusion criteria
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
Women who plan to undergo In Vitro Maturation (IVM);
Women who plan to undergo Preimplantation Genetic Diagnosis (PGD) /Preimplantation Genetic Screening (PGS).
Women who have Women who have hydrosalpinx visible on ultrasound.
Women who have experienced recurrent spontaneous abortions, defined as 2 or more previous pregnancy losses.
Women who have been developed a "freeze-all" treatment plan for purpose of subsequent surgery, such as salpingectomy due to hydrosalpinx after oocytes retrieval.
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jiayin Liu, MD &PhD
Organizational Affiliation
The First Affiliated Hospital with Nanjing Medical University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Zi-Jiang Chen, MD &PhD
Organizational Affiliation
Center for Reproductive Medicine, affiliated to Shandong University
Official's Role
Principal Investigator
Facility Information:
Facility Name
The First Affiliated Hospital of Anhui Medical University
City
Hefei
State/Province
Anhui
Country
China
Facility Name
Shengjing Hospital of China Medical University
City
Shenyang
State/Province
Dongbei
Country
China
Facility Name
The Third Affiliated Hospital of Guangzhou Medical University
City
Guangzhou
State/Province
Guangdong
Country
China
Facility Name
Guangxi Maternal and Child Health Hospital
City
Nanning
State/Province
Guangxi
Country
China
Facility Name
Henan Provincial People's Hospital
City
Zhengzhou
State/Province
Henan
Country
China
Facility Name
The Third Affiliated Hospital of Zhengzhou University
City
Zhengzhou
State/Province
Henan
Country
China
Facility Name
Clinical Center of Reproductive Medicine at the First Affiliated Hospital of Nanjing Medical University
City
Nanjing
State/Province
Jiangsu
ZIP/Postal Code
210000
Country
China
Facility Name
General Hospital of Ningxia Medical University
City
Yinchuan
State/Province
Ningxia
Country
China
Facility Name
Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University
City
Jinan
State/Province
Shandong
Country
China
Facility Name
Renji Hospital affiliated to Shanghai Jiaotong University School of Medicine
City
Shanghai
State/Province
Shanghai
Country
China
Facility Name
Suzhou Municipal Hospital
City
Suzhou
State/Province
Suzhou
Country
China
12. IPD Sharing Statement
Plan to Share IPD
No
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Cumulative Live Birth Rates After Cleavage-stage Versus Blastocyst-stage Embryo Transfer
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