Middle East Fertility Society Journal Middle East Fertility Society ISSN: 1110-5690 Vol. 11, Num. 2, 2006, pp. 127-134

Middle East Fertility Society Journal Vol. 11, No. 2, 2006, pp. 127-134

Evaluation of the effect of the adoption of ultrasound guidance for embryo replacement on the pregnancy outcome for multiple providers

Mohamed A. Bedaiwy, M.D.

Departments of Obstetrics and Gynecology, Assiut University Hospital, Assiut, Egypt; The Cleveland Clinic Foundation, Cleveland, Ohio; University of Toronto and Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.

Correspondence: Mohamed Bedaiwy, MD, Division of Reproductive Sciences, Department of Obstetrics and Gynecology, University of Toronto, 600 University Avenue, Except for the need for one more person during Room 876,Toronto, Ontario M5G 1X5, Canada .(FAX: 416-ET, ultrasound guided transcervical embryo 972-0036). Email address: bedaiwymmm@yahoo.com

Received on 31 May, 2006;
revised an accepted on July 5, 2006

Code number: mf06024

ABSTRACT

Objective: To evaluate the clinical effects of adopting the policy of transabdominal ultrasound–assisted embryo transfer on outcomes of in vitro fertilization–embryo transfer (IVF-ET) in comparison to the “clinical touch” method of transcervical embryo transfer by 3 different providers.
Design: A cohort study in a university-based IVF practice.
Materials and methods(s): Four hundred sixty-two sequential patients who underwent transcervical transfer of fresh embryos 1-year before (group I) and 1-year after (group II) the adoption of US guidance were included. The clinical touch and the US guided embryo transfers were performed by 3 experienced physicians. On selected days, at time of embryo transfer, transabdominal ultrasound was performed to guide catheter placement depth approximately 1.5 cm from the uterine fundus. The presence of at least one gestational sac on ultrasound was compared in the two study groups. Additionally, the clinical pregnancy rate (presence of fetal cardiac activity observed on ultrasound), and the implantation rate (number of gestational sacs identified on ultrasound per number of embryos transferred) between groups was evaluated. Characteristics of the two cohorts were analyzed to verify similarities between the treatment and control groups, including age of recipient, and difficulty of transfer, the use of a tenaculum, and the quality and number of embryos transferred.
Result(s): US guidance did not reduce the time of the ET procedure. In addition, it did not reduce the percentage of bloody catheters at the end of the procedure. More importantly, no statistical difference was seen in the presence or number of gestational sacs following embryo transfer either before or after the adoption of the transabdominal ultrasound guidance for all 3 providers.
Conclusion(s): Providers’ performance has not improved by the adoption of US guidance. There is no other additional advantage for using transabdominal ultrasound to perform embryo transfer. Although there is a trend towards a higher pregnancy if US guidance is adopted, in experienced hands, the “clinical touch” method of embryo transfer yields equivalent results to transabdominal ultrasound–guided embryo placement.

Key Words: IVF-ET, Embryo transfer; transabdominal ultrasonography

Pregnancy rates in IVF-ET programs have increased with improvements in technology. In spite of improvements in ovarian stimulation and.embryo culture, implantation and pregnancy rates remain suboptimal. One variable that received little attention is the role of ultrasound guidance and ET providers. Ultrasound guidance has been adopted by many centers to verify accurate embryo placement and to improve pregnancy outcomes. Except for the need for one more person during ET, ultrasound guided transcervical embryo transfer has no disadvantages.

Table 1. Demographic features and indications for assisted reproduction technologies before and after the adoption of ultrasound guided embryo transfer for all providers

† N = Number of cycles for age, parity, infertility, and infertility factors.

The literature is replete with reports showing similar pregnancy between the “clinical touch” technique and ultrasound transfer (1-5). On the other side, many investigators demonstrated a beneficial effect of ultrasound-guidance (6-9). However, the impact of ultrasound guidance on the pregnancy rate per provider (before and after the adoption of ultrasound guidance) received little attention. The objectives of this study were 1) to evaluate the impact of adopting ultrasound guidance on the overall pregnancy rate in a tertiary care facility and 2) to evaluate whether US guided ET improves the pregnancy rate for the same provider.

MATERIALS AND METHODS

A total of 462 IVF cycles in 462 patients were included between 2000 and 2001. One hundred and ninety-four patients underwent ET without US guidance (group I) and 268 patients underwent ET with US guidance (group II). Three providers performed all transfers before and after the adoption of US guidance.

Controlled Ovarian Stimulation

All patients underwent pituitary down regulation with the GnRH agonist leuprolide acetate (Lupron; Tap Pharmaceutical Inc., Deerfield, IL) administered as a daily subcutaneous (s.c.) dose of 10 U (0.5 mg) initiated on cycle day 21. The dose was subsequently reduced to 5 U (0.25 mg) once serum estradiol levels were suppressed to ≤50 pg/mL and continued until the day of hCG administration. Controlled ovarian hyperstimulation with a daily s.c. dose of 300 IU recombinant FSH (Gonal F, Serono, Randolph, MA) or Follistim (Organon, West Orange, NJ) was begun following pituitary down regulation.

The ovarian response was monitored by serial serumestradiollevels and transvaginal ultrasonograms beginning on day 5 of stimulation. The FSH dose andsubsequentmonitoringwasindividualized based

Table 2. Parameters of controlled ovarian hyperstimulation pregnancy rates before and after the adoption of ultrasound guided embryo transfer for all providers

† N = Number of cycles.

on these results. Stimulation was continued until at least two follicles reached a mean diameter of ≥18 mm, at which time hCG 10,000 IU s.c. was administered 36 hours before oocyte recovery.

Oocyte Retrieval

Oocytes were collected by transvaginal ultrasound guided needle aspiration of the follicles. The procedure was performed under deep conscious sedation. The retrieved oocytes were rinsed, graded and placed in HEPES buffered human tubal fluid (HTF) (Irvine Scientific, Santa Ana, CA) at 37^oC under 5% CO2, 5% O2 and 90% N2.

Sperm Collection and Preparation

Semen samples were obtained by masturbation concurrently with the oocyte retrieval following a 3 – 5 day period of abstinence. Spermatozoa were prepared by a density gradient centrifugation technique. Samples were loaded onto a single 90% ISolate (Irvine Scientific, Santa Ana, CA) layer and centrifuged at 1600 rpm for 20 minutes at room temperature. The resulting pellet was washed by centrifugation for additional 7 minutes and resuspended in HTF media supplemented with 5% synthetic serum substitute (SSS; Irvine Scientific, Santa Ana, CA) at room temperature until the time of IVF or ICSI. In conventional IVF, 150 to 200 x 103 sperm were added to each culture dish containing 4-5 oocytes. A single morphologically normal appearing spermatozoon was selected for ICSI.

Gamete and Embryo Culture

After cumulus dissection and wash, the oocytes were placed in 1mL of HTF supplemented with 5% SSS. Fertilization was confirmed 14-16 hours postinsemination by the presence of 2 pronuclei and extrusion of the second polar body. Normally fertilized oocytes were cultured in groups of 4-5 in 1 mL of HTF with SSS until early afternoon of day 3. They were then placed in 1 mL of blastocyst media (Irvine Scientific, Santa Ana, CA) following a 5 drop rinse in the same medium. A second change over to fresh blastocyst medium was done on the morning of day 5 after embryo evaluation and before embryo transfer. Embryo transfers were scheduled between noon and 14:00 h 3 or 5 days after oocyte retrieval.

Table 3. Patient characteristics and clinical results for periods before and after adoption of US guided ET for provider#1

Embryo Evaluation

Embryos were evaluated on days 3 and 5 with an Olympus X70 inverted microscope (x600, Olympus America, Melville, NY), equipped with Hoffman Modulation Optics (Narishige, Tokyo, Japan). Cell number, degree and pattern of fragmentation were recorded on day 3. The degree of fragmentation was defined as the embryonic volume occupied by enucleated cytoplasmic fragment and expressed as a percentage.

Development on day 5 was recorded as follows. A distinct inner cell mass (ICM), organized as a compacted mass of cells was considered normal. A cohesive layer of numerous tightly packed cells in the trophectoderm (TE) was also considered normal. Highly irregular ICM and/or TE cells were considered abnormal and arrested on days 5 and 6.

Embryo Transfer

Patients undergoing transabdominal ultrasound–guided embryo transfer were instructed to keep a full bladder prior to transfer to assist visualization during the procedure. The patient was placed in the dorsolithotomy position and a sterile speculum was inserted into the vagina. When the speculum was adequately positioned to visualize the cervix, the cervix was washed with a sponge soaked with transfer media. Embryos were prepared in the laboratory by the embryologist prior to the transfer. When ultrasound was used, the position of the uterus and cervix was ascertained before placement of the transfer catheter. A flexible Wallace catheter (Portex, Hythe, England) was used in all cases except when deemed inadequate and exchanged for a Tom Cat catheter (Kendall, Mansfield, MA).

In all cases, mock ET was performed at a time before the embryo transfer date, usually at the time of oocyte retrieval, using a Tom Cat catheter to measure the distance from the external cervical os to the uterine fundus; notations describing the position of the uterus and the catheter path were recorded in the patient’s chart to assist ease of transfer. In cases where ultrasound guidance was used, the catheter was advanced so that the tip was approximately 1.5?cm from the uterine fundus. In cases where the “clinical touch” method was used, placement depth was estimated by advancing the catheter to approximately 1 cm proximal to the previously recorded uterine sounding depth. In all cases, following embryo transfer, confirmation of transfer was performed by inspection of the transfer catheter under a microscope for retained embryos. Immediately following the procedure, notes were taken and reported after the ET.

Table 4. Patient characteristics and clinical results for periods before and after adoption of US guided ET for provider#2

Statistical Methods

Descriptive statistics are presented as frequency (percent) or mean±SD. All tests were two-tailed with a significance level of 0.05. Analysis was done with SAS 8.2 (SAS Institute Inc., Cary, NC), and graphics were produced with S-plus 6.1 (Insightful Corp., Seattle, WA).

RESULTS

Group I consisted of 194 patients (mean 33.7 ±SD 4.3 yrs), and the group II consisted of 268 patients (mean 33.5 ± SD 4.3 yrs). No statistical difference was found in the mean age of patients in the two groups (P =.67). Similarly, no difference was observed regarding the parity of both groups. However, a significant difference in the BMI was seen between the 2 groups (P <.01) where group II has a significantly higher BMI (Table 1). On stratifying the 2 groups by diagnosis, more patients with male factor infertility were treated before the adoption of ultrasound guidance (40.7% vs 24.6%) respectively. On the other side the distribution of other diagnoses was comparable before and after the adoption of the US guidance.

Ovarian stimulation characteristics and in vitro embryonic parameters

A significantly longer duration of ovarian stimulation was observed in group I vs group II (Table2; P<0.001). Similarly; a significantly higher dose of gonadotrophins was used in group I; P=0.002. However, the estradiol level on day 7 of stimulation and the peak estradiol level at the day of HCG administration were comparable in the two groups. Although the number of stimulation days and the amount of FSH used was significantly higher in group I, the numbers of oocytes retrieved were comparable between the 2 groups (12.5 ± SD 7.1 vs. 12.77 ± 6.5; P =.688) for group I and II respectively. In addition, comparable in vitro embryonic culture parameters were ascertained by comparable fertilization rate and blastocyst development rates between the groups.

Table 5. Patient characteristics and clinical results for periods before and after adoption of US guided ET for provider # 3

Embryo transfer parameters

There was no difference in the mean number of embryos transferred between group I and II (2.7 ±1.1 vs. 2.8 ± 0.8; P =.35). There is also equal distribution of the embryo transfer day; day 3 vs day 5 in both groups. In addition, the level of difficulty of the transfer technique was comparable in the 2 groups as evidenced by equivalent transfer duration in both groups (P=0.3; table 2). The percentage of bloody transfers was 18.5% in group I versus 20.03% in group II; denoting same level of difficulty.

Clinical outcome parameters

There were no significant differences regarding the clinical pregnancy rate, implantation rates and the multiple pregnancy rates before and after the adoption of ultrasound guidance (table 2). The clinical pregnancy rate before the adoption of ultrasound guidance (the presence of at least one fetal heart beat on ultrasound) was 36.6%, compared to 41.4% in the control group (P =.33). There was no difference in the distribution of ongoing multiple gestation rates between group I and II, as defined by the presence of fetal cardiac activity (26.8% vs. 35.1%; P =.258).

Effect of ultrasound guidance on the provider’s own outcome

On stratifying the cycles before and after the adoption of the ultrasound according to the providers, there was no significance improvement in the pregnancy rate per provider (tables3-5). The clinical pregnancy rate for the first provider before and after the adoption of ultrasound guidance was 38.8% vs 41.9% respectively (P=0.7); while the same values for the second and the third providers were 38.1% vs 41.6% and 32.8% vs 40.7% respectively. All of the transfers in both groups were performed with a Wallace catheter, whereas twenty transfers (20/194) in the group I (10.3%) required the use of a Tom Cat catheter compared to (32/286) in group II (11.1%). A tenaculum was used in 3 transfers (1.5%) in the group I and 3 transfers (1.04%) in group II. This again a further evidence of the same level of difficulty encountered before and after the adoption of ultrasound guidance.

DISCUSSION

Optimizing embryo transfer technique has been studied extensively in the past decade with conflicting conclusions. Ultrasound guidance of the embryo transfer has been shown to improve the outcome by some investigators and not to do so by others. However, the question of whether the adoption of ultrasound guidance improves the pregnancy rate per provider remains unanswered. The hypothetical benefit of ultrasound guidance lies in the correct positioning of the ET catheter avoiding low corporeal misplacement or otherwise. Incorrect ET catheter placement was shown to happen in approximately one quarter of the ETs performed in one center (10). In another study, incorrect placement was shown to happen in 15% of the 67 patients enrolled in this investigation (11).

The use of the -so called-clinical touch ET depends exclusively on the level of training and experience of the provider. Obviously, it is a totally subjective process that could vary from a provider to another. Such a level of expertise could be solely dependant on the number of transfers performed by the provider or otherwise (12). Whether the use of ultrasound guidance could be one of these factors was the main question addressed in this study.

Since the success rate can vary among individuals performing transfers, we evaluated the outcomes of embryo transfer performed by the same physician before and after the adoption of US guidance where only one experienced sonographer guided all the transfers. Despite the limitation of our study being retrospective, the characteristics of the comparison groups are similar regarding the age of the patients, the distribution of day 3 and day 5 transfers, and the number and quality of embryos transferred. Despite the fact that longer ovarian stimulation and higher doses of gonadotrophins were used before the adoption of ultrasound guidance, similar estradiol levels were observed throughout the stimulation and almost the same number of eggs was retrieved. Patients receiving US-guided transfers were significantly heavier than clinical touch-ET. More importantly, however, on adjusting for the BMI, there was no change in the clinical pregnancy rate of the patients who had ultrasound-assisted transfers or transfers by the “clinical touch” technique. We found that adopting the US-guidance policy did not improve the overall pregnancy rate nor the pregnancy rate for each one of the 3 providers involved. In addition, the transfer procedure difficulty was maintained at the same level as evidenced by comparable duration of transfer and percentage of bloody procedure.

In a recent meta-analysis Sallam et al., concluded that ultrasound-guided embryo transfer increases the clinical pregnancy and ongoing pregnancy rates significantly compared to the clinical touch method (6). The overall pregnancy rate reported in this study was 36.5% when US guidance was instituted. This was comparable to the pregnancy rate in our clinical touch ET group (36.6%) when US guidance was not used at all. Although, there was a trend towards a higher pregnancy rate when US guidance was adopted, it does not reach the level of statistical significance. In addition, another meta-analysis demonstrated that none of the prospective randomized studies included has enough power to detect a 5% difference in clinical pregnancy rates (13). Careful assessment of the depth of the uterine cavity may be helpful prior to the adoption of the clinical touch ET. For instance, by measuring uterine depth by ultrasonography or doing a mock ET at the time of transfer may be helpful. Although no difference was seen in pregnancy outcome in our experience when using ultrasound guidance, it has been shown to be associated with easier transfers (4, 8), decreased use of a tenaculum, and decreased presence of blood in the catheter following transfer (4). On the other side, these advantages were not verified by others (2, 7) (3, 14) or in our study.

In conclusion, the adoption of ultrasoundguidance policy during embryo transfer may be useful for junior staff for training purposes. It also could help confirm accurate placement of catheter in patients with a history of difficult embryo transfer. A large prospective study with enough power would be necessary to allay the controversy regarding the importance of routine simultaneous ultrasound monitoring during embryo transfer.

ACKNOWLEDGMENTS

The author wants to acknowledge Tommaso Falcone MD, Jeffery M Goldberg, M.D, Marjan

REFERENCES

1. Kan AK, Abdalla HI, Gafar AH, Nappi L, Ogunyemi BO, Thomas A, Ola-ojo OO. Embryo transfer: ultrasound-guided versus clinical touch. Hum Reprod 1999;14:1259-1261.
2. Coroleu B, Barri PN, Carreras O, Martinez F, Veiga A, Balasch J. The usefulness of ultrasound guidance in frozenthawed embryo transfer: a prospective randomized clinical trial. Hum Reprod 2002;17:2885-2890.
3. Garcia-Velasco JA, Isaza V, Martinez-Salazar J, Landazabal A, Requena A, Remohi J, Simon C. Transabdominal ultrasound-guided embryo transfer does not increase pregnancy rates in oocyte recipients. Fertil Steril 2002;78:534-539.
4. Mirkin S, Jones EL, Mayer JF, Stadtmauer L, Gibbons WE, Oehninger S. Impact of transabdominal ultrasound guidance on performance and outcome of transcervical uterine embryo transfer. J Assist Reprod Genet 2003;20:318-322.
5. Flisser E, Grifo JA, Krey LC, Noyes N. Transabdominal ultrasound-assisted embryo transfer and pregnancy outcome. Fertil Steril 2006;85:353-357.
6. Sallam HN, Sadek SS. Ultrasound-guided embryo transfer: a meta-analysis of randomized controlled trials. Fertil Steril 2003;80:1042-1046.
7. Coroleu B, Carreras O, Veiga A, Martell A, Martinez F, Belil I, Hereter L, et al. Embryo transfer under ultrasound guidance improves pregnancy rates after in-vitro fertilization. Hum Reprod 2000;15:616-620.
8. Matorras R, Urquijo E, Mendoza R, Corcostegui B, Exposito A, Rodriguez-Escudero FJ. Ultrasound-guided embryo transfer improves pregnancy rates and increases the frequency of easy transfers. Hum Reprod 2002;17:17621766.
9. Prapas Y, Prapas N, Hatziparasidou A, Vanderzwalmen P, Nijs M, Prapa S, Vlassis G. Ultrasound-guided embryo transfer maximizes the IVF results on day 3 and day 4 embryo transfer but has no impact on day 5. Hum Reprod 2001;16:1904-1908.
10. Woolcott R, Stanger J. Potentially important variables identified by transvaginal ultrasound-guided embryo transfer. Hum Reprod 1997;12:963-966.
11. Shamonki MI, Spandorfer SD, Roberts JE, Rosenwakes Z. Ultrasound-guided embryo transfer: does it improve IVF success? Fertil Steril 2003;80:S127-128.
12. Papageorgiou TC, Hearns-Stokes RM, Leondires MP, Miller BT, Chakraborty P, Cruess D, Segars J. Training of providers in embryo transfer: what is the minimum number of transfers required for proficiency? Hum Reprod 2001;16:1415-1419.
13. Buckett WM. A meta-analysis of ultrasound-guided versus clinical touch embryo transfer. Fertil Steril 2003;80:10371041.
14. Tang OS, Ng EH, So WW, Ho PC. Ultrasound-guided embryo transfer: a prospective randomized controlled trial. Hum Reprod 2001;16:2310-2315.

© Copyright 2006 - Middle East Fertility Society

The following images related to this document are available:

Photo images