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Las características formales de este grupo escolar —proyectado en 1969— vienen determinadas por las grandes cubiertas y la forma dentada de las plantas. La primera de ellas es consecuencia del interés por lograr una unidad de concepto y de volumen, manteniendo, al mismo tiempo, la tradición arquitectónica de la zona. En cuanto a la forma dentada, es la respuesta a la idea de obtener unas óptimas condiciones de iluminación en cada una de las aulas. El edificio se compone de tres niveles superiores, planta baja y semisótano. En este último se hallan: el gimnasio, los vestuarios de alumnos y los locales técnicos que sirven a la escuela. La planta baja, en la que se encuentra el acceso principal, comprende una pequeña zona administrativa, el comedor con su cocina, una clase de niñas, tres de párvulos, cuatro de niños y una multifuncional. El resto de las plantas albergan, con el mismo esquema organizativo, ocho aulas de niñas y cinco de niños, junto a una serie de locales auxiliares tales como salas de profesores, bibliotecas, clases de usos varios, archivos, aulas de trabajos manuales, etc. La construcción se completa con una amplia zona deportiva y de recreo.

El edificio, de aproximadamente 790 m2 construidos, se destina a comedor y hospedaje para personas en tránsito, estando emplazado en Echarri - Aranaz, junto a la carretera, en el calvero de un bosque. Cuenta con una extensa planta baja y dos niveles superiores, de superficie más reducida, que se elevan, a modo de cuerpo lateral, sobre uno de los costados del edificio. El conjunto de la edificación distribuye los servicios de bar, comedor, cocina, administración, y un total de 8 dormitorios dobles y 2 sencillos. Una importante cubierta a dos aguas, que abarca a las dos plantas más altas, junto a otra de varias aguas, que con sus distintos planos se ajusta al perímetro irregular de la construcción en planta baja, imprimen al edificio las características propias de la arquitectura popular de la reglón, que se ve así homologada en un planteamiento arquitectónico moderno.

Este edificio es de una gran movilidad formal de plantas y alzados y se destina a viviendas residenciales, de cuidada distribución interior. Toda la dinámica que se aprecia, responde exactamente a estudios minuciosos tendentes a cumplir las Ordenanzas municipales, a ocupar el máximo volumen permitido y a procurar a todas las viviendas las mejores condiciones de orientación y soleamiento.

BACKGROUND: Spermatozoa can be retrieved from the testis and epididymis of men with obstructive azoospermia (OA) and used for ICSI. However, it is unknown whether the outcome of ICSI depends on the cause of obstruction or the origin of surgically retrieved spermatozoa. METHODS: A cohort of 171 men with OA and normal spermatogenesis were included in this retrospective study. They were divided into three groups according to the site and origin of obstruction: 83 men had congenital bilateral absence of vas deferens; 55 and 33 had acquired epididymal and deferent duct obstructions, respectively. The outcome of 368 ICSI cycles was determined and compared according to the origin of spermatozoa: epididymal (n = 253) or testicular (n = 115). RESULTS: Fertilization and clinical pregnancy rates did not differ between spermatozoa of different origin (58.9% versus 51.9% and 22.1% versus 24.3% with epididymal and testicular spermatozoa, respectively). However, the miscarriage rate was significantly higher for testicular spermatozoa (35.7% versus. 12.5% P < 0.05, χ2 test). Findings were similar whatever the aetiology of the OA. CONCLUSION: This study suggests that the use of testicular spermatozoa, even those generated during normal spermatogenesis, alters embryonic development and that epididymal spermatozoa should be preferentially used, irrespective of the aetiology of OA. [ABSTRACT FROM AUTHOR]

BACKGROUND: Fetal DNA circulating in maternal serum offers a possibility for non-invasive prenatal diagnosis but its kinetics during very early pregnancy is still unclear. In order to clarify this point, the studies on the kinetics of fetal DNA appearance in maternal serum were conducted on patients undergoing assisted reproduction. METHODS: Using a quantitative real time PCR assay, the presence of SRY gene sequences was evaluated in the serum of patients at the onset of pregnancy. RESULTS: Twenty-seven patients were originally studied but first trimester abortion occurred in five cases. Among the 22 ongoing pregnancies, ten were found to bear at least one male fetus and all sera from these women gave positive results for SRY gene detection. The SRY gene was found to be detectable as soon as day 18 after embryo transfer in one case and it had been found in the other nine patients by day 37. CONCLUSIONS: Fetal DNA is found in maternal serum even before the fetal circulation is established, which is highly suggestive that it is released, at least in part, from the trophoblast. Detection of fetal DNA in maternal serum very early in pregnancy may have clinical implications such as with the management of pregnant women carrying a fetus at risk for congenital adrenal hyperplasia. [ABSTRACT FROM AUTHOR]

BACKGROUND The outcome of in vitro fertilization (IVF) has been widely investigated over the last 30 years, but evaluation was mostly based on pregnancy rate per oocyte retrieval. Our objective was to estimate the cumulative live birth rate after four IVF aspirations, using multiple imputation that takes into account treatment interruptions. METHODS We analysed data from 3037 couples beginning IVF treatment between 1998 and 2002 in two French IVF units. Multiple imputations were used at each aspiration to impute the IVF outcome (delivery or not) for couples who interrupted treatment. The global success rate after four aspirations was then computed. RESULTS At the first aspiration, 21% of couples obtained a live birth and 24% discontinued treatment. The multiple imputation method provided an estimated cumulative live birth rate at each aspiration as if no couple discontinued treatment: 35% at the second aspiration and 41% at the third. The cumulative success rate after four aspirations was estimated at 46% (95% CI: 44–48%). CONCLUSIONS Multiple imputation is a promising method for estimating the cumulative success rate of IVF. It could provide new insight on IVF evaluation and should be tested in further studies. [ABSTRACT FROM AUTHOR]

La iglesia que se describe en el artículo tiene la forma de un amplio trapecio, en planta, cubriéndose con una estructura metálica a base de cuatro pórticos fundamentales que se apoyan sobre otros tantos muros de hormigón armado. Tanto la organización y funcionamiento de la planta, como el tratamiento de ambientes y el uso de los materiales más adecuados, asi como el empleo de paramentos transparentes que comunican con la naturaleza circundante y otros muchos detalles de orden técnico y plástico, hacen de este edificio un magnífico logro arquitectónico.

Study Question: What is the frequency and the associated factors of very early dropout following unsuccessful clomiphene citrate (CC)/gonadotropin treatment in the context of full coverage of treatment cost., Summary Answer: Despite free treatment, almost one in four women had a very early dropout following unsuccessful CC/gonadotropin treatment, with patients below the poverty line being more likely to drop out early., What Is Known Already: Success of infertility care is tarnished by very high dropout rates. Infertility care dropout has been considered as resulting principally from financial barriers because of the high cost of treatment. Nearly all previous work addressed dropout following IVF/ICSI. Factors associated with dropout following CC/gonadotropins may be different and also need to be investigated., Study Design, Size, Duration: Nationwide population-based cohort study., Participants/materials, Setting, Methods: Using the French national health insurance and hospital databases, we included in the cohort 27 416 women aged 18-49 years unsuccessfully treated with CC/gonadotropins in 2017. The main outcome was very early dropout, defined as discontinuation of all infertility treatment after unsuccessful treatment for 1-3 months. Very early treatment dropout was analysed by multivariate logistic regression., Main Results and the Role of Chance: Among women unsuccessfully treated with CC/gonadotropins, 22% dropped out of infertility care within 3 months. In multivariate analysis, higher early dropout following unsuccessful CC/gonadotropin treatment was associated with older and younger ages (≥35 and <25 years), being below the poverty line, being treated with CC prescribed by a general practitioner and lack of infertility tests or monitoring., Limitations, Reasons for Caution: This study is based on health administrative data that do not include reasons for dropout and record only a limited amount of information. It is thus not possible to analyse the reason for early dropout., Wider Implications of the Findings: Despite full coverage of all infertility treatment, women under the poverty line have a higher risk of very early dropout following unsuccessful CC/gonadotropin treatment. Better understanding is needed of the non-financial barriers and difficulties faced by these patients. To address disparities in infertility treatment, practitioner training could be reinforced to adapt to patients from different social and cultural backgrounds., Study Funding/competing Interest(s): This work was supported by the ANR StimHo project, grant ANR-17-CE36-0011-01 from the French Agence Nationale de la Recherche. The authors have no conflict of interest to declare., Trial Registration Number: N/A., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Background: Access to IVF/ICSI is facilitated when the financial barrier is removed. In a national context where in vitro fertilisation (IVF)/intracytoplasmic sperm Injection (ICSI) treatment is cost-free, how many women do not access IVF/ICSI and what are the factors associated with non-access?, Methods: Using French national health insurance databases, the cohort included 20,240 women aged 18-43 years living in France who underwent unsuccessful treatment (no pregnancy) with clomiphene citrate (CC) and/or gonadotropins with treatment started between January and August 2016. The outcome measure was non-access to IVF/ICSI during the 24-month following start of infertility care. Factors associated with non-access to IVF/ICSI were explored using mixed effects logistic regression., Results: In the cohort, 65.4% of women did not access IVF/ICSI. In multivariable analysis, non-access to IVF/ICSI was higher in younger women (18-25 years: (OR 2.17, 95% CI: 1.85-2.54) and in older women (40-43 years: (OR=3.60, 95% CI: 3.25-3.98)). Non-access was higher among women below the poverty line (OR=3.76, 95% CI: 3.34-4.23) and showed a significant upward trend with increasing deprivation of place of residence. Distance to the nearest fertility centre was not significantly associated with non-access to IVF/ICSI., Conclusions: In a national context of cost-free ART treatment, a large proportion of women did not access treatment, with a strong social gradient that raises important issues. We need to understand the underlying social mechanisms to develop an efficient and equitable health policy regarding infertility care., (© 2023. The Author(s).)

The aim of this study was to explore the achievement of parenthood 8 years after starting IVF, considering multiple pathways to parenthood during and after IVF treatment. Medical data on 6507 couples who began IVF between 2000 and 2002 were obtained from the databases of eight French IVF centres. Information on long-term outcome was available for participants in the 2008-2010 postal survey. Multiple imputation methods were used to account for missing data. Eight years after starting IVF, 71% (95% CI 69 to 74) of treated couples had a child. This included 41% live births after IVF in the IVF centre, 7% live births after another treatment or after IVF in another centre, 12% live births after spontaneous conception and 11% adoptions. This study provides a longitudinal overview of paths to parenthood among couples successfully and unsuccessfully treated by IVF. These results should give hope to infertile couples as seven out of 10 couples finally became parents. However, IVF is not the only path to parenthood, and couples should be informed of the other possible avenues., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)

SHANK genes code for scaffold proteins located at the post-synaptic density of glutamatergic synapses. In neurons, SHANK2 and SHANK3 have a positive effect on the induction and maturation of dendritic spines, whereas SHANK1 induces the enlargement of spine heads. Mutations in SHANK genes have been associated with autism spectrum disorders (ASD), but their prevalence and clinical relevance remain to be determined. Here, we performed a new screen and a meta-analysis of SHANK copy-number and coding-sequence variants in ASD. Copy-number variants were analyzed in 5,657 patients and 19,163 controls, coding-sequence variants were ascertained in 760 to 2,147 patients and 492 to 1,090 controls (depending on the gene), and, individuals carrying de novo or truncating SHANK mutations underwent an extensive clinical investigation. Copy-number variants and truncating mutations in SHANK genes were present in ∼1% of patients with ASD: mutations in SHANK1 were rare (0.04%) and present in males with normal IQ and autism; mutations in SHANK2 were present in 0.17% of patients with ASD and mild intellectual disability; mutations in SHANK3 were present in 0.69% of patients with ASD and up to 2.12% of the cases with moderate to profound intellectual disability. In summary, mutations of the SHANK genes were detected in the whole spectrum of autism with a gradient of severity in cognitive impairment. Given the rare frequency of SHANK1 and SHANK2 deleterious mutations, the clinical relevance of these genes remains to be ascertained. In contrast, the frequency and the penetrance of SHANK3 mutations in individuals with ASD and intellectual disability-more than 1 in 50-warrant its consideration for mutation screening in clinical practice.

Crisponi syndrome (CS) and cold-induced sweating syndrome type 1 (CISS1) share clinical characteristics, such as dysmorphic features, muscle contractions, scoliosis, and cold-induced sweating, with CS patients showing a severe clinical course in infancy involving hyperthermia associated with death in most cases in the first years of life. To date, 24 distinct CRLF1 mutations have been found either in homozygosity or in compound heterozygosity in CS/CISS1 patients, with the highest prevalence in Sardinia, Turkey, and Spain. By reporting 11 novel CRLF1 mutations, here we expand the mutational spectrum of CRLF1 in the CS/CISS1 syndrome to a total of 35 variants and present an overview of the different molecular and clinical features of all of them. To catalog all the 35 mutations, we created a CRLF1 mutations database, based on the Leiden Open (source) Variation Database (LOVD) system (https://grenada.lumc.nl/LOVD2/mendelian&#95;genes/variants). Overall, the available functional and clinical data support the fact that both syndromes actually represent manifestations of the same autosomal-recessive disorder caused by mutations in the CRLF1 gene. Therefore, we propose to rename the two overlapping entities with the broader term of Crisponi/CISS1 syndrome., (© 2014 WILEY PERIODICALS, INC.)

Even when IVF is reimbursed by the social insurance system, as in France, high discontinuation rates have been reported and some patients drop out as soon as the first failed IVF cycle. This study aims to investigate medical factors associated with treatment discontinuation in an IVF centre after the first unsuccessful cycle. The study included 5135 couples recruited in eight French IVF centres and who had had an unsuccessful first IVF cycle in these centres in 2000-2002 (i.e. no live birth). Of these couples with a first failed IVF, 1337 did not have a second IVF in the centre (26%, 'early discontinuation group') and 3798 continued treatment with a second IVF in the centre. The characteristics of couples who discontinued IVF treatment were compared with those who continued using logistic regressions. Older women, women with duration of infertility >5years, with female factor or unexplained infertility, with 0 or 1 oocyte retrieved and no embryo transfer during the first IVF were more likely to discontinue treatment early. Risk of early discontinuation was associated with medical factors that are also well known to be associated with impaired chance of successful IVF. Even when IVF is reimbursed by the social insurance system, as in France, high discontinuation rates have been reported and some patients drop out as soon as the first failed IVF cycle. This study aims to investigate medical factors associated with treatment discontinuation in an IVF centre after the first unsuccessful cycle. The study included 5135 couples recruited in eight French IVF centres who had had an unsuccessful first IVF cycle in these centres in 2000-2002 (i.e. who remained childless after a first cycle). Of these couples with a first failed IVF, 1337 did not have a second IVF in the centre and 3798 continued treatment with a second IVF in the centre. The characteristics of couples who discontinued IVF treatment were compared with those who continued. After a first failed IVF cycle, more than one-quarter (26%) of couples discontinued IVF treatment. Older women, women with duration of infertility >5years, with female factor or unexplained infertility, with 0 or 1 oocyte retrieved and with no embryo transfer during the first IVF were more likely to discontinue treatment early. The risk of early discontinuation was associated with medical factors that are also well known to be associated with impaired chance of success during IVF treatment. A next step would be to examine whether the early discontinuation results from a decision of the couple themselves, from medical, psychological and/or social staff counselling or from some combination of all of these factors., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The study of the genetic and selective landscape of immunity genes across primates can provide insight into the existing differences in susceptibility to infection observed between human and non-human primates. Here, we explored how selection has driven the evolution of a key family of innate immunity receptors, the Toll-like receptors (TLRs), in African great ape species. We sequenced the 10 TLRs in various populations of chimpanzees and gorillas, and analysed these data jointly with a human data set. We found that purifying selection has been more pervasive in great apes than in humans. Furthermore, in chimpanzees and gorillas, purifying selection has targeted TLRs irrespectively of whether they are endosomal or cell surface, in contrast to humans where strong selective constraints are restricted to endosomal TLRs. These observations suggest important differences in the relative importance of TLR-mediated pathogen sensing, such as that of recognition of flagellated bacteria by TLR5, between humans and great apes. Lastly, we used a population genetics-phylogenetics method that jointly analyses polymorphism and divergence data to detect fine-scale variation in selection pressures at specific codons within TLR genes. We identified different codons at different TLRs as being under positive selection in each species, highlighting that functional variation at these genes has conferred a selective advantage in immunity to infection to specific primate species. Overall, this study showed that the degree of selection driving the evolution of TLRs has largely differed between human and non-human primates, increasing our knowledge on their respective biological contribution to host defence in the natural setting.

Background: As discontinuation in in vitro fertilization (IVF) programs has been associated with a poor prognosis, one hypothesis is that some couple-specific predictive factors in IVF may be shared with opposite effect by both success (i.e. live birth) and treatment discontinuation processes. Our objective was to perform a joint analysis of these two processes to examine the hypothesis of a link between the two processes., Methods: Analyses were conducted on a retrospective cohort of 3,002 women who began IVF between 1998 and 2002 in two French IVF centers: a Parisian center and a center in a medium-sized city in central France. A shared random effects model based on a joint modelization of IVF treatment success and discontinuation was used to study the link between the two processes., Results: Success and discontinuation processes were significantly linked in the medium-sized city center, whereas they were not linked in the Parisian center. The center influenced risk of treatment discontinuation but not chance of success. The well-known inverse-J relation between the woman's age and chance of success was observed, as expected. Risk of discontinuation globally increased as the woman's age increased., Conclusions: The link between success and discontinuation processes could depend on the fertility center. In particular, the woman's decision to pursue or to discontinue IVF in a particular center could depend on the presence of other IVF centers in the surrounding area.

Background: A good response rate has been considered as a proof of a study's quality. Decreasing participation and its potential impact on the internal validity of the study are of growing interest. Our objective was to assess factors associated with contact and response to a postal survey in a epidemiological study of the long-term outcome of IVF couples., Methods: The DAIFI study is a retrospective cohort including 6,507 couples who began an IVF program in 2000-2002 in one of the eight participating French IVF centers. Medical data on all 6,507 couples were obtained from IVF center databases, and information on long-term outcome was available only for participants in the postal survey (n = 2,321). Logistic regressions were used to assess firstly factors associated with contact and secondly factors associated with response to the postal questionnaire among contacted couples., Results: Sixty-two percent of the 6,507 couples were contacted and 58% of these responded to the postal questionnaire. Contacted couples were more likely to have had a child during IVF treatment than non-contactable couples, and the same was true of respondents compared with non-respondents. Demographic and medical characteristics were both associated with probability of contact and probability of response. After adjustment, having a live birth during IVF treatment remained associated with both probabilities, and more strongly with probability of response. Having a child during IVF treatment was a major factor impacting on participation rate., Conclusions: Non-response as well as non-contact were linked to the outcome of interest, i.e. long-term parenthood success of infertile couples. Our study illustrates that an a priori hypothesis may be too simplistic and may underestimate potential bias. In the context of growing use of analytical methods that take attrition into account (such as multiple imputation), we need to better understand the mechanisms that underlie attrition in order to choose the most appropriate method.

Objective: To determine the frequency of live births following spontaneous pregnancy (BSP) and to examine their associated factors among couples who have unsuccessfully or successfully experienced fertility treatments., Design: Retrospective cohort., Setting: Eight IVF centers., Patient(s): A total of 2,134 couples who began IVF treatment in the centers in 2000-2002 and were followed up by a postal questionnaire sent 7-9 years after they started treatment in the inclusion center., Intervention(s): None., Main Outcome Measure(s): Rates of BSP and factors associated with BSP. Univariate and multivariate analyses were conducted using logistic regression., Result(s): The BSP rate was 17% (218/1,320) among couples who had previously had a child through medical treatment and 24% (193/814) among couples who had remained childless after treatment. In both groups, the probability of BSP was higher among younger women and increased with a smaller number of IVF attempts. Probability was also higher when the cause of infertility was unexplained., Conclusion(s): Our results should give hope to couples who have been unsuccessfully treated by IVF, especially young couples with unexplained infertility. Nonetheless, it should be remembered that the BSP rates are cumulative rates observed over a long period of time and that these couples have a very low monthly probability of conceiving., (Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objectives. To analyze the impact of oocyte denudation and microinjection timings on intracytoplasmic sperm injection (ICSI) outcomes. Study Design. We included ICSI cycles with the following parameters: rank 1 or 2, female age <36 years, male factor infertility, long protocol using GnRH agonist and rFSH for ovarian stimulation, and use of freshly ejaculated sperm (n = 110). Several ICSI parameters were analyzed according to the time between oocyte retrieval and denudation (T(1)) and the time between denudation and ICSI (T(2)) using a statistical logistic regression analysis. Results. Neither T(1) nor T(2) had a significant influence on the Metaphase II (MII) rate but the fertilisation rate (FR) showed a significant improvement when T(1) was longer (optimal results at T(1) = 3 hours) while FR significantly decreased with the increase of T(2). Optimal implantation (IR) and pregnancy (PR) rates were obtained when T(1) was around 2 hours. Conclusion. Incubation of oocytes around 2 hours between retrieval and denudation may not increase MII rate but appears to lead to the optimal combination of FR and IR.

Treatment discontinuations are an important issue in IVF programmes. In the French context, financial constraint does not intervene in discontinuation until older ages. This study examined treatment discontinuation in IVF programmes, according to the woman's age and when there is no financial burden for couples. Medical records were collected for 3037 women who began their IVF programme between 1998 and 2002 in two French IVF units. Up to four attempts were taken into consideration. Cumulative success (delivery) rates were calculated, as well as discontinuation rates. Multiple imputation was applied to estimate a theoretical cumulative success rate as if no woman discontinued treatment before the end of the IVF programme without delivering. Cumulative discontinuation rates at the end of the IVF programme increased with the woman's age (41% for age <35, 56% for age 35-39, 80% for age ⩾40). The benefit in terms of delivery rates of pursuing treatment would be smaller for older women (∼10% for age <35, 7% for age 35-39, 4% for age ⩾40). Even when treatment is reimbursed, the discontinuation rate is high for older women, suggesting that the strong decrease in success rate with age induces older women to discontinue. Treatment discontinuations are an important issue in IVF programmes. In the French context, financial constraint does not intervene in discontinuation until older ages. We aimed to examine treatment discontinuation in IVF programmes, according to the woman's age and when there is no financial burden for couples. Medical records were collected for 3037 women who began their IVF programme between 1998 and 2002 in two French IVF units. Up to four attempts were taken into consideration. Cumulative success (delivery) rates were calculated, as well as discontinuation rates. Multiple imputation was applied to estimate a theoretical cumulative success rate as if no woman discontinued treatment before the end of the IVF programme without delivering. Cumulative discontinuation rates at the end of the IVF programme increased with the woman's age (41% for age <35, 56% for age 35-39, 80% for age ⩾40). The benefit in terms of delivery rates of pursuing treatment would be smaller for older women (∼10% for age <35, 7% for age 35-39, 4% for age ⩾40). Even when treatment is reimbursed, the discontinuation rate is high for older women, suggesting that the strong decrease in success rate with age induces older women to discontinue., (Copyright © 2011 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Objective: To assess the efficacy of elective single embryo transfer (e-SET) compared to a double embryo transfer (DET) in a selected population including obstetrical and neonatal outcome of fresh and frozen-thawed cycles., Design: Prospective nonrandomized study., Setting: Department of reproductive medicine., Patient(s): Elective single embryo transfer was proposed to women < 36 years with adequate ovarian function, in their first or second IVF or intracytoplasmic sperm injection (ICSI) attempt with ejaculated sperm, with at least 4 mature oocytes and 2 fertilized top quality embryos. Patients who refused e-SET had two top embryos transferred (DET group)., Intervention(s): Medical management and IVF-ICSI., Main Outcome Measure(s): Cumulative delivery rate, twin delivery rate, obstetrical and neonatal outcome., Result(s): According to patients' decision, 53 women had an e-SET and 98 a DET. The cumulative delivery rate per patient was 54.7% in the e-SET group and 49.0% in the DET group (P>0.05). Twin delivery rate was significantly different between the two groups (3.5% versus 37.5% respectively, P<0.05). Neonatal outcome in twins resulting from IVF-ICSI was found to be poorer than in singletons, considering the mean gestational age, mode of delivery, birthweight, and risk of neonatal intensive care unit admission for the infants., Conclusion(s): In a selected population, the elective transfer of one embryo with high implantation potential helped to avoid twin pregnancies without decreasing delivery rate., (Copyright (c) 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To explore the long-term outcome of patients who began IVF treatment by considering not only treatment outcome in the center but also the parenthood project outcome after discontinuation of unsuccessful IVF., Design: Retrospective cohort follow-up study., Setting: Two French IVF centers., Patient(s): Seven hundred twenty-four patients who began IVF treatment in 1998., Intervention(s): Postal and phone contacts with unsuccessful IVF patients., Main Outcome Measure(s): Long-term outcome of parenthood project., Result(s): Of the 724 patients, a minimum of 53% and a maximum of 81% finally succeeded in their parenthood project during or after IVF treatment (depending on the hypotheses that the 204 patients not contacted either failed or succeeded in their parenthood project). An intermediate hypothesis gave an estimation of 66% of patients finally succeeding in having a child (40% during IVF treatment in the center and 26% after). Achievement of the parenthood project after IVF discontinuation was due mainly to adoption of a child (46%) or a birth following a spontaneous pregnancy (42%)., Conclusion(s): Unsuccessful patients should not lose hope, because nearly half may subsequently succeed in having a child.

Objective: To report a successful pregnancy after a semi-natural IVF cycle for a BRCA1 gene mutation carrier., Design: Case report., Setting: University hospital., Patient(s): A 26-year-old patient with BRCA1 gene mutation., Intervention(s): Semi-natural IVF cycle and intracytoplasmic sperm injection., Main Outcome Measure(s): Pregnancy rate., Result(s): A modified natural IVF cycle was performed, resulting in pregnancy and delivery., Conclusion(s): A modified natural IVF cycle is an effective and safe solution for BRCA1 or BRCA2 mutation gene carrier women with couple infertility.

Objective: To report a case of successful delivery of a healthy baby after intracytoplasmic sperm injection (ICSI) in a patient with no mature oocytes at the time of oocyte retrieval., Design: Case report., Setting: Department of Reproductive Medicine., Patient: After a controlled ovarian hyperstimulation cycle, a total of seven immature oocytes were collected., Intervention(s): Medical management., Main Outcome Measure(s): The timing of polar body extrusion was checked every 2 hours, and ICSI was performed as soon as the first polar body was extruded., Result(s): Following incubation in culture medium, five oocytes reached the metaphase II stage within 8-8.5 hours. Three oocytes were fertilized after ICSI, and two of three cleaved embryos were transferred on day 3. The embryo transfer was followed by a single pregnancy and the delivery of a healthy baby., Conclusion: This case report demonstrates that embryos obtained from in vitro matured oocytes retain the developmental competence for full-term. It illustrates the importance of regularly monitoring the polar body extrusion when all collected oocytes are immature.

Background: The outcome of in vitro fertilization (IVF) has been widely investigated over the last 30 years, but evaluation was mostly based on pregnancy rate per oocyte retrieval. Our objective was to estimate the cumulative live birth rate after four IVF aspirations, using multiple imputation that takes into account treatment interruptions., Methods: We analysed data from 3037 couples beginning IVF treatment between 1998 and 2002 in two French IVF units. Multiple imputations were used at each aspiration to impute the IVF outcome (delivery or not) for couples who interrupted treatment. The global success rate after four aspirations was then computed., Results: At the first aspiration, 21% of couples obtained a live birth and 24% discontinued treatment. The multiple imputation method provided an estimated cumulative live birth rate at each aspiration as if no couple discontinued treatment: 35% at the second aspiration and 41% at the third. The cumulative success rate after four aspirations was estimated at 46% (95% CI: 44-48%)., Conclusions: Multiple imputation is a promising method for estimating the cumulative success rate of IVF. It could provide new insight on IVF evaluation and should be tested in further studies.

Objective: To examine the safety and effectiveness of assisted reproduction using sperm washing for HIV-1-serodiscordant couples wishing to procreate where the male partner is infected., Design and Methods: A retrospective multicentre study at eight centres adhering on the European network CREAThE and involving 1036 serodiscordant couples wishing to procreate. Sperm washing was used to obtain motile spermatozoa for 3390 assisted reproduction cycles (2840 intrauterine inseminations, 107 in-vitro fertilizations, 394 intra-cytoplasmic sperm injections and 49 frozen embryo transfers). An HIV test was performed in female partners at least 6 months after assisted reproduction attempt. The outcome measures recorded were number of assisted reproduction cycles, pregnancy outcome and HIV test on women post-treatment., Results: A total of 580 pregnancies were obtained from 3315 cycles. Pregnancy outcome was unknown in 47 cases. The 533 pregnancies resulted in 410 deliveries and 463 live births. The result of female HIV testing after assisted reproduction was known in 967 out of 1036 woman (7.1% lost to follow-up). All tests recorded were negative. The calculated probability of contamination was equal to zero (95% confidence interval, 0-0.09%)., Conclusion: This first multicentre retrospective study of assisted reproduction following sperm washing demonstrates the method to be effective and to significantly reduce HIV-1 transmission risk to the uninfected female partner. These results support the view that assisted reproduction with sperm washing could not be denied to serodiscordant couples in developed countries and, where possible, could perhaps be integrated into a global public health initiative against HIV in developing countries.

Purpose: The pregnancy outcome and the chances of birth were assessed according to embryo quality after IVF or ICSI., Methods: The implantation rate (IR), the loss of gestational sacs rate (LGSR), and birth rate (BR) were determined according to the cleavage stage and the integrity of blastomeres after day-2 homogeneous embryo transfers (n = 1812)., Results: The LGSR was higher after transfers of 2-3-cell or 5-6-cell embryos and was significantly increased when more than 20% of the embryo volume was fragmented in 4-cell embryos. After transfers of 4-cell embryos without fragmentation, the BR was significantly higher than the BR after transfers of 4-cell embryos with 1-20% fragmentation (16.6% vs 13.1%). The difference was the consequence of a higher IR (20.4% vs 17.3%) but also of a lower LGSR (18.9% vs 24.2%)., Conclusions: Not only implantation and the ability to give a pregnancy, but also the capacity to give a live birth are dependent on the embryo quality.

The objective of this study was to compare the implantation rate, pregnancy rate and endometrial thickness of frozen-thawed embryo transfers using endometrial preparation with either an artificial cycle or stimulated cycle. This was a prospective randomized trial at a single academic IVF centre. Seventy-seven patients undergoing artificial cycles received oral oestradiol; patients with endometrium < 7 mm on day 9-10 were switched to vaginal oestradiol. Eighty-six patients undergoing stimulated cycles received recombinant FSH followed by human gonadotrophin hormone injection. Vaginal progesterone was begun 2 or 3 days prior to embryo transfer. There was no difference in implantation rate (8.5% versus 7.3%), pregnancy rate (16% versus 13%), cancellation rate (both 23%) or endometrium thickness (8.7 +/- 1.1 mm versus 8.7 +/- 1.0 mm) between artificial and stimulated cycles. Stimulated cycles had a higher incidence of thin endometrium (27% versus 5%, P < 0.01). In artificial cycles, patients switched to vaginal oestradiol had improved pregnancy rate (31%) versus patients who received oral oestradiol alone (13%) (P = 0.05). It is concluded that artificial and stimulated cycles produce comparable pregnancy rates, implantation rates, cancellation rates and endometrial thickness, although stimulated cycles have a higher incidence of thin endometrium. Vaginal oestradiol supplementation improved implantation rates.

Background: Sterility in men with cystic fibrosis (CF) raises the question of the use of assisted reproductive techniques (ART). A multidisciplinary network including adult CF centre and reproductive medicine units was set up to answer requests for ART., Methods: This retrospective study included 25 men with CF between 1994 and 2004. Clinical status, semen analysis, CF mutations analysis and artificial insemination by donor (AID) or ICSI after surgical retrieval of sperm were monitored., Results: All CF men had azoospermia. Two chose AID first (one delivery); 23 chose ICSI. Sperm were surgically retrieved in 21 cases, and ICSI was performed in 19. Pregnancies occurred in 12 of these 19 couples (63%) (two ectopic pregnancies, two spontaneous abortions, one termination of pregnancy for polymalformed twins and 11 single deliveries in nine couples). Two couples tried AID after ICSI failed; one had twins. Another adopted a child, and two had a spontaneous pregnancy. After a follow-up of 4.1+/-2.3 years, two patients died, two underwent lung transplantation and 21 remained stable., Conclusion: ART can help men with CF to become a father, but their health status and short survival need careful counselling and multidisciplinary medical care.

Background: Spermatozoa can be retrieved from the testis and epididymis of men with obstructive azoospermia (OA) and used for ICSI. However, it is unknown whether the outcome of ICSI depends on the cause of obstruction or the origin of surgically retrieved spermatozoa., Methods: A cohort of 171 men with OA and normal spermatogenesis were included in this retrospective study. They were divided into three groups according to the site and origin of obstruction: 83 men had congenital bilateral absence of vas deferens; 55 and 33 had acquired epididymal and deferent duct obstructions, respectively. The outcome of 368 ICSI cycles was determined and compared according to the origin of spermatozoa: epididymal (n = 253) or testicular (n = 115)., Results: Fertilization and clinical pregnancy rates did not differ between spermatozoa of different origin (58.9% versus 51.9% and 22.1% versus 24.3% with epididymal and testicular spermatozoa, respectively). However, the miscarriage rate was significantly higher for testicular spermatozoa (35.7% versus. 12.5% P < 0.05, chi2 test). Findings were similar whatever the aetiology of the OA., Conclusion: This study suggests that the use of testicular spermatozoa, even those generated during normal spermatogenesis, alters embryonic development and that epididymal spermatozoa should be preferentially used, irrespective of the aetiology of OA.

Objective: To evaluate the rate of multiple pregnancies in intrauterine insemination cycles stimulated with a minimal dose of recombinant follicle stimulating hormone (rec-FSH)., Design: Retrospective study., Setting: University Medical Center., Population: A total of 1256 patients underwent 3219 consequent intrauterine insemination cycles with minimal ovarian stimulation., Methods: Patients received 50 or 75 IU of rec-FSH from day four to day seven. The dose was adjusted according to oestradiol (E(2)) levels in order to achieve a maximum of two follicles on the day of hCG administration., Main Outcome Measures: Peak E(2) levels, the number of follicles >15 mm and pregnancy rates were calculated. The predictive value of E(2) levels for multiple gestations was also estimated., Results: Of 3219 cycles, 334 resulted in pregnancies (10%). Of these, 238 (91%) were singletons, 28 (8%) twins and 1 (0.3%) was a triplet. The cumulative overall pregnancy rate was 43%. Patients over 40 years old had a significantly lower pregnancy rate per cycle and overall live birth rate (P < 0.05). Most pregnancies (83%) occurred during the first three cycles. Pregnancy rates per cycle varied from 8% for tubal factor to 14% for anovulation infertility., Conclusions: Minimal FSH stimulation in intrauterine insemination cycles may reduce the rates of twins and high order multiple pregnancies without affecting overall pregnancy rates.

Background: Fetal DNA circulating in maternal serum offers a possibility for non-invasive prenatal diagnosis but its kinetics during very early pregnancy is still unclear. In order to clarify this point, the studies on the kinetics of fetal DNA appearance in maternal serum were conducted on patients undergoing assisted reproduction., Methods: Using a quantitative real time PCR assay, the presence of SRY gene sequences was evaluated in the serum of patients at the onset of pregnancy., Results: Twenty-seven patients were originally studied but first trimester abortion occurred in five cases. Among the 22 ongoing pregnancies, ten were found to bear at least one male fetus and all sera from these women gave positive results for SRY gene detection. The SRY gene was found to be detectable as soon as day 18 after embryo transfer in one case and it had been found in the other nine patients by day 37., Conclusions: Fetal DNA is found in maternal serum even before the fetal circulation is established, which is highly suggestive that it is released, at least in part, from the trophoblast. Detection of fetal DNA in maternal serum very early in pregnancy may have clinical implications such as with the management of pregnant women carrying a fetus at risk for congenital adrenal hyperplasia.

Background: Many HIV-infected men and women have a strong desire for a child. Assisted reproductive technologies (ART) are an option for HIV-serodifferent couples to reduce the risk of HIV transmission from an infected man to the woman. Potential HIV contamination of selected spermatozoa after semen processing is an important issue in this context., Methods: HIV in processed semen obtained in our laboratory since 1995 were analysed. HIV RNA and DNA detection was performed in the selected spermatozoa of 125 men. HIV RNA was analysed in blood and semen plasma as well as HIV DNA in non-sperm cells., Results: HIV RNA and DNA were detected in the selected spermatozoa of eight and two men (6.4% and 1.6%), respectively. HIV RNA was detected with a median load of 5 copies/10(6) spermatozoa. Six of the eight men were untreated, one was taking nucleoside analogue therapy and one was on highly active antiretroviral treatment (HAART). HIV RNA detection was more likely to be positive in selected spermatozoa of men with high seminal plasma viral load. HIV RNA was detected in 26% and 11% of selected spermatozoa fractions when the seminal plasma load was > 10,000 copies/ml and 20-10,000 copies/ml, respectively, but in none when the seminal plasma tested negative., Conclusion: Selected spermatozoa may be positive for HIV RNA detection even in treated patients. Viral validation of processed semen is necessary in ART programmes for serodifferent couples, particularly in men with only partially or poorly controlled HIV infection., (Copyright 2002 Lippincott Williams & Wilkins)

Background: High, normal and poor responders are usually defined by reference to subjectively selected estradiol E2 levels at days 4-6 and the day of hCG administration (d-hCG). The purpose of this study was to use E2 percentile curves from day 5 until d-hCG to determine high, normal and poor responders, and to predict IVF outcome., Methods: In this retrospective study, 762 patients underwent 905 cycles with a GnRH agonist/recombinant FSH short protocol. They were divided into three groups according to their age. Percentile E2 curves according to E2 levels were plotted. High responders were those patients with E2 levels above the 90th percentile, normal responders had E2 between the 10th and 90th percentiles, and poor responders had E2 below the 10th percentile., Results: IVF outcome, expressed as number of oocytes, total embryos obtained and number of high grade embryos, was significantly better for patients with E2 above the 90th percentile at d-hCG for the three age groups and at day 5 for group A (<35 years). Pregnancy rates were higher for high responders, but the difference did not reach statistical significance., Conclusions: Percentile curves can be useful in controlled ovarian stimulation cycles to define high, normal and poor responders, and also to predict IVF outcome.

Background: Couples in whom the man is infected by human immunodeficiency virus (HIV) increasingly request assisted reproductive technology (ART) to allow safe procreation. Semen quality is critical in such situations., Methods: Semen characteristics were evaluated in 189 HIV-infected men requesting ART. At the time of semen analysis all men were healthy and 177 were receiving anti-retroviral therapy. Comparisons were made with HIV-seronegative men, partners of women requiring IVF because of tubal infertility, after matching for age and sexual abstinence delay., Results: The most significant semen alterations found in the HIV-infected men were reduced percentages of rapidly progressive sperm [median (range), 10% (0-30%) compared with 15% (5-30%) in the controls, P < 0.001], and increased concentrations of non-spermatic cells [3 x 10(6)/ml (0.2-16 x 10(6)/ml) compared with 1.1 x 10(6)/ml (0.1-14 x 10(6)/ml) in the controls, P < 0.001]. HIV-infected men also showed lower ejaculate volumes [2.8 ml (0.6-9.3 ml) compared with 3.6 ml (1.1-11 ml), P < 0.05] and total sperm counts [262.5 x 10(6) (0-1003 x 10(6)) compared with 310.5 x 10(6) (48.3-1679 x 10(6)), P < 0.05]., Conclusions: Semen evaluation in a large population of HIV-infected men requesting ART evidenced several alterations. Some of these anomalies might be related to anti-retroviral treatments.

Background: The cryopreservation of ovarian tissue may enable women exposed to gonadotoxic treatments to have children at a later date., Methods: Between April 1998 and October 2000, we evaluated the feasibility of long-term ovarian tissue cryopreservation in 51 women who were all at risk of becoming sterile following treatment., Results: Ovarian tissue was not cryopreserved in 20 cases because of the woman's age or premature ovarian failure. In 31 patients, ovarian tissue was frozen by a slow cooling technique using DMSO and sucrose as cryoprotectants. The patients were aged 2.7-34 years and 16 of them were <18 years old. Cryopreservation could be performed in all cases. Ovarian cortex histology was performed for all patients to evaluate the concentration of follicles. The mean number of primordial and primary follicles per mm(2) was 20.36 +/- 19.03 before 10 years of age, 4.13 +/- 2.9 between 10 and 15 years of age and 1.63 +/- 3.35 after 15 years of age. An average mean number of 26 +/- 8.2 ovarian fragments (range 13-50) were cryopreserved per patient for future autografts or for in-vitro growth of follicles., Conclusion: Cryopreservation of ovarian tissue may be systematically proposed to young women and girls at risk of becoming sterile as a result of gonadotoxic treatment.