ICSI Versus Conventional IVF in Couples With Unexplained Infertility

NCT07294027 | Not Yet Recruiting

• 1 other identifier: 2025-0689
• Study Type: interventional
• Target: 848
• Locations: 1 country
• Sites: 7

Brief Summary

This multicenter, open-label, parallel-group, randomized controlled trial aims to compare the live birth rate, fertilization outcomes, other pregnancy outcomes and safety between ICSI and conventional IVF among couples with unexplained infertility in China.

Conditions

Unexplained Infertility

Keywords

Unexplained infertility; Conventional in vitro fertilization; Intracytoplasmic sperm injection

Outcome Measures

Primary Outcomes (1)

• Live birth rate after the first embryo transfer cycle

  Live birth is defined as the birth of at least one newborn after 24 weeks' gestation that exhibits any sign of life (twin will be a single count).

  At birth

Secondary Outcomes (42)

• Cumulative ongoing pregnancy rate within one year

  At 12 weeks of gestation; At 12 months after randomization

• Number of retrieved oocyte

  2 hours after oocyte retrieval

• MII rate

  2 hours after oocyte retrieval

• Fertilization rate per oocyte inseminated/injected

  At 16-18 hours after insemination or injection

• Fertilization rate per oocyte retrieved

  At 16-18 hours after insemination or injection

Study Arms (2)

Intracytoplasmic Sperm Injection (ICSI)

ACTIVE COMPARATOR

All patients will receive controlled ovarian hyperstimulation (COH) treatment, which is performed by standard routines at each study center. The COH treatment includes either GnRH agonist protocol or GnRH antagonist protocol. Oocyte retrieval is scheduled for 36 (±2) hours after hCG injection. The retrieved cumulus oocyte complexes (COCs) will be allocated to undergo ICSI procedure according to the result of randomization. The first embryo transfer is performed using fresh embryo transfer (if without contraindication), limited to transferring 1-2 cleavage embryos or 1 blastocyst. The remaining available embryos will be frozen.

Procedure: ICSI

Conventional in vitro fertilization (c-IVF)

ACTIVE COMPARATOR

All patients will receive controlled ovarian hyperstimulation (COH) treatment, which is performed by standard routines at each study center. The COH treatment includes either GnRH agonist protocol or GnRH antagonist protocol. Oocyte retrieval is scheduled for 36 (±2) hours after hCG injection. The retrieved cumulus oocyte complexes (COCs) will be allocated to undergo conventional IVF procedure according to the result of randomization. The first embryo transfer is performed using fresh embryo transfer (if without contraindication), limited to transferring 1-2 cleavage embryos or 1 blastocyst. If the embryos in the IVF group are fertilized through different methods (some with late-RICSI), the first embryo transfer is limited to embryos fertilized through conventional IVF. The remaining available embryos will be frozen.

Procedure: IVF

Interventions

ICSI PROCEDURE

Insemination will be performed by using ICSI, 2 hours after oocyte retrieval. COCs will be stripped by using hyaluronidase. Only matured oocytes (MII stage) will be injected. Fertilization check will be performed at period of 16-18 hours after injection. Other standard assisted reproductive treatments are similar and parallel between two groups.

Intracytoplasmic Sperm Injection (ICSI)

IVF PROCEDURE

Insemination will be performed by using conventional IVF, 2-4 hours after oocyte retrieval. Collected COCs will be inseminated (1-5×105 sperm/ml) and cultured overnight in culture medium. Fertilization check will be performed at period of 16-18 hours after insemination. If the IVF group experiences total fertilization failure or a fertilization rate of less than 25%, late rescue ICSI (Late-RICSI) will be performed on all MII stage oocytes using semen retained on the day of egg retrieval. The injection method is same as standard ICSI. Other standard assisted reproductive treatments are similar and parallel between two groups.

Conventional in vitro fertilization (c-IVF)

Eligibility Criteria

• Age: 20 Years - 38 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Aged 20-38 years
• \< BMI \< 24kg/m2
• Couples diagnosed with primary unexplained infertility:
• Regular menses or confirmed ovulation;
• Normal ovarian reserve;
• Patent fallopian tubes;
• Normal uterus and cervix;
• Normal endocrine profile;
• Semen analysis meeting WHO 6th edition criteria
• Normal karyotypes in both partners, no family history of genetic disorders
• First IVF/ICSI cycle
• Received GnRH agonist protocol or GnRH antagonist protocol
• Willing to provide informed consent and comply with follow-up

You may not qualify if:

• Preimplantation genetic testing (PGT) cycles
• In vitro maturation (IVM) cycles
• Using donor sperm/oocyte
• Using frozen sperm/oocyte
• \<5 oocytes retrieved
• Abnormal semen parameters on the day of oocyte retrieval
• Untreated or poorly controlled endocrine disorders
• Abnormal immune related examinations
• Major organ/system disorders (cardiac, hepatic, renal, oncologic, hematologic, psychiatric, etc.)
• Concurrent participation in other clinical trials.

Sponsors & Collaborators

• Renmin Hospital of Wuhan University: collaborator
• Jiaxing Maternity and Child Health Care Hospital: collaborator
• Ningbo Women & Children's Hospital: collaborator
• Beijing Obstetrics and Gynecology Hospital: collaborator
• Xiangyang Central Hospital: collaborator
• Huangshi Central Hospital: collaborator
• Second Affiliated Hospital, School of Medicine, Zhejiang University: lead

Study Sites (7)

Beijing Obstetrics and Gynecology Hospital, Capital Medical University

Beijing, Beijing Municipality, China

Location

Huangshi Central Hospital

Huangshi, Hubei, 435000, China

Location

Renmin Hospital of Wuhan University

Wuhan, Hubei, 430060, China

Location

Xiangyang Central Hospital

Xiangyang, Hubei, 441021, China

Location

Second Affiliated Hospital, School of Medicine, Zhejiang University

Hangzhou, Zhejiang, 310052, China

Location

Jiaxing Maternity and Child Health Care Hospital

Jiaxing, Zhejiang, 314051, China

Location

Ningbo Women & Children's Hospital

Ningbo, Zhejiang, 315012, China

Location

MeSH Terms

Interventions

Sperm Injections, Intracytoplasmic

Intervention Hierarchy (Ancestors)

Fertilization in Vitro; Reproductive Techniques, Assisted; Reproductive Techniques; Therapeutics; Investigative Techniques

Study Officials

• Min Jin, PhD

  Second Affiliated Hospital, School of Medicine, Zhejiang University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Min Jin, PhD

CONTACT

+86-15925602121; min_jin@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: To safeguard patients' right to know and in accordance with previous similar studies, this study adopted an open-label design. Both participants and recruiters will be aware of the group assignments. However, the doctors performing embryo transfers, medical staff conducting routine prenatal check-ups and laboratory technicians analyzing biological samples will not be directly informed of whether patients participate in this clinical study and their grouping status.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a multicenter study. Each center enrolls participants using a competitive enrollment method and performs online randomization through the trial system. Using block randomization with a 1:1 allocation ratio, participants were assigned to either the ICSI group or the IVF group, with a block length set at 8. The trial system administrators were not involved in the treatment process. Eligible patients who provided informed consent were registered in the trial system by medical staff at each center on the day of oocyte retrieval. After entering participant information, the system automatically assigned patients based on pre-set parameters.

Study Record Dates

• First Submitted: August 27, 2025
• First Posted: December 19, 2025
• Study Start: January 1, 2026
• Primary Completion (Estimated): July 30, 2028
• Study Completion (Estimated): July 30, 2028
• Last Updated: December 19, 2025

Record last verified: 2025-08

Locations

CN (7)