Evaluation of an Undisturbed Embryo Culture System for Embryo Development in IVF/ICSI Cycles

NCT07522281 | Not Yet Recruiting

• 1 other identifier: 2025ZSLYFEC-014
• Study Type: interventional
• Target: 478
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a prospective, multicenter, randomized controlled clinical trial designed to evaluate whether a fully undisturbed closed embryo culture system can improve the developmental potential of embryos cultured in vitro and provide high-quality evidence for its clinical application. Participants must meet all of the following criteria to be eligible for this study: 1）Patients meeting the indications for IVF or ICSI; 2)No more than two previous IVF/ICSI embryo transfer cycles; 3) Willingness to culture all fertilized embryos to the blastocyst stage (Day 5/6); 4) AMH ≥1.2 ng/mL and AFC ≥7; 5) Fewer than 20 oocytes retrieved and serum estradiol level on the day of hCG administration \<5000 pg/mL. Exclusion Criteria (Participants meeting any of the following criteria will be excluded): 1）History of low fertilization rate in previous cycles (fertilization rate \<25%); 2）Oocyte donation or sperm donation cycles; 3）Either partner has a known chromosomal abnormality on karyotype analysis, or the couple plans to undergo preimplantation genetic testing (PGT); 4）Conditions that may affect oocyte quality, including premature ovarian insufficiency, endometriosis, ovarian endometrioma, or a history of two or more pelvic surgeries; 5）Requirement for surgical sperm retrieval, including microsurgical sperm retrieval or testicular sperm extraction; 6）Significant untreated uterine factors that may impair embryo implantation, including: submucosal uterine fibroids; two or more intramural fibroids, with the largest diameter ≥3 cm and significant compression of the uterine cavity causing cavity distortion; untreated moderate to severe intrauterine adhesions; one or more endometrial polyps with a maximum diameter ≥1.0 cm, or two or more space-occupying endometrial polyps within the uterine cavity; untreated moderate to severe hydrosalpinx (diameter ≥3 cm); 7）History of fertilization or oocyte maturation disorders, including fertilization failure in a previous ICSI cycle or previous oocyte maturation disorder. After ovarian stimulation, all cumulus-oocyte complexes (COCs) from each patient will be randomly allocated in a 1:1 ratio to the control group or the experimental group.In the control group, oocytes will be fertilized using Vitrolife fertilization medium and cultured in a conventional sequential culture system consisting of a benchtop incubator and sequential culture media. In the experimental group, oocytes will be fertilized using Gems FEM fertilization medium and cultured in an undisturbed system consisting of a Geri incubator and Gems one-step culture medium. After culture of all embryos to the blastocyst stage, a single best-quality blastocyst (better than 4BC) will be selected for transfer according to the Gardner morphological grading system, provided that patient interests are not compromised. The primary outcome is clinical pregnancy rate, defined as the proportion of clinical pregnancy cycles among all embryo transfer cycles. Clinical pregnancy will be assessed 4-7 weeks after embryo transfer by ultrasound detection of an intrauterine gestational sac or pathological confirmation of miscarriage tissue. Secondary outcomes include fertilization rate, normal fertilization rate after ICSI, cleavage rate, Day 3 good-quality embryo rate, Day 3 usable embryo rate, good-quality blastocyst formation rate, Day 5/6 usable blastocyst rate, blastocyst formation rate, implantation rate, biochemical pregnancy rate, early miscarriage rate, ongoing pregnancy rate, live birth rate. Based on an average clinical pregnancy rate of 50%, and assuming a non-inferiority margin of 12% (Δ = -0.12), with α = 0.05, β = 0.20, 80% power, and 1:1 allocation, at least 430 cycles will be required. After allowing for a 10% dropout rate, a total of 478 cycles (239 per group) will be enrolled. Participant recruitment is planned from November 1, 2025, to December 30, 2027, across the following 12 study centers: Center for Reproductive Medicine, The Sixth Affiliated Hospital, Sun Yat-sen University (leading center); Center for Reproductive Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology; Reproductive Center, Northwest Women's and Children's Hospital; Shenzhen Zhongshan Obstetrics and Gynecology Hospital; Assisted Reproduction Center, Jiangxi Maternal and Child Health Hospital; Center for Reproductive Medicine, West China Second University Hospital, Sichuan University; Center for Reproductive Medicine, General Hospital of Ningxia Medical University; Reproductive Center, Affiliated Hospital of Jining Medical University; Center for Reproductive Medicine, Nanjing Maternal and Child Health Care Hospital; Reproductive Center, Chenzhou First People's Hospital; Center for Reproductive Medicine, Changde First People's Hospital; and Center for Reproductive Medicine, The First Affiliated Hospital of Hainan Medical University.

Conditions

Embryo Culture; Embryo Culture Media; Embryo Quality

Outcome Measures

Primary Outcomes (1)

• clinical pregnancy rate

  The percentage of clinical pregnancy cycles among all embryo transfer cycles.

  Detection of an intrauterine gestational sac by ultrasonography 4-7 weeks after embryo transfer, or pathological confirmation of products of miscarriage

Study Arms (2)

Gems FEM fertilization medium+Geri incubator and Gems one-step culture medium

EXPERIMENTAL

In the experimental group, oocytes will be fertilized using Gems FEM fertilization medium and cultured to the blastocyst stage in an undisturbed culture system consisting of a Geri incubator and Gems one-step culture medium. Embryos in the experimental group will be cultured continuously without interruption until the blastocyst stage (Day 5/6). Embryologists will assess and assign Gardner scores to the embryos based on the morphology of the trophectoderm (TE) and inner cell mass (ICM), in combination with embryo morphokinetic data.

Device: Gems FEM fertilization medium + Geri incubator+Gems one-step medium

Vitrolife fertilization medium+benchtop incubator +sequential culture media

OTHER

In the control group, oocytes will be fertilized using Vitrolife fertilization medium and cultured in a conventional sequential culture system consisting of a benchtop incubator and sequential culture media. Embryos in the control group will be cultured using the Vitrolife sequential culture system. After fertilization, embryos will first be cultured in G1 medium until the cleavage stage, and on Day 3 the culture medium will be changed to G2 blastocyst medium for continued culture until the blastocyst stage (Day 5/6). After blastocyst formation, embryologists will assign Gardner scores based on the morphological characteristics of the trophectoderm (TE) and inner cell mass (ICM).

Other: Vitrolife fertilization medium+benchtop incubator + Vitrolife sequential culture media

Interventions

Gems FEM fertilization medium + Geri incubator+Gems one-step medium DEVICE

In the experimental group, oocytes will be fertilized using Gems FEM fertilization medium and cultured to the blastocyst stage in an undisturbed culture system consisting of a Geri incubator and Gems one-step culture medium (Undisturbed embryos culture system).

Gems FEM fertilization medium+Geri incubator and Gems one-step culture medium

Vitrolife fertilization medium+benchtop incubator + Vitrolife sequential culture media OTHER

In the control group, oocytes will be fertilized using Vitrolife fertilization medium, and the resulting embryos will be cultured to the blastocyst stage in a sequential culture system consisting of a benchtop incubator and sequential culture media (Traditional embryos sequential culture system)

Vitrolife fertilization medium+benchtop incubator +sequential culture media

Eligibility Criteria

• Age: 20 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Patients entering an ART cycle at the reproductive medicine center after study initiation and meeting the indications for IVF or ICSI;
• No more than two previous IVF/ICSI embryo transfer cycles;
• Agreement to culture all fertilized embryos to the blastocyst stage (Day 5/Day 6);
• AMH ≥1.2 ng/mL and AFC ≥7;
• Fewer than 20 oocytes retrieved and serum estradiol level on the day of hCG administration \<5000 pg/mL.

You may not qualify if:

• History of low fertilization rate in previous cycles (fertilization rate \<25%);
• Oocyte donation or sperm donation cycles;
• Either partner has a known chromosomal abnormality on karyotype analysis, or the couple plans to undergo preimplantation genetic testing (PGT);
• Conditions that may affect oocyte quality, including premature ovarian insufficiency, endometriosis, ovarian endometrioma, or a history of two or more pelvic surgeries;
• Requirement for surgical sperm retrieval, including microsurgical sperm retrieval or testicular sperm extraction;
• Significant untreated uterine factors that may impair embryo implantation, including: submucosal uterine fibroids; two or more intramural fibroids, with the largest diameter ≥3 cm and significant compression of the uterine cavity causing cavity distortion; untreated moderate to severe intrauterine adhesions; one or more endometrial polyps with a maximum diameter ≥1.0 cm, or two or more space-occupying endometrial polyps within the uterine cavity; untreated moderate to severe hydrosalpinx (diameter ≥3 cm);
• History of fertilization or oocyte maturation disorders, including fertilization - failure in a previous ICSI cycle or previous oocyte maturation disorder.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Central Study Contacts

Xiaoyan Liang, archiater

CONTACT

020-38048013; liangxy2@mail.sysu.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Reproductive Medicine

Study Record Dates

• First Submitted: April 3, 2026
• First Posted: April 13, 2026
• Study Start: April 15, 2026
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 30, 2027
• Last Updated: April 15, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share