The Value of Prednisolone With Aspirin Before Embryo Transfer in Intracytoplasmic Sperm Injection (ICSI) Cycles

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.