Comparing two routes of administration of progesterone hormone for support in fertilization via intrauterine insemination
| ISRCTN | ISRCTN38513865 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN38513865 |
- Submission date
- 22/08/2020
- Registration date
- 04/11/2020
- Last edited
- 05/11/2020
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Urological and Genital Diseases
Plain English summary of protocol
Background and study aims
Infertility is when a couple cannot get pregnant (conceive) despite having regular unprotected sex. It is estimated that around 1 in 7 couples experience infertility. Fertility treatments can include assisted conception such as intrauterine insemination (IUI). Intrauterine Insemination (IUI) is a treatment that involves inserting sperm inside a woman's uterus. The goal of this treatment is to increase the number of sperm that reach the fallopian tubes and subsequently increase the chance of fertilization.
Alongside IUI, support for the preparation of the lining of the uterus to receive a fertilized egg may also be given. The luteal phase of the menstrual cycle, which occurs after ovulation (when the ovaries release an egg), involves the lining of the uterus becoming thicker to prepare for a possible pregnancy. Progesterone supplementation is the first-line of treatment during IUI if there is a deficiency in the luteal phase. Previous studies suggest that progesterone supplementation improves clinical pregnancy and live birth IUI treatment.
Progesterone can be administered via the mouth (oral), vagina, or injection into a large muscle. Vaginal administration results in higher uterine concentrations, but is often uncomfortable in the presence of vaginal bleeding, or may be washed out if bleeding is severe. The vaginal route also associated with vaginal irritation, discharge, bleeding, and interference with sex. Oral administration requires a higher concentration in order to compensate for the breakdown of the drug in the liver, but is generally the easiest and most acceptable method for the patient. Oral dydrogesterone is a synthetic progesterone with that could overcome these issues.
A previous study has shown that oral dydrogestrone is as effective as vaginal progesterone for luteal phase support in women undergoing IUI cycles and that participants were more satisfied with the oral medication.
The aim of this study is to compare the effect of oral dydrogesterone with vaginal progesterone for the luteal phase support on the pregnancy outcomes of IUI cycles.
Who can participate?
Patients who will be undergoing IUI treatment.
What does the study involve?
Participants will be identified by the researcher from the clinic’s census book during IUI treatment and will be assessed for eligibility. The researcher will explain the study to the patients and obtain their informed consent to participate.
Participants will be randomly assigned into 2 groups, A and B. Those in group A will receive Dydrogesterone (a tablet taken by mouth) 10mg twice per day, and those in group B will receive progesterone (also known as Uterogestan, applied in the vagina) 200mg twice per day. This medication will be taken before IUI and for 2 weeks after IUI.
A blood test of a hormone used to diagnose pregnancy, beta human chorionic gonadotropin (BHCG), will be checked two weeks after IUI. If this test is positive then the medication will be continued until 12 weeks of pregnancy. Measuring this hormone is a standard procedure at the study center. A transvaginal ultrasound will be performed at 6 weeks of pregnancy to confirm clinical pregnancy. This is a standard procedure at the study center. If blood tests and ultrasound confirm pregnancy, the patient will be followed up again at 12 weeks of pregnancy.
Participants will be able to report on their satisfaction with the medications and the study in questionnaires provided after 2 weeks on the study medication.
What are the possible benefits and risks of participating?
The chance of possible benefits to the participants is not known. Information obtained from this study will help improve the treatment or management of other patients with the same disease or condition.
This study uses two medications, these may cause some discomfort (vaginal irritation, and excessive vaginal discharge) but no serious adverse effects are expected. These medicines are not recommended for use in patients with a known allergy to Dydrogesterone or micronized vagina progesterone. If a participant develops any complications, the primary doctor will be informed and the participant will be managed accordingly.
Where is the study run from?
Reproductive Clinic of University Malaya Medical Center (Malaysia) and Hospital Tengku Ampuan Rahimah (Malaysia)
When is the study starting and how long is it expected to run for?
From July 2020 to May 2021
Who is funding the study?
University Malaya Medical Center (Malaysia)
Who is the main contact?
Dr Nabilah Abd Rahim
ummc@ummc.edu.my
Contact information
Scientific
University Malaya Medical Centre
Lembah Pantai
Kuala Lumpur
59100
Malaysia
 ORCID ID |
0000-0002-5539-1737 |
|---|---|
| Phone | +60 (0)3-7949 4422 |
| ummc@ummc.edu.my |
Study information
| Study design | Multicenter randomized controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | No participant information sheet available |
| Scientific title | Comparison of oral dydrogesterone with vaginal progesterone for luteal phase support in intrauterine insemination |
| Study objectives | Oral dydrogesterone is non-inferior to vaginal progesterone for luteal phase support in woman undergoing IUI cycles |
| Ethics approval(s) | Approved 13/07/2020, University of Malaya Medical Center Clinical Research Ethics Committee (University Malaya Medical Center, Lembah Pantai, 59100 Kuala Lumpur, Malaysia; +60 (0)3-79493209/225; iresearch@ummc.edu.my), ref: 202039-8363 |
| Health condition(s) or problem(s) studied | Female infertility |
| Intervention | This is a randomized controlled trial, carried out in the reproductive unit in University Malaya Medical Centre and in multicenter hospitals that have sufficient and appropriate expertise and experience in intrauterine insemination (IUI). All patients who will be undergoing IUI treatment and who fulfill the inclusion criteria will be recruited to participate in the study. The recruitment procedure will be as follows: 1. The patients will be identified by the researcher from the clinic’s census book during IUI treatment and follow up 2. The patients will be assessed for eligibility before recruited into this study using the Eligibility Form 3. The researcher will explain the study protocol to the patients and obtain their informed consent 4. The researcher will obtain socio-demographic data from the patient directly and from their medical records 5. Patients who do not fulfill inclusion criteria will be excluded. Proforma will be filled up once the patients are recruited in the study 6. Randomization will be done once the consent form is signed by the patient 7. Patients will be randomized into 2 groups, A and B. Randomisation will be using a random number generator at Random.org in random one block 8. The random allocation sequence will be placed in sealed numbered opaque envelopes for a strict number order assignment to participants 9. Randomisation will be done by opening the lowest remaining numbered sealed envelope 10. Those in group A will receive oral Dydrogesterone 10mg twice per day and those in group B will receive vaginal micronized progesterone (Uterogestan) 200mg twice per day until IUI 11. The decision to proceed with IUI is made by the usual care provider 12. Luteal phase support will be started after IUI with Dydrogesterone 10mg twice per day in group A, and vaginal micronized progesterone 200mg twice per day in group B for 2 weeks after IUI occurs 13. Serum Beta human chorionic gonadotropin (BHCG) will be checked two weeks after IUI. If serum BHCG is positive (>25) then the medication will be continued until 12 weeks of pregnancy. Measuring serum BHCG is a standard procedure for IUI at the study center. 3 ml of blood for each serum BHCG will be taken and will be sent to the UMMC laboratory. 14. Patient satisfaction will be obtained from patients based on questionnaires after 2 weeks on the study medication 15. A transvaginal ultrasound will be performed at 6 weeks of pregnancy to confirm clinical pregnancy. TVS is a standard procedure for IUI at the study center 16. If serum BHCG is >25 and clinical pregnancy is confirmed, the patient will be followed up again at 12 weeks of pregnancy for a trans abdominal ultrasound scan to confirm the viability of the pregnancy. If serum BHCG is <25, the participants will be counseled if they are keen to continue with another cycle of IUI or to proceed with IVF. 17. The patient will be terminated from the study if they develop an allergic reaction towards the medication or refuse to continue with the study 18. Clinical pregnancy rates, abortion rates, and patient satisfaction in both groups will be compared and will be recorded in case record form |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Oral dydrogesterone 10mg BD and vaginal micronized progesterone 200mg BD (Uterogestan) |
| Primary outcome measure | 1. Clinical pregnancy rate outcome measured using serum BHCG at 2 weeks, transvaginal ultrasound scan at 6 weeks, and follow-up appointment trans abdominal ultrasound scan at 12 weeks 2. Miscarriage rate measured using serum BHCG at 2 weeks, transvaginal ultrasound at 6 weeks, and follow-up appointment trans abdominal ultrasound scan at 12 weeks |
| Secondary outcome measures | 1. Patient satisfaction measured using investigator-designed questionnaires at 2 weeks |
| Overall study start date | 01/07/2020 |
| Completion date | 31/05/2021 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Female |
| Target number of participants | 160 |
| Key inclusion criteria | 1. Infertile women 2. Aged <40 years 3. Undergoing ovarian stimulation with gonadotropins for intrauterine insemination treatment 4. Normal hormonal assay 5. Normal pelvis in transvaginal sonography |
| Key exclusion criteria | 1. Basal levels of FSH ≥10 mlU/ml 2. Endometriosis stage 3 or 4 3. Severe male factor infertility |
| Date of first enrolment | 01/09/2020 |
| Date of final enrolment | 01/03/2021 |
Locations
Countries of recruitment
- Malaysia
Study participating centres
Lembah Pantai
Kuala Lumpur
59100
Malaysia
Jalan Langat
Selangor
41200
Malaysia
Sponsor information
Hospital/treatment centre
Lembah Pantai
Kuala Lumpur
59100
Malaysia
| Phone | +60 (0)3-7949 4422 |
|---|---|
| ummc@ummc.edu.my | |
| Website | https://www.ummc.edu.my/ |
"ROR" |
https://ror.org/00vkrxq08 |
Funders
Funder type
Hospital/treatment centre
No information available
Results and Publications
| Intention to publish date | 01/03/2022 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Other |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal |
| IPD sharing plan | The datasets generated and/or analysed during the current study during this study will be included in the subsequent results publication |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol file | version V1.0 | 09/03/2020 | 05/11/2020 | No | No |
Additional files
- ISRCTN38513865_PROTOCOL_V1.0_9Mar2020.pdf
- Uploaded 05/11/2020
Editorial Notes
05/11/2020: Internal review and uploaded protocol version 1.0, 9 March 2020 (not peer reviewed).
02/11/2020: Trial’s existence confirmed by the University of Malaya Medical Center Clinical Research Ethics Committee.
