Effect of Intrauterine Injection of Hcg Before ET on Clinical Outcomes in IVF/ICSI Cycles
Condition: Infertility; ART
MeSH terms: Infertility
Study type: Interventional

Summary: 
      Subfertility is the inability to conceive after 12 months of regular unprotected sexual
      intercourse. Around 15% of couples suffer from subfertility. As a treatment for subfertility,
      Assisted Reproductive Techniques (ART) have been a choice for subfertile couples. In Egypt in
      2010, Pregnancy Rate was calculated to be 36.2%, Live Birth Rate to be 25.7%.

      Implantation is the process by which the embryo adheres to the wall of the uterus.
      Endometrial receptivity plays the most important role for successful implantation after
      embryo quality. It is estimated that up to 70% of early pregnancy losses are due to failure
      of implantation.

      Despite extensive research, the embryo-maternal dialogue that orchestrates the implantation
      process is still not fully understood. Much effort has been done in the last decades to
      detect factors affecting Implantation and improve endometrial receptivity.

      Human Chorionic Gonadotropin (hCG) is a placental glycoprotein hormone that required to
      maintain pregnancy. Recent research data demonstrates that hCG is secreted very early by the
      embryo before implantation to facilitate it. hCG has been proved to cause attraction of
      inflammatory cells, promote angiogenesis, regulate chemical mediators at the endometrium.
      These effects proceed the classical role of hCG during pregnancy and could be a directly
      involved in and facilitating the implantation process.

      Studies have been conducted to study the effect of injection of different concentrations of
      hCG inside the uterine cavity before Embryo Transfer (ET) to improve endometrial receptivity
      and outcomes of In-Vitro Fertilization (IVF) or Intra-Cytoplasmic Sperm Injection (ICSI)
      cycles.

      A recent systematic review was conducted on 12 studies performing intrauterine injection of
      different doses of hCG before ET. Results of this study showed that there is increased
      pregnancy outcome after injection of intrauterine 500 IU of hCG. The study recommended a
      definitive large clinical trial with live birth as the primary outcome. There was no evidence
      that miscarriage was influenced by intrauterine hCG administration, irrespective of embryo
      stage at transfer or dose of intrauterine hCG.

      Aim of the study:

      To detect whether intrauterine injection of hCG before ET improves clinical outcomes in
      IVF/ICSI cycles.
    

Detailed description: 
      This study is a Randomized Controlled Trial (RCT) to be done at ART center of Women's Health
      Hospital, Assiut university, Egypt.

      All steps for IVF/ICSI procedure, from the beginning of the induction for controlled ovarian
      stimulation until just before the procedure of ET, will be done for all enrolled patients as
      routinely decided according to the local protocol of the ART center in Women Health Hospital,
      Assiut University. In the day of ET, number and quality of Embryos will be decided according
      to the routine practice guided by the local protocol.

      The intervention preparation will be prepared by adding one vial of hCG containing 5000 IU to
      1mL of tissue culture medium (Continuous Single Culture, IrvineScientific). To obtain 500 IU
      of hCG, 0.1 milliLiter (mL) of the preparation will be injected inside the uterus before ET
      in the study group. For the control group, 0.1 mL of the tissue culture medium without hCG
      will be injected inside the uterus before the ET. For both groups we will use Intra-Uterine
      Insemination (IUI) catheter (Sperm Trans, Sperm Processor) to inject the solution inside the
      uterine cavity 4 minutes before ET.

      We will standardize the procedure of ET for all women apart from the intervention versus
      control step. All women participating in the study will be put in lithotomy position. Cusco's
      speculum will be introduced to visualize the cervix. Guided by transabdominal ultrasound with
      a full bladder, the ET catheter (Cook Sydney IVF Catheter) will be introduced through the
      cervical os into the uterine cavity. After introduction of the catheter into the uterine
      cavity loaded embryos will be injected inside the cavity 0.5 cm from the fundus.

      Biochemical pregnancy test will be done 14 days after ET by measuring hCG in the woman's
      serum. If the test result is positive (according to the standard values that is used in the
      laboratory), a transvaginal ultrasound will be done 3 weeks following the positive
      biochemical test, to document the visualization of gestational sac, fetal pole and cardiac
      pulsation.

      Pregnancy rate (PR) is calculated by the number of women with positive biochemical pregnancy
      test to the number of women enrolled in each group. The clinical pregnancy was defined as a
      viable pregnancy when there is evidence of a gestational sac, embryo and fetal heart rate at
      the time of ultrasound evaluation. Clinical Pregnancy Rate (cPR) is calculated by the
      percentage of detected clinical pregnancies using ultrasound to the IVF/ICSI cycles in each
      group. Implantation rate (IR) is calculated by the number of visualized embryos by
      transvaginal ultrasound to the number of transferred embryos. While Live Birth Rate (LBR) is
      calculated by the number of live births to the number of transferred embryos. Miscarriage
      rate (MR) is calculated by the ratio of miscarriages to the number of confirmed pregnancies.
    

Intervention name(s): Human Chorionic Gonadotropin
Intervention type(s): Drug
Intervention description(s): 500 IU of human Chorionic Gonadotropin
Other intervention name(s): Epifasi
Intervention MeSH terms: Chorionic Gonadotropin
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Randomized Controlled Trial
Masking: Double (Participant, Care Provider)
Primary purpose: Prevention
Keywords: hCG; Intrauterine hCG; IVF; ICSI