Effect of Intrauterine Injection of Hcg Before ET on Clinical Outcomes in IVF/ICSI Cycles

September 26, 2022 updated by: Karim Abdallah, Assiut University

Effect of Intrauterine Injection of Human Chorionic Gonadotropin Before Embryo Transfer on Clinical Outcomes in In-vitro Fertilization/Intracytoplasmic Sperm Injection Cycles: a Randomized Controlled Trial

Subfertility is the inability to conceive after 12 months of regular unprotected sexual intercourse. Around 15% of couples suffer from subfertility. As a treatment for subfertility, Assisted Reproductive Techniques (ART) have been a choice for subfertile couples. In Egypt in 2010, Pregnancy Rate was calculated to be 36.2%, Live Birth Rate to be 25.7%.

Implantation is the process by which the embryo adheres to the wall of the uterus. Endometrial receptivity plays the most important role for successful implantation after embryo quality. It is estimated that up to 70% of early pregnancy losses are due to failure of implantation.

Despite extensive research, the embryo-maternal dialogue that orchestrates the implantation process is still not fully understood. Much effort has been done in the last decades to detect factors affecting Implantation and improve endometrial receptivity.

Human Chorionic Gonadotropin (hCG) is a placental glycoprotein hormone that required to maintain pregnancy. Recent research data demonstrates that hCG is secreted very early by the embryo before implantation to facilitate it. hCG has been proved to cause attraction of inflammatory cells, promote angiogenesis, regulate chemical mediators at the endometrium. These effects proceed the classical role of hCG during pregnancy and could be a directly involved in and facilitating the implantation process.

Studies have been conducted to study the effect of injection of different concentrations of hCG inside the uterine cavity before Embryo Transfer (ET) to improve endometrial receptivity and outcomes of In-Vitro Fertilization (IVF) or Intra-Cytoplasmic Sperm Injection (ICSI) cycles.

A recent systematic review was conducted on 12 studies performing intrauterine injection of different doses of hCG before ET. Results of this study showed that there is increased pregnancy outcome after injection of intrauterine 500 IU of hCG. The study recommended a definitive large clinical trial with live birth as the primary outcome. There was no evidence that miscarriage was influenced by intrauterine hCG administration, irrespective of embryo stage at transfer or dose of intrauterine hCG.

Aim of the study:

To detect whether intrauterine injection of hCG before ET improves clinical outcomes in IVF/ICSI cycles.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This study is a Randomized Controlled Trial (RCT) to be done at ART center of Women's Health Hospital, Assiut university, Egypt.

All steps for IVF/ICSI procedure, from the beginning of the induction for controlled ovarian stimulation until just before the procedure of ET, will be done for all enrolled patients as routinely decided according to the local protocol of the ART center in Women Health Hospital, Assiut University. In the day of ET, number and quality of Embryos will be decided according to the routine practice guided by the local protocol.

The intervention preparation will be prepared by adding one vial of hCG containing 5000 IU to 1mL of tissue culture medium (Continuous Single Culture, IrvineScientific). To obtain 500 IU of hCG, 0.1 milliLiter (mL) of the preparation will be injected inside the uterus before ET in the study group. For the control group, 0.1 mL of the tissue culture medium without hCG will be injected inside the uterus before the ET. For both groups we will use Intra-Uterine Insemination (IUI) catheter (Sperm Trans, Sperm Processor) to inject the solution inside the uterine cavity 4 minutes before ET.

We will standardize the procedure of ET for all women apart from the intervention versus control step. All women participating in the study will be put in lithotomy position. Cusco's speculum will be introduced to visualize the cervix. Guided by transabdominal ultrasound with a full bladder, the ET catheter (Cook Sydney IVF Catheter) will be introduced through the cervical os into the uterine cavity. After introduction of the catheter into the uterine cavity loaded embryos will be injected inside the cavity 0.5 cm from the fundus.

Biochemical pregnancy test will be done 14 days after ET by measuring hCG in the woman's serum. If the test result is positive (according to the standard values that is used in the laboratory), a transvaginal ultrasound will be done 3 weeks following the positive biochemical test, to document the visualization of gestational sac, fetal pole and cardiac pulsation.

Pregnancy rate (PR) is calculated by the number of women with positive biochemical pregnancy test to the number of women enrolled in each group. The clinical pregnancy was defined as a viable pregnancy when there is evidence of a gestational sac, embryo and fetal heart rate at the time of ultrasound evaluation. Clinical Pregnancy Rate (cPR) is calculated by the percentage of detected clinical pregnancies using ultrasound to the IVF/ICSI cycles in each group. Implantation rate (IR) is calculated by the number of visualized embryos by transvaginal ultrasound to the number of transferred embryos. While Live Birth Rate (LBR) is calculated by the number of live births to the number of transferred embryos. Miscarriage rate (MR) is calculated by the ratio of miscarriages to the number of confirmed pregnancies.

Study Type

Interventional

Enrollment (Actual)

181

Phase

  • Not Applicable

Contacts and Locations

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

Study Locations

      • Assiut, Egypt, 71515
        • Assiut University - Women's Health Hospital

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

18 years to 43 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • infertility, male or female factor
  • Women undergoing ICSI/IVF

Exclusion Criteria:

  • functional azoospermia
  • submucous uterine myomas or previous myomectomy
  • endometriosis
  • hydrosalpinges without prior excision or occlusion of the tubal ostia

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: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Control Group
Experimental: Intervention Group
Group that will receive intrauterine injection of human Chorionic Gonadotropin before ET
500 IU of human Chorionic Gonadotropin
Other Names:
  • Epifasi

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Live Birth Rate (LBR)
Time Frame: 9 months
calculated by the number of live births to the number of transferred embryos
9 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical Pregnancy Rate (cPR)
Time Frame: 5 weeks
calculated by the percentage of detected clinical pregnancies using ultrasound to the IVF/ICSI cycles in each group
5 weeks
Implantation Rate (IR)
Time Frame: 5 weeks
calculated by the number of visualized embryos by transvaginal ultrasound to the number of transferred embryos
5 weeks
Miscarriage rate (MR)
Time Frame: 3 months
calculated by the ratio of miscarriages to the number of confirmed pregnancies.
3 months

Collaborators and Investigators

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

Investigators

  • Principal Investigator: Ahmed Makhlouf, MD, Assiut University
  • Study Chair: Hazem Saadeldine, MD, Assiut University
  • Study Chair: Esraa Badran, MD, Assiut University
  • Study Director: Karim Abdallah, M.Sc, Assiut University

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.

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 8, 2018

Primary Completion (Actual)

October 4, 2020

Study Completion (Actual)

October 4, 2020

Study Registration Dates

First Submitted

August 1, 2017

First Submitted That Met QC Criteria

August 1, 2017

First Posted (Actual)

August 3, 2017

Study Record Updates

Last Update Posted (Actual)

September 28, 2022

Last Update Submitted That Met QC Criteria

September 26, 2022

Last Verified

September 1, 2022

More Information

Terms related to this study

Other Study ID Numbers

  • IntraUterine HCG Assiut

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

All of the individual participant data collected during the trial, after deidentification to Researchers who provide a methodologically sound proposal To achieve aims in the approved proposal.

IPD Sharing Time Frame

Immediately after publication indefinitely.

IPD Sharing Access Criteria

Proposals should be directed to karimsayed88@hotmail.com. To gain access, data requestors will need to sign a data access agreement.

IPD Sharing Supporting Information Type

  • Study Protocol
  • Statistical Analysis Plan (SAP)
  • Analytic Code

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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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