Metformin in Intracytoplasmic Sperm Injection Cycles

NCT03088631 | Completed Phase 2

• 1 other identifier: MICSI
• Study Type: interventional
• Target: 320
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• 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.

  12 days

Secondary Outcomes (5)

• ongoing pregnancy rate

  12 weeks

• Good quality embryo rate

  20 days

• Progesterone-to-mature oocyte index (PMOI)

  17 days

• Progesterone/estradiol ratio

  12 days

• Implantation rate

  7 weeks

Study Arms (2)

Metformin group

ACTIVE COMPARATOR

Drug: Metformin

Placebo group

PLACEBO COMPARATOR

Other: Placebo

Interventions

Metformin 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.

Metformin group

Placebo OTHER

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

Placebo group

Eligibility Criteria

• Age: 18 Years - 38 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Assiut University: lead

Study Sites (1)

Women Health Hospital - Assiut university

Asyut, 71111, Egypt

Location

Related Publications (1)

• 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.

  PMID: 33687163 DERIVED

MeSH Terms

Interventions

Metformin

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Lecturer of obstetrics and gynecology

Model Details: 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.

Study Record Dates

• First Submitted: March 18, 2017
• First Posted: March 23, 2017
• Study Start: March 1, 2017
• Primary Completion: March 1, 2019
• Study Completion: April 1, 2019
• Last Updated: September 17, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will share

Locations

EG (1)