Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Renmin Hospital of Wuhan University | OTHER |
| Jiaxing Maternity and Child Health Care Hospital | OTHER |
| Ningbo Women & Children's Hospital | OTHER |
Not provided
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Intracytoplasmic Sperm Injection (ICSI) | Active Comparator | All patients will receive controlled ovarian hyperstimulation (COH) treatment, which is performed by standard routines at each study center. The COH treatment includes either GnRH agonist protocol or GnRH antagonist protocol. Oocyte retrieval is scheduled for 36 (±2) hours after hCG injection. The retrieved cumulus oocyte complexes (COCs) will be allocated to undergo ICSI procedure according to the result of randomization. The first embryo transfer is performed using fresh embryo transfer (if without contraindication), limited to transferring 1-2 cleavage embryos or 1 blastocyst. The remaining available embryos will be frozen. |
|
| Conventional in vitro fertilization (c-IVF) | Active Comparator | All patients will receive controlled ovarian hyperstimulation (COH) treatment, which is performed by standard routines at each study center. The COH treatment includes either GnRH agonist protocol or GnRH antagonist protocol. Oocyte retrieval is scheduled for 36 (±2) hours after hCG injection. The retrieved cumulus oocyte complexes (COCs) will be allocated to undergo conventional IVF procedure according to the result of randomization. The first embryo transfer is performed using fresh embryo transfer (if without contraindication), limited to transferring 1-2 cleavage embryos or 1 blastocyst. If the embryos in the IVF group are fertilized through different methods (some with late-RICSI), the first embryo transfer is limited to embryos fertilized through conventional IVF. The remaining available embryos will be frozen. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ICSI | Procedure | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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). | At birth |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | At 12 weeks of gestation; At 12 months after randomization |
Not provided
Inclusion Criteria:
Aged 20-38 years
18.5 < BMI < 24kg/m2
Couples diagnosed with primary unexplained infertility:
Regular menses or confirmed ovulation;
Normal ovarian reserve;
Patent fallopian tubes;
Normal uterus and cervix;
Normal endocrine profile;
Semen analysis meeting WHO 6th edition criteria
First IVF/ICSI cycle
Received GnRH agonist protocol or GnRH antagonist protocol
Willing to provide informed consent and comply with follow-up
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Min Jin, PhD | Contact | +86-15925602121 | min_jin@zju.edu.cn |
| Name | Affiliation | Role |
|---|---|---|
| Min Jin, PhD | Second Affiliated Hospital, School of Medicine, Zhejiang University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Beijing Obstetrics and Gynecology Hospital, Capital Medical University | Beijing | Beijing Municipality | China |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D020554 | Sperm Injections, Intracytoplasmic |
| ID | Term |
|---|---|
| D005307 | Fertilization in Vitro |
| D027724 | Reproductive Techniques, Assisted |
| D012099 | Reproductive Techniques |
| D013812 | Therapeutics |
Not provided
Not provided
| Beijing Obstetrics and Gynecology Hospital |
| OTHER |
| Xiangyang Central Hospital | OTHER |
| Huangshi Central Hospital | OTHER |
This is a multicenter study. Each center enrolls participants using a competitive enrollment method and performs online randomization through the trial system. Using block randomization with a 1:1 allocation ratio, participants were assigned to either the ICSI group or the IVF group, with a block length set at 8. The trial system administrators were not involved in the treatment process. Eligible patients who provided informed consent were registered in the trial system by medical staff at each center on the day of oocyte retrieval. After entering participant information, the system automatically assigned patients based on pre-set parameters.
Not provided
Not provided
To safeguard patients' right to know and in accordance with previous similar studies, this study adopted an open-label design. Both participants and recruiters will be aware of the group assignments.
However, the doctors performing embryo transfers, medical staff conducting routine prenatal check-ups and laboratory technicians analyzing biological samples will not be directly informed of whether patients participate in this clinical study and their grouping status.
Not provided
|
| IVF | Procedure | 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. |
|
| Number of retrieved oocyte | Number of oocyte obtained on the day of oocyte retrieval | 2 hours after oocyte retrieval |
| MII rate | [Only in ICSI group] The proportion of MII oocytes to the total number of retrieved oocytes. | 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). | 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. | At 16-18 hours after insemination or injection |
| Normal fertilization rate | Normal fertilization is defined as the appearance of 2PN | At 16-18 hours after insemination or injection |
| Abnormal fertilization rate | Abnormal fertilization is defined as the appearance of 1PN or ≥3PN | 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. | At 16-18 hours after injection |
| Cleavage rate | The proportion of normal cleavage observed on Day 2 in normally fertilized oocytes | 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. | 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. | 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. | 3 days after oocyte retrieval |
| Blastocyst formation rate | The proportion of the number of blastocysts formed to the number of embryos undergoing blastocyst culture. | 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. | 6 days after oocyte retrieval |
| Good quality blastocyst rate | The proportion of good quality blastocysts to the total number of blastocysts. | 6 days after oocyte retrieval |
| Number of available blastocyst | Number of blastocysts of BC, CB grade and above, according to the Gardner scoring system. | 6 days after oocyte retrieval |
| Number of available embryo | The total number of embryos that can be utilized for transplantation or cryopreservation. | 6 days after oocyte retrieval |
| Total fertilization failure rate | Total fertilisation failure rate is defined as the absence of any zygotes with 2PN | 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. | 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. | 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. | 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). | 30 days after embryo transfer |
| Implantation rate | Implantation rate is defined as the number of gestational sacs per number of embryos transferred. | 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. | 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. | 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. | 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. | At 24 weeks of gestation; At 12 months after randomization |
| Gestational diabetes mellitus | Abnormal OGTT test | 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. | 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. | 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. | From 20 weeks of gestation up to 4-6 weeks after birth |
| Gestational age at delivery | At birth |
| Preterm birth | Pregnancy terminates after 28 weeks and before 37 weeks of gestation. | 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. | At birth |
| Iatrogenic preterm birth | Termination of pregnancy due to iatrogenic factors between 28 to 37 weeks of gestation. | At birth |
| Birth weight | Weight of newborn, classified as very low birth weight (<1500g), low birth weight (1500-2500g), macrosomia (>4000g). | At birth |
| Small for gestational age | Birth weight below the 10th percentile for gestational age. | At birth |
| Large for gestational age | Birth weight above the 90th percentile for gestational age. | At birth |
| Birth defect / Congenital anomaly | Any birth defect or congenital anomaly will be included. | At birth; At 4-6 weeks after birth |
| NICU admission | The admittance of the newborn to NICU. | 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. | At 4-6 weeks after birth |
| Neonatal mortality | Death of a live born baby within 28 days of birth. | At 4-6 weeks after birth |
| Huangshi Central Hospital | Huangshi | Hubei | 435000 | China |
|
| Renmin Hospital of Wuhan University | Wuhan | Hubei | 430060 | China |
|
| Xiangyang Central Hospital | Xiangyang | Hubei | 441021 | China |
|
| Second Affiliated Hospital, School of Medicine, Zhejiang University | Hangzhou | Zhejiang | 310052 | China |
|
| Jiaxing Maternity and Child Health Care Hospital | Jiaxing | Zhejiang | 314051 | China |
|
| Ningbo Women & Children's Hospital | Ningbo | Zhejiang | 315012 | China |
|
| D008919 | Investigative Techniques |