Cat eye syndrome: Clinical, cytogenetics and familial findings in a large cohort of 43 patients highlighting the importance of congenital heart disease and inherited cases.

Cat Eye Syndrome (CES) is a rare genetic disease caused by the presence of a small supernumerary marker chromosome derived from chromosome 22, which results in a partial tetrasomy of 22p-22q11.21. CES is classically defined by association of iris coloboma, anal atresia, and preauricular tags or pits, with high clinical and genetic heterogeneity. We conducted an international retrospective study of patients carrying genomic gain in the 22q11.21 chromosomal region upstream from LCR22-A identified using FISH, MLPA, and/or array-CGH. We report a cohort of 43 CES cases. We highlight that the clinical triad represents no more than 50% of cases. However, only 16% of CES patients presented with the three signs of the triad and 9% not present any of these three signs. We also highlight the importance of other impairments: cardiac anomalies are one of the major signs of CES (51% of cases), and high frequency of intellectual disability (47%). Ocular motility defects (45%), abdominal malformations (44%), ophthalmologic malformations (35%), and genitourinary tract defects (32%) are other frequent clinical features. We observed that sSMC is the most frequent chromosomal anomaly (91%) and we highlight the high prevalence of mosaic cases (40%) and the unexpectedly high prevalence of parental transmission of sSMC (23%). Most often, the transmitting parent has mild or absent features and carries the mosaic marker at a very low rate (<10%). These data allow us to better delineate the clinical phenotype associated with CES, which must be taken into account in the cytogenetic testing for this syndrome. These findings draw attention to the need for genetic counseling and the risk of recurrence.

Contraception during medical studies: A French study of 2,323 residents.

OBJECTIVE: The main objective of this work was to establish the contraceptive profile of French female medical residents and to assess the impact of workload on their choice of contraception method as well as difficulties encountered. STUDY DESIGN: We conducted a descriptive, cross-sectional, prospective national study over six months, between May and October 2019, using an anonymous online survey sent to all female medical residents in France. We formed two study groups according to reported working hours: W+ and W-. Grouping was based on three criteria: weekly workload, weekly night duty, and weekend duty per month. RESULTS: Of the 17,120 active female residents, the response rate was 15.42%. Oral contraception was the most commonly used method. The contraceptive profile of female residents was similar to that of the general French population. The W+ group of residents experienced more frequent contraceptive difficulties that had no impact on their choice of contraception. Despite the difficulties of using contraception, the W+ group used effective corrective methods, allowing them to prevent unplanned pregnancies. Residents in the W+ group reported more irregular gynecological follow-up. CONCLUSION: Better gynecological monitoring during medical studies would optimize contraceptive choices made by female medical residents in France.

Should intrauterine inseminations still be proposed in cases of unexplained infertility? Retrospective study and literature review.

OBJECTIVE: Unexplained infertility is defined by the absence of identifiable causes of infertility. The results of randomized studies and meta-analysis regarding the treatment of unexplained infertility are discordant due to methodological problems. DESIGN: The aim of this study is to compare the clinical pregnancy rate per cycle (CPR/c) in IUI and IVF/ICSI in cases of unexplained infertility, according to the woman's age group and to identify the factors which predict success. INTERVENTIONS: We performed a retrospective study in two ART centers, comparing overall clinical pregnancy, ongoing pregnancy and live birth rates in IVF/ICSI and IUI. We also compared pregnancy and birth rates according to different female age groups. RESULTS: 855 IVF/ICSI and 804 IUI cycles were compared. We found a significant difference (p < 0.001) in the pregnancy and live birth rates per cycle between IUI and IVF/ICSI, overall and in the different female age groups, except in women aged 40 and over. The greatest chances of pregnancy with IUI are found in women with secondary unexplained infertility, during the first two cycles and with a bi-follicular response to stimulation. In IVF/ICSI, pregnancy rates are higher in women with secondary unexplained infertility, in the first two cycles, in IVF and in women receiving a transfer of two embryos regardless of the embryonic stage. CONCLUSION: We recommend IVF/ICSI treatment rather than IUI for unexplained infertility (OR CPR/c 4.20 with 95% CI [3.72-4.68]). This is in accordance with NICE, which advises the use of IVF after 2 years.

Follicular GH and IGF1 Levels Are Associated With Oocyte Cohort Quality: A Pilot Study.

Introduction: Oocyte quality contributes to the development of an optimal embryo and thus a successful pregnancy. The objective of this study was to analyse the association between oocyte cohort quality and the follicular levels of growth hormone (GH), insulin-like growth factor 1 (IGF1), 25-hydroxy vitamin D (25OHD), thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4) and antithyroid antibodies, as a function of intracytoplasmic sperm injection (ICSI) outcomes. Material and methods: We conducted a prospective comparative pilot study from January 2013 to December 2017. 59 ICSI cycles constituted an abnormal oocyte cohort (n=34 cycles, in which more than 50% of oocytes presented at least one morphological abnormality) and a normal oocyte cohort (n=25 cycles, in which 50% or less of the oocytes presented at least one morphological abnormality). GH, IGF1, 25OHD, TSH, fT3, fT4 and antithyroid antibodies were measured in follicular fluid. Results: The fertilisation rate was lower in the abnormal oocyte cohort (65.5% vs. 80%, respectively, p=0.012). Oocytes' proportion with at least one abnormality was 79.4% in the abnormal oocyte cohort and 29.0% in the normal oocyte cohort. The mean number of morphological abnormalities per oocyte was significantly higher in the abnormal oocyte cohort. The follicular levels of GH (4.98 vs. 2.75 mIU/L, respectively; p <0.01) and IGF1 (72.1 vs. 54.2 ng/mL, respectively; p=0.05) were higher in the normal oocyte cohort. There was no association with follicular levels of TSH, fT3, fT4, antithyroid antibodies, or 25OHD. Conclusion: Oocyte cohort quality appears to be associated with follicular levels of GH and IGF1.

Growth hormone replacement improved oocyte quality in a patient with hypopituitarism: A study of follicular fluid.

BACKGROUND: Growth hormone (GH) is known to be involved in ovarian folliculogenesis and oocyte maturation. In patients with poor ovarian response without growth hormone deficiency (GHD), adjuvant GH treatment improves in-vitro fertilization (IVF) results. Improvement of oocyte quality in IVF by GH replacement was reported in only a few patients with GHD. We report on a new case with study of follicular fluid. METHODS: A 29-year-old patient with hypopituitarism was referred to our infertility center. She was undergoing hormonal replacement for hypogonadotropic hypogonadism and diabetes insipidus, and did not consider at first GH replacement. Four IVF procedures were performed between 2011 and 2014. Growth hormone replacement (somatotropin 1.1mg/day) was initiated before the fourth IVF procedure and unmasked central hypothyroidism; levothyroxine (75mg/day) was introduced. It took 10 months to reach the treatment objectives for insulin-like growth factor 1 (IGF1), free triiodothyronine (fT3) and free thyroxine (fT4). GH, IGF1 and thyroid hormones were measured in the blood and follicular fluid before and after GH and thyroid hormone replacement. Oocyte and embryo quality were also compared. RESULTS: The first 3 IVF procedures were performed without GH replacement. 62% to 100% of mature oocytes presented one or more morphologic abnormalities: diffuse cytoplasmic granularity, large perivitelline space with fragments, fragmentation of the first polar body, ovoid shape, or difficult denudation. Embryo quality was moderate to poor (grade B to D), and no pregnancy was obtained after embryo transfer. After GH replacement, hormones levels increased in follicular fluid: GH [7.68 vs. 1.39 mIU/L], IGF1 [109 vs. <25ng/mL], fT3 [3.7 vs. 2.5pmol/L] and fT4 [1.45 vs. 0.84ng/mL]. Concomitantly, there was dramatic improvement in oocyte quality (no abnormal morphologies) and embryo quality (grade A), allowing an embryo transfer with successful pregnancy. CONCLUSIONS: This is the first report illustrating changes in hormonal levels in follicular fluid and the beneficial effect of GH replacement on oocyte and embryo quality during an IVF procedure in a patient with hypopituitarism. These results suggest that GH replacement is beneficial for oocyte quality in patients with GHD.

Can Ratios Between Prognostic Factors Predict the Clinical Pregnancy Rate in an IVF/ICSI Program with a GnRH Agonist-FSH/hMG Protocol? An Assessment of 2421 Embryo Transfers, and a Review of the Literature.

None of the models developed in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) is sufficiently good predictors of pregnancy. The aim of this study was to determine whether ratios between prognostic factors could predict the clinical pregnancy rate in IVF/ICSI. We analyzed IVF/ICSI cycles (based on long GnRH agonist-FSH protocols) at two ART centers (the second to validate externally the data). The ratios studied were (i) the total FSH dose divided by the serum estradiol level on the hCG trigger day, (ii) the total FSH dose divided by the number of mature oocytes, (iii) the serum estradiol level on the trigger day divided by the number of mature oocytes, (iv) the serum estradiol level on the trigger day divided by the endometrial thickness on the trigger day, (v) the serum estradiol level on the trigger day divided by the number of mature oocytes and then by the number of grade 1 or 2 embryos obtained, and (vi) the serum estradiol level on the trigger day divided by the endometrial thickness on the trigger day and then by the number of grade 1 or 2 embryos obtained. The analysis covered 2421 IVF/ICSI cycles with an embryo transfer, leading to 753 clinical pregnancies (31.1% per transfer). Four ratios were significantly predictive in both centers; their discriminant power remained moderate (area under the receiver operating characteristic curve between 0.574 and 0.610). In contrast, the models' calibration was excellent (coefficients: 0.943-0.978; p < 0.001). Our ratios were no better than existing models in IVF/ICSI programs. In fact, a strongly discriminant predictive model will be probably never be obtained, given the many factors that influence the occurrence of a pregnancy.

CENTRAL RETINAL VEIN OCCLUSION IN OTHERWISE HEALTHY CHILDREN AND ADOLESCENTS: Association With Multigenetic Variants of Thrombophilia.

PURPOSE: To report cases of central retinal vein occlusion in otherwise healthy children showing combined genetic variants of thrombophilia. METHODS: Ophthalmological, pediatric records and genetic analyses of thrombophilia-associated variants were retrospectively reviewed in four children diagnosed with central retinal vein occlusion. Genetic screening, including Factor XII, platelet glycoprotein (GP) IIIa PlA1/A2 (rs5918), and GPIa/IIa C807T (rs1126643) and G873A (rs1062535) mutations, was performed by PCR amplification and Sanger sequencing of PCR products. The genotyping of prothrombin G20210A, Leiden Factor V G1691A, methylenetetrahydrofolate reductase (MTHFR) C677T/A1298C mutations, and plasminogen activator inhibitor-1 4G/5G polymorphisms was performed by real-time PCR with Fluorescence Resonance Energy Transfer (FRET) probes. RESULTS: The genotyping analysis identified combined genetic variants of thrombophilia in each patient. Mutations for MTHFR (C677T) and GPIIIa PlA1/A2 were detected in Case 1, mutations for MTHFR (C677T), GPIIIa PlA1/A2, and GPIa/IIa in Case 2, mutations for MTHFR (C677T) and GPIa/IIa in Case 3, and mutation for MTHFR (A12986C), GPIIIa Pl A1/A2, and GPIa/IIa in Case 4. Preventive low-dose aspirin therapy was prescribed to all patients. During a follow-up of 5 and 8 years, neither central retinal vein occlusion recurrence nor any other thrombotic event was observed in Cases 1 and 2, respectively. CONCLUSION: In otherwise healthy children presenting central retinal vein occlusion, genetic investigations for thrombophilia-associated variants should be considered, given the possible long-term benefit of aspirin prophylaxis.

Endometrium immunomodulation by intrauterine insemination administration of treated peripheral blood mononuclear cell prior frozen/thawed embryos in patients with repeated implantation failure.

In assisted reproductive technology (ART) programmes, approximately 10% of infertile patients have at least two or three repeated implantation failures (RIFs) after an in vitro fertilization (IVF) protocol. Successful implantation mainly depends on local immune tolerance mechanisms involving a spectrum of cytokines, interleukins and growth factors. The latter have played pivotal roles in the recruitment of immune cells (and notably T-lymphocyte cells). In total, 250 couples participating in frozen-thawed embryo transfer programme were incorporated in a randomized clinical trial (peripheral blood mononuclear cells (PBMC) subgroup: n=122; control subgroup: n=128). In the PBMC group, a blood sample was collected 5 days before the scheduled frozen-thawed embryo transfer; PBMCs were isolated using Ficoll separation and then cultured for 72 h. Two days prior to embryo transfer, 0.4 ml of cultured PBMCs were transferred into the patient's uterus. Although the clinical pregnancy rate was higher in the PBMC group (34.4%) than in the control group (23.4%), this difference was not statistically significant (P=0.05 in a chi-squared test). Nevertheless, when we limited the analysis to patients with ≥3 RIFs (n=138), there was a significant difference in the clinical pregnancy rate between the PBMC group (38.6%) and the control group (19.7%; P=0.01). Our results imply that PBMC transfer can be part of effective fertility treatment for patients with RIF.

Follicular fluid and supernatant from cultured cumulus-granulosa cells improve in vitro maturation in patients with polycystic ovarian syndrome.

OBJECTIVE: To study the effectiveness of a new in vitro maturation (IVM) approach based on heterologous follicular fluid (HFF) and supernatant of cumulus-granulosa cells (CGCs) mimicking the intact follicular microenvironment to rescue immature denuded oocytes (IDOs) of patients with polycystic ovary syndrome (PCOS) whose IVM or IVF outcomes remain poor. DESIGN: Randomized controlled trial. SETTING: University-affiliated private center. PATIENT(S): One hundred fifty-nine IDOs were obtained from 47 patients with PCOS. First, a simple IVM system (S-IVM; 40 IDOs; control group) was compared with different protocols based on the addition of autologous follicular fluid (AFF-IVM; 44 IDOs), HFF (HFF-IVM; 42 IDO), or HFF with CGC isolated from seven women without PCOS and presenting 100% in vivo oocyte maturation (HFF/CGC-IVM; 33 IDOs). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): IVM outcomes were compared among the four groups (S-IVM, AFF-IVM, HFF-IVM, HFF/CGC-IVM); then the vitro and in vivo maturation results (from controlled ovarian stimulation of PCOS patients) were compared for each group. RESULT(S): The HFF/CGC-IVM method gave the best yield of developed blastocysts per IDO compared with S-IVM, AFF-IVM, and HFF-IVM (27% vs. 2%, 2%, and 12%, respectively). The IVM rate with the HFF/CGC-IVM method was even higher than that compared with the in vivo maturation rate (79% vs. 42%), with significant improvement in the cleavage rate (71% vs. 61%). CONCLUSION(S): This adapted IVM system could be used to reach an acceptable result in meiotic competence and competent metaphase II oocytes capable of developing into intact embryos after fertilization and before transfer.

Corneal epithelial stem cells for corneal injury.

INTRODUCTION: Ocular surface diseases with limbal insufficiency represent a therapeutic challenge for restoring vision. This corneal deficiency includes both classical ocular diseases (as chemical burns) and rare ocular diseases (as congenital aniridia and ocular cicatricial pemphigoid). AREAS COVERED: Our understanding of limbal epithelial stem cells (LESCs) has increased the potential for treatment options. Pharmacological treatment strategies (as regenerating agent ophthalmic solutions) and especially surgical treatment strategies are available. Isolated LESCs can be produced by limbal primary cultures obtained from explants or cell suspensions. We review the latest cornea surgery techniques. EXPERT OPINION: The adjunction of human limbal mesenchymal cells as a support for limbal stem cell primary cultures appears to be of great interest. Recently, human-induced pluripotent stem cells have allowed the generation of minicorneal organoids. This potential means of creating a three-dimensional cornea with in vitro maturation opens up important research areas for corneal regeneration therapy.

Does the dysregulation of matrix metalloproteinases contribute to recurrent implantation failure?

INTRODUCTION: The progress in in vitro fertilization (IVF) techniques for infertility management has led to the investigation of embryo implantation site proteins such as Matrix metalloproteinases (MMPs), which may have a key role in embryo-endometrium crosstalk and in the molecular mechanisms of the embryo implantation. Areas covered: Numerous studies have generated much information concerning the relation between the different proteins at the site of implantation such as cytokines, growth factors, adhesion molecules and MMPs. However, the exact role of the MMPs in embryo implantation and the impact of their dysregulation in recurrent implantation failure have yet to be characterized. Expert commentary: The proteomic investigation of the MMPs and their molecular pathways may enable scientists and clinicians to correct this dysregulation (via appropriate means of prevention and treatment), better manage embryo transfer during IVF cycles, and thus increase the ongoing pregnancy rate.

Paternal age: Negative impact on sperm genome decays and IVF outcomes after 40 years.

This study assessed sperm quality declining on relation to paternal age and its impact on in vitro fertilization (IVF) outcomes in order to estimate the APA (Advanced Paternal Age) cutoff. For this, 83 couples undergoing IVF treatment for male factor infertility were enrolled. The women age was ≤39 years, whereas the men were divided in two groups: APA (n = 41; age ≥ 40 years) and young (Y) (n = 42; age < 40 years). Conventional semen parameters (volume, concentration, motility, vitality, and morphology) were analyzed in the collected sperm samples. Furthermore, sperm genome decays (SGD) was assessed by TUNEL assay (DNA fragmentation), aniline blue staining (chromatin decondensation), and fluorescent in situ hybridization (aneuploidy). No significant difference was found concerning the conventional semen parameters between APA and Y groups. Conversely, SGD analysis showed increased DNA fragmentation; chromatin decondensation and sperm aneuploidy rates in the APA group (respectively, 41%, 43%, and 14% vs. 25%, 23%, and 4% in Y group). IVF outcomes also were affected by paternal age as indicated by the rates of cancelled embryo transfers, clinical pregnancy and miscarriage in the two groups APA and Y (29%, 17%, and 60% vs. 10%, 32%, and 42%). Finally, statistical analysis of the results suggests that the age of 40 should be considered as the APA cutoff during ART attempts.

New intragenic rearrangements in non-Finnish mulibrey nanism.

Prenatal growth is a complex dynamic process controlled by various genetic and environmental factors. Among genetic syndromes characterized by growth restriction, MULIBREY nanism represents a rare autosomal recessive condition presenting with severe pre- and post-natal growth failure, characteristic dysmorphic features but normal neurological development. The phenotype of MULIBREY nanism is variable and overlaps with others such as the Silver-Russell syndrome. We report here three patients in two distinct non-Finnish families from North France who were first suspected to have Silver-Russell syndrome which failed to be confirmed on molecular analyses. Clinical features in the three patients led us to also consider the diagnosis of MULIBREY nanism. Sequencing of the TRIM37 gene showed the three patients shared a novel nonsense mutation (c.181 C>T p.Arg61*) in a heterozygous state. Quantitative fluorescent multiplex PCR identified a new deletion of exons 15 and 16 in TRIM37 in one isolated patient and another deletion of exon 9 in two siblings. Breakpoints of both the deletions were localized in Alu sequences. Given the high number of Alu repeats, which predispose to gene rearrangements, one should always consider such genetic rearrangements in the molecular diagnosis of non-Finnish MULIBREY nanism patients. Early diagnosis of the disease would prompt careful cardiac follow up of such patients as cardiological complication is a characteristic feature of the MULIBREY nanism as described in this report.

Impact of oocytes with CLCG on ICSI outcomes and their potential relation to pesticide exposure.

BACKGROUND: Oocyte quality is a key limiting factor in female fertility which is primarily reflected in morphological features. Centrally located cytoplasm granulation (CLCG) is one type of cytoplasmic dimorphism exhibited by oocytes that could be linked to pesticide exposure with a significant risk of decreased ICSI outcomes. METHODS: This retrospective study included 633 women who were part of an intracytoplasmic spermatozoa injection (ICSI) program between 2009 and 2011. The participants lived in the Picardy region of France and had been exposed to pesticides. The participants were divided in two groups based on prevalence of oocytes with CLCG (LCLCG [n = 83]: low prevalence of oocytes with CLCG under 25%. HCLCG [n = 68]: high prevalence of CLCG over 75%). The embryological and clinical outcomes were analysed for both groups and were calculated using the difference between the two values. RESULTS: Results for couples with HCLCG compared to LCLCG showed a decrease in embryo cleavage, ongoing pregnancy, and live birth rates (82%, 14%, 13% vs 99%, 32%, 30%, respectively).The early miscarriage rate was increased (47% vs 11%), with an OR of 3.1 (95%CI [2.1-4.1]). Due to high pesticide exposure (over 3000 g/ha), there is a higher risk of a resulting disturbed oocyte cohort with a high prevalence of CLCG over 75%. CONCLUSION: The high prevalence of oocytes with CLCG over 75% has a negative effect on embryos and the general ICSI clinical outcomes. Furthermore, a putative association between pesticide exposure and risk of CLCG was identified, justifying the need for further research and a potential need to find alternative assisted reproductive technologies for these couples. TRIAL REGISTRATION: Tabacfertimasc. ID number: ID2011-A00634-37 ; registered 2011/2/8.

Comparison of two preventive treatments for patients with recurrent miscarriages carrying a C677T methylenetetrahydrofolate reductase mutation: 5-year experience.

Objective To investigate the effect of anticoagulant treatment on pregnancy outcomes in patients with previous recurrent miscarriages (RM) who carry a methylenetetrahydrofolate reductase ( MTHFR) gene mutation. Methods In this longitudinal retrospective study, patients with RM were treated during pregnancy with either: (i) 100 mg/day aspirin and 5 mg/day folic acid (group 1); or the same protocol plus 0.4 mg/day enoxaparin (group 2). An age-matched group of triparous women without RM or thrombophilia was used as the control group (group 3). Results This study enrolled 246 women with RM (123 per treatment group) and age-matched controls ( n = 117). The delivery rate was significantly lower in group 1 than group 2 (46.3% versus 79.7%, respectively). The miscarriage rate was significantly lower in group 2 compared with group 1 (20.3% versus 51.2%, respectively). In the control group 3, the delivery rate was 86.3% and the miscarriage rate was 12.8%. Conclusion Treatment with low-dose aspirin, enoxaparin and folic acid was the most effective therapy in women with RM who carried a C677T MTHFR mutation.

Effect of Gonadotropin Types and Indications on Homologous Intrauterine Insemination Success: A Study from 1251 Cycles and a Review of the Literature.

OBJECTIVE: To evaluate the IUI success factors relative to controlled ovarian stimulation (COS) and infertility type, this retrospective cohort study included 1251 couples undergoing homologous IUI. RESULTS: We achieved 13% clinical pregnancies and 11% live births. COS and infertility type do not have significant effect on IUI clinical outcomes with unstable intervention of various couples' parameters, including the female age, the IUI attempt rank, and the sperm quality. CONCLUSION: Further, the COS used seemed a weak predictor for IUI success; therefore, the indications need more discussion, especially in unexplained infertility cases involving various factors. Indeed, the fourth IUI attempt, the female age over 40 years, and the total motile sperm count <5 × 106 were critical in decreasing the positive clinical outcomes of IUI. Those parameter cut-offs necessitate a larger analysis to give infertile couples more chances through IUI before carrying out other ART techniques.

Different Levels of DNA Methylation Detected in Human Sperms after Morphological Selection Using High Magnification Microscopy.

Objective. To analyze DNA methylation levels between two groups of spermatozoa taken from the same sample, following morphological selection by high magnification (HM) at 6100x microscopy. A prospective study was conducted and studied 876 spermatozoa from 10 randomly selected men. Sperm morphology was characterized at HM according to criteria previously established. High-scoring Score 6 and low-scoring Score 0 sperm were selected. Sperm DNA methylation level was assessed using an immunoassay method targeting 5-methylcytosine residues by fluorescence microscopy with imaging analysis system to detect DNA methylation in single spermatozoon. Results. In total, 448 S6 spermatozoa and 428 S0 spermatozoa were analyzed. A strong relationship was found between sperm DNA methylation levels and sperm morphology observed at HM. Sperm DNA methylation level in the S6 group was significantly lower compared with that in the S0 group (p < 10(-6)), OR = 2.4; and p < 0.001, as determined using the Wilcoxon test. Conclusion. Differences in DNA methylation levels are associated with sperm morphology variations as observed at HM, which allows spermatozoa with abnormal levels to be discarded and ultimately decrease birth defects, malformations, and epigenetic diseases that may be transmitted from sperm to offspring in ICSI.

Intrauterine insemination of cultured peripheral blood mononuclear cells prior to embryo transfer improves clinical outcome for patients with repeated implantation failures.

Implantation failure is a major limiting factor in assisted reproduction improvement. Dysfunction of embryo-maternal immuno-tolerance pathways may be responsible for repeated implantation failures. This fact is supported by immunotropic theory stipulating that maternal immune cells, essentially uterine CD56+ natural killer cells, are determinants of implantation success. In order to test this hypothesis, we applied endometrium immuno-modulation prior to fresh embryo transfer for patients with repeated implantation failures. Peripheral blood mononuclear cells were isolated from repeated implantation failure patients undergoing assisted reproductive technology cycles. On the day of ovulation induction, cells were isolated and then cultured for 3 days and transferred into the endometrium cavity prior to fresh embryo transfer. This immunotherapy was performed on 27 patients with repeated implantation failures and compared with another 27 patients who served as controls. Implantation and clinical pregnancy were increased significantly in the peripheral blood mononuclear cell test versus control (21.54, 44.44 vs. 8.62, 14.81%). This finding suggests a clear role for endometrium immuno-modulation and the inflammation process in implantation success. Our study showed the feasibility of intrauterine administration of autologous peripheral blood mononuclear cells as an effective therapy to improve clinical outcomes for patients with repeated implantation failures and who are undergoing in vitro fertilization cycles.

Growth hormone deficiency and pituitary malformation in a recurrent Cat-Eye syndrome: a family report.

Growth hormone deficiency affects roughly between one in 3000 and one in 4000 children with most instances of growth hormone deficiency being idiopathic. Growth hormone deficiency can also be associated with genetic diseases or chromosome abnormalities. Association of growth hormone deficiency together with hypothalamic-pituitary axis malformation and Cat-Eye syndrome is a very rare condition. We report a family with two brothers presenting with growth delay due to a growth hormone deficiency associated with a polymalformation syndrome. They both displayed pre-auricular pits and tags, imperforate anus and Duane retraction syndrome. Both parents and a third unaffected son displayed normal growth pattern. Cerebral MRI showed a hypothalamic-pituitary axis malformation in the two affected brothers. Cytogenetic studies revealed a type I small supernumerary marker chromosome derived from chromosome 22 resulting in a tetrasomy 22pter-22q11.21 characteristic of the Cat-Eye syndrome. The small supernumerary marker chromosome was present in the two affected sons and the mother in a mosaic state. Patients with short stature due to growth hormone deficiency should be evaluated for chromosomal abnormality. Family study should not be underestimated.

Contribution of Electronic Medical Records to the Management of Rare Diseases.

PURPOSE: Electronic health record systems provide great opportunity to study most diseases. Objective of this study was to determine whether electronic medical records (EMR) in ophthalmology contribute to management of rare eye diseases, isolated or in syndromes. Study was designed to identify and collect patients' data with ophthalmology-specific EMR. METHODS: Ophthalmology-specific EMR software (Softalmo software Corilus) was used to acquire ophthalmological ocular consultation data from patients with five rare eye diseases. The rare eye diseases and data were selected and collected regarding expertise of eye center. RESULTS: A total of 135,206 outpatient consultations were performed between 2011 and 2014 in our medical center specialized in rare eye diseases. The search software identified 29 congenital aniridia, 6 Axenfeld/Rieger syndrome, 11 BEPS, 3 Nanophthalmos, and 3 Rubinstein-Taybi syndrome. DISCUSSION: EMR provides advantages for medical care. The use of ophthalmology-specific EMR is reliable and can contribute to a comprehensive ocular visual phenotype useful for clinical research. CONCLUSION: Routinely EMR acquired with specific software dedicated to ophthalmology provides sufficient detail for rare diseases. These software-collected data appear useful for creating patient cohorts and recording ocular examination, avoiding the time-consuming analysis of paper records and investigation, in a University Hospital linked to a National Reference Rare Center Disease.