Local Uterine Application of Low Molecular Weight Heparin (LMWH) in Intra-cytoplasmic Sperm Injection (ICSI) a Randomised Controlled Pilot Study
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- The Egyptian IVF-ET Center
- Enrollment
- 120
- Locations
- 1
- Primary Endpoint
- pregnancy rate
Study Overview
Brief Summary
Heparin also has the ability to bind with and modulate a wide variety of proteins, which can influence a number of physiological processes involved in implantation & trophoblastic development. These processes include adhesion of the blastocyst to the endometrial surface & trophoblastic differentiation & invasion.
A recent Cochrane review hinted towards research to study the possible effects of the local (uterine), & NOT SYSTEMIC application of heparin during Assisted reproductive technology (ART). Based on the above evidence the investigators hypothesize that low molecular weight heparin given intrauterine at mock embryo transfer after oocyte pick up will help improve pregnancy rates in patients undergoing ART.
Detailed Description
Following ethical approval of the committee of Egyptian IVF-ET center, a pilot prospective randomized controlled study will include 40 patients, in which the study arm (group A ) will be injected with LMWH intrauterine during mock embryo transfer, just after ovum pickup, while the control arm (group B) will be injected intrauterine with similar volume tissue culture media (G.2 plus ref. 10132, Vitrolife) also after ovum pickup. Admission into either group will be through randomization after inclusion & exclusion criteria have been met and before start of controlled ovarian stimulation protocol.
The standard long gonadotrophin-releasing hormone (GnRH) agonist protocol will be used for patients with predicted normal response based on clinical & hormonal profile ; 1 mg of leuprolide acetate daily s.c injection (Lucrin ®; Abbott, Hoofddorp, The Netherlands) is applied from the mid luteal phase onward till the day of human chorionic gonadotropin (HCG) injection.
Gonadotropins in the form of human menopausal gonadotropin (HMG) (Merional ®, IBSA, Institut Biochimique SA, Lugano, Switzerland) will be given by intramuscular injection (IM) from the 2nd day of menstruation, The starting dose range from 150 to 450 IU depending on the basal follicle stimulating hormone (FSH) level, Antral follicle count (AFC) , Patient's age and body mass index (BMI).
In all protocols, stimulation is monitored by trans vaginal ultrasonography and serial estradiol (E2) measurements starting from day 7 of the cycle and the gonadotropin dose is adjusted individually according to follicular response.
After the development of at least three leading follicles≥18 mm, 10,000 unit of HCG (Choriomon, IBSA, Institut Biochimique SA) is given IM, and a trans-vaginal ultrasound-guided oocyte retrieval is performed 36 hours later.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Investigator)
Eligibility Criteria
- Ages
- 20 Years to 37 Years (Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Normal serum prolactin level & thyroid stimulating hormone (TSH)
- •Unexplained infertility
- •Tubal factor infertility
- •BMI <30 kg/m2
Exclusion Criteria
- •Reduced ovarian reserve by AFC, Anti-mullerian hormone (AMH)
- •Presence of non disconnected hydrosalpinges
- •Frozen embryo transfer cycles
- •Uterine Anomalies
- •Submucous fibroids and polyps
- •Uterine synechia
- •Contraindication of pregnancy e.g.: Somatic and mental diseases, which are contraindications for carrying of a pregnancy and childbirth, inborn malformations or acquired deformations of uterus cavity which make embryo implantation or carrying of a pregnancy impossible ,ovarian tumors
Arms & Interventions
Group A
After scheduled oocyte pick up, a mock embryo transfer will be done using labotec catheter (Labotec, Gottingen Germany), and an injection of Enaoxaprin sodium (LMWH) (Clexane® Sanofi S.A Paris, France) will be given intrauterine in group A patients, 500 IU of LMWH which is 5mg, in 0.05 ml.
Intervention: Enaoxaprin sodium (Drug)
Group B
The control arm (group B) will be injected intrauterine with similar volume of tissue culture media (G.2 plus ref. 10132, Vitrolife)
Intervention: tissue culture media (Drug)
Outcomes
Primary Outcomes
pregnancy rate
Time Frame: 14 days
safety
Secondary Outcomes
- Early miscarriage rate(12 weeks)
- Implanation rate(3 weeks after ET)
Investigators
Mona Aboulghar
Professor Obstetrics and Gynecology Fetal Medicine unit Cairo University, IVF Consultant Egyptian IVF center -Maadi Cairo
The Egyptian IVF-ET Center