Cumulative Live Birth Rates After Cleavage-stage Versus Blastocyst-stage Embryo Transfer

Infertility Clinical Trial

— CLBR-CBSET  

Official title:

Cumulative Live Birth Rates After Cleavage-stage Versus Blastocyst-stage Embryo Transfer: A Multicenter, Prospective, Randomized Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03152643
• Other study ID #: CLBR-CBSET
• Status: Completed
• Phase: N/A
• Start date: September 29, 2018
• Est. completion date: February 18, 2022

Study information

• Verified date: June 2022
• Source: The First Affiliated Hospital with Nanjing Medical University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 992
• Est. completion date: February 18, 2022
• Est. primary completion date: September 6, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 20 Years to 40 Years

Eligibility

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.

Related Conditions & MeSH terms

• Infertility

Intervention

Procedure:
• blastocyst-stage embryo transfer
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.
• cleavage-stage embryo transfer
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.

Locations

Country	Name	City	State
China	The Third Affiliated Hospital of Guangzhou Medical University	Guangzhou	Guangdong
China	The First Affiliated Hospital of Anhui Medical University	Hefei	Anhui
China	Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University	Jinan	Shandong
China	Clinical Center of Reproductive Medicine at the First Affiliated Hospital of Nanjing Medical University	Nanjing	Jiangsu
China	Guangxi Maternal and Child Health Hospital	Nanning	Guangxi
China	Renji Hospital affiliated to Shanghai Jiaotong University School of Medicine	Shanghai	Shanghai
China	Shengjing Hospital of China Medical University	Shenyang	Dongbei
China	Suzhou Municipal Hospital	Suzhou	Suzhou
China	General Hospital of Ningxia Medical University	Yinchuan	Ningxia
China	Henan Provincial People's Hospital	Zhengzhou	Henan
China	The Third Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan

Sponsors (11)

Lead Sponsor	Collaborator
The First Affiliated Hospital with Nanjing Medical University	General Hospital of Ningxia Medical University, Guangxi Maternal and Child Health Hospital, Henan Provincial People's Hospital, RenJi Hospital, Shandong Provincial Hospital, Shengjing Hospital, Suzhou Municipal Hospital, The First Affiliated Hospital of Anhui Medical University, The Third Affiliated Hospital of Guangzhou Medical University, Third Affiliated Hospital of Zhengzhou University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	30 months
Secondary	biochemical pregnancy rate	Biochemical pregnancy is defined as a serum ß-HCG level of at least 25 IU/L 14 days after embryo transfer.	30 months
Secondary	clinical pregnancy rate	Clinical pregnancy is defined by the presence of intrauterine gestation sacs at 30-35 days after embryo transfer.	30 months
Secondary	ongoing pregnancy rate	Ongoing pregnancy is defined as a viable pregnancy at 12 weeks gestation.	30 months
Secondary	Pregnancy loss rate	Pregnancy loss is defined as a pregnancy that results in a spontaneous abortion or therapeutic abortion that occurred throughout pregnancy.	30 months
Secondary	moderate or severe OHSS rate	Number of patients with moderate or severe OHSS/ number of COS cycles.	12 months
Secondary	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.	24 months
Secondary	sex ratio	the ratio of males to females in the newborns	30 months
Secondary	multiple pregnancy	Number of multiple pregnancies / number of clinical pregnancies.	30 months
Secondary	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	30 months
Secondary	congenital anomalies	structural or functional anomalies that occur during intrauterine life and can be identified prenatally, at birth or later in life.	30 months
Secondary	implantation rate	the number of gestational sacs detected with sonography at 6 weeks of pregnancy/the number of embryos transferred	30 months
Secondary	Birth weight	Weight of newborns at delivery	30 months