Intracytoplasmic Sperm Injection in Non-male Factor Infertility in Advanced Maternal Age

Study Overview
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Brief Summary
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This will be a prospective, randomized (1:1 ratio) clinical trial for non-male factor infertility in advanced maternal age with or without intracytoplasmic sperm injection(ICSI). Qualified 1422 patients are randomized into either of two groups: group A will undergo conventional in-vitro fertilization(IVF)(711 cases), Group B will undergo intracytoplasmic sperm injection (ICSI) (711 cases). All participants will receive the same protocol for ovarian stimulation and standardized luteal phase support. The target population will be patients with non-male factor infertility aged ≥38years with FSH ≤15. Women with other reasons of infertility (eg. anovulation, endometriosis, and premature ovarian failure) are excluded. The randomization will take place before controlled ovarian stimulation by a computer randomization system. The accumulated live birth rate , pregnancy complications will be followed up by checking medical records and telephone calls.

Official Title
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Intracytoplasmic Sperm Injection in Non-male Factor Infertility in Advanced Maternal Age

Conditions
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ART, Infertility, Female

Intervention / Treatment
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* Procedure: ICSI
* Procedure: IVF


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female patients ages ≥38 years old with FSH ≤15; Spouse with normal sperm analysis according to WHO fifth edition criteria(sperm parameter values: total sperm count of at least 39 million, concentration≥15 × 106/ml, total motility ≥40%, progressive motility ≥32%， strict morphology ≥4% normal forms)； Female patients who intended to undergo IVF and had signed a written consent form. Exclusion Criteria: More than three previous IVF cycles (including both failed cycles and cycles that ended in live births) Female patients with Ovulation dysfunction related disease, such as endometriosis, polycystic ovarian syndrome(tubal factors are not included); undiagnosed infertility; Female patients who have previously been diagnosed with a uterine abnormality such as a malformed uterus(uterus unicornis, septate uterus, duplex uterus or uterus bicomis), adenomyosis, submucous myoma or intrauterine adhesion; Spouse who have experienced recurrent spontaneous abortions (including biochemical pregnancy abortion), defined as three or more previous pregnancy losses; Patients or their partners with an abnormal chromosome karyotype not including chromosome polymorphisms, which mainly refer to the variants in the chromosomal heterochromatin region the use of donor oocytes or sperm; the use of frozen oocytes or sperm; Femal patients with medical conditions that contraindicate assisted reproductive technology and/or pregnancy, such as poorly controlled type 1 or type 2 diabetes mellitus; undiagnosed liver disease or dysfunction(based on serum liver enzyme test results); renal disease or abnormal serum renal function; significant anemia; history of deep venous thrombosis, pulmonary embolus or cerebrovascular accident; uncontrolled hypertension or known symptomatic heart disease; history of (or suspected) cervical carcinoma, endometrial carcinoma or breast carcinoma; and undiagnosed vaginal bleeding; Spouse with medical conditions that contraindicate assisted reproductive technology and/or pregnancy, such as poorly controlled type 1 or type 2 diabetes mellitus; undiagnosed liver disease or dysfunction(based on serum liver enzyme test results); renal disease or abnormal serum renal function; significant anemia; history of deep venous thrombosis, pulmonary embolus or cerebrovascular accident; uncontrolled hypertension or known symptomatic heart disease; Female patients or their partners who are unable to comply with the study Procedures; Female patients who had previously been randomized to either of the two study groups in this trial.

Ages Eligible for Study
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Minimum Age: 38 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IVF<br>embryos are cultured using conventional in vitro fertilization.A maximum of 2 embryos will be transferred for each treatment cycle. | Procedure: IVF<br>* A process of fertilisation where an an egg is combined with sperm outside the body, in vitro.<br>* Other names: in vitro fertilization;|
| Experimental: ICSI<br>embryos are fertilized using ICSI.A maximum of 2 embryos will be transferred for each treatment cycle. | Procedure: ICSI<br>* A technique that involves microinjection of spermatozoa into mature oocytes.<br>* Other names: Intracytoplasmic Sperm Injection;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| accumulated live birth rate | This will be based on the outcome of either the ICSI or the outcome of the IVF as will all other secondary outcomes | 42 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fertilization rate | Fertilization rate was defined as the percentage of fetal heart beat among total retrieved oocytes | 1 day after fertilization | 
| Embryo quality | Embryo quality was evaluated by microscopy. | 3day after fertilization | 
| clinical pregnancy rate | Clinical pregnancy was defined as an observation of gestational sac via ultrasonography. | 35 days after embryo transfer | 
| implantation rate | Implantation rate was defined as the percentage of fetal heart beat among total transferred embryos at 12 weeks' gestational age. | 11-12 weeks after embryo transfer | 
| biochemical pregnancy rate | Biochemical pregnancy was defined as numbers of women with an elevated serum β-hCG level of more than 10 mIU/ml. | 2 weeks after embryo transfer | 
| pregnancy loss rate | Pregnancy loss is defined as any reason that resulted in failure of an embryo to develop, embryonic or fetal death, or spontaneous expulsion of a pregnancy. | 28 gestational weeks in maximum | 
| ectopic pregnancy rate | Ectopic pregnancy is defined as an embryo implanted outside the uterine. | 12 gestational weeks in maximum |