Embryo transfer (ET) is one of the most important
steps in assisted reproductive technology
(ART) cycles. The goal of ET is to deliver good
quality embryos in early stages of development
(zygote to blastocyst) to a uterus with suitable
endometrium. It has been demonstrated that even
with the transfer of high quality embryos, the success
rate of the ART program is low and only 15-
20% of the transferred embryos will implant (
There are multiple factors affecting the success
of embryo transfer such as: embryo quality,
uterine contractions, use of tenaculum, easy or difficult transfer, volume of transfer media, transfer technique, and depth of uterine transfer, while some of these factors are more important than others. One of the factors impacting the ART cycles’ outcome is the embryo transfer technique (
In a study by Woolcutt et al. regarding "blind transfer", they have reported high rate of touching fundus or tubal ostia (
There has been some controversy over the advantage of performing ultrasonography during ET. The positive impact of this procedure on the pregnancy rate has been reported in several studies (
This was a prospective randomized clinical trial performed during January 2010 to June 2011. One hundred and forty women undergoing intracytoplasmic sperm injection (ICSI) during this period in Infertility and Reproductive Health Research Center (IRHRC), Shahid Beheshti University of Medical Sciences, Tehran, Iran, were enrolled in the study. Donor cycles and frozen ET were excluded. The study was approved by the Research Committee of the Infertility and Reproductive Research Centre of Shahid Beheshti University. A signed written consent was obtained from all participants.
The type of stimulatory cycle [agonist (Superfact; Hoechst, Frankfurt, Germany) or antagonist (Cetrotide, EMDSerono, Inc., Germany)] was selected based on the age of woman and other factors. Ovarian stimulation was done using recombinant follicle-stimulating hormone (r-FSH; Gonal-F; Serono Laboratories Ltd., Geneva, Switzerland) or purified FSH (Merional or Fostimon; IBSA, Switzerland), in single or combination formula.
When the leading follicles reached 17-18mm in diameter, human chorionic gonadotropin (hCG) 10,000 units (IBSA, Switzerland) was administered. The uterine length was measured, on the day of hCG administration, by recording the distance from the external os to the end of uterine cavity using vaginal sonography. Oocyte retrieval was performed 34-36 hours later, while the day of ET was determined by convenience. The patients were randomly divided into two groups. In group I, ET was performed using conventional (blind) method based on the sense and experience of the physician. In group II, the ET was performed based on previously measured uterine length using vaginal ultrasound and the embryo deposition was done at the depth of 1-1.5 cm from the top of uterine cavity. Furthermore, all ETs on even days were enrolled in group I, whereas all ETs on odd days were enrolled in group II.
All women were placed in the lithotomy position (with an empty bladder) and a sterile metal speculum was placed to expose the cervix. The cervical mucus was cleared using ringer solution, then the external os washed with media (Ham’s F-10 liquid, Sigma, Germany). In all cases, a Cook catheter (COOK Medical, USA) was used. First the outer catheter and then the inner catheter that was loaded with the embryos was placed. In group I, embryos were blindly deposited at the middle portion of the uterine cavity, approximately at 5-6 cm distance from the external os and based on physician experience.
In group II, embryos were deposited at 1-1.5 cm from the uterine fundus based on the previously measured uterine length without touching fundus and without ultrasound use during the procedure.
After slow withdrawal of the catheter and speculum, all women rested for an hour.
The difficulty of the ET was determined by the physician. When the catheter easily passing through the cervical canal was denoted easy, whereas any resistance to the insertion of the catheter, requiring a tenaculum, or future time-consuming manipulations were denoted difficult ET.
For supporting the luteal phase, all patients received Cyclogest vaginal suppository (400 mg BID) (Actover, Alpharma, England). Fourteen days after ovum retrieval, beta-hCG (β-hCG) level was measured. Ultrasound was performed three weeks later to determine clinical pregnancy and at 10-12 weeks of gestation, to determine ongoing pregnancy.
Appropriate statistical analysis was performed using Student’s t test and Chi-square or Fisher’s exact test. The software that we used was PASW statistics version18. The power analysis of study was 80% and a p value <0.05 was considered statistically significant.
A total of 140 fresh and non-donor embryo transfers were performed. The conventional blind method was performed on eighty cases of group I and the previously measured uterine length method using vaginal ultrasound was performed on 60 cases of group II. The baseline and clinical characteristics of patients including age, duration and type of infertility, and etiology of infertility were compared between two groups (
According to our results, although the chemical pregnancy rate was higher in group II (42.1 vs. 28.7%), the difference was not statistically significant (p=0.105). The clinical pregnancy, ongoing pregnancy and implantation rates were higher in group II (33.9 vs. 17.7% and 22.1 vs. 12.8%, respectively), indicating that the difference is statistically significant.
Abortion rate was higher in group I (34.7 vs. 0%). Except for the demise of one embryo in a twin pregnancy, no other abortion in the first trimester was recorded in group II. No ectopic pregnancy was detected in both groups (
The comparison of baseline and clinical characteristics between two groups
|Patient||Group I N=80||Group II N=60||P value|
|31.68 ± 0.69||31.4 ± 82||0.790b (NS)|
|Primary||61 (76.2%)||52 (86.7%)|
|Female factors||24 (30.8%)||16 (26.7%)|
|Tubal factor||25 (31.2%)||17 (28.3%)|
|Male factors||37 (47.4%)||31 (51.7%)|
|Female and male||11 (14.1%)||9(15%)|
Signification at the 5 precent level.
a; Mean ± standard deviation, b; T test, c; Chi-square analysis, d; Fisher exact test and NS; Non-significant.
The comparison of the other studied variables between two groups
|Group I N=80||Group II N=60||P value|
|Hard||8 (10%)||2 (3.3%)|
|74.94 ± 1.33||74.97 ± 1.21||0.989 (NS)|
|8.43 ± 0.20||8.40 ± 0.24||0.923c (NS)|
|8.62 ± 0.57||9.73 ± 0.80||0.252 (NS)|
|5.14 ± 0.40||5.50 ± 0.45||0.555c (NS)|
|2.42 ± 0.08||2.45 ± 0.10||0.848c (NS)|
|8.58 ± 0.24||8.72 ± 0.31||0.73 (NS)|
|63.60 ± 2.18||69.20 ± 1.98||0.060c (NS)|
Signification at the 5 precent level.
NS; Non-significant, ET; Embryo transfer, a; Chi-square analysis, b; Fisher exact test, c; T test, and d; Mean ± standard deviation.
The comparison of pregnancy results between two groups
|Group I N=80||Group II N=60||P value|
|23 (28.7%)||24 (42.1%)||0.105a (NS)|
|17 (21.2%)||19 (33.9%)||0.0135a*|
|14 (17.7%)||19 (33.9%)||0.0131a*|
|8 (34.7%)||0 (0%)||0.005a*|
|12.86 ± 2.71||22.12 ± 4.57||0.086c*|
NS; Non-significant, ET; Embryo transfer, a; Chi-square analysis, b; Mean ± standard deviation, c; T test and *; significant(s).
Despite many advances in the practice of ART cycles, the implantation and clinical pregnancy success rates are low even for patients with many oocytes and good quality embryos (
In many IVF centres in Iran, the conventional (blind) method is used. Although ultrasonic-guided ET have been suggested to improve the outcomes in some studies (
Increased clinical and ongoing pregnancy and implantation rates in this method may be due to determination of exact and suitable depth of uterus for embryos placement that indicates the importance of the fundal site of uterus for better implantation. The length of uterus is a factor affecting the outcome of ART, whereas this measurement is different among women and changes during the drug stimulation and cycle to cycle (
A decrease in abortion rate in our study is another point to support the importance of better site determination in ET success.
One of the different points between two groups in our study was the time of ET, suggesting that in group II, the day 3 ET showed better result as compared to the day 2 ET, but was not significantly different. This difference may affect the results, but some studies have showed that day 2 ET and day 3 ET have had similar reproductive outcomes (
It seems that the detection of uterine length by ultrasound during the treatment cycle and performance of ET at the depth of 1-1.5 cm from fundus may improve the outcome of ART cycles as compared to a blind approach, while leads to a decreases in abortion rate.