Metformin in Intracytoplasmic Sperm Injection Cycles

NCT ID: NCT03088631

Last Updated: 2019-09-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 320 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-03-01
• Study Completion Date: 2019-04-01

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.

Conditions

Intracytoplasmatic Sperm Injection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Metformin group

Group Type: ACTIVE_COMPARATOR

Metformin

Intervention Type: DRUG

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 group

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

will receive corn-flour placebo tablets (three tablets daily).

Interventions

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.

Intervention Type: DRUG

Placebo

will receive corn-flour placebo tablets (three tablets daily).

Intervention Type: OTHER

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 38 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Assiut University

OTHER

Sponsor Role: lead

Responsible Party

Reda S. Hussein

Lecturer of obstetrics and gynecology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Women Health Hospital - Assiut university

Asyut, , Egypt

Countries

Egypt

References

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.

Reference Type: DERIVED

PMID: 33687163 (View on PubMed)

Other Identifiers

MICSI

Identifier Type: -

Identifier Source: org_study_id