Back to resultsICSI Versus Conventional IVF in Couples With Non-severe Male Infertility (ICSI/IVF-NSMI)
Primary Purpose
Male Infertility
Status
Completed
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
ICSI
Conventional IVF
Sponsored by
About this trial
This is an interventional treatment trial for Male Infertility focused on measuring Male infertility, In vitro fertilization, Intracytoplasmic sperm injection
Eligibility Criteria
Inclusion Criteria:
- Infertile couples scheduled for their first or second IVF/ICSI cycle.
- Men with non-severe male infertility: Sperm concentration 5,000,000-15,000,000/ml or sperm with progressive motility (type A+B) 10-32%.
- Women received either gonadotrophin-releasing hormone agonist protocol or gonadotrophin-releasing hormone antagonist protocol as their controlled ovarian hyperstimulation treatment.
- Informed consent obtained.
Exclusion Criteria:
- Couple with contraindication for IVF or ICSI.
- Couples receiving donor sperm or donor eggs.
- Couples undergoing PGD and PGS.
- Sperm concentration with progressive motility used for insemination <100,000/ml on the day of oocyte retrieval.
- Women with 0 oocytes after oocyte retrieval.
- Using frozen semen.
- Poor fertilization in previous cycle (≤ 25%).
Sites / Locations
- First Affiliated Hospital of Anhui Medical University
- Peking University third Hospital
- Haidian Maternal and Child Health Hospital
- The Third Affiliated Hospital of Guangzhou Medical University
- The Sixth Affiliated Hospital of Sun Yat-Sen University
- The Second Hospital of Hebei Medical University
- General Hospital of Ningxia Medical University
- International Peace Maternity and Child Health Hospital of Shanghai Jiao Tong University
- First Affiliated Hospital of Kunming Medical University
- Women's Hospital of Zhejiang University
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Intracytoplasmic Sperm Injection
Conventional IVF
Arm Description
On the day of oocyte retrieval, qualified participants will be randomized into either of two groups. Participants in group A will undergone Intracytoplasmic Sperm Injection (ICSI) procedure, other standard assisted reproductive treatments are similar and parallel between two groups.
On the day of oocyte retrieval, qualified participants will be randomized into either of two groups. Participants in this group will undergone Conventional In Vitro Fertilization (IVF) procedure, other standard assisted reproductive treatments are similar and parallel between two groups.
Outcomes
Primary Outcome Measures
Ongoing pregnancy leading to live birth after the first cycle with embryo transfer
A delivery of one or more living infants (≥22 weeks gestation or birth weight more than 1,000g).
Secondary Outcome Measures
Fertilization
Number of zygotes with 2 PN (per oocyte retrieved and per women randomized).
Total fertilization failure
No oocyte formed 2 PN in this given cycle.
Available embryo
Number of embryos ≥4 cells and ≤30% fragmentation on day 3 observation.
Good quality embryo
Number of embryos with ≥6 cells and ≤30% fragmentation developed from 2PN embryos on day 3 observation.
Implantation
Number of gestational sacs observed per embryo transferred.
Clinical pregnancy
One or more observed gestational sac or definitive clinical signs of pregnancy under ultrasonography at 7 weeks after embryo transfer (including clinically documented ectopic pregnancy).
Multiple pregnancy
Pregnancy with two or more gestational sacs or positive heart beats at 7 weeks of gestation.
Ongoing pregnancy
Presence of a gestational sac and fetal heartbeat after 12 weeks of gestation.
Moderate/severe ovarian hyperstimulation syndrome (OHSS)
exaggerated systemic response to ovarian stimulation characterized by a wide spectrum of clinical and laboratory manifestations. It is classified as mild, moderate, or severe according to the degree of abdominal distention, ovarian Enlargement, and respiratory, hemodynamic, and metabolic complications.
Miscarriage
Spontaneous loss of an intra-uterine pregnancy prior to 22 completed weeks of gestational age.
Ectopic pregnancy
Implantation takes place outside the uterine cavity, confirmed by sonography or laparoscopy.
Gestational diabetes mellitus (GDM)
Hypertensive disorders of pregnancy
Comprising pregnancy induced hypertension (PIH); pre-eclampsia (PET) and eclampsia.
Antepartum haemorrhage
Including placenta previa, placenta accreta and unexplained.
Preterm birth
Birth of a fetus delivered after 28 and before 37 completed weeks of gestational age in participants confirmed ongoing pregnancy.
Birth weight
Including low birth weight (defined as weight < 2500 gm at birth), very low birth weight (defined as < 1500 gm at birth), high birth weight (defined as >4000 gm at birth) and very high birth weight (defined as >4500 gm at birth).
Large for gestational age
Birth weight >90th centile for gestation, based on standardised ethnicity based charts.
Small for gestational age
Less than 10th centile for gestational age at delivery based on standardised ethnicity based charts.
Congenital anomaly
Any congenital anomaly will be included.
Perinatal mortality
Fetal or neonatal death occurring during late pregnancy (at 28 completed weeks of gestational age and later), during childbirth, or up to seven completed days after birth.
Neonatal mortality
death of a live born baby within 28 days of birth
Full Information
NCT ID
NCT03298633
First Posted
September 22, 2017
Last Updated
July 25, 2023
Sponsor
Jie Qiao
Collaborators
International Peace Maternity and Child Health Hospital, Women's Hospital School Of Medicine Zhejiang University, Sixth Affiliated Hospital, Sun Yat-sen University, First Affiliated Hospital of Kunming Medical University, Beijing Haidian Maternal and Child Health Hospital, The First Affiliated Hospital of Anhui Medical University, The Second Hospital of Hebei Medical University, The Third Affiliated Hospital of Guangzhou Medical University, General Hospital of Ningxia Medical University
1. Study Identification
Unique Protocol Identification Number
NCT03298633
Brief Title
ICSI Versus Conventional IVF in Couples With Non-severe Male Infertility
Acronym
ICSI/IVF-NSMI
Official Title
Intracytoplasmic Sperm Injection (ICSI) Versus Conventional in Vitro Fertilization (IVF) in Couples With Non-severe Male Infertility: a Randomized Controlled Trial
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Completed
Study Start Date
April 4, 2018 (Actual)
Primary Completion Date
January 31, 2023 (Actual)
Study Completion Date
March 31, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Jie Qiao
Collaborators
International Peace Maternity and Child Health Hospital, Women's Hospital School Of Medicine Zhejiang University, Sixth Affiliated Hospital, Sun Yat-sen University, First Affiliated Hospital of Kunming Medical University, Beijing Haidian Maternal and Child Health Hospital, The First Affiliated Hospital of Anhui Medical University, The Second Hospital of Hebei Medical University, The Third Affiliated Hospital of Guangzhou Medical University, General Hospital of Ningxia Medical University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
A multicenter, parallel-controlled(1:1 treatment ratio), open-label, randomized clinical trials regarding fertilization and pregnancy outcomes between ICSI and conventional IVF among couples with no-severe male-factor infertility in China.
Detailed Description
A multicenter, large-scale, randomized controlled clinical trial will enroll 2,346 couples with non-severe male infertility undergoing their first or second 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 2 years with a total of 7 visits from controlled ovarian hyperstimulation, pregnancy to delivery. On the day of oocyte retrieval, eligible participants will be allocated to two groups at a ratio of 1:1- ICSI protocol, and conventional IVF protocol. All participants will be randomized through stratified block randomization according to the study sites.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Male Infertility
Keywords
Male infertility, In vitro fertilization, Intracytoplasmic sperm injection
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Eligible patients that have provided informed consent will be randomized to either ICSI or conventional IVF. Randomization and allocation of patients to study groups will be performed on the day of oocyte retrieval. Stratified permuted block randomization will be centrally controlled by administrative staffs in the trial center, who are not involved in the treatment procedure. When there is an eligible participant to be enrolled into the study, nurses from the specific site will login the trial system to get allocation of patients according to a computer-generated randomization list in a 1:1 ratio, with a variable block size of 2, 4 or 8 and stratified by center.
Masking
None (Open Label)
Masking Description
The blinding method in out study is open-label in general. However, in order to avoid psychological effect for participants and unexpected drop-off, the trial is designed to inform participants their insemination method on the day of fresh embryo transfer or the day of embryo freezing. Prior to this, randomization will be strictly performed and keep secret to participants and clinicians.
Allocation
Randomized
Enrollment
2387 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Intracytoplasmic Sperm Injection
Arm Type
Active Comparator
Arm Description
On the day of oocyte retrieval, qualified participants will be randomized into either of two groups. Participants in group A will undergone Intracytoplasmic Sperm Injection (ICSI) procedure, other standard assisted reproductive treatments are similar and parallel between two groups.
Arm Title
Conventional IVF
Arm Type
Active Comparator
Arm Description
On the day of oocyte retrieval, qualified participants will be randomized into either of two groups. Participants in this group will undergone Conventional In Vitro Fertilization (IVF) procedure, other standard assisted reproductive treatments are similar and parallel between two groups.
Intervention Type
Other
Intervention Name(s)
ICSI
Intervention Description
All patients will receive controlled ovarian hyperstimulation (COH) treatment, which is performed by standard routines at each study center. The COH treatment includes either gonadotrophin-releasing hormone agonist (GnRH-a) protocol or gonadotrophin-releasing hormone antagonist (GnRH-ant) protocol.Oocyte retrieval is scheduled for 36 (±2) after hCG injection.The retrieved cumulus oocyte complexes (COC) will be allocated to undergo routine ICSI procedure according to the result of randomization in each study site.
Intervention Type
Other
Intervention Name(s)
Conventional IVF
Intervention Description
All patients will receive controlled ovarian hyperstimulation (COH) treatment, which is performed by standard routines at each study center. The COH treatment includes either gonadotrophin-releasing hormone agonist (GnRH-a) protocol or gonadotrophin-releasing hormone antagonist (GnRH-ant) protocol.Oocyte retrieval is scheduled for 36 (±2) after hCG injection.The retrieved cumulus oocyte complexes (COC) will be allocated to undergo conventional IVF procedure according to the result of randomization in each study site.
Primary Outcome Measure Information:
Title
Ongoing pregnancy leading to live birth after the first cycle with embryo transfer
Description
A delivery of one or more living infants (≥22 weeks gestation or birth weight more than 1,000g).
Time Frame
After 22 weeks of gestation
Secondary Outcome Measure Information:
Title
Fertilization
Description
Number of zygotes with 2 PN (per oocyte retrieved and per women randomized).
Time Frame
16-20 hours after oocyte retrieval
Title
Total fertilization failure
Description
No oocyte formed 2 PN in this given cycle.
Time Frame
72 hours after oocyte retrieval
Title
Available embryo
Description
Number of embryos ≥4 cells and ≤30% fragmentation on day 3 observation.
Time Frame
72 hours after oocyte retrieval
Title
Good quality embryo
Description
Number of embryos with ≥6 cells and ≤30% fragmentation developed from 2PN embryos on day 3 observation.
Time Frame
72 hours after oocyte retrieval
Title
Implantation
Description
Number of gestational sacs observed per embryo transferred.
Time Frame
28 days after embryo transfer
Title
Clinical pregnancy
Description
One or more observed gestational sac or definitive clinical signs of pregnancy under ultrasonography at 7 weeks after embryo transfer (including clinically documented ectopic pregnancy).
Time Frame
7 weeks after embryo transfer
Title
Multiple pregnancy
Description
Pregnancy with two or more gestational sacs or positive heart beats at 7 weeks of gestation.
Time Frame
7 weeks after embryo transfer
Title
Ongoing pregnancy
Description
Presence of a gestational sac and fetal heartbeat after 12 weeks of gestation.
Time Frame
12 weeks after embryo transfer
Title
Moderate/severe ovarian hyperstimulation syndrome (OHSS)
Description
exaggerated systemic response to ovarian stimulation characterized by a wide spectrum of clinical and laboratory manifestations. It is classified as mild, moderate, or severe according to the degree of abdominal distention, ovarian Enlargement, and respiratory, hemodynamic, and metabolic complications.
Time Frame
From date of controlled ovarian hyperstimulation until the date of oocyte retrieval, assessed about 14-16 days.
Title
Miscarriage
Description
Spontaneous loss of an intra-uterine pregnancy prior to 22 completed weeks of gestational age.
Time Frame
22 weeks of gestation
Title
Ectopic pregnancy
Description
Implantation takes place outside the uterine cavity, confirmed by sonography or laparoscopy.
Time Frame
7 weeks of gestation
Title
Gestational diabetes mellitus (GDM)
Time Frame
24-37 weeks of pregnancy
Title
Hypertensive disorders of pregnancy
Description
Comprising pregnancy induced hypertension (PIH); pre-eclampsia (PET) and eclampsia.
Time Frame
28-37 weeks of pregnancy
Title
Antepartum haemorrhage
Description
Including placenta previa, placenta accreta and unexplained.
Time Frame
28-37 weeks of pregnancy
Title
Preterm birth
Description
Birth of a fetus delivered after 28 and before 37 completed weeks of gestational age in participants confirmed ongoing pregnancy.
Time Frame
28-37 weeks of pregnancy
Title
Birth weight
Description
Including low birth weight (defined as weight < 2500 gm at birth), very low birth weight (defined as < 1500 gm at birth), high birth weight (defined as >4000 gm at birth) and very high birth weight (defined as >4500 gm at birth).
Time Frame
Within 2 weeks after live birth
Title
Large for gestational age
Description
Birth weight >90th centile for gestation, based on standardised ethnicity based charts.
Time Frame
Within 2 weeks after live birth
Title
Small for gestational age
Description
Less than 10th centile for gestational age at delivery based on standardised ethnicity based charts.
Time Frame
Within 2 weeks after live birth
Title
Congenital anomaly
Description
Any congenital anomaly will be included.
Time Frame
Within 2 weeks after live birth
Title
Perinatal mortality
Description
Fetal or neonatal death occurring during late pregnancy (at 28 completed weeks of gestational age and later), during childbirth, or up to seven completed days after birth.
Time Frame
Within 6 weeks after live birth
Title
Neonatal mortality
Description
death of a live born baby within 28 days of birth
Time Frame
Within 6 weeks after live birth
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Infertile couples scheduled for their first or second IVF/ICSI cycle.
Men with non-severe male infertility: Sperm concentration 5,000,000-15,000,000/ml or sperm with progressive motility (type A+B) 10-32%.
Women received either gonadotrophin-releasing hormone agonist protocol or gonadotrophin-releasing hormone antagonist protocol as their controlled ovarian hyperstimulation treatment.
Informed consent obtained.
Exclusion Criteria:
Couple with contraindication for IVF or ICSI.
Couples receiving donor sperm or donor eggs.
Couples undergoing PGD and PGS.
Sperm concentration with progressive motility used for insemination <100,000/ml on the day of oocyte retrieval.
Women with 0 oocytes after oocyte retrieval.
Using frozen semen.
Poor fertilization in previous cycle (≤ 25%).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jie Qiao, M.D.
Organizational Affiliation
Peking University Third Hospital
Official's Role
Study Director
Facility Information:
Facility Name
First Affiliated Hospital of Anhui Medical University
City
Hefei
State/Province
Anhui
ZIP/Postal Code
230022
Country
China
Facility Name
Peking University third Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100191
Country
China
Facility Name
Haidian Maternal and Child Health Hospital
City
Beijing
State/Province
Beijing
Country
China
Facility Name
The Third Affiliated Hospital of Guangzhou Medical University
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510150
Country
China
Facility Name
The Sixth Affiliated Hospital of Sun Yat-Sen University
City
Guangzhou
State/Province
Guangdong
Country
China
Facility Name
The Second Hospital of Hebei Medical University
City
Shijiazhuang
State/Province
Hebei
ZIP/Postal Code
050000
Country
China
Facility Name
General Hospital of Ningxia Medical University
City
Yinchuan
State/Province
Ningxia
ZIP/Postal Code
750004
Country
China
Facility Name
International Peace Maternity and Child Health Hospital of Shanghai Jiao Tong University
City
Shanghai
State/Province
Shanghai
Country
China
Facility Name
First Affiliated Hospital of Kunming Medical University
City
Kunming
State/Province
Yunnan
Country
China
Facility Name
Women's Hospital of Zhejiang University
City
Hangzhou
State/Province
Zhejiang
Country
China
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
31575574
Citation
Zheng D, Zeng L, Yang R, Lian Y, Zhu YM, Liang X, Tang L, Wang H, Cao Y, Hao G, Liu J, Zhao J, Wang R, Mol BW, Li R, Huang HF, Qiao J. Intracytoplasmic sperm injection (ICSI) versus conventional in vitro fertilisation (IVF) in couples with non-severe male infertility (NSMI-ICSI): protocol for a multicentre randomised controlled trial. BMJ Open. 2019 Sep 30;9(9):e030366. doi: 10.1136/bmjopen-2019-030366.
Results Reference
derived
Learn more about this trial
ICSI Versus Conventional IVF in Couples With Non-severe Male Infertility
We'll reach out to this number within 24 hrs