Infertility
Conditions
Keywords
Cumulative live birth rates, cleavage-stage embryo transfer, blastocyst transfer
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.
Interventions
PROCEDUREblastocyst-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.
PROCEDUREcleavage-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.
Sponsors
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
The First Affiliated Hospital with Nanjing Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
20 Years to 40 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| cumulative live birth rate | 30 months | 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
| Measure | Time frame | Description |
|---|---|---|
| implantation rate | 30 months | the number of gestational sacs detected with sonography at 6 weeks of pregnancy/the number of embryos transferred |
| Birth weight | 30 months | Weight of newborns at delivery |
| biochemical pregnancy rate | 30 months | Biochemical pregnancy is defined as a serum β-HCG level of at least 25 IU/L 14 days after embryo transfer. |
| clinical pregnancy rate | 30 months | Clinical pregnancy is defined by the presence of intrauterine gestation sacs at 30-35 days after embryo transfer. |
| ongoing pregnancy rate | 30 months | Ongoing pregnancy is defined as a viable pregnancy at 12 weeks gestation. |
| congenital anomalies | 30 months | structural or functional anomalies that occur during intrauterine life and can be identified prenatally, at birth or later in life. |
| moderate or severe OHSS rate | 12 months | Number of patients with moderate or severe OHSS/ number of COS cycles. |
| ectopic pregnancy | 24 months | 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 | 30 months | the ratio of males to females in the newborns |
| multiple pregnancy | 30 months | Number of multiple pregnancies / number of clinical pregnancies. |
| incidence of obstetric and perinatal complications | 30 months | Number of pregnancies with complications / number of pregnancies; ;number of live births with neonatal complications / number of live births |
| Pregnancy loss rate | 30 months | Pregnancy loss is defined as a pregnancy that results in a spontaneous abortion or therapeutic abortion that occurred throughout pregnancy. |
Countries
China
Outcome results
None listed