Human Reproduction, Vol. 14, No. 5, 1259-1261,
May 1999
© 1999 European Society of Human Reproduction and Embryology
Embryo transfer: ultrasound-guided versus clinical touch
Fertility and Endocrinology Centre, In-Vitro Fertilization Unit, Lister Hospital, London SW1W 8RH, UK
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Abstract |
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In this prospective control study, the pregnancy and implantation rates were compared between ultrasound-guided and clinical touch uterine embryo transfers. In addition, a subset of patients was sought that would particularly benefit from embryo transfer under ultrasound guidance. A total of 187 patients (93 ultrasound and 94 clinical touch) was enrolled. Allocation was random and depended on whether their embryo transfers were done during the 1 h each day in which the ultrasound was available. Pregnancy and implantation rates of 37.8 and 20.4% respectively were achieved when ultrasound was used, compared with 28.9 and 16.2% respectively with clinical touch. This difference was not statistically significant. There was no significant difference in the pregnancy rate when the number of embryos transferred was controlled. Older women (
37 years old) had an apparently higher pregnancy rate (38.1 versus 20.4%; not significant) with ultrasound guidance during embryo transfer. In the subgroup where the clinician rated the transfer procedure as difficult, there appeared to be a substantial improvement in the pregnancy rate in the group that used ultrasound (54.5 versus 10.0%; not significant). Although our results were not statistically significant, we believe that ultrasound-guided embryo transfers should be used in clinically difficult embryo transfers and in older women, as it appears to improve the pregnancy rate over clinical touch transfers.
Key words: clinical/embryo transfer/IVF/prospective study/ultrasound-guided
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Introduction |
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TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
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Ever since the birth of the first in-vitro fertilization (IVF) baby in 1978 (Edwards et al., 1980
), the advancement in ovulation stimulation regimes, oocyte collection and culture mediums has been phenomenal. However, the technique of uterine embryo transfer remains largely unchanged, since it was first described. Conversely, although there have been vast improvements with ovulation induction, fertilization and embryo cleavage, the majority of transferred embryos fail to implant. This failure may be ascribed to deficiencies in either intrinsic embryo quality or uterine receptivity as suggested by Speirs (1988), or it could also logically be due to the technique of embryo transfer. Another more obscure factor affecting embryo implantation may include uterine contractions. Fanchin et al. (1998) noted that more uterine contractions at the time of embryo transfer were associated with a lower clinical and ongoing pregnancy rate.
The technique of embryo transfer at our centre and in the majority of the centres world-wide relies on the clinical touch in positioning the transfer catheter in the upper part of the uterine cavity. It would appear that any assistance such as ultrasound guidance in ensuring that the embryos are indeed placed in this position would be desirable. Using clinical touch first and then checking with a transvaginal ultrasound, Woolcott and Stanger (1997) found 17.4% (21/121) of guiding cannulae inadvertently abutting the fundal endometrium and 7.4% (9/121) abutting the internal tubal ostia. Most studies trying to address the issue of whether ultrasound guidance is beneficial to embryo transfer conclude that although the pregnancy rate may not be significantly raised, ultrasound guidance provides both the clinicians and the patients with a greater degree of confidence in the embryo transfer procedure (Strickler et al., 1985; Leong et al., 1986; Hurley et al., 1991). The objective of this prospective control study is to assess the use of transabdominal ultrasound scan guidance during embryo transfer to examine if it would improve the pregnancy and implantation rate compared to the present practice of clinical touch embryo transfer. In addition, we divided our study population according to the (i) number of embryo transferred, (ii) age of patients and (iii) ease of embryo transfer to delineate a subgroup of patients that would particularly benefit from their embryos being transferred under ultrasound guidance.
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Materials and methods |
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Between February 1997 and September 1997, all women undergoing uterine embryo transfers after IVF were enrolled into the study unless they had the following exclusion criteria: age >42 years old, more than three previous assisted conception cycles, or previous difficult or anticipated difficult embryo transfer and transfers requiring general anaesthesia for the patient.
On each of the embryo transfer days during the study period, a continuous 1 h time period was allocated for the use of the ultrasound for embryo transfers. Eligible women who had their embryo transfers during this time slot had their embryo transfers performed under ultrasound guidance (`ultrasound' group). The control group was made up of eligible women who had their embryo transfers in the usual clinical manner without the aid of ultrasound in the following hour (`clinical' group). If the `ultrasound' group was in the last hour of embryo transfer on any one day, then the `clinical' group was taken as all the patients in the preceding hour. The 1-h time period for the `ultrasound' group was not the same each day and was determined by the availability of the ultrasonographer. Neither the patients nor the person allocating the embryo transfer times knew when the ultrasonographer was doing the scanning on the day of embryo transfer.
Using this allocation process, a total of 195 women was enrolled in the study: 98 in the `ultrasound' group and 97 in the clinical group. No significant difference was observed between the two groups when comparing their age, whether they were primary or secondary infertile, duration and cause of infertility and the mean number of previous assisted conception attempts. The mean numbers of embryos available for transfer and embryos actually transferred were similar in both groups (Table I). All eligible women were told to come in on the day with a relatively full bladder but were not told whether or not they would have their embryo transfers done under ultrasound guidance. It should be noted that it is the usual clinical practice of the unit not to use ultrasound for routine embryo transfers.
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Five clinicians and two ultrasonographers were involved in the study. The pregnancy rates achieved, matched for patient's age and number of embryos transferred, after embryo transfer by each of the five clinicians in the 3 months before the study began were similar and not significantly different. Both ultrasonographers were specialists in infertility. A Siemens Sonoline AC ultrasound machine with a 3.5 mHz transabdominal probe was used on all women in the `ultrasound' group.
The ovulation induction regime used was down-regulation with a gonadotrophin releasing hormone analogue followed by follicle stimulating hormone in either a short (15% of both groups) or long protocol (85% of both groups). Human chorionic gonadotrophin was given i.m. 34–38 h prior to vaginal oocyte retrieval. A maximum of three embryos was transferred, 2 (69% of both groups) or 3 (31% of both groups) days following oocyte retrieval using a Wallace embryo transfer catheter (catalogue number 1816; Simcare Manufacturing Ltd, West Sussex, UK). In both `ultrasound' and `clinical' groups, the clinicians started the embryo transfer in the same way, i.e. cleaning the external genitalia with a moist swab before insertion of a sterile speculum into the vagina. The external cervical os was then cleaned with a moist cotton bud and mucus in the cervical canal was removed with a mucus extractor. The Wallace catheter was loaded in the following way: 1 µl air gap followed by 15 µl of Medicult Universal IVF medium (catalogue number 1031; Medicult a/s, Copenhagen, Denmark) containing the embryo(s) and finally another 1 µl air gap was aspirated at the end. The catheter was then handed to the clinician who inserted it through the cervical canal. At this stage there was a difference between the two groups. In the `clinical' group, when the clinician was satisfied that he/she had placed the catheter as close to the fundus as possible without touching it, the plunger was depressed; but in the `ultrasound' group, the ultrasonographers used a transabdominal ultrasound to guide the clinician in the positioning of the tip of the catheter to within 1 cm of the fundus of the uterine cavity. The plunger was then depressed and the air bubble observed to be expelled from the catheter tip. The clinician was then required to rate the embryo transfer procedure in terms of ease of transfer before they left the embryo transfer room. The rating system guideline was: very easy: transfer catheter went straight through the cervix; easy: required either the separation of the transfer catheter to advance the sheath or a stiffer catheter to facilitate the transfer; difficult: required a tenaculum in addition to those requirements in the `easy' category.
A positive pregnancy outcome was a positive blood pregnancy test performed 2 weeks after the embryo transfer and an ultrasound scan showing at least one sac in the uterine cavity 2 weeks after the positive pregnancy test. The implantation rate was defined as the number of sacs seen on ultrasound in relation to the number of embryos replaced. Subanalysis included the pregnancy rate controlled for the number of embryos transferred, the women's age and ease of transfer.
For categorical data like pregnancy outcome and implantation, Pearson's 
2 test was used to test for statistical difference between the two groups. Fisher's Exact test was used if the numbers in any one cell were less than five. For continuous data, Student's t-test was used. A P value < 0.05 was considered statistically significant.
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Results |
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TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
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The pregnancy rate was not significantly different between each of the five clinicians or between each of the two ultrasonographers. None of the enrolled patients required a general anaesthetic. There was an apparently improved pregnancy rate of 37.8% when ultrasound was used compared to 28.9% with clinical touch, but this difference was not statistically significant. Similarly, the implantation rate appeared higher in the ultrasound-guided group (20.4 versus 16.2%; not significant) (Table II
).
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When the analysis was performed controlling for the number of embryos transferred, there was no significant difference in the two groups whether one, two or three embryos were transferred. When controlled for the age of the women (<37 versus
37 years old), again the results were not significantly different (38.1 versus 20.4% respectively). Clinicians rated 75.4% of all transfers as `very easy', 13.8% as `easy' and 10.8% as `difficult'. If we excluded the `very easy' group, the pregnancy rate in the `ultrasound' group was 50.0 versus 27.3% in the clinical touch group (not significant). If we only examined transfers which were rated `difficult', the difference in favour of the `ultrasound' group appeared larger (54.5 versus 10.0%; not significant by Fisher's Exact test) (Table II
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Discussion |
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TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
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The failure of most embryos to implant following their transfer into the uterine cavity has prompted interest in ultrasound-guided embryo transfer in an attempt to improve pregnancy rate. Strickler et al. (1985) and Leong et al. (1986) were first to raise the possibility that ultrasound guidance may improve pregnancy rate. Hurley et al. (1991) in a study involving 94 patients in the (transvaginal) ultrasound guided group showed that pregnancy rates were apparently increased over a control group of 246 patients, although statistical significance was reached only in the sub-group of single embryo transfers. The case for ultrasound guidance is further supported in a study by Prapas et al. (1995), who found that the pregnancy rate (36.06 versus 22.6%) in the ultrasound control group (n = 61) was significantly higher than in the `clinical touch' group (n = 71). However, Al-Shawaf et al. (1993), in a prospective study involving 44 women in the ultrasound group and 27 women in the non-ultrasound group, found that ultrasound did not affect the pregnancy outcome (29.0 versus 30.3%).
To our knowledge, this is the largest prospective study comparing clinical and ultrasound-guided embryo transfer. Like previous studies, we failed to find a significant difference in the pregnancy rate with the use of ultrasound guidance. However, there was an apparently substantial improvement in the pregnancy rate in the subgroups of older women and where the embryo transfer procedure was rated as `difficult' by the clinician which just failed to reach statistical significance. We believe that this apparent improvement can be ascribed to the accurate positioning of the embryo transfer catheter tip near the fundus of the uterus which can be confidently achieved with the use of ultrasound scan guidance. It negates factors such as inadvertent abutting of the catheter tip against the fundal endometrium or tubal ostia (Woolcott and Stanger, 1997). In our experience, on occasions, it has been observed that the catheter can curl and that the tip would actually be directed towards the cervix without any awareness of this malposition by the clinician. It is interesting to note that ultrasound was particularly helpful in women >36 years of age. It appears that precise placement of embryos is more important in this group than in younger women where perhaps better embryo quality or uterine receptivity may be able to make up for less than accurate placement.
The procedure was readily accepted by the patients who were reassured by the visualisation of the transfer process. The acceptance by the clinicians was also high with no significant added time, and the procedure was done with more confidence as the catheter is advanced to the fundus of the uterus under ultrasound scan guidance. It has thus been proposed, in the light of this study, that difficult embryo transfers, especially in older women, be conducted under ultrasound guidance.
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Notes |
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1 To whom correspondence should be addressed
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References |
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TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
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al-Shawaf, T., Dave, R., Harper, J. et al. (1993) Transfer of embryos into the uterus: how much do technical factors affect pregnancy rates? J. Assist. Reprod. Genet., 10, 31–36.[Web of Science][Medline]
Edwards, R.G., Steptoe, P.C. and Purdy, J.M. (1980) Establishing full-term human pregnancies using cleaving embryos grown in vitro. Br. J. Obstet. Gynaecol., 87, 737–756.[Web of Science][Medline]
Fanchin, R., Righini, F.O., Taylor, S. et al. (1998) Uterine contractions at the time of embryo transfer alter pregnancy rates after in-vitro fertilization. Hum. Reprod., 13, 1968–1974.
Hurley, V.A., Osborn, J.C., Leoni, M.A. et al. (1991) Ultrasound-guided embryo transfer: a controlled trial [see comments]. Fertil. Steril., 55, 559–562.[Web of Science][Medline]
Leong, M., Leung, C., Tucker, M. et al. (1986) Ultrasound-assisted embryo transfer. J. In Vitro Fert. Embryo Transf., 3, 383–385.
Prapas, Y., Prapas, N., Hatziparasidou, A. et al. (1995) The echoguide embryo transfer maximizes the IVF results. Acta Eur. Fertil., 26, 113–115.[Medline]
Speirs, A.L. (1988) The changing face of infertility. Am. J. Obstet. Gynecol., 158, 1390–1394.[Medline]
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Submitted on August 27, 1998; accepted on December 16, 1998.
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