Preimplantation Genetic Screening in Patients With Male Factor Infertility

This will be a prospective, randomized (1:1 ratio) clinical trial for patients with severe male-factor infertility with or without preimplantation genetic screening (PGS). Qualified 450 patients are randomized into either of two groups: group A will undergo intracytoplasmic sperm injection (ICSI) without PGS (225 cases), Group B will undergo ICSI with PGS (225 cases). The partners of all participants will receive the same protocol for ovarian stimulation and standardized luteal phase support.

The target population will be patients with severe male-factor infertility aged between 20 and 55 years, diagnosed by the ESHER Criteria (Non-obstructive oligospermia，asthenspermia). Women with other reasons of infertility (eg. advanced age, anovulation, endometriosis, and premature ovarian failure) are excluded.

The randomization will take place 3-6 days after the oocyte pick-up day by a computer randomization system. The pregnancy test results, pregnancy complications, congenital anomalies, neonatal complications will be followed up by checking medical records and telephone calls.

Study Overview

• Status: Recruiting
• Conditions: Infertility, Male; Diagnosis, Preimplantation
• Intervention / Treatment: Procedure: ICSI without PGS; Procedure: ICSI with PGS

• Study Type: Interventional
• Enrollment (Anticipated): 450
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: He-feng Huang, MD; Phone Number: +86-21-18017310186; Email: hefenghuang@126.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200030
      • Recruiting
      • International Peace Maternity & Child Health Hospital
      • Contact: He-feng Huang, MD; Phone Number: +86-21-18017310186; Email: hefenghuang@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 55 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion criteria

1. Male partner age of 20-55 years old, Chinese.
2. Male partner has severe male infertility (defined as a semen concentrate less than 5×10^6/ml, and/or with a progressive motility less than 10%).
3. Proposed ICSI to assist pregnancy.
4. Fully explain the nature of the research and obtain the informed consent of the subject before carrying out any procedure in the research protocol. If a subject is not capable of expressing opinions, the legal representative of the subject can sign the informed consent on behalf of the subject.

Exclusion criteria

Any one of the following criteria should be excluded from this study:

1. Male partner had been diagnosed with obstructive azoospermia, sexual dysfunction, and immune infertility.
2. Female partner at 38 years of ages and older.
3. Female partner has uterine abnormalities such as uterine malformations (unicornuate uterus, mediastinal uterus, double uterus, double horn uterus, etc.), adenomyosis, submucosal fibroids or intrauterine adhesions.
4. Female partner has a history of recurrent abortion, including biochemical pregnancy (≥3 time miscarriages).
5. One of the couples has abnormal chromosomal karyotypes, excluding chromosomal polymorphisms.
6. Female partner has contraindications for assisted reproduction, such as poorly controlled type I or type II diabetes mellitus; undiagnosed liver disease or abnormal liver function (abnormal serum liver enzymes); kidney disease or abnormal kidney function; severe anemia; history of deep venous thrombosis; history of pulmonary embolism; history of cerebrovascular accident; poorly controlled hypertension or diagnosed heart disease; history of cervical cancer, endometrial cancer or breast cancer; unexplained vaginal bleeding.
7. Male partner has contraindications for assisted reproduction, such as poorly controlled type I or type II diabetes mellitus; undiagnosed liver disease or abnormal liver function (abnormal serum liver enzymes); kidney disease or abnormal kidney function; severe anemia; history of deep venous thrombosis; history of pulmonary embolism; history of cerebrovascular accident; poorly controlled hypertension or diagnosed heart disease.
8. One of the couple refuses to cooperate with the study.
9. Patients who have been included in the experimental group or control group of this study.

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: ICSI without PGS; Selection of embryos are based on blastocyst morphology criteria on day 5. A maximum of 2 embryos will be transferred for each treatment cycle.	Procedure: ICSI without PGS; Selection of embryos are based on morphology criteria on the 5th day of ICSI.
Experimental: ICSI with PGS; PGS will be applied to select embryos on day 5, only euploid embryos will be transferred. A maximum of 2 embryos will be transferred for each treatment cycle.	Procedure: ICSI with PGS; PGS will be applied to selected embryos on the 5th day of ICSI.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
live birth rate	This will be based on the outcome of either the PGS+ICSI or the outcome of the ICSI after first embryo transfer cycle.	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
neonatal complication rate	Neonatal complication includes neonatal respiratory disorders, neonatal cerebral palsy, neonatal encephalopathy and other disease that should been sent into neonatal ICU.	1 day after delivery
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
Congenital Anomalies rate	Congenital anomaly included deformity and development abnormality of any organs or systems.	1 day after delivery

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Cornelisse S, Zagers M, Kostova E, Fleischer K, van Wely M, Mastenbroek S. Preimplantation genetic testing for aneuploidies (abnormal number of chromosomes) in in vitro fertilisation. Cochrane Database Syst Rev. 2020 Sep 8;9(9):CD005291. doi: 10.1002/14651858.CD005291.pub3.
• Lin XH, Guo MX, Wu DD, Lu Y, Zhang JL, Zhou CL, Jin L, Wang L, Zhang C, Xu CM, Chen SC, Zhang SY, Sun XX, Wu YT, Sun Y, Huang HF. Preimplantation genetic testing for aneuploidy in severe male factor infertility: protocol for a multicenter randomised controlled trial. BMJ Open. 2022 Jul 13;12(7):e063030. doi: 10.1136/bmjopen-2022-063030.

Study record dates

Study Major Dates

• Study Start (Actual): July 18, 2017
• Primary Completion (Anticipated): August 30, 2022
• Study Completion (Anticipated): June 30, 2023

Study Registration Dates

• First Submitted: October 19, 2016
• First Submitted That Met QC Criteria: October 19, 2016
• First Posted (Estimate): October 21, 2016

Study Record Updates

• Last Update Posted (Actual): June 6, 2022
• Last Update Submitted That Met QC Criteria: June 1, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infertility; Infertility, Male
• Other Study ID Numbers: IPMCH2016001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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