Department of Obstetrics and Gynecology, Hyogo College of Medicine, 11 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan
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Abstract |
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Key words: : embryo cryopreservation/in-vitro fertilization/prenatal diagnosis/renal mesoblastic nephroma
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Introduction |
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Here we report a case of fetal renal mesoblastic nephroma, occurring after a transfer of cryopreserved embryos, that was prenatally diagnosed using ultrasonography at 28 weeks' gestation. There have been some reports showing fetal congenital malformations resulting from transfer of cryopreserved embryos (Trounson, 1986; Frydman et al., 1989
; Wada et al., 1994
; Sutcliffe et al., 1995
). This is the first demonstration of congenital mesoblastic nephroma resulting from a transfer of IVF and cryopreserved embryos.
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Case report |
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IVFembryo transfer was performed for this patient to overcome the possible causes of infertility associated with sperm immobilizing antibodies (Shibahara et al., 1996). Briefly, the patient was stimulated using a combination of a gonadotrophin-releasing hormone (GnRH) agonist starting in the luteal phase (suppression protocol) followed by gonadotrophins as we previously reported (Shibahara et al., 1996
, 1997a
,Shibahara et al., b
, 1998
). Following a 46 h preincubation time, oocytes collected transvaginally were washed thoroughly in B2 medium (Ménézo, Paris, France) to avoid contamination of sperm immobilizing antibodies secreted in the follicular fluid before insemination. Insemination was carried out with 50x103/ml motile spermatozoa, harvested using the swim-up method. Fertilization was assessed by the presence of two distinct pronuclei (PN) at ~18 h after insemination. Cleavage was assessed at 40 h after retrieval and transfer of a maximum of three embryos was performed at 48 h post retrieval.
Following an unsuccessful initial IVFembryo transfer treatment, 11 oocytes were collected and inseminated in a second treatment attempt. Ten oocytes cleaved and three 2- to 4-cell embryos with the highest morphology score were selected for transfer to the patient on the second day after oocyte retrieval. Surplus embryos were cryopreserved following the modified method as reported by Katayama et al. (Katayama et al., 1990) using a slow-freezing protocol with 1,2-propanediol (PROH) (Sigma, St Louis, MO, USA).
Following the second unsuccessful embryo transfer with fresh embryos, a further transfer using four frozen embryos was attempted in a spontaneous cycle. All the four thawed embryos transferred had less than 10% fragmentation. A urinary pregnancy test was positive 14 days after the transfer of four frozen and thawed embryos and a single pregnancy was achieved. After consultation, amniocentesis was performed at 16 weeks' gestation as the patient was 37 years old. Chromosomal analysis identified a normal karyotype. No pathological findings were detected by sonography at 20 weeks' gestation. The pregnancy course was uneventful until the end of the second trimester when the patient was found to have polyhydroamnios after sonography at 28 weeks' gestation. She had no complications that might cause hydramnios, including diabetes mellitus, pre-eclampsia or Rh incompatibility. At the time of admission, a sonographic re-examination was carried out and a well-encapsulated hetero-echogenic abdominal mass measuring 6x6x5 cm in size was identified (Figure 1). This tumour arose from the left renal fossa and compressed the involved kidney. The right kidney was normal in size and shape. A presumptive diagnosis of congenital mesoblastic nephroma complicated by polyhydramnios was made. Fetal well-being was serially monitored by non-stress tests and all showed a reactive response. The patient received weekly therapeutic amniocentesis to relieve her cardiopulmonary discomfort. At 34 weeks' gestation, the renal tumour increased and reached 7x6x6 cm in size. A Caesarean section was performed and a 2564 g male infant with Apgar scores of 6 at 1 min and 7 at 5 min was delivered in November 1992. The baby did well and did not develop respiratory distress syndrome. Following stabilization and a serial preoperative evaluation of the baby, a left nephrectomy was performed 5 days after the delivery. Histological examination confirmed mesoblastic nephroma (Figure 2
). The postoperative course was uneventful.
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Discussion |
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The prenatal diagnosis of fetal tumours has an important implication for maternal and fetal well-being, as well as neonatal management. The most commonly diagnosed fetal tumours are cervical teratoma, hepatic tumours, neuroblastoma, mesoblastic nephroma, and sacrococcygeal teratoma (Garmel et al., 1994). Since the first case of mesoblastic nephroma detected prenatally by ultrasound, was described (Ehman et al. 1983
) other authors have also detected these tumours prenatally with ultrasound imaging (Romano, 1984
; Guilian, 1984
; Geirsson et al., 1985
; Howey et al., 1985
; Walter and McGahan, 1985
; Yamboa et al., 1986
; Apuzzio et al., 1986
; Burtner and Willard, 1988
; Kuo et al., 1989
; Ohmichi et al., 1989
; Rempen et al., 1992
; Matsumura et al., 1993
; Fung et al., 1995
; Liu et al., 1996
). However, our case is the first demonstration of a congenital mesoblastic nephroma occurring after transfer of cryopreservedthawed embryos. Sonographic identification was based on polyhydramnios and a unilateral, well-capsulated solid renal mass. Polyhydramnios associated with mesoblastic nephroma has been described in most of the published case reports. However, the mechanism of the polyhydramnios is not clear yet. There are some indications that impaired gastrointestinal function due to a mass effect of the tumour (Geirsson et al., 1985
; Howey et al., 1985
) and an increase in renal blood flow or impaired renal concentrating ability (Geirsson et al., 1985
) with subsequent increase in fetal urine production (Ohmichi et al., 1989
) might be the cause. Recently, the calcium level has been evaluated (Ehman et al. 1983
) and the conclusion made that hypercalcaemia might be the mechanism underlying polyhydramnios in cases of congenital mesoblastic nephroma. In our case, however, hypercalcaemia was not identified during the course of this study.
Because of the benign nature of most mesoblastic nephromas, it is recommended to allow the pregnancy to go to term (Guilian, 1984). In our case, the patient received weekly therapeutic amniocentesis to relieve her cardiopulmonary discomfort. To avoid a long stressful follow-up as well as severe discomfort, a Caesarean section was undertaken at 34 weeks' gestation. A total nephrectomy was performed and the postoperative course was uneventful. The development of the baby has been normal to this point.
We conclude that antenatal assessment of fetal congenital tumours is very important in the cases of polyhydramnios. It has been suggested that cryopreservation does not influence the progress of human embryos beyond implantation; however, careful assessment of fetal development, careful perinatal examinations and a long follow-up of children are still required after transfer of cryopreservedthawed embryos because Dulioust et al. (Dulioust et al. 1995) found a significant difference in morphophysiological and behavioural features of mice in a long-term study comparing cryopreserved and control embryos.
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Notes |
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References |
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Submitted on October 5, 1998; accepted on January 19, 1999.