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

The Value of Addition of Prednisolone to Acetylsalicylic Acid Prior to Embryo Transfer in Patients With First ICSI Cycles: A Randomized Controlled Trial

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.

Study Overview

• Status: Completed
• Conditions: Infertility
• Intervention / Treatment: Drug: Acetyl Salicylic acid; Drug: prednisolone

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.

• Study Type: Interventional
• Enrollment (Actual): 250
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt, 11956
    • KasralainiH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 39 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Women in reproductive age diagnosed with infertility for IVF/ICSI, female age (18- <40 years, normal serum hormonal profile on day 3 of the cycle [including estradiol (E2), FSH, 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 (positive anticardiolipin antibody or lupus anticoagulant on 2 separate occasions at least 6 weeks apart), thrombophilia (factor V Leiden mutation, activated protein C resistance (APCR) resistance, protein C or S deficiency, prothrombin gene mutation, antithrombin III deficiency), 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 BMI >35
• Decline consent to randomization

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Aspirin; Patients will receive daily oral low dose Acetylsalicylic acid (75 mg) starting day 20 of the previous cycle withGonadotrophin releasing hormone agonist (GnRH agonist)	Drug: Acetyl Salicylic acid; daily oral low dose Acetylsalicylic acid (75 mg) : Antiplatelet agent
Active Comparator: Aspirin and prednisolone; Patients will receive daily oral low dose Acetylsalicylic acid (75 mg) and Low dose prednisolone (10 mg/day) starting day 20 of the previous cycle withGonadotrophin releasing hormone agonist (GnRH agonist).	Drug: Acetyl Salicylic acid; daily oral low dose Acetylsalicylic acid (75 mg) : Antiplatelet agent; Drug: prednisolone; daily oral low dose prednisolone (10 mg/day) :a glucocorticoid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
clinical pregnancy rate per cycle.	Detection of gestational sac , embryo pole and fetal pulsations by transvaginal ultrasound	7 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
number of oocytes retrieved per cycle.	number of oocytes retrieved during ovum pickup per cycle.	3 weeks
fertilization rate per cycle.	The number of oocytes fertilized by intracytoplasmic sperm injection per cycle.	3weeks
number of embryos per cycle.	number of embryos of any grade ( first, second, third or fourth grade) per cycle	3weeks
embryo quality per cycle.	embryo quality by grade ( first, second, third or fourth) per cycle.	3weeks
chemical pregnancy rate per cycle.	Positive beta hCG in serum per cycle.	5 weeks
twins rate per cycle.	Detection of 2 gestational sacs with positive fetal poles and pulsations per cycle.	9 weeks
miscarriage rate per cycle.	Early pregnancy loss per cycle.	16 weeks

Collaborators and Investigators

• Sponsor: Kasr El Aini Hospital
• Investigators: Principal Investigator: Amira S Dieb, MD, KasralainiH

Study record dates

Study Major Dates

• Study Start (Actual): April 23, 2018
• Primary Completion (Actual): October 31, 2018
• Study Completion (Actual): October 31, 2018

Study Registration Dates

• First Submitted: April 2, 2018
• First Submitted That Met QC Criteria: April 18, 2018
• First Posted (Actual): April 19, 2018

Study Record Updates

• Last Update Posted (Actual): April 4, 2019
• Last Update Submitted That Met QC Criteria: April 2, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infertility; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dermatologic Agents; Antifungal Agents; Keratolytic Agents; Aspirin; Prednisolone; Salicylic Acid; Salicylates
• Other Study ID Numbers: 1199012

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No