Recurrent Implantation Failure
Conditions
Keywords
Recurrent Implantation Failure, Peripheral blood mononuclear cell, Human chorionic gonadotropin
Brief summary
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.
Detailed description
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.
Interventions
OTHERPeripheral Blood Monouclear Cell
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.
OTHERPhosphate Baffer Saline
Only 500 microlitres PBS will be injected into the uterine cavity, instead of PBMCs, two days before embryo transfer (ET) using ET catheter.
Sponsors
SCARM Institute, Tabriz, Iran
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
The participants and the person who analyzed the results were blinded in this study. Participants were aware of the study before being randomized and informed consent was obtained from them. It should be noted that the person analyzing the results had no other role in this study.
Eligibility
Sex/Gender
FEMALE
Age
20 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
All patients were evaluated in accordance with the following inclusion and
Exclusion criteria
; Inclusion Criteria: 1. Having at least three implantation failures following IVF 2. Having primary infertility 3. Age under 45 years old 4. Having regular menstrual cycles 5. BMI under 30
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| pregnancy occurrence | 12 days after embryo transfer | Laboratory tests (beta-hCG test) |
| examination of inflammatory cytokines (IL-1B, TNF-a and INF-Y) secretion levels in supernatant | 48 hours after culturing | ELISA technique |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical pregnancy rate in patients with recurrent implantation failure (RIF) | in 5-6 weeks | detection the number and location of gestational sacs by ultrasound |
| The live birth rate by patients with recurrent implantation failure (RIF) | After about 9 months of positive βHCG test | By gynecologists and obstetricians will monitor |
| The miscarriage rate in patients with recurrent implantation failure (RIF) | When ever during the pregnancy period (up to 9 months) | By gynecologists and obstetricians will monitor |
Countries
Iran
Outcome results
None listed