Clinical trial NCT06379659: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Thin Endometrium
Infertility Female
Infertility
Keywords: Infertility
Infertility, Female
endometrial thickness
Thin Endoetrium
Growth Hormone
Human Growth Hormone
Somatropin
Intra-uterine infusion
Lead sponsor: Isfahan University of Medical Sciences
Sponsor class: OTHER
First posted: 2024-04-23
Enrollment: 54
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

Brief 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.

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

Eligibility criteria: 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

Primary outcomes:
measure: Endometrial thickness
timeFrame: 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:
measure: Clinical Pregnancy Rate
timeFrame: 6-8 of gestational week
measure: Response to treatment
timeFrame: 2 days following the last dose of placebo or growth hormone
measure: Implantation rate
timeFrame: 6-8 of gestational week
measure: IVF cancellation rate
timeFrame: 2 days following the last dose of placebo or growth hormone
measure: Early pregnancy complications
timeFrame: During the first 12 weeks of pregnancy
Other outcomes:
Locations:
city: Isfahan
country: Iran, Islamic Republic of
facility: Isfahan Shahid Beheshti hospital, Hazrat e Maryam Fertility Center
Study officials:
References:
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
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):251-255. doi: 10.22074/ijfs.2022.541389.1210.
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.
citation: 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.
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 Mar 20.
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.