Effect of Intrauterine Navigation Using Intrauterine Insemination Catheter for Mock Embryo Transfer Prior to Day 3 Embryo Transfer on Pregnancy Rate: A Pilot Study
Effect of Intrauterine Navigation Using Intrauterine Insemination Catheter for Mock Embryo Transfer Prior to Day 3 Embryo Transfer on Pregnancy Rate: A Pilot Study
Objective: To evaluate the effect of intrauterine navigation using intrauterine insemination
 catheter (IUI) one day prior to day 3 embryo transfer (ET) on pregnancy rate.

 Design: Pilot randomized controlled study. Setting: Tertiary referral center, King Fahad
 Medical City. Patients: Patients who underwent ET during the period of the study after two or
 less in-vitro fertilization failures and fulfilled the inclusion criteria.

 Interventions: Mock ETs were performed on day 2 post oocytes retrieval using intrauterine
 insemination catheter, followed by day 3 ET.

 Main Outcome Measure: Pregnancy rate.

 Key Words: embryo transfer, mock embryo transfer, endometrial receptivity, endometrial
 scratching, IVF.
Materials and Methods Population Forty-five patients were selected for this prospective
 randomized control trial. It was conducted between October 2016 and October 2017 in the
 Reproductive Endocrinology and Infertility Medicine Department of King Fahad Medical City
 (KFMC).

 We included nulliparous patients who were < 42 years of age with body mass index (BMI) < 30
 kg/m2 and normal endometrial cavity, used fresh sperm or oocytes, had two or more embryos
 available for transfer on day 3 post ovum pick-up (OPU), and no more than 3 previous
 unsuccessful ART cycles. Patients with uterine fibroids, uterine anomalies, intra-uterine
 adhesions, and uterine polyps, patients with chronic diseases in the as uncontrolled diabetes
 or hypertension, or if the patient had difficult mock ET . patients with severe male factors
 for infertility requiring surgical retrieval of sperms were excluded from the study.

 Ethical clearance of this study was obtained from the ethical committee of KFMC (IRB
 00008644). Written informed consent was obtained from all the participants.

 Stimulation Protocols Participants were assigned either to the antagonist or agonist
 protocol. In the agonist stimulation protocol, pituitary desensitization was achieved by
 using 3.75 mg leuprolide acetate (Lupron Depot, Abbott Laboratories, Chicago, USA)
 intramuscularly in the luteal phase of the previous cycle. The participants received 75-450
 IU/d of either recombinant follicle-stimulating hormone (FSH) (Gonal-F; Serono, Munich,
 Germany) or highly purified human menopausal gonadotrophin (hMG) (Merional; IBSA, Lugno,
 Switzerland). The dosage was adjusted according to the serum E2 levels and vaginal ultrasound
 folliculometry. In the antagonist protocol group, 0.25 mg/d cetrorelix acetate (Cetrotide;
 Serono, Munich, Germany) was added on the day 5 of stimulation. When the sizes of three or
 more follicles became ≥16 mm, the patient was given 10,000 IU of chorionic gonadotrophin
 (Pregnyl; MERK, Hally, Germany) intramuscularly.

 Oocyte Retrieval and Fertilization Transvaginal oocyte retrieval was scheduled 36 h after the
 administration of hCG and was performed under local anesthesia. Fertilization was achieved by
 intracytoplasmic sperm injection (ICSI). Pronuclear observation to determine fertilization
 was performed 16-18 h after insemination. A commercial sequential IVF medium (Cook, Eight
 Miles Plains, Queensland, Australia) was used for procedures involving the handling of
 gametes and embryos. All embryos were transferred on their respective day 3 post OPU.

 Mock Embryo Transfer On day 2 post OPU, one day before the actual ET, the participants, in
 the study group, were taken into the operating room with a moderately full bladder at 10 am.
 The patient was placed in the lithotomy position and a sterile speculum was inserted into the
 vagina. The cervix was cleaned with sterile swabs and sterile water, and a mock transfer was
 performed using a soft catheter (Wallace Intrauterine Insemination Catheter; Sims Portex
 Ltd., Hythe, Kent, UK). The catheter has an outer sheet with memory , to aid insertion, and a
 soft inner catheter with atraumatic tip. Under ultrasound guidance, only the soft inner
 catheter was introduced beyond the internal cervical os till it was 0.5 cm from the fundus.
 It was, then, gently withdrawn out of the uterus, and the speculum was removed.

 Embryo Transfer On the morning of ET, the patient was taken to the operating room with a
 moderately full bladder. To facilitate safe handling of the embryos, the operating room was
 connected to the embryology laboratory through a sliding door. The patient was placed in the
 lithotomy position and the embryos were loaded by the embryologist into the soft catheter. A
 maximum of two embryos were transferred per cycle. The physician then inserted the catheter
 into the uterus till it was approximately 1.5 cm from the fundus, and expelled the embryos.
 The catheter was then slowly removed from the uterus and returned to the embryologist for
 inspection for any remnant embryos (retained embryos for reloading), blood, or mucus.

 Intravaginal progesterone (Cyclogest; 400 mg, Actavis, Devon, UK) was administered every 12 h
 for luteal support.

 Quantitative assessment of serum ß-HCG level was performed two weeks after ET. Patients who
 showed high levels of serum ß-HCG were considered as pregnant and were asked to return at 6
 weeks of gestation for ultrasonographic confirmation. When they returned, clinical pregnancy
 was determined by the observation of a gestational sac with fetal heart beat on transvaginal
 ultrasound. The clinical embryo implantation rate was defined as the number of gestational
 sacs observed at 6 weeks of gestation divided by the total number of embryos transferred.

 Statistical Methods Statistical analyses were performed using SPSS (version 12.0; SPSS, Inc.,
 Chicago, IL, USA). Results were tabulated and presented in percentages. Statistical analyses
 were carried out using the chi-squared test or the Fisher Exact test for categorical
 variables, and the unpaired two-way Student's t-test for continuous variables. A value of P ≤
 0.05 was accepted as statistically significant.
Inclusion Criteria:

 We included nulliparous patients who were < 42 years of age with body mass index (BMI) < 30
 kg/m2 and normal endometrial cavity, used fresh sperm or oocytes, had two or more embryos
 available for transfer on day 3 post ovum pick-up (OPU), and no more than 3 previous
 unsuccessful ART cycles

 Exclusion Criteria:

 Patients with uterine fibroids, uterine anomalies, intra-uterine adhesions, and uterine
 polyps, patients with chronic diseases in the as uncontrolled diabetes or hypertension, or
 if the patient had difficult mock ET . patients with severe male factors for infertility
 requiring surgical retrieval of sperms were excluded from the study.

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