The Value of Prednisolone With Aspirin Before Embryo Transfer in Intracytoplasmic Sperm Injection (ICSI) Cycles
Condition: Infertility
MeSH terms: Infertility
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      This study is a prospective, double-blind, randomized controlled trial . It includes 250
      infertile patients scheduled for ICSI cycle. The patients will be randomly allocated into two
      equal groups; daily oral low dose Acetylsalicylic acid and group B patients will receive
      daily oral low dose Acetylsalicylic acid and Low dose prednisolone. All 250 participants
      undergo similar ICSI cycles. Primary outcome is clinical pregnancy rate per cycle. Secondary
      outcomes include number of oocytes retrieved, fertilization rate, number of embryos, embryo
      quality, chemical pregnancy rate, twins rate and miscarriage rate per cycle.
    

Detailed description: 
      This study is a prospective, randomized, controlled trial. Patients undergoing ICSI for their
      first cycle are enrolled in this study. Participants are then randomized into two groups ;
      group A patients will receive daily oral low dose Acetylsalicylic acid (75 mg) and group B
      patients will receive daily oral low dose Acetylsalicylic acid (75 mg) and Low dose
      prednisolone (10 mg/day).

      Randomization will be done by withdrawing closed envelopes for each patient .

      Inclusion criteria:

      Women in reproductive age diagnosed with infertility for ICSI, female age (18- <40 years,
      normal serum hormonal profile on day 3 of the cycle [including estradiol (E2), follicle
      stimulating hormone (FSH), Luteinizing hormone (LH), prolactin, thyroid stimulating hormone,
      normal uterine cavity diagnosed at hysteroscopy.

      Exclusion criteria:

        -  Women with platelet dysfunction, thrombocytopenia, gastrointestinal ulcers, recurrent
           gastritis, Acetylsalicylic acid hypersensitivity, patients on corticosteroids will be
           excluded from the study.

        -  Also women with known cause for recurrent miscarriage: antiphospholipid syndrome,
           abnormal thyroid function tests, parental balanced translocation or uterine anomaly
           (known subseptate uterus or cervical weakness diagnosed at hysteroscopy).

        -  Contraindications to steroid therapy: hypertension, diabetes, mental health problems or
           obesity with Body mass index (BMI) >35

        -  Decline consent to randomization

      Methodology in details:

      All patients will be subjected to the following:

        -  -Informed consent after explaining the aim of the study, procedure and possible hazards.

        -  -History taking includes full obstetric history, medical and surgical history and
           demographic distribution.

        -  Full physical examination. -

        -  -Ultrasound examination (2D): Transvaginal sonography (TVS) is done on day 2 to 5 to
           assess antral follicle count (AFC), uterus and adnexa .

        -  -Each group will start intake of Acetyl-Salicylic Acid (ASA) or ASA with Prednisolone on
           day 19th - 20th of the previous cycle and continue until confirmation of pregnancy by
           detection of fetal heart activity on ultrasound.

        -  -Long protocol steps:

             -  Start from day 19th - 20th by GnRH agonist ;Triptorelin 0.1mg subcutaneous
                (Decapeptyl, Ferring). -1st visit : after 2 weeks of start of GnRH agonist or day 2
                of cycle, we confirm down regulation by a serum level of E2to be <50 pg/ml,
                endometrial thickness <5mm, no ovarian cyst by ultrasound. Then we add
                Gonadotropins as Intramuscular (I.M.) injections of 150-300 I.U. of highly purified
                Human Menopausal Gonadotropins daily (Merional, 75 I.U. /vial, IBSA). The dose is
                adjusted according to the age, BMI, AFC, serum levels of anti-mullerian hormone
                (AMH), follicle stimulating hormone (FSH) and ovarian response.

             -  2nd visit : on 6th - 7 th days of Gonadotrophins and then every other day to do
                folliculometry by TVS and E2 level in serum.

             -  We do trigger by Human Chorionic Gonadotrophin (HCG)10000 IU I.M.(Pregnyl, Organon)
                when at least 3 follicles reach 18mm in mean diameter or more and E2 level is less
                than 2500 pg/ml. Ovum pickup is done 34 hours after HCG injection and embryo
                transfer using Wallace catheter on day 2 to 3.

        -  -Luteal support: Natural Progesterone 400 mg 1x2, Folic acid once daily,
           Amoxicillin-Clavulanic Acid 1gm 1x2x7 ,Progesterone 100mg I.M. daily for 10 days,
           Acetylsalicylic Acid once daily

        -  -Quantitative ß- HCG in serum after 14 days of embryo transfer. -TVS to detect clinical
           pregnancy at 6-7 weeks of gestation.

      Primary outcome:

      The primary outcome is clinical pregnancy rate per cycle.

      Secondary outcome:

      Secondary outcome measures are number of oocytes retrieved, fertilization rate, number of
      embryos, embryo quality, chemical pregnancy rate, twins rate and miscarriage rate per cycle.
    

Intervention name(s): prednisolone; Acetyl Salicylic acid
Intervention type(s): Drug; Drug
Intervention description(s): daily oral low dose prednisolone (10 mg/day) :a glucocorticoid; daily oral low dose Acetylsalicylic acid (75 mg) : Antiplatelet agent
Intervention MeSH terms: Aspirin; Salicylic Acid; Prednisolone; Salicylates
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Other