ICSI Versus Conventional IVF in Couples With Non-severe Male Infertility (ICSI/IVF-NSMI)

Intracytoplasmic Sperm Injection (ICSI) Versus Conventional in Vitro Fertilization (IVF) in Couples With Non-severe Male Infertility: a Randomized Controlled Trial

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.

Study Overview

• Status: Completed
• Conditions: Male Infertility
• Intervention / Treatment: Other: ICSI; Other: Conventional IVF

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.

• Study Type: Interventional
• Enrollment (Actual): 2387
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Danni Zheng, Bachelor; Phone Number: +86-010-82266630; Email: danilinda136@163.com
• Study Contact Backup: Name: Rui Yang, M.D.; Phone Number: +86-010-82265080; Email: yrjeff@126.com

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230022
      • First Affiliated Hospital of Anhui Medical University
  • Beijing
    • Beijing, Beijing, China, 100191
      • Peking University Third Hospital
    • Beijing, Beijing, China
      • Haidian Maternal and Child Health Hospital
  • Guangdong
    • Guangzhou, Guangdong, China, 510150
      • The Third Affiliated Hospital of Guangzhou Medical University
    • Guangzhou, Guangdong, China
      • The Sixth Affiliated Hospital of Sun Yat-sen University
  • Hebei
    • Shijiazhuang, Hebei, China, 050000
      • The Second Hospital of Hebei Medical University
  • Ningxia
    • Yinchuan, Ningxia, China, 750004
      • General Hospital of Ningxia Medical University
  • Shanghai
    • Shanghai, Shanghai, China
      • International Peace Maternity and Child Health Hospital of Shanghai Jiao Tong University
  • Yunnan
    • Kunming, Yunnan, China
      • First Affiliated Hospital of Kunming Medical University
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Women's Hospital of Zhejiang University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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%).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Intracytoplasmic Sperm Injection; 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.	Other: ICSI; 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.
Active Comparator: Conventional IVF; 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.	Other: Conventional IVF; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	After 22 weeks of gestation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fertilization	Number of zygotes with 2 PN (per oocyte retrieved and per women randomized).	16-20 hours after oocyte retrieval
Total fertilization failure	No oocyte formed 2 PN in this given cycle.	72 hours after oocyte retrieval
Available embryo	Number of embryos ≥4 cells and ≤30% fragmentation on day 3 observation.	72 hours after oocyte retrieval
Good quality embryo	Number of embryos with ≥6 cells and ≤30% fragmentation developed from 2PN embryos on day 3 observation.	72 hours after oocyte retrieval
Implantation	Number of gestational sacs observed per embryo transferred.	28 days after embryo transfer
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).	7 weeks after embryo transfer
Multiple pregnancy	Pregnancy with two or more gestational sacs or positive heart beats at 7 weeks of gestation.	7 weeks after embryo transfer
Ongoing pregnancy	Presence of a gestational sac and fetal heartbeat after 12 weeks of gestation.	12 weeks after embryo transfer
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.	From date of controlled ovarian hyperstimulation until the date of oocyte retrieval, assessed about 14-16 days.
Miscarriage	Spontaneous loss of an intra-uterine pregnancy prior to 22 completed weeks of gestational age.	22 weeks of gestation
Ectopic pregnancy	Implantation takes place outside the uterine cavity, confirmed by sonography or laparoscopy.	7 weeks of gestation
Gestational diabetes mellitus (GDM)		24-37 weeks of pregnancy
Hypertensive disorders of pregnancy	Comprising pregnancy induced hypertension (PIH); pre-eclampsia (PET) and eclampsia.	28-37 weeks of pregnancy
Antepartum haemorrhage	Including placenta previa, placenta accreta and unexplained.	28-37 weeks of pregnancy
Preterm birth	Birth of a fetus delivered after 28 and before 37 completed weeks of gestational age in participants confirmed ongoing pregnancy.	28-37 weeks of 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).	Within 2 weeks after live birth
Large for gestational age	Birth weight >90th centile for gestation, based on standardised ethnicity based charts.	Within 2 weeks after live birth
Small for gestational age	Less than 10th centile for gestational age at delivery based on standardised ethnicity based charts.	Within 2 weeks after live birth
Congenital anomaly	Any congenital anomaly will be included.	Within 2 weeks after live birth
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.	Within 6 weeks after live birth
Neonatal mortality	death of a live born baby within 28 days of birth	Within 6 weeks after live birth

Collaborators and Investigators

• Sponsor: Jie Qiao
• Collaborators: The First Affiliated Hospital of Anhui Medical University; The Second Hospital of Hebei Medical University; The Third Affiliated Hospital of Guangzhou Medical University; Women's Hospital School Of Medicine Zhejiang University; Sixth Affiliated Hospital, Sun Yat-sen University; General Hospital of Ningxia Medical University; Beijing Haidian Maternal and Child Health Hospital; International Peace Maternity and Child Health Hospital; First Affiliated Hospital of Kunming Medical University
• Investigators: Study Director: Jie Qiao, M.D., Peking University Third Hospital

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): April 4, 2018
• Primary Completion (Actual): January 31, 2023
• Study Completion (Actual): March 31, 2023

Study Registration Dates

• First Submitted: September 22, 2017
• First Submitted That Met QC Criteria: September 26, 2017
• First Posted (Actual): October 2, 2017

Study Record Updates

• Last Update Posted (Actual): July 27, 2023
• Last Update Submitted That Met QC Criteria: July 25, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Intracytoplasmic sperm injection; In vitro fertilization; Male infertility
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Infertility; Infertility, Male
• Other Study ID Numbers: ICSI/IVF-NSMI

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