Recurrent Implantation FaliurePhase 2/3Thy-α1 for RIFNCT07675980
Thymosin-α1 for Recurrent Implantation Failure
A Phase 2/3 study testing Thymosin Alpha1 in people with Recurrent Implantation Faliure, run by Fakih IVF Fertility Center at 1 site in United Arab Emirates.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 40 years, women only
- Conditions the study is for
- Recurrent Implantation Faliure
- What is being tested?
- Thymosin Alpha1
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 136 participants
- Where
- 1 siteUnited Arab Emirates
- Study dates
- 11 Feb 2026to Jun 2027
- Phase
- Phase 2/3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- -Women 18-40 years
- -RIF- ≥2 failed embryo transfers with PGT-a tested euploid embryos
- - Normal parental karyotypes
- - Normal uterine cavity on imaging
- - Negative antiphospholipid panel
- - Thyroid and prolactin controlled within local reference standards
Who cannot join
- Identified/correctable non-immune cause of RPL (chromosomal, anatomic, endocrine)
- - Active malignancy
- -Active infection
- - Uncontrolled systemic disease
- - Current systemic immunosuppression
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United Arab Emirates1 site, 1 recruiting
- Recruiting
Fakih IVF
Abu Dhabi
Dr. Lamiya Mohiyiddeen, 0585707393, lamiya.mohiyiddeen@firstivf.ae
Fatma Bathawab, fatma.bathawab@fakihivf.com
About this study
Official title: Thymosin-α1 for Recurrent Implantation Failure Following Transfer of PGT-a Tested Embryo: A Randomized, Double-Blind, Placebo-Controlled Trial
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.
Read the detailed description
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.
- Conditions
- Recurrent Implantation Faliure
- Being tested
- Thymosin Alpha1, Placebo Control
- Keywords
- Thymosin, recurrent implantation failure, Thymosin alpha, PGT-a tested embryos
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Thymosin Alpha1Drug
Start at luteal start in ART cycles and continue until 10+6 weeks' gestation.
Placebo ControlOther
Matching placebo injections on the same schedule and duration.
| Study group | Role | What they receive |
|---|---|---|
| thymosin-α1 | Experimental | Thymosin α1 in recurrent implantation failure patients Receives: Drug: Thymosin Alpha1 |
| Placebo | Placebo comparator | Placebo arm. Receives: Other: Placebo Control |
What is being measured
The primary outcome is the main question the study is designed to answer.
Live birth more than 24 weeks
From date of randomization (luteal start ART) until end of intervention at 10 + 6 weeks and assessed up to live birth or miscarriage. Approximately 40 weeks.
Measured: Approximately 40 weeks
Determine whether Tα1 increases live birth versus placebo.
Live birth (singleton or multiple)
Measured: Approximately 40 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jun 2026
- Study start11 Feb 2026
- Primary completionFeb 2027 (estimated)
- Study completionJun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Recurrent Implantation FaliureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Thymosin alpha will be started during luteal phase of frozen embryo transfer cycle and continued till 12 weeks of pregnancy.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 136 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fakih IVF Fertility Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Lamiya Mohiyiddeen, Fakih IVF Fertility Center
- Investigators
- Michael Fakih, MD, Principal investigator, Fakih IVF Abu Dhabi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07675980
- Sponsor's protocol ID
- FAKIH-2025-13
- Other IDs
- DOH/ADHRTC/2026/345
- Acronym
- Thy-α1 for RIF
- Status last verified
- Jun 2026
- First submitted
- 9 Jun 2026
- Last updated
- 15 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Graham JJ, Longhi MS, Heneghan MA. T helper cell immunity in pregnancy and influence on autoimmune disease progression. J Autoimmun. 2021 Jul;121:102651. doi: 10.1016/j.jaut.2021.102651. Epub 2021 May 18.
PubMed 34020252Dominari A, Hathaway Iii D, Pandav K, Matos W, Biswas S, Reddy G, Thevuthasan S, Khan MA, Mathew A, Makkar SS, Zaidi M, Fahem MMM, Beas R, Castaneda V, Paul T, Halpern J, Baralt D. Thymosin alpha 1: A comprehensive review of the literature. World J Virol. 2020 Dec 15;9(5):67-78. doi: 10.5501/wjv.v9.i5.67.
PubMed 33362999Kaufmann RA, Welch RA, Mutchnick MG. Low periconceptional maternal serum thymosin alpha 1 levels are associated with blighted pregnancies. Am J Reprod Immunol. 1993 Apr;29(3):171-5. doi: 10.1111/j.1600-0897.1993.tb00583.x.
PubMed 8373526Robertson SA. Immune tolerance in pregnancy. Nat Rev Immunol. 2020;20:67-82
Garaci E, Favalli C, Pica F, Sinibaldi Vallebona P, Palamara AT, Matteucci C, Pierimarchi P, Serafino A, Mastino A, Bistoni F, Romani L, Rasi G. Thymosin alpha 1: from bench to bedside. Ann N Y Acad Sci. 2007 Sep;1112:225-34. doi: 10.1196/annals.1415.044. Epub 2007 Jun 28.
PubMed 17600290Lin, Y. et al. Maternal serum thymosin α1 and β4 levels in early pregnancy and risk of miscarriage. [Chinese study showing lower Tα1 in miscarriage]
Romani L, et al. Thymosin alpha-1: a safe and effective immune modulator in clinical practice. Expert Opin Biol Ther. 2016;16(5):691-707.
Goldstein AL, et al. Biological activities of thymosin alpha 1: clinical applications in disease modulation. Int Immunopharmacol. 2004;4(13):1781-1789.
Li J, et al. Case report: successful pregnancy following thymosin-α1 therapy in recurrent implantation failure. Pharm J. 2018.
Garofalo C, et al. Serum thymosin alpha-1 levels in early pregnancy and risk of miscarriage. Hum Reprod. 1992;7(9):1336-1339.
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Thymosin-α1 for Recurrent Implantation Failure Following Transfer of PGT-a Tested Embryo: A Randomized, Double-Blind, Placebo-Controlled Trial
- ClinicalTrials.gov ID
- NCT07675980
- Acronym / sponsor ID
- Thy-α1 for RIF / FAKIH-2025-13
- Conditions
- Recurrent Implantation Faliure
- Keywords
- Thymosin, recurrent implantation failure, Thymosin alpha, PGT-a tested embryos
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 136 participants (estimated)
- Lead sponsor
- Fakih IVF Fertility CenterUniversity, hospital or other
- Study start
- 11 Feb 2026 (actual)
- Primary completion
- Feb 2027 (estimated)
- Study completion
- Jun 2027 (estimated)
- First posted
- 30 Jun 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Thymosin alpha will be started during luteal phase of frozen embryo transfer cycle and continued till 12 weeks of pregnancy.
| Arm | Type | Receives |
|---|---|---|
| thymosin-α1 | Experimental | Drug: Thymosin Alpha1Thymosin α1 in recurrent implantation failure patients |
| Placebo | Placebo comparator | Other: Placebo ControlPlacebo arm. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- -Women 18-40 years
- -RIF- ≥2 failed embryo transfers with PGT-a tested euploid embryos
- - Normal parental karyotypes
- - Normal uterine cavity on imaging
- - Negative antiphospholipid panel
Key exclusion criteria (5 listed)
- Identified/correctable non-immune cause of RPL (chromosomal, anatomic, endocrine)
- - Active malignancy
- -Active infection
- - Uncontrolled systemic disease
- - Current systemic immunosuppression
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Thymosin Alpha1Start at luteal start in ART cycles and continue until 10+6 weeks' gestation. | Drug | thymosin-α1 |
| Placebo ControlMatching placebo injections on the same schedule and duration. | Other | Placebo |
Primary outcome
Live birth more than 24 weeks
Time frame: Approximately 40 weeks
From date of randomization (luteal start ART) until end of intervention at 10 + 6 weeks and assessed up to live birth or miscarriage. Approximately 40 weeks.
Determine whether Tα1 increases live birth versus placebo.
Time frame: Approximately 40 weeks
Live birth (singleton or multiple)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2026.
- Background: PubMed 34020252Graham JJ, Longhi MS, Heneghan MA. T helper cell immunity in pregnancy and influence on autoimmune disease progression. J Autoimmun. 2021 Jul;121:102651. doi: 10.1016/j.jaut.2021.102651. Epub 2021 May 18.
- Background: PubMed 33362999Dominari A, Hathaway Iii D, Pandav K, Matos W, Biswas S, Reddy G, Thevuthasan S, Khan MA, Mathew A, Makkar SS, Zaidi M, Fahem MMM, Beas R, Castaneda V, Paul T, Halpern J, Baralt D. Thymosin alpha 1: A comprehensive review of the literature. World J Virol. 2020 Dec 15;9(5):67-78. doi: 10.5501/wjv.v9.i5.67.
- Background: PubMed 8373526Kaufmann RA, Welch RA, Mutchnick MG. Low periconceptional maternal serum thymosin alpha 1 levels are associated with blighted pregnancies. Am J Reprod Immunol. 1993 Apr;29(3):171-5. doi: 10.1111/j.1600-0897.1993.tb00583.x.
- BackgroundRobertson SA. Immune tolerance in pregnancy. Nat Rev Immunol. 2020;20:67-82
- Background: PubMed 17600290Garaci E, Favalli C, Pica F, Sinibaldi Vallebona P, Palamara AT, Matteucci C, Pierimarchi P, Serafino A, Mastino A, Bistoni F, Romani L, Rasi G. Thymosin alpha 1: from bench to bedside. Ann N Y Acad Sci. 2007 Sep;1112:225-34. doi: 10.1196/annals.1415.044. Epub 2007 Jun 28.
- BackgroundLin, Y. et al. Maternal serum thymosin α1 and β4 levels in early pregnancy and risk of miscarriage. [Chinese study showing lower Tα1 in miscarriage]
- BackgroundRomani L, et al. Thymosin alpha-1: a safe and effective immune modulator in clinical practice. Expert Opin Biol Ther. 2016;16(5):691-707.
- BackgroundGoldstein AL, et al. Biological activities of thymosin alpha 1: clinical applications in disease modulation. Int Immunopharmacol. 2004;4(13):1781-1789.
- BackgroundLi J, et al. Case report: successful pregnancy following thymosin-α1 therapy in recurrent implantation failure. Pharm J. 2018.
- BackgroundGarofalo C, et al. Serum thymosin alpha-1 levels in early pregnancy and risk of miscarriage. Hum Reprod. 1992;7(9):1336-1339.
- Individual participant dataSharing planned: No
Related trials for Recurrent Implantation Faliure
Active, not recruiting
Subendometrial Injection Versus Intrauterine Infusion of Platelet Rich Plasma for Women With Recurrent Implantation Failure
Recurrent Implantation Faliure, Infertility
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Michael Fakih, MD principal investigator
Fakih IVF Abu Dhabi
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Thymosin Alpha1 in people with Recurrent Implantation Faliure, run by Fakih IVF Fertility Center at 1 site in United Arab Emirates.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 15 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Arab Emirates. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Dr. Lamiya Mohiyiddeen, MD, FRCOG (+971543676002, lamiya.mohiyiddeen@fakihivf.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Live birth more than 24 weeks (time frame: Approximately 40 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07675980, which also lists 10 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2026.