1 Department of Obstetrics and Gynecology, 2 The Sara Racine IVF Unit, Lis Maternity Hospital, and 3 The Pathology Institute, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Israel
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Abstract |
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Key words: assisted reproductive technology/embryo transfer/ICSI/perinatal outcome/placental pathology
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Introduction |
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The purpose of the study was to make a prospective, random and blind comparison of the morphological and histopathological features of placentae of term, singleton, pregnancies obtained by ART [in-vitro fertilization (IVF) and embryo transfer and ICSI and embryo transfer] with those of matched pregnancies, conceived spontaneously.
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Materials and methods |
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Placental investigation included a detailed morphological evaluation that encompassed: placental shape, weight and thickness through a mid-placental section, and calculation of placenta:fetus weight ratio. Umbilical length and thickness were recorded, and umbilical cord insertion was divided into two categories: (i) normal, which comprised central and lateral cord insertion, and (ii) abnormal, which constituted marginal (<2 cm from the placental margin) and velamentous umbilical cord insertion (McLennan, 1968; Benirschke and Kaufmann, 1990
; Altshuler, 1997
). Following immediate macroscopic evaluation, the placentae were immersed in buffered 10% neutral formalin, and detailed microscopic evaluation was performed on several paraffin sections of each placenta, umbilical cord and membranes. Samples were obtained from tissues of both normal and abnormal appearance.
The histological examination embodied a careful evaluation of the trophoblast, decidua and blood vessels. Pathological abnormalities included: alteration of blood vessels (i.e. muscular hypertrophy of the media and fibrinoid changes in the vessel wall), inflammatory reactions (i.e. chorioamnionitis, villitis, villitis of unknown aetiology and funisitis), increased number of syncytial knots (>30%); changes in villous histology (i.e. thrombosis, fibrosis and haemorrhage); infarctions (at least two infarcts of 2 cm in diameter) and intervillous fibrin deposition (Benirschke, 1960
; Benirschke and Kaufmann, 1990
; Altshuler, 1997
).
Statistical analysis was performed by 2 and Fisher exact tests. The Student t-test and the one-way analysis of variance (ANOVA) were used to compare group means. Significance was assumed at P < 0.05.
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Results |
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Discussion |
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In comparison with our study, previous studies were either non-controlled (Englert et al., 1987) or not randomly and blindly performed (Englert et al., 1987
; Jauniaux et al., 1990
; Gavriil et al., 1993
; Williams and Jeffery, 1994
). Furthermore, in none of these studies (Englert et al., 1987
; Jauniaux et al., 1990
; Gavriil et al., 1993
) was the histopathological evaluation performed by the same pathologist, and placentae of pregnancies obtained by ICSI and embryo transfer were not investigated.
In accordance with other authors (Englert et al., 1987; Jauniaux et al., 1990
; Gavriil et al., 1993
), we observed a higher incidence of abnormal umbilical cord insertion in placentae of ART-conceived pregnancies.
These findings suggest that term pregnancies obtained by ART may be at increased risk for the adverse consequences associated with abnormal cord insertion, such as vasa praevia, fetal haemorrhage and fetal anomalies (McLennan, 1968; Burton and Saunders, 1988
; Benirschke and Kaufmann, 1990
). Although in this study both groups had a similar perinatal outcome, a larger study is required to detect significant differences in perinatal variables. Likewise, these results may support the theory of abnormal blastocystendometrial orientation in ART-obtained pregnancies, as suggested by other authors (Englert et al., 1987
; Jauniaux et al., 1990
; Gavriil et al., 1993
).
Abnormal blastocystendometrial orientation may be a result of embryo injection into the endometrium during embryo transfer. However, even a properly performed embryo transfer results in earlier placement of the embryo in the uterine cavity by 2 days. Proper attachment and implantation depends on an exact sequence of molecular events (Sueoka et al., 1997) that occur in the embryo and endometrium. The earlier presence of the embryo in the uterus may disturb the process of polar trophoblast differentiation, and proper blastocystendometrial orientation.
Nevertheless, the similar incidence of placental malformation in both groups does not support superficial placentation in ART pregnancies, as suggested by others (Englert et al., 1987; Jauniaux et al., 1990
; Gavriil et al., 1993
).
In both groups, the mean placental weight was within normal limits (<600 g) (Altshuler, 1997). However, there was an apparent trend towards a higher mean placental weight and placental:fetal weight ratio in the study group. Since these differences were neither related to the ART procedure, nor to the infertility aetiology, we may postulate that common factors, such as the ovulation induction protocols and multiple embryo transfer used during ART, may account for these differences. One possible explanation may be that endometrial hyperstimulation caused by the high oestrogen and progesterone levels, coupled with multiple embryo transfer, may induce more extensive pregnancy-related endometrial alterations (histologically and biochemically). This may result in an increased placental:fetal weight ratio and placental thickness, provided a singleton pregnancy results. Furthermore, this professed enhanced stimulation of the endometrium may improve the implantation of a singleton pregnancy, and the prospect of reaching term may be better. This assumption is supported by the observed similar pregnancy complication, perinatal outcome and placental histopathological features in these randomly selected matched groups.
Interestingly, in a recent study, Ribbert et al. found higher human chorionic gonadotrophin (HCG) levels in pregnancies obtained through IVF (Ribbert et al., 1996). Since the levels of HCG may reflect placental mass, our finding of apparently increased placental weight in these pregnancies may explain the elevated HCG concentrations. According to our results, neither the specific ART method employed, nor the infertility aetiology had any effect on placental morphological or histopathological features, or on maternal or neonatal outcome. Therefore, it seems that neither infertility per se (Tuck et al., 1988
; Ghazi et al., 1991
; Li et al., 1991
; Williams et al., 1991
) nor ART itself (Petersen et al., 1995
) contribute to the adverse outcome in term, singleton, ART-obtained pregnancies through impaired placentation (Doyle et al., 1992
; Wang et al., 1994
; FIVNAT, 1995
; Tanbo and Abyholm 1996
).
Furthermore, according to our study, if maternal age and parity is controlled, the outcome of these pregnancies is similar to spontaneously conceived pregnancies, although this should be confirmed in a larger investigation.
In conclusion, we found that placentae of term ART-conceived pregnancies are thicker, seem to be heavier and to have a higher incidence of abnormal cord insertion than placentae of spontaneously conceived pregnancies. Since these differences were not related to the specific ART method employed, or infertility factor, our findings suggest that these differences may be related to multiple embryo transfer, and/or to the non-physiological hormonal milieu resulting from ovulation induction protocols used in ART.
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Notes |
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References |
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Submitted on June 24, 1998; accepted on December 21, 1998.