This multicenter, open-label, parallel-group, randomized controlled trial aims to compare the live birth rate, fertilization outcomes, other pregnancy outcomes and safety between ICSI and conventional IVF among couples with unexplained infertility in China.
A multicenter, large-scale, randomized controlled clinical trial will enroll 848 couples with unexplained infertility undergoing their first cycle of IVF or ICSI. The study will recruit participants from 6 Reproductive Medical Centers across mainland China. The participation in this study will be approximately 1 years with a total of 9 visits from controlled ovarian hyperstimulation, pregnancy to delivery. On the day of oocyte retrieval, eligible participants will be allocated to either the ICSI group or the IVF group in a 1:1 ratio. All participants will be randomized through block randomization, and each center will enroll participants using a competitive enrollment method.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
848
Insemination will be performed by using ICSI, 2 hours after oocyte retrieval. COCs will be stripped by using hyaluronidase. Only matured oocytes (MII stage) will be injected. Fertilization check will be performed at period of 16-18 hours after injection. Other standard assisted reproductive treatments are similar and parallel between two groups.
Insemination will be performed by using conventional IVF, 2-4 hours after oocyte retrieval. Collected COCs will be inseminated (1-5×105 sperm/ml) and cultured overnight in culture medium. Fertilization check will be performed at period of 16-18 hours after insemination. If the IVF group experiences total fertilization failure or a fertilization rate of less than 25%, late rescue ICSI (Late-RICSI) will be performed on all MII stage oocytes using semen retained on the day of egg retrieval. The injection method is same as standard ICSI. Other standard assisted reproductive treatments are similar and parallel between two groups.
Beijing Obstetrics and Gynecology Hospital, Capital Medical University
Beijing, Beijing Municipality, China
Huangshi Central Hospital
Huangshi, Hubei, China
Renmin Hospital of Wuhan University
Wuhan, Hubei, China
Xiangyang Central Hospital
Xiangyang, Hubei, China
Live birth rate after the first embryo transfer cycle
Live birth is defined as the birth of at least one newborn after 24 weeks' gestation that exhibits any sign of life (twin will be a single count).
Time frame: At birth
Cumulative ongoing pregnancy rate within one year
Achieving ongoing pregnancy within 12 months after randomization, regardless of the number of embryo transfers performed (limited to embryos obtained in the current study). Ongoing pregnancy refers to the presence of a gestational sac and fetal heart beat after 12 weeks of gestation.
Time frame: At 12 weeks of gestation; At 12 months after randomization
Number of retrieved oocyte
Number of oocyte obtained on the day of oocyte retrieval
Time frame: 2 hours after oocyte retrieval
MII rate
\[Only in ICSI group\] The proportion of MII oocytes to the total number of retrieved oocytes.
Time frame: 2 hours after oocyte retrieval
Fertilization rate per oocyte inseminated/injected
The proportion of fertilized oocytes to inseminated oocytes (IVF group) / injected oocytes (ICSI group).
Time frame: At 16-18 hours after insemination or injection
Fertilization rate per oocyte retrieved
The proportion of fertilized oocytes to the total number of retrieved oocytes.
Time frame: At 16-18 hours after insemination or injection
Normal fertilization rate
Normal fertilization is defined as the appearance of 2PN
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Second Affiliated Hospital, School of Medicine, Zhejiang University
Hangzhou, Zhejiang, China
Jiaxing Maternity and Child Health Care Hospital
Jiaxing, Zhejiang, China
Ningbo Women & Children's Hospital
Ningbo, Zhejiang, China
Time frame: At 16-18 hours after insemination or injection
Abnormal fertilization rate
Abnormal fertilization is defined as the appearance of 1PN or ≥3PN
Time frame: At 16-18 hours after insemination or injection
Degeneration rate of ICSI oocytes
\[Only in ICSI group\] The proportion of oocytes that undergo degeneration assessed on Day 2 among all oocytes receiving ICSI.
Time frame: At 16-18 hours after injection
Cleavage rate
The proportion of normal cleavage observed on Day 2 in normally fertilized oocytes
Time frame: At 16-18 hours after insemination or injection
Day 2 embryo formation rate
The proportion of 4-cell stage embryos formed on Day 2 compared to normal fertilized oocytes.
Time frame: 2 days after oocyte retrieval
Day 3 embryo formation rate
The proportion of 8-cell stage embryos formed on Day 3 compared to normal fertilized oocytes.
Time frame: 3 days after oocyte retrieval
Good quality embryo rate on Day 3
The proportion of I-II grade embryos with 6-10 cells on Day 3 compared to normal fertilized oocytes, according to Peter's scoring criteria.
Time frame: 3 days after oocyte retrieval
Blastocyst formation rate
The proportion of the number of blastocysts formed to the number of embryos undergoing blastocyst culture.
Time frame: 6 days after oocyte retrieval
Good quality blastocyst formation rate
The proportion of the number of blastocysts classified as 3BB or higher grade (according to Gardner scoring system) to the number of embryos undergoing blastocyst culture.
Time frame: 6 days after oocyte retrieval
Good quality blastocyst rate
The proportion of good quality blastocysts to the total number of blastocysts.
Time frame: 6 days after oocyte retrieval
Number of available blastocyst
Number of blastocysts of BC, CB grade and above, according to the Gardner scoring system.
Time frame: 6 days after oocyte retrieval
Number of available embryo
The total number of embryos that can be utilized for transplantation or cryopreservation.
Time frame: 6 days after oocyte retrieval
Total fertilization failure rate
Total fertilisation failure rate is defined as the absence of any zygotes with 2PN
Time frame: At 16-18 hours after insemination or injection
Cycle cancellation rate
The proportion of cycles with total fertilization failure or no available embryo to all oocyte retrieval cycles.
Time frame: 6 days after oocyte retrieval
Moderate/severe ovarian hyperstimulation syndrome (OHSS)
The exaggerated systemic response to ovarian stimulation. It is classified into mild, moderate, and severe based on the degree of bloating, ovarian volume enlargement, and respiratory, hemodynamic, and metabolic complications.
Time frame: At 10days after trigger; At 14 days after embryo transfer
Positive pregnancy rate
Positive pregnancy test is defined as a serum human chorionic gonadotropin level greater than 10mIU/mL after embryo transfer.
Time frame: 10-14 days after embryo transfer; At 12 months after randomization
Clinical pregnancy rate
Clinical pregnancy is defined as ultrasound detection of at least one gestational sac or other clear pregnancy manifestations under ultrasound (including clear ectopic pregnancy).
Time frame: 30 days after embryo transfer
Implantation rate
Implantation rate is defined as the number of gestational sacs per number of embryos transferred.
Time frame: 30 days after embryo transfer; At 12 months after randomization
Ongoing pregnancy rate
Ongoing pregnancy refers to the presence of a gestational sac and fetal heart beat after 12 weeks of gestation.
Time frame: At 12 weeks of gestation; At 12 months after randomization
Ectopic pregnancy
Ectopic pregnancy is defined as the presence of the gestational sac outside the uterine cavity detected by ultrasound.
Time frame: 30 days after embryo transfer; At 12 months after randomization
Multiple pregnancy rate
Multiple pregnancy is defined as the detection of two or more gestational sacs or positive heart beats by ultrasound.
Time frame: 30 days after oocyte retrieval; At 12 months after randomization
Miscarriage rate
Miscarriage refers to the loss of an intra-uterine pregnancy before 24 weeks of gestation.
Time frame: At 24 weeks of gestation; At 12 months after randomization
Gestational diabetes mellitus
Abnormal OGTT test
Time frame: At 24-28 weeks of gestation
Hypertensive disorders of pregnancy
The hypertensive disorders of pregnancy include gestational hypertension, chronic hypertension, pre-eclampsia, chronic hypertension with preeclampsia, eclampsia and HELLP syndrome.
Time frame: From 20 weeks of gestation up to at birth
Antepartum haemorrhage
Vaginal bleeding caused by placenta previa, placental implantation, or unknown reasons in mid or late pregnancy.
Time frame: From 20 weeks of gestation up to at birth
Thrombotic diseases
If the participant experiences clinical symptoms such as lower limb pain, chest pain, hemoptysis, etc., and there is a high suspicion of thrombotic disease in clinical practice, confirmation will be made through examinations such as vascular ultrasound and CT angiography.
Time frame: From 20 weeks of gestation up to 4-6 weeks after birth
Gestational age at delivery
Time frame: At birth
Preterm birth
Pregnancy terminates after 28 weeks and before 37 weeks of gestation.
Time frame: At birth
Spontaneous preterm birth
Termination of pregnancy due to premature rupture of membranes or spontaneous uterine contractions between 28 to 37 weeks of gestation.
Time frame: At birth
Iatrogenic preterm birth
Termination of pregnancy due to iatrogenic factors between 28 to 37 weeks of gestation.
Time frame: At birth
Birth weight
Weight of newborn, classified as very low birth weight (\<1500g), low birth weight (1500-2500g), macrosomia (\>4000g).
Time frame: At birth
Small for gestational age
Birth weight below the 10th percentile for gestational age.
Time frame: At birth
Large for gestational age
Birth weight above the 90th percentile for gestational age.
Time frame: At birth
Birth defect / Congenital anomaly
Any birth defect or congenital anomaly will be included.
Time frame: At birth; At 4-6 weeks after birth
NICU admission
The admittance of the newborn to NICU.
Time frame: At 4-6 weeks after birth
Perinatal mortality
Fetal or neonatal death occurring after 28 weeks of gestation, during delivery, or within 7 days after birth.
Time frame: At 4-6 weeks after birth
Neonatal mortality
Death of a live born baby within 28 days of birth.
Time frame: At 4-6 weeks after birth