Efficacy of Recombinant Human G-CSF in Women With Unexplained Recurrent Miscarriage (GEM)

July 20, 2026 updated by: Lamiya Mohiyiddeen, Fakih IVF Fertility Center

A Randomised, Double Blind, Placebo-controlled Study to Evaluate the Efficacy of Recombinant Human G-CSF in Women With Unexplained Recurrent Miscarriage After IVF With PGT-A Screened Euploid Embryo Transfer

Recurrent pregnancy loss (RPL), commonly referred to as recurrent miscarriage, affects approximately 1-2% of couples attempting to conceive. In nearly half of these cases, no definitive cause can be identified despite thorough clinical evaluation. A circumstance that is both distressing and disorienting for affected families, particularly in settings such as the United Arab Emirates (UAE), where childbearing carries significant personal and cultural weight.

One leading hypothesis is that the underlying problem may not lie with the embryo itself, but with the way the mother's immune system responds to a developing pregnancy. Under normal physiological conditions, the maternal body must establish immune tolerance toward an embryo that is genetically half-foreign in origin. In some women, this tolerance mechanism may be impaired, reducing the likelihood that a pregnancy will successfully implant and progress.

This study will evaluate whether granulocyte colony-stimulating factor (G-CSF) a naturally occurring substance that normally stimulates the production of immune cells can help address this issue by modulating an overactive immune response and enhancing the uterine environment's capacity to support pregnancy. Notably, the study will enroll only women whose embryos have undergone genetic testing and been confirmed to be chromosomally normal. This eliminates embryo quality as a contributing factor to pregnancy loss and allows for a clearer assessment of whether G-CSF itself influences outcomes.

Earlier small-scale studies, including preliminary work conducted at our own centre, have shown encouraging results. This new trial builds on that foundation by enrolling a larger cohort, comparing G-CSF against a placebo (an inactive comparison treatment), and evaluating a simpler route of administration; subcutaneous injection, rather than direct infusion into the uterus. Together, these design features aim to provide the most reliable evidence to date on whether this treatment can meaningfully help couples affected by unexplained recurrent pregnancy loss.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Recurrent pregnancy loss (RPL) defined as two or more consecutive miscarriages before 20 weeks' gestation affects 1-2% of couples worldwide and remains one of the most distressing, poorly resolved conditions in reproductive medicine. In nearly half of cases, no definitive cause is identified. This burden is especially pronounced in the UAE and wider GCC region, where delayed childbearing and the strong sociocultural weight placed on fertility amplify the psychological, marital, and financial toll of unexplained RPL.

Despite decades of research, treatment remains largely empirical. Immune dysregulation is increasingly implicated as a central mechanism, with proposed pathways including aberrant natural killer (NK) cell activation, impaired regulatory T-cell expansion, inadequate decidualization, and an unfavorable Th1/Th17 cytokine profile, collectively compromising endometrial receptivity and embryo survival. However, most supporting studies have been small, uncontrolled, and unable to distinguish maternal immunological causes from embryo genetic abnormalities, leaving clinicians with few evidence-based options.

Granulocyte colony-stimulating factor (G-CSF), a hematopoietic cytokine with immunomodulatory and endometrial effects, has emerged as a promising candidate. Preclinical and early clinical data suggest it enhances endometrial proliferation and vascularization, supports folliculogenesis and oocyte competence, and promotes immune tolerance by expanding regulatory T-cells while reducing NK cell cytotoxicity. Small trials in both recurrent implantation failure and RPL populations have reported benefits in implantation and live birth rates, though results have been inconsistent - largely due to the same methodological limitations noted above, plus a failure to control for embryo aneuploidy as a confounder.

Our own retrospective pilot study of 19 patients receiving intrauterine G-CSF supports this rationale: 70.5% achieved a positive β-hCG, 66.7% progressed to ongoing pregnancy, and no adverse effects were observed. These findings demonstrate both feasibility and preliminary efficacy at our centre. However, intrauterine infusion is invasive, costly, and less patient-friendly; existing literature suggests subcutaneous administration may achieve comparable efficacy with greater convenience, but this route has not yet been evaluated in this specific population.

The GEM Trial is designed to resolve these open questions directly. By enrolling women with unexplained RPL undergoing IVF with preimplantation genetic testing for aneuploidy (PGT-A), the trial eliminates embryo chromosomal abnormality as a confounder, enabling a precise, mechanistically targeted test of the immunological hypothesis. It will be the first placebo-controlled, genetically controlled trial of G-CSF in this population, and the first to formally assess subcutaneous delivery.

If successful, the GEM Trial could establish a new standard of care for unexplained RPL offering a more convenient, evidence-based treatment option to thousands of couples and positioning the UAE as a global leader in reproductive immunology research.

Study Type

Interventional

Enrollment (Estimated)

150

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United Arab Emirates
      • Abu Dhabi, United Arab Emirates
        • Recruiting
        • Fakih IVF Fertility Centre LLC
        • Contact:
        • Contact:
        • Principal Investigator:
          • Michael Fakih, MD
        • Principal Investigator:
          • Lamiya Mohiyiddeen, MD, FRCOG
        • Principal Investigator:
          • Yasmin Sajjad, MD, FRCOG

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion:

  1. Women aged 18-44 years
  2. ≥2 unexplained pregnancy losses
  3. Undergoing IVF with PGT-A tested embryos
  4. BMI 19-35 kg/m² 6.

Exclusion:

  1. Parental karyotype abnormalities
  2. Correctable uterine abnormalities
  3. Systemic autoimmune disease / thrombophilia
  4. Uncontrolled systemic illness (e.g. diabetes, infection)
  5. Previous G-CSF therapy
  6. Hypersensitivity to rhG-CSF or E. coli proteins
  7. HIV, malignancy within 5 years, or severe cardiovascular/respiratory history

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Recombinant G-CSF 130 mcg SC
Subcutaneous injection of Recombinant G-CSF daily from embryo transfer until 12 weeks' gestation
Drug: Recombinant G-CSF
Subcutaneous injection of Recombinant G-CSF daily from embryo transfer until 12 weeks' gestation
Placebo Comparator: Placebo Control: Placebo SC
Subcutaneous injection of placebo daily from embryo transfer until 12 weeks' gestation
Drug: Placebo control
Subcutaneous injection of Recombinant G-CSF daily from embryo transfer until 12 weeks' gestation

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical pregnancy rate
Time Frame: From enrollment to 16 weeks gestation
Clinical pregnancy confirmation by transvaginal ultrasound at 16 weeks' gestation.
From enrollment to 16 weeks gestation

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Live birth rate
Time Frame: From enrollment to approximately 40 weeks' gestation.
From enrollment to approximately 40 weeks' gestation.
Ongoing Pregnancy Rate
Time Frame: From 16 weeks to 34 weeks gestation.
16 - 34 weeks gestation by serial ultrasound.
From 16 weeks to 34 weeks gestation.
Early Pregnancy Loss rate
Time Frame: From FET (Fetal Embryo Transfer) to 12 weeks gestation
Pregnancy loss confirmed by a transvaginal ultrasound.
From FET (Fetal Embryo Transfer) to 12 weeks gestation
Rate of Adverse pregnancy outcomes (APOs)
Time Frame: From enrollment to approximately 40 weeks gestation
Rate of Miscarriage, stillbirth, neonatal outcomes (birth weight, NICU admission, congenital anomalies) and maternal outcomes assessed using several methods including transvaginal ultrasound and clinical assessment.
From enrollment to approximately 40 weeks gestation
Rate of Adverse events
Time Frame: From enrollment up to approximately 40 weeks gestation (delivery)
Safety data including pregnancy related, fetal or maternal adverse events e.g. infections, cytopenias, hypersensitivity etc.
From enrollment up to approximately 40 weeks gestation (delivery)
Rate of immunogenicity
Time Frame: From enrollment to up to approximately 40 weeks gestation (delivery)
Anti-drug antibody (ADA) formation (serology in subset).
From enrollment to up to approximately 40 weeks gestation (delivery)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fakih IVF Fertility Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 10, 2026

Primary Completion (Estimated)

August 10, 2027

Study Completion (Estimated)

October 10, 2027

Study Registration Dates

First Submitted

July 14, 2026

First Submitted That Met QC Criteria

July 20, 2026

First Posted (Actual)

July 24, 2026

Study Record Updates

Last Update Posted (Actual)

July 24, 2026

Last Update Submitted That Met QC Criteria

July 20, 2026

Last Verified

July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FAKIH-2025-10
  • DOH/ADHRTC/2026/34566666666666 (Other Identifier: Department of Health Abu Dhabi)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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