Human Reproduction, Vol. 17, No. 10, 2632-2635,
October 2002
© 2002 European Society of Human Reproduction and Embryology
The degree of difficulty of embryo transfer is an independent factor for predicting pregnancy
1 Department of Obstetrics and Gynecology, University of Oulu, 2 Family Federation of Finland, 90220 Oulu and 3 AVA Clinic, Fertility Center, 33100 Tampere, Finland
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Abstract |
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BACKGROUND: The role of embryo transfer as regards the success of IVF/ICSI treatments is recognized but has not been comprehensively evaluated. In order to determine its importance, the degree of difficulty of 4807 embryo transfers after IVF/ICSI was analysed retrospectively. METHODS: Logistic regression analysis identified the age of the subject, type of treatment (IVF versus ICSI), number of embryos transferred and degree of difficulty of embryo transfer as independent factors predicting pregnancy. The main focus of the study was to evaluate the importance of the difficulty of embryo transfer after taking into account the other confounding variables. RESULTS: Embryo transfer was classified as easy (2821), intermediate (1644) or difficult (342). The transfer was considered difficult if it was time consuming, the catheter met great resistance, there was a need to change the catheter, if sounding or cervical dilatation was needed or if blood was found in any part of the catheter. Easy or intermediate transfers resulted in a 1.7-fold higher pregnancy rate than difficult transfers (P < 0.0001; 95% confidence interval: 1.3–2.2). CONCLUSIONS: This study demonstrates that the degree of difficulty of embryo transfer is an independent factor as regards achieving pregnancy after IVF/ICSI. All efforts should be made to avoid difficult embryo transfers. Physicians should be alert to the factors associated with embryo transfer and should be instructed to use a stepwise approach in difficult transfers.
Key words: catheter/difficulty/embryo transfer/logistic regression
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Introduction |
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TopAbstractIntroductionMaterials and methodsResultsDiscussionAcknowledgementsReferences |
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The success of IVF depends on multiple factors (al-Shawaf et al., 1993
; Roseboom et al., 1995; Schoolcraft et al., 2001). Some are related to characteristics such as age of the subject, aetiology of infertility, duration of infertility and uterine receptivity. Others are related to the type of treatment (IVF or ICSI), the number of oocytes recovered and the number and quality of transferred embryos. Although embryo transfer is considered to be of the utmost importance for the success of treatment (Rhonda et al., 2000) there are only a few comprehensive studies on this issue. This is probably due to the fact that embryo transfer is considered to be an easy and simple procedure. However, there are many factors that may affect its success. These include the individual experience of the provider (Karande et al., 1999; Hearns-Stokes et al., 2000; Rhonda et al., 2000), the type of catheter, presence of a full or empty bladder, the use of ultrasonography, and the presence of blood or mucus in the catheter (Nabi et al., 1997; Awonuga et al., 1998; Goudas et al., 1998; Schoolcraft et al., 2001; van Weering et al., 2002). The objective of this study was to investigate, using multiple logistic regression analysis, whether the degree of difficulty of embryo transfer is an independent factor as regards the success of IVF/ICSI.
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Materials and methods |
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TopAbstractIntroductionMaterials and methodsResultsDiscussionAcknowledgementsReferences |
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Data on 4807 IVF/ICSI cycles performed during 1994–2000 were collected from three Finnish fertility centres with similar computerized databases (Babe 3.0; XtremeSolutions, Oulu, Finland). The participating centres were the IVF Unit of the University Hospital of Oulu, the Family Federation of Finland, Oulu, and the AVA Clinic, Fertility Center in Tampere, Finland.
Stimulation protocol
The characteristics of the stimulation protocol for controlled ovarian stimulation have been previously described (Tomas et al., 1998). Briefly, a long protocol was adopted, starting with GnRH agonist in the preceding late luteal phase. Basal vaginal ultrasonography was then performed to confirm ovarian suppression, after which urinary (n = 2263) or recombinant (n = 2544) gonadotrophins were given daily. Follicular growth was followed by transvaginal ultrasonography. An i.m. injection of 5000–10 000 IU hCG was given when at least two follicles were >17 mm in diameter. Oocyte retrieval was performed 36 h after the hCG injection. Embryo transfer was carried out on day 2 or 3 after oocyte retrieval. Treatments involving blastocysts or assisted hatching were not included in this study, and neither were frozen–thawed embryo transfers.
The technique of embryo transfer
Embryos were classified just before transfer, according to the number and regularity of the blastomeres and the degree of fragmentation. One or two embryos were usually prepared for transfer (three or more embryos were transferred in 382 cycles, all before 1999). The subjects arrived with an empty bladder and assumed the lithotomy position. After insertion of a sterile bivalve speculum, the cervix was cleaned with culture medium. No ultrasonography or mock embryo transfer was performed before the transfer.
The catheter was loaded with the embryo(s) and was smoothly introduced through the cervical canal up to 1–2 cm from the uterine fundus, while trying to avoid touching the fundus. The embryos were then expelled gently, after which the catheter was slowly removed while being rotated. The catheter was checked under a microscope for embryo retention or the presence of blood. In the majority of transfers, a soft embryo catheter was used (Cook K-Soft; Cook, Brisbane, Australia, n = 1887; Wallace; SIMS Portex Ltd, Kent, UK, n = 1377; or Gynetics, n = 869). In 674 transfers, a hard catheter (TDT, n = 566; Casmed, n = 45; other types, n = 63) was used. The choice of catheter was based on the preference of the doctor or on previous history of the patient.
In the case of any difficulty, a stepwise approach was used. In many cases, the catheter was introduced while gently pulling the cervix with forceps. In certain circumstances, a harder catheter (TDT or Casmed) had to be used after an initial attempt with a soft catheter. If necessary, uterine sounding or dilatation of the cervix was performed.
All embryo transfers were performed by physicians who classified the transfer as being easy, intermediate or difficult, according to the problems encountered during the procedure. An easy embryo transfer was defined when it took place smoothly, without the use of any other instrumentation, the catheter was clean of blood and there was no need to change the catheter. Embryo transfer was classified as intermediate when the primary catheter met some resistance, leading to the use of cervical forceps and/or the outer sheath catheter, after which the transfer was smooth and there was no blood contamination. Embryo transfer was considered difficult if at least one of the following problems occurred: greater resistance was met, the procedure was time consuming, there was a need to change to a harder catheter, uterine sounding or cervical dilatation was carried out or there was blood in any part of the catheter.
Statistical analysis
Multiple logistic regression analysis was used to analyse the success of the treatment. Initially, univariate analysis identified potential factors affecting the occurrence of clinical pregnancy. These included the age of the woman, body mass index, main diagnosis of infertility, sperm characteristics, type of gonadotrophin (urinary versus recombinant), number of ampoules needed (
75 IU), type of GnRH agonist (nasal spray versus long-acting formulations), duration of the stimulation, the physician performing the embryo transfer, type of catheter, quality of the embryo(s) and the difficulty of embryo transfer.
These factors were then included in a model for multivariate logistic regression analysis. Variables that clearly lost their importance were excluded from the final model, which included the variables that best explained the outcome. The degree of difficulty of embryo transfer was studied in this perspective. The results of multivariate analysis are presented as odds ratios (ORs) and their 95% confidence intervals (CIs).
The main outcome variable in this study was clinical pregnancy, defined as the presence of fetal heartbeat in transvaginal ultrasonography.
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Results |
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TopAbstractIntroductionMaterials and methodsResultsDiscussionAcknowledgementsReferences |
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The degree of difficulty of 4807 embryo transfers after IVF/ICSI cycles performed in three IVF centres in Finland was analysed. There were 2821 (58.7%) easy, 1644 (34.2%) intermediate and 342 (7.1%) difficult embryo transfers. Because the pregnancy rates in the easy and intermediate embryo transfer groups were similar (30.3 versus 30.4% respectively), the results in these two groups were combined and compared with those in the difficult embryo transfer group. The characteristics of the subjects in the difficult and non-difficult embryo transfer groups are presented in Table I
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In multiple logistic regression analysis, the age of the woman, type of treatment (IVF or ICSI), number of embryos transferred and the difficulty of embryo transfer were identified as independent factors (Table II
). The clinical pregnancy rate after easy or intermediate embryo transfers was 30.3%, and after difficult transfers, 21.1% (P = 0.0002). The easy and intermediate groups did not differ in this regard (30.3 versus 30.4%). In terms of OR, the chance of clinical pregnancy after a difficult transfer was 1.7 times lower than after an easy or intermediate transfer (95% CI: 1.3–2.2).
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In addition to the difficulty of embryo transfer, the age of the woman, the mode of treatment (IVF/ICSI) and the number of embryos transferred were found to be independent factors influencing the treatment outcome (Table II
). To exclude the possible effect of the transfer of multiple embryos on the results, the difficulty of embryo transfer was also analysed in the subgroup of women with two embryos transferred. In this subgroup also, the age of the woman, the type of treatment and the difficulty of embryo transfer remained as independent factors as regards prediction of pregnancy.
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Discussion |
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TopAbstractIntroductionMaterials and methodsResultsDiscussionAcknowledgementsReferences |
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The present study demonstrates that the difficulty of embryo transfer is an independent variable as regards the success of IVF/ICSI. Most importantly, logistic regression analysis showed that this finding was independent of the subject, stimulation characteristics or the physician performing the embryo transfer. Subjects with an easy or intermediate embryo transfer became pregnant significantly more often than those with a difficult transfer. Although other factors such as embryo quality and developmental potential (Diedrich et al., 1989
; Giorgetti et al., 1995) play a significant role, the present results particularly emphasise the importance of the degree of difficulty of embryo transfer on the outcome of IVF/ICSI. These findings support the results of previous studies (Englert et al., 1986; Lass et al., 1999; Wood et al., 2000), although contradictory data also exist (Tur-Kaspa et al., 1998; Burke et al., 2000). This discrepancy may be due to different criteria for the difficulty of embryo transfer. In contrast to our study, Tur-Kaspa et al. graded cases with mild uterine manipulation as difficult (Tur-Kaspa et al., 1998), and in the study of Burke et al. the criteria were not explained (Burke et al., 2000).
In difficult embryo transfers the lower pregnancy rate may be related to several factors. Laceration of the cervix or touching the endometrium in the uterine fundus may diminish the potential for implantation (Woolcott and Stanger, 1997; Lesny et al., 1998). In an ultrasonographic study performed in association with ‘blind’ embryo transfer, it was demonstrated that in >17% of embryo transfers the catheter touched the fundus and in 7.4%, the tubal ostia, which can disturb implantation (Woolcott and Stanger, 1997). The presence of mucus in the catheter may retain the embryos (Nabi et al., 1997) and uterine contractions may interfere with implantation (Fanchin et al., 1998; Lesny et al., 1999). Whether the contractions that were possibly related to manipulation could be avoided by using anaesthesia is unsure. Furthermore, infections may also play a part, since an increased amount of positive bacteriological cultures has been found on the tip of catheters in unsuccessful cycles (Egbase et al., 1996).
In the present study 7.1% of the transfers were difficult, jeopardizing the outcome of the treatment. Ultrasonography has been proposed in regard to reducing the number of difficult transfers (Strickler et al., 1985; Woolcott and Stanger, 1997; Broussin et al., 1998; Wood et al., 2000), although better pregnancy rates have not been observed (al-Shawaf et al., 1993). Some authors recommend the use of a mock transfer prior to embryo transfer (Mansour et al., 1990; Schoolcraft et al., 2001). Although mock transfer may be useful in some cases, its predictive value is still undefined (Stafford-Bell, 1999). Therefore, we do not perform mock transfer. Distension of the bladder, use of antibiotics, depth of the transfer, speed of injection and the type of catheter may also influence the outcome of the treatment (Schoolcraft et al., 2001). In our study we could not compare different types of catheter (i.e. soft versus hard), because a soft catheter was used in the vast majority (86%) of embryo transfers. The use of cervical dilatation at the time of oocyte retrieval may be justified in certain circumstances (Stafford-Bell, 1999). Transmyometrial transfer has been shown to be a useful technique (Kato et al., 1993) and can be applied with success in situations of difficult access to the uterine cavity (Sharif et al., 1996). It can be argued that in the case of a complicated embryo transfer with bleeding and excess manipulation, it would be better to freeze all the embryos and perform the transfer at a later date.
We are aware that there are differences in embryo transfer techniques between physicians that may be reflected in the outcome (Karande et al., 1999; Rhonda et al., 2000). As regards individual physicians in the present study, the pregnancy rate was consistently higher after an easy or intermediate embryo transfer than after a difficult one. Because a total of 15 doctors performed the transfers, it was not possible to evaluate this variable in the final model of the regression analysis.
In conclusion, this study demonstrates that the degree of difficulty in embryo transfer after IVF/ICSI is an independent factor as regards the success of the treatment. An easy or intermediate transfer results in a 1.7-fold better pregnancy rate than a difficult one. Hence, more attention should be paid to the teaching of embryo transfer techniques, and each fertility centre should establish a standardized, stepwise protocol for difficult embryo transfers.
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Acknowledgements |
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TopAbstractIntroductionMaterials and methodsResultsDiscussionAcknowledgementsReferences |
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This study was supported by grants from the Sigrid Juselius Foundation and the Academy of Finland.
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Notes |
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4 Present address: AVA Clinic, Fertility Center, Pc. D. Pedro IV, 74–3A, 1100–202 Lisbon, Portugal
5 To whom correspondence should be addressed at: AVA Clinic, Fertility Center, Pc. D Pedro IV, 74–3A, 1100–202 Lisbon, Portugal. E-mail: ctomas{at}avaclinic.com
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Submitted on December 3, 2001; resubmitted on March 21, 2002; accepted on May 14, 2002.
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