The Egyptian IVF-ET Center, 3 Road 161 Hadayek El-Maadi, Cairo 11431, Egypt
1 To whom correspondence should be addressed. or Email: ivf{at}link.net
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Abstract |
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Key words: embryo transfer technique/ICSI/implantation rate/IVF/pregnancy rate
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Introduction |
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The aim of this work is to modify the embryo transfer technique to prevent expulsion of the embryos from the uterine cavity after embryo transfer by applying gentle mechanical pressure on the portiovaginalis of the cervix using the vaginal speculum.
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Materials and methods |
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Design and procedures
The pituitary was down-regulated using long-protocol GnRH agonist analogue. It was given in the form of subcutaneous tripterolin 0.1 mg/day (decapeptyl; Ferring, GmbH, Kiel, Germany) starting in the late luteal phase until HCG injection. After pituitary down-regulation was confirmed by estradiol level <50 pg/ml, ovarian stimulation was started by giving HMG 150300 IU/day (Menogone; Ferring) for 7 days, and then the dose was modified according to the response. HCG (10 000 IU) (Pregnyl; Nile Co., Cairo, Egypt) was given intramuscularly when the leading three follicles reached 18 mm in mean diameter. Oocyte pick-up was carried out 36 h after HCG injection through the ultrasonic transvaginal route. Oocyte injection and embryo culture was as described previously (Mansour et al., 1996).
Embryo transfer was performed 4872 h after oocyte pick-up by the same gynecologist (R.M.) for this study. Eligible patients were randomly allocated to the study or control group using sealed dark envelopes prepared by the embryologist. Details of the recruitment and randomization of patients are given in the flow diagram (Figure 1). In both groups, the embryo transfer was done at the lithotomy position. The previously taken ultrasound picture of the uterus and dummy embryo transfer (Mansour et al., 1990) were revised to get an idea of the length and direction of the uterine cavity. After visualizing the portiovaginalis of the cervix using Cusco's speculum, the cervix was cleaned using sterile gauze and tissue culture media (DPBS or Ham's F10). The cervical mucus was aspirated gently and repeatedly at the external cervical os using a 1 ml syringe. A dummy embryo transfer was done using a sterile Wallace catheter (1816 N, HG; Wallace Ltd, Colchester, UK) to make sure that it could be introduced easily through the internal os. If it could not be introduced, a more rigid catheter (Cook, Queensland, Australia) was tried. After performing the dummy embryo transfer, the embryos were loaded into a new catheter, either Wallace or Cook according to the dummy embryo transfer, as follows. The embryo transfer catheter was rinsed then filled with tissue culture medium. About 1020 ml tissue culture medium was aspirated, then the embryos (up to three) were aspirated in
1020 ml tissue culture medium so that the embryos would be away from the tip of the catheter. If the Wallace catheter was used, the soft internal catheter, protruding from the external rigid sheath, was introduced gently through the internal cervical os and stopped
1 cm below the fundus. The outer rigid sheath was stopped just at the internal cervical os and not pushed beyond it. If the Cook catheter was used, the tip of the inner catheter was positioned flush with the external sheath until it passed the internal cervical os, then the internal sheath one was advanced 2 cm into the uterine cavity. The uterine cavity length and direction was determined previously by ultrasonography and a dummy embryo transfer.
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Data are presented as mean±standard deviation. Different outcome measures were compared using Student's t-test or 2-test where appropriate. P-values <0.05 were considered to be significant. Statistics were done using Arcus Quickstat (version I).
The sample size of 654 women provides 80% power and a two-sided significance level of 0.05 to test whether the modified embryo transfer technique is equivalent or even superior to the control group in an IVF/embryo transfer program. This sample size has adequate power to detect a difference of 10% in pregnancy rate/treated cycle.
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Results |
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Discussion |
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The idea behind this study is very simple. It depends on applying gentle pressure on the cervical canal at the time of the reflex uterine contractions that result from passing the embryo transfer catheter through the internal os, because these contractions may lead to the extrusion of the embryos after embryo transfer. By closing the vaginal speculum, light pressure from the two valves of the speculum is applied on the portiovaginalis of the cervix. This results in gently pressing the anterior and posterior lips of the cervix together, possibly obstructing the cervical canal up to the internal os. This simple technique significantly improved the pregnancy rate when compared with the control group.
The study does not suggest a mechanism by which the higher pregnancy rate was obtained in the study group. Only a methodological approach looking at the outcome of mock embryo transfer demonstrating displacement of markers following occlusion or no occlusion of the cervix might allow an explanation. The improvement in the results may have resulted from phenomena not directly linked to attempting to occlude the cervix, such as the increase in wait time before ejecting the embryos.
It was reasonably tolerable for the patients to have the speculum left in place for an average of 6.5 min after embryo transfer. The time taken to perform embryo transfer in the study group was only an average of 8.5 min longer than in the control group, and did not make a difference to the patient or the doctor.
In conclusion, this is a simple modification of the embryo transfer technique that significantly improved the implantation and clinical pregnancy rates. Since the completion of the study, this modified embryo transfer technique has been a routine procedure for all cases. The method is to apply gentle mechanical pressure on the portiovaginalis of the cervix using the vaginal speculum before and after ejecting the embryos into the uterine cavity to prevent their extrusion. Further experimental studies are being undertaken using dummy embryo transfer to explain the mechanism of action of this technique.
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References |
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Submitted on November 13, 2003; accepted on September 29, 2004.
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