Children born after cryopreservation of embryos or oocytes: a systematic review of outcome data.

BACKGROUND: An estimated 3.5 million children have been born to date using assisted reproduction technologies. We reviewed the data in order to evaluate current knowledge of medical outcome for IVF/ICSI children born after cryopreservation, slow freezing and vitrification of early cleavage stage embryos, blastocysts and oocytes. METHODS: A systematic review was performed. We searched the PubMed, Cochrane and Embase databases from 1984 to September 2008. Inclusion criteria for slow freezing of early cleavage stage embryos were controlled studies reporting perinatal or child outcomes. For slow freezing and vitrification of blastocysts and oocytes, and vitrification of early cleavage stage embryos, case reports on perinatal or child outcomes were also included. Three reviewers independently read and evaluated all selected studies. RESULTS: For early cleavage embryos, data from controlled studies indicated a better or at least as good obstetric outcome, measured as preterm birth and low birthweight for children born after cryopreservation, as compared with children born after fresh cycles. Most studies found comparable malformation rates between frozen and fresh IVF/ICSI. For slow freezing of blastocysts and for vitrification of early cleavage stage embryos, blastocysts and oocytes, limited neonatal data was reported. We found no long-term child follow-up data for any cryopreservation technique. CONCLUSION: Data concerning infant outcome after slow freezing of embryos was reassuring. Properly controlled follow-up studies of neonatal outcome are needed after slow freezing of blastocysts and after vitrification of early cleavage stage embryos, blastocysts and oocytes. In addition, child long-term follow-up studies for all cryopreservation techniques are essential.

Umbilical cord compression diagnosed by means of ultrasound.

Two-dimensional ultrasound in combination with a pulsed Doppler may be used during parturition to distinguish between the various causes of fetal heart decelerations during active labor: "placental insufficiency", umbilical cord compression, and, fetal head compression. One case of umbilical cord compression is presented to illustrate the possibilities.

The pregnant population and a fetal crown-rump length screening program.

Ultrasound screening for estimation of gestational age is one of the most important advances made in obstetrics. In this study on the effects of our crown-rump length (CRL) screening program, a most significant (25%) proportion of the pregnant women had a difference between menstrual age and gestational age estimated on the basis of crown-rump length, exceeding 7 days. Regular menstrual cycles and reliable menstrual history could only reduce this frequency to 19%. Postmature deliveries (greater than 294 days menstrual age) were reduced from one in fifteen to one in three hundred. A screening program with CRL is useless if the woman books in too late, since a CRL above 90 mm is unreliable because of differences in fetal bending of the spine. In our catchment area more than 78% of the women delivered booked early enough for a fetal CRL measurement. If this result can be expected in a population, CRL measurement should be used because of its better accuracy than biparietal diameter measurement for the estimation of gestational age.

Conceptual dating using ultrasonically measured fetal femur length and abdominal diameters in early pregnancy.

The association between fetal anthropometric measurements and conceptual age was determined for the femur length and the mean of two abdominal diameters for conceptual ages between 10 and 20 completed weeks. The conceptual age used for reference was determined by the fetal crown-rump length measured at an earlier examination. Two equations are presented for the calculation of conceptual age from isolated estimations of the femur length or the mean of two abdominal diameters. Mean abdominal diameter and femur length measurement values were found to have similar precisions of dating.

Placental transport of maternal immunoglobulin G.

PROBLEM: How does the placental transport of immunoglobulin G (IgG) vary with gestational age? METHOD OF STUDY: MEDLINE was searched for the appearance of "pregnancy" and "IgG" in the title or abstract from 1966 up to 1995. All publications were reviewed for any kind of IgG data from the fetus and the mother and "known" gestational age. In total, 96 publications from the MEDLINE search fulfilled the search criteria. Seven of ninety-six publications contained IgG and gestational age data from the fetus and/or the mother. Five other publications that fulfilled the same criteria were also available and were also included. RESULTS: Fetal serum IgG concentrations were found to increase with gestational age according to the formula: fetal IgG = 13.564 - 1.094 x gestational age (GA) + 0.026 x GA2 (R2 = 0.877). The fetomaternal (f/m) ratio was also found to increase with gestational age according to the formula: f/m IgG = 0.399 - 0.059 x GA + 0.003 x GA2 - 2.065 x 10(-5) x GA3 (R2 = 0.831). CONCLUSIONS: The fetal IgG concentrations exceed maternal IgG concentrations after the 35th week of pregnancy. The fetal IgG concentrations are extremely low in the beginning of pregnancy, they exceed 2.5 g/L at > 25 pregnancy weeks, and they reach 5 g/L at pregnancy week 30.

Accuracy of conceptual age estimation from fetal crown-rump length.

The accuracy of conceptual age estimated by crown-rump length is not fully assessed by Robinson and Fleming in their excellent study. They avoid the problem by using the expression "menstrual maturity." We have evaluated predictors of fetal age from crown-rump length measurements where conceptual age was calculated either from the day of artificial insemination by donor (AID) or from the day of ovulation as judged from recordings of basal body temperature (BBT). When the date of AID was used as the conception date, better mathematical fits (R2 = 0.92) were obtained than when the thermal nadir was used (R2 = 0.86). The distribution around the regression line in the AID group is skewed with the 5th-95th percentile range being 3.7 days above the line and 7.3 days below the line. Similar results were obtained in the BBT group. Possible reasons for these findings are discussed.

Consumption of anti-D in the erythroblastotic fetus.

BACKGROUND: Maternal serum anti-D is actively transported across the placenta into the fetal blood where it adheres to D-positive erythrocytes. The anti-D coated red cells attach to Fc-receptors on fetal reticuloendothelial cells and are subsequently phagocytosed and hemolysed. It is not known if anti-D is consumed or recirculated in this process. MAIN QUESTION: Is anti-D in the fetus consumed in the hemolytic process in the erythroblastotic fetus and can the consumption be modulated by high-dose immunoglobulins (i.v.IG) given to the mother? METHODS: Fetal/maternal serum anti-D concentration ratios were calculated for simultaneously taken blood samples from three groups of Rh(D) immunized pregnant women; six women with fetuses who were of Rh(D) negative phenotype, 19 women with fetuses who were Rh(D) positive and received no treatment and, seven women who were treated with i.v.IG because they bore anemic, Rh(D) positive fetuses. RESULTS: Fetuses with a Rh(D) negative phenotype expressed an increase in fetal/maternal anti-D concentration ratios from 10 to 55% between 25 and 31 gestational weeks, while Rh(D) positive fetuses without i.v.IG treatment had stable values at the 10% level between 24 and 35 gestational weeks. During i.v.IG-treatment of the mothers, Rh(D) positive fetuses showed an increase in ratio from 10 to 30% between 26 and 34 gestational weeks. There was a statistically significant (p<0.001) difference between regression results of the three groups. CONCLUSIONS: Fetal anti-D is consumed in the hemolytic process and the consumption can be modulated by i.v.IG given to the mother.

Conceptual dating by ultrasonic measurement of the fetal biparietal diameter in early pregnancy.

The accuracy and precision of gestational dating, based on single measurements of the fetal biparietal diameter (BPD), was estimated in a consecutive series of 970 apparently normal, singleton pregnancies. The BPD sizes used varied between 11 and 60 mm, corresponding to 9-22 postconceptional weeks. The 'conceptual ages', used for reference, were estimated by means of ultrasonic measurements of the fetal crown--rump lengths (CRL). The association between the estimated conceptual age (dependent variable) and BPD size (independent variable) was found to be well represented (R2 = 0.972) by a second order polynomial: conceptual age = 44.7 + 1.069 X BPD + 0.01382 X BPD X BPD. To check the validity of the proposed equation, we used 23 fetuses conceived by artificial insemination with donor semen as controls. There was good agreement between the virtual conceptual ages of the control cases and their corresponding BPD-estimated conceptual ages (0.5 days mean difference, 3.6 days SD) when the suggested regression equation was used. The estimated precision of BPD-dating was minumum +/- 4.4 days (= +/- 2SD) at 9-10 completed postconceptional weeks. At 14 completed weeks the corresponding precision was found to be +/- 11 days (+/- 2SD). At the end of the studied BPD size interval, i.e. 56-60 mm BPD corresponding to 22 conceptual weeks, the precision was +/- 15 days. From an obstetrical point of view it seems obvious that the imprecision of gestational dating associated with BPD measurements greater than 35 mm should call for ultrasonic dating procedures to be performed earlier in pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Alloimmunization during pregnancy treated with high dose intravenous immunoglobulin. Effects on fetal hemoglobin concentration and anti-D concentrations in the mother and fetus.

BACKGROUND: High dose intravenous immunoglobulin has been reported to be advantageous in the treatment of alloimmunization during pregnancy. The mode of action is unknown. METHOD: High dose intravenous immunoglobulin was used as the sole prenatal treatment in six severely rhesus(D) sensitized pregnant women. Maternal and fetal anti-D concentrations as well as fetal hemoglobin concentrations were studied. Seven pregnancies in rhesus(D) sensitized women served as controls. They received no treatment because they had milder forms of erythroblastosis fetalis or, in one case, a rhesus(D) negative fetus. RESULT: No obvious inhibitory effect of the treatment on maternal anti-D production and transplacental anti-D passage to the fetus was found. The fetal hemoglobin concentrations remained stable at about 80 g/L (hematocrit 27%) in five of six treated patients while there was a significant decrease in the control group. CONCLUSION: High dose intravenous immunoglobulin treatment seems to act mainly on fetal red cell destruction rate, possibly by blocking Fc receptor mediated macrophage phagocytosis. We claim that the treatment can successfully be used to prevent further deterioration of fetal anemia in rhesus(D) immunizations if started before severe fetal anemia (hemoglobin concentration < 70 g/L, hematocrit < 23%) and imminent hydrops fetalis arises.

Fetal intracardiac transfusions in patients with severe rhesus isoimmunisation.

Six patients with pregnancies of 19-31 weeks' duration showing evidence of erythroblastosis fetalis were treated with 25 fetal intracardiac blood transfusions. Complications related to the procedure occurred on five occasions in three patients. In two of the six patients the fetus died, but it was unlikely that death was related to the intracardiac transfusions. Fetal intracardiac blood transfusion may result in potentially severe complications but offers an alternative when transfusion cannot be performed into the umbilical cord.

Feto-placental blood volume in severely anemic erythroblastotic fetuses.

The feto-placental blood volume was studied using a hemoglobin hemodilution technique in 15 erythroblastotic fetuses at 43 intravascular transfusions. Four severely anemic fetuses (Hb 30 g/l) had significantly larger blood volumes than 11 moderately anemic fetuses (Hb 30-79 g/l), 169 +/- 37 versus 105 +/- 32 ml/kg fetal body weight (p less than 0.001). We speculate that hypovolemia might be an adaptive change to maintain an adequate hemoglobin concentration. An escape of fluid from the intra- to the extra-vascular space will probably compensate for the reduction in total red cell mass and thus slightly increase the hemoglobin concentration. Theoretically, interstitial fluid accumulation will continue until the hydrostatic pressure of the extravascular tissue balances that of the capillary. This compensatory mechanism seems to function until the hemoglobin concentration drops below, 30 g/l, at which point the blood volume will increase, suggesting a change from a hypo- to a hyper-volemic state.

Fetal growth and fetal glucose and C-peptide levels in relation to the degree of anemia in fetuses affected by rhesus iso-immunization.

Fetal growth rate was determined by measuring the fetal biparietal diameter at 63 two-week time points during the second trimester in 14 patients with severe Rhesus isoimmunization. Growth rate was found to be related to the fetal hemoglobin concentration which was determined at the end of each 2-week period. Fetuses with a hemoglobin concentration of less than 30% of the normal value had a significantly decreased growth rate (p less than 0.01). These fetuses had also reduced C-peptide (p less than 0.05) and increased glucose levels (p less than 0.1) compared with less anemic fetuses. The physiological background to impaired fetal growth in cases of severe fetal anamia at Rhesus iso-immunization is discussed.