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Metformin in Intracytoplasmic Sperm Injection Cycles

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ClinicalTrials.gov Identifier: NCT03088631
Recruitment Status : Completed
First Posted : March 23, 2017
Last Update Posted : September 17, 2019
Sponsor:
Information provided by (Responsible Party):
Reda S. Hussein, Assiut University

Brief 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. 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.


Condition or disease Intervention/treatment Phase
Intracytoplasmatic Sperm Injection Drug: Metformin Other: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 320 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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 (Participant, Investigator)
Primary Purpose: Prevention
Official Title: Role of Metformin in Prevention of Premature Luteinization in Intracytoplasmic Sperm Injection Cycles
Actual Study Start Date : March 1, 2017
Actual Primary Completion Date : March 1, 2019
Actual Study Completion Date : April 1, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Metformin group Drug: Metformin
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.

Placebo Comparator: Placebo group Other: Placebo
will receive corn-flour placebo tablets (three tablets daily).




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. ongoing pregnancy rate [ Time Frame: 12 weeks ]
    The number of cases with pregnancy more than 12 weeks of gestation divided by the cycles initiated per 100.

  2. Good quality embryo rate [ Time Frame: 20 days ]
    The number of good day 3 embryos per all two-pronuclear embryos.

  3. Progesterone-to-mature oocyte index (PMOI) [ Time Frame: 17 days ]
    calculated by dividing the serum P level (ng/ml) by the number of mature oocytes.

  4. Progesterone/estradiol ratio [ Time Frame: 12 days ]
    calculated as [progesterone (ng/mL) × 1000]/esatradiol (pg/mL)

  5. Implantation rate [ Time Frame: 7 weeks ]
    The number of gestational sacs observed by trans-vaginal ultrasound divided by the number of embryos transferred.



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Ages Eligible for Study:   18 Years to 38 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03088631


Locations
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Egypt
Women Health Hospital - Assiut university
Assiut, Egypt, 71111
Sponsors and Collaborators
Assiut University

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Responsible Party: Reda S. Hussein, Lecturer of obstetrics and gynecology, Assiut University
ClinicalTrials.gov Identifier: NCT03088631     History of Changes
Other Study ID Numbers: MICSI
First Posted: March 23, 2017    Key Record Dates
Last Update Posted: September 17, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Metformin
Hypoglycemic Agents
Physiological Effects of Drugs