NCT03152643

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
992

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started Sep 2018

Longer than P75 for not_applicable

Geographic Reach
1 country

11 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 9, 2017

Completed
6 days until next milestone

First Posted

Study publicly available on registry

May 15, 2017

Completed
1.4 years until next milestone

Study Start

First participant enrolled

September 29, 2018

Completed
2.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 6, 2021

Completed
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

February 18, 2022

Completed
Last Updated

June 9, 2022

Status Verified

June 1, 2022

Enrollment Period

2.9 years

First QC Date

May 9, 2017

Last Update Submit

June 8, 2022

Conditions

Infertility

Keywords

Cumulative live birth ratescleavage-stage embryo transferblastocyst transfer

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (12)

  • biochemical pregnancy rate

    30 months

  • clinical pregnancy rate

    30 months

  • ongoing pregnancy rate

    30 months

  • Pregnancy loss rate

    30 months

  • moderate or severe OHSS rate

    12 months

  • +7 more secondary outcomes

Study Arms (2)

blastocyst-stage embryo transfer group

EXPERIMENTAL

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.

Procedure: blastocyst-stage embryo transfer

cleavage-stage embryo transfer group

EXPERIMENTAL

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.

Procedure: cleavage-stage embryo transfer

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.

blastocyst-stage embryo transfer group
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.

cleavage-stage embryo transfer group

Eligibility Criteria

Age20 Years - 40 Years
Sexfemale
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (11)

The First Affiliated Hospital of Anhui Medical University

Hefei, Anhui, China

Location

Shengjing Hospital of China Medical University

Shenyang, Dongbei, China

Location

The Third Affiliated Hospital of Guangzhou Medical University

Guangzhou, Guangdong, China

Location

Guangxi Maternal and Child Health Hospital

Nanning, Guangxi, China

Location

Henan Provincial People's Hospital

Zhengzhou, Henan, China

Location

The Third Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, China

Location

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

Nanjing, Jiangsu, 210000, China

Location

General Hospital of Ningxia Medical University

Yinchuan, Ningxia, China

Location

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

Jinan, Shandong, China

Location

Renji Hospital affiliated to Shanghai Jiaotong University School of Medicine

Shanghai, Shanghai Municipality, China

Location

Suzhou Municipal Hospital

Suzhou, Suzhou, China

Location

Related Publications (1)

  • 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.

    PMID: 39237545DERIVED

MeSH Terms

Conditions

Infertility

Interventions

Embryo Transfer

Condition Hierarchy (Ancestors)

Genital DiseasesUrogenital Diseases

Intervention Hierarchy (Ancestors)

Reproductive Techniques, AssistedReproductive TechniquesTherapeuticsInvestigative Techniques

Study Officials

  • Jiayin Liu, MD &PhD

    The First Affiliated Hospital with Nanjing Medical University

    PRINCIPAL INVESTIGATOR

  • Zi-Jiang Chen, MD &PhD

    Center for Reproductive Medicine, affiliated to Shandong University

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 9, 2017

First Posted

May 15, 2017

Study Start

September 29, 2018

Primary Completion

September 6, 2021

Study Completion

February 18, 2022

Last Updated

June 9, 2022

Record last verified: 2022-06

Data Sharing

IPD Sharing
Will not share

Locations

CN(11)