Autologous Decidual-like Natural Killer Cells Therapy for Reproductive Failure

A Prospective, Multicenter, Randomized Controlled Clinical Study on Autologous Decidual-like NK Cells Therapy for Reproductive Failure Associated With Abnormal Uterine Natural Killer Cells

The aim of this study is to verify the efficacy of in vitro induction of autologous decidual-like NK cells therapy for reproductive failure associated with uterine NK cells abnormalities.

Study Overview

• Status: Not yet recruiting
• Conditions: Abortion, Missed; Infertility Unexplained; Reproductive Disorder
• Intervention / Treatment: Biological: NK cell perfusion group

Detailed Description

Participants with reproductive failure and reproductive intentions will be recruited and screened. After obtaining their informed consent, menstrual blood analysis will be performed. Participants with menstrual blood NK cell abnormalities will be randomly assigned to either the NK cell perfusion group or control group in a ratio of 2:1. After completing two rounds of NK cell therapy, the NK cell perfusion group will enter the follow-up period, while the control group will not receive interventions after randomization and enter the follow-up period directly. The following information will be recorded for all participants who undergo menstrual blood NK cell analysis, including menstrual blood analysis results, attempts to conceive, and pregnancy outcomes during the follow-up period.

• Study Type: Interventional
• Enrollment (Estimated): 159
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yali Hu; Phone Number: 11201 86-025-83106666; Email: glyyhuyali@163.com
• Study Contact Backup: Name: Hui Zhu; Phone Number: 54330 86-025-8310666; Email: zhuhui1231@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Reproductive failure with abnormal endometrial natural killer (NK) cells in menstrual blood;
• With a clear intention to conceive;
• Normal ovarian function, or premature ovarian insufficiency with ≥2 high-quality cryopreserved embryos available for transfer;
• Endometrial thickness measured by transvaginal ultrasound during the periovulatory period ≥7 mm;
• Body mass index (BMI) between 18 kg/m² and 28 kg/m²;
• Willing to comply with the follow-up plan of this study.

Exclusion Criteria:

• Use of progesterone receptor modulators;
• One of the couple's chromosomal karyotype abnormalities, with no euploid embryo identified via preimplantation genetic testing for aneuploidy;
• Severe endometriosis or adenomyosis, uterine fibroids affecting uterine cavity morphology, uterine malformations, intrauterine adhesions, or thin endometrium;
• Uncontrolled autoimmune or endocrine disorders;
• Contraindications to pregnancy;
• History of malignant tumors;
• Participating in other clinical studies;
• Allergy to blood products.

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
Experimental: NK cell perfusion group; Accepting NK cell therapy	Biological: NK cell perfusion group; Completing two rounds of NK cell therapy
No Intervention: Control group; Not accepting NK cell therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ongoing pregnancy rate	Ongoing pregnancy is defined as at least 12 weeks of gestation, with ultrasound indicating fetal cardiac activity and fetal size consistent with the gestational age	6 months, if a participant is confirmed to get a clinically pregnancy during this period, the follow-up endpoint will be extended until there is a pregnancy outcome

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement rate of NK cells	Improvement rate of NK cells in menstrual blood analysis after intrauterine perfusion of autologous decidual-like NK cells	6 months
Clinical pregnancy rate	Clinical pregnancy is defined as the presence of a gestational sac in the uterine cavity as indicated by ultrasound at 5-7 weeks of gestation	6 months
Miscarriage rate	Miscarriage is defined as the pregnancy loss before 28 weeks of gestation	6 months, if a participant is confirmed to get a clinically pregnancy during this period, the follow-up endpoint will be extended until there is a pregnancy outcome
Preterm birth rate	Preterm birth is defined as delivery at 28 to 37 weeks of gestation	6 months, if a participant is confirmed to get a clinically pregnancy during this period, the follow-up endpoint will be extended until there is a pregnancy outcome
Live birth rate	Live birth is defined as delivery of any number of neonates born at 26 or more weeks' gestation with signs of life	6 months, if a participant is confirmed to get a clinically pregnancy during this period, the follow-up endpoint will be extended until there is a pregnancy outcome

Collaborators and Investigators

• Sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
• Collaborators: The First Affiliated Hospital of Anhui Medical University; The University of Science and Technology of China; Sir Run Run Shaw Hospital; Second Affiliated Hospital of Soochow University; The First Affiliated Hospital of University of Science and Technology of China
• Investigators: Principal Investigator: Yali Hu, The Affiliated Drum Tower Hospital of Nanjing University

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2025
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2028

Study Registration Dates

• First Submitted: November 13, 2025
• First Submitted That Met QC Criteria: November 13, 2025
• First Posted (Actual): November 17, 2025

Study Record Updates

• Last Update Posted (Actual): November 17, 2025
• Last Update Submitted That Met QC Criteria: November 13, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Recurrent Pregnancy Loss; Unexplained Infertility; Repeated Implantation Failure; Decidual Natural Killer Cells
• Additional Relevant MeSH Terms: Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Pregnancy Complications; Abortion, Spontaneous; Abortion, Missed
• Other Study ID Numbers: SC2025-0013-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No