CClinicalTrials.gg
CompletedNCT03298633ICSI/IVF-NSMIUpdated Jul 27, 2023

ICSI Versus Conventional IVF in Couples With Non-severe Male Infertility

An interventional study of ICSI and Conventional IVF in Male Infertility, sponsored by Jie Qiao. Completed at 10 sites in China. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-07-27.

Sponsored by Jie Qiao · Not applicable, Interventional, and Treatment

Phase
Not applicable
Study type
Interventional
Enrollment
2,387
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Male Infertility

Keywords

  • Male infertility
  • In vitro fertilization
  • Intracytoplasmic sperm injection
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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%).
04

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
2,387 participants (actual)

Study arms

  • 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

  • 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

Interventions

  • OtherICSI

    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.

  • OtherConventional 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.

05

What researchers measure

Primary outcomes

  1. 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).

    Time frame: After 22 weeks of gestation

Secondary outcomes

  1. Fertilization

    Number of zygotes with 2 PN (per oocyte retrieved and per women randomized).

    Time frame: 16-20 hours after oocyte retrieval

  2. Total fertilization failure

    No oocyte formed 2 PN in this given cycle.

    Time frame: 72 hours after oocyte retrieval

  3. Available embryo

    Number of embryos ≥4 cells and ≤30% fragmentation on day 3 observation.

    Time frame: 72 hours after oocyte retrieval

  4. Good quality embryo

    Number of embryos with ≥6 cells and ≤30% fragmentation developed from 2PN embryos on day 3 observation.

    Time frame: 72 hours after oocyte retrieval

  5. Implantation

    Number of gestational sacs observed per embryo transferred.

    Time frame: 28 days after embryo transfer

  6. 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).

    Time frame: 7 weeks after embryo transfer

  7. Multiple pregnancy

    Pregnancy with two or more gestational sacs or positive heart beats at 7 weeks of gestation.

    Time frame: 7 weeks after embryo transfer

  8. Ongoing pregnancy

    Presence of a gestational sac and fetal heartbeat after 12 weeks of gestation.

    Time frame: 12 weeks after embryo transfer

  9. 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.

    Time frame: From date of controlled ovarian hyperstimulation until the date of oocyte retrieval, assessed about 14-16 days.

  10. Miscarriage

    Spontaneous loss of an intra-uterine pregnancy prior to 22 completed weeks of gestational age.

    Time frame: 22 weeks of gestation

  11. Ectopic pregnancy

    Implantation takes place outside the uterine cavity, confirmed by sonography or laparoscopy.

    Time frame: 7 weeks of gestation

  12. Gestational diabetes mellitus (GDM)

    Time frame: 24-37 weeks of pregnancy

  13. Hypertensive disorders of pregnancy

    Comprising pregnancy induced hypertension (PIH); pre-eclampsia (PET) and eclampsia.

    Time frame: 28-37 weeks of pregnancy

  14. Antepartum haemorrhage

    Including placenta previa, placenta accreta and unexplained.

    Time frame: 28-37 weeks of pregnancy

  15. Preterm birth

    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

  16. 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).

    Time frame: Within 2 weeks after live birth

  17. Large for gestational age

    Birth weight \>90th centile for gestation, based on standardised ethnicity based charts.

    Time frame: Within 2 weeks after live birth

  18. Small for gestational age

    Less than 10th centile for gestational age at delivery based on standardised ethnicity based charts.

    Time frame: Within 2 weeks after live birth

  19. Congenital anomaly

    Any congenital anomaly will be included.

    Time frame: Within 2 weeks after live birth

  20. 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.

    Time frame: Within 6 weeks after live birth

  21. Neonatal mortality

    death of a live born baby within 28 days of birth

    Time frame: Within 6 weeks after live birth

06

Study locations

10 sites
  • First Affiliated Hospital of Anhui Medical University
    Hefei, Anhui 230022, China
  • Peking University third Hospital
    Beijing, Beijing 100191, China
  • Haidian Maternal and Child Health Hospital
    Beijing, Beijing, China
  • The Third Affiliated Hospital of Guangzhou Medical University
    Guangzhou, Guangdong 510150, China
  • The Sixth Affiliated Hospital of Sun Yat-Sen University
    Guangzhou, Guangdong, China
  • The Second Hospital of Hebei Medical University
    Shijiazhuang, Hebei 050000, China
  • General Hospital of Ningxia Medical University
    Yinchuan, Ningxia 750004, China
  • International Peace Maternity and Child Health Hospital of Shanghai Jiao Tong University
    Shanghai, Shanghai, China
  • First Affiliated Hospital of Kunming Medical University
    Kunming, Yunnan, China
  • Women's Hospital of Zhejiang University
    Hangzhou, Zhejiang, China
07

References and documents

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. PubMed 31575574 ↗

Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT03298633
Lead 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
Responsible party
Jie Qiao (President, Peking University Third Hospital) — Sponsor-investigator
First posted
Oct 2, 2017
Start date
Apr 4, 2018
Primary completion
Jan 31, 2023
Completion
Mar 31, 2023
Last update
Jul 27, 2023

Study contacts

Jie Qiao, M.D.
study director · Peking University Third Hospital

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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