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Biomedical subjects

J Cohen

Publications and source records attributed to J Cohen.

At least 631 records · Page 35Linked to original sources

Intracytoplasmic sperm injection: a novel treatment for all forms of male factor infertility.

OBJECTIVE: To demonstrate the effectiveness of intracytoplasmic sperm injection to treat male factor infertility and to report on the achievement of fertilization and pregnancy compared with standard in vitro insemination. DESIGN: Controlled clinical study. SETTING: Couples suffering from male factor infertility treated in an academic research environment. PATIENTS: Two hundred twenty-seven couples in whom the male partners were presumed to be the cause of repeated failed attempts at IVF or whose semen parameters were unacceptable for conventional IVF. INTERVENTIONS: Oocytes for this study were harvested after superovulation with GnRH agonist and gonadotropins. After removing the cumulus cells, a single spermatozoon was injected directly into the cytoplasm of metaphase II oocytes, and the outcome was analyzed in terms of semen parameters and origin of semen sample. MAIN OUTCOME MEASURES: Fertilization and pregnancy rates (PRs) in relation to sperm parameters and origin of semen sample. RESULTS: Two hundred twenty-seven couples were treated by intracytoplasmic sperm injection resulting in an ongoing pregnancy rate of 37.0% per retrieval (84/227). There were 47 singleton pregnancies (5 of which were vanishing twin pregnancies), 30 twin gestations, 6 triplet pregnancies, and 1 quadruplet pregnancy. The concentration of the total motile spermatozoa present in the ejaculate as well as the origin of the samples influenced the fertilization rate but not the pregnancy outcome. CONCLUSIONS: Intracytoplasmic sperm injection can be used successfully to treat couples who have failed IVF or who have too few spermatozoa for conventional methods of in vitro insemination. Sperm parameters do not clearly affect the outcome of this technique.

Adult↗

Endometriosis: a stage by stage analysis--the role of in vitro fertilization.

OBJECTIVE: To investigate the impact of endometriosis stage on IVF. PATIENTS: A retrospective study of 214 patients diagnosed with endometriosis who underwent 360 cycles of IVF at The New York Hospital-Cornell Medical Center. Meanwhile, 111 pure mechanical (tubal) infertility patients treated in 160 cycles at the same time were designated as the control group for comparison. MAIN OUTCOME MEASURES: Patient's hormone and semen profiles, hormonal response and outcome to stimulation, as well as the outcome of pregnancy, abortion, and delivery rate were analyzed. RESULTS: No differences in the pregnancy outcome between the endometriosis and control groups were noted when compared among the subgroups of pure endometriosis, endometriosis plus tubal factor, endometriosis plus others (primarily endometriosis plus male factor), and control. Comparing the outcomes in pure endometriosis cases by staging, we could not find any discrepancies in terms of pregnancy rates (PRs) according to the severity of the disease. The addition of GnRH analogur down-regulation to gonadotropin stimulation resulted in an increase in PR. A relatively high delivery rate (38.9% per cycle, 41.9% per retrieval, and 43.2% per transfer) was achieved when the pure endometriosis patients were treated with concomitant leuprolide acetate down-regulation and gonadotropin. CONCLUSION: We have observed that pregnancy outcome in patients with endometriosis was not different than the outcome for patients with mechanical (tubal) infertility. There were no differences in PRs by stage of endometriosis.

Adult↗

Cystic fibrosis gene mutations do not affect sperm function during in vitro fertilization with micromanipulation for men with bilateral congenital absence of vas deferens.

OBJECTIVE: To assess the effects of cystic fibrosis transmembrane-conductance regulator (CFTR) gene mutations on sperm function and fertility in men with bilateral congenital absence of the vas deferens. DESIGN: Prospective. SETTING: Division of urologic microsurgery and associated hospital-based IVF unit. MAIN OUTCOME MEASURES: Fertilization and pregnancy rates. PATIENTS: Men referred to our fertility unit for treatment of bilateral congenital absence of the vas deferens, using sperm surgically retrieved from the epididymis with IVF and micromanipulation. RESULTS: Of 45 men with bilateral congenital absence of the vas, 54% (19/35) tested were found to be carriers of CFTR gene mutations, with one compound heterozygote. Epididymal sperm from men affected with CFTR mutations fertilized 19% (29/152) of oocytes, whereas men without mutations fertilized 22% (44/204) of oocytes. Pregnancy rates (PRs) were 36% (5/14) for cycles involving men with CFTR mutations and 33% (5/15) for other patients with congenital absence of the vas deferens but without detectable CFTR mutations. CONCLUSIONS: The presence of detectable CFTR mutations does not affect fertilization rates or PRs for men with bilateral congenital absence of the vas deferens when IVF and micromanipulation are applied.

Cystic Fibrosis↗

Micropuncture retrieval of epididymal sperm with in vitro fertilization: importance of in vitro micromanipulation techniques.

OBJECTIVES: To evaluate the importance of in vitro micromanipulation techniques, specifically intracytoplasmic sperm injection (ICSI), for the fertility treatment of men with congenital absence of the vas deferens (CAV) or other unreconstructable male reproductive tract obstruction. METHODS: Results using ICSI during in vitro fertilization (IVF) were compared to previously published results of IVF alone and IVF with other micromanipulation techniques at the same infertility center. Main outcome parameters evaluated were: fertilization rate per oocyte, clinical pregnancy rate, and ongoing pregnancies and deliveries. RESULTS: IVF with ICSI yielded a fertilization rate per oocyte of 140 of 312 (45%) and a clinical pregnancy rate of 14 of 27 (52%) per cycle of sperm and egg retrieval. Ongoing pregnancies or deliveries have occurred for 13 of 27 (48%) cycles with ICSI. These results were better than our previously published results of IVF alone or in conjunction with the micromanipulation techniques of subzonal insertion (SuZI) or partial zona dissection (PZD) that yielded a 119 of 631 (19%; P < 0.0001) fertilization rate, clinical pregnancy rate of 14 of 51 (27%; P < 0.001) and ongoing pregnancy or delivery for 12 of 51 cycles (24%; P < 0.001). CONCLUSIONS: Epididymal sperm retrieval should be performed only when micromanipulation is available in conjunction with IVF to maximize chances of fertilization and subsequent pregnancies. The use of ICSI for epididymal sperm appears to maximize chances of pregnancy for couples with surgically unreconstructable obstructive male infertility.

Cytoplasm↗

Management of septic shock.

Septic shock due to bacterial and other infections remains an increasing cause of hospital mortality and morbidity. Early recognition and prompt management with diagnostic evaluation, antimicrobial therapy, surgery when indicated and advanced life support undoubtedly saves many lives. Once treatment has been instituted, careful and frequent monitoring is required to optimise therapy and detect complications at an early stage. However, once shock and organ failure have become established the mortality remains high and has changed little in the last few years despite improvements in intensive management. A variety of other approaches to treatment are under investigation but as yet there are insufficient data to recommend their use.

Anti-Bacterial Agents↗

Highly effective method of human oocyte activation.

Fresh and aged unfertilised human oocytes were activated by electroporation and by exposure to isotonic solution of mannitol supplemented with low concentrations of calcium, magnesium and chloride. Over 95% of the fresh oocytes were activated, all showing formation of one pronucleus and extrusion of the second polar body. Oocytes activated 1 and 2 days post-collection showed activation rates of 66.6% and 64.1%, respectively; however, the proportion of one-pronucleate oocytes in these groups was significantly lower (61.6% and 23.5%, respectively). There was no difference in the activation efficiency between the two activation modes. Twelve activated oocytes from the freshly collected group cleaved when left in culture. It is concluded that, in the human, a brief exposure to isotonic solution of mannitol with low concentrations of calcium, magnesium and chloride is a very effective activation stimulus.

Calcium↗

Intracytoplasmic sperm injection in dysmorphic human oocytes.

Fertilisation and development of dysmorphic human oocytes recovered from hyperstimulated ovaries have been evaluated following intracytoplasmic sperm injection (ICSI) for treatment of male infertility. A total of 2968 oocytes at metaphase II of meiosis were injected, of which 806 (27.2%) were dysmorphic at the light microscopic level. Cytoplasmic abnormalities included granularity, areas of necrosis, organelle clustering, vacuoles, and accumulating saccules of smooth endoplasmic reticulum. Anomalies of the first polar body and zona pellucida, as well as non-spherical shapes of oocytes, were also noted. Contrary to previous findings linking some dysmorphisms to non-assisted fertilisation failure, in this study no single abnormality led to a reduction in the fertilisation rate, nor was fertilisation compromised in oocytes with multiple abnormalities. The incidence of normal fertilisation (two pronuclei and two polar bodies) was 69% in both the dysmorphic and non-dysmorphic oocytes. While overall pregnancy and implantation results were not altered in the group of patients (n = 242) in whom at least one dysmorphic oocyte was injected, exclusive replacement of embryos which originated from dysmorphic oocytes led to a higher incidence of early pregnancy loss. It is concluded that aberrations in the morphology of human oocytes--most probably a product of controlled ovarian stimulation--are of little or no consequence to fertilisation or early cleavage after ICSI. It is possible, however, that these embryos have a reduced potential for implantation and further development.

Embryo Implantation↗

Prenatal sonographic diagnosis of Treacher Collins syndrome: a case and review of the literature.

We report the prenatal ultrasonographic diagnosis of a fetus with mandibulofacial dysostosis (Treacher Collins syndrome). Sonographic findings included: polyhydramnios, microcephaly, abnormal fetal facial features (slanting forehead, microphthalmos, micrognathia), and abnormal fetal swallowing. A review of the current literature pertaining to prenatal diagnosis of this condition is presented.

Adolescent↗

Development and implementation of intracytoplasmic sperm injection (ICSI).

The purpose of this paper is to elucidate the experimental steps that led to the development of intracytoplasmic sperm injection (ICSI) and its application in the human. ICSI has become the most successful micromanipulation procedure for treating male infertility. A total of 355 in vitro fertilization (IVF) cycles utilizing ICSI are described; 180 couples were previously treated in 509 IVF cycles but achieved no fertilization and 175 couples could not be treated by IVF because of extremely poor semen parameters. Of the 3063 metaphase II (M II) oocytes retrieved, 2970 were injected with a survival rate of 93.6%, yielding 1917 bipronuclear zygotes (64.5%). In 148 patients, a foetal heart was evidenced by ultrasound; 11 of these patients miscarried between 7 and 13 weeks of gestation. The ongoing pregnancy rate was 38.6% (137/355) per retrieval and 40.5% (137/338) per embryo replacement. At the time of writing, there were 22 deliveries and one therapeutic abortion for a trisomy 21 chromosomal abnormality. In addition, 66 singleton, 37 twin, 10 triplet and 1 quadruplet pregnancies were ongoing. The concentration of motile spermatozoa in the ejaculate only slightly influenced the fertilization rate (P < 0.001) and the pregnancy outcome (P < 0.01). A preliminary injection procedure utilizing intracytoplasmic injection of isolated sperm heads was performed in 35 M II human oocytes with resultant fertilization and cleavage rates of 74% and 73% respectively. Skills in ICSI were acquired by injecting hamster and unfertilized human oocytes with human sperm. ICSI can be used to successfully treat couples who have failed IVF or who have too few spermatozoa for conventional in vitro insemination.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Injecting and sexual risk-taking behaviour among regular amphetamine users.

A sample of 301 regular amphetamine users were interviewed regarding injecting and sexual risk-taking behaviours. Two-thirds of subjects were injecting the drug, with males being 1.8 times more likely to do so. Nearly half (41%) of injectors had shared injecting equipment in the preceding month. Females were twice as likely as males to report recent needle sharing. Having a regular sexual partner who injects amphetamines, using benzodiazepines and experiencing higher levels of psychopathology were independently associated with needle sharing. The number of sexual partners in the preceding six months was independently associated with having had paid sex in that period, and higher levels of polydrug use.

Adolescent↗

Adjunctive therapy for septic shock: a review of experimental approaches.

Septic shock remains a major cause of morbidity and mortality, especially in the intensive care setting. A vast array of treatment strategies is under investigation; despite success in animal models, no effective adjunctive therapy has yet been approved for clinical use. This paper reviews the development of experimental therapies for sepsis and discusses those treatments that show promise for application in humans. Approaches to treatment fall into three broad categories: strategies directed against bacterial components, those directed against host-derived inflammatory mediators, and those designed to limit tissue damage. Because septic shock is a dynamic and evolving condition, different strategies may be needed at different stages in the pathogenesis of sepsis. Through carefully performed trials and thoughtful selection of combination therapy aimed at different points in the pathological process, it may be possible in the future to modify the course of this serious condition.

Acute-Phase Proteins↗

A comprehensive support program: effect on depression in spouse-caregivers of AD patients.

Caregivers of Alzheimer's disease patients often suffer from depression. Using a longitudinal treatment/control study, we examined the effects of a comprehensive support program on depression in spouse-caregivers. This psychosocial intervention program treats the primary caregiver and family members over the entire course of the disease through individual and family counseling, the continuous availability of ad hoc counseling, and support group participation. In the first year after intake, the control group became increasingly more depressed, whereas the treatment group remained stable. By the eighth month, treated caregivers were significantly less depressed than those in the control group. These results suggest that enhancing long-term social support can have a significant impact on depression in caregivers.

Activities of Daily Living↗

Chromosomal status of uni-pronuclear human zygotes following in-vitro fertilization and intracytoplasmic sperm injection.

Uni-pronuclear embryos (n = 42) were analysed by fluorescence in-situ hybridization (FISH) with two to four chromosome pair-specific probes. Half of these embryos resulted from conventional insemination and half from intracytoplasmic sperm injection (ICSI). The majority of uni-pronuclear embryos from conventional insemination were normally diploid (61.9%) whereas only 9.5% of uni-pronuclear ICSI embryos (P < 0.001) were diploid. In addition, a significantly higher number of uni-pronuclear embryos from conventional insemination had a Y chromosome (10/21, 47.6%) when compared with ICSI embryos (2/21, 9.5%) (P = 0.015). It is concluded that the majority of uni-pronuclear embryos following regular in-vitro fertilization are fertilized, whereas those from ICSI are parthenogenetically activated. The latter embryos should not be considered for embryo replacement.

Adult↗

Genetics of abnormal human fertilization.

The purpose of this study was to assess the genetic status of abnormal zygotes following assisted fertilization. Dispermic, monopronucleated and digynic zygotes were allowed to cleave intact or after enucleation, and on the biopsied blastomeres, multiplex polymerase chain reaction and fluorescent in-situ hybridization were performed. It was found that the distal pronucleus was usually male in origin in dispermic embryos, and that the sex ratio was restored when they were enucleated; however, they became mosaic at metaphase and their genetic heterogeneity was not restored after enucleation. Monopronucleated zygotes derived from standard in-vitro insemination can be transferred to the patient, since they usually showed normal diploid complement in their cells. On the contrary, single-pronucleated zygotes derived from intracytoplasmic sperm injection were usually activated parthenogenetically, but not fertilized. Digynic embryos, unlike dispermic ones, had a very low incidence of mosaicism, and when present, such mosaicism originated at a later embryo division. Most of the digynic embryos were triploid, indicating that the first division was normal and bipolar; moreover, when the female pronucleus was removed, they became diploid and their genetic status was considered normal. The recognition and understanding of fertilization abnormalities allow the identification of methods leading to their avoidance or correction.

Blastomeres↗

Protective effects of a recombinant amino-terminal fragment of human bactericidal/permeability-increasing protein in an animal model of gram-negative sepsis.

Bactericidal/permeability-increasing protein (BPI) has bactericidal properties and also binds lipopolysaccharide (LPS). The ability of a recombinant amino-terminal fragment of BPI to protect mice from death after challenge with a number of different strains of Escherichia coli was tested. BPI prevented death in animals challenged with the J5 rough strain but not with smooth strains O111:B4 and O7K1. Protection was associated with a reduction in serum LPS and tumor necrosis factor-alpha levels but not with reduction in blood bacterial counts. BPI was effective at protecting against death in mice injected with purified O111:B4 LPS. Lack of protection after injection with live O111:B4 and O7K1 may be due to production by these models of approximately 1000-fold higher blood bacterial count compared with J5. Thus, BPI is a promising therapy in the treatment of gram-negative septic shock, although the range of organisms against which it is effective remains to be determined.

Animals↗

Monozygotic triplet pregnancy following transfer of frozen-thawed embryos.

We report a case of monozygotic triplet pregnancy after the transfer of three frozen-thawed embryos. The outcome of the pregnancy was the birth of three healthy normal boys. The pregnancy was a monochorionic triamniotic triplet pregnancy. This is the first such case of triplets, although it seems that zygote splitting is significantly more common than normal in patients undergoing in-vitro fertilization.

Adult↗

Efficacy and safety of recombinant follicle stimulating hormone (Puregon) in infertile women pituitary-suppressed with triptorelin undergoing in-vitro fertilization: a prospective, randomized, assessor-blind, multicentre trial.

The objective of this study was to compare the efficacy and safety of a recombinant follicle stimulating hormone (FSH) preparation (Org 32489, Puregon) with a urinary FSH preparation (Metrodin) in infertile women undergoing in-vitro fertilization (IVF and embryo transfer and who were pituitary-suppressed with triptorelin. In an assessor-blind, group-comparative, multicentre study, 60 women were randomized to Org 32489 and 39 to urinary FSH. An evaluation of the main parameter, the mean total number of oocytes recovered, indicated a similar efficacy for the two preparations: 9.7 with Org 32489 versus 8.9 with urinary FSH. In addition, there were no significant between-group differences with respect to other efficacy variables such as the total dose used, the duration of the treatment, the number of follicles > or = 17 mm in diameter and embryo quality. The ongoing pregnancy rates per attempt (30.2 versus 17.4%) and per transfer (34.0 versus 18.8%) were higher with Org 32489, but this difference was not statistically significant. No clinically relevant differences between Org 32489 and urinary FSH were seen with respect to safety variables. Serum antibodies were not detected in any of the subjects. It is concluded that Org 32489 compares favourably with urinary FSH in the treatment of infertile pituitary-suppressed women undergoing IVF and embryo transfer.

Abdominal Pain↗