Intracytoplasmatic Sperm InjectionPhase 2NCT03088631
Metformin in Intracytoplasmic Sperm Injection Cycles
A Phase 2 study testing Metformin in people with Intracytoplasmatic Sperm Injection, run by Assiut University at 1 site in Egypt.
Trial summary
The relationship between serum progesterone level on the day of human chorionic gonadotropin administration and outcome of in vitro fertilization /intracytoplasmic sperm injection and embryo transfer has been controversial for several decades. Read more about this study
- Who is it for?
- Ages 18 to 38 years, women only
- Conditions the study is for
- Intracytoplasmatic Sperm Injection
- What is being tested?
- Metformin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 320 participants
- Where
- 1 siteEgypt
- Study dates
- 1 Mar 2017to 1 Apr 2019
- 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 38 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- First or second trial ICSI cycle.
- Age: 20 -38 years
- BMI: patients with BMI ≥ 30 kg/m2 were advised to lose weight for 6 months through lifestyle modifications.
- AMH ≥1 ng/ml
- Basal FSH < 10 IU/ml.
- Normal uterine cavity evidenced by HSG or office hysteroscopy
- Normal levels of prolactin and TSH before starting COS cycle
Who cannot join
- Patients with recurrent two or more failed intra-cytoplasmic sperm injection cycles.
- Uterine anomalies or Synechiae.
- Severe male factor infertility
- Patients known to have diabetes, renal, liver disease, alcoholism, or drug abuse were excluded
- Patients who were on metformin treatment were asked to have a one month washout period before study participation.
- Poor responders
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Role of Metformin in Prevention of Premature Luteinization in Intracytoplasmic Sperm Injection Cycles
The relationship between serum progesterone level on the day of human chorionic gonadotropin administration and outcome of in vitro fertilization /intracytoplasmic sperm injection and embryo transfer has been controversial for several decades. some studies presented data against the negative effect of premature luteinization and reported that elevated serum progesterone had no adverse effect on pregnancy rates in fresh embryo-transfer cycles within different ovarian responses. However, most studies have evaluated the association between serum progesterone level and clinical outcome in fresh in vitro fertilization /intracytoplasmic sperm injection cycles and advocated that serum progesterone elevation on the day of human chorionic gonadotropin administration may adversely affect the clinical outcome by jeopardizing endometrial receptivity.
In addition, the underlying mechanism through which premature luteinization influences clinical outcomes is elusive. some proposed that premature luteinization cause impairment of the endometrial receptivity, which may indicate a change in the implantation window, is more likely to be affected than the oocyte.whereas some documented that the compromised quality of oocytes might also be a cause.
Read more
The cut-off point of premature luteinization is not well established until now. Premature luteinization has been variously defined based on serum P levels, with thresholds of 0.9-1.5 ng/mL being used.
Previous studies have shown that metformin inhibits the first steps of steroidogenesis dose-dependently reducing granulosa cells progesterone output. Moreover, other authors have recently reported that low dose metformin could improve in vitro fertilization outcome in non poly-cystic ovarian syndrome repeaters. So, considering the safety of this drug before pregnancy, metformin can be given to consenting patients from first ultrasound monitoring until ovulation triggering.
- Conditions
- Intracytoplasmatic Sperm Injection
- Being tested
- Metformin, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
will receive metformin (1500 mg/day) starting with the commencement of oral contraceptive pills in the preceding cycle until the day of human chorionic gonadotropin triggering.
PlaceboOther
will receive corn-flour placebo tablets (three tablets daily).
| Study group | Role | What they receive |
|---|---|---|
| Metformin group | Active comparator | Not described Receives: Drug: Metformin |
| Placebo group | Placebo comparator | Not described Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of premature luteinization in both groups
Serum progesterone measurement ≥ 1.5 ng/ml by Mini-vidas assay was used to diagnose cases of premature luteinization.
Measured: 12 days
Secondary outcomes (5)
ongoing pregnancy rate
The number of cases with pregnancy more than 12 weeks of gestation divided by the cycles initiated per 100.
Measured: 12 weeks
Good quality embryo rate
The number of good day 3 embryos per all two-pronuclear embryos.
Measured: 20 days
Progesterone-to-mature oocyte index (PMOI)
calculated by dividing the serum P level (ng/ml) by the number of mature oocytes.
Measured: 17 days
Progesterone/estradiol ratio
calculated as [progesterone (ng/mL) × 1000]/esatradiol (pg/mL)
Measured: 12 days
Implantation rate
The number of gestational sacs observed by trans-vaginal ultrasound divided by the number of embryos transferred.
Measured: 7 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Mar 2017
- Study start1 Mar 2017
- Primary completion1 Mar 2019
- Study completion1 Apr 2019
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 Intracytoplasmatic Sperm InjectionStudies 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 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Eligible women who gave their informed consent were randomized into two groups: (I) metformin group and (II) placebo group. Randomization was conducted using a computer generated table of random numbers with allocation concealment. Randomization was not changed after it had been done.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 320 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assiut University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Reda S. Hussein, Assiut University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03088631
- Sponsor's protocol ID
- MICSI
- Status last verified
- Apr 2019
- First submitted
- 18 Mar 2017
- Last updated
- 17 Sep 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
Hussein RS, Elnashar I, Amin AF, Zhao Y, Abdelmagied AM, Abbas AM, Abdelaleem AA, Farghaly TA, Abdalmageed OS, Youssef AA, Badran E, Abou-Taleb HA. Effect of Metformin on Premature Luteinization and Pregnancy Outcomes in Intracytoplasmic Sperm Injection-Fresh Embryo Transfer Cycles: A Randomized Double-Blind Controlled Trial. Int J Fertil Steril. 2021 Apr;15(2):108-114. doi: 10.22074/IJFS.2020.134643. Epub 2021 Mar 11.
PubMed 33687163
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of Metformin in Prevention of Premature Luteinization in Intracytoplasmic Sperm Injection Cycles
- ClinicalTrials.gov ID
- NCT03088631
- Acronym / sponsor ID
- MICSI
- Conditions
- Intracytoplasmatic Sperm Injection
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 320 participants (actual)
- Lead sponsor
- Assiut UniversityUniversity, hospital or other
- Study start
- 1 Mar 2017 (actual)
- Primary completion
- 1 Mar 2019 (actual)
- Study completion
- 1 Apr 2019 (actual)
- First posted
- 23 Mar 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.
The relationship between serum progesterone level on the day of human chorionic gonadotropin administration and outcome of in vitro fertilization /intracytoplasmic sperm injection and embryo transfer has been controversial for several decades. some studies presented data against the negative effect of premature luteinization and reported that elevated serum progesterone had no adverse effect on pregnancy rates in fresh embryo-transfer cycles within different ovarian responses. However, most studies have evaluated the association between serum progesterone level and clinical outcome in fresh in vitro fertilization /intracytoplasmic sperm injection cycles and advocated that serum progesterone elevation on the day of human chorionic gonadotropin administration may adversely affect the clinical outcome by jeopardizing endometrial receptivity.
In addition, the underlying mechanism through which premature luteinization influences clinical outcomes is elusive. some proposed that premature luteinization cause impairment of the endometrial receptivity, which may indicate a change in the implantation window, is more likely to be affected than the oocyte.whereas some documented that the compromised quality of oocytes might also be a cause.
The cut-off point of premature luteinization is not well established until now. Premature luteinization has been variously defined based on serum P levels, with thresholds of 0.9-1.5 ng/mL being used.
Previous studies have shown that metformin inhibits the first steps of steroidogenesis dose-dependently reducing granulosa cells progesterone output. Moreover, other authors have recently reported that low dose metformin could improve in vitro fertilization outcome in non poly-cystic ovarian syndrome repeaters. So, considering the safety of this drug before pregnancy, metformin can be given to consenting patients from first ultrasound monitoring until ovulation triggering.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Eligible women who gave their informed consent were randomized into two groups: (I) metformin group and (II) placebo group. Randomization was conducted using a computer generated table of random numbers with allocation concealment. Randomization was not changed after it had been done.
| Arm | Type | Receives |
|---|---|---|
| Metformin group | Active comparator | Drug: Metformin |
| Placebo group | Placebo comparator | Other: Placebo |
Who may qualify
- Ages
- 18 to 38 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- First or second trial ICSI cycle.
- Age: 20 -38 years
- BMI: patients with BMI ≥ 30 kg/m2 were advised to lose weight for 6 months through lifestyle modifications.
- AMH ≥1 ng/ml
- Basal FSH < 10 IU/ml.
Key exclusion criteria (6 listed)
- Patients with recurrent two or more failed intra-cytoplasmic sperm injection cycles.
- Uterine anomalies or Synechiae.
- Severe male factor infertility
- Patients known to have diabetes, renal, liver disease, alcoholism, or drug abuse were excluded
- Patients who were on metformin treatment were asked to have a one month washout period before study participation.
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 |
|---|---|---|
| Metforminwill receive metformin (1500 mg/day) starting with the commencement of oral contraceptive pills in the preceding cycle until the day of human chorionic gonadotropin triggering. | Drug | Metformin group |
| Placebowill receive corn-flour placebo tablets (three tablets daily). | Other | Placebo group |
Primary outcome
Incidence of premature luteinization in both groups
Time frame: 12 days
Serum progesterone measurement ≥ 1.5 ng/ml by Mini-vidas assay was used to diagnose cases of premature luteinization.
5 secondary outcomes
ongoing pregnancy rate
Time frame: 12 weeks
Good quality embryo rate
Time frame: 20 days
Progesterone-to-mature oocyte index (PMOI)
Time frame: 17 days
Progesterone/estradiol ratio
Time frame: 12 days
Implantation rate
Time frame: 7 weeks
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 17 Sep 2019.
- Derived from this study: PubMed 33687163Hussein RS, Elnashar I, Amin AF, Zhao Y, Abdelmagied AM, Abbas AM, Abdelaleem AA, Farghaly TA, Abdalmageed OS, Youssef AA, Badran E, Abou-Taleb HA. Effect of Metformin on Premature Luteinization and Pregnancy Outcomes in Intracytoplasmic Sperm Injection-Fresh Embryo Transfer Cycles: A Randomized Double-Blind Controlled Trial. Int J Fertil Steril. 2021 Apr;15(2):108-114. doi: 10.22074/IJFS.2020.134643. Epub 2021 Mar 11.
- Individual participant dataSharing planned: Yes
Related trials for Intracytoplasmatic Sperm Injection
Not yet recruiting
Use of the SiDTM v2.0 Algorithm to Assist Embiyologists in Sperm Selection During ICSI Procedures
Male Fertility, Testicular
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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Metformin in people with Intracytoplasmatic Sperm Injection, 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 7 inclusion and 6 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 17 Sep 2019. 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. Some participants in this study may receive a placebo. 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 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?
Incidence of premature luteinization in both groups (time frame: 12 days). 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 NCT03088631, 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 17 Sep 2019.