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RESEARCH QUESTION: What is the outcome of fertility-preservation treatments in women with endometrioma, especially those with endometrioma larger than 4 cm? DESIGN: Retrospective cohort study. Women with definitive diagnosis of ovarian endometriosis (by histology or ultrasound), who underwent fertility-preservation treatment in two IVF units between 2016 and 2021, were included. As some women cryopreserved oocytes and other embryos, the primary outcome was the number of metaphase II (MII) oocytes retrieved. RESULTS: Seventy-one women with ovarian endometriosis (OMA) underwent 138 fertility-preservation cycles. The median age of patients was 31 years. Forty out of 71 (56%) women underwent at least one surgery for OMA before fertility-preservation treatment. Multivariate analysis of each patient's first cycle was used. Women who underwent OMA surgery before fertility-preservation treatment had a 51.7% reduction (95% CI 26.1 to 68.5, Pâ¯=â¯0.001) in the number of MII oocytes compared with women with OMA who did not undergo surgery. Among a subgroup who did not undergo surgery, those with an endometrioma larger than 4 cm had similar anti-Müllerian hormone concentration (2.6 ng/ml versus 2.1 ng/ml), number of oocytes retrieved (9 versus 9) and number of MII oocytes (7.6 versus seven 7) compared with women with an endometrioma of 4 cm or less. CONCLUSIONS: Discussing fertility-preservation treatment options with patients with OMA is recommended, especially if surgery is planned.
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Endometriosis , Preservación de la Fertilidad , Infertilidad Femenina , Humanos , Femenino , Masculino , Endometriosis/complicaciones , Endometriosis/cirugía , Preservación de la Fertilidad/métodos , Estudios Retrospectivos , Infertilidad Femenina/etiología , Infertilidad Femenina/terapia , Recuperación del OocitoRESUMEN
PURPOSE: To detect which factors influence decision-making among pregnant FMR1 premutation carriers regarding the preferred mode of genetic diagnosis: IVF-PGT-M (in vitro fertilization with preimplantation genetic testing for monogenic gene diseases), or CVS (chorionic villus sampling), or AC (amniocentesis) after spontaneous conception. METHODS: In Israel FMR1 premutation preconception genetic screening is offered, free of charge, to every woman in her reproductive years. FMR1 premutation carriers with ≥ 70 CGG repeats, or a history of FXS offspring, are offered IVF-PGT-M. This is a historical cohort study including all pregnant FMR1 premutation carriers who underwent prenatal diagnosis between the years 2011 and 2016 at a tertiary medical center. Data were collected from electronic charts and through phone interviews. RESULTS: One hundred seventy-five women with high-risk pregnancies who were offered IVF-PGT-M were evaluated. In 37 pregnancies (21%), the women decided to undergo IVF-PGT-M. Using the generalized estimating equations (GEE) statistical method including seven parameters, we found that previous termination of pregnancy due to FXS and advanced woman's age were significantly associated with making the decision to undergo IVF-PGT-M. Previously failed IVF was the most significant parameter in a woman's decision not to undergo IVF-PGT-M. CONCLUSION: The most dominant factor affecting the decision of FMR1 premutation carriers to choose spontaneous conception with prenatal diagnosis versus IVF-PGT-M is a previous experience of failed IVF treatments. Women whose IVF treatments failed in the past tended to try to conceive naturally and later, during the course of the pregnancy, perform CVS or AC. Conversely, women who previously experienced a termination of pregnancy (TOP) due to an affected fetus, and older women, preferred to undergo IVF-PGT-M procedures.
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Toma de Decisiones , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Pruebas Genéticas/métodos , Mutación , Diagnóstico Preimplantación/métodos , Diagnóstico Prenatal/métodos , Técnicas Reproductivas Asistidas/tendencias , Adulto , Estudios de Cohortes , Femenino , Síndrome del Cromosoma X Frágil/diagnóstico , Síndrome del Cromosoma X Frágil/genética , Heterocigoto , Humanos , EmbarazoRESUMEN
Fragile X syndrome (FXS) is the most prevalent known genetically inherited cause for autism and intellectual disability. Premutation state can cause several clinical disorders as well. We aimed to perform a nesting approach to acquire data with regard to first degree relatives of index fragile X cases at the largest child development center in Israel in order to map characteristics of Israeli FXS permutation women carriers. Seventy-nine women were referred due to a related fragile X syndrome patient, mainly an offspring or sibling. General information regarding demographics, ethnicity, and associated medical conditions were collected using interviews and structured questionnaires. Thirteen (17 %) of the women who were referred as "carrier" were proven to be actually full mutation. The mean years of education were 14 (±1.51, range 12-17). Twenty-one women (27 %) originated from Tunisia (mainly from the island of Djerba). Ten women (13 %) reported delivery of their affected offspring beyond 41 gestational weeks. Twenty-two percent of women with premutation reported symptoms consistent with learning difficulties, mainly dyscalculia, and 14 % reported ADHD symptoms. Awareness about clinical disorders of the carriers was existent only in 25 % of the patients. Increased awareness and knowledge dissemination concerning premutation symptomatology and associated medical conditions are warranted. We suggest a national registry to be installed in different countries in order to identify fragile X premutation carriers at increased risk for various medical complications.
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Familia , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Heterocigoto , Escolaridad , Femenino , Síndrome del Cromosoma X Frágil/epidemiología , Síndrome del Cromosoma X Frágil/genética , Asesoramiento Genético , Predisposición Genética a la Enfermedad , Pruebas Genéticas , Conocimientos, Actitudes y Práctica en Salud , Humanos , Israel/epidemiología , Mutación , Encuestas y Cuestionarios , Centros de Atención TerciariaRESUMEN
The aim of this study was to evaluate whether long noncoding RNA accumulation play a role in the pathophysiology of fragile X-associated premature ovarian insufficiency (FXPOI). The study population consisted of 22 consecutive fragile X mental retardation 1 (FMR1) premutation carriers (CGGn 55-199 repeats) undergoing in vitro fertilization and pre-implantation genetic diagnosis (IVF-PGD) treatment. The control group consists of 11 patients, with <55 CGG repeats, undergoing IVF-ICSI for male factor infertility, matched by age, treated in the same period. After oocyte retrieval, granulosa cells from follicular fluid were washed and stored at -80 °C. RNA was transcribed to generate cDNA and the RNA levels were measured using RT-PCR. Transcripts levels in granulosa cells of long noncoding RNA's FMR4 and FMR6 were measured. In FMR1 premutation carriers there was a significant nonlinear association between the number of CGG repeats and the levels of FMR6 (p = 0.03), but not FMR4. The highest level of FMR6 was seen in women with mid-size CGG repeats (80-120). In addition, a significant negative linear correlation was observed between the number of oocytes retrieved and the RNA levels in granulosa cells of FMR6 (r = -0.53, p = 0.01) but not FMR4. Our study supports previous findings suggesting RNA toxic gain-of-function as one of the possible pathophysiologic mechanisms underlying FXPOI.
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Insuficiencia Ovárica Primaria/etiología , ARN Largo no Codificante/metabolismo , Adulto , Estudios de Casos y Controles , Femenino , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Células de la Granulosa/metabolismo , Humanos , Insuficiencia Ovárica Primaria/metabolismo , ARN/metabolismoRESUMEN
INTRODUCTION: The aim of this study was to evaluate the role of oxidative stress in the process of ovarian aging. METHODS: Follicular fluid (FF) from two randomly selected sibling follicles was collected from women undergoing in-vitro fertilization and tested for hydrogen peroxide (H(2)O(2)) levels. RESULTS: Group A consists of seven women with whom each of the two sibling separate follicle yielded an oocyte that was later discordantly developed to a low- and top-quality embryo. Group B consists of 13 patients in whom one of the sibling follicle yielded an oocyte while the other did not (empty follicle). High-quality embryos were derived from follicles with lower H(2)O(2) levels compared to follicles from which poor-quality embryos developed (1.004 units ± 0.260 versus 1.145 units ± 0.236, p < 0.02). H(2)O(2) levels were significantly higher (0.951 units ± 0.233 versus 0.623 units ± 0.309, p < 0.001) in sibling follicles containing oocyte compared to empty follicles. CONCLUSION: During the process of ovarian ageing, there might be a gradual increase in H(2)O(2) level in the follicle. Finally, when the follicle ages and becomes empty of oocyte H(2)O(2) levels drops significantly. Therefore, H(2)O(2) levels in FF may serve as a possible marker to determine ovarian aging and follicular metabolic age.
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Envejecimiento/metabolismo , Folículo Ovárico/metabolismo , Estrés Oxidativo/fisiología , Especies Reactivas de Oxígeno/química , Adulto , Biomarcadores/química , Femenino , Fertilización In Vitro/métodos , Líquido Folicular/química , Humanos , Peróxido de Hidrógeno/química , Oocitos/fisiologíaRESUMEN
OBJECTIVE: To compare the outcome of vitrification versus slow freezing cryopreservation for cleavage stage day 2-3 embryos. DESIGN: A retrospective observational study. SETTING: All thawed embryos assisted reproduction cycles between January 2010 and December 2012 at a single IVF laboratory of a Tertiary Medical Center. PATIENTS: Five hundred and thirty-nine cycles of day 2-3 thawed embryos. INTERVENTIONS: In 327 of the thawed cycles, the embryos were vitrified and in 212 of the cycles the embryos were derived from slow freezing embryos. MAIN OUTCOMES MEASURE: Embryo survival rate, blastomere surviving rate and pregnancy rate. RESULTS: Embryo survival rate was significantly higher after vitrification compared with slow freezing (81.6%, 647/793 versus 70.0%, 393/562 embryos, p < 0.0001). The clinical pregnancy rate per ET was significantly higher following vitrification compared to slow freezing, 20.0%, 63/314 versus 11.9%, 23/193, respectively (p = 0.02). CONCLUSIONS: Vitrification of day 2-3 cleavage stage embryos yields better cycle outcome in all the parameters compared to slow freezing.
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Blastómeros , Fase de Segmentación del Huevo , Criopreservación/métodos , Transferencia de Embrión , Embrión de Mamíferos , Infertilidad Femenina/terapia , Vitrificación , Adulto , Ectogénesis , Técnicas de Cultivo de Embriones , Femenino , Fertilización In Vitro , Humanos , Israel/epidemiología , Embarazo , Índice de Embarazo , Estudios Retrospectivos , Factores de Tiempo , Supervivencia TisularRESUMEN
AIMS: To determine the incidence and severity of acute pelvic inflammatory disease (PID) or tubo-ovarian abscess (TOA) in hospitalised women with and without a history of endometriosis. METHODS: Retrospective analysis of hospital records retrieved for all women hospitalised with PID or TOA between January 2008 and December 2011 in a tertiary referral centre. Women were compared with regard to a history of endometriosis for demographic, clinical and fertility data. RESULTS: 26 (15%) of the 174 women hospitalised due to PID or TOA were excluded because of age older than 45 years, leaving 148 for analysis. The mean age was 35.7 ± 9.3 years and mean duration of hospitalisation was 5.9 ± 3.7 days. The women were divided into two groups: Group 1 with endometriosis (n = 21) and Group 2 without endometriosis (n = 127). Women in Group 1 as compared with Group 2 were significantly more likely to have undergone a fertility procedure prior to being admitted to the hospital with PID (9/27 (45%) vs 22/121 (17%), P < 0.001); particularly in vitro fertilisation (IVF) (7/ 27 (33%) vs 12/121 (9%), P < 0.006); Women in Group 1 more frequently experienced a severe and complicated course involving longer duration of hospitalisation (8.8 ± 4.7 vs 4.4 ± 2.3 days, P < 0.0001) and antibiotic treatment failure (10/27 (48%) vs 8/121 (6%), P < 0.0001). CONCLUSIONS: Pelvic inflammatory disease in women with endometriosis is more severe and refractory to antibiotic treatment, often requiring surgical intervention. It is likely that endometriosis is a risk factor for the development of severe PID, particularly after IVF treatment.
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Antibacterianos/uso terapéutico , Endometriosis/complicaciones , Enfermedad Inflamatoria Pélvica/etiología , Adulto , Farmacorresistencia Microbiana , Femenino , Fertilización In Vitro/efectos adversos , Humanos , Persona de Mediana Edad , Paridad , Enfermedad Inflamatoria Pélvica/clasificación , Enfermedad Inflamatoria Pélvica/tratamiento farmacológico , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: To evaluate the outcome of pelvic inflammatory disease (PID) in patients with endometriosis with and without ovarian endometrioma. DESIGN: A retrospective cohort study. SETTING: A single university-affiliated tertiary center. PATIENT(S): A total of 116 patients with endometriosis hospitalized because of PID between the years 2011-2021. Fifty-nine patients with an ovarian endometrioma component were compared with 57 patients with endometriosis without endometrioma. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The primary outcome was severe PID defined as the need for surgical intervention or drainage. Secondary outcomes included tubo-ovarian abscess, number of hospitalization days, a positive cervical bacterial culture or urine sexually trasmitted disease polymerase chain reaction (STD PCR) test, and readmission because of partially treated or relapsing PID. RESULT(S): PID in patients with endometrioma was found less likely to respond to antibiotic treatment with increased risk for surgical intervention or drainage compared with endometriosis patients without endometrioma (adjusted odds ratio, 3.5; confidence interval, 1.25-9.87). On admission, patients with endometrioma were older (26.5 vs. 31.0) and less likely to have an intrauterine device (19.3% vs. 5.1%) compared with patients without endometrioma. The rate of the tubo-ovarian abscess (52.5% vs. 19.3%) was significantly higher in patients with endometrioma. Readmission rate, positive bacterial culture, and hospitalization duration were higher in the endometrioma group; however, they did not reach statistical significance. Recent oocyte retrieval and patient's age were not associated with an increased risk of severe PID. CONCLUSION(S): Endometrioma patients with PID are less likely to respond to antibiotic treatment and present a higher risk for surgical intervention.
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Endometriosis , Enfermedades del Ovario , Enfermedad Inflamatoria Pélvica , Femenino , Humanos , Endometriosis/complicaciones , Endometriosis/diagnóstico , Endometriosis/tratamiento farmacológico , Absceso/diagnóstico , Absceso/etiología , Absceso/cirugía , Estudios Retrospectivos , Enfermedad Inflamatoria Pélvica/complicaciones , Enfermedad Inflamatoria Pélvica/diagnóstico , Enfermedad Inflamatoria Pélvica/tratamiento farmacológico , Antibacterianos/efectos adversos , Enfermedades del Ovario/complicaciones , Enfermedades del Ovario/diagnóstico , Enfermedades del Ovario/tratamiento farmacológicoRESUMEN
CONTEXT: FMR1 premutation (PM) carriers are at increased risk of ovarian impairment resulting in diminished ovarian response (DOR) to exogenous follicle-stimulating hormone (FSH) stimulation. Expanded CGG repeat transcript and RAN-associated protein (FMRpolyG) have been shown to accumulate in cellular aggregates and sequester proteins, thus impairing their function. Sam68 is a multifunctional RNA-binding protein highly expressed in the gonads involved in FSH receptor (FSHR) transcript maturation during FSH-dependent follicular development. OBJECTIVE: The present study examined a possible pathophysiological explanation for DOR to exogenous FSH stimulation in FMR1 PM carriers. METHODS: We used both a human granulosa cell (GC) line model and human GCs from FMR1 PM carriers to evaluate whether Sam68 is sequestered with expanded CGG repeat transcript. RESULTS: We show that Sam68 is sequestered in GCs, most likely by interaction with the expanded CGG repeat transcript. The sequestration may lead to reduced levels of free Sam68 available for FHSR precursor transcript processing, causing dysregulation of FSHR transcript maturation, and a consequent decrease in FSHR protein levels. CONCLUSION: Sam68 sequestration may underlie the diminished ovarian response to FSH stimulation in FMR1 PM carriers.
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Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil , Células de la Granulosa , Femenino , Humanos , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/metabolismo , Heterocigoto , Células de la Granulosa/metabolismo , Ovario/metabolismo , Hormona Folículo Estimulante/metabolismoRESUMEN
Objective: This study aimed to examine the associations between follicular distribution pattern (FDP) in polycystic ovaries and menstrual disturbances in women with infertility. Materials and Methods: A retrospective review of patients was performed (n=73). Ultrasound images from cycle day 2-5 of a spontaneous or progestin induced menstrual cycle were reviewed. Ovaries were classified as polycystic ovarian morphology (PCOM) if they contained ≥12-follicles measuring 2-9 mm in diameter. Images of PCOM ovaries were classified as having a peripheral cystic pattern (PCP) with follicles arranged at the periphery of the ovary, or general cystic pattern (GCP) if follicles were dispersed heterogeneously throughout the ovarian stroma. Menstrual disturbance was assessed by questionnaire, and oligomenorrhea was defined as cycles >35 days in length. Results: PCP was more strongly associated with menstrual irregularity that GCP. 94% of subjects with bilateral PCP-experienced oligomenorrhea compared with 65% of women with a unilateral PCP ovary [odds ratio (OR) 9; p<0.05]. 29% of women with bilateral GCP ovaries experienced menstrual disturbances, less than bilateral PCP (OR 36; p=0.002), but similar to unilateral PCP (OR 3; p=0.07). Serum testosterone and luteinizing hormone (LH) levels were significantly correlated with the ovarian FDP. Conclusion: There is a relationship between menstrual irregularity or certain types of serum steroids and ovarian morphology. It remains unknown if morphology, testosterone or LH causes the menstrual disturbance or if they are co-initiated by an intervening factor.
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Progestin-primed ovarian stimulation (PPOS) regimen was established for assisted reproduction. However, its feasibility and outcomes in polycystic ovary syndrome (PCOS) patients need further evaluation. The outcomes of infertile patients with PCOS (study group) and normal ovaries (control group with unexplained infertility and tubal factor infertility) who underwent PPOS and IVF/ICSI protocol were retrospectively studied. The baseline information, primary, and secondary outcomes of patients were collected. The dynamic changes of hormones were closely monitored. 198 PCOS patients and 374 controls were included in this study. After controlled ovarian hyperstimulation (COH), 15 oocytes were retrieved from PCOS patients on average, which was more than those from the controls (p < 0.001). The oocytes and embryos obtained from the PCOS patients exhibited better developmental potential as the number of fertilized oocytes, cleaved embryos, top-quality embryos, viable embryos, cryopreserved embryos, the rate of fertilization, and viable embryo per oocyte retrieved in PCOS patients were significantly higher than those in the controls (all p < 0.001). No significant difference between the two groups was identified regarding the primary outcome, ongoing pregnancy, and other secondary outcomes. No moderate to severe ovarian hyperstimulation syndrome (OHSS) was diagnosed in either group. With the proposed PPOS protocol, the quantity, quality, developmental potential of oocytes, and embryos obtained from PCOS patients were superior to those from controls. The protocol was efficient and safe in terms of pregnancy, obstetric, and perinatal outcomes. OHSS was effectively mitigated in the patients, with or without PCOS, who underwent COH.
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Fertilización In Vitro/estadística & datos numéricos , Inducción de la Ovulación/métodos , Síndrome del Ovario Poliquístico/epidemiología , Resultado del Embarazo/epidemiología , Progestinas/administración & dosificación , Adulto , China/epidemiología , Femenino , Humanos , Embarazo , Estudios RetrospectivosRESUMEN
Breast cancer affects more than 1 million women per year worldwide. Through this study, we developed a nanoparticle-based drug delivery system to target breast cancer cells. Aspirin has been found to inhibit thromboembolic diseases with its tumor-preventing activity. As a consequence, it relieves disease symptoms and severity. Here, mesoporous silica nanoparticles (MNPs) have been used to deliver aspirin to the tumor location. MNP-based aspirin in folic acid (F)-conjugated polydopamine (MNP-Asp-PD-PG-F) vehicles are prepared for targeted breast cancer therapy. The vehicle hinges on MNP altered with polymer polyethylene glycol (PG), polydopamine (PD), and F. The delivery vehicle was studied for in vitro drug release, cytotoxicity, and breast cancer cell proliferation. F-conjugated drug delivery vehicles let MNPs achieve an elevated targeting efficacy, ideal for cancer therapy. It was also observed that compared to free aspirin, our drug delivery system (MNP-Asp-PD-PG-F) has a higher cytotoxic and antiproliferative effect on breast cancer cells. The drug delivery system can be proposed as a targeted breast cancer therapy that could be further focused on other targeted cancer therapies. Delivering aspirin by the PD-PG-F system on the tumor sites promises a therapeutic potential for breast cancer treatment.
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Women who carry the FMR1 premutation may suffer from ongoing deterioration of ovarian function. The lucidity of the molecular mechanism of FXTAS is emerging and findings from research in the field of FXTAS could elucidate the pathogenesis of FXPOI. To date there are three possible mechanisms for ovarian dysfunction in FMR1 permutation carriers. The first is the RNA toxic gain-of-function mechanism initiating loss of function of over 30 specific RNA-binding proteins. The second is associated to the formation of an abnormal polyglycine-containing protein (FMRpolyG), and the third is related to novel lncRNAs, named FMR4 and FMR6. Herein we describe our laboratory methodology, focusing on the culturing and manipulation of granulosa cells from human female premutation carriers, trying to reveal the actual possible mechanisms liable to FXPOI. Detecting the precise pathways in premutation carrier might facilitate in offering these women the opportunity to make an informed decision regarding their reproductive and family planning.
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Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Síndrome del Cromosoma X Frágil/fisiopatología , Células de la Granulosa/patología , Mutación , Insuficiencia Ovárica Primaria/fisiopatología , Animales , Portador Sano , Femenino , Síndrome del Cromosoma X Frágil/genética , Células de la Granulosa/metabolismo , Humanos , Ratones , Insuficiencia Ovárica Primaria/genética , Repeticiones de TrinucleótidosRESUMEN
Abnormalities in the X-linked FMR1 gene are associated with a constellation of disorders, which have broad and profound implications for the person first diagnosed, and extended family members of all ages. The rare and pleiotropic nature of the associated disorders, both common and not, place great burdens on (1) the affected families, (2) their care providers and clinicians, and (3) investigators striving to conduct research on the conditions. Fragile X syndrome, occurring more severely in males, is the leading genetic cause of intellectual disability. Fragile X associated tremor and ataxia syndrome (FXTAS) is a neurodegenerative disorder seen more often in older men. Fragile X associated primary ovarian insufficiency (FXPOI) is a chronic disorder characterized by oligo/amenorrhea and hypergonadotropic hypogonadism before age 40 years. There may be significant morbidity due to: (1) depression and anxiety related to the loss of reproductive hormones and infertility; (2) reduced bone mineral density; and (3) increased risk of cardiovascular disease related to estrogen deficiency. Here we report the case of a young woman who never established regular menses and yet experienced a 5-year diagnostic odyssey before establishing a diagnosis of FXPOI despite a known family history of fragile X syndrome and early menopause. Also, despite having clearly documented FXPOI the woman conceived spontaneously and delivered two healthy children. We review the pathophysiology and management of FXPOI. As a rare disease, the diagnosis of FXPOI presents special challenges. Connecting patients and community health providers with investigators who have the requisite knowledge and expertise about the FMR1 gene and FXPOI would facilitate both patient care and research. There is a need for an international natural history study on FXPOI. The effort should be coordinated by a global virtual center, which takes full advantage of mobile device communication systems.
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Introduction: Fragile X syndrome (FXS) is a common form of X-linked intellectual and developmental disability with a prevalence of 1/4000-5000 in males and 1/6000-8000 in females. Most cases of the syndrome result from expansion of a premutation (55-200 CGGs) to a full mutation (>200 CGGs) repeat located in the 5' untranslated region of the fragile X mental retardation (FMR1) gene. The risk for full mutation expansions increases dramatically with increasing numbers of CGG repeats. Recent studies, however, revealed AGG interruptions within the repeat area function as a "protective factor" decreasing the risk of intergenerational expansion. Materials and Methods: This study was conducted to validate the relevance of AGG analysis for the ethnically diverse Israeli population. To increase the accuracy of our results, we combined results from Israel with those from the New York State Institute for Basic Research in Developmental Disabilities (IBR). To the best of our knowledge this is the largest cohort of different ethnicities to examine risks of unstable transmissions and full mutation expansions among FMR1 premutation carriers. Results: The combined data included 1471 transmissions of maternal premutation alleles: 369 (25.1%) stable and 1,102 (74.9%) unstable transmissions. Full mutation expansions were identified in 20.6% (303/1471) of transmissions. A total of 97.4% (388/397) of transmissions from alleles with no AGGs were unstable, 79.6% (513/644) in alleles with 1 AGG and 46.7% (201/430) in alleles with 2 or more AGGs. The same trend was seen with full mutation expansions where 40% (159/397) of alleles with no AGGs expanded to a full mutation, 20.2% (130/644) for alleles with 1 AGG and only 3.2% (14/430) in alleles with 2 AGGs or more. None of the alleles with 3 or more AGGs expanded to full mutations. Conclusion: We recommend that risk estimates for FMR1 premutation carriers be based on AGG interruptions as well as repeat size in Israel and worldwide.
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OBJECTIVE: To evaluate fertility outcomes in infertile women with severe endometriosis (The revised American Fertility Society classification [AFS] 3-4) and repeated IVF failures, who underwent surgery due to exacerbation of endometriosis-related symptoms. DESIGN: Retrospective cohort study. SETTING: University hospital. PATIENT(S): All women who failed IVF treatment before surgery and who underwent laparoscopic surgery for severe endometriosis between January 2006 and December 2014. INTERVENTION(S): All patients were operated by highly skilled surgeons specializing in laparoscopic surgery for advanced endometriosis. Only patients with evidence of endometriosis in the pathology specimens were included in this study. MAIN OUTCOME MEASURE(S): Delivery rate after surgery. RESULT(S): Seventy-eight women were included in the present study. All women were diagnosed with severe endometriosis during surgery (AFS 3-4) and all women had experienced failed IVF treatments before surgery. All women were symptomatic before their surgery. After surgical treatment 33 women (42.3%) delivered. Three women (9%) conceived spontaneously and all other women conceived after IVF treatment. Women who delivered were younger (32.5 [±4.1] years vs. 35.5 [±3.8] years), were less often diagnosed with diminished ovarian reserve before surgery (6% vs. 28.8%), and were more often diagnosed with normal uterine anatomy (by preoperative transvaginal ultrasound and during operation). In addition, performing salpingectomy during surgery was associated with a trend of improvement in delivery rates after surgery (70% in women who delivered vs. 51% in women who failed to deliver). CONCLUSION(S): Symptomatic women with severe endometriosis and repeated IVF implantation failures may benefit from extensive laparoscopic surgery when performed by an experienced multidisciplinary surgical team to improve IVF outcome.
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Endometriosis/cirugía , Fertilidad , Fertilización In Vitro/efectos adversos , Procedimientos Quirúrgicos Ginecológicos/métodos , Infertilidad Femenina/terapia , Laparoscopía , Adulto , Endometriosis/complicaciones , Endometriosis/diagnóstico , Endometriosis/fisiopatología , Femenino , Procedimientos Quirúrgicos Ginecológicos/efectos adversos , Hospitales Universitarios , Humanos , Infertilidad Femenina/diagnóstico , Infertilidad Femenina/etiología , Infertilidad Femenina/fisiopatología , Laparoscopía/efectos adversos , Nacimiento Vivo , Edad Materna , Reserva Ovárica , Embarazo , Índice de Embarazo , Retratamiento , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Insuficiencia del TratamientoRESUMEN
OBJECTIVE: This study was designed to evaluate the role of zygote intrafallopian transfer (ZIFT) procedure in patients with repeated failure of implantation. STUDY DESIGN: A total of 141 ZIFT cycles of 132 women and 145 embryo transfer (ET) cycles of 97 women in whom five or more embryos were transferred were included in this study. Transcervical uterine embryo transfer and ZIFT cycle outcome in patients with five or more previous implantation failure were compared. Embryos were transferred by laparoscopy into the fallopian tube 24-27 h following oocytes retrieval in the ZIFT group. In the ET group, embryos were transferred transcervically on the third day following oocytes retrieval. RESULTS: The mean age was 34+/-4.9 and 34.9+/-5.0 years in ZIFT and ET group, respectively. No difference was determined between the two groups regarding the basal FSH, E2 value on the day of HCG injection and the number of oocytes retrieved or fertilized. The implantation rate was 6.5% versus 7.2%, clinical pregnancy rate was 22.7% versus 24.8% and live birth rate was 21.2% versus 16.5% in ZIFT and ET groups, respectively. CONCLUSIONS: Implementation of ZIFT procedure in patients with repeated implantation failure is not superior to transcervical uterine embryo transfer.
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Implantación del Embrión , Transferencia de Embrión , Infertilidad Femenina/terapia , Índice de Embarazo , Transferencia Intrafalopiana del Cigoto , Adulto , Femenino , Humanos , Embarazo , Embarazo MúltipleRESUMEN
Platelets are known to play a central role in primary hemostasis as well as in the pathophysiology of thrombotic disorders. However, in addition to hemostasis, platelets are involved in a variety of pathophysiological responses including immune responses, inflammation, angiogenesis, tissue regeneration, and cancer metastasis. Recent studies revealed a significant role for platelet-derived microparticles (PMP), in these responses. PMP communicate with, and deliver signals to, other cells, induce signals, and change their phenotype during inflammation, angiogenesis, and tumor metastasis. The current report describes the recent development in this field with a focus on the role of platelets and PMP in all of the above responses.
Asunto(s)
Plaquetas/metabolismo , Micropartículas Derivadas de Células/metabolismo , Transducción de Señal , Animales , Plaquetas/inmunología , Micropartículas Derivadas de Células/inmunología , Humanos , Inflamación/sangre , Inflamación/inmunología , Metástasis de la Neoplasia , Neoplasias/sangre , Neoplasias/patología , Neovascularización Fisiológica , RegeneraciónRESUMEN
The purpose of this study was to examine the growth and key functional abilities of primary cultures of salivary epithelial cells toward developing an artificial salivary gland. Cultures of epithelial cells originating from submandibular glands of BALB/c mice were established. Parenchymal cells were isolated by a Percoll gradient technique and thereafter seeded on irradiated NIH 3T3 fibroblasts serving as a feeder layer. The isolated cells were termed autologous salivary gland epithelial (ASGE) cells and could be cultivated for at least five passages (time limit of experiments). ASGE cells presented the typical organizational behavior of epithelial cells and electron microscopy, as well as immunostaining for cytokeratins, confirmed their epithelial origin. Furthermore, measurements of transepithelial resistance and water permeability indicated the ability of the ASGE cells to form a functional epithelial barrier. This study suggests that primary salivary epithelial cells can be obtained that exhibit critical characteristics needed for use with an artificial secretory device.