Thin EndometriumPhase 1/2NCT06379659
Effectiveness of Intrauterine Growth Hormone Administration as an add-on Therapy to Conventional Hormone Therapy Compared to Placebo in Patients With Thin Endometrium Undergoing Frozen Thawed Embryo Transfer
A Phase 1/2 study testing Growh hormone in people with Thin Endometrium and Infertility Female, run by Isfahan University of Medical Sciences at 1 site in Iran.
Trial summary
The purpose of this clinical trial is to see if intrauterine growth hormone infusions can help subjects reach a suitable endometrial thickness in patients who are resistant to routine hormonal therapy for embryo transfer in the In Vitro Fertilization (IVF) cycle. Read more about this study
- Who is it for?
- Ages 18 to 45 years, women only
- Conditions the study is for
- Thin Endometrium, Infertility Female, Infertility
- What is being tested?
- Growh hormone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 54 participants
- Where
- 1 siteIran
- Study dates
- 1 May 2024to 14 Sep 2024
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
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 45 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- At least a history of cycle cancellation due to a thin endometrium less than 7 mm following standard hormonal treatment
- Availability of ≥1 embryo with good quality
- Normal baseline hormones value including: Testosterone, Progesterone, Prolactin, Luteinizing Hormone (LH), Follicle Stimulating Hormone (FSH)
Who cannot join
- Internal genital anomalies
- Active intrauterine infection Endometrial thickness≥7 on the 10th day of menstrual cycle
- History of Asherman syndrome
- History of cancer
- History of uterine surgery in past 3 months
- Intrauterine polyps visible in Transvaginal Ultrasonography
Show all 9Show fewer
- Visible intrauterine adhesion
- Pathospermia in partner
- Premature ovarian failure
Trial locations and contacts
1 site in 1 country.
Iran1 site
Isfahan Shahid Beheshti hospital, Hazrat e Maryam Fertility Center
Isfahan, 8174673461
About this study
Official title: Effectiveness of Intrauterine Growth Hormone Infusion as an add-on Therapy to Conventional Hormone Therapy Compared to Placebo in Patients With Thin Endometrium Undergoing Frozen Thawed Embryo Transfer: A Double-blinded Parallel Exploratory Randomized Controlled Clinical Trial
The purpose of this clinical trial is to see if intrauterine growth hormone infusions can help subjects reach a suitable endometrial thickness in patients who are resistant to routine hormonal therapy for embryo transfer in the In Vitro Fertilization (IVF) cycle.
The primary aim of this study is to assess the effectiveness of injecting Growth hormone directly into the uterus to enhance endometrial thickness. Additionally, we aim to compare the likelihood of pregnancy between patients receiving the Growth hormone infusion and those receiving a placebo.
Read the detailed description
Infertility impacts approximately 10-15% of couples globally, with over 1 million couples affected in Iran alone, adversely affecting their quality of life. However, Assisted Reproductive Technology (ART), notably In Vitro Fertilization (IVF), has markedly enhanced fertility outcomes for couples facing infertility.
The primary reason for IVF failure is often attributed to difficulties with embryo implantation. A crucial determinant in preparing the uterus for successful implantation is achieving an adequate endometrial thickness. A thin endometrium, typically defined as less than 7 mm in thickness, is associated with a significantly reduced likelihood of successful pregnancy following implantation. As a result, patients with thin endometrium are often deemed unsuitable candidates for implantation.
Despite exploring various pharmacological options, certain patients remain unable to achieve the minimum required endometrial thickness for successful implantation. Prior investigations have examined the impact of subcutaneous growth hormone injections on endometrial thickness in individuals with thin endometrium, yielding mixed results across studies. Direct infusion of drugs into the uterine cavity presents a potential route for localized treatment, thereby minimizing systemic effects under specific circumstances. Thus, different studies explored the possible intra-uterine effect of drugs such as Granulocyte colony stimulating factor (GCSF), and Human chorionic gonadotropin (hCG). To date, only an animal study and two small studies without control group have investigated the efficacy of direct intrauterine infusion of growth hormone in increasing endometrial thickness among patients with thin endometrium. However, the absence of randomized controlled trials with placebo groups limits our understanding of the effectiveness of intrauterine growth hormone therapy in this patient population. Thus, we aimed to design an exploratory randomized clinical trial with parallel placebo group to evaluate the effectiveness of intrauterine Growth Hormone infusion as an add-on therapy to conventional hormone therapy compared to placebo in patients with thin endometrium undergoing frozen thawed embryo transfer
- Conditions
- Thin Endometrium, Infertility Female, Infertility
- Being tested
- Growh hormone, Placebo
- Keywords
- Infertility, Infertility, Female, endometrial thickness, Thin Endoetrium, Growth Hormone, Human Growth Hormone, Somatropin, Intra-uterine infusion
- Medical subject headings
- Infertility, Female, Infertility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Growh hormoneDrug
In this group, patients will receive growth hormone solution containing 1.99 milligrams of the drug dissolved in 1.5 milliliters of 0.9% saline solution (normal saline), in addition to standard hormonal therapy, starting from cycle day 10. Treatment sessions will be conducted at two-day intervals. In case of non-response to treatment (failure to reach a minimum endometrial thickness of 7 millimeters in the subsequent assessment), the patient will receive a maximum of 4 doses, and if response to treatment is observed, growth hormone infusion will be discontinued. All infusions will be administered intrauterinely via an Intrauterine Insemination (IUI) catheter.
PlaceboOther
Similar to the intervention group, from cycle day 10, an equal volume of 0.9% saline solution (normal saline) will be administered in addition to standard hormonal therapy. Treatment sessions will be conducted at two-day intervals. In case of non-response to treatment (failure to reach a minimum endometrial thickness of 7 millimeters in the subsequent assessment), the patient will receive a maximum of 4 doses, and if response to treatment is observed, placebo infusion will be discontinued. All infusions will be administered intrauterinely via an Intrauterine Insemination (IUI) catheter.
| Study group | Role | What they receive |
|---|---|---|
| Growth hormone | Active comparator | Not described Receives: Drug: Growh hormone |
| Placebo | Placebo comparator | Not described Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Endometrial thickness
Measurement of endometrial thickness will be performed utilizing transvaginal sonography due to its closer proximity to the endometrium and with an empty bladder. To minimize the potential bias of measuring endometrial thickness during uterus contraction, occur during contractions, measurements will be taken only after the patient's contractions have ceased.
Measured: Baseline (On the 10th day of menstrual cycle), and On the day of response to treatment (in case of response) and in case of non-response to treatment on the 18th day of the mesntrual cycle
Secondary outcomes (5)
Clinical Pregnancy Rate
The number of fetuses that have a heartbeat and are not ectopic evaluated by Transvaginal Ultrasonography
Measured: 6-8 of gestational week
Response to treatment
The number of patients that reach at least 7 mm of endometrial thickness
Measured: 2 days following the last dose of placebo or growth hormone
Implantation rate
The number of gestational sacs to the number of transferred embryos evaluated by Transvaginal ultrasonography
Measured: 6-8 of gestational week
IVF cancellation rate
The number of patients who do not reach enough endometrial thickness for transferring despite maximum treatment
Measured: 2 days following the last dose of placebo or growth hormone
Early pregnancy complications
Including early miscarriage (miscarriage in less than 12th gestational week) and Ectopic pregnancy
Measured: During the first 12 weeks of pregnancy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Apr 2024
- Study start1 May 2024
- Primary completion29 Jul 2024
- Study completion14 Sep 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Thin EndometriumStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This study was designed as a randomized controlled exploratory clinical trial, controlled with a parallel placebo group and random allocation using an online based system.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Lead sponsor
- Isfahan University of Medical Sciences
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Hatav Ghasemi Tehrani, Isfahan University of Medical Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06379659
- Sponsor's protocol ID
- IR.MUI.MED.REC.1402.449
- Other IDs
- IRCT20110908007513N18
- Status last verified
- Sep 2024
- First submitted
- 11 Apr 2024
- Last updated
- 19 Sep 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual Participant Data (IPD) may be shared following the publication of the study, as per specific requests from the researchers.
Publications
Yu H, Gao S, Tang H, Chen H, Deng Z, Yang L, et al. Growth hormone intrauterine perfusion combined with replacement cycle in the treatment of non-response thin endometrium: report of 5 cases. Int J Clin Exp Med. 2016;9(6):11982-9
Hosseini Aghdam S, Ghasemzadeh A, Farzadi L, Hamdi K, Baradaran-Binazir M, Nouri M, Fattahi A, Dttrich R. Growth Hormone: A Potential Treatment of Patients with Refractory Thin Endometrium: A Clinical Trial Study. Int J Fertil Steril. 2022 Oct 9;16(4):251-255. doi: 10.22074/ijfs.2022.541389.1210.
PubMed 36273309Li W, Cao Z, Yu X, Hu W. Effect of growth hormone on thin endometrium via intrauterine infusion. Ann Transl Med. 2021 Aug;9(16):1325. doi: 10.21037/atm-21-3583.
PubMed 34532462Altmae S, Aghajanova L. Growth Hormone and Endometrial Receptivity. Front Endocrinol (Lausanne). 2019 Sep 24;10:653. doi: 10.3389/fendo.2019.00653. eCollection 2019.
PubMed 31616379Liu KE, Hartman M, Hartman A. Management of thin endometrium in assisted reproduction: a clinical practice guideline from the Canadian Fertility and Andrology Society. Reprod Biomed Online. 2019 Jul;39(1):49-62. doi: 10.1016/j.rbmo.2019.02.013. Epub 2019 Mar 20.
PubMed 31029557Fu LL, Xu Y, Yan J, Zhang XY, Li DD, Zheng LW. Efficacy of granulocyte colony-stimulating factor for infertility undergoing IVF: a systematic review and meta-analysis. Reprod Biol Endocrinol. 2023 Apr 3;21(1):34. doi: 10.1186/s12958-023-01063-z.
PubMed 37013570Ghasemi Tehrani H, Zamani Dehkordi N, Hematian M, Ataei-Goujani H, Rahmati R, Naghshineh E, Lotfizadeh M, Mehrabian F. A randomized controlled trial of intrauterine growth hormone for thin endometrium. Sci Rep. 2026 Jul 15. doi: 10.1038/s41598-026-62005-4. Online ahead of print.
PubMed 42457811
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effectiveness of Intrauterine Growth Hormone Infusion as an add-on Therapy to Conventional Hormone Therapy Compared to Placebo in Patients With Thin Endometrium Undergoing Frozen Thawed Embryo Transfer: A Double-blinded Parallel Exploratory Randomized Controlled Clinical Trial
- ClinicalTrials.gov ID
- NCT06379659
- Acronym / sponsor ID
- IR.MUI.MED.REC.1402.449
- Conditions
- Thin Endometrium, Infertility Female, Infertility
- Keywords
- Infertility, Infertility, Female, endometrial thickness, Thin Endoetrium, Growth Hormone, Human Growth Hormone, Somatropin, Intra-uterine infusion
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 54 participants (actual)
- Lead sponsor
- Isfahan University of Medical SciencesUniversity, hospital or other
- Study start
- 1 May 2024 (actual)
- Primary completion
- 29 Jul 2024 (actual)
- Study completion
- 14 Sep 2024 (actual)
- First posted
- 23 Apr 2024 (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.
The purpose of this clinical trial is to see if intrauterine growth hormone infusions can help subjects reach a suitable endometrial thickness in patients who are resistant to routine hormonal therapy for embryo transfer in the In Vitro Fertilization (IVF) cycle.
The primary aim of this study is to assess the effectiveness of injecting Growth hormone directly into the uterus to enhance endometrial thickness. Additionally, we aim to compare the likelihood of pregnancy between patients receiving the Growth hormone infusion and those receiving a placebo.
Detailed description
Infertility impacts approximately 10-15% of couples globally, with over 1 million couples affected in Iran alone, adversely affecting their quality of life. However, Assisted Reproductive Technology (ART), notably In Vitro Fertilization (IVF), has markedly enhanced fertility outcomes for couples facing infertility.
The primary reason for IVF failure is often attributed to difficulties with embryo implantation. A crucial determinant in preparing the uterus for successful implantation is achieving an adequate endometrial thickness. A thin endometrium, typically defined as less than 7 mm in thickness, is associated with a significantly reduced likelihood of successful pregnancy following implantation. As a result, patients with thin endometrium are often deemed unsuitable candidates for implantation.
Despite exploring various pharmacological options, certain patients remain unable to achieve the minimum required endometrial thickness for successful implantation. Prior investigations have examined the impact of subcutaneous growth hormone injections on endometrial thickness in individuals with thin endometrium, yielding mixed results across studies. Direct infusion of drugs into the uterine cavity presents a potential route for localized treatment, thereby minimizing systemic effects under specific circumstances. Thus, different studies explored the possible intra-uterine effect of drugs such as Granulocyte colony stimulating factor (GCSF), and Human chorionic gonadotropin (hCG). To date, only an animal study and two small studies without control group have investigated the efficacy of direct intrauterine infusion of growth hormone in increasing endometrial thickness among patients with thin endometrium. However, the absence of randomized controlled trials with placebo groups limits our understanding of the effectiveness of intrauterine growth hormone therapy in this patient population. Thus, we aimed to design an exploratory randomized clinical trial with parallel placebo group to evaluate the effectiveness of intrauterine Growth Hormone infusion as an add-on therapy to conventional hormone therapy compared to placebo in patients with thin endometrium undergoing frozen thawed embryo transfer
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
- Model description
- This study was designed as a randomized controlled exploratory clinical trial, controlled with a parallel placebo group and random allocation using an online based system.
| Arm | Type | Receives |
|---|---|---|
| Growth hormone | Active comparator | Drug: Growh hormone |
| Placebo | Placebo comparator | Other: Placebo |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- At least a history of cycle cancellation due to a thin endometrium less than 7 mm following standard hormonal treatment
- Availability of ≥1 embryo with good quality
- Normal baseline hormones value including: Testosterone, Progesterone, Prolactin, Luteinizing Hormone (LH), Follicle Stimulating Hormone (FSH)
Key exclusion criteria (9 listed)
- Internal genital anomalies
- Active intrauterine infection Endometrial thickness≥7 on the 10th day of menstrual cycle
- History of Asherman syndrome
- History of cancer
- History of uterine surgery in past 3 months
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 |
|---|---|---|
| Growh hormoneIn this group, patients will receive growth hormone solution containing 1.99 milligrams of the drug dissolved in 1.5 milliliters of 0.9% saline solution (normal saline), in addition to standard hormonal therapy, starting from cycle day 10. Treatment sessions will be conducted at two-day intervals. In case of non-response to treatment (failure to reach a minimum endometrial thickness of 7 millimeters in the subsequent assessment), the patient will receive a maximum of 4 doses, and if response to treatment is observed, growth hormone infusion will be discontinued. All infusions will be administered intrauterinely via an Intrauterine Insemination (IUI) catheter. | Drug | Growth hormone |
| PlaceboSimilar to the intervention group, from cycle day 10, an equal volume of 0.9% saline solution (normal saline) will be administered in addition to standard hormonal therapy. Treatment sessions will be conducted at two-day intervals. In case of non-response to treatment (failure to reach a minimum endometrial thickness of 7 millimeters in the subsequent assessment), the patient will receive a maximum of 4 doses, and if response to treatment is observed, placebo infusion will be discontinued. All infusions will be administered intrauterinely via an Intrauterine Insemination (IUI) catheter. | Other | Placebo |
Primary outcome
Endometrial thickness
Time frame: Baseline (On the 10th day of menstrual cycle), and On the day of response to treatment (in case of response) and in case of non-response to treatment on the 18th day of the mesntrual cycle
Measurement of endometrial thickness will be performed utilizing transvaginal sonography due to its closer proximity to the endometrium and with an empty bladder. To minimize the potential bias of measuring endometrial thickness during uterus contraction, occur during contractions, measurements will be taken only after the patient's contractions have ceased.
5 secondary outcomes
Clinical Pregnancy Rate
Time frame: 6-8 of gestational week
Response to treatment
Time frame: 2 days following the last dose of placebo or growth hormone
Implantation rate
Time frame: 6-8 of gestational week
IVF cancellation rate
Time frame: 2 days following the last dose of placebo or growth hormone
Early pregnancy complications
Time frame: During the first 12 weeks of pregnancy
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
- Results publicationYu H, Gao S, Tang H, Chen H, Deng Z, Yang L, et al. Growth hormone intrauterine perfusion combined with replacement cycle in the treatment of non-response thin endometrium: report of 5 cases. Int J Clin Exp Med. 2016;9(6):11982-9
- Results publication: PubMed 36273309Hosseini Aghdam S, Ghasemzadeh A, Farzadi L, Hamdi K, Baradaran-Binazir M, Nouri M, Fattahi A, Dttrich R. Growth Hormone: A Potential Treatment of Patients with Refractory Thin Endometrium: A Clinical Trial Study. Int J Fertil Steril. 2022 Oct 9;16(4):251-255. doi: 10.22074/ijfs.2022.541389.1210.
- Results publication: PubMed 34532462Li W, Cao Z, Yu X, Hu W. Effect of growth hormone on thin endometrium via intrauterine infusion. Ann Transl Med. 2021 Aug;9(16):1325. doi: 10.21037/atm-21-3583.
- Results publication: PubMed 31616379Altmae S, Aghajanova L. Growth Hormone and Endometrial Receptivity. Front Endocrinol (Lausanne). 2019 Sep 24;10:653. doi: 10.3389/fendo.2019.00653. eCollection 2019.
- Results publication: PubMed 31029557Liu KE, Hartman M, Hartman A. Management of thin endometrium in assisted reproduction: a clinical practice guideline from the Canadian Fertility and Andrology Society. Reprod Biomed Online. 2019 Jul;39(1):49-62. doi: 10.1016/j.rbmo.2019.02.013. Epub 2019 Mar 20.
- Results publication: PubMed 37013570Fu LL, Xu Y, Yan J, Zhang XY, Li DD, Zheng LW. Efficacy of granulocyte colony-stimulating factor for infertility undergoing IVF: a systematic review and meta-analysis. Reprod Biol Endocrinol. 2023 Apr 3;21(1):34. doi: 10.1186/s12958-023-01063-z.
- Derived from this study: PubMed 42457811Ghasemi Tehrani H, Zamani Dehkordi N, Hematian M, Ataei-Goujani H, Rahmati R, Naghshineh E, Lotfizadeh M, Mehrabian F. A randomized controlled trial of intrauterine growth hormone for thin endometrium. Sci Rep. 2026 Jul 15. doi: 10.1038/s41598-026-62005-4. Online ahead of print.
- Individual participant dataSharing planned: No. Individual Participant Data (IPD) may be shared following the publication of the study, as per specific requests from the researchers.
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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. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Growh hormone in people with Thin Endometrium and Infertility Female, run by Isfahan University of Medical Sciences at 1 site in Iran.
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 3 inclusion and 9 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: finished, as of the sponsor's last update on 19 Sep 2024. 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 Iran. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Endometrial thickness (time frame: Baseline (On the 10th day of menstrual cycle), and On the day of response to treatment (in case of response) and in case of non-response to treatment on the 18th day of the mesntrual cycle). 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 NCT06379659, which also lists 7 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 19 Sep 2024.