Scaphotrapeziotrapezoid joint loading during key pinch grip before and after trapeziometacarpal arthroplasty: a cadaver study.

In a previous cadaver study, we directly measured the load acting on the trapeziometacarpal joint for increasingly greater key pinch forces. We noted that the joint load ranges from 2 kg to 4 kg during progressively greater key pinch from 0.5 kg to 1.5 kg. Using the same experimental approach, the aim of the current study was to measure and compare the load acting on the scaphotrapeziotrapezoid joint for the same levels of isometric key pinch force, and how it changes after trapeziometacarpal arthroplasty. We performed a cadaver study using 7 fresh-frozen, unembalmed adult forearms and hands (2 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). Before the trapeziometacarpal joint surgery, median load values recorded in the scaphotrapeziotrapezoid joint were 1.2 kg (IQR, 1.0-1.4), 1.6 kg (IQR, 1.6-2.5) and 2.4 kg (IQR, 2.3-3.4) during 0.5 kg, 1 kg and 1.5 kg key pinch, respectively. After the trapeziometacarpal arthroplasty, median joint contact forces did not change significantly relative to the original configuration. Our findings indicate that the loads measured in the scaphotrapeziotrapezoid joint during a simple key pinch are in fact lower than those measured inside the trapeziometacarpal joint. After trapeziometacarpal arthroplasty, the values are similar with no increase in load, suggesting that clinically asymptomatic scaphotrapeziotrapezoid radiographic involvement may not be a contraindication to arthroplasty.

The Conventional Gait Model's sensitivity to lower-limb marker placement.

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.

Trapeziometacarpal joint loading during key pinch grip: A cadaver study.

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.

Assessment of trapezial prosthetic cup migration: A biomechanical study.

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.

Efficacy of assisted reproductive technology after ovarian tissue transplantation in a cohort of 11 patients with or without associated infertility factors.

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.

[Adverse obstetric and perinatal outcome with in vitro fertilization technology: A French nationwide population-based study]. / Risques de morbidité maternelle et périnatale en fécondation in vitro : une étude nationale de cohorte française.

OBJECTIVES: The objective of this study was to quantify the risk of maternal and perinatal morbidity with in vitro fertilization (IVF) technology compared to non-IVF pregnancies in a recent French national cohort. METHOD: The data was extracted from the hospital information data system, including all pregnancies with a delivery from 2013 to 2016. The risks of preterm birth, maternal morbidity (venous and arterial thrombosis, gestational diabetes, vascular disorders, placenta previa, placenta abruption), hypotrophy and congenital malformation were compared in both groups in univariate and multivariate analysis after adjustment on the characteristics of women (age, parity, obesity, tobacco dependence, history of diabetes or high blood pressure), multiple deliveries and sex of children. RESULTS: In all, 2,875,662 pregnancies and 2,922,712 births were analyzed, of which 49,224 were derived from IVF (1.7%). In multivariate analysis, all risks were significantly higher in IVF: premature deliveries (ORajusted=1.28; CI95%=1.24-1.32), maternal morbidity (ORajusted=1.24; CI95%=1.21-2.28), (mainly for thrombosis venous, placenta previa and placenta abruption). The risks of hypotrophy (ORajusted=1.13; CI95%=1.10-1.16) and congenital malformations (ORajusted=1.11; CI95%=1.05-1.17) were slightly increased. CONCLUSION: The results of this study on a large cohort of recent births in France confirm that there was an increased risk of maternal and perinatal morbidities in IVF. These risks were similar to those published in the international literature. This study is the starting point for a forthcoming surveillance.

Disparities in reproductive outcomes according to the endometrial preparation protocol in frozen embryo transfer : The risk of early pregnancy loss in frozen embryo transfer cycles.

PURPOSE: The purpose of this study was to determine the effect of stimulated and artificial endometrial preparation protocols on reproductive outcomes in frozen embryo transfer (FET) cycles. METHODS: We performed a retrospective study of 1926 FET cycles over a 3.5-year period in the Fertility Unit at a University Hospital. Stimulated and artificial protocols were used for endometrial preparation. The embryos for FET were obtained from either in vitro fertilization or intracytoplasmic sperm injection cycles. Live birth rate and early pregnancy loss rates were retrospectively compared. In artificial protocols, oral or vaginal administration of oestradiol 2 mg two or three times a day was followed by vaginal supplementation with progesterone 200 mg two or three times a day. In stimulated protocols, recombinant follicle-stimulating hormone was administered from day 4 onward. Vaginal ultrasound was used for endometrial and ovarian monitoring. A pregnancy test was performed 14 days after FET. If it was positive, oestradiol and progesterone were administered up until the 12th week of gestation in artificial cycles. We defined early pregnancy losses as biochemical pregnancies (preclinical losses) and miscarriages. RESULTS: Data on 865 artificial cycles (45% of the total) and 1061 stimulated cycles (55%) were collected. Early pregnancy loss rate was significantly lower for stimulated cycles (34.2%) than for artificial cycles (56.9%), and the live birth rate was significantly higher for stimulated cycles (59.7%) than for artificial cycles (29.1%). CONCLUSION: In frozen embryo transfer, artificial cycles were associated with more early pregnancy loss and lower live birth rate than stimulated cycles.

To be or not to be [fertile], that is the question.

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.

CONTEXTE: Dans la littérature, peu d'articles traitent du ressenti des hommes vis à vis de leurs spermatozoïdes. Que signifie pour un homme "avoir ou non des spermatozoïdes"? Voilà la question que nous nous sommes posée. MATERIEL ET METHODES: Pour y répondre nous avons élaboré un questionnaire qui a été rempli en ligne par 441 hommes hétérosexuels âgés de 18 à 45 ans et sans enfants. RESULTATS: A la question, "que signifie pour vous avoir des spermatozoïdes?", la majorité d'entre eux a répondu "être père". Les hommes en couple ont statistiquement répondu plus fréquemment "être père" (p < 0.05) et significativement moins fréquemment "être un (vrai) homme", "être viril", "être capable d'avoir une érection/éjaculation" comparativement aux hommes célibataires (p = 0.001). A la question, "qu' éprouveriez vous si on vous annonçait que vous n'aviez pas de spermatozoïdes ou moins que la normale?" la majorité d'entre eux à répondu "je serais déçu". Les hommes en couples ont répondu significativement plus fréquemment qu'ils se sentiraient honteux (p < 0.05) ou coupables vis à vis de leur partenaire (p < 0.0001). CONCLUSIONS: Ces résultats préliminaires doivent nous aider à mieux comprendre le ressenti des hommes vis à vis de leurs spermatozoïdes et nous aider, nous spécialistes de l'infertilité, à mieux annoncer des infertilités par azoospermie ou oligospermie en adoptant une démarche de conseil psychologique, sexuel et conjugal dans l'annonce de cette infertilité masculine. En effet "ne pas avoir un nombre élevé de spermatozoïdes et a fortiori ne pas en avoir du tout" peut avoir un impact négatif sur l'homme en termes d'humeur, de culpabilité et d'estime de soi.

High-magnification selection of spermatozoa prior to oocyte injection: confirmed and potential indications.

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.

Tumor necrosis factor-308 polymorphism increases the embryo implantation rate in women undergoing in vitro fertilization.

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.

Small human sperm vacuoles observed under high magnification are pocket-like nuclear concavities linked to chromatin condensation failure.

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.

Selection of normal spermatozoa with a vacuole-free head (x6300) improves selection of spermatozoa with intact DNA in patients with high sperm DNA fragmentation rates.

Intracytoplasmic morphologically selected sperm injection (IMSI, 6300× magnification with Nomarski contrast) of a normal spermatozoon with a vacuole-free head could improve the embryo's ability to grow to the blastocyst stage and then implant. However, the most relevant indications for IMSI remain to be determined. To evaluate the potential value of IMSI for patients with a high degree of sperm DNA fragmentation (n = 8), different types of spermatozoa were analysed in terms of DNA fragmentation. Motile normal spermatozoa with a vacuole-free head selected at 6300× magnification had a significantly lower mean DNA fragmentation rate (4.1 ± 1.1%, n = 191) than all other types of spermatozoa: non-selected spermatozoa (n = 8000; 26.1 ± 1.5% versus 4.1 ± 1.1%; P < 0.005), motile spermatozoa (n = 444; 20.8 ± 2.7% versus 4.1 ± 1.1%; P < 0.001) and motile, normal spermatozoa selected at 200× magnification (n = 370; 18.7 ± 2.7% versus 4.1 ± 1.1%; P < 0.001) and then motile, morphometrically normal spermatozoa with anterior vacuoles (n = 368; 15.9 ± 2.9% versus 4.1 ± 1.1%; P < 0.05) or posterior vacuoles (n = 402; 22.5 ± 3.6% versus 4.1 ± 1.1%; P < 0.001) selected at 6300× magnification. For patients with high sperm DNA fragmentation rates, selection of normal spermatozoa with a vacuole-free head (6300×) yields the greatest likelihood of obtaining spermatozoa with non-fragmented DNA.

Follicular fluid protein content (FSH, LH, PG4, E2 and AMH) and polar body aneuploidy.

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.

Large human sperm vacuoles observed in motile spermatozoa under high magnification: nuclear thumbprints linked to failure of chromatin condensation.

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.

[Psychological assistance for men with failures of procreation: look out for the secret wound!]. / Prise en charge psychologique des échecs de procréation, au masculin : une blessure peut en cacher une autre.

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 differs between women more than 38 and women less than 30 years of age.

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.

Preconceptional diagnosis for Robertsonian translocation as an alternative to preimplantation genetic diagnosis in two situations: a pilot study.

INTRODUCTION: Preimplantation genetic diagnosis (PGD) is widely used for women heterozygous for a Robertsonian translocation. Preconceptional diagnosis (PCD), performed before fertilization, may be an alternative to PGD, especially in countries where PGD is restricted or prohibited, as in France. It could also give different information and clarify the influence of reproductive and obstetric history. METHODS: In our study, translocation was diagnosed before ICSI in five cases (group A), and after newborn or fetal aneuploidy or miscarriage in two cases, (group B). RESULTS: First polar body (PB1) analysis using acrocentric centromeric probes was done for 85 PB1s, and aneuploidy rate was at 42.4%. Oocyte aneuploidy rate differed (p<0.0001) between groups A and B (30% vs 84%). Despite the small group sizes, we demonstrate a correlation (p=0.0358) of aneuploidy rate in polar bodies after 2 or more attempts. Three live births were recorded, all in group A. DISCUSSION: PCD could thus be an alternative to PGD. This pilot study also provides new prognostic information taking into account the women's natural history, but further confirmation is required.

Gamete cytogenetic study in couples with implantation failure: aneuploidy rate is increased in both couple members.

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.

Stability of aneuploidy rate in polar bodies in two cohorts from the same patient.

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.

Oocyte aneuploidy mechanisms are different in two situations of increased chromosomal risk: older patients and patients with recurrent implantation failure after in vitro fertilization.

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.