1 IVF Centre, Maternity Hospital, Kuwait and 2 Department of Obstetrics & Gynaecology, St Bartholomew's & The Royal London School of Medicine & Dentistry, Royal London Hospital, London E1 1BB, UK
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Abstract |
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Key words: ectopic/embryo transfer/implantation/pregnancy/uterus
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Introduction |
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Materials and methods |
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The details of the ovarian stimulation regimen have been previously described (Egbase et al., 1996). Transvaginal oocyte retrieval was performed 3536 h after the human chorionic gonadotrophin (HCG) trigger (10 000 IU) injection. Intra-operative antibiotics (Metronidazole 1 g i.v. and cephatriaxone 2 g i.v.) were administered during oocyte retrieval (Egbase et al., 1999
). The oocytes were subjected to conventional IVF or ICSI according to the cause of infertility (Egbase et al., 1997
). Transcervical intrauterine transfer of up to three embryos in 1525 µl of culture medium (IVF-20; IVF Science Scandinavia, Vitrolife Productions AB, Gothenburg, Sweden) flanked with air bubbles was performed in all patients ~48 h after oocyte retrieval using an EdwardsWallace embryo replacement catheter (SimCare, Lancing, W Sussex, UK). This catheter is marked with 1 cm graduations allowing the clinician (P.E.) to advance it to 5 mm from the uterine fundus based on the previously determined length of the uterine cavity from the external cervical os. Thus, the embryos were routinely deposited 5 mm from the fundus irrespective of the length of the uterine cavity. When there was difficulty in passing the catheter, the cervix was held with a tenaculum and a Wallace malleable stylet with an outer sheath (Simcare, Lansing, West Sussex, UK) was carefully introduced through the cervical canal. Once it passed the internal cervical os, the stylet was removed and the inner Teflon of the EdwardsWallace embryo replacement catheter loaded with embryos was introduced through the outer sheath already in place in the cervical canal. Again, the catheter was advanced to 5 mm from the uterine fundus before depositing the embryos. All embryo transfer procedures were performed in the modified lithotomy position and patients with anteverted uteri were routinely required to have a half-full bladder prior to the embryo transfer (Lewin et al., 1997
).
Implantation and clinical pregnancy rates were both determined by the presence of a regular gestation sac with embryonic/fetal heart activity at pelvic ultrasonography performed 45 weeks after embryo transfer, while the ectopic pregnancy rate was calculated per reported pregnancies, i.e. clinical and ectopic pregnancies.
Statistical analysis
Relevant differences observed between groups were subjected to the 2-test to determine their statistical significance (P < 0.0005).
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Results |
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Discussion |
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It is not clear if there is such an optimum site within the uterine cavity and this probably explains why clinicians deposit embryos following IVF at various sites within the uterine cavity. Waterstone et al. (1991) suggested that deposition of embryos in the lower uterine cavity resulted in a much better pregnancy rate while Yovich et al. (1985) and Nazari et al. (1993) associated a higher incidence of ectopic pregnancies following IVFembryo transfer with placement of embryos close to the uterine fundus. On the contrary, Knutzen et al. (1992), using a radio-opaque dye bolus to mimic the fate of embryos in mock embryo transfer, showed that 68% of the bolus was retained in position when placed at 5 mm to the fundus. In a recent survey (Kovacs, 1999), clinicians performing transcervical embryo transfer rated not touching the fundus as the third most important factor in the technique of embryo transfer but there was no mention of the optimum site within the uterine cavity at which the clinicians would routinely prefer to deposit the embryos. Wood et al. (2000) amongst others suggest that ultrasound-aided embryo transfer was superior to a blind attempt to put the embryo near the fundus.
In this study and as is the routine practice in our unit, the embryos are routinely placed ~5 mm from the fundus, a distance determined from the previous measurement of the uterine cavity at the mock embryo transfer. The length of the normal uterine cavity, including the cervical canal, is considered to be not <7 cm and is usually 7.58 cm (Tindall, 1987). The long protocol administration of GnRH agonist for 1014 days is unlikely significantly to influence the length of the uterine cavity. The implantation and clinical pregnancy rates were similar whether the uterine cavity was small in size (<7 cm), normal size (79 cm) or large (>9 cm) when the embryos were routinely placed 5 mm from the fundus. It is not known if varying the distance from the fundus in relation to the length of the uterine cavity would have an impact, although there is evidence that pinopodes that characterize endometrial receptivity are probably present 2 cm down from the fundus (Nikas et al., 1995
).
The incidence of ectopic pregnancy per reported pregnancy was 14.9% (7/47) when the uterine cavity was small, 1.8% (5/276) when the uterine cavity was normal size and 0/28 in patients with large uterine cavities. The statistically significant higher ectopic pregnancy rate seen in patients with small uterine cavity (external cervical os to the uterine fundus <7 cm) compared with patients with normal uterine cavity lengths suggests that ectopic pregnancy may be related to the size of the uterine cavity but is not necessarily exclusive of the clinical technique of placing the embryos 5 mm from the fundus in IVFembryo transfer as previously suggested (Yovich et al., 1985; Nazari et al., 1993
). This is the first report in the medical literature implicating the size of the uterine cavity in the aetiology of ectopic pregnancy. The incidence of tubal infertility was similar in the three groups of patients (Table II
) and amongst the patients with ectopic pregnancy in group 1 (2/7) and group 2 (1/5). In addition to tubal factor infertility (Strandell et al., 1999
), the fundal distance between the tubal ostia, likely to be related to the uterine size, could be a critical factor in the aetiology of ectopic pregnancies in IVF/ICSIembryo transfer. Also it is unclear if the intensity of waves of uterine contractions at the time of embryo transfer (Fanchin et al., 1998
) is related to size of the uterus or if such uterine activity is more likely to predispose to tubal displacement of embryos in patients with small uteri. In a series of mock embryo transfers, Knutzen et al. (1992) demonstrated complete, partial or temporary displacement of dye used to mimic embryos to the Fallopian tubes in 38.2% of cases associated with uterine contraction as the mock embryo transfer catheter was removed from the uterus. Although difficult embryo transfer probably increases the odds ratio for ectopic pregnancy in IVFembryo transfer (Lesny et al., 1999
), the incidence of difficult embryo transfer in this study was similar in relation to both the length and position of the uteri. Further studies are required to examine the role of the size of the uterine cavity and any related mechanisms in the aetiology of ectopic pregnancies in IVF/ICSIembryo transfer and possibly in spontaneous conception. Patients can be reassured that the position of the uterus (anterveted or retroverted) does not adversely affect implantation or clinical pregnancy rates, confirming the earlier findings in a smaller group of patients (Agarwal et al., 1994
).
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Notes |
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References |
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Submitted on February 7, 2000; accepted on June 13, 2000.