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

• ICSI (Procedure), also known as Intracytoplasmic Sperm Injection: A technique that involves microinjection of spermatozoa into mature oocytes.
• IVF (Procedure), also known as in vitro fertilization: A process of fertilisation where an an egg is combined with sperm outside the body, in vitro.

Primary outcomes

• accumulated live birth rate [42 weeks]: This will be based on the outcome of either the ICSI or the outcome of the IVF as will all other secondary outcomes

Secondary outcomes

• Fertilization rate [1 day after fertilization]: Fertilization rate was defined as the percentage of fetal heart beat among total retrieved oocytes
• Embryo quality [3day after fertilization]: Embryo quality was evaluated by microscopy.
• clinical pregnancy rate [35 days after embryo transfer]: Clinical pregnancy was defined as an observation of gestational sac via ultrasonography.
• implantation rate [11-12 weeks after embryo transfer]: Implantation rate was defined as the percentage of fetal heart beat among total transferred embryos at 12 weeks' gestational age.
• biochemical pregnancy rate [2 weeks after embryo transfer]: Biochemical pregnancy was defined as numbers of women with an elevated serum β-hCG level of more than 10 mIU/ml.
• pregnancy loss rate [28 gestational weeks in maximum]: 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.
• ectopic pregnancy rate [12 gestational weeks in maximum]: Ectopic pregnancy is defined as an embryo implanted outside the uterine.

Sex: Female, ages: 38 Years to 50 Years

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.

• He-Feng Huang, MD, Principal investigator, Shanghai Jiao Tong University School of Medicine