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

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.

Study Overview

• Status: Unknown
• Conditions: Infertility, Female; ART
• Intervention / Treatment: Procedure: IVF; Procedure: ICSI

• Study Type: Interventional
• Enrollment (Anticipated): 1422
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200030
      • International Peace Maternity & Child Health Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 38 years to 50 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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
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
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
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

Collaborators and Investigators

• Sponsor: International Peace Maternity and Child Health Hospital
• Investigators: Principal Investigator: He-Feng Huang, MD, Shanghai Jiao Tong University School of Medicine

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): September 1, 2017
• Primary Completion (ANTICIPATED): September 1, 2018
• Study Completion (ANTICIPATED): September 1, 2019

Study Registration Dates

• First Submitted: April 16, 2017
• First Submitted That Met QC Criteria: April 16, 2017
• First Posted (ACTUAL): April 19, 2017

Study Record Updates

• Last Update Posted (ACTUAL): April 19, 2017
• Last Update Submitted That Met QC Criteria: April 16, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infertility; Infertility, Female
• Other Study ID Numbers: IPMCH2017001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No