Fertility DisordersPhase 2NCT04850261
Injection Free IVF
A Phase 2 study testing hCG Injection and Nafarelin nasal spray in people with Fertility Disorders, run by Insel Gruppe AG, University Hospital Bern.
Trial summary
Investigation of Natural Cycle In vitro Fertilisation (NC-IVF) treatment with ovulation induction with a nasal GnRH agonist instead of regular NC-IVF treatment with subcutaneous application of hCG with the objective of increasing treatment tolerability and reducing discomfort while being equally successful in terms of… Read more about this study
- Who is it for?
- Ages 18 to 42 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Fertility Disorders
- What is being tested?
- hCG Injection and Nafarelin nasal spray
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 1 May 2021to 31 Mar 2024
- Phase
- Phase 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 42 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Indication for IVF
- Wish to perform NC-IVF
- Regular menstruation cycles (26-32 days)
- Orthotopic localization of ovaries
- Age 18-42
- Written informed consent
Who cannot join
- Endometrioses III°-IV°
- ≥ 3 embryo transfers in previous IVF therapies without pregnancy
- Contraindications or allergies against study medications
- < 18 and > 42 years of age
- Known or suspected non-compliance
- Inability of the participant to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc.
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- Participation in another study with investigational drug within the 30 days preceding and during the present study
- Previous enrolment into the current study
- Enrolment of the investigators, their family members, employees and other dependent persons
About this study
Official title: Injection Free Natural Cycle In Vitro Fertilisation by Using a Nasal GnRH Agonist to Induce Ovulation. Is it More Comfortable for Patients and Equally Effective as Subcutaneous hCG Injection?
Investigation of Natural Cycle In vitro Fertilisation (NC-IVF) treatment with ovulation induction with a nasal GnRH agonist instead of regular NC-IVF treatment with subcutaneous application of hCG with the objective of increasing treatment tolerability and reducing discomfort while being equally successful in terms of embryo transfer rates.
Read the detailed description
In vitro Fertilisation (IVF) treatments can be performed without gonadotropins to reduce side effects. These kinds of IVF treatments are called Natural Cycle IVF (NC-IVF). As NC-IVFs are almost equally effective as classical IVF with gonadotropins but less stressful, they are preferred by many women.
However, a relevant burden in NC-IVF still is the ovulation induction by self-injection of human Chorionic Gonadotropin (hCG).
Replacing hCG injection by a nasally applicable Gonadotropin-Releasing Hormone agonist (GnRHa) might reduce this discomfort. GnRHa are already used to induce ovulation in classical IVF treatments.
The objective of our study ist to answer the question whether NC-IVF treatment with a nasal GnRH agonist can increase treatment tolerability and reduce discomfort while being equally successful in terms of embryo transfer rates than NC-IVF treatment with subcutaneous application of hCG.
The study will be a randomized controlled proof-of-concept trial. It will be performed in two steps whereas the power analysis only relates to the first step which is prospective-randomized and will be performed as follows:
Step 1:
Prior to the start of the first NC-IVF treatment cycle the patients will be randomized in equal parts by electronic randomisation to receive either the standard therapy with hCG injection (Intervention A) or the study therapy with nasal GnRHa (Intervention B).
- Intervention A: As soon as the expected follicle size is >15 mm, ovulation will be induced by injecting 5.000 IU hCG. The follicle aspiration, including flushing of the follicle will be performed 36 hours later. The transfer of the embryo will be performed 2-5 days after the aspiration.
In order to determine estradiol- and progesterone concentrations blood will be taken 10±1 days after the hCG application. Pregnancy will be confirmed or excluded by hCG testing in serum or urine 14-21 days after the follicle aspiration. In case of positive hCG testing, clinical pregnancy will be confirmed by vaginal ultrasound 4-6 weeks after follicle aspiration.
- Intervention B: The study therapy (Intervention B) will be performed identically as Intervention A with the following exception: Instead of injecting subcutaneous hCG the patients will apply 1 hub of a GnRHa nasal spray (200 microg Nafarelin) to induce ovulation.
Step 2:
If there is no pregnancy achieved in the first treatment cycle, the patients will switch to the respective other intervention (cross-over design). This procedure allows for an intraindividual comparison of the main outcomes (treatment tolerability and discomfort). Again, the two interventions will be performed as described in step 1.
Questionnaires:
At the beginning of the study, all participants will fill in the Fertility Quality of Life (FertiQoL) Core questionnaire.
For each treatment cycle, they will additionally fill in the FertiQoL Treatment questionnaire and a set of visual analog scale (VAS) questions concerning the level of discomfort encountered in the treatment.
- Conditions
- Fertility Disorders
- Being tested
- hCG Injection, Nafarelin nasal spray
- Keywords
- In vitro fertilization, IVF, GnRHa, Ovulation induction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
hCG InjectionDrug
Ovulation will be induced by subcutaneous hCG injection
Nafarelin nasal sprayDrug
Ovulation will be induced by nasal application of Nafarelin
| Study group | Role | What they receive |
|---|---|---|
| Intervention A: hCG injection | Active comparator | Ovulation induction by subcutaneous injection of 5.000 IU hCG Receives: Drug: hCG Injection |
| Intervention B: nasal application of Nafarelin | Experimental | Ovulation induction by nasal application of 200 microgram Nafarelin Receives: Drug: Nafarelin nasal spray |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment tolerability
Treatment tolerability will be measured with the Treatment tolerability subscale of the Fertility Quality of Life (FertiQoL) Treatment questionnaire. The subscale assesses the experience of mental and physical symptoms and disruption in daily life due to treatment. It consists of 4 items. Each item has a set of 5 possible responses, from which patients have to chose the one that most closely reflects how they think and feel.
Measured: It will be assessed between Ovulation induction and follicle aspiration. It takes about 3 minutes to complete in the questionnaire
Discomfort of treatment
The level of discomfort of the treatment encountered by the patients will be measured with 3 Visual Analogue Scale (VAS) questions ranging from 1 - 10 to specifically compare the discomfort imposed by the two treatments.
Measured: It will be assessed between Ovulation induction and follicle aspiration. It takes about 2 minutes to complete in the questionnaire
Secondary outcomes (1)
Embryo transfer rate
Number of embryos transferred in the two groups
Measured: It will be documented after the embryo transfer (2-5 days after follicle aspiration)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Apr 2021
- Study start1 May 2021 (estimated)
- Primary completion31 Mar 2024 (estimated)
- Study completion31 Mar 2024 (estimated)
Why it stopped: The planned study medication was no longer available in Switzerland
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Fertility DisordersStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Prospective, randomized, active controlled proof-of concept trial (phase II)
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Insel Gruppe AG, University Hospital Bern
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Michael von Wolff, Prof., Principal investigator, University Womens Hospital, Bern, Switzerland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04850261
- Sponsor's protocol ID
- BASEC Project-ID 2020-03007
- Status last verified
- Oct 2024
- First submitted
- 1 Mar 2021
- Last updated
- 30 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Injection Free Natural Cycle In Vitro Fertilisation by Using a Nasal GnRH Agonist to Induce Ovulation. Is it More Comfortable for Patients and Equally Effective as Subcutaneous hCG Injection?
- ClinicalTrials.gov ID
- NCT04850261
- Acronym / sponsor ID
- BASEC Project-ID 2020-03007
- Conditions
- Fertility Disorders
- Keywords
- In vitro fertilization, IVF, GnRHa, Ovulation induction
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: The planned study medication was no longer available in Switzerland
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Insel Gruppe AG, University Hospital BernUniversity, hospital or other
- Study start
- 1 May 2021 (estimated)
- Primary completion
- 31 Mar 2024 (estimated)
- Study completion
- 31 Mar 2024 (estimated)
- First posted
- 20 Apr 2021 (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.
Investigation of Natural Cycle In vitro Fertilisation (NC-IVF) treatment with ovulation induction with a nasal GnRH agonist instead of regular NC-IVF treatment with subcutaneous application of hCG with the objective of increasing treatment tolerability and reducing discomfort while being equally successful in terms of embryo transfer rates.
Detailed description
In vitro Fertilisation (IVF) treatments can be performed without gonadotropins to reduce side effects. These kinds of IVF treatments are called Natural Cycle IVF (NC-IVF). As NC-IVFs are almost equally effective as classical IVF with gonadotropins but less stressful, they are preferred by many women.
However, a relevant burden in NC-IVF still is the ovulation induction by self-injection of human Chorionic Gonadotropin (hCG).
Replacing hCG injection by a nasally applicable Gonadotropin-Releasing Hormone agonist (GnRHa) might reduce this discomfort. GnRHa are already used to induce ovulation in classical IVF treatments.
The objective of our study ist to answer the question whether NC-IVF treatment with a nasal GnRH agonist can increase treatment tolerability and reduce discomfort while being equally successful in terms of embryo transfer rates than NC-IVF treatment with subcutaneous application of hCG.
The study will be a randomized controlled proof-of-concept trial. It will be performed in two steps whereas the power analysis only relates to the first step which is prospective-randomized and will be performed as follows:
Step 1:
Prior to the start of the first NC-IVF treatment cycle the patients will be randomized in equal parts by electronic randomisation to receive either the standard therapy with hCG injection (Intervention A) or the study therapy with nasal GnRHa (Intervention B).
- Intervention A: As soon as the expected follicle size is >15 mm, ovulation will be induced by injecting 5.000 IU hCG. The follicle aspiration, including flushing of the follicle will be performed 36 hours later. The transfer of the embryo will be performed 2-5 days after the aspiration.
In order to determine estradiol- and progesterone concentrations blood will be taken 10±1 days after the hCG application. Pregnancy will be confirmed or excluded by hCG testing in serum or urine 14-21 days after the follicle aspiration. In case of positive hCG testing, clinical pregnancy will be confirmed by vaginal ultrasound 4-6 weeks after follicle aspiration.
- Intervention B: The study therapy (Intervention B) will be performed identically as Intervention A with the following exception: Instead of injecting subcutaneous hCG the patients will apply 1 hub of a GnRHa nasal spray (200 microg Nafarelin) to induce ovulation.
Step 2:
If there is no pregnancy achieved in the first treatment cycle, the patients will switch to the respective other intervention (cross-over design). This procedure allows for an intraindividual comparison of the main outcomes (treatment tolerability and discomfort). Again, the two interventions will be performed as described in step 1.
Questionnaires:
At the beginning of the study, all participants will fill in the Fertility Quality of Life (FertiQoL) Core questionnaire.
For each treatment cycle, they will additionally fill in the FertiQoL Treatment questionnaire and a set of visual analog scale (VAS) questions concerning the level of discomfort encountered in the treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Prospective, randomized, active controlled proof-of concept trial (phase II)
| Arm | Type | Receives |
|---|---|---|
| Intervention A: hCG injection | Active comparator | Drug: hCG InjectionOvulation induction by subcutaneous injection of 5.000 IU hCG |
| Intervention B: nasal application of Nafarelin | Experimental | Drug: Nafarelin nasal sprayOvulation induction by nasal application of 200 microgram Nafarelin |
Who may qualify
- Ages
- 18 to 42 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Indication for IVF
- Wish to perform NC-IVF
- Regular menstruation cycles (26-32 days)
- Orthotopic localization of ovaries
- Age 18-42
Key exclusion criteria (9 listed)
- Endometrioses III°-IV°
- ≥ 3 embryo transfers in previous IVF therapies without pregnancy
- Contraindications or allergies against study medications
- < 18 and > 42 years of age
- Known or suspected non-compliance
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 |
|---|---|---|
| hCG InjectionOvulation will be induced by subcutaneous hCG injection | Drug | Intervention A: hCG injection |
| Nafarelin nasal sprayOvulation will be induced by nasal application of Nafarelin | Drug | Intervention B: nasal application of Nafarelin |
Primary outcome
Treatment tolerability
Time frame: It will be assessed between Ovulation induction and follicle aspiration. It takes about 3 minutes to complete in the questionnaire
Treatment tolerability will be measured with the Treatment tolerability subscale of the Fertility Quality of Life (FertiQoL) Treatment questionnaire. The subscale assesses the experience of mental and physical symptoms and disruption in daily life due to treatment. It consists of 4 items. Each item has a set of 5 possible responses, from which patients have to chose the one that most closely reflects how they think and feel.
Discomfort of treatment
Time frame: It will be assessed between Ovulation induction and follicle aspiration. It takes about 2 minutes to complete in the questionnaire
The level of discomfort of the treatment encountered by the patients will be measured with 3 Visual Analogue Scale (VAS) questions ranging from 1 - 10 to specifically compare the discomfort imposed by the two treatments.
1 secondary outcome
Embryo transfer rate
Time frame: It will be documented after the embryo transfer (2-5 days after follicle aspiration)
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Oct 2024.
- Individual participant dataSharing planned: No
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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.
Michael von Wolff, Prof. principal investigator
University Womens Hospital, Bern, Switzerland
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing hCG Injection and Nafarelin nasal spray in people with Fertility Disorders, run by Insel Gruppe AG, University Hospital Bern.
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 6 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: withdrawn, as of the sponsor's last update on 30 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
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.
What does this phase mean?
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 was withdrawn before enrolling participants, so there are no results.
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?
Treatment tolerability (time frame: It will be assessed between Ovulation induction and follicle aspiration. It takes about 3 minutes to complete in the questionnaire). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 30 Oct 2024.