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

The First Affiliated Hospital with Nanjing Medical University992 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Interventions

blastocyst-stage embryo transferPROCEDURE

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 transferPROCEDURE

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.

Eligibility

Sex: FEMALEMin age: 20 YearsMax age: 40 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (11)

The First Affiliated Hospital of Anhui Medical University

Hefei, Anhui, China

Shengjing Hospital of China Medical University

Shenyang, Dongbei, China

The Third Affiliated Hospital of Guangzhou Medical University

Guangzhou, Guangdong, China

Guangxi Maternal and Child Health Hospital

Nanning, Guangxi, China

Henan Provincial People's Hospital

Zhengzhou, Henan, China

The Third Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, China

Clinical Center of Reproductive Medicine at the First Affiliated Hospital of Nanjing Medical University

Nanjing, Jiangsu, China

General Hospital of Ningxia Medical University

Yinchuan, Ningxia, China

Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University

Jinan, Shandong, China

Renji Hospital affiliated to Shanghai Jiaotong University School of Medicine

Shanghai, Shanghai Municipality, China

...and 1 more locations

Outcomes

Primary Outcomes

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.

Time frame: 30 months

Secondary Outcomes

biochemical pregnancy rate

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

clinical pregnancy rate

Clinical pregnancy is defined by the presence of intrauterine gestation sacs at 30-35 days after embryo transfer.

Time frame: 30 months

ongoing pregnancy rate

Ongoing pregnancy is defined as a viable pregnancy at 12 weeks gestation.

Time frame: 30 months

Pregnancy loss rate

Pregnancy loss is defined as a pregnancy that results in a spontaneous abortion or therapeutic abortion that occurred throughout pregnancy.

Time frame: 30 months

moderate or severe OHSS rate

Number of patients with moderate or severe OHSS/ number of COS cycles.

Time frame: 12 months

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.

Time frame: 24 months

sex ratio

the ratio of males to females in the newborns

Time frame: 30 months

multiple pregnancy

Number of multiple pregnancies / number of clinical pregnancies.

Time frame: 30 months

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

Time frame: 30 months

congenital anomalies

structural or functional anomalies that occur during intrauterine life and can be identified prenatally, at birth or later in life.

Time frame: 30 months

implantation rate

the number of gestational sacs detected with sonography at 6 weeks of pregnancy/the number of embryos transferred

Time frame: 30 months

Birth weight

Weight of newborns at delivery

Time frame: 30 months

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

Overview

Conditions

Interventions

Eligibility

Locations (11)

Outcomes

Primary Outcomes

Secondary Outcomes