MedPath

Metformin in Intracytoplasmic Sperm Injection Cycles

Phase 2
Completed
Conditions
Intracytoplasmatic Sperm Injection
Interventions
Other: Placebo
Registration Number
NCT03088631
Lead Sponsor
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
320
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Placebo groupPlacebo-
Metformin groupMetformin-
Primary Outcome Measures
NameTimeMethod
Incidence of premature luteinization in both groups12 days

Serum progesterone measurement ≥ 1.5 ng/ml by Mini-vidas assay was used to diagnose cases of premature luteinization.

Secondary Outcome Measures
NameTimeMethod
ongoing pregnancy rate12 weeks

The number of cases with pregnancy more than 12 weeks of gestation divided by the cycles initiated per 100.

Progesterone/estradiol ratio12 days

calculated as \[progesterone (ng/mL) × 1000\]/esatradiol (pg/mL)

Good quality embryo rate20 days

The number of good day 3 embryos per all two-pronuclear embryos.

Progesterone-to-mature oocyte index (PMOI)17 days

calculated by dividing the serum P level (ng/ml) by the number of mature oocytes.

Implantation rate7 weeks

The number of gestational sacs observed by trans-vaginal ultrasound divided by the number of embryos transferred.

Trial Locations

Locations (1)

Women Health Hospital - Assiut university

🇪🇬

Assiut, Egypt

Women Health Hospital - Assiut university
🇪🇬Assiut, Egypt
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