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Completed

NCT Number: NCT03267797

hCG-activated PBMC-therapy in RIF Patients

Despite the many research done in the field of infertility and in vitro fertilization (IVF), more than half of the embryos transmitted in the IVF and intracytoplasmic sperm injection (ICSI) do not implant successfully. Currently, pregnancy failure following at least three IVF/ET cycle, so that one or two high-quality embryos transmitted in each cycle is defined as recurrent implantation failure (RIF). Maternal and fetal factors can be a reason for implantation failure; maternal factors include endometrial receptivity, uterine anatomic abnormalities, and immunologic factors. Implantation failure with embryonic reasons includes genetic abnormalities and any factor that affects the implantation and growth of the embryo within the uterus. In recent years, the involvement of immune-related factors mainly natural killer cells (NK), dendritic cells (DCs), macrophages (MQ), regulatory T cells (Treg) and Th-1, in the endometrial differentiation and development and endometrial receptivity, as well as induction of immunological tolerance to the fetus, have been reported.

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Key information

Age range

20 year–45 year

Sex eligibility

Female

Study type

Interventional

Phase

Not applicable

Primary location

Valiasr Hospital

Tabriz, Iran

About this study

248 women with the history of implantation failure volunteered to receive PBMC-therapy. After immunologic consultation and doing flow cytometry analysis, 100 women with at least three IVF/ET failure who had low Th-17/Treg ratio in comparison with healthy control were enrolled in this study. These 100 patients divided randomly into two groups, 50 patients received PBMC and 50 patients as the control group received PBS. PBMCs were obtained from patients themselves five days before embryo transfer (ET) and were cultured with hCG for 48 hours. Frothy-eight hours later, PBMCs were then administered into the uterine cavity of that patient from the study group two days before ET. PBS was inseminated into the uterine cavity of the control group instead of PBMC. The concentration of inflammatory cytokines was examined in the supernatant of cultured PBMCs 2, 24 and 48 hour after incubation by ELISA. The pregnancy occurrence was confirmed 12 days after ET through positive pregnancy test (β-hCG test). The success of implantation and the occurrence of clinical pregnancy were evaluated by ultrasound through the observation of the number and the location of gestational sacs at 5-6 weeks and confirming the embryo heart pulsation.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

All patients were evaluated in accordance with the following inclusion and exclusion criteria;

Inclusion criteria

  • Having at least three implantation failures following IVF
  • Having primary infertility
  • Age under 45 years old
  • Having regular menstrual cycles
  • BMI under 30

Exclusion criteria

  • Having polycystic ovary syndrome
  • The presence of uterine pathology;
  • Poor ovarian reserve
  • Having chromosomal abnormalities
  • Presence of auto anti-bodies such as anti-TPO, anti-TG, ACA, APA, ANA, and anti-dsDNA
  • Presence of mutations involving the coagulation system such as deficiency of factor XII, Pro C, Pro S
  • Positive HIV, HCV or HBV tests

Treatment and study plan

Peripheral Blood Monouclear Cell

Other

Blood samples (20 mL) were taken from individual patients at the time of ovulation induction. Then PBMC were isolated and cultured (20-30 million cells) 48 hour at the presence of hCG (10IU/ml daily). Afterward,15-20 million PBMCs in 500 microlitres PBS were injected into the uterine cavity two days before embryo transfer (ET) using ET catheter.

Other names: PBMC

Phosphate Baffer Saline

Other

Only 500 microlitres PBS will be injected into the uterine cavity, instead of PBMCs, two days before embryo transfer (ET) using ET catheter.

Other names: PBS

Primary outcomes

  1. pregnancy occurrence

    Time frame: "12 days after embryo transfer"

    Laboratory tests (beta-hCG test)

  2. examination of inflammatory cytokines (IL-1B, TNF-a and INF-Y) secretion levels in supernatant

    Time frame: "48 hours after culturing"

    ELISA technique

Secondary outcomes

  1. Clinical pregnancy rate in patients with recurrent implantation failure (RIF)

    Time frame: "in 5-6 weeks"

    detection the number and location of gestational sacs by ultrasound

  2. The live birth rate by patients with recurrent implantation failure (RIF)

    Time frame: "After about 9 months of positive βHCG test"

    By gynecologists and obstetricians will monitor

  3. The miscarriage rate in patients with recurrent implantation failure (RIF)

    Time frame: "When ever during the pregnancy period (up to 9 months)"

    By gynecologists and obstetricians will monitor

Sponsors and collaborators

Lead sponsor

SCARM Institute, Tabriz, Iran

Other Gov

Registry information

Official study title

Intrauterine Administration of Autologous hCG-activated Peripheral Blood Mononuclear Cells Improves Pregnancy Outcomes in Patients With Recurrent Implantation Failure; a Double-blind Randomized Control Trial Study

Important dates

Study start
2017
Primary completion
2018
Study completion
2019
First posted
Aug 30, 2017
Registry last updated
Aug 26, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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