InfertilityNCT03238807
Effect of Intrauterine Injection of Hcg Before ET on Clinical Outcomes in IVF/ICSI Cycles
A study testing Human Chorionic Gonadotropin in people with Infertility and ART, run by Assiut University at 1 site in Egypt.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 43 years, women only
- Conditions the study is for
- Infertility, ART
- What is being tested?
- Human Chorionic Gonadotropin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 181 participants
- Where
- 1 siteEgypt
- Study dates
- 8 Jul 2018to 4 Oct 2020
- Phase
- Interventional
- 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 43 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- infertility, male or female factor
- Women undergoing ICSI/IVF
Who cannot join
- functional azoospermia
- submucous uterine myomas or previous myomectomy
- endometriosis
- hydrosalpinges without prior excision or occlusion of the tubal ostia
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read more
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.
Read the 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.
- Conditions
- Infertility, ART
- Being tested
- Human Chorionic Gonadotropin
- Keywords
- hCG, Intrauterine hCG, IVF, ICSI
- Medical subject headings
- Infertility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Human Chorionic GonadotropinDrug
Also called Epifasi
500 IU of human Chorionic Gonadotropin
| Study group | Role | What they receive |
|---|---|---|
| Intervention Group | Experimental | Group that will receive intrauterine injection of human Chorionic Gonadotropin before ET Receives: Drug: Human Chorionic Gonadotropin |
| Control Group | No intervention | Control Group |
What is being measured
The primary outcome is the main question the study is designed to answer.
Live Birth Rate (LBR)
calculated by the number of live births to the number of transferred embryos
Measured: 9 months
Secondary outcomes (3)
Clinical Pregnancy Rate (cPR)
calculated by the percentage of detected clinical pregnancies using ultrasound to the IVF/ICSI cycles in each group
Measured: 5 weeks
Implantation Rate (IR)
calculated by the number of visualized embryos by transvaginal ultrasound to the number of transferred embryos
Measured: 5 weeks
Miscarriage rate (MR)
calculated by the ratio of miscarriages to the number of confirmed pregnancies.
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Aug 2017
- Study start8 Jul 2018
- Primary completion4 Oct 2020
- Study completion4 Oct 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for InfertilityStudies of the same condition, open and under way.
- More trials run by Assiut UniversityThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized Controlled Trial
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 181 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assiut University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Karim Abdallah, Assiut University
- Investigators
- Ahmed Makhlouf, MD, Principal investigator, Assiut UniversityHazem Saadeldine, MD, Study chair, Assiut UniversityEsraa Badran, MD, Study chair, Assiut UniversityKarim Abdallah, M.Sc, Study director, Assiut University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03238807
- Sponsor's protocol ID
- IntraUterine HCG Assiut
- Status last verified
- Sep 2022
- First submitted
- 1 Aug 2017
- Last updated
- 28 Sep 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
Abdallah KS, Makhlouf A, Badran E, El-Nashar IM, Al-Hussaini TK, Farghaly T, Mohamed HS, Mol BW, Abdelmagied AM. Intrauterine injection of HCG before embryo transfer: a parallel, double-blind randomized trial. Reprod Biomed Online. 2021 Oct;43(4):663-669. doi: 10.1016/j.rbmo.2021.06.011. Epub 2021 Jun 20.
PubMed 34412973
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT03238807
- Acronym / sponsor ID
- IntraUterine HCG Assiut
- Conditions
- Infertility, ART
- Keywords
- hCG, Intrauterine hCG, IVF, ICSI
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 181 participants (actual)
- Lead sponsor
- Assiut UniversityUniversity, hospital or other
- Study start
- 8 Jul 2018 (actual)
- Primary completion
- 4 Oct 2020 (actual)
- Study completion
- 4 Oct 2020 (actual)
- First posted
- 3 Aug 2017 (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.
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.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
- Model description
- Randomized Controlled Trial
| Arm | Type | Receives |
|---|---|---|
| Intervention Group | Experimental | Drug: Human Chorionic GonadotropinGroup that will receive intrauterine injection of human Chorionic Gonadotropin before ET |
| Control Group | No intervention | –Control Group |
Who may qualify
- Ages
- 18 to 43 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- infertility, male or female factor
- Women undergoing ICSI/IVF
Key exclusion criteria (4 listed)
- functional azoospermia
- submucous uterine myomas or previous myomectomy
- endometriosis
- hydrosalpinges without prior excision or occlusion of the tubal ostia
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 |
|---|---|---|
| Human Chorionic GonadotropinAlso: Epifasi500 IU of human Chorionic Gonadotropin | Drug | Intervention Group |
Primary outcome
Live Birth Rate (LBR)
Time frame: 9 months
calculated by the number of live births to the number of transferred embryos
3 secondary outcomes
Clinical Pregnancy Rate (cPR)
Time frame: 5 weeks
Implantation Rate (IR)
Time frame: 5 weeks
Miscarriage rate (MR)
Time frame: 3 months
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 28 Sep 2022.
- Results publication: PubMed 34412973Abdallah KS, Makhlouf A, Badran E, El-Nashar IM, Al-Hussaini TK, Farghaly T, Mohamed HS, Mol BW, Abdelmagied AM. Intrauterine injection of HCG before embryo transfer: a parallel, double-blind randomized trial. Reprod Biomed Online. 2021 Oct;43(4):663-669. doi: 10.1016/j.rbmo.2021.06.011. Epub 2021 Jun 20.
- Individual participant dataSharing planned: Yes. 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.
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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.
Ahmed Makhlouf, MD principal investigator
Assiut University
Hazem Saadeldine, MD study chair
Assiut University
Esraa Badran, MD study chair
Assiut University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Human Chorionic Gonadotropin in people with Infertility and ART, run by Assiut University at 1 site in Egypt.
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 2 inclusion and 4 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 28 Sep 2022. 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 Egypt. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
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?
Live Birth Rate (LBR) (time frame: 9 months). 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 NCT03238807, which also lists 1 linked publication.
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 28 Sep 2022.