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

Infertility Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06379659
• Other study ID #: IR.MUI.MED.REC.1402.449
• Secondary ID: IRCT201109080075
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: May 2024
• Est. completion date: November 2024

Study information

• Verified date: April 2024
• Source: Isfahan University of Medical Sciences
• Contact: Hatav Ghasemi Tehrani
• Phone: 0989131134081
• Email: hatav.tehrani2014[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 54
• Est. completion date: November 2024
• Est. primary completion date: July 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

• 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)

Exclusion Criteria:

• 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

• Visible intrauterine adhesion

• Pathospermia in partner

• Premature ovarian failure

Related Conditions & MeSH terms

• Infertility
• Infertility Female
• Infertility, Female
• Thin Endometrium

Intervention

Drug:
• Growh hormone
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.

Other:
• Placebo
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.

Locations

Country	Name	City	State
Iran, Islamic Republic of	Isfahan Shahid Beheshti hospital, Hazrat e Maryam Fertility Center	Isfahan

Sponsors (1)

Lead Sponsor	Collaborator
Isfahan University of Medical Sciences

Country where clinical trial is conducted

Iran, Islamic Republic of, 

References & Publications (6)

Altmae S, Aghajanova L. Growth Hormone and Endometrial Receptivity. Front Endocrinol (Lausanne). 2019 Sep 24;10:653. doi: 10.3389/fendo.2019.00653. eCollection 2019. — View Citation

Fu 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. — View Citation

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 — View Citation

Li 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. — View Citation

Liu 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 — View Citation

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	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	Clinical Pregnancy Rate	The number of fetuses that have a heartbeat and are not ectopic evaluated by Transvaginal Ultrasonography	6-8 of gestational week
Secondary	Response to treatment	The number of patients that reach at least 7 mm of endometrial thickness	2 days following the last dose of placebo or growth hormone
Secondary	Implantation rate	The number of gestational sacs to the number of transferred embryos evaluated by Transvaginal ultrasonography	6-8 of gestational week
Secondary	IVF cancellation rate	The number of patients who do not reach enough endometrial thickness for transferring despite maximum treatment	2 days following the last dose of placebo or growth hormone
Secondary	Early pregnancy complications	Including early miscarriage (miscarriage in less than 12th gestational week) and Ectopic pregnancy	During the first 12 weeks of pregnancy