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Metformin in Intracytoplasmic Sperm Injection Cycles

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

Status
Completed
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT03088631
Enrollment
320
Registered
2017-03-23
Start date
2017-03-01
Completion date
2019-04-01
Last updated
2019-09-17

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Intracytoplasmatic Sperm Injection

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.

Interventions

DRUGMetformin

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.

OTHERPlacebo

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

Sponsors

Assiut University
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)

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.

Eligibility

Sex/Gender
FEMALE
Age
18 Years to 38 Years
Healthy volunteers
No

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

Design outcomes

Primary

MeasureTime frameDescription
Incidence of premature luteinization in both groups12 daysSerum progesterone measurement ≥ 1.5 ng/ml by Mini-vidas assay was used to diagnose cases of premature luteinization.

Secondary

MeasureTime frameDescription
ongoing pregnancy rate12 weeksThe number of cases with pregnancy more than 12 weeks of gestation divided by the cycles initiated per 100.
Good quality embryo rate20 daysThe number of good day 3 embryos per all two-pronuclear embryos.
Progesterone-to-mature oocyte index (PMOI)17 dayscalculated by dividing the serum P level (ng/ml) by the number of mature oocytes.
Progesterone/estradiol ratio12 dayscalculated as \[progesterone (ng/mL) × 1000\]/esatradiol (pg/mL)
Implantation rate7 weeksThe number of gestational sacs observed by trans-vaginal ultrasound divided by the number of embryos transferred.

Countries

Egypt

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 15, 2026