Efficacy and safety of tacrolimus in clinical pregnancy onset of repeated implantation failure (RIF) patients with elevated T-cell helper1/T-cell helper2 (Th1/Th2) ratio: a randomized controlled trial

Efficacy and safety of tacrolimus in clinical pregnancy onset of repeated implantation failure (RIF) patients with elevated T-cell helper1/T-cell helper2 (Th1/Th2) ratio

Randomized, placebo-controlled, double-blind, two-group, single-center, and parallel clinical trial on 80 patients.

Patients will be selected from the patients of the infertility clinic of Imam Khomeini Hospital (RA) in Sari City who have a history of RIF and are at least 39 years old and meet other inclusion criteria. After confirmation, patients will enter the groups with a ratio of 1:1. After determining the patient group by randomization envelopes; Patients will refer to a specific center to receive medicine or placebo according to the determined group. Medicine delivery people will not be involved in the intervention and treatment process. Placebos will be the same in terms of color, smell and taste. In this way, all patients and people involved in the intervention process will be blinded.

Inclusion criteria: - The patient should be ≤ 39 years old. - The patient should have ≥ 3 failures in the IVF. - Th1/Th2 cell ratio should be greater than or equal to 10.3. Exclusion criteria: - Patients with abnormal karyotypes, uterine abnormalities or defects, infections, endocrine diseases, and coagulation abnormalities or thrombosis.

Group A will include patients who will receive tacrolimus at a dose of 3 mg/daily. The initiation of tacrolimus in this group will start two days before embryo transfer to the uterus and continue until the pregnancy test is positive (about 14 days after transfer). Group B will consist of patients who will receive placebo.

Clinical pregnancy onset

The randomization list of patients will be generated using the block-balanced randomization method with the help of the Randomization.com website from the original generator section with blocks number of 4. Then, the list will be entered in the sealed envelopes in order. After preparing the sealed envelopes, the list will be destroyed.

Blinding will be done with the help of randomization envelopes, in such a way that after preparing the drug and placebo with the same shape, color, smell, and size, the drug or placebo is put in the envelope according to the order and group specified based on the randomization list. The randomization envelope will be in the form of a package/packet, which will include the defining group according to the randomization list and the related drug or placebo. When the patient enters the study, this package is delivered to the patient. The researcher who produces the random list and prepares the package is not involved in the intervention process, but has knowledge about which group A or B is related to the drug group and which group is related to the placebo group. The physician evaluating the variables and outcomes will not be aware of the group of the patient.

The study report in the form of an article, the English protocol of the study and the raw data of the study will be available for publication after completion.

The access period starts 2 months after the results are published

All readers and researchers

there are no limitations

Saeid Taghiloo saeid.taghiloo@yahoo.com

By email with the approval of the group active in the study