A Multicenter Prospective Randomized Controlled Clinical Trial Comparing Constant (5%) Versus Sequential (5%-2%) Oxygen Concentration Embryo Culture Protocols in Assisted Reproductive Technology

NCT ID: NCT07050537

Last Updated: 2025-07-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

980 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-03-01

Study Completion Date

2027-08-31

Brief Summary

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To evaluate whether there were significant differences in the effects of constant (5%) versus sequential (5%-2%) oxygen concentration protocols in embryo culture on term live birth rates.

This study will be conducted in five centers including the Clinical Center of Reproductive Medicine, First Affiliated Hospital of Nanjing Medical Universit. 980 women who wish to undergo blastocyst transplantation will be included in the study.

The study data will be analyzed statistically.

Detailed Description

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While blastocyst transfer has been shown to improve live birth rates, concerns exist regarding potential telomere shortening in offspring, which is associated with premature aging and various health issues. Our previous study further explores the role of oxygen tension in telomere length regulation, identifying hypoxia-inducible factor 1α (Hif1α) degradation as a key factor. Based on these findings, the study proposes a prospective, randomized controlled clinical trial comparing constant (5%) versus sequential (5%-2%) oxygen concentration protocols in embryo culture to assess their impact on term live birth rates and offspring telomere length.

This study will be conducted in five centers including the Clinical Center of Reproductive Medicine, First Affiliated Hospital of Nanjing Medical Universit. 980 women who wish to undergo blastocyst transplantation will be included in the study.

Female infertile patients who consent to blastocyst transfer will be considered for inclusion in the study. Patients will be randomly assigned to a constant (5%) or sequential (5%-2%) oxygen concentration protocols in embryo culture. This study will record live birth rates, perinatal and perinatal complications, and offspring health status of women in both groups of embryo culture regimens to assess the effects of different embryo culture regimens on term live birth rates and offspring health.

Conditions

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Fertility Issues Blastocyst IVF Embryo Culture

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Participants

Study Groups

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Constant (5%) oxygen concentration protocols in embryo culture

Patients randomly assigned to use constant (5%) oxygen concentration protocols in embryo culture

Group Type PLACEBO_COMPARATOR

Constant oxygen concentration protocols in embryo culture

Intervention Type PROCEDURE

Participants were randomly assigned to constant (5%) oxygen concentration group and received different blastocyst culture protocols.

Sequential (5%-2%) oxygen concentration protocols in embryo culture

Patients randomly assigned to use Sequential (5%-2%) oxygen concentration protocols in embryo culture

Group Type EXPERIMENTAL

Sequential oxygen concentration protocols in embryo culture

Intervention Type PROCEDURE

Participants were randomly assigned to sequential (5%-2%) oxygen concentration group and received different blastocyst culture protocols.

Interventions

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Constant oxygen concentration protocols in embryo culture

Participants were randomly assigned to constant (5%) oxygen concentration group and received different blastocyst culture protocols.

Intervention Type PROCEDURE

Sequential oxygen concentration protocols in embryo culture

Participants were randomly assigned to sequential (5%-2%) oxygen concentration group and received different blastocyst culture protocols.

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

1. Female: age ≥20 and ≤40 years, male: age ≥20 and ≤50 years;
2. Proposed 1st or 2nd cycle of IVF or ICSI fertilization;
3. ≥ 4 transferable embryos at oocyte stage.

Exclusion Criteria

1. Diagnosis of abnormal uterine cavity morphology (confirmed by 3D ultrasound or hysteroscopy), including uterine malformations (mediastinal uterus, unicornuate uterus, bicornuate uterus), submucosal uterine fibroids, or uterine adhesions;
2. Patients who are proposed to undergo IVM;
3. Patients who are proposed to undergo PGD/ PGS;
4. Patients with untreated severe hydrosalpinx (confirmed by ultrasound or HSG);
5. Patients with a history of recurrent miscarriage (2 or more previous pregnancy losses, excluding biochemical pregnancies);
6. Patients who plan to freeze whole embryos and are unable to complete a single embryo transfer within six months;
7. Patients with contraindications to assisted reproductive technology and pregnancy, or suffering from diseases that have a definite effect on pregnancy: including uncontrolled hypertension, heart disease with definite symptoms, uncontrolled diabetes, undefined diagnosis of liver or kidney disease or liver or kidney insufficiency, severe anemia, history of previous venous thrombosis, pulmonary embolism or cerebrovascular events, history of malignant tumors, suspected malignant tumors, and undiagnosed abnormal uterine bleeding.
Minimum Eligible Age

20 Years

Maximum Eligible Age

40 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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The First Affiliated Hospital with Nanjing Medical University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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The Third Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, China

Site Status RECRUITING

Changzhou Maternal And Child Health Care Hospital

Changzhou, Jiangsu, China

Site Status RECRUITING

Nanjing Women and Children's Healthcare Hospital

Nanjing, Jiangsu, China

Site Status RECRUITING

Reproductive Medicine of First Affiliated Hospital with Nanjing Medical University

Nanjing, Jiangsu, China

Site Status RECRUITING

Suzhou Municipal Hospital

Suzhou, Jiangsu, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Xiang Ma

Role: CONTACT

+86 18001581878

Haofeng Wang

Role: CONTACT

+86 18018387209

Facility Contacts

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Binnan Ren, MD

Role: primary

+86 13253619382

Xiyang Xia, MD

Role: primary

+86 13861266074

Mengqian Chen, MD

Role: primary

+86 15105183515

Xiang Ma, MD. PHD

Role: primary

+86 18001581878

Haofeng Wang

Role: backup

+86 18018387209

Aiyan Zheng, MD

Role: primary

+86 18662180810

References

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De Munck N, Janssens R, Segers I, Tournaye H, Van de Velde H, Verheyen G. Influence of ultra-low oxygen (2%) tension on in-vitro human embryo development. Hum Reprod. 2019 Feb 1;34(2):228-234. doi: 10.1093/humrep/dey370.

Reference Type BACKGROUND
PMID: 30576441 (View on PubMed)

Kaser DJ, Bogale B, Sarda V, Farland LV, Williams PL, Racowsky C. Randomized controlled trial of low (5%) versus ultralow (2%) oxygen for extended culture using bipronucleate and tripronucleate human preimplantation embryos. Fertil Steril. 2018 Jun;109(6):1030-1037.e2. doi: 10.1016/j.fertnstert.2018.02.119.

Reference Type BACKGROUND
PMID: 29935641 (View on PubMed)

Brouillet S, Baron C, Barry F, Andreeva A, Haouzi D, Gala A, Ferrieres-Hoa A, Loup V, Anahory T, Ranisavljevic N, Gaspari L, Hamamah S. Biphasic (5-2%) oxygen concentration strategy significantly improves the usable blastocyst and cumulative live birth rates in in vitro fertilization. Sci Rep. 2021 Nov 17;11(1):22461. doi: 10.1038/s41598-021-01782-6.

Reference Type BACKGROUND
PMID: 34789773 (View on PubMed)

Chakravarti D, LaBella KA, DePinho RA. Telomeres: history, health, and hallmarks of aging. Cell. 2021 Jan 21;184(2):306-322. doi: 10.1016/j.cell.2020.12.028. Epub 2021 Jan 14.

Reference Type BACKGROUND
PMID: 33450206 (View on PubMed)

Lopez-Otin C, Blasco MA, Partridge L, Serrano M, Kroemer G. Hallmarks of aging: An expanding universe. Cell. 2023 Jan 19;186(2):243-278. doi: 10.1016/j.cell.2022.11.001. Epub 2023 Jan 3.

Reference Type BACKGROUND
PMID: 36599349 (View on PubMed)

Wang C, Gu Y, Zhou J, Zang J, Ling X, Li H, Hu L, Xu B, Zhang B, Qin N, Lv H, Duan W, Jiang Y, He Y, Jiang T, Chen C, Han X, Zhou K, Xu B, Liu X, Tao S, Jiang Y, Du J, Dai J, Diao F, Lu C, Guo X, Huo R, Liu J, Lin Y, Xia Y, Jin G, Ma H, Shen H, Hu Z. Leukocyte telomere length in children born following blastocyst-stage embryo transfer. Nat Med. 2022 Dec;28(12):2646-2653. doi: 10.1038/s41591-022-02108-3. Epub 2022 Dec 15.

Reference Type BACKGROUND
PMID: 36522605 (View on PubMed)

Other Identifiers

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RCT-ECP

Identifier Type: -

Identifier Source: org_study_id

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