Impact of implementation of a breech clinic in a tertiary hospital.

BACKGROUND: The incidence of breech presentation in single pregnancies at term is between three to 5 %. In order to support eligible women in their choice of mode of delivery, a dedicated breech clinic with a care pathway was developed in December 2015 in a tertiary referral centre in Brussels. The primary objective of this study was to evaluate the vaginal birth rate before and after the introduction of a dedicated breech clinic. The secondary objective was to compare the early neonatal outcomes before and after the breech clinic was introduced. METHODS: This was a single centre retrospective and prospective study. The inclusion criteria were term (from 37 weeks), singleton fetus and breech presentation at delivery. The exclusion criteria were suspected intrauterine growth restriction, severe fetal malformations and intrauterine fetal demise. We used a composite outcome as an indicator of neonatal morbidity and mortality. RESULTS: After the introduction of the breech clinic, we observed a significant increase in planned vaginal delivery from 7.4% (12/162) to 53.0% (61/115) (OR: 13.5; 95% CI: 6.7-27.0). The effective vaginal breech delivery rate (planned and unexpected) significantly increased from 4.3% (7/162) pre-implementation of breech clinic to 43.5% (50/115) post-implementation (OR: 17.0; 95% CI: 7.3-39.6). Neonatal outcomes were not statistically different between the before and after periods. CONCLUSION: The introduction of a dedicated breech clinic has led to an increase in vaginal deliveries for breech babies without adversely affecting neonatal outcomes.

The Belgian Obstetric Surveillance System to monitor severe maternal morbidity.

BACKGROUND: In 2011 the Belgian Obstetric Surveillance System (B.OSS) was set up to monitor severe maternal morbidity in Belgium. AIM: The aim of B.OSS is to get an accurate picture of the obstetric complications under investigation and secondly, to improve the quality and safety of obstetric care in Belgium by practical recommendations based on the results. METHODOLOGY: Data are obtained through prospective active collection of cases by a monthly call according to the principle of nothing-to-report, along with data collection forms that confirm the diagnosis and gather detailed information. Data-collection occurs web-based since August 2013 through www.b-oss.be. RESULTS: B.OSS achieves excellent participation rates and response rates. The results of the first registration round are gradually brought out by means of scientific publications and presentations, biennial reports, newsletters and the website. The international comparison of results within the International Network of Obstetric Survey Systems (INOSS) gives important added value. No alternative mandatory data sources are appropriate to check for underreporting. CONCLUSIONS: B.OSS is successful in monitoring severe maternal morbidity thanks to the willingness of the Belgian OB-GYNs. The results of the first studies suggest the need to develop nationally adopted guidelines. Furthermore, the results invite to critically evaluate the current organisation of obstetric health care in Belgium. B.OSS aims to monitor the impact on patient safety in future surveys, when guidelines and recommendations are put into practice.

Nationwide population-based cohort study of uterine rupture in Belgium: results from the Belgian Obstetric Surveillance System.

OBJECTIVES: We aimed to assess the prevalence of uterine rupture in Belgium and to evaluate risk factors, management and outcomes for mother and child. DESIGN: Nationwide population-based prospective cohort study. SETTING: Emergency obstetric care. Participation of 97% of maternity units covering 98.6% of the deliveries in Belgium. PARTICIPANTS: All women with uterine rupture in Belgium between January 2012 and December 2013. 8 women were excluded because data collection forms were not returned. RESULTS: Data on 90 cases of confirmed uterine rupture were obtained, of which 73 had a previous Caesarean section (CS), representing an estimated prevalence of 3.6 (95% CI 2.9 to 4.4) per 10 000 deliveries overall and of 27 (95% CI 21 to 33) and 0.7 (95% CI 0.4 to 1.2) per 10 000 deliveries in women with and without previous CS, respectively. Rupture occurred during trial of labour after caesarean section (TOLAC) in 57 women (81.4%, 95% CI 68% to 88%), with a high rate of augmented (38.5%) and induced (29.8%) labour. All patients who underwent induction of labour had an unfavourable cervix at start of induction (Bishop Score ≤7 in 100%). Other uterine surgery was reported in the history of 22 cases (24%, 95% CI 17% to 34%), including 1 case of myomectomy, 3 cases of salpingectomy and 2 cases of hysteroscopic resection of a uterine septum. 14 cases ruptured in the absence of labour (15.6%, 95% CI 9.5% to 24.7%). No mothers died; 8 required hysterectomy (8.9%, 95% CI 4.6% to 16.6%). There were 10 perinatal deaths (perinatal mortality rate 117/1000 births, 95% CI 60 to 203) and perinatal asphyxia was observed in 29 infants (34.5%, 95% CI 25.2% to 45.1%). CONCLUSIONS: The prevalence of uterine rupture in Belgium is similar to that in other Western countries. There is scope for improvement through the implementation of nationally adopted guidelines on TOLAC, to prevent use of unsafe procedures, and thereby reduce avoidable morbidity and mortality.

[Assisted reproductive technologies and the embryo status]. / La procréation médicalement assistée et le statut de l'embryon.

The status of the human embryo has always be a subject of philosophical and theological thoughts with major social consequences, but, until the 19th century, it has been mainly an abstraction. The arrival of the human embryo in vitro, materialized by Louise Brown's birth in 1978 and above all by the supernumerary embryos produced by the Australian team of Trounson and Wood following the introduction of ovarian stimulation, will turn theoretical thoughts into a reality. Nobody may ignore the hidden intentions behind the debate, as to recognise a status to a few days old embryo will immediately have a major impact on the status of a few weeks old foetus and therefore on the abortion rights. We will see that the embryo status, essentially based as well on a vision on the good and evil as on social order, cannot be based on a scientific analysis of the reproduction process but comes from a society's choice, by essence " arbitrary " and always disputable. This does not preclude the collectivity right and legitimacy to give a precise status and it is remarkable to observe the law is careful not to specify which status to give to the human embryo. It is more thru handling procedures and functioning rules that the law designed the embryo position, neither with a status of a person, nor of a thing. It nevertheless remains true that there is a constant risk that the legislation gives the embryo a status that would call into question it's unique characteristic of early reproductive stage, jeopardizing at once the hard-won reproductive freedom (reproductive choice) as well as freedom of research on embryonic stem cells, one of the most promising field of medical research.

Si le statut de l'embryon a fait l'objet de tous temps d'une réflexion philosophique et théologique aux conséquences sociales importantes, celle-ci a été, jusqu'au XIXe siècle, essentiellement abstraite. L'irruption de l'embryon humain in vitro, matérialisé par la naissance de Louise Brown en 1978 et surtout par la constitution d'embryons surnuméraires suite aux travaux de l'équipe australienne de Trounson et Wood sur la stimulation ovarienne, vont donner à cette réflexion un tour très concret. On ne peut ignorer en outre que cette réflexion n'est pas exempte d'arrière-pensées, puisque donner un statut à l'embryon de quelques jours impacte immédiatement le statut du foetus de quelques semaines et donc le droit à l'avortement. On reverra cependant que ce statut, essentiellement basé sur une certaine vision du bien et du mal et de l'ordre social, ne peut reposer sur une analyse scientifique de la reproduction humaine mais doit naître d'un choix de société d'une certaine façon " arbitraire " et éternellement contestable. Cela n'enlève ni le droit ni la légitimité de toute collectivité de préciser ce statut, et il est remarquable que les législations qui nous entourent se gardent bien de le définir. C'est plutôt à travers les procédures de gestion et les règles de fonctionnement que le législateur a dessiné la place de l'embryon, en ne lui donnant ni un statut de personne, ni d'objet. Il n'en reste pas moins que le risque subsiste de voir conférer à l'embryon un statut qui remettrait en cause sa simple caractéristique de stade précoce de notre reproduction, mettant du même coup en danger une liberté reproductive (reproductive choice) chèrement acquise et la liberté de la recherche sur les cellules souches embryonnaires, un des champs les plus prometteurs de la recherche médicale.

[Delivery by midwife in full autonomy. Literature review and analysis of 80 months of activity at the University Hospital Erasme]. / L'accouchement par sage-femme en pleine autonomie. Revue de la littérature et analyse de 80 mois d'activité à l'Hôpital Universitaire Erasme.

INTRODUCTION: The last century focused all its attention on the care of the pathological pregnancies with remarkable results, at the price of fatal overmedicalisation in normal pregnancies. Efforts centered on the pregnant patients at low risk are being developped. OBJECTIVES: To compare obstetric and neonatal outcomes obtained by independent midwives (IM) to a group control of pregnant women at low risk at Hospital Erasme. MATERIAL AND METHODS: Retrospective constitution of a multivariated cohort case-witnesses 1:2 of patients at low risk including 128 followed in antenatal and delivered by the IM and 256 followed in antenatal and delivered by the group control Erasme (E) RESULTS: The rate of spontaneous vaginal delivery is significantly higher in the group IM (88,28 % versus 77,7 % in the group E). The rates of epidurals (66,79 % versus 37,50 %) and episiotomies (24,61 % versus 8,60 %) are significantly higher in the group E. Transfers to the neonatal unit are more frequent in the group E. CONCLUSION: The obstetrics attitudes are less interventionist in the IM group. The reasons can be linked to bias selection or to different obstetrics practices in both groups. Positive effects in terms of maternal and neonatal outcomes are quite positive.

Progesterone levels in letrozole associated controlled ovarian stimulation for fertility preservation in breast cancer patients.

STUDY QUESTION: Are progesterone levels after letrozole-associated controlled ovarian stimulation (COS) for fertility preservation in breast cancer patients, lower than after standard in vitro fertilization (IVF) cycles? SUMMARY ANSWER: During the luteal phase of letrozole-associated COS cycles (triggered with human chorionic gonadotrophin (hCG)) progesterone levels are similarly elevated to those obtained after standard COS without letrozole. WHAT IS KNOWN ALREADY: Current fertility preservation strategies for breast cancer patients include association of COS with the aromatase inhibitor letrozole to harvest several mature oocytes while maintaining low estradiol levels. Data on progesterone levels are however lacking despite growing evidence of the role of progesterone in breast tumorigenesis. STUDY DESIGN, SIZE, DURATION: This is a prospective observational study comparing estradiol and progesterone levels of 21 breast cancer patients undergoing letrozole-associated COS with 21 infertile patients undergoing standard COS for IVF and/or intra cytoplasmic sperm injection (ICSI). PARTICIPANTS/MATERIALS, SETTING, METHODS: All patients underwent COS with a GnRH antagonist protocol. In the fertility preservation group, ovulation induction was started in the follicular or luteal phase depending on the chemotherapy schedule and in 10 cases a GnRH antagonist was administered during luteal phase to induce luteolysis. Final oocyte maturation was induced by hCG in all patients. Estradiol and progesterone levels were measured on the day of hCG, at oocyte retrieval, and on days 3 and 8 after oocyte retrieval. Hormone levels in fertility preservation patients were compared with those observed in infertility patients. MAIN RESULTS AND THE ROLE OF CHANCE: While estradiol levels were significantly lower in the fertility preservation group compared with the control group (P < 0.001), progesterone levels were similar at all times, including patients receiving a GnRH antagonist during the luteal phase. LIMITATIONS, REASONS FOR CAUTION: The studied populations (breast cancer and infertile patients) are different, which may induce selection bias. The small sample size limits the study's statistical power and the possibility to perform multivariate analysis. Recruitment of the study and control patients was completed at the same time; however, enrollment of controls started at a later time. WIDER IMPLICATIONS OF THE FINDINGS: While the use of letrozole in fertility preservation patients has a favorable effect on estrogen levels, no benefit is seen for progesterone levels which are high and comparable with progesterone levels after standard COS in IVF patients. As progesterone has been associated with tumor cell proliferation, caution is mandatory. Modified protocols including GnRH agonist triggering should be investigated.

AMH mutations with reduced in vitro bioactivity are related to premature ovarian insufficiency.

STUDY QUESTION: Could anti-Müllerian hormone (AMH) mutations be implicated in the development of idiopathic premature ovarian insufficiency (POI)? SUMMARY ANSWER: Three rare or unknown missense variants of the AMH gene were identified in a cohort of 55 POI patients; all three variants showed a drastically reduced in vitro bioactivity. WHAT IS KNOWN ALREADY: Genetic factors are implicated in 5-15% of cases of POI. However, only a few genes have been shown to be involved in its development. AMH inhibits the recruitment of primordial follicles in the ovary and defective or absent AMH leads to premature depletion of the primordial follicle pool in AMH null mice. STUDY DESIGN, SIZE, DURATION: The whole coding sequence and the exon-intron junction of the AMH gene was sequenced in a cohort of 55 POI patients recruited over a period of 8 years. The studied variants were also sequenced in 197 ethnically matched controls. PARTICIPANTS/MATERIALS, SETTING, METHODS: POI was defined as amenorrhea of more than 4 months with increased FSH before the age of 40. Patients with POI resulting from radio- or chemotherapy, surgery, chromosomal anomalies or FMR1 gene pre-mutation were excluded from the study. Recombinant human wild-type (wt) and mutated AMH proteins were produced in HEK293 T cells. KK-1 cells transfected with the AMH receptor type 2 (AMHR2) and a BMP responsive element coupled to a luciferase reporter vector were stimulated with different concentrations of wt AMH and the three tested variants. MAIN RESULTS AND THE ROLE OF CHANCE: The whole coding sequence of the AMH gene could be performed and analyzed for 50 POI patients: 16 variants were found, including 6 missense variants from which 1 was unknown (R444H) and 2 were very rare (G264R and D288E). The variant D288E was also found in one of the patient's mother who also underwent POI at 32 years old. The stimulation of the AMHR2 assessed by the luciferase activity was drastically reduced for the three variants when compared with the wt AMH. LIMITATIONS, REASONS FOR CAUTION: The study is limited by a relatively small number of patients in the POI cohort. WIDER IMPLICATIONS OF THE FINDINGS: This is the first time that the bioactivity of AMH variants related to POI patients is tested in vitro. The functional study showed a drastic reduction of the protein activity for the three variants, supporting their contribution to the development of the ovarian insufficiency. The familial segregation further supports the implication of AMH in the development of POI. STUDY FUNDING/COMPETING INTERESTS: The study was performed thanks to funding from the 'Fondation Erasme'. No conflicts of interest are declared.

Safety and usefulness of cryopreservation of ovarian tissue to preserve fertility: a 12-year retrospective analysis.

STUDY QUESTION: Do the benefits of ovarian tissue cryopreservation outweigh the risks for patients seeking to preserve fertility before gonadotoxic treatment in various indications? SUMMARY ANSWER: In >90% of the patients undergoing cryopreservation of ovarian tissue, oncological treatment was associated with a reduced ovarian reserve and in 30% of patients, premature ovarian failure (POF) occurred within 5 years. WHAT IS KNOWN ALREADY: Ovarian tissue cryopreservation is an effective fertility preservation option, especially for pre-pubertal patients and patients who have a short time between diagnosis of a disease and gonadotoxic treatment. STUDY DESIGN, SETTING, DURATION: This study retrospectively analysed ovarian function and fertility recovery rates, as well as ovarian tissue characteristics, of patients who underwent ovarian tissue cryopreservation at Erasme Hospital between 1999 and 2011. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: A total of 225 patients referred from 15 Belgian oncological units underwent cryopreservation of ovarian tissue before gonadotoxic therapy for malignant or benign diseases. There were 28 patients (12.4%) who died during follow-up due to recurrence of disease. One severe adverse event occurred during anaesthesia for ovarian tissue collection, leading to the death of the patient. Ovarian function and fertility outcomes were available for 114 patients including 13 girls who were pre-pubertal at the time of the procedure. Eight patients had undergone ovarian tissue transplantation in order to restore their fertility after remission of the disease. MAIN RESULTS AND THE ROLE OF CHANCE: Breast cancer and haematological disease were the most frequent indications for ovarian tissue cryopreservation. Overall, 90% of post-pubertal patients were diagnosed with poor ovarian reserve (AMH < 0.5 ng/ml) after a mean of 50 months of follow-up (11-125 months), including 30% with POF (FSH > 40 IU/ml). Breast cancer patients had a lower rate of POF than did post-pubertal patients with haematological diseases (11 versus 34.5%, respectively), despite the older age (mean 31 versus 23.5 years old, respectively) of the breast cancer patients. Ovarian function returned in 71 post-pubertal patients without the need for grafts of cryopreserved tissue. Spontaneous pregnancies were reported for 33 of them, leading to 34 live births. Among the 13 pre-pubertal patients who reached pubertal age during the follow-up, 10 had POF. Eight patients received cryopreserved ovarian grafts to reverse POF and three of them have already become pregnant. LIMITATIONS, REASONS FOR CAUTION: This study is a retrospective analysis. The cohort was not compared with a control group of patients who did not undergo the procedure. WIDER IMPLICATIONS OF THE FINDINGS: After careful evaluation of the surgical risks, ovarian tissue cryopreservation can be proposed as an efficient option to preserve the fertility of children and young adults facing gonadotoxic therapies. However, alternative procedures such as oocyte or embryo cryopreservation should be considered as first options especially for older patients or if there is high risk of neoplastic cells within the ovaries. STUDY FUNDING/COMPETING INTEREST: This study was supported by the Télévie, FNRS-FRSM and Fondation Belge contre le cancer. There are no competing interests to report.

[Simulation training in the management of obstetric emergencies. A review of the literature]. / L'intérêt de la simulation dans l'apprentissage de la prise en charge des urgences obstétricales. Revue de la littérature.

UNLABELLED: To assess the value of simulation based training in the management of obstetric emergencies. METHOD: A search by keywords: obstetrics, gynecology, simulation, drills, emergency training restricted to randomized trials led to a selection of eight articles. RESULTS: Shoulder dystocia simulation unmasked deficiencies in performing Mc Robert maneuver in nearly 20% of doctors in training as well as ineffective and potentially harmful maneuver such as pressure on the uterine fundus. Delivery of the impacted shoulder improved from 42.9% to 83.3% after simulation training leading to a shorter head to body delivery interval. In postpartum haemorrhage simulation, lack of knowledge on prostaglandins and alkaloids of ergot, delay to transfer the patient to the operating room (82% of cases) and a poor communication between different professionals were identified. Post simulation improvement was seen in knowledge, technical skills, team spirit and structured communication. In severe preeclampsia simulation, mistakes such as injection of undiluted magnesium sulphate, caesarean section on an unstable patient were identified and reduced by 75%. Management of magnesium sulphate toxicity was also improved after simulation training. CONCLUSION: This review confirms the potential of simulation in training health professionals on management of obstetrics emergencies. Although the integration of this training modality into the curriculum of health care professionals in obstetrics and gynaecology seems beneficial, questions on the cost, the minimum standard of facilities, type of mannequins, human resources and frequency of drills required to achieve the learning objectives remain unanswered.

[Is ovarian function impaired in HIV patients? A clinical pilot study in Burkina Faso]. / La fonction ovarienne est-elle altérée chez les patientes séropositives pour le VIH? Une étude pilote au Burkina Faso.

A lot of studies published on the ten last years showed a decrease of fertility among HIV positive women. The present research aims to see if this decrease is linked to an ovarian failure, using AMH as principal marker of ovarian function. In this pilot study, 54 HIV-positive and 39 HIV-negative women were compared on the basis of their ovarian function, fecundity and possible ovarian failure. A blood sample was taken for hormonal titrations, HIV seropositivity, viral load and CD4 T cell count. An interview explored demographic characteristics, obstetrical and infectious history, and menstrual characteristics. This study was performed in Burkina Faso between January and February 2008. There is no significant difference after adjusting for age of AMH level between the two groups. However, in our study, 5.5% of HIV positive women had a premature menopause, which is a significant variation from the premature menopause rates of the African population, which is 1.4%. In conclusion, this study put the HIV impact on ovarian function into perspective but the high premature menopause rates could suggest an ovarian attack by the virus or the treatment.

The history of Belgian assisted reproduction technology cycle registration and control: a case study in reducing the incidence of multiple pregnancy.

STUDY QUESTION: What is the effect of a legal limitation of the number of embryos that can be transferred in an assisted reproductive technology (ART) cycle on the multiple delivery rate? SUMMARY ANSWER: The Belgian national register shows that the introduction of reimbursement of ART laboratory costs in July 2003, and the imposition of a legal limitation of the number of embryos transferred in the same year, were associated with a >50% reduction of the multiple pregnancy rate from 27 to 11% between 2003 and the last assessment in 2010, without any reduction of the pregnancy rate per cycle. WHAT IS KNOWN ALREADY: Individual Belgian IVF centres have published their results since the implementation of the law, and these show a decrease in the multiple pregnancy rate on a centre by centre basis. However, the overall national picture remains unpublished. STUDY DESIGN, SIZE, DURATION: Cohort study from 1990 to 2010 of all ART cycles in Belgium (2685 cycles in 1990 evolving to 19 110 cycles in 2010), with a retrospective analysis from 1990 to 2000 and prospective online data collection since 2001. PARTICIPANTS/MATERIALS, SETTING, METHODS: Registration evolved from paper written reports per centre to a compulsory online registration of all ART cycles. From 2001 up to mid-2009, data were collected from Excel spread sheets or MS Access files into an MS Access database. Since mid-2009, data collection is done via a remote and secured web-based system (www.belrap.be) where centres can upload their data and get immediate feedback about missing data, errors and inconsistencies. MAIN RESULTS AND THE ROLE OF CHANCE: National Belgian registration data show that reimbursement of IVF laboratory costs in July 2003, coupled to a legal limitation in the number of embryos transferred in utero, were associated with a 50% reduction of the multiple pregnancy rate from 27 to 11% without reduction of the pregnancy rate per cycle, and with an increase in the number of fresh and frozen ART cycles due to improved access to treatment. LIMITATIONS, REASONS FOR CAUTION: There is potential underreporting of complications of ART treatment, pregnancy outcome and neonatal health. WIDER IMPLICATIONS OF THE FINDINGS: Over the 20 years of registration, the pregnancy rate has remained constant, despite the reduction in the number of embryos transferred, optimization of laboratory procedures and stimulation protocols, introduction of quality systems and implementation of the EU Tissue Directive over the period 2004-2010. STUDY FUNDING/COMPETING INTEREST(S): No external funding was sought for this study. None of the authors has any conflict of interest to declare.

Pregnancy outcome after oocyte donation in patients with Turner's syndrome and partial X monosomy.

BACKGROUND: Fertility expectations for patients with Turner's syndrome (TS) have clearly changed in the last three decades. However, medical risks during pregnancy are supposed to be highly increased. The aim of the study was to assess clinical outcome and obstetrical complications in a series of patients with TS in an oocyte donor programme. METHODS: A retrospective study was carried out on 24 women with TS seeking a pregnancy in the Fertility Clinic of the Erasme Hospital from 1992 up until March 2011. RESULTS: Twenty-three patients with TS were included in an oocyte donation cycle. Forty-nine oocyte donation cycles were performed, which led to 45 fresh and 10 frozen-thawed embryo transfers. Altogether, 18 pregnancies were obtained, 10 deliveries (9 singletons and 1 pair of twins), 3 miscarriages and 5 biochemical pregnancies. The clinical pregnancy rate per transfer was 24.4% in fresh cycles and 20% in frozen replacement cycles. Complications of pregnancy occurred in 5 of 10 pregnancies (50%), which led to three premature deliveries because of pregnancy-induced hypertensive disorders. The mean birthweight (g) (±SD) for singletons and twins was 2728 ± 577 and 2335 ± 318, respectively. Four babies were below the 10th percentile. No cardiac complications were observed in any of the pregnant women. CONCLUSIONS: Pregnancy rates after oocyte donation in patients with TS are comparable with those previously published but a high risk of pregnancy hypertensive disorders and a high risk of low birthweight can be highlighted from our study. Strict inclusion criteria and single embryo transfer are necessary to minimize complications during pregnancy in this high-risk group.

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.

Cryopreservation of human failed maturation oocytes shows that vitrification gives superior outcomes to slow cooling.

This study investigated whether failed maturation oocytes could be used to evaluate different cryopreservation procedures. A total of 289 failed maturation oocytes (GV and MI stages), obtained from 169 patients undergoing IVF treatment (mean age 33.84±5.0) were divided into two different slow-cooling groups (1.5 mol/l 1,2-propanediol+0.2 mol/l sucrose in either NaCl (group A) or choline chloride (ChCl) (group B) based cryopreservation solutions) and one vitrification group (15% ethylene glycol+15% dimethyl sulphoxide). Survival rate, in vitro maturation (IVM) rate, fertilization and developmental rate of cryopreserved oocytes were assessed. Regardless of the stage at which cryopreservation was performed (GV+MI), the slow cooling with ChCl based medium always gave significantly lower survival rate than the slow cooling in NaCl based medium (p=0.01) and vitrification (p<0.001). An extended study also showed statistically reduced survival rate between slow-cooling NaCl based medium and vitrification (p<0.05). Global results of in vitro maturation and fertilization showed worse results between both slow-cooling NaCl and ChCl based media versus vitrification. In conclusion, for oocytes that had failed to mature, vitrification gave better survival, maturation, fertilization and also cleavage rates than the slow-cooling protocols. Four cells embryos were obtained only from vitrified in vitro matured MI oocytes.

Variants of the BMP15 gene in a cohort of patients with premature ovarian failure.

BACKGROUND: Bone morphogenetic protein 15 (BMP15) is an oocyte-derived growth factor acting as a major player in follicle differentiation in mammals. Mutations in the BMP15 gene, some of which lead to defective secretion of bioactive dimers, have been associated with premature ovarian failure (POF) in humans. METHODS: Fifty patients diagnosed with POF with a normal karyotype were included in the study. After DNA extraction and amplification by PCR, the entire coding sequence and intron-exon junctions of BMP15 gene were analysed in the cohort of POF patients and in a control group of 214 patients. RESULTS: Nine variants of the BMP15 gene including six missense substitutions and one insertion of three nucleotides were identified in the POF group. Three of them were previously described as single nucleotide polymorphisms and were also found in the control group. Two variants (H81R and G199R) have not been previously described and were not identified among controls but were not predicted to be deleterious. One variant (A180T) was identified among two POF cases, and also in two controls. One variant (F194S), predicted as potentially deleterious, was identified for the first time in a POF patient but also identified in one control. One variant (L148P), potentially deleterious, previously reported in POF patients, was identified for the first time among controls. The variant 788insTCT, previously identified among POF patients, probably has a low biological impact as it was also found in control patients and is a common polymorphism in sub-Saharan African populations. CONCLUSIONS: Various missense variants of the BMP15 gene were identified among patients with POF. For most variants, the impact of the amino-acid substitution on the protein structure and function was predicted to be low. The two variants predicted as potentially deleterious were also identified among controls and could be considered as rare polymorphisms. Although some of these variants could contribute to the development of POF in a complex manner, the demonstration of their role in the pathogenesis of POF requires additional functional studies.

Human cystic fibrosis embryonic stem cell lines derived on placental mesenchymal stromal cells.

This study describes the production of two new human embryonic stem cell (hESC) lines affected by cystic fibrosis. These cell lines are heterozygous compounds, each a carrier of the DF508 mutations associated either with E585X or with 3849+10 kb C-->T. The derivation process was performed on irradiated human placental mesenchymal stromal cells and designed to minimize contact with xeno-components. This new source of feeder cells is easy to obtain and devoid of ethical concerns. The cells have a great capacity to proliferate which reduces the need for continuous preparation of new feeder cell lines. In addition, three normal hESC lines were obtained in the same conditions. The five stem cell lines retained hESC-specific features, including an unlimited and undifferentiated proliferation capacity, marker expression and the maintenance of stable karyotype. They also demonstrated pluripotency in vitro, forming cell lineages of the three germ layers, as indicated by immunolocalization of beta-tubulin, alpha-fetoprotein and actin. These new genetic cell lines represent an important in-vitro tool to study the physiological processes underlying this genetic disease, drug screening, and tissue engineering.

Orthotopic and heterotopic ovarian tissue transplantation.

BACKGROUND: Transplantation of ovarian tissue is, at present, the only clinical option available to restore fertility using cryopreserved ovarian tissue. More than 30 transplantations of cryopreserved tissue have been reported, and six babies have been born, worldwide, following this procedure. Despite these encouraging results, it is essential to optimize the procedure by improving the follicular survival, confirming safety and developing alternatives. Here, we review the different factors affecting follicular survival and growth after grafting. METHODS: Relevant studies were identified by searching Pubmed up to January 2009 with English language limitation. The following key words were used: (ovarian tissue or whole ovary) AND (transplantation) AND (cryopreservation or pregnancy). Using the literature and personal experience, we examined relevant data on the different exogenous and clinical factors affecting follicular development after grafting. RESULTS: Clinical factors such as the patient's age and the transplantation sites influenced the lifespan of the graft. A heterotopic transplantation site is not optimal but offers some advantages and it may also promote the hormonal environment after a combined heterotopic and orthotopic transplantation. Exogenous factors such as antioxidants, growth factors or hormones were tested to improve follicular survival; however, their efficiency regarding further follicular development and fertility potential remains to be established. CONCLUSION: Additional evidence is required to define optimal conditions for ovarian tissue transplantation. Alternatives such as whole ovary or isolated follicles transplantations require further investigation but are likely to be successful in humans in the future.

Preimplantation genetic diagnosis in an HIV-serodiscordant couple carrier for sickle cell disease: lessons from a case report.

Since 1999, the Erasme Hospital Fertility Clinic has carried a special programme for patients with HIV seropositivity. The philosophy of the programme is to give access to these patients in a secure environment to the same technological facilities available to any other patients. Many of these patients being native from sub-Saharan countries, they are often sickle cell disease (SCD) carriers, a common autosomal recessive disorder in these regions, and a severe affection in homozygotes. We hereby report, for the first time, the birth of a healthy sickle haemoglobin (HbS) heterozygous baby after preimplantation genetic diagnosis (PGD) for SCD in an HIV-serodiscordant couple of HbS mutation carriers with longstanding infertility. The prospective mother was 35 years old and HIV positive with an undetectable viral load under highly active antiretroviral therapy. One carrier embryo was transferred and resulted in the birth of a healthy HbS carrier baby girl. Despite stimulation difficulties, sometimes described in HIV patients, PGD represents an interesting additional technology, especially in populations where the coexistence of both diseases is frequent. PGD could even be preferred to prenatal diagnosis for couples of HbS carriers if the woman is HIV positive, as invasive prenatal samplings carry a risk of materno-foetal viral transmission.