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

• ClinicalTrials.gov Identifier: NCT03503227
• Recruitment Status: Completed
• First Posted: April 19, 2018
• Last Update Posted: April 4, 2019
• Sponsor: Kasr El Aini Hospital
• Information provided by (Responsible Party): Amira S Dieb, Kasr El Aini Hospital

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Infertility	Drug: prednisolone; Drug: Acetyl Salicylic acid	Phase 2; Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 250 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Other
• Official Title: The Value of Addition of Prednisolone to Acetylsalicylic Acid Prior to Embryo Transfer in Patients With First ICSI Cycles: A Randomized Controlled Trial
• Actual Study Start Date: April 23, 2018
• Actual Primary Completion Date: October 31, 2018
• Actual Study Completion Date: October 31, 2018

Arms and Interventions

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: prednisolone; daily oral low dose prednisolone (10 mg/day) :a glucocorticoid; Drug: Acetyl Salicylic acid; daily oral low dose Acetylsalicylic acid (75 mg) : Antiplatelet agent

Outcome Measures

Primary Outcome Measures :

1. clinical pregnancy rate per cycle. [ Time Frame: 7 weeks ]
   Detection of gestational sac , embryo pole and fetal pulsations by transvaginal ultrasound

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

Egypt

KasralainiH

Cairo, Egypt, 11956

Sponsors and Collaborators

Kasr El Aini Hospital

Investigators

• Principal Investigator: Amira S Dieb, MD; KasrAlainiH

More Information

• Responsible Party: Amira S Dieb, Ob/Gyn Lecturer, Kasr El Aini Hospital
• ClinicalTrials.gov Identifier: NCT03503227
• Other Study ID Numbers: 1199012
• First Posted: April 19, 2018
• Last Update Posted: April 4, 2019
• Last Verified: April 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

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