Maternal serum screening for fetal Down's syndrome, a retrospective study.

A retrospective study of the different biochemical markers used in screening for Down's syndrome was carried out on serum from 18,600 women between their 15th and 18th week of pregnancy. Thirty-two sera were from women with fetal Down's syndrome. The retrospective study of these 32 sera involves: (a) the screening of the maternal serum concentrations of human chorionic gonadotropin (hCG) and of alpha-fetoprotein (AFP); (b) the evaluation of the risk of Down's syndrome when screening maternal serum concentrations of hCG alone, then the combination of the two markers and finally the maternal serum concentrations of unconjugated estriol (uE3). The mean of MOM (multiples of the median) for the pathological sera were calculated for hCG (1.91), for AFP (0.63), for the ratio hCG over AFP (3.02) and for uE3 (0.72). With the use of hCG alone we estimated a 41% detection rate for an amniocentesis rate of 5.3%, whereas when hCG was combined with AFP the detection rate approached 65% for an amniocentesis rate of 5.5% at a risk cut-off of 1:300. The results of the uE3 determination confirm the validity of this marker. The comparison of these results with other retrospective studies shows the incidence of different factors in the detection rate such as the choice of markers, the age group studied, the modes of calculating the risk and the actual cut-off chosen.

Pregnancy outcome after artificial insemination or IVF with frozen semen donor: a collaborative study of the French CECOS Federation on 21,597 pregnancies.

OBJECTIVE: To assess pregnancies and conceptus after artificial insemination (AID) or IVF with frozen semen donor (IVF-D) on sufficiently large study population in order to distinguished minor variations. STUDY DESIGN: From 1987 to 1994, all pregnancies obtained after AID or IVF-D were registered prospectively in the French CECOS Federation data base. Different factors were recorded for this study: first menarche age of the recipient women, cycle length, insemination date in the conception cycle, maternal age at delivery, hormonal treatments, donor age, sperm conservation length and follow up of the pregnancy: miscarriage, tubal pregnancy, time at delivery, sex of the foetus, weight, malformation. RESULTS: 21,597 pregnancies obtained after AID and 3381 after IVF-D were registered. 2% were lost to follow up. Foetal loss rate is 18% after AID and 21.5% after IVF-D (p < 0.001). The tubal pregnancy rate is 0.9% after AID and 1.7% after IVF-D (p < 0.0001). 18,128 children were born after AID and 3313 after IVF-D. After AID, the twin pregnancy rate is 6.9% and the multiple pregnancy (> or = 3 foetus) rate is 0.7%. After IVF-D, these rates are 24.8% and 4.2% respectively (p < 0.0001). After AID the mean weight at delivery, sex ratio, premature rate, intra uterine growth retardation rate are not different from national rates published in 1995. The foetus malformation rate (including medical abortions) is 1.9% after AID and 2.7% after IVF-D (p < 0.009). After AID the trisomy 21 rate increases with the mother age but also with the donors age if the maternal age is equal. The birth defects rate is not different from those registered in Paris, Strasbourg and Marseille. The birth defects rate observed after IVF-D is not different from the rate observed after IVF with husband semen. (2.74% versus 2.99%; p = 0.16). CONCLUSION: After AID the miscarriage and tubal pregnancy rate, the children's weight, the premature rate is not different from that of the general French population. Sex ratio is normal as is the global malformation rate. The multiple pregnancy rate (x 7 for twin and by 10 for multiple pregnancies more than 3 foetus) is high, showing the influence of ovulation induction treatment. The birth chromosomal abnormalities rate is normal and correlated not only to the mother's age but also to the donor's age. This result without clear biological explanation will require further verification in a greater population. Practically speaking, these observations encourages lowering the age limit for semen donors less than 45 years. IVF-D practice instead of AID doubles the tubal pregnancy rate (0.9% versus 1.7% and increases the twin pregnancy rate by 2.5% and the multiple pregnancy (> or = 3 fetus) rate by 3. It is necessary to promote good practice for AID for which the pregnancy rate is very different from one centre to another within the centres with AID low results a too high rate of IVF-D. Finally we can say that pregnancies from IVF-D or IVF with husband semen are not significantly different. In other words pregnancy outcome is not changed after sperm cryopreservation.

[Value of karyotyping women patients of couples referred for sterility]. / Place du caryotype féminin en assistance médicale à la procréation (AMP).

It has been known for some 25 years that there is a causal relation between chromosomal aberrations and male infertility and that the major indication for karyotyping an infertile man is still usually an abnormal sperm analysis. The value of karyotyping women in the routine work-up of couples referred for sterility has long been debated. A French recent cytogenetic study found an overall increased frequency of chromosomal aberrations in the female and confirmed that in some cases of poor reproductive outcome there may be a contribution of maternal chromosome aberrations. Indeed, the existence of a chromosome abnormality in the female partner was associated with the group of infertile men in which there was no apparent cause of infertility. These results emphasise the need for thorough genetic work-up in couples referred for sterility. This work-up should include karyotyping of the female for some indications explained in this work.

[X-linked recessive chondrodysplasia punctata. Cytogenetic study and role of molecular biology]. / Chondrodysplasie ponctuée récessive liée à l'X. Etude cytogénétique et place de la biologie moléculaire.

UNLABELLED: Among the many acquired or constitutional causes of chondrodysplasia punctata, the X-linked recessive form is well individualized. CASE REPORT: A male newborn presented a dysmorphic syndrome with a marked nasal hypoplasia, a macroglossia and a short neck. The diagnosis of chondrodysplasia punctata was made by radiography whereas the chromosomal chart revealed the existence of an additional Y fragment in Xpter, effectuating a partial disomy Yp and a monosomy Xpter. Molecular biology showed a deletion of very small size, isolated and located between the gene missing aryl sulfatase E and the microsatellite DXS 1233, sping gene MRX2 (non-specific gene of mental retardation), and making it possible to give the reassuring elements as regards the psychomotor prognosis, sometimes compromised in this disorder. CONCLUSION: In case of chondrodysplasia punctata with dysmorphy, it is important to execute a chromosomal chart in the search for a chromosomal reorganization on the X and a study in molecular biology.

[Sampling, culturing and karyotyping of chorionic villi]. / Prélèvement, culture et caryotype des villosités choriales.

The authors report on 69 samples of chorionic villi taken from patients who were undergoing therapeutic termination of pregnancy. These samples were taken using small forceps which were guided by ultrasound. The reliability and the chances of culturing these villi in order to work out the caryotype of the fetus and to study the enzymes is discussed.

[Cancer genetics: estimation of the needs of the population in France for the next ten years]. / Oncogénétique : estimation des besoins de la population en France pour les dix ans à venir.

Organised since 1990 in France, cancer genetics has been strengthened since 2003 by the programme "Plan Cancer" which resulted in an improvement of the organisation of activities. The aim of this review is to present an update of the estimation of the needs of the population in this field for the next ten years, provided by a group of experts mandated by the French National Cancer Institute. Identification and management of major hereditary predispositions to cancer have a major impact on decrease in mortality and incidence. Sensitivity of criteria for the detection of BRCA1/2 mutations could be substantially improved by enlarging the indication for genetic testing to isolated cases of ovarian cancer occurring before 70 years and to familial cases occurring after this age limit. In the Lynch syndrome, the present criteria would have an excellent sensitivity for the detection of mutations in the mismatch repair (MMR) genes if the pre-screening of tumours on microsatellite instability (MSI) phenotype was effective, but these criteria are actually poorly applied. However, genetic testing should not be proposed to all the patients affected by tumours belonging to the spectrum of major predispositions and a fortiori to unaffected persons unless an affected relative has been identified as a carrier. The prescription of tests should continue to be strictly controlled and organised, in patients as well as in at-risk relatives. The enlargement of criteria and the improvement in the spreading of recommendations should result in an increase of genetic counselling activity and of the prescriptions of tests by a factor 2 to 4, and to a lesser extent in the clinical management of at risk persons. In a near future, it appears important to mandate experts on specific issues such as the determinants of the lack of effective application of tumour screening for MSI phenotype, the recommendations for the identification and the management of MYH-associated polyposis, or the predictive value of tumour characteristics for the identification of BRCA1/2 mutations. The expected increase in cancer genetics activity will need an optimal organisation to increase the throughput. Such measures will help in facing up to new predispositions that will probably be identified in common cancers.

[1997 results of medical assisted procreation with third party donations and autopreservation. CECOS French Federation]. / Bilan 1997 de l'assistance médicale à la procréation avec tiers donneur et de l'autoconservation. Fédération Française des CECOS.

During the year 1997, the French Federation of CECOS recorded the results of the 23 CECOS centers and IFRAERES in Toulouse. 1620 first demands of procreation with sperm donors were registed (versus 1,690 in 1996) but only 3,235 patients received at least one donation in the year, 22% less than 1996. From 10,935 cycles (AID or IVFD), 1,333 pregnancies were obtained, scoring the identical amount in terms of pregnancies as in 1996 but with less 30% in terms of cycles. The analysis of the 1,298 deliveries of the 1996 pregnancies show a malformation rate of 1.9%. 419 male volunteers came forward as sperm donors (5% more than 1996). In gamete autocryopreservation, the number of semen preservation is globally increasing (11.2% more than 1996), mainly because the capacity of a better reutilization with ICSI.

[1998 french results on medically assisted reproduction with gamete cryopreservation and donation. French Federation of CECOS]. / Bilan français 1998 de l'assistance médicale à la procréation avec tiers donneur et de l'autoconservation. Fédération Française des CECOS.

During the year 1998, the French Federation of CECOS recorded the results of the 23 CECOS centers and IFRAERES in Toulouse. 1,573 first demands of procreation with sperm donors were registed (versus 1,620 in 1997). From 9,339 cycles (AID or IVFD), 1351 pregnancies were obtained, scoring the identical amount in terms of pregnancies as in 1997 but with less 9% in terms of cycles. Ovulation monitoring and IVFD are more and more used. The analysis of the 1,169 deliveries of the 1997 pregnancies shows a malformation rate of 1.8%. 658 male volunteers came forward as semen donors (51% more than in 1997). In gamete autocryopreservation, the number of semen preservation is globaly increasing (16% more than in 1997), mainly due to the capacity of a better reutilisation with ICSI. At the end of 1998, 15 Centres was looking after 21,222 cryopreserved embryos, 25% in the aim of a near future use.

[Contribution of applied cytogenetics to medically assisted procreation]. / Apports de la cytogénétique appliquée aux procréations médicalement assistées.

The cytogenetic studies of gametes and embryos reveal the incidence of chromosomic abnormalities in medically assisted pregnancies. When extended to natural fecundation, these data enable a better comprehension of the place and the role of the selection in the quality of the conceptus.

Multicentre approaches to donor insemination in the French CECOS Federation: nationwide evaluation, donor matching, screening for genetic diseases and consanguinity. Centre d'Etudes et de Conservation des Oeufs et du Sperme humain.

The French CECOS Federation collates the results of its 22 sperm banks and provides annual reports on their activity. These records allow studies on many different aspects; annual nationwide evaluation, matching of donors and recipients, follow-up of pregnancies, research into artificial procreation, and natural fertility. Risk of transmitted hereditary disease is minimised by genetic screening which establishes the genealogy of donor candidates and includes karyotyping and other biological investigations when a particular risk is suspected. The real risk of consanguinity is very small. Limiting the number of children born from a given sperm donor can be defined at the local level.

The presence of alpha-interferon in human amniotic fluid.

Almost all the samples of amniotic fluid from 62 pregnant women from the 16th week to the end of the pregnancy contained detectable amounts of alpha-type interferon. The presence of this substance in amniotic fluid during pregnancy raises the question of the physiological significance of this finding. It is postulated that the amniotic type of alpha-interferon might be a product of a constitutive gene, rather than induced by latent virus infection.

[Prenatal diagnosis of chromosome abnormalities. Three years of experience]. / Diagnostic prenatal des anomalies chromosomiques. Resultats de trois annees

Six hundred and eighty one diagnoses were established by means of cell culture and chromosome analysis on amniotic fluid obtained either by late amniocentesis or at the time of therapeutic abortion. Each prenatal diagnosis involved: 1. Genetic consultation. 2. Supervision of the pregnancy before amniocentesis. 3. Amniocentesis in the obstetric department. 4. Confirmation of the diagnosis when an abnormality of the foetus was discolvered. 5. Supervision of the pregnancy following the anmiocentesis and examination of the infant at birth and during the first year of life. The indications for chromosome studies and the results are discussed.

First-trimester prenatal diagnosis of mucolipidosis II (I-cell disease) by chorionic biopsy.

We investigated the possibility of mucolipidosis type II (ML II) prenatal diagnosis by lysosomal enzyme determination on trophoblast biopsy obtained at 10 weeks of gestation in two pregnancies at risk. Diagnosis of ML II was made in both cases on fresh chorionic villi on the basis of depressed beta-galactosidase activity, and after abortion, the diagnosis was confirmed on fresh fetal tissues and on cells cultured from trophoblast and fetuses. We stress the importance of culturing cells from the trophoblast biopsy to ensure a reliable diagnosis.

Unexpected structural chromosome rearrangements in prenatal diagnosis.

Among 5315 prenatal diagnoses performed for various indications (maternal age, neural tube defect, metabolic diseases, X-linked diseases, pathologic pregnancies) 29 unexpected structural chromosome rearrangements were found in fetal cells. Fourteen were de novo chromosome rearrangements, six unbalanced, and eight balanced. Fifteen were inherited and balanced rearrangements. This high frequency of structural anomalies is discussed.

[Results of oocyte donation in France (Study Group on Oocyte Donation)]. / Bilan du don d'ovocytes en France (GEDO).

The French study group on oocyte donation, named GEDO, reports the results concerning the oocyte donation activity in France during 1998, including information from all the centers in effective operation except one. These data describe the recipients' and donors' situation and give the analysis of the results obtained.

Informed consent to serum screening for Down syndrome: are women given adequate information?

To assess the information given to women during a maternal serum screening (MSS) programme, we prospectively applied a questionnaire to 504 pregnant women attending for amniocentesis after a screen-positive result. The survey based on 200 usable questionnaires (39.7 per cent of our study population) showed that MSS was imposed as mandatory by 41.5 per cent of providers and done without their patients' agreement by 16 per cent. After release of the test results, 6.5 per cent of women believed that they were carrying a Down syndrome-affected fetus and 21.5 per cent thought the risk was about 50-50. A total of 38.5 per cent of the pregnant women were not informed of the risk of miscarriage after amniocentesis and 67.5 per cent believed that there was no possibility of a false-negative result with MSS. Information given over the telephone was particularly poorly understood compared with information provided during an outcome visit, since women who learned of their test result during such a visit scored significantly higher (69 per cent) when questioned about the risk of carrying a Down syndrome-affected fetus, compared with women informed of their test results by telephone (38.7 per cent) or by letter (47 per cent). We therefore suggest routine consultation with an antenatal care professional before testing to enable pregnant women to give their informed consent to MSS.

[Results of oocyte donation in France (GEDO)]. / Bilan du don d'ovocytes en France (GEDO).

The French study group on oocyte donation, named GEDO, reports the results concerning the oocyte donation activity in France from 1994 to 1997, with the informations of all the centers, in effective operation. These data describe the recipients' and donors' situation and give the analysis of the results obtained.

Incidence of birth defects after artificial insemination with frozen donor spermatozoa: a collaborative study of the French CECOS Federation on 11,535 pregnancies.

Artificial insemination using cryogenically preserved spermatozoa has been widely used in human reproduction for several decades. No evaluation of the resulting pregnancies and conceptions has been undertaken in sufficiently large study populations for minor variations to be distinguished. This study involves 11,535 pregnancies conceived by artificial insemination using donor spermatozoa and followed from the time that pregnancy was diagnosed. The pregnancies followed a normal course with, in particular, no excessive fetal losses. While the global incidence of birth defects was similar to that of natural conception, our observations raise doubts concerning trisomy 21. The frequency of trisomy 12 was somewhat elevated when compared with French malformation registries. A recruitment bias could, in part, explain this discrepancy, but donor age cannot be excluded as an influencing factor.