Clínica e Centro de Pesquisa em Reprodução Humana `Roger Abdelmassih', Rua Maestro Elias Lobo, 805 01433000, São Paulo, Brazil
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Abstract |
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Key words: blastocyst/heterotopic pregnancy/ICSI/IVF/ovarian pregnancy
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Introduction |
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The ultrasonographic technologies, especially transvaginal probes, have facilitated earlier diagnosis of HP and EP. Laparoscopy has become the ideal form of diagnostic confirmation of EP and HP and a safe surgical resolution procedure (Pistofidis et al., 1995; Wang et al., 1998
). However, the diagnosis and therapy of EP and HP following ovarian hyperstimulation are complicated by the co-existence of multiple luteal cysts in the hyperstimulated ovaries and an intrauterine pregnancy (IUP). This is especially true for OHP.
The aim of this report is to highlight the possibility of an association between blastocyst transfer and ovarian pregnancy, presenting two successfully treated ovarian pregnancies (a primary ectopic and a heterotopic) in infertile patients who underwent intracytoplasmic sperm injection (ICSI), prolonged in-vitro culture and embryo transfer at blastocyst stage.
Our cases differ from others previously reported in that both implantations occurred on the ovaries after ICSI and blastocyst transfer in two patients who otherwise had no predisposing factors for ectopic implantation.
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Case report |
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Discussion |
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There were two expanded blastocysts transferred to each patient and an ovarian HP and ovarian EP occurred. For such conditions to occur, at least one of the transferred embryos must find its way from the uterine cavity to the ectopic location either during the procedure or shortly thereafter (Tal et al., 1996). This is especially true in the cases presented here as the embryos were transferred at the expanded blastocyst stage only a few hours before hatching and attaching to the recipients.
In our ovarian ectopic cases there were no predisposing factors for HP or EP. The volume of transfer was small. There was no pelvic pathology, a predisposing factor for EP (Verhulst et al., 1993), and only two embryos were transferred to each patient (Tummon et al., 1994
).
On day 27 and day 40 after transfer in the cases of OEP and OHP respectively, the patients reported to our centre presenting moderate to severe abdominal pain, abdominal distension and peritoneal irritation signs. Both OHP and ovarian OEP are frequently asymptomatic and clinical presentation is highly variable.
The most common symptom is abdominal pain. Vaginal bleeding is a rare sign in OHP cases, probably due to the co-existence of the IUP. During a USG examination, an OHP is easily misdiagnosed with a luteal cyst, especially because the concurrent presence of an IUP is reassuring.
In the cases presented here, echographic diagnosis was clearly complicated by preceding ovarian stimulation that resulted in the formation of multiple `corpora lutea', making the identification of the ectopic sac extremely difficult. The association of HP or EP with hyperstimulated ovaries is a factor that may retard this diagnosis, even in those cases where an ultrasound scan is performed early (Wang et al., 1998). De Muylder et al. reported that presurgical USG diagnosis was not conclusive in a case of OHP (De Muylder et al., 1994
). In our cases ultrasonographic findings, such as moderate quantity of echogenic fluid in the pouch of Douglas and hypoechogenic masses on the left uterine adnexa, and the values of serum ß-HCG on day 12 after transfer, led us to suspect ectopic implantations.
A diagnostic laparoscopy was necessary, which was also therapeutic, for the definitive diagnosis in both cases. The excellent results of the procedures allowed us to preserve the ovaries. In a recently reported case of primary ovarian pregnancy there was also preservation of the ovary during the laparoscopy (Einenkel et al., 2000), although oophorectomy was performed in most previously reported cases (De Muylder et al., 1994
; Ranieri et al., 1994
).
The IUP outcome until term is ~66% of all the HP cases including tubal, cervical, cornual, abdominal and ovarian implantations. Early use of diagnostic laparoscopy has also been useful in improving the IUP outcome of HP cases (Pistofidis et al., 1995).
Non-surgical procedures have also been reported in the literature, especially selective embryo reduction using KCl injection by transvaginal sonography guidance to resolve tubal and cervical HP (Baker et al., 1997; Honey et al., 1999
). This approach needs a perfect identification of the boundaries of the ectopic gestation so it may be difficult to apply in cases of ovarian pregnancies.
One of the most important aspects of this report is that, in both cases, ectopic implantation of embryos on the ovaries occurred after blastocyst transfer. Prolonged in-vitro culture of pre-implantation human embryos and blastocyst-stage transfer is only recently gaining more advocation and popularity to maintain or increase pregnancy rate and to decrease multiple pregnancies. However, possible complications associated with this approach are not yet studied or determined. Until now there was only one publication where a significantly higher incidence of monozygotic twin gestations was observed after blastocyst transfer in comparison with day 2 and day 3 embryo transfer, indicating new or altered pathological consequences of this technique (da Costa et al., 2001). The facts that (i) from 129 pregnancies after blastocyst transfer the two ectopic implantations were both on the ovary, while from 814 pregnancies after day 2 and day 3 transfer no ovarian implantation or heterotopic pregnancies occurred, and (ii) none of the two patients with ovarian ectopic/heterotopic pregnancies had any predisposing factors, while 12 of the 14 ectopic (tubal) pregnancies of day 2 and day 3 embryo transfer had predisposing tubal factors, indicate the possibility that blastocyst-stage embryo transfer may be associated with different complications.
These outcomes raise the possibility that prolonged embryo culture and blastocyst transfer may be associated with a somewhat higher risk of pathological outcome. By highlighting this experience we seek to raise awareness of this possibility, which may be confirmed or refuted by larger scale studies.
Further improvement in the clinical outcome of these cases will mainly come from increased clinician awareness and early invasive diagnostic techniques.
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Notes |
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References |
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da Costa, A.L.E., Abdelmassih, S., Oliveira, F.G. et al. (2001) Monozygotic twins and transfer at the blastocyst stage after ICSI. Hum. Reprod., 16, 333336.
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Submitted on April 17, 2001; accepted on June 24, 2001.