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

NCT ID: NCT03152643

Last Updated: 2022-06-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 992 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-09-29
• Study Completion Date: 2022-02-18

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.

Conditions

Infertility

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

blastocyst-stage embryo transfer group

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.

Group Type: EXPERIMENTAL

blastocyst-stage embryo transfer

Intervention Type: PROCEDURE

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 group

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.

Group Type: EXPERIMENTAL

cleavage-stage embryo transfer

Intervention Type: PROCEDURE

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.

Interventions

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.

Intervention Type: PROCEDURE

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.

Intervention Type: PROCEDURE

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.

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Shandong Provincial Hospital

OTHER_GOV

Sponsor Role: collaborator

RenJi Hospital

OTHER

Sponsor Role: collaborator

Guangxi Maternal and Child Health Hospital

OTHER

Sponsor Role: collaborator

Third Affiliated Hospital of Zhengzhou University

OTHER

Sponsor Role: collaborator

Shengjing Hospital

OTHER

Sponsor Role: collaborator

The Third Affiliated Hospital of Guangzhou Medical University

OTHER

Sponsor Role: collaborator

General Hospital of Ningxia Medical University

OTHER

Sponsor Role: collaborator

Suzhou Municipal Hospital

OTHER

Sponsor Role: collaborator

Henan Provincial People's Hospital

OTHER

Sponsor Role: collaborator

The First Affiliated Hospital of Anhui Medical University

OTHER

Sponsor Role: collaborator

The First Affiliated Hospital with Nanjing Medical University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jiayin Liu, MD &PhD

Role: PRINCIPAL_INVESTIGATOR

The First Affiliated Hospital with Nanjing Medical University

Zi-Jiang Chen, MD &PhD

Role: PRINCIPAL_INVESTIGATOR

Center for Reproductive Medicine, affiliated to Shandong University

Locations

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

Suzhou Municipal Hospital

Suzhou, Suzhou, China

Countries

China

References

Ma X, Wang J, Shi Y, Tan J, Guan Y, Sun Y, Zhang B, Zhao J, Liu J, Cao Y, Li H, Zhang C, Chen F, Yi H, Wang Z, Xin X, Kong P, Lu Y, Huang L, Yuan Y, Liu H, Li C, Mol BWJ, Hu Z, Zhang H, Chen ZJ, Liu J. Effect of single blastocyst-stage versus single cleavage-stage embryo transfer on cumulative live births in women with good prognosis undergoing in vitro fertilization: Multicenter Randomized Controlled Trial. Nat Commun. 2024 Sep 5;15(1):7747. doi: 10.1038/s41467-024-52008-y.

Reference Type: DERIVED

PMID: 39237545 (View on PubMed)

Other Identifiers

CLBR-CBSET

Identifier Type: -

Identifier Source: org_study_id