Different routes of progesterone administration for sustaining implantation in in vitro fertilisation patients: impact on pregnancy and live birth rates
| ISRCTN | ISRCTN52148405 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN52148405 |
| Secondary identifying numbers | oneday20161 |
- Submission date
- 02/08/2023
- Registration date
- 15/08/2023
- Last edited
- 27/12/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Pregnancy and Childbirth
Plain English summary of protocol
Background and study aims
Progesterone administration is considered an essential therapy for luteal phase support in patients undergoing in-vitro fertilization (IVF) technologies This study aims to compare the administration of a combined protocol of vaginal gel progesterone (90 mg/daily) and oral dydrogesterone (20 mg/daily), with the administration of micronized vaginal progesterone alone (800 mg daily) to support the luteal phase during embryo implantation in patients undergoing in vitro fertilization.
Who can participate
Infertile patients undergoing standard in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment at One Day Medical Center IVF Unit
What does the study involve
Ovarian stimulation:
All the patients will undergo a mild ovarian stimulation protocol:
Subcutaneous injections of recombinant follicle-stimulating hormone (rFSH) will be started at a dose of 75-150 IU (international unit). Growing ovarian follicles will be detected and measured using ultrasonography at two-day intervals. Estradiol blood level will be measured at two days intervals. Subcutaneous injections of Gonadotropin-releasing hormone antagonist (GnRH ant) (0.25 mg/day) will be administered when the leading follicle measures 14 mm. The rFSH dose will be adjusted when necessary according to the follicular size and estradiol level. Final oocyte maturation will be induced by subcutaneous injection of a dose of 10,000 IU of Human Chorionic Gonadotropin (hCG).
Oocyte recovery and embryo transfer
Oocyte retrieval will be carried out at 34-36 hours after hCG injection. Recovered oocytes will be inseminated by standard IVF or ICSI. Up to 3 embryos will be transferred into the patient's uterus on day three after the oocyte insemination.
What are the possible benefits and risks of participating?
Benefits: the applied supplementation therapy for luteal phase support after embryo replacement could increase the pregnancy and live birth rates.
Risks: the applied supplementation therapy for luteal phase support after embryo replacement could reduce the chance of pregnancy and live birth.
Where is the study run from?
One Day Medical Center s.r.l. (Italy)
When is the study starting and how long is it expected to run for?
October 2016 to December 2022
Who Is funding the study?
One Day Medical Center s.r.l. (Italy)
Who is the main contact?
Leonardo Rinaldi, Leo.rinaldi@tiscali.it
Contact information
Principal Investigator
Via Attilio Ambrosini 114
Roma
00147
Italy
| Phone | +39 (0)3356798557 |
|---|---|
| leo.rinaldi@tiscali.it |
Study information
| Study design | Prospective open randomized study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Medical and other records |
| Study type | Treatment, Efficacy |
| Scientific title | Oral dydrogesterone associated with vaginal micronized progesterone supplementation vs vaginal micronized progesterone alone supplementation for luteal phase support in in vitro fertilization patients: effects on pregnancy and live birth rates |
| Study objectives | To compare the administration of a combined protocol of progesterone vaginal gel and oral dydrogesterone, with the administration of micronized vaginal progesterone alone for luteal phase support in patients undergoing GnRH antagonist-mild stimulation regimen |
| Ethics approval(s) |
Approved 10/12/2016, One Day Ethics Commission (Via Attilio Ambrosini 114, Roma, 00147, Italy; +39 (0)645212028; amministrazione@onedaymedicalcenter.it), ref: ethics12-2016 |
| Health condition(s) or problem(s) studied | Luteal phase supplementation in assisted reproduction |
| Intervention | All the patients are going to have a mild ovarian stimulation protocol: rFSH will be started at a dose of 75-150 IU on the base of AMH level. GnRH antagonist (0.25 mg/day) will be administered when the leading follicle measures 14 mm. The FSH dose will be adjusted when necessary according to the follicular size and estradiol level. Final oocyte maturation will be induced by a dose of 10,000 IU of hCG. Recovered oocytes will be inseminated by standard IVF or intracytoplasmic sperm injection (ICSI). Up to three embryos will be transferred on day 3 after oocyte insemination. Randomization will be performed using a computer-generated random assignment schedule for each patient. Sealed and numbered envelopes will be used to conceal the treatment allocation until randomization. On the day of oocyte recovery, the patients will be randomized into two groups: Group A will receive vaginal administration of capsules of micronized progesterone (800 mg/day) for luteal phase support; Group B will receive a combination of vaginal administration of a gel of micronized progesterone (90 mg/day) and oral dydrogesterone 10 mg twice a day for luteal phase support. The duration of the treatment is 14 - 21 days; follow-up will be around 9 months for each patient, from the established pregnancy to the delivery. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | Dose response |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Oral dydrogesterone, micronized vaginal progesterone |
| Primary outcome measure | Clinical pregnancy measured using a blood test to evaluate the level of human chorionic gonadotropin (hCG), which indicates the eventual embryo implantation and pregnancy, 14 days after embryo replacement in the patient's uterus |
| Secondary outcome measures | Embryo implantation rate measured using ultrasonography at 4 weeks following a positive hCG test to confirm the clinical pregnancy |
| Overall study start date | 15/10/2016 |
| Completion date | 23/12/2022 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 27 Years |
| Upper age limit | 41 Years |
| Sex | Female |
| Target number of participants | 650 |
| Total final enrolment | 620 |
| Key inclusion criteria | 1. Infertility attributable to tubal factors, moderate endometriosis, male factor, or idiopathic infertility 2. Serum hormonal profile within the normal range (AMH >1 ng/ml) 3. Regular menstrual cycles 4. The presence of a normal uterine cavity 5. Body mass index (BMI) of 20–26 kg/m² |
| Key exclusion criteria | 1. Infertility attributable to genetic factors or severely reduced ovarian reserve 2. Serum hormonal profile showing a reduced ovarian reserve (AMH <0.9 ng/ml) 3. Irregular menstrual cycles or amenorrhea 4. Congenital or acquired uterine malformation 5. A body mass index (BMI) <20 or >26 kg/m² |
| Date of first enrolment | 01/01/2017 |
| Date of final enrolment | 01/11/2022 |
Locations
Countries of recruitment
- Italy
Study participating centre
Roma
00147
Italy
Sponsor information
Hospital/treatment centre
Via Attilio Ambrosini 114
Roma
00147
Italy
| Phone | +39 (0)645212038 |
|---|---|
| amministrazione@onedaymedicalcenter.it |
Funders
Funder type
Hospital/treatment centre
No information available
Results and Publications
| Intention to publish date | 01/12/2023 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not expected to be made available |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are not expected to be made avalilable due to lack of consensus |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | 21/12/2024 | 27/12/2024 | Yes | No |
Editorial Notes
27/12/2024: Publication reference added.
14/08/2023: Trial's existence confirmed by One Day Ethics Commission (Italy).
