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Abstract Clinical gait analysis supports treatment decisions for patients with motor disorders. Measurement reproducibility is affected by extrinsic errors such as marker misplacement—considered the main factor in gait analysis variability. However, how marker placement affects output kinematics is not completely understood. The present study aimed to evaluate the Conventional Gait Model’s sensitivity to marker placement. Using a dataset of kinematics for 20 children, eight lower-limb markers were virtually displaced by 10 mm in all four planes, and all the displacement combinations were recalculated. Root-mean-square deviation angles were calculated for each simulation with respect to the original kinematics. The marker movements with the greatest impact were for the femoral and tibial wands together with the lateral femoral epicondyle marker when displaced in the anterior–posterior axis. When displaced alone, the femoral wand was responsible for a deviation of 7.3° (± 1.8°) in hip rotation. Transversal plane measurements were affected most, with around 40% of simulations resulting in an effect greater than the acceptable limit of 5°. This study also provided insight into which markers need to be placed very carefully to obtain more reliable gait data.

BACKGROUND: Maternal ageing is the only aetiological factor unequivocally linked to aneuploidy. Two mechanisms seem to explain these abnormalities in oocytes: non-disjunction and premature unbalanced separation of sister chromatids (PSSC). Previous studies of unfertilized oocytes argue for a major role of PSSC in the aetiology of aneuploidy for women of advanced age, but in vitro ageing of the oocytes could influence the results. METHODS: Owing to the high prevalence of aneuploidy in women of advanced age, chromosomal screening of the first polar body just before ICSI was offered to women (from 38 years of age) included in an assisted reproduction programme. RESULTS: Among 141 oocytes from 29 women (mean age 40 years and 2 months), 43 (30.5%) were abnormal. Sixty-five abnormalities were found and PSSC was involved in 80% of cases. CONCLUSION: These results are in accordance with previous studies and confirm, in ‘fresh’ oocytes, the major role of PSSC in the aetiology of aneuploidy in women of advanced age. [ABSTRACT FROM AUTHOR]

We find new representations for Itzykson-Zuber like angular integrals for arbitrary b, in particular for the orthogonal group O(n), the unitary group U(n) and the symplectic group Sp(2n). We rewrite the Haar measure integral, as a flat Lebesge measure integral, and we deduce some recursion formulae on n. The same methods give also Shatashvili's type moments. Finally, we prove that, in agreement with Brezin and Hikami's observation, the angular integrals are linear combinations of exponentials whose coefficients are polynomials in the reduced variables (xi [?] xj)(yi [?] yj). [ABSTRACT FROM AUTHOR]

Introduction: Around 2% of oligospermic patients requiring intracytoplasmic injection (ICSI) carry a karyotype abnormality associated to an increased aneuploidy risk. IMSI (intracytoplasmic morphologically selected sperm injection) is an efficient technique for patients with ICSI failure. The observed benefit could be linked to euploid spermatozoa selection. The aim of the study was to compare the incidence of the different segregation products of translocations in spermatozoa selected as for conventional ICSI (x400) or IMSI with a high magnification (x6000). Materials/Methods: Six patients with reciprocal translocation: 46,XY,t(10;13)(q11;q34); 46,XY,t(5;8) (p15.1;q22.1); 46,XY,t(4;11)(p15.2;q21); 46,XY,t(5;21) (q15;q22.2); 46,XY,t(8;9)(q21.1 ;q22.2); 46,XY,t(6;10)(p23. q11.2), and five patients with Robertsonian translocation: 3 45,XY, rob(13;14), 45,XY, rob(15;21); 45,XY, rob(13;15) were included. Two selections of spermatozoa were tested, first x400 as for ICSI, secondly x6000 as for IMSI. ICSI-selected and IMSI-top spermatozoa, according to Bartoov's classification, were individually aspirated in an ICSI pipette and grouped for fluorescence in-situ hybridization (FISH) performed with translocation-specific probes (Abbott) and with X,Y,18 centromeric probes. Results: In ejaculated sperm of reciprocal translocation carriers, the incidence of abnormal segregation varied from 32.6% to 53.6%, mean 43.61%. The frequency of X,Y,18 aneuploidies was 1.90%. Sperm selection did not influence the global rate of abnormalities (43.61%, 43.24%, 44.21% respectively, before selection after x400 or x6000 selection). Otherwise the repartition of the segregations was modified. Adjacent 1 segregation was less frequent after x400 selection (n = 574, P = 0.031) or x6000 selection (n = 492, P = 0.014) than in the whole sperm (n = 6042). IMSI selection also decreased adjacent 2 segregation frequency (P = 0.0001) but increased 3:1 segregation frequency (P = 0.0001). For Robertsonian translocation carriers, the aneuploidy rate seemed slightly increased by selection for IMSI (P = 0.02) (22.64%, n = 4778; 29.85%, n = 414; 37.38%, n = 323, respectively for whole sperm, x 400 and x 6000 selection). X,Y,18 aneuploidies remained stable. Conclusion: Morphological selection of the spermatozoa did not modify the global incidence of aneuploid spermatozoa in patients with balanced reciprocal translocations. Only the situation where the malsegregation induces a modification of the structure with reconstructed 'aberrant' chromosomes but not of the number of chromosomes (Adjacent 1, Adjacent 2) might be eliminated by the high-magnification morphological selection probably via a modification of the chromatin structure and/or apoptosis signs. 'Simple' aneuploidies with a structurally normal chromosome or fused full chromosomes such as Robertsonian translocations derivates were not selected at all. Finally, testicular apoptosis of germinal cells is probably an important selection factor interacting with morphology and explaining some paradoxical results of our work. [ABSTRACT FROM AUTHOR]

In this cadaveric study, we compared the performance of the TOUCH® dual mobility trapeziometacarpal prosthesis implanted sequentially in the trapeziometacarpal joint and scaphometacarpal joint. Intraprosthetic mobility, implant dislocation, intraprosthetic impingement and the effect on scaphoid position were evaluated in six hands using radiographic measurements. The standard necks of 6-10 mm were used for trapeziometacarpal arthroplasty. Scaphometacarpal arthroplasty after trapeziectomy was technically feasible but required specially designed prosthetic necks 12-26 mm in length. Compared to trapeziometacarpal arthroplasty, scaphometacarpal arthroplasty increased the intraprosthetic mobility by 7%-39%. While no complications occurred with trapeziometacarpal arthroplasty, there were two instances of implant dislocation and seven instances of intraprosthetic impingement with scaphometacarpal arthroplasty. Unlike trapeziometacarpal arthroplasty, scaphometacarpal arthroplasty altered scaphoid position by translating it in an ulnar and proximal direction relative to the radius., Competing Interests: Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Mariette Bergère, Damien Motte, Julier Mottet and Bernard Prandi are employed by KeriMedical SA. Lionel Athlani has a remunerated research contract with KeriMedical SA.

To our knowledge, no study has directly measured the loads in the trapeziometacarpal joint during an isometric key pinch. The aim of this study was to measure the load acting on the trapeziometacarpal joint for increasingly greater key pinch forces (0.5 kg-1.5 kg). We performed a cadaver study using 10 fresh-frozen, unembalmed adult forearms and hands (5 right and 5 left). Thumb pinch was simulated by loading the main actuator tendons involved in the key pinch grip (i.e., adductor pollicis, flexor pollicis longus, extensor pollicis longus, extensor pollicis brevis and abductor pollicis longus tendons). Measurements were made inside the joint using a force-sensing resistor sensor (Tekscan® FlexiForce™ force sensor). All specimens were tested twice in a row in the same condition. The median load values recorded in the trapeziometacarpal joint were 1.9 kg (IQR 2.2-1.5), 3 kg (IQR 3.4-2.7) and 4.1 kg (IQR 4.4-3.9) during 0.5 kg, 1 kg, and 1.5 kg key pinch, respectively. For each specimen, similar load values were observed during both loading trials. Our findings indicate that the loads measured directly in the trapeziometacarpal joint during a simple key pinch are materially lower than those estimated in biomechanical models of the thumb (generally greater than 10 kg for 1 kg of applied force) probably due to intersubject variability. This pilot study will serve as a basis for further studies, for example, comparing biomechanical thumb models and experimental measurements under the same set-up conditions., (Copyright © 2021 SFCM. Published by Elsevier Masson SAS. All rights reserved.)

We performed a biomechanical study using 60 Sawbones® rigid foam blocks of two simulated densities (osteoporotic, n = 30 and non-osteoporotic, n = 30) and 10 cadaveric trapezium bones from fresh-frozen, unembalmed adult cadaver hands to assess the trapezial prosthetic cup migration with progressively greater compression loads (10-40 kg). Two cups from the Touch® prosthesis were compared: 9-mm conical cup and 9-mm spherical cup. Uniaxial compression tests were carried out using an MTS Criterion® Series 40 Electromechanical Testing System. Cup migration was measured in millimeters (mm) at 10, 20, and 40 kg of compression load. Median cup migration values were similar in the cadaveric trapezium bones and Sawbones® non-osteoporotic blocks, and higher in the Sawbones® osteoporotic blocks. In the cadaveric trapezium bones and the Sawbones® non-osteoporotic blocks, migration values were less than or equal to 0.1 mm for 10 and 20 kg loads; it was 0.2 mm for 40 kg load. In the Sawbones® osteoporotic blocks, migration values were less than or equal to 0.3 mm for 10 and 20 kg loads; it was 0.4-0.5 mm for 40 kg load. There was no significant difference between the two cup shapes in both cadaveric trapezium bones and Sawbones® non-osteoporotic blocks. In Sawbones® osteoporotic blocks, the largest difference between the two cup shapes was 0.1 mm for loads up to 40 kg, which corresponded to our measurement accuracy. Our findings indicate that the trapezial component of total trapeziometacarpal joint arthroplasty undergoes very weak migration for axial compression loads up to 40 kg, presumably below the threshold of clinical relevance. The cup shape did not have an obvious influence; however, low bone mineral density may result in greater cup migration., (Copyright © 2021 SFCM. Published by Elsevier Masson SAS. All rights reserved.)

Purpose: IVF treatment in women with grafted frozen-thawed ovarian tissue is associated with poor reproductive outcomes. The aim of this study was to evaluate the efficacy of ovarian tissue transplantation (OTT) followed by assisted reproductive technology (ART) in women with or without associated infertility factors., Methods: This is a prospective cohort study with retrospective data collection including eleven women, four of whom having an infertility factor (IF), who had undergone OTT in one university center between 2005 and 2017, followed by ART in six in vitro fertilization (IVF) centers., Results: In total, 25 of the 85 cycles initiated (29%) were canceled, resulting in 60 oocyte retrievals. Ninety-five oocytes were retrieved: 36 were abnormal or immature, 29/39 fertilized (74%) after ICSI and 13/20 (65%) after IVF. Thirty-five embryos were transferred in seven patients (5/7 patients without IF and 2/4 patients with IF). After ART, one patient with IF experienced two pregnancies, one resulting in a live birth. For all patients, pregnancy rates and live birth rates were 7.4% and 3.7% per embryo transfer, respectively. Nine pregnancies and four live births occurred after spontaneous conception in five patients without IF, none in the infertility group., Conclusion: This study confirms that IVF treatment in women with grafted frozen-thawed ovarian tissue is associated with poor outcomes. However, the chances of natural conception are high in women without IF. Patients with IF, without the possibility of spontaneous pregnancy, should be informed of poor reproductive outcomes after OTT followed by ART., Trial Registration Number: NCT02184806.

Many therapeutic agents offer a low useful dose (dose responsible for efficacy)/useless dose (dose eliminated or responsible for toxicity) ratio, mainly due to the fact that therapeutic agents must ensure in one single object all the functions required to deliver the treatment, which leads to compromises in their physico-chemical design. Here we introduce the concept of priming the body to receive the treatment by uncorrelating these functions into two distinct objects sequentially administered: a nanoprimer occupying transiently the main pathway responsible for therapeutic agent limited benefit/risk ratio followed by the therapeutic agent. The concept was evaluated for different nature of therapeutic agents: For nanomedicines we designed a liposomal nanoprimer presenting preferential hepatic accumulation without sign of acute toxicity. This nanoprimer was able to increase the blood bioavailability of nanomedicine correlated with a lower hepatic accumulation. Finally this nanoprimer markedly enhanced anti-tumor efficacy of irinotecan loaded liposomes in the HT-29 tumor model when compared to the nanomedicine alone. Then, for small molecules we demonstrated the ability of a cytochrome inhibitor loaded nanoprimer to increase efficacy of docetaxel treatment. These results shown that specific nanoprimers could be designed for each family of therapeutic agents to answer to their specific needs.

Objective: To assess sperm quality as a function of the sampling site (testis or epididymis) in obstructive azoospermia (OA)., Materials and Methods: DNA fragmentation rates in spermatozoa sampled from the testis and epididymis (from patients with different etiologies of OA) were assessed in a dUTP nick-end labeling assay., Results: Twenty-one OA patients were included: 5 had congenital bilateral absence of the vas deferens, 8 had genital tract infections, and 8 had idiopathic OA. A total of 8506 spermatozoa sampled from the testis, 18,358 sampled from the caput epididymis, and 18,881 sampled from the corpus/cauda epididymis were assessed. For each patient, spermatozoa from the testis had a lower overall DNA fragmentation rate (6.71% ± 0.75 in average) than epididymal spermatozoa from the caput (14.86% ± 1.89 in average; P = .0007) or the corpus/cauda (32.61% ± 3.11 in average; P < .0001). The DNA fragmentation rates did not differ significantly as a function of the etiology of OA. In this small series, all deliveries were obtained with sperm samples with a low DNA fragmentation rate and delivery rates tended to be higher when testicular sperm (rather than epididymal sperm) was used (35.7% vs 12.1%, respectively; P = .06)., Conclusion: Our data argue in favor of using testicular sperm (rather than epididymal sperm) for patients with obstructive azoospermia., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: According to our literature analysis, there are no data focused on spermatozoa emotional representations in childless men and data on the emotional repercussions of a diagnosis of infertility on men are still scarce. Thus, in this work, we investigated what the presence or absence of spermatozoa in the semen symbolize for men., Material and Methods: To answer this question, 441 childless heterosexual men participated in an anonymous, prospective, Internet-based survey., Results: In response to the question "What would having a high or normal sperm count symbolize for you?" the most frequent answer was "ability to father a child". Men living with a partner were significantly more likely than single men to answer "ability to father a child" ( p  < 0.05) and less likely to answer "virility" and/or "ability to have an erection/ejaculation" ( p  = 0.001). In response to the question "If you found out that you had a low sperm count or no spermatozoa at all, how would you feel?", most of the men stated that they would be disappointed. Men living with a partner were more likely to state that they would feel ashamed ( p  < 0.05) or guilty with regard to their partner ( p  < 0.0001)., Conclusions: These preliminary results should help us to improve (i) the way that male infertility is announced (it is easier to find the right words if one understands the possible importance of having a high sperm count) and (ii) the psychological, marital and sexual counselling provided to men with a diagnosis of infertility.

Intracytoplasmic morphologically selected sperm injection (IMSI) involves the use of differential interference contrast microscopy at high magnification (at least ·6300) to improve the observation of live human spermatozoa (particularly by showing sperm head vacuoles that are not necessarily seen at lower magnifications) prior to intracytoplasmic sperm injection (ICSI) into the oocyte. However, a decade after IMSI’s introduction, the technique’s indications and ability to increase pregnancy and/or birth rates (relative to conventional ICSI) are subject to debate. In an attempt to clarify this debate, this work performed a systematic literature review according to the PRISMA guidelines. The PubMed database was searched from 2001 onwards with the terms ‘IMSI’, ‘MSOME’ and ‘high-magnification, sperm’. Out of 168 search results, 22 relevant studies reporting IMSI outcomes in terms of blastocyst, pregnancy, delivery and/or birth rates were selected and reviewed. The studies’ methodologies and results are described and discussed herein. In view of the scarcity of head-to-head IMSI versus ICSI studies, the only confirmed indication for IMSI is recurrent implantation failure following ICSI. All other potential indications of IMSI require further investigation., (Copyright © 2013 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Study Question: Do TNF-308 and -238 polymorphisms impact the embryo implantation rate after in vitro fertilization (IVF) in women without female infertility factor?, Summary Answer: The presence of the TNF-308A allele is associated with high implantation and multiple pregnancy rates in women without known infertility factors after ovarian hyperstimulation with exogenous FSH., What Is Already Known: Multiple pregnancies are frequent after the use of Assisted Reproductive Technologies. Single embryo transfer (SET) has been proposed as a simple way to prevent these risks. However, the extension of SET indications to patients not selected based on specific criteria is controversial because of reduced pregnancy rates. To date, the predictive value of the parameters used for SET (age, gynecological history of the patient and uterine characteristics) allows a pregnancy rate of ~30%., Study Design, Size, Duration: The potential predictive value of TNF polymorphisms (-308, rs1800629 and -238, rs361525) on implantation rate was evaluated in 424 women requiring IVF due to male fertility factors. This cohort retrospective study was conducted over 4 years in University-affiliated hospitals., Participants, Setting, Methods: The entire patient group included 424 women undergoing intracytoplasmic sperm injection (ICSI) due to male fertility factors without the contribution of any female factor. From among this group, a selected patient group included 120 women with a normal karyotype, age under 38 years, serum follicle-stimulating hormone (Day-3 FSH) levels below 10 IU/l, a long agonist desensitization protocol associated with recombinant FSH treatment and a Caucasian background., Main Results and the Role of Chance: The TNF-238 polymorphism was not associated with implantation rate. In contrast, the presence of the TNF-308A allele was associated with increased Day 3-E2 levels as well as higher implantation and multiple pregnancy rates after fresh embryo transfer in women from the entire and selected patient groups. Moreover, in the selected patient group, the presence of the TNF-308A allele was also associated with a decrease in the miscarriage rate. The benefit of the TNF-308A allele in predicting implantation rates was not observed after the use of frozen embryos., Limitations, Reasons for Caution: Future studies are needed to evaluate whether the TNF-308A allele might also be a biomarker in women with infertility factors., Wider Implications of the Finding: The TNF-308A allele may represent a good candidate for a potential predictive, non-invasive biomarker in the SET strategy. However, its impact should be evaluated in prospective studies., Study Funding/competing Interest: This study was conducted with financial support from the French Institute for Health and Medical Research (INSERM), Organon France for a FARO (Fond d'Aide à la Recherche Organon) fellowship (to V.T.) and CHU Nice PHRC (PHRC 09-279).There are no competing interests.

Since an embryo's ability to grow to the blastocyst stage and implant can be improved by selection of a normal spermatozoon with a vacuole-free head, this study set out to determine the nature of small sperm vacuoles observed under high magnification (>×6300). For 15 infertile men with various sperm profiles, high-magnification microscopy was used to select motile, morphometrically normal spermatozoa with no vacuoles (n=450) or more than two small vacuoles (each of which occupied less than 4% of the head's area; n=450). Spermatozoa acrosome reaction status and degree of chromatin condensation were analysed. Three-dimensional deconvolution microscopy was used to accurately image the nucleus and acrosome at all depths in all spermatozoa. In all 450 spermatozoa with small vacuoles, the latter were seen to be abnormal, DNA-free nuclear concavities. Spermatozoa with small vacuoles were significantly more likely than vacuole-free spermatozoa to have noncondensed chromatin (39.8% versus 9.3%, respectively; P<0.0001). There was no significant difference between the two groups of spermatozoa in terms of acrosome reaction status. No association between chromatin condensation and acrosome reaction status was observed. Small human sperm vacuoles observed under high magnification are pocket-like nuclear concavities related to failure of chromatin condensation., (Copyright © 2013 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

For nonobstructive azoospermic (NOA) patients with a normal karyotype or for Klinefelter syndrome (47,XXY) patients, intracytoplasmic sperm injection is associated with an increased aneuploidy risk in offspring. We examined testicular cells from patients with different azoospermia etiologies to determine the origin of the aneuploid spermatozoa. The incidence of chromosome abnormalities was investigated in all types of azoospermia. Four study subgroups were constituted: Klinefelter patients (group 1), NOA patients with spermatogenesis failure but a normal karyotype (group 2), obstructive azoospermic patients with normal spermatogenesis (group 3), and control patients with normal sperm (group 4). The pachytene stage (in the three azoospermic groups) and postmeiotic cells (in all groups) were analyzed with fluorescence in situ hybridization. No aneuploid pachytene spermatocytes were observed. Postmeiotic aneuploidy rates were higher in the two groups with spermatogenesis failure (5.3% and 4.0% for groups 1 and 2, respectively) than in patients with normal spermatogenesis (0.6% for group 3 and group 4). Whatever the etiology of the azoospermia, the spermatozoa originated from euploid pachytene spermatocytes. These results strengthen the hypothesis whereby sperm aneuploidy in both Klinefelter patients and NOA patients with a normal karyotype results from meiotic abnormalities and not from aneuploid spermatocytes. The fact that sperm aneuploidy was more frequent when spermatogenesis was altered suggests a deleterious testicular environment. The study results also provide arguments for offering preimplantation genetic diagnosis or prenatal diagnosis when a pregnancy occurs for fathers with NOA (whatever the karyotype).

Even though cryopreservation of human spermatozoa is known to alter sperm motility and viability, it may also induce nuclear damages. The present study set out to determine whether or not cryopreservation alters motile sperm morphology under high magnification and/or is associated with chromatin decondensation. For 25 infertile men, we used high-magnification microscopy to determine the proportions of various types of motile spermatozoa before and after freezing-thawing: morphometrically normal spermatozoa with no vacuole (grade I), ≤ 2 small vacuoles (grade II), at least 1 large vacuole or >2 small vacuoles (grade III), and morphometrically abnormal spermatozoa (grade IV). The spermatozoa's chromatin condensation and viability were also assessed before and after freezing-thawing. Cryopreservation induced sperm nuclear vacuolization. It decreased the proportion of grade I + II spermatozoa (P < .001). It induced a decrease in the sperm viability rate (P < .001) and increased the proportion of sperm with noncondensed chromatin (P < .001). The latter parameter was strongly correlated with sperm viability (r = 0.71; P < .001). However, even motile sperm presented a failure of chromatin condensation after freezing-thawing, because the proportion of sperm with noncondensed chromatin was correlated with high-magnification morphology (r = -0.49 and 0.49 for the proportions of grade I + II and grades III + IV, respectively; P < .001). Cryopreservation alters the organelle morphology of motile human spermatozoa and induces sperm chromatin decondensation. High-magnification microscopy may be useful for evaluating frozen-thawed spermatozoa before use in assisted reproductive technology procedures (such as intrauterine insemination, in vitro fertilization, and intracytoplasmic sperm injection) and for performing research on cryopreservation methods. If frozen-thawed sperm is to be used for intracytoplasmic sperm injection, morphological selection under high magnification may be of particular value.

Purpose: Our objective was to identify a marker for oocyte aneuploidy in follicular fluid (FF) in women with an increased risk of oocyte aneuploidy after controlled ovarian hyperstimulation., Materials and Methods: Three groups of oocytes were constituted for polar body screening by FISH (chromosomes 13, 16, 18, 21 and 22): Group 1, advanced maternal age (n = 156); Group 2, implantation failure (i.e. no pregnancy after the transfer of more than 10 embryos; n = 101) and Group 3, implantation failure and advanced maternal age (n = 56). FSH and other proteins were assayed in the corresponding FF samples., Results: Of the 313 oocytes assessed, 35.78 % were abnormal. We found a significant difference between the follicular FSH levels in normal oocytes and abnormal oocytes (4.85 ± 1.75 IU/L vs. 5.41 ± 2.47 IU/L, respectively; p = 0.021). We found that the greater the number of chromosomal abnormalities per oocyte (between 0 and 3), the higher the follicular FSH level., Conclusion: High FF FSH levels were associated with oocyte aneuploidy in women having undergone controlled ovarian hyperstimulation.

Introduction: Obtaining an adequate number of high-quality oocytes is a major challenge in controlled ovarian hyperstimulation (COH). To date, a range of hormonal and clinical parameters have been used to optimize COH but none have significant predictive value. This variability could be due to the genetic predispositions of single-nucleotide polymorphisms (SNPs). Here, we assessed the individual and combined impacts of thirteen SNPs that reportedly influence the outcome of in vitro fertilisation (IVF) on the ovarian response to rFSH stimulation for patients undergoing intracytoplasmic sperm injection program (ICSI)., Results: Univariate analysis revealed that only FSHR, ESR2 and p53 SNPs influenced the number of mature oocytes. The association was statistically significant for FSHR (p=0.0047) and ESR2 (0.0017) in the overall study population and for FSHR (p=0.0009) and p53 (p=0.0048) in subgroup that was more homogeneous in terms of clinical variables. After Bonferroni correction and a multivariate analysis, only the differences for FSHR and ESR2 polymorphisms were still statistically significant. In a multilocus analysis, only the FSHR and AMH SNP combination significantly influenced oocyte numbers in both population (p<0.01)., Discussion: We confirmed the impact of FSHR and ESR2 polymorphisms on the IVF outcome. Furthermore, we showed for the first time that a p53 polymorphism (which is already known to impact embryo implantation) could influence the ovarian response. However, given that this result lost its statistical significance after multivariate analysis, more data are needed to draw firm conclusions. Only the FSHR and AMH polymorphism combination appears to influence mature oocyte numbers but this finding also needs to be confirmed., Materials and Methods: A 13 gene polymorphisms: FSHR(Asn680Ser), p53(Arg72Pro), AMH(Ile49Ser), ESR2(+1730G>A), ESR1(-397T>C), BMP15(-9C>G), MTHFR1(677C>T), MTHFR2(1298A>C), HLA-G(-725C>G), VEGF(+405G>C), TNFα(-308A>G), AMHR(-482 A>G), PAI-1 (4 G/5 G), multiplex PCR assay was designed to genotype women undergoing ICSI program. We analyzed the overall study population (n=427) and a subgroup with homogeneous characteristics (n=112).

Background: An embryo's ability to grow and implant can be improved by selection of a normal spermatozoon with a vacuole-free head. However, large vacuoles in spermatozoa have yet to be fully characterized. The present study aimed to determine whether these vacuoles are of nuclear, membrane and/or acrosomal origin., Methods: We studied 15 infertile patients with differing sperm profiles. For each sperm sample, we used high-magnification (×10 000) contrast microscopy to select and assess 30 normal 'top' spermatozoa and 30 spermatozoa with a large sperm-head vacuole (≥ 25% of the head's cross-sectional area). We subsequently analysed the spermatozoa's degree of chromatin condensation (aniline blue staining), DNA fragmentation (terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labelling assay) and chromosome content (fluorescence in situ hybridization X,Y,18). Atomic force microscopy enabled us to map the plasma sperm membrane in detail. Three-dimensional deconvolution microscopy enabled us to reconstruct images of the nucleus and acrosome in 'top' and 'vacuolated' spermatozoa., Results: We studied a total of 450 'top' spermatozoa and 450 vacuolated spermatozoa. The rate of non-condensed chromatin was higher for 'vacuolated' spermatozoa than for 'top' spermatozoa (36.2 ± 1.9 versus 7.6 ± 1.3%, respectively; P < 0.0001). 'Top' and 'vacuolated' spermatozoa did not differ significantly in terms of DNA fragmentation (0.7 ± 0.4 versus 1.3 ± 0.4% respectively; P = 0.25) or aneuploidy (1.1 ± 0.5 versus 2.2 ± 0.7% respectively; P = 0.21). The majority of aneuploid spermatozoa (9 out of 15) lacked chromatin condensation. In all vacuolated spermatozoa, the acrosome was intact, the plasma membrane was sunken but intact and the large vacuole was identified as an abnormal, 'thumbprint'-like nuclear concavity covered by acrosomal and plasmic membranes., Conclusions: The large vacuole appears to be a nuclear 'thumbprint' linked to failure of chromatin condensation.

Introduction: Preconception diagnosis requires first polar body biopsy. When the hole in the zona pellucida is made with a laser beam, heat propagation could, like the biopsy itself, be deleterious. Our aim was to evaluate the effect of this technique on human in vitro matured oocyte and embryo development., Methods: One hunded fifty five retrieved immature oocytes from 75 women, matured in vitro, were distributed in 3 groups: 50 oocytes in a control group, without laser drilling and first polar body biopsy, 52 oocytes in a group with only laser drilling, and 53 oocytes in a group with both laser drilling and first polar body biopsy. Safety was evaluated using four criteria: [1] oocyte lysis rate, [2] oocyte activation rate, [3] oocyte development after calcium ionophore treatment, [4] and embryo chromosome breakage incidence after Tarkowski preparation., Results: No difference in the four criteria was observed between the 3 oocyte groups., Conclusions: We did not find evidence of deleterious effect of laser drilling and first polar body biopsy on in vitro matured oocytes, according to our criteria.

When one thinks of the failures of ART one naturally thinks of the suffering that they generate; but behind this pain, there is the suffering of infertility and, behind this latter, other distress we showed at the time of a recent research that they could play a part in infertility itself. The psychotherapy will help assume the failures, so that the traumatisms do not come to solidify in an impossible mourning, covering non elaborate former grieves. A sublimation of the desire of reproduction can make it possible for the unfertile man to peacefully consider other forms of paternity. For it to be possible, it is necessary that the subject should not be in the refusal of the psychic effraction, which the announcement of its infertility produces. When it is the case, to put on the couple on psychological assistance may help to restore a share of the narcissistic wounds; more particularly the one related to the suffering of the couple that often comes to be added to the wound of infertility.

Pronuclear morphology has been reported as a good tool for studying embryo development and euploidy. Comparing two groups of women with different aneuploidy risk, women more than 38 years old (n = 28) known to be at high risk of aneuploidy, and women under 30 years old (n = 35), this study investigated whether pronuclear morphology could be used routinely as an alternative to preimplantation genetic screening (PGS) in countries where PGS is prohibited. Pronuclear morphology was evaluated for 301 zygotes and related to embryo quality and pregnancy outcome. For the older women, an increased frequency of zygotes with abnormal polar body and pronuclei alignment was observed, i.e. type gamma, with 93% aneuploidy risk (26.0 versus 15.1% P < 0.05) and fewer zygotes with a good development prognosis (36.4 versus 47.8%; P < 0.05). A1alpha configuration was associated with good implantation rate and was not related to day 2 embryo quality. This configuration was less frequent in the group of women more than 38 years old and among non-pregnant women under 30 years, compared with pregnant women under 30 years old. Pronuclear morphology seemed linked to age, but not associated with embryo quality. A larger study allowing correlation analysis is necessary to confirm the value of these criteria and the link to a woman's age.

Objective: To examine sperm meiotic segregation in a man with mosaic ring chromosome 21., Design: Case report., Setting: Hospital departments of reproductive biology, cytogenetics, gynecology, and obstetrics., Patient(s): One patient referred for cryptozoospermia, heterozygous for a ring chromosome., Intervention(s): Fluorescence in situ hybridization with chromosome 21-specific probes after sperm selection., Result(s): A total of 169 spermatozoa were selected; 92.3% carried a normal 21 chromosome, 6.5% the ring chromosome, and 1.2% both., Conclusion(s): Ring chromosome frequency in mature sperm cells was low and may be due to preferential meiosis of normal spermatogonia,which could explain the cryptozoospermia and unexpected ratio in this case.

Purpose: Implantation failure is known to be associated with an increased risk of aneuploidy in embryos, a situation leading to a pre-implantation genetic screening, not allowed in different countries like France. Our aim was to evaluate the gamete aneuploidy incidence in this context, using first polar body and spermatozoa aneuploidy screening., Methods: Three groups were considered: 11 couples with pregnancy obtained after IVF for female infertility (group 1); 20 couples with pregnancy obtained after IVF for male infertility (group 2); and 35 couples with implantation failure (group 3). In group 3, 28 couples treated by ICSI volunteered for first polar body analysis (PB1)., Results: Spermatozoa aneuploidy rate was increased in groups 2 (1.6%) and 3 (2.1%) in comparison to group 1 (0.6%). PB1 aneuploidy rate was 35.4% in group 3. Finally, eight couples (32%) had no particular chromosomal risk in gametes, 15/25 (60%) presented an increased spermatic (>2%) or oocyte (>1/3) aneuploidy rate, and 2/25 (8%) had both., Conclusion: Those results confirm that implantation failure has a heterogeneous origin, that gamete chromosome abnormality rate is one of the major contributing factors, and that 1st Polar body and spermatozoa aneuploidy screening or pre-implantation genetics screening may be indicated for these couples.

The aim of this study was to evaluate the stability of the aneuploidy rate of the first polar body. Knowing the stability of the oocyte aneuploidy rate for each patient would allow the first analysis to be used as a prognostic tool for further attempts at intracytoplasmic sperm injection (ICSI). After a first unsuccessful ICSI attempt with preconceptional screening, 24 women underwent a second attempt. First polar body aneuploidy rates were compared in the course of two successive ovarian stimulations. The first polar body was biopsied after laser dissection of the zona pellucida and five chromosomes were analysed using the MultiVysion polar body multicolour probe panel. A total of 200 polar bodies were analysed; 91 and 109 in the first and second ICSI attempts, respectively. The total aneuploidy rate was identical in the first and second attempts; 44.0% (40/91) and 44.0% (48/109), respectively. The first evaluation of the aneuploidy rate was statistically (P = 0.0007) correlated with the second, with a correlation coefficient, r = 0.707. The stability of the aneuploidy rate in different cohorts from the same patient, if confirmed in a larger series, makes this parameter a useful tool for counselling couples.

Objective: To clarify the mechanisms underlying oocyte abnormalities in meiosis: meiotic nondisjunction of a whole chromosome or premature separation of sister chromatids in two situations of increased chromosomal risk., Design: Preconception diagnosis by first polar-body analysis in two situations of increased chromosomal risk., Setting: Departments of reproductive biology, cytogenetics, gynecology, and obstetrics., Patient(s): First polar body analysis was proposed to 76 patients (91 cycles) for advanced age (AMA; n = 30, 36 cycles), recurrent implantation failure (RIF; >10 embryos transferred without implantation; n = 32, 36 cycles), or both (AMA + RIF; n = 14, 19 cycles), before their intracytoplasmic sperm injection procedure., Intervention(s): First polar-body analysis using fluorescence in situ hybridization., Main Outcome Measure(s): Mechanisms and frequency of aneuploidy., Result(s): Three hundred eighty-four oocytes were analyzed by fluorescence in situ hybridization, 130 from women >38 years of age, 171 from women with RIF, and 83 from women with both indications. The oocyte abnormality rate was similar in the three groups, respectively, 38.5%, 40.4%, and 45.8%. The aneuploidy mechanisms were different for women >38 years of age who had no previous implantation failure (AMA) compared with women of whatever age who had implantation failure (P<.05 vs. RIF; P<.001 vs. AMA+RIF), with, respectively, for the AMA, RIF, and AMA+RIF groups, 72.2%, 56.6%, and 49.2% premature separation of sister chromatids and 27.8%, 43.4%, and 50.8% meiotic nondisjunction. In the two implantation-failure groups, we distinguished a subgroup (22% in the RIF group and 33% in AMA+RIF group) of patients with >2/3 abnormal oocytes, suggesting a meiosis alteration., Conclusion(s): The mechanisms accounting for oocyte aneuploidy differed in the two clinical situations of advanced maternal age and RIF. Advanced maternal-age aneuploidy was linked to a loss of sister chromatid cohesion that led to one single chromatid abnormality, whereas implantation failure is a much more heterogeneous situation.

Objective: To determine whether the size of CAG repeat in exon 1 of the androgen receptor (AR) gene is related to impaired spermatogenesis in older men., Design: Study of two groups of older men: one with preserved spermatogenesis and the other with arrested spermatogenesis., Setting: University teaching hospital., Patient(s): Twenty-eight men aged from 53 to 102 years., Intervention(s): The DNA fragment encoding the AR polyglutamine tract was amplified from DNA of testis tissue., Main Outcome Measure(s): The size of the CAG repeat was evaluated by using fluorescent-labeled polymerase chain reaction performed on an ABI Prism 377 DNA sequencer followed by automated analysis with Genscan 3.1.2 software., Result(s): Mean CAG repeat length was 22.76 +/- 3 in the group of 13 aged men with preserved spermatogenesis and 21.86 +/- 2.23 in the group of 15 aged men with arrested spermatogenesis., Conclusion(s): Impaired spermatogenesis in elderly men does not seem to be correlated with the AR gene CAG repeat length, which therefore does not appear to be a risk factor for impaired spermatogenesis in older men.

In our species, reproduction failure rate is high. Clinical evidence is miscarriage where chromosomal origin was largely involved (66% of cases). The development of assisted reproduction techniques made possible to analyse unfertilized oocytes and preimplantation embryos. The results have shown a high rate of chromosome abnormalities before implantation (50%). Two mechanisms were identified which could generate aneuploidy, the meiosis non-disjunction and the premature separation of sister chromatids (PSSC). A FISH analysis of the first polar body, a cell complementary to the oocyte after meiosis, can be performed before intracytoplasmic sperm injection. We studied 2 distinct populations (patients over 38 years old and patients with recurrent implantation failure) and we confirmed that PSSC is the major mechanism linked to advanced maternal age in human.

Objective: To evaluate the influence of aging on testicular histology and the aneuploidy rate in testis postmeiotic cells., Design: Comparison between older men and younger men., Setting: Deceased donors and patients who requested assisted reproductive technology (ART)., Patient(s): Thirty-six older men (61-102 years old) and 10 younger men (29-40 years old)., Intervention(s): Testes were obtained from 35 deceased donors, and testicular biopsies were obtained from 11 patients who requested ART., Main Outcome Measure(s): Histomorphometry of testis and fluorescent in situ hybridization (FISH), with a three-probe set X, Y, and 18., Result(s): The histomorphometric study showed a thickening of the basal membrane when spermatogenesis was arrested. The number of germinal and Sertoli cells decreased as age increased. The rate of aneuploidy of postmeiotic cells was 1.1% for the control group, 1.29% for older subjects with preserved spermatogenesis, and 14.28% for the subjects with an arrested spermiogenesis. Only this last figure was higher than the control group., Conclusion(s): The rate of aneuploidy in older subjects (61-95 years old) with preserved spermatogenesis was not statistically different from that found in the control group; it was increased in older subjects with arrested spermatogenesis.

Objective: To study the effects of undetectable inhibin B concentrations on the outcomes of testicular sperm extraction (TESE) and of intracytoplasmic sperm injection (ICSI)., Design: Retrospective study., Setting: Obstetrics, gynecology, and reproductive biology departments., Patient(s): We carried out TESE on 75 men with nonobstructive azoospermia: 42 men had an inhibin B concentration of or = 15 pg/mL (group 2). Twenty-five ICSI cycles were carried out using sperm from men in group 1 (group A1), and 35 ISCI cycles were carried out using sperm from men in group 2 (group A2). The outcomes of ICSI in groups A1 and A2 were compared with those of 81 ICSI cycles performed for obstructive azoospermia (group B)., Intervention(s): Testicular sperm extraction, testicular spermatozoa cryopreservation, and ICSI., Main Outcome Measure(s): Testicular sperm extraction outcome, pregnancy, and delivery., Result(s): Sperm were significantly less likely to be successfully recovered from men in group 1 than from those in group 2 (21% vs. 48%). The inhibin B concentration was significantly lower in men in whom TESE failed, but the FSH concentration did not differ. The implantation rate per embryo transferred was twofold lower in group A1 (7.4%) than in group B (16%), but this difference is not statistically significant., Conclusion(s): Patients with undetectable inhibin B concentration should be informed of the low chances of positive testicular biopsy, and more embryos should be transferred to improve the success rate.

Objective: To describe a successful pregnancy and delivery after testicular sperm extraction (TESE) despite an undetectable concentration of serum inhibin B in a man with nonobstructive azoospermia., Design: Case report., Setting: Obstetrics and gynecology and reproductive biology departments., Patient(s): A 31-year-old woman and a 32-year-old man with nonobstructive azoospermia and an undetectable inhibin B serum level., Intervention(s): TESE, testicular spermatozoa cryopreservation, intracytoplasmic sperm injection (ICSI)., Main Outcome Measure(s): Pregnancy and delivery., Result(s): Successful pregnancy and delivery of a normal healthy child following a third ICSI cycle with frozen-thawed spermatozoa extracted from the testis., Conclusion(s): This case report shows that there is no minimal level of inhibin B below which TESE is always unsuccessful. The delivery of a normal healthy baby is strong evidence to perform TESE in these circumstances.