Clinical trial NCT04850261: Injection Free IVF
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?
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Fertility Disorders
Keywords: In vitro fertilization, IVF
GnRHa
Ovulation induction
Lead sponsor: Insel Gruppe AG, University Hospital Bern
Sponsor class: OTHER
First posted: 2021-04-20
Enrollment: 0
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 42
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective, randomized, active controlled proof-of concept trial (phase II)
Primary purpose: TREATMENT

Brief 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 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.

Eligibility criteria: Inclusion Criteria:

* Indication for IVF
* Wish to perform NC-IVF
* Regular menstruation cycles (26-32 days)
* Orthotopic localization of ovaries
* Age 18-42
* Written informed consent

Exclusion Criteria:

* 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.
* 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

Primary outcomes:
measure: Treatment tolerability
timeFrame: It will be assessed between Ovulation induction and follicle aspiration. It takes about 3 minutes to complete in the questionnaire
measure: Discomfort of treatment
timeFrame: It will be assessed between Ovulation induction and follicle aspiration. It takes about 2 minutes to complete in the questionnaire
Secondary outcomes:
measure: Embryo transfer rate
timeFrame: It will be documented after the embryo transfer (2-5 days after follicle aspiration)
Other outcomes:
measure: Oocyte collection rate
timeFrame: It will be reported by the IVF-laboratory 2-5 days after the follicle aspiration
measure: Number of mature Oocytes
timeFrame: It will be reported by the IVF-laboratory 2-5 days after the follicle aspiration
measure: Fertilisation rate per aspirated oocyte
timeFrame: It will be reported by the IVF-laboratory 2-5 days after follicle aspiration
measure: Estradiol concentration 10 ±1 day after follicle aspiration
timeFrame: Blood withdrawal (5 min.) 9-11 days after follicle aspiration
measure: Progesterone concentration 10 ±1 day after follicle aspiration
timeFrame: Blood withdrawal (5 min.) 9-11 days after follicle aspiration
measure: Clinical pregnancy rate per initiated cycle
timeFrame: Pregnancy test 14-21 days after follicle aspiration
measure: Duration of luteal phase
timeFrame: 14-21 days after follicle aspiration, if pregnancy test ist negative
Locations:
Study officials:
affiliation: University Womens Hospital, Bern, Switzerland
name: Michael von Wolff, Prof.
role: PRINCIPAL_INVESTIGATOR
References: