Pseudodicentric Chromosome Originating from an X-Autosome Translocation in a Male Patient with Cryptozoospermia.

Genetic factors are responsible for 15% of male infertility conditions. Numerical and structural chromosomal anomalies are validated genetic factors leading to spermatogenic quantitative defects, with a frequency depending on the severity of the phenotype. Among the structural chromosomal rearrangements, dicentric chromosomes are generally observed in robertsonian translocations or in cases of Y chromosome isodicentrics. In X-autosome translocations, male carriers are generally infertile, regardless of the position of the breakpoint, due to interrupted spermatogenesis. We report an infertile man bearing an unusual balanced (X;22) translocation, with a centromeric X breakpoint generating a derivative pseudodicentric chromosome psu dic(22;X). Extensive cytogenetic analyses were necessary to determine the precise nature of the derivative chromosome. The likely cause of the reproductive phenotype of the patient is discussed based on meiotic chromosomal conformation.

Analysis of NR5A1 in 142 patients with premature ovarian insufficiency, diminished ovarian reserve, or unexplained infertility.

Ovarian deficiency, including diminished ovarian reserve and premature ovarian insufficiency, represents one of the main causes of female infertility. Little is known of the genetic basis of diminished ovarian reserve, while premature ovarian insufficiency often has a genetic basis, with genes affecting various processes. NR5A1 is a key gene required for gonadal function, and variants are associated with a wide phenotypic spectrum of disorders of sexual development, and are found in 0.26-8% of patients with premature ovarian insufficiency. As there is some debate about the extent of involvement of NR5A1 in the pathogenesis of ovarian deficiency, we performed an in-depth analysis of NR5A1 variants detected in a cohort of 142 patients with premature ovarian insufficiency, diminished ovarian reserve, or unexplained infertility associated with normal ovarian function. We identified rare non-synonymous protein-altering variants in 2.8 % of women with ovarian deficiency and no such variants in our small cohort of women with infertility but normal ovarian function. We observed previously reported variants associated with premature ovarian insufficiency in patients with diminished ovarian reserve, highlighting a genetic relationship between these conditions. We confirmed functional impairment resulting from a p.Val15Met variant, detected for the first time in a patient with premature ovarian insufficiency. The remaining variants were associated with preserved transcriptional activity and localization of NR5A1, indicating that rare NR5A1 variants may be incorrectly curated if functional studies are not undertaken, and/or that NR5A1 variants may have only a subtle impact on protein function and/or confer risk of ovarian deficiency via oligogenic inheritance.

Pseudodicentric Chromosome Originating from Autosomes 9 and 21 in a Male Patient with Oligozoospermia.

Genetic factors are responsible for 15% of male infertility conditions. Numerical and structural chromosomal anomalies (related to the Y chromosome or to the autosomes) are validated genetic factors leading to spermatogenic quantitative defects with a frequency depending on the severity of the phenotype. The most frequent structural chromosomal rearrangements of autosomes are translocations and inversions, whereas dicentric chromosomes involving autosomes are rare. We report a man bearing a pseudodicentric chromosome (9;21) and presenting with oligozoospermia. Extensive cytogenetic analyses were necessary to determine the precise nature of the derivative chromosome and to discount the presence of interstitial telomeric sequences. Defects in spermatogenesis and abnormal segregation at meiosis for existing spermatozoa are proposed and are the likely cause of the reproductive phenotype of the patient.

[Autophagy and spermatozoa]. / Autophagie et spermatozoïde.

Spermiogenesis, the ultimate stage of spermatogenesis, is a process involving autophagy. At this stage, the acrosome is generated by vesicular fusion and most of the cytoplasm disappears. Autophagy, literally "eating oneself", allowing the elimination and replacement of proteins and nonfunctional organelles, ensures the recycling of cellular constituents and is a highly conserved cellular mechanism within eukaryotic cells. The machinery of autophagy is present in the spermatozoon, regulating the vitality and mobility of the cells. The environmental and behavioral impact on autophagy and the consequences on spermatogenesis are beginning to be studied. The purpose of this review is to synthesize current knowledge about autophagy in the mature male gamete.

TITLE: Autophagie et spermatozoïde. ABSTRACT: La spermiogenèse, étape ultime de la spermatogenèse, est un processus qui fait intervenir des acteurs qui participe à l'autophagie. C'est en effet lors de cette étape que se forme l'acrosome par fusion vésiculaire et que disparaît la majeure partie du cytoplasme du spermatozoïde. L'autophagie (littéralement « se manger soi-même ¼), en permettant l'élimination et le remplacement continuel des protéines et des organites non fonctionnels, assure le recyclage des constituants de la cellule. C'est un mécanisme cellulaire très conservé au sein des cellules eucaryotes. La machinerie de l'autophagie est également présente dans les spermatozoïdes. Elle régule la vitalité de ces cellules et leur mobilité. Les conséquences environnementales et comportementales sur l'autophagie et sur la spermatogenèse commencent à être étudiées. Le but de cette revue est de synthétiser les connaissances actuelles concernant les processus d'autophagie dans le gamète mâle mature.

Pregnancies and obstetrical prognosis after oocyte donation in Turner Syndrome: A multicentric study.

INTRODUCTION: Turner syndrome is one of the most frequent chromosomal abnormalities in women, with a prevalence estimated to be 1 of 2500 live birth. Pregnancy in women with Turner syndrome is known to be at high risk, whether it is spontaneous or after oocyte donation, because of miscarriages and potential cardio-vascular complications which can be life-threatening. All of these patients should therefore be screened with a comprehensive cardio-vascular assessment before pregnancy, and have a close follow-up during and after pregnancy. PATIENTS AND METHODS: It is a retrospective study, conducted in 10 of the 27 French oocyte donation centers between 2012 and 2016, on all the patients presenting with Turner syndrome included in an oocyte donation program. RESULTS: 151 embryo transfers were realized in 73 patients, resulting in 39 pregnancies. Among these pregnancies, 24 children were born healthy, 11 spontaneous miscarriages, 3 voluntary abortions, 1 extra-uterine pregnancy and 1 maternal death from non-cardio-vascular origin occurred. Pregnancies were complicated by gravid arterial hypertension in 28.2% of cases, preeclampsia in 10.3% of cases, and gestational diabetes in 7.7% of cases. CONCLUSION: This study bring out obstetrical complications of the same magnitude than the ones described in the literature. Lead over a period of 4 years, in 10 French oocyte donation centers, it doesn't reveal any cardio-vascular complications, conversely to other studies published before French and American recommendations. This study reinforces the usefulness of specific recommendations for the care of these particular patients.

Autophagy is increased in cryptorchid testis resulting in abnormal spermatozoa.

Autophagy is involved in spermatogenesis by regulating germ cell maturation. This catabolic process increases with hyperthermic conditions to prevent the accumulation of damaged organelles. Cryptorchidism is associated with impairment of germ cell maturation revealed by the presence of immature forms of sperm cells in ejaculates. The aim of the present study was to evaluate the status of autophagy in sperm cells from cryptorchid patients. Semen samples of cryptorchid patients and normozoospermic controls were analyzed by immunocytochemistry and electron microscopy. Autophagy proteins, autophagy-related protein 9 (ATG9) and microtubule-associated protein, 1A/1B-light chain 3 (LC3) were localized by immunocytochemistry on the acrosome and on the equatorial segment of sperm cells. LC3 was also detected in the midpiece of cryptorchid sperm tail. Autophagy substrate p62 protein was present in the acrosome and in the postequatorial segment of sperm in control samples, but not in the cryptorchid ones. Transmission electron microscopy revealed double-membrane-limited autophagosomes in postequatorial part of spermatozoa head and midpiece in cryptorchid samples. Partly degraded mitochondria were frequently discerned in autophagic vacuoles. In conclusion, autophagy is increased in sperm cells from patients with cryptorchid history comparatively to control. Our work provides insights into the role of autophagy in the maturation and survival of human male gametes in pathological conditions. Thus, regulating autophagy could represent a potential way to improve sperm quality in cryptorchid men.

What are the Predictive Factors for Preeclampsia in Oocyte Recipients?

OBJECTIVES: Oocyte donation pregnancies are more frequently complicated by preeclampsia (PE), which cause significant fetal-maternal morbidity and mortality. Our objective was to determine risk factors for PE in oocyte recipients (OR). Our secondary objective was to describe the course of pregnancy and the neonatal outcome in this group. METHODS: This was a historical-prospective study. One hundred and fifty OR who gave birth to children at over 22 weeks of amenorrhea between January 2010 and June 2018 were included in the study. RESULTS: Risk factors for PE in OR found in univariate analysis were as follows: primiparity, primipaternity, body mass index (BMI), and anti-Müllerian hormone (AMH) of the OR and age and AMH of the oocyte donors (OD). In multivariate analysis, the BMI of the OR (odds ratio [OR]: 1.2, 95% confidence interval [CI]: [1.1-1.4], P = 0.0474) and the AMH of the OD (OR: 1.2, 95% CI: [1.2-1.4], P = 0.0481) were found to be statistically significant risk factors for PE. In addition, we observed an increase in the rate of prematurity in the OR that were not associated with fetal growth retardation, despite the occurrence of PE. CONCLUSION: In OR, the allogeneic nature of pregnancy induces an increased risk of PE, the pathophysiology of which seems different from that in other methods of conception. Thus, risk factors for PE should be reconsidered to take into account the impact of certain characteristics of OD such as age and AMH.

Pregnancy outcome in Turner syndrome: A French multi-center study after the 2009 guidelines.

OBJECTIVE: This study aimed to assess the application of the French guidelines for pregnancies in Turner syndrome (TS) and their impact on perinatal prognosis. STUDY DESIGN: We performed a French multi-center retrospective study (14 centers), including TS pregnant patients (spontaneously or by Assisted Reproductive Technology (ART)) between January 2006 and July 2017. Only clinical pregnancies were analyzed. The adjustment of medical follow-up modalities to French guidelines was evaluated for all pregnancies after 2009. Pregnancies from oocyte donation (OD) after 2009 were compared to those of a cohort of TS pregnancies obtained by OD before 2009, which were reported by the French Study Group for Oocyte Donation. RESULTS: One hundred seventy pregnancies in 103 patients were included: 35 spontaneous, 5 by means of intra-conjugal ART, and 130 with OD. No serious maternal complications were observed. We reported two stillbirths and one intra uterine fetal death. The French guidelines were partially respected. The preconceptional assessment was carried out in 74% of cases. Cardiology follow-up during pregnancy was performed in accordance with guidelines in 74% of patients. Postpartum cardiac ultrasonography was performed in 45% of pregnancies but only in 11% within 8 days post-partum. When compared to the 2009 historical cohort, the rates of high blood pressure (19% vs. 38%; p < 0.005) pre-eclampsia (8% vs. 21%; p < 0.005) and prematurity <35 weeks (15% vs 38%; p < 0.0001) were lower. CONCLUSIONS: The implementation of guidelines has allowed the standardization of TS pregnancy care and improved perinatal indicators for both mothers and children. However, an effort must be done, in a postpartum survey.

Comparison of human embryomorphokinetic parameters in sequential or global culture media.

A prospective study on randomized patients was conducted to determine how morphokinetic parameters are altered in embryos grown in sequential versus global culture media. Eleven morphokinetic parameters of 160 single embryos transferred were analyzed by time lapse imaging involving two University-affiliated in vitro fertilization (IVF) centers. We found that the fading of the two pronuclei occurred earlier in global (22.56±2.15 hpi) versus sequential media (23.63±2.71 hpi; p=0.0297). Likewise, the first cleavage started earlier at 24.52±2.33 hpi vs 25.76±2.95 hpi (p=0.0158). Also, the first cytokinesis was shorter in global medium, lasting 18±10.2 minutes in global versus 36±37.8 minutes in sequential culture medium (p <0.0001). We also observed a significant shortening in the duration of the 2-cell stage in sequential medium: 10.64 h±2.75 versus 11.66 h±1.11 in global medium (p=0.0225) which suggested a faster progression of the embryos through their first mitotic cell cycle. In conclusion, morphokinetic analysis of human embryos by Time lapse imaging reveals significant differences in five kinetic variables according to culture medium. Our study highlights the need to adapt morphokinetic analysis accordingly to the type of media used to best support human early embryo development.

Ovarian Metastases from Breast Cancer: A Series of 28 Cases.

BACKGROUND/AIM: Ovarian metastases from breast cancer present diagnostic and therapeutic challenges. We conducted a two-center retrospective study to analyze the characteristics and evolution of patients with histologically proven ovarian metastases from breast cancer. PATIENTS AND METHODS: The records of 28 patients were analyzed, taking into consideration clinical and biological characteristics of primary breast tumors and ovarian metastases. Moreover, the outcomes of patients after diagnosis of metastases were analyzed by comparing two patient groups defined by whether the surgical treatment of ovarian metastases was optimal (residual tumor <2 cm) or not (residual tumor >2 cm). RESULTS: Ovarian metastases are largely found in primary breast cancer patients with poor prognostic factors (large tumor size, positive lymph nodes, high-grade) and lobular histology, occurring on average 5 years after the diagnosis of breast cancer. Their symptoms are mild and measurement of serum markers cancer antigen (CA) 125 and CA 15-3 is useful. Their prognosis is bleak due to frequent co-existence with other metastatic sites. Lobular histology of the initial breast tumor is the only significant poor prognostic factor in our study. CONCLUSION: Women with lobular carcinoma of the breast and poor prognostic factors may benefit from ovarian surveillance based on CA 125. Following the discovery of ovarian metastases from breast cancer, further investigations are warranted to determine the extent of disease, specifically whether multiple metastases are present. Treatment of a solitary ovarian metastasis is based on surgery leaving no residual disease and adjuvant systemic treatment.