Anonymity and secrecy options of recipient couples and donors, and ethnic origin influence in three types of oocyte donation.

BACKGROUND: This study compares recipient couples' and donors' motivations towards the type of donation and attitudes concerning secrecy or disclosure of the mode of conception in three oocyte donation groups: couples and their donor for a known donation, couples and their donor for a permuted anonymous donation (known-anonymous) and couples without a donor, on a waiting list for a donation (anonymous). METHODS: Data collected by two psychologists through semi-structured interviews of 135 recipient couples and 90 donors before oocyte donation were analysed retrospectively. RESULTS: In known donation (42 couples), donors were preferentially family members with a blood tie (54.7%). Choosing their donor seemed mainly for the couple's reassurance rather than to access the child's origins as 50% wanted secrecy. On the other hand, in known-anonymous donation (48 couples), donors were more frequently chosen among friends (41.6%; P = 0.038). These couples were either open to disclosure (45.8%; P = 0.002) or remained hesitant (39.6%). In anonymous donation (45 couples), 49% chose not to seek a donor mostly in order to maintain secrecy towards the child (77.3%). Among the 51% who sought but could not find a donor, only 30.4% wanted secrecy. Recipients from North Africa and from Europe preferred anonymous or known-anonymous donation (83.3 and 75.6%), whereas sub-Saharan Africans opted more often for known donation (63%; P < 0.001). Among Europeans (90 couples), 50% were in favour of disclosure compared with only 8.9% of recipients from North or sub-Saharan Africa (45 couples; P < 0.001). CONCLUSIONS: A diversity of attitudes and cultural differences exist among recipient couples and donors regarding oocyte donation; this pleads for maintaining access to different types of oocyte donation as well as for psychological counselling prior to treatment.

[Guidelines on cardiovascular disease prevention in clinical practice. Belgian Working Group on Cardiovascular Prevention and Rehabilitation]. / Recommandations relatives a la prévention des maladies cardiovasculaires en pratique clinique. Groupe de travail belge de prévention des maladies cardiovasculaires.

Since more than 15 years, expert groups and various European Scientific Societies have written Guidelines on Cardiovascular Disease Prevention. Because of the rapid evolution of science, it is necessary to adapt regularly these guidelines. The last version dates from 2007 and has been written by the " Fourth Joint Task Force of European and other Societies on Cardiovascular Disease Prevention in Clinical Practice ". In this issue, the more recent Guidelines are summarised and we focus on highlighting the aspects of these Guidelines that have changed since the previous version published in this journal in 2005.

[What kind of support do couples expect when undergoing IVF treatment? Study and perspectives]. / Quel soutien les couples en traitement de FIV attendent-ils de l'équipe soignante? Enquête et pistes de réflexion.

OBJECTIVES: To assess the management of the supportive aspects of treatment for couples having attempted an in vitro fertilization treatment. MATERIAL AND METHODS: Three groups of couples were contacted by questionnaire (successful treatment, unsuccessful treatment treatment, outcome still unknown). RESULTS: 48% considered it necessary to offer psychological support after the diagnosis. 80% considered it difficult to have a thorough representation of the physical aspects of an In Vitro Fertilization treatment but mostly they were surprised by their lack of an accurate emotional representation. All couples expected an availability and receptiveness from the infertility team but the unsuccessful treatment group was less satisfied and felt significantly (P < 0.001) less well supported. The most difficult moments mentioned were the numerous moments of waiting and the announcement of the final result. Emotional support was regularly provided by the nurses but 20% wanted psychological counselling. Two thirds of all couples considered that a psychological follow-up should be proposed to couples for whom the treatment remain unsuccessful. CONCLUSIONS: Results show the need for better emotional preparation of couples. As for the emotional support during treatment, the need for psychological counselling appears after the diagnosis of infertility as well as a constant demand of availability and empathy on behalf of the team. Post-treatment counselling may be particularly important also. Failure as well as lack of support at that time seemed to colour the way couples regard the whole support provided during treatments.

ART in HIV-infected couples: has the time come for a change of attitude?

Today, in developed countries, many HIV-infected people remain in good health thanks to antiviral medication. A growing number of them want to have children. Medical possibilities for preventing contamination of the partners of seropositive men, through assisted reproduction, and of children thanks to antiviral medicines during pregnancy, are summarized. These changes result in ethical considerations which lead the authors to question the conventional systematic medical advice against pregnancy and has encouraged them to assist reproduction for a number of these couples. Today, the balance between the importance of the message of prevention and the benefit for patients of being assisted in their desire for a child has tilted towards medical intervention. It would seem legitimate today to intervene in the most favourable situations rather than see these couples take the risk of spontaneous conception outside health care structures. This implies the need to adapt medical structures (separate laboratory, appropriate procedure, precise protocols). This approach, which is coherent from the scientific point of view, respects both the autonomy of people carrying HIV as well as the essential interests of the child, in being born uninfected, and also has the enormous advantage of allowing access to parenthood without destroying the consistency of the message of prevention of sexual contamination.

[Medically assisted reproduction and the desire for a child by HIV infected couples: has the time for a change in attitude come?]]. / Assistance médicale à la procréation et désir d'enfant de couples infectés par le VIH: le temps d'un changement d'attitude est-il venu?

Today, in developed countries, many HIV-infected people remain in good health thanks to antiviral medication. A growing number of them want to have children. Medical possibilities for preventing contamination of the partners of seropositive men through assisted reproduction and of children thanks to antiviral medicines during pregnancy are summarized. These changes result in ethical considerations which lead the authors to question the conventional systematic medical advise against pregnancy and has encouraged them to assist reproduction for a number of these couples. Today, the balance between the importance of the message of prevention and the benefit for patients of being assisted in their desire for a child has tilted towards medical intervention. It would seem legitimate today to intervene in the most favourable situations rather than see these couples take the risk of spontaneous conception outside health care structures. This implies to adapt medical structure (separate laboratory, appropriate procedure, precise protocols). This approach, which is coherent from the scientific point of view, respects both the autonomy of people carrying HIV as well as the essential interest for the child, in "being" born uninfected and also has the enormous advantage of allowing access to parenthood without destroying the consistency of the message of prevention of sexual contamination.

[Aspects of scientific research and technical progress in human fertility]. / Aspects de recherche scientifique et progres techniques en fertilite humaine.

The development of an outstanding in vitro fertilization program greatly benefits from the contribution of research because it remains an unfailing source of questions on human reproduction, as much in the fields of physiology and pathology as in those of psychology and sociology. This paper shows five major themes that are tackled by the laboratory of biology and psychology of human fertility and the Fertility Clinic, whether it's endocrinology (the ovarian renin and angiotensin regulation), cellular metabolism (embryo metabolism), genetics (preimplantation genetic diagnosis) or cancerology (ovarian tissue conservation before or after chemo- or radiotherapy), all of these are crossed by the fifth (the psychological and ethical aspects of in vitro fertilization) which gives a human dimension to the biological work, since it's a very special biology that it's our own reproduction, the very base of the specie's survival.

Stenting of "unprotected" left main coronary artery stenoses: early and late results.

OBJECTIVE: To assess short and long term efficacy of coronary stent implantation for unprotected left main coronary artery stenosis. DESIGN: Retrospective follow up study. SETTING: Tertiary referral centre for interventional cardiology and cardiac surgery. PATIENTS: Eighteen consecutive patients (12 men; age 70.8 years) between May 1993 and July 1996. Ten patients presented with stable angina and underwent the procedure electively, eight patients presented either with unstable angina or myocardial infarction and underwent the procedure in emergency. INTERVENTION: Johnson and Johnson Palmaz-Schatz stents were used in 16 patients, and a Microstent and a Gianturco-Roubin in one patient each. An intra-aortic balloon pump was prophylactively used for two patients in the elective group. In the acute group, six required an intra-aortic balloon pump. MAIN OUTCOME MEASURES: Procedural success rate and major adverse cardiac events. RESULTS: Successful stent implantation was achieved in all patients. In the elective group, no major adverse cardiac event occurred during the procedure, but one patient had to undergo repeated angioplasty before discharge. All patients of the elective group were discharged alive and there has been one non-cardiac death during a follow up of (mean (SD)) 10 (4) months. In the emergency group, one patient died during the procedure, one patient developed a non Q-wave myocardial infarction, one patient underwent emergency coronary bypass surgery, while another patient died suddenly before hospital discharge. Six patients of the emergency group were discharged alive and there has been one non-cardiac death during a follow up of 7 (4) months. CONCLUSIONS: Elective stent implantation for unprotected left main coronary artery stenosis is safe and effective in selected stable patients. Urgent stent implantation, however, cannot be considered as a definitive procedure in emergency situation.

[Oocyte donation: ethical aspects related to the donor]. / Don d'ovocyte: aspects éthiques liés à la donneuse.

This paper analyses the reasons that brings couples to apprehend very differently the oocyte and sperm donation and highlights the difficulty of donor recruitment in those programs. The various types of donors (occasional, relational, IVF patient and professional) are described with their motivations, resistances, advantages and disadvantages. The contradictory consequences between free or paid donation, the particular risks of eggs donation (in comparison to sperm donation) for the donor as for the recipient are also highlighted. The problem of anonymity is also analysed in ethical terms but also in terms of technical efficacy: it is shown that anonymity, by authorizing sharing oocytes between recipients increases treatment efficacy by avoiding wasting this rare and precious resource of oocytes offered as a donation.

Reduced cholesterol absorption in hamsters by crilvastatin, a new 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor.

Crilvastatin, a new drug from the pyrrolidone family, has been previously shown to inhibit the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase, in vitro and in vivo, to reduce the absorption of dietary cholesterol and to stimulate the activity of cholesterol 7 alpha-hydroxylase in the rat. The aim of this study was to evaluate the effects of crilvastatin on cholesterol and bile acid metabolism in the hamster. In hamsters fed on a lithogenic diet for 8 weeks, crilvastatin treatment (200 mg/day per kg body weight) did not change plasma lipid levels, failed to improve bile parameters and did not prevent gallstone formation. In hamsters fed on a basal cholesterol-rich (0.2%) diet for 8 weeks, crilvastatin at the same dose reduced the cholesterol level in the plasma by 20%, with a decrease of both low-density and high-density lipoprotein cholesterol. The drug did not significantly stimulate the biliary secretion of bile acids but significantly decreased the activity of acyl coenzyme A:cholesterol acyltransferase in the small intestine by 64%. This effect was enhanced when cholestyramine, a bile acid-sequestering resin, was given in combination with crilvastatin. Crilvastatin alone did not change the activity of cholesterol 7 alpha-hydroxylase in the liver, despite the marked reduction in both hepatic cholesterogenesis and intestinal absorption of dietary cholesterol (the absorption coefficient was 44 +/- 2% in treated hamsters vs. 61 +/- 7% in controls).

Differences in hypolipidaemic effects of two statins on Hep G2 cells or human hepatocytes in primary culture.

1. The objective of this study was to compare in cultured human hepatocytes or Hep G2 cells, changes in the fate of unesterified low density lipoprotein (LDL)-cholesterol induced by crilvastatin, a new cholesterol lowering drug and a reference statin, simvastatin. 2. The experiments were carried out for 20 h, each well contained 4.2 x 10(5)/cm2 Hep G2 cells or 0.5 x 10(5)/Cm2 human hepatocytes, 130 microM ursodeoxycholate, 0.68 microCi or 1.59 microCi unesterified human [14C]-LDL-cholesterol, crilvastatin or simvastatin at 0 or 50 microM (both cell types) or 300 microM (Hep-G2 cells). Incubation with the two drugs resulted in increased amounts of unesterified [14C]-LDL-cholesterol taken by the two cell types, compared to control. 3. Crilvastatin 50 microM led to significantly higher quantities of [14C]-glyco-tauro-conjugated bile salts, compared to simvastatin. Statins reduced the apo B100 level secreted by the two cell types (simvastatin) or human hepatocytes (crilvastatin). Crilvastatin enhanced both the level of apo A1 secreted by the Hep G2 cells and the level of APF, a high density lipoprotein (HDL) and biliary apoprotein. 4. Crilvastatin not only acts by stimulating LDL-cholesterol uptake by hepatocytes, but also by enhancing the catabolism of LDL-cholesterol in bile salts and probably by stimulating HDL and/or bile component secretion. Such a mechanism was not previously described for HMG CoA reductase inhibitors. Our results on APF show that this apoprotein could be considered also as an indicator of changes in bile and/or HDL compartments. 5. The human hepatocyte model appeared to be a suitable and relevant model in the pharmacological-metabolic experiments carried out in this study. It led to more consistent data than those obtained with Hep G2 cells.

[Fate of supernumerary embryos and risk of multiple pregnancy in in-vitro fertilization: attitude of involved couples]. / Devenir des embryons surnuméraires et risque de grossesse multiple en fécondation in vitro: qu'en pensent les couples concernés?

To determine the fate of their possible additional embryos and to face the multiple pregnancy risk are problems each couple undergoing in vitro fertilization is confronted. The supernumerary embryos can be frozen but the couple have to decide before the treatment the fate of the possible embryos that would not be transferred at the end of the storage period. The opinion of 236 couples concerning these questions were evaluated through a questionnaire and an interview. Ninety-eight percent chose for their embryos to be frozen. Despite the fact that they frequently designed donation as the ideal choice only half of them chose that issue. To give priority to educational aspects in parental bonding led them to accept for their embryos to become children in another couple. On the contrary, if the couple's opinions focused on genetic aspects, they would regard these children as their own. In this case they opted for destruction or experimentation (in both cases the embryos will be finally destroyed), even if they consider that the in vitro embryo is already a child. The statue of the embryo do not interfere with the choice for the fate of the supernumerary embryos. Religion, to have children already, and the project to adopt in case of treatment failure did not influence their choice. Regarding the possible multiple pregnancy risk, couples attitude differs from twins to triplets. Twins are nearly always accepted and even considered by one-third of patients a suitable result for the treatment. On the opposite, one-third refuse the perspective of triplets. Fourteen percent of couples declare in this case they would ask for fetal reduction.

Crilvastatin, a new 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, inhibits cholesterol absorption in genetically hypercholesterolemic rats.

Crilvastatin is a new drug from the pyrrolidone family, which acts as a non-competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. The long-term effects of oral crilvastatin treatment (200 mg per day per kg body weight for 4 and 10 weeks) were investigated on in vivo cholesterogenesis in male adult normocholesterolemic (SW) and genetically hypercholesterolemic (RICO) rats. In both strains of rats, the treatment had no effect on the plasma cholesterol level, but efficiently inhibited cholesterol synthesis in liver and intestine, as shown by the decreased incorporation of exogenous [14C]acetate into hepatic (3.5-fold in SW, 1.7-fold in RICO rats) and intestinal (2.5-fold in SW, 3.3-fold in RICO rats) sterols. In RICO rats in which the dietary cholesterol absorption coefficient was two-fold lower in treated (38%) than in untreated (78%) rats, this drug reduced intestinal cholesterol absorption. As a result, the total plasma cholesterol input (absorption + synthesis), measured by isotope analysis in RICO rats, was markedly lower in treated (11.3 mg per day) than in untreated animals (28.8 mg per day).

Psychological study of in vitro fertilization-embryo transfer participants' attitudes toward the destiny of their supernumerary embryos.

OBJECTIVE: To study the motivations underlying IVF-ET participants' choice to donate or destroy their supernumerary embryos. DESIGN: Couples' opinions are studied through a questionnaire and a psychological interview. PARTICIPANTS: Two hundred couples about to undergo IVF-ET. SETTING: The fertility unit of an academic hospital. MAIN OUTCOME MEASURES: Couples' choice for supernumerary embryos' destiny; opinions on embryo status, on importance of genetic lineage in the filial bonding, on gamete donation, and on multiple pregnancy risk. RESULTS: Donation is the most frequent choice but destruction is tolerated by almost all the couples (92%). Couples considering the embryo as a child choose destruction as frequently as donation but refuse experimentation on the embryo. Donation is highest among couples who stress education more than genetic lineage in parental bonding. This is confirmed by the choice of the couples requiring donor gametes. Couples express differing attitudes toward risks of twins and risks of triplets: twins are much more desired than triplets, which are frequently refused. CONCLUSIONS: Couples' opinions on the respective importance of genetic lineage and education in defining parental bonding are more determinant in their decision to destroy or to donate their supernumerary embryos than their opinions on the in vitro embryo status, which only determines their attitude toward experimentation.

Effect of crilvastatin, a new cholesterol lowering agent, on unesterified LDL-cholesterol metabolism into bile salts by rat isolated hepatocytes.

1. The aim of these experiments was to determine the effect of crilvastatin, a new cholesterol lowering agent, on the metabolism of unesterified low density lipoprotein (LDL)-cholesterol by rat freshly isolated hepatocytes. This preclinical model was developed as an alternative to in vivo experiments, to mimic the metabolic effects of a molecule on its target cells and to define optimal conditions for future experimentation on human hepatocytes. 2. Cells were obtained from normolipidaemic or hypercholesterolaemic rats, hypercholesterolaemia was nutritionally induced. Incubations were performed in a medium containing 600 microM taurocholate and 50 microM or 300 microM crilvastatin. 3. This molecule was shown in vitro to be carried by physiological transporters, i.e., albumin-bile salt micellar associations and LDL. Crilvastatin induced a significance increase in the synthesis and secretion by hepatocytes of bile salts resulting from the metabolism of unesterified LDL-cholesterol in both normolipidaemic and hypercholesterolaemic rats. Stimulation involved non-conjugated as well as tauro- and glyco-conjugated bile salts. These findings corroborate preliminary studies showing in vivo that crilvastatin enhances the secretion of bile acids by stimulating the uptake and incorporation of LDL-cholesterol by the liver.

Cardiac transplantation in giant cell myocarditis. A case report.

The present report describes a 15-year-old boy who underwent an urgent cardiac transplantation for giant cell myocarditis because of fulminant progressive heart failure, complicated by ventricular tachycardia, unresponsive to classical inotropic medical treatment. The physiopathology and the treatment are discussed.

Mechanisms of action in the liver of crilvastatin, a new hydroxymethylglutaryl-coenzyme A reductase inhibitor.

Crilvastatin is a drug from the pyrrolidone family that had been shown to induce non-competitive inhibition of rat hydroxymethylglutaryl-coenzyme A reductase activity in vitro. The aim of this study was to evaluate the activity of crilvastatin on the hepatic metabolism of cholesterol in rats. Crilvastatin increased low density lipoprotein (LDL)-cholesterol uptake by the liver more than high density lipoprotein (HDL) uptake, thus increasing by up 30% the clearance of excess plasma cholesterol. In normolipidemic rats, crilvastatin significantly enhanced acyl coenzyme A:cholesterol acyl transferase and cholesterol 7 alpha-hydroxylase activity. In rats with a previous high cholesterolemia, crilvastatin also enhanced cholesterol 7 alpha-hydroxylase activity and did not increase liver acyl coenzyme A:cholesterol acyl transferase activity. These findings suggest that a drug such as crilvastatin could have a hypocholesterolemic effect by a mechanism other than the sole inhibition of cholesterol synthesis, possibly by stimulating cholesterol and bile salt secretion via the biliary tract in previously hypercholesterolemic rats.

[Current program of in-vitro fertilization at the Erasmus Hospital: initial results and original ethical aspects]. / Nouveau programme de fécondation in vitro à l'hôpital Erasme: premiers résultats et aspects éthiques originaux.

The clinical results including all in vitro fertilization (IVF) cycles with oocyte pick-up in 1990 are presented. Different types of treatment including classical IVF and embryo transfer, laparoscopic replacement of zygotes in the fallopian tube (ZIFT), IVF with donor sperm (IVF-D), cross fertilization test, embryo freezing, oocyte donation and IVF with epididymal sperm were performed. The total pregnancy rate obtained reaches 38% per oocyte pick-up, 30% of clinical pregnancies (including 4 pregnancies obtained with frozen and thawed embryos). The anticipated "Take Home Baby Rate" will be around 25% per oocyte pick-up, 26 of these 40 pregnancies being today over 20 weeks of gestation. Particular ethical aspects of the program are presented: a study on couple's attitudes regarding embryo freezing as well as the final destination of possibly remaining supernumerary embryos will stress the importance of a precise clear decision on that matter before entering IVF treatment. Indeed the couple's idea on embryo destiny were very precise but also very different. The oocyte donation program has the originality of preserving the donor's anonymity by exchanging the donors recruited by the patients. It will be stressed that this kind of approach combines higher pregnancy chances for the patients, respect of ethical principles linked to gamete donation and gives satisfaction to the patients. The global normalized pregnancy cumulative curve shows that 60% of the couples entering IVF treatment will obtain a child within the first three pick-up cycles.

[AIDS: is it an indication for artificial insemination with anonymous donor sperm?]. / Le SIDA: indication d'insémination artificielle avec sperme de donneur anonyme?

Such demands raise difficulties, as the physician has to consider (and has to be the defender of) the coming child. A thorough psychological investigation must be conducted, as the couple's motives and those of each partner considered separately are not necessarily in agreement. Most important for the couple are the persistence of common projects and the strengthening of the bonds. The husband wants to survive through a child, to give an ultimate present and to increase the chance of keeping his partner. The wife shows her faithfulness and diminishes her partner's guilt feelings. She is, anyway, in a difficult situation if trying not to become pregnant, especially if she had already expressed a wish for maternity in normal circumstances. Unconscious mechanisms can intervene, such as fantasmatic adultery (through IAD) which reequilibrates the couple: the husband who brought the HIV has to be forgiven, or punished. Also, and most importantly, one has to analyze the prospects for the child, who is at risk of loosing his father, and also his mother: a later transmission of the virus to her cannot be excluded. The child will be confronted by illness and death of his father, and by heavy family secrets. The attitude of the medical team remains problematic: no clearcut attitude prevails.

Quantitative structure-activity relationships for dicoumarol antivitamins K in the uncoupling of mitochondrial oxidative phosphorylation.

The dynamic structure of dicoumarols substituted on the methylene bridge has been studied by nuclear magnetic resonance (nmr) spectroscopy. These molecules may be considered as dimers with restricted rotation around the methylene bridge, held by intramolecular hydrogen bonds; the presence of the substituent R modifies this dynamic process, mainly the facility of exchange of the two hydroxyl protons. These compounds have been compared in respect to their potency in uncoupling oxidative phosphorylation in pig heart mitochondria; the data have been correlated with constants used to characterize the substituent R; to make a potent uncoupler, R should be as small and as hydrophilic as possible. These results are discussed in consonance with the postulated mechanisms of action of the uncouplers, but no simple conclusion can be drawn, especially concerning the role of the dissociable protons.