Clinical trial evaluating the safety and efficacy of Thymosin-α1 (Tα1) as an adjunctive immunomodulatory therapy in women with unexplained recurrent implantation failure (RIF) undergoing IVF/ICSI cycles.

Despite significant advancements in assisted reproductive technologies (ART), recurrent implantation failure (RIF) remains a persistent challenge. Growing evidence implicates dysregulation of both local endometrial and systemic immune components in the pathophysiology of RIF.

This has led to increasing attention on immune dysregulation, including aberrant cytokine signaling, altered Th1/Th2 balance, heightened NK cell cytotoxicity, and impaired maternal-fetal tolerance as possible contributors. These immunological pathways are critical for embryo implantation and pregnancy continuation; their disruption can create an environment hostile to the developing conceptus.

Thymosin-α1 (Tα1) is a naturally occurring thymic peptide with immune-modulatory properties. It has been historically used in the management of chronic viral infections and certain cancers, where it demonstrated the ability to enhance T-cell function, rebalance cytokine networks, and improve immune resilience. Its safety profile in non-obstetric conditions is well established.

Although comprehensive safety evaluation of thymosin alpha in pregnant women has not yet been completed, emerging evidence from observational studies, case reports, and proposed clinical trials suggests that thymosin alpha is generally regarded as safe during pregnancy, with no reported adverse effects linked to its use to date. Specifically, a published case report documented successful pregnancy following thymosin alpha administration in a woman with recurrent implantation failure, noting an absence of fetal anomalies or significant adverse events and emphasizing the need for further prospective trials to establish broader safety and efficacy. Preliminary clinical protocols continue to monitor for adverse events in patients undergoing reproductive treatments, and none have identified safety concerns thus far.

Emerging reproductive data suggest a potential role of Tα1 in implantation and pregnancy maintenance. Observational work reported lower maternal Tα1 levels in women whose pregnancies ended in miscarriage compared with those that continued to viability; this effect was not seen with thymosin-β4, suggesting specificity. Mechanistically, Tα1 enhances T-cell maturation, restores Th1/Th2 balance, and promotes regulatory T-cell activity-processes central to maternal immune tolerance during early pregnancy.

Taken together, these findings highlight a gap: Tα1 has biological plausibility and early signals but no definitive RCT evidence. This underlines the need for a rigorous, placebo-controlled study of Tα1 in women with RIF. To our knowledge, this is the first randomized placebo-controlled study looking at Tα1 in RIF patients undergoing treatment using PGT-a tested embryos.

Inclusion Criteria:

1. -Women 18-40 years
2. -RIF- ≥2 failed embryo transfers with PGT-a tested euploid embryos
3. - Normal parental karyotypes
4. - Normal uterine cavity on imaging
5. - Negative antiphospholipid panel
6. - Thyroid and prolactin controlled within local reference standards

Exclusion Criteria:

1. Identified/correctable non-immune cause of RPL (chromosomal, anatomic, endocrine)
2. - Active malignancy
3. -Active infection
4. - Uncontrolled systemic disease
5. - Current systemic immunosuppression

Biological gender female.

This is double blind randomized controlled trial