Human Reproduction, Vol. 14, No. 5, 1324-1327,
May 1999
© 1999 European Society of Human Reproduction and Embryology
Case Report:Prenatal sonographic diagnosis of a fetal renal mesoblastic nephroma occurring after transfer of a cryopreserved embryo
Department of Obstetrics and Gynecology, Hyogo College of Medicine, 1–1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan
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Here we report the first case of prenatally diagnosed fetal renal mesoblastic nephroma occurring after transfer of a cryopreserved embryo. A 37 year old woman, having immunological infertility, was treated by in-vitro fertilization (IVF) and embryo transfer. Following unsuccessful IVF using fresh embryos, the patient conceived after transfer of cryopreserved–thawed embryos. The chromosomal analysis identified a normal karyotype at 16 weeks' gestation when amniocentesis was performed. The pregnancy course was uneventful until 28 weeks' gestation when polyhydramnios associated with fetal renal tumour was detected using ultrasonography. A male infant weighing 2564 g was born via Caesarean section at 34 weeks' gestation. A left nephrectomy was performed 5 days after delivery and the tumour was identified histologically as a mesoblastic nephroma. The postoperative course was uncomplicated to this point.
Key words: : embryo cryopreservation/in-vitro fertilization/prenatal diagnosis/renal mesoblastic nephroma
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Introduction |
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One and a half decades have passed since the first human pregnancy through cryopreservation, thawing and transfer of an embryo was reported (Trounson and Mohr, 1983
). Embryo cryopreservation is now routinely used in in-vitro fertilization (IVF) and embryo transfer programmes. The aim of cryopreservation of embryos in IVF–embryo transfer includes storage for future use, which reduces the incidence of multiple pregnancies by reducing the number of fresh embryos transferred and postpones fresh embryo transfer to reduce the risk of developing ovarian hyperstimulation syndrome. Although good clinical pregnancy rates following transfer of cryopreserved–thawed embryos have been reported (Lornage et al., 1990; Irianni et al., 1992), there are few studies which include a follow-up of the pregnancy and children conceived through cryopreserved embryos.
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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A 34 year old woman with a 5 year history of primary infertility was referred to our hospital for further investigation and treatment in May 1990. She had been diagnosed as having unexplained infertility and was treated with several cycles of unsuccessful intrauterine insemination (IUI) by a local gynaecologist. Her menarche had been at the age of 12 years and her menstrual cycle was regular. Physical and endocrinological examinations were normal. Hysterosalpingography demonstrated a normal shape of uterine cavity and bilateral tubal patency. Immunological infertility was confirmed when sperm immobilizing antibodies in the patient's serum were detected using a semiquantitative sperm immobilization test (SIT) (Isojima et al., 1968
) and a quantitative SIT (Isojima and Koyama, 1974). The SI50 (50% sperm immobilization units) titre in the patient's serum was calculated once a month for 3 consecutive months and the values were 75.0, 72.9 and 78.0 respectively, indicating she had a high titre of sperm immobilizing antibody (Koyama et al., 1988; Kobayashi et al., 1990). Her partner's semen characteristics were normal according to criteria established by the World Health Organization (1992). Laparoscopy and a dye test demonstrated a normal pelvis with patent tubes. The peritoneal sperm recovery test carried out under laparoscopy was negative, indicating that sperm migration was hindered at the level of the Fallopian tubes by the complement-dependent sperm immobilizing antibody (Shibahara et al., 1995), which indicated that IUI would not be useful for treating this patient's infertility.
IVF–embryo 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 4–6 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 IVF–embryo 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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The incidence of major congenital abnormalities in IVF pregnancies is not considered to be higher than that in spontaneously conceived pregnancies (Steptoe et al., 1986
). However, little information is available regarding the birth characteristics, incidence of congenital malformations and perinatal mortality of the babies resulting from transfer of cryopreserved embryos. The first report (Frydman et al., 1989) described the obstetric outcome in 50 pregnancies resulting from the transfer of human embryos that had been cryopreserved for up to 2 years, and one pregnancy was terminated at 22 weeks because a major fetal limb malformation without chromosomal abnormality was detected. The same malformation was also reported by Trounson (Trounson 1986) after embryo cryopreservation. So far, there have been no other reports of such major fetal limb malformation after transfer of cryopreserved embryos. However, Wada et al. (Wada et al. 1994) reported that the incidence of major congenital malformations in the cryopreserved group (1%) was significantly lower than that in the IVF group (3%). The first incidence of fetal malformation in the cryopreserved group was gross hydrocephalus and the second was cleft palate. They speculated that the reason for the reduced incidence of congenital malformations in the cryopreserved group could be related to the loss of some embryos during the cryopreservation–thaw process, as it has been reported that about 20–30% of embryos do not survive the freeze–thaw process (Sathanandan et al., 1991; Wada et al., 1993). The rates of minor and major congenital anomalies have been reported to be similar to those in normally conceived children (Sutcliffe et al. 1995). They identified Down's syndrome, Beckwith–Wiedemann syndrome and hypophosphataemic rickets as major congenital malformations in the cryopreserved embryo group. Bonduelle et al. (Bonduelle et al. 1998) reported that there was no higher incidence of congenital malformations in children born after replacement of cryopreserved embryos obtained after intracytoplasmic sperm injection (ICSI) than with those in which fresh embryos were used. Based on their clinical investigations, they concluded that the cryopreservation process did not adversely affect the progress of embryo development beyond implantation. Recent reviewers also supported their conclusions (Wood, 1997; Mandelbaum et al., 1998).
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 cryopreserved–thawed 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 cryopreserved–thawed 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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1 To whom correspondence should be addressed
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Submitted on October 5, 1998; accepted on January 19, 1999.
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