Clinical trial NCT03088631: Metformin in Intracytoplasmic Sperm Injection Cycles
Official title: Role of Metformin in Prevention of Premature Luteinization in Intracytoplasmic Sperm Injection Cycles
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Intracytoplasmatic Sperm Injection
Lead sponsor: Assiut University
Sponsor class: OTHER
First posted: 2017-03-23
Enrollment: 320
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 38
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: PREVENTION

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.


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

Primary outcomes:
measure: Incidence of premature luteinization in both groups
timeFrame: 12 days
Secondary outcomes:
measure: ongoing pregnancy rate
timeFrame: 12 weeks
measure: Good quality embryo rate
timeFrame: 20 days
measure: Progesterone-to-mature oocyte index (PMOI)
timeFrame: 17 days
measure: Progesterone/estradiol ratio
timeFrame: 12 days
measure: Implantation rate
timeFrame: 7 weeks
Other outcomes:
Locations:
city: Assiut
country: Egypt
facility: Women Health Hospital - Assiut university
Study officials:
References:
citation: 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.