1 Academic Department of Obstetrics and Gynaecology, 2 Department of Biological Sciences, University of Hull, Cottingham Road, Kingston Upon Hull HU6 7RX and 3 The Hull IVF Unit, Princess Royal Hospital, Saltshouse Road, Kingston Upon Hull HU8 9HE, UK
![]() |
Abstract |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Key words: difficult embryo transfer/junctional zone contractions/transmyometrial embryo transfer
![]() |
Introduction |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Several studies have investigated the role of junctional zone (JZ) contractions in IVFembryo transfer cycles. It has been shown that these contractions can interfere with the success rate of IVF (Fanchin et al., 1998), possibly by expelling embryos from the uterine cavity. Our unit has recently shown that difficult transcervical embryo transfers, and the use of a tenaculum, could stimulate JZ contractions (Lesny et al., 1998
, 1999a
). The following study was therefore designed to assess the effect of TMET on JZ contractions.
![]() |
Materials and methods |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
The age of the patients varied from 2737 years (median = 31). Male factor was responsible for subfertility in five cases, two patients suffered from unexplained subfertility, one from severe endometriosis and two from tubal factor subfertility.
Medication
Ovulation induction prior to IVF was achieved with a standard regimen of pituitary down-regulation with 800 µg of GnRH agonist (Nafarelin; Searle Pharmaceuticals, High Wycombe, UK) administered daily from the mid-luteal phase, followed by appropriate doses of urofollitrophin (Metrodin High Purity; Serono Laboratories UK Ltd, Welwyn Garden City, UK). When the lead follicle reached a diameter of 20 mm, 10 000 IU HCG (Profasi; Serono) was given. Luteal support was provided by vaginal micronized progesterone (Utrogestan; Basins Iscovesco Laboratories, Paris, France) in a dosage of 600 mg/night from the day of oocyte retrieval for 80 days. All patients received 600 mg of Ibuprofen (Brufen; Knoll Ltd, Nottingham, UK) 2 h before oocyte retrieval. Midazolam (Hypnovel; Roche products, Welwyn Garden City) was used for sedation and Alfentanil (Rapifen; Janssen-Cilag Ltd, High Wycombe) was given for analgesia during oocyte retrieval and embryo transfer.
Transmyometrial embryo transfer
The patient was placed in lithotomy position with an empty bladder. The procedure was performed under transvaginal ultrasound scan guidance (ATL Ultramark 4, 5MHz transducer; Advanced Technology Laboratories, Seattle, USA).
A Towako needle (Cook Ltd, Letchworth, Herts, UK) with its stylet was passed through the anterior vaginal fornix, through the myometrium of the anterior uterine wall with its adjacent endometrium and into the endometrium of the posterior wall. In cases of a retroverted uterus, the Towako needle was passed through the posterior vaginal fornix and through the myometrium and endometrium of the posterior uterine wall into the endometrium of the anterior uterine wall. The needle was then gently pulled back into the uterine cavity and the stylet was removed. To shorten the procedure, the embryologist had begun to load the 2.0 French polyethylene transfer catheter with embryos suspended in 20 µl of culture medium (Medi-Cult IVF Culture Medium; Medi-Cult Ltd, Redhill, UK) when the clinician started to insert the needle. The catheter was passed through the needle by the embryologist who performed the transfer of the embryos. Their correct placement was confirmed by a flow of fluid seen inside the uterine cavity. The needle and the catheter were removed and checked for retention of embryos.
Imaging techniques
A transvaginal ultrasound scan of the mid-sagittal plane of the uterus was performed for 2 min before and for 3 min after TMET. The images were videotaped (VHS P4341: Goldstar, South Korea), digitized by computer and converted to x5 normal speed using Speed Razor Mach III (Synch Corporation, 1993, Bethesda, USA). A frame time-coding system allowed us to evaluate timing of events with an accuracy of ±0.04 s. Contraction pattern and frequency were assessed and agreed by two independent observers. The wave classification system introduced by IJland was used (IJland et al., 1996). This system subdivides five types of endometrial movements: no activity; waves from the cervix to the fundus; waves from the fundus to the cervix; opposing waves, starting simultaneously at the fundus and the cervix; and random waves, originating at various foci.
These observations were evaluated on Statistics Package for Social Sciences for Windows (SPSS UK Ltd, St. Andrews House, Woking, Surrey, UK) using Wilcoxon's matched-pairs test.
![]() |
Results |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
|
|
|
![]() |
Discussion |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
TMET has been used as an alternative to transcervical embryo transfer. The Towako Maternity Clinic group used this method when a difficult transcervical embryo transfer occurred in a previous cycle (Kato et al., 1993), whilst Sharif used the method after a difficult or impossible transcervical mock embryo transfer immediately before the real transfer (Sharif et al., 1996
). However, in addition to an impossible or difficult transcervical embryo transfer, it has been suggested that a TMET should be performed for other indications such as `fragile' embryos (Kato et al., 1993
) or multiple implantation failure (Asaad and Carver-Ward, 1997
; Groutz et al., 1997
).
In this study, we have investigated the occurrence of JZ contractions after TMET. We have demonstrated that TMET is a powerful stimulus to JZ contractility; a significantly increased number of random, opposing and cervicofundal contractions after the insertion of the Towako needle were noted. Only three out of the 10 patients developed fundocervical contractions and although a statistically significant difference in the frequency of this type of contraction could not be demonstrated, there appeared to be an increasing trend after TMET. These findings resembled the pattern of JZ contractions observed in our study, where stimulation of JZ contractions was caused by the application of a tenaculum to the cervix (Lesny et al., 1999a). The negative effect of increased JZ contractility on pregnancy rate has been documented in an elegant study (Fanchin et al., 1998
) and is now well accepted. Thus, the increased JZ contractility in all our patients after insertion of a Towako needle must be treated with great caution, as one would expect a rather quiescent endometrium at the time of embryo transfer. Three patients achieved a clinical pregnancy but, due to the small numbers involved in this study, no conclusion can be made regarding the frequency of contractions and success of the cycle. The occurrence of an ectopic pregnancy despite the transfer of the embryos in the midcavity is remarkable and has been reported previously (Lesny et al., 1999b
); this further demonstrates that JZ contractions are able to relocate embryos from the uterine cavity.
Based on this study, TMET should be avoided if possible. However, the main indications for TMET are cervical factors such as cervical stenosis or an acute angle of the cervical canal and in these cases the alternative would be a difficult transcervical embryo transfer, possibly after cervical dilatation. It has been shown previously that these difficult embryo transfers are associated with an increase in JZ contractions (Lesny et al., 1998). These two methods of embryo transfer have been compared in one study, but no advantage in either method could be found (Groutz et al., 1997
). However, this study was performed on a small number of patients and the indication to either method was not only a difficult transcervical embryo transfer, but also multiple implantation failure in previous cycles.
An alternative to dilatation directly prior to embryo transfer could be cervical dilatation after pituitary suppression prior to gonadotrophin stimulation, which would facilitate transcervical embryo transfer. This method has been described by the Bourn Hall group and resulted in a decreased incidence of difficult embryo transfer (Abusheikha et al., 1999).
The question, `Which is the most successful method of embryo transfer in cases of complicating cervical factors?' remains unanswered at present. TMET seems an attractive alternative, although the increase in JZ contractions, as demonstrated in our study, forms a theoretical objection. Although this study has shown a significant physical response to TMET, we are reluctant to draw any conclusions regarding the effect of this response on the pregnancy rate, due to the small number of patients involved. We therefore suggest a large prospective study to establish the most effective method of embryo transfer for this small, but important, subgroup of patients.
![]() |
Acknowledgements |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
![]() |
Notes |
---|
![]() |
References |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Abusheikha, N., Lass, A., Akagbosu, F. and Brinsden, P. (1999) How useful is cervical dilatation in patients with cervical stenosis who are participating in an in vitro fertilizationembryo transfer program? The Bourn Hall experience. Fertil. Steril., 72, 610612.[ISI][Medline]
Fanchin, R., Righini, C., Olivennes, F., Taylor, S., de Ziegler, D. and Frydman, R. (1998) Uterine contractions at the time of embryo transfer alter pregnancy rates after in-vitro fertilization. Hum. Reprod., 13, 19681974.[Abstract]
Groutz, A., Lessing, J.B., Wolf, Y., Azem, F., Yovel, I. and Amit, A. (1997) Comparison of transmyometrial and transcervical embryo transfer in patients with previously failed in vitro fertilizationembryo transfer cycles and/or cervical stenosis. Fertil. Steril., 67, 10731076.[ISI][Medline]
Hurley, V.A., Osborn, J.C., Leoni, M.A. and Leeton, J. (1991) Ultrasound-guided embryo transfer: a controlled trial. Fertil. Steril., 55, 559562.[ISI][Medline]
IJland, M.M., Evers, J.L., Dunselman, G.A., van Katwijk, C., Lo, C.R. and Hoogland, H.J. (1996) Endometrial wavelike movements during the menstrual cycle. Fertil. Steril., 65, 746749.[ISI][Medline]
Kato, O., Kataksuka, R and Asch, R.H. (1993) Transvaginaltransmyometrial embryo transfer: the Towako method; experience of 104 cases. Fertil. Steril., 59, 5153.[ISI][Medline]
Kovacs, G.T. (1999) What factors are important for successful embryo transfer after in-vitro fertilization? Hum. Reprod., 14, 590592.
Lesny, P., Killick, S.R., Tetlow, R.L., Robinson, J. and Maguiness, S.D. (1998) Embryo transfercan we learn anything new from the observation of junctional zone contractions? Hum. Reprod., 13, 15401546.[Abstract]
Lesny, P., Killick, S.R., Robinson, J., Raven, G. and Maguiness, S.D. (1999a) Junctional zone contractions and embryo transfer: is it safe to use a tenaculum? Hum. Reprod., 14, 23672370.
Lesny, P., Killick, S.R., Robinson, J., Titterington, J. and Maguiness, S.D. (1999b) Ectopic pregnancy after transmyomerial embryo transfer: case report. Fertil. Steril., 72, 357359.[ISI][Medline]
Noyes, N., Licciardi, F., Grifo, J., Krey, L. and Berkeley, A. (1999) In vitro fertilization outcome relative to embryo transfer difficulty: a novel approach to the forbidden cervix. Fertil. Steril., 72, 261265.[ISI][Medline]
Sharif, K., Afnan, M., Lenton, W., Bilalis, D., Hunjan, M. and Khalaf, Y. (1996) Transmyometrial embryo transfer after difficult immediate mock transcervical transfer. Fertil. Steril., 65, 10711074.[ISI][Medline]
Wood, C., McMaster, R., Rennie, G., Trounson, A. and Leeton, J. (1985) Factors influencing pregnancy rates following in vitro fertilization and embryo transfer. Fertil. Steril., 43, 245250.[ISI][Medline]
Woolcott, R. and Stanger, J. (1997) Potentially important variables identified by transvaginal ultrasound scan guided embryo transfer. Hum. Reprod., 12, 963966.[ISI][Medline]
accepted on October 19, 2001.