Metformin in Intracytoplasmic Sperm Injection Cycles

Intracytoplasmatic Sperm Injection Clinical Trial

Official title:

Role of Metformin in Prevention of Premature Luteinization in Intracytoplasmic Sperm Injection Cycles

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03088631
• Other study ID #: MICSI
• Status: Completed
• Phase: Phase 2
• Start date: March 1, 2017
• Est. completion date: April 1, 2019

Study information

• Verified date: April 2019
• Source: Assiut University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 320
• Est. completion date: April 1, 2019
• Est. primary completion date: March 1, 2019
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 38 Years

Eligibility

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

Related Conditions & MeSH terms

• Intracytoplasmatic Sperm Injection

Intervention

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.

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

Locations

Country	Name	City	State
Egypt	Women Health Hospital - Assiut university	Assiut

Sponsors (1)

Lead Sponsor	Collaborator
Assiut University

Country where clinical trial is conducted

Egypt, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	ongoing pregnancy rate	The number of cases with pregnancy more than 12 weeks of gestation divided by the cycles initiated per 100.	12 weeks
Secondary	Good quality embryo rate	The number of good day 3 embryos per all two-pronuclear embryos.	20 days
Secondary	Progesterone-to-mature oocyte index (PMOI)	calculated by dividing the serum P level (ng/ml) by the number of mature oocytes.	17 days
Secondary	Progesterone/estradiol ratio	calculated as [progesterone (ng/mL) × 1000]/esatradiol (pg/mL)	12 days
Secondary	Implantation rate	The number of gestational sacs observed by trans-vaginal ultrasound divided by the number of embryos transferred.	7 weeks