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Biomedical subjects

K B Isaacson

Publications and source records attributed to K B Isaacson.

At least 19 recordsLinked to original sources
PubMed1999

Effect of a baseline ovarian cyst on the outcome of in vitro fertilization-embryo transfer.

OBJECTIVE: To determine the significance of prestimulation ovarian cysts on the response to controlled ovarian hyperstimulation and the outcome of IVF. DESIGN: Retrospective study. SETTING: In vitro fertilization unit in an academic center. PATIENT(S): One hundred thirty-seven patients undergoing IVF. INTERVENTION(S): The outcome of 71 patients who had an ovarian cyst of >10 mm detected at ultrasound examination performed on day 3 was compared with that of 66 patients who underwent a similar protocol and did not have an ovarian cyst. MAIN OUTCOME MEASURE(S): Parameters evaluated were the E2 level on the day of hCG administration, the number of follicles, the number of oocytes retrieved, the number of embryos transferred, and the pregnancy rate. RESULT(S): The E2 level on the day of hCG administration and the number of mature oocytes retrieved were lower in the group with a baseline cyst. The pregnancy rate also was significantly lower in the group with a cyst (24% versus 41%). The presence of a baseline ovarian cyst decreases the odds of pregnancy 0.37-fold (95% confidence interval, 0.16-0.87). CONCLUSION(S): A baseline ovarian cyst on cycle day 3 was associated with a poorer outcome after IVF-ET.

Adult↗
PubMed1999

Complications of hysteroscopy.

Most of the complications of hysteroscopy are avoidable and, fortunately, rare. With improved training, experience, and technology, most of these complications should become extinct. There will always be some unavoidable complications as well as difficulties resulting from inexperience. A goal for the future is to teach operating room personnel how to recognize and treat these complications to ensure the best patient outcome possible. Once gynecologic surgeons recognize the safety and efficacy of diagnostic and operative hysteroscopy as a minimally invasive option to treat benign uterine pathology, these procedures will proliferate and result in better patient care and improved quality of life.

Adult↗
PubMed1999

Operative hysteroscopy in physiologic distention media.

Distention media are essential in operative hysteroscopy to ensure good visualization within the uterine cavity. Carbon dioxide, dextran-70, glycine, sorbitol, mannitol, saline, and Ringer's lactate solution have all been used, but are associated with difficulties that prevent their use with instruments that achieve appropriate current densities. Three new distention media are now available that correct problems associated with the earlier products. (J Am Assoc Gynecol Laparosc 6(1):113-118, 1999)

Electrosurgery↗
PubMed1998

Elevated expression of the proapoptotic BCL-2 family member, BAK, in the human endometrium coincident with apoptosis during the secretory phase of the cycle.

OBJECTIVE: To characterize the distribution of BAK (BCL-2 homologous antagonist/killer) protein in the human endometrium relative to the occurrence of apoptosis. DESIGN: A prospective, controlled study. SETTING: An academic hospital. PATIENT(S): Premenopausal women with histologically normal endometrium who were undergoing hysterectomy and curettage. INTERVENTION(S): Endometrial tissues were collected. MAIN OUTCOME MEASURE(S): Detection of BAK protein by immunohistochemical and immunoblot analyses, and of apoptosis by in situ DNA end-labeling. RESULT(S): BAK protein was detected in secretory endometrium and was confined to the glandular epithelial cells of the functionalis layer. Immunoreactive BAK was absent from most of the cells of the proliferative endometrium. By immunoblot analysis, we confirmed the immunohistochemical data by demonstrating that a 30-kD protein corresponding to BAK was elevated in lysates prepared from secretory, as compared with proliferative, endometrium. The elevated levels of BAK coincided with the onset of apoptosis in endometrial glandular epithelial cells during the secretory phase of the menstrual cycle. CONCLUSION(S): BAK protein localizes to glandular epithelial cells on the verge of apoptosis in the human endometrium. Thus, BAK likely functions with other members of the BCL-2 family in the regulation of apoptosis in the human uterus.

Adult↗
PubMed1998

Impact of varying stages of endometriosis on the outcome of in vitro fertilization-embryo transfer.

PURPOSE: The impact of severity of endometriosis on the outcome of in vitro fertilization (IVF) was analyzed in an uncontrolled, retrospective study in an academic IVF program. METHODS: Sixty-one patients with a primary diagnosis of endometriosis undergoing 85 cycles of IVF were included in the study. Patients were divided according to the severity of disease based on the revised American Fertility Society (AFS) classification into groups A (stages I/II, or minimal/ mild) and B (stages III/IV, or moderate/severe). Group A included 32 patients undergoing 45 IVF-embryo transfer (ET) cycles; group B included 29 patients undergoing 40 IVF cycles. Exclusion criteria were age older than 40 years, basal day 3 follicle stimulating hormone (FSH) greater than 20 IU/L, male-factor infertility, assisted hatching, and gamete intrafallopian transfer cases. Stimulation for IVF cycles was standard using pituitary down-regulation with gonadotropin-releasing hormone agonist in a midluteal protocol. Controlled ovarian hyperstimulation (COH) was achieved using a combination of FSH and human menopausal gonadotropin. Outcomes assessed included response to COH and number, maturity, and quality of oocytes retrieved. Fertilization, implantation, and pregnancy rates after IVF-ET were also analyzed. RESULTS: The response to COH and the number, maturity, and quality of the oocytes was comparable between patients with varying severity of endometriosis. Fertilization rates for oocytes of patients in group B (stages III/IV) were significantly impaired compared to those in group A (stages I/II) (P = 0.004). The rates for implantation, clinical pregnancy, and miscarriage were comparable between the two groups. CONCLUSIONS: The reduced fertilization potential of the oocytes obtained from patients with severe endometriosis in the absence of male-factor infertility suggests an adverse biological impact of the advanced disease on the oocytes. The outcome of IVF-ET, however, is unaffected by increasing severity of endometriosis. This suggests that IVF may compensate for or overcome this reduction in the biological potential of the oocytes associated with severe disease, thus accounting for a comparable outcome irrespective of the severity of endometriosis.

Adult↗
PubMed1998

Malignancy may adversely influence the quality and behaviour of oocytes.

A case series of eight cycles of in-vitro fertilization (IVF) in five women diagnosed with malignant disorders is presented. These patients chose to defer definitive treatment for a chance for preservation of potential fertility. The response of these patients to ovarian stimulation, and the outcome, was compared with 17 IVF cycles in 12 age-matched patients with isolated tubal infertility. An apparent adverse influence of malignant disease on the quality and behaviour of oocytes was observed. Despite a comparable total number of oocytes per cycle in the two groups, a significantly reduced percentage of mature oocytes was retrieved per cycle from patients with malignant diseases. The oocytes from patients with malignant disorders were of a poorer quality and exhibited a significantly impaired fertilization rate compared to the controls. We propose that neoplastic processes, irrespective of the site or cell of origin, may have a detrimental impact on the biology of oocytes, an effect akin to that seen on spermatozoa in men with certain malignancies.

Adenocarcinoma↗
PubMed1997

Increased expression of complement component 3 in human ectopic endometrium compared with the matched eutopic endometrium.

OBJECTIVE: To compare the gene expression of complement component 3 (C3) in human eutopic and ectopic endometrium. DESIGN: A prospective, controlled study. SETTING: Academic hospital. PATIENT(S): Women with documented endometriosis. INTERVENTION(S): Eutopic and ectopic endometrial tissues were collected simultaneously at laparoscopy. MAIN OUTCOME MEASURE(S): Detection of C3 messenger RNA (mRNA) by in situ hybridization and C3 protein by immunohistochemistry and Western blot. RESULT(S): Expression of C3 mRNA increased in ectopic endometrium compared with that in the matched eutopic endometrium. The quantitative analysis of C3 mRNA by grain count (mean +/- SE) showed 175.60 +/- 40.02 and 39.97 +/- 8.17 grains per micron2 in ectopic and eutopic glands, respectively, and 67.65 +/- 29.82 and 15.02 +/- 5.80 grains per micron2 in ectopic and eutopic stroma, respectively. Expression of C3 mRNA in ectopic glands was significantly higher than that in eutopic glands. The pattern of immunoreactive staining of C3 protein was consistent with that of C3 mRNA. A higher level of C3 protein in ectopic endometrium than eutopic endometrium was detected by immunohistochemistry and Western blot. CONCLUSION(S): Expression of C3 mRNA and protein significantly increased in human ectopic endometrium compared with that in the matched eutopic endometrium.

Adult↗
PubMed1997

Outcome of IVF in DES-exposed daughters: experience in the 90s.

PURPOSE: The outcome of in vitro fertilization (IVF) in a group of infertile women with a history of in utero exposure to diethylstilbestrol (DES) was analyzed. Records from an academic IVF program were retrospectively reviewed. METHODS: Seventeen infertile women with a self-reported history of exposure to DES in utero, attending the IVF unit at Massachusetts General Hospital (MGH) for assisted reproductive technology (ART), underwent 27 IVF cycles. Analysis of the outcome of IVF including implantation and ongoing pregnancy rates was performed. The data were compared with results from a group of 20 infertile patients with idiopathic infertility undergoing 27 IVF cycles at MGH during the same period. The patients in the two groups were matched for age, basal day 3 levels of follicle stimulating hormone and serum estradiol, and the number and quality of embryos transferred. RESULTS: The response to controlled ovarian hyperstimulation was comparable in the two groups. Significantly lower implantation and ongoing pregnancy rates following IVF and embryo transfer were seen in the utero DES-exposed group compared to the control patients. CONCLUSIONS: Infertile patients with a history of in utero exposure to DES exhibit a significantly impaired implantation rate following IVF, and the outcome of ART remains poor.

Adult↗
PubMed1997

Endometrial alpha-2 macroglobulin; localization by in situ hybridization and effect on mouse embryo development in vitro.

alpha-2 macroglobulin (A2M) is a 718,000-kDA broad spectrum plasma protease inhibitor whose production by the human endometrium was recently reported. The multifunctional A2M receptor, also known as low-density lipoprotein receptor-related protein, was also recently immunolocalized to the endometrial stroma. The objective of this study was to further characterize the endometrial site of expression of A2M, and to study its effects on mouse embryo development in vitro, to gain some insight into the functional significance of its endometrial production. Formalin-fixed, paraffin-embedded human endometrium from hysterectomy and endometrial biopsy specimen was used for in situ hybridization analysis, with 35S-labeled riboprobes representing subcloned A2M complementary DNA (cDNA) fragments. Duplicate sections of human endometrium were hybridized with sense and antisense probe and coated with photographic emulsion. Resultant autoradiograms were analyzed qualitatively by light- and darkfield microscopy and quantitatively by a computerized analysis of the signal intensity. Immunohistochemistry and immunoblotting for endometrial tissues were performed using an affinity-purified polyclonal antibody to human A2M. The effect of A2M on mouse embryo development was studied by exposure of one cell mouse embryo in culture to physiological concentrations of biologically active and inactive A2M. Expression signals for A2M were more numerous and intense in the secretory endometrium, compared with proliferative endometrium. Endothelial cells lining the endometrial blood vessels seemed to be the main source of A2M expression. The A2M expression signals in secretory endothelium were 2- to 3-fold stronger than the proliferative endothelium, suggesting transcriptional activation of A2M expression in the secretory endothelium. Glandular expression was observed in secretory endometrium from two patients with endometriosis. Ectopic endometrial tissues also produced A2M. A2M at concentrations of 400-500 mumol/L significantly inhibited blastocyst development of mouse embryos in vitro. A2M is expressed predominantly by the endometrial endothelial cells and may be involved in endometrial physiology. Physiological concentrations of A2M inhibit mouse embryo development in vitro, suggesting that endometrial production of A2M may play a role in regulating preimplantation embryo development.

Adult↗
PubMed1997

Differential expression of members of the bcl-2 gene family in proliferative and secretory human endometrium: glandular epithelial cell apoptosis is associated with increased expression of bax.

Glandular epithelial cells of the human endometrium initiate apoptosis in the secretory phase of the cycle. To better understand the regulation of apoptosis in this paradigm of endocrine-regulated cell turnover, we studied the expression of the cell death regulatory genes, bax, bcl-2, and bcl-x, in human proliferative and secretory endometria relative to the absence or presence of apoptosis. As assessed by immunohistochemistry, levels of BAX protein were modest in proliferative endometrium and increased dramatically in the secretory phase when apoptosis was most prevalent. Expression of BAX was predominantly localized to epithelial cells of the functionalis layer of the secretory endometrium. In contrast, BCL-2 immunoreactivity was maximal during the proliferative phase and decreased in the secretory phase. Moreover, BCL-2 was topographically concentrated in the basalis layer. Immunoreactive BCL-X protein was observed mostly in glandular epithelial cells of the human endometrium. Compared with proliferative endometrium, secretory endometrium showed stronger BCL-X staining, especially in the functionalis layer. By Western blotting we confirmed that both proliferative and secretory endometrium expressed the long or antiapoptosis form as well as the short or proapoptosis form of the BCL-X protein. Taken together, our results demonstrate a coordinated pattern of expression of bcl-2 gene family members in human endometrium during the menstrual cycle, with a shift toward greater levels of the proapoptosis protein, BAX, occurring in glandular epithelial cells during the secretory phase of the cycle. Therefore, we conclude that cyclic changes in endometrial growth and regression may be precisely regulated by shifts in the ratio or balance of BCL-2 and related proteins in glandular epithelial cells.

Apoptosis↗
PubMed1996

High incidence of triploidy in in-vitro fertilized oocytes from a patient with a previous history of recurrent gestational trophoblastic disease.

The patient described has a history of recurrent gestational trophoblastic disease following spontaneous conception. She subsequently underwent two cycles of in-vitro fertilization (IVF) for management of infertility related to tubal obstruction. IVF of the oocytes retrieved showed a significantly high incidence of abnormal fertilization resulting in the development of triploid embryos. This report explores the possible association of an oocyte defect predisposing to abnormal fertilization, resulting in a high incidence of triploid embryos. Since the development of partial hydatidiform moles is related to the origin of triploidy, this phenomenon is suggested to explain the occurrence of recurrent trophoblastic disease in this patient. We propose the use of intracytoplasmic sperm injection (ICSI) as a therapeutic option to minimize the incidence of triploidy in future IVF cycles; donor oocyte IVF would be another alternative.

Adult↗
PubMed1996

Localization of the expression of complement component 3 in the human endometrium by in situ hybridization.

C3 production by the human endometrium has been previously described. The objective of the current study was to localize the site of expression and regulation of the third component of complement, C3, in the endometrium. Eight secretory and eight proliferative archival endometrial samples from hysterectomy and endometrial biopsy specimens were used for in situ hybridization analysis. This analysis was performed with a radiolabeled riboprobe synthesized from a 736-bp template representing sequence 1944-2680 of the human C3 complementary DNA. Duplicate sections were hybridized with sense and antisense riboprobes. Resultant autoradiograms were analyzed qualitatively by light- and darkfield microscopy. In proliferative endometrium, minimal expression of C3 was observed and was limited to a few stromal patches and glands throughout the section. In the secretory samples, prominent C3 expression was observed in both the glands and stroma of the basalis layer. Endometrial lymphocytes did not express C3. Endometrial stromal and glandular cells express the C3 gene. Endometrial lymphocytes did not express C3, but other nondistinct lymphoid elements scattered in the stroma may be expressing C3. There was a visibly more intense expression of C3 in the basalis layer of the secretory endometrium than in proliferative endometrium. The spatial and temporal pattern of C3 expression may have implications in normal menstrual physiology and in the immunological response of the endometrium to the invading trophoblast during placentation.

Adult↗
PubMed1995

Target antigen(s) in endometrial autoimmunity of endometriosis.

OBJECTIVE: To obtain the molecular weights (MW) of endometrial antigens eliciting immunoglobulin (Ig) G auto-antibodies in all endometriosis patients irrespective of their place of origin or race, and to verify their specificity and immunogenicity. STUDY DESIGN AND RESULTS: We tested the serum and peritoneal fluid (P.F.) of 76 endometriosis patients and 24 controls from 4 cities against endometrial and implant antigens by Western blot analysis. Endometrial and implant antigens with MW of 34, 46/48, 64, 84, 94 and 120 kDa bound with IgG in serum and PF of most patients, but not the controls. Antigen(s) with MW of 64 kDa was reactive against serum or P.F. IgG of patients from all cities. Specificity: Endometrial and implant extracts did not react with monoclonal antibodies to WBC subsets and 5 sera with nuclear antibodies. Also, the presence of nuclear and endometrial antibodies did not correlate in 20 other patients with endometriosis. Immunogenicity: We immunized rabbits with the native and eluted (MW 29 to 68 kDa and > or = 68 kDa) endometrial and implant proteins. The antiserum had specific IgG binding to the same glandular epithelial antigens as those bound by the patient's serum. CONCLUSIONS: Endometrial antigens with MW of 34, 46/48, 64, 94 and 120 kDa, especially 64 kDa appear to be specific, immunogenic and relevant to endometrial autoimmunity in all patients with endometriosis.

Adult↗
PubMed1991

The effect of estradiol on the production and secretion of complement component 3 by the rat uterus and surgically induced endometriotic tissue.

We have recently demonstrated that glandular epithelial cells isolated from human endometriotic tissue synthesize and secrete complement component 3 (C3). Furthermore, because C3 is capable of producing many of the immunological activities known to be associated with human endometriosis, we studied the production, secretion, and regulation of C3 using the rat model for endometriosis. Endometriosis was surgically induced in 20 adult female rats. The animals were then ovariectomized and one half were treated with estradiol (E2) for 3 days. Uterine luminal epithelial cells synthesized and secreted C3 only after E2 administration, whereas the uteri from control animals did not produce C3. In contrast, the ectopic endometrium from control animals produced and secreted C3, and this expression was strongly upregulated by in vivo E2 administration. We conclude that surgically induced endometriosis in the rat has properties biochemically independent from the intact uterus and may serve as a useful model to further investigate the regulation of C3 synthesis from human endometriosis.

Animals↗
PubMed1990

Endometrial synthesis and secretion of complement component-3 by patients with and without endometriosis.

In the present study we examined complement-3 (C3) synthesis and secretion from early proliferative endometrium of infertile patients with and without endometriosis. One gram of tissue was obtained by endometrial sampling at the time of diagnostic laparoscopy and incubated for 12 to 16 hours in the presence of radioactive methionine. Immunoprecipitation was performed with rabbit antihuman C3 immunoglobulin G and only a single 180-kDa radiolabeled protein (C3) was immunoprecipitated. This protein dissociates into 113- and 69-kDa subunits in the presence of dithiothreitol. The amount of C3 produced and secreted by the endometrium was quantitated as a percentage of counts per minute recovered by immunoprecipitation. Patients with minimal endometriosis produced significantly greater amounts of endometrial C3 than patients with no endometriosis or patients with severe endometriosis.

Complement C3↗
PubMed1989

Production and secretion of complement component 3 by endometriotic tissue.

Many investigators have described a variety of immune phenomena associated with endometriosis. Among these are elevated titers of activated macrophages, monokines, and lymphokines in the peritoneal fluid of patients with endometriosis. In 1980, Weed and Arquembourg first described the deposition of complement component C3 in epithelial cells of endometrial glands in patients with endometriosis. In this study our objective was to examine the synthesis and secretion of proteins by endometriotic tissue. Tissues were incubated in Minimal Essential Medium without methionine containing 50 microCi/mL [35S]methionine for 12-16 h at 37 C in 5% CO2-95% air. Twenty thousand trichloroacetic acid-precipitable counts were placed on a 7.5% sodium dodecyl sulfate-polyacrylamide gel, and the radiolabeled proteins were detected by fluorography. We examined the radiolabeled secretory proteins obtained from 17 endometriotic implants and/or endometrioma cyst walls as well as 8 control tissues. A 180 kDa protein was produced in much greater quantities by endometriotic tissue than by control tissues. In the presence of reducing agent this protein dissociated into 113- and 69-kDa subunits. To identify and quantitate this protein we performed immunoprecipitations on the incubated medium using antihuman C3 immunoglobulin G. Up to 16% of the precipitable counts were recovered with this antibody from endometriotic tissue, while a maximum of only 4.6% was recovered from control tissue. In addition, we isolated and incubated the epithelial glandular cells, stromal cells, and remaining cells from two endometriomas. The great majority of the newly synthesized and secreted C3 was found in the glandular epithelial cell incubation. Up to 60% of the total precipitable counts were recovered from the glandular cells using this antibody. Only one protein was immunoprecipitated. The immunoprecipitated protein had a mol wt of 180 kDa under nonreducing conditions and dissociated into two subunits of 113 and 69 kDa in the presence of dithiothreitol. We conclude that the glandular epithelial cells found in endometriotic implants produce and secrete complement component, C3 which could be responsible for many of the immunological phenomena now well described in endometriosis.

Adult↗
PubMedDate not supplied

Temporal trends in human semen parameters in New England in the United States, 1989-2000.

The current study explores trends in semen parameters in New England in the United States. A retrospective review was performed of 551 semen analysis records from 1989 to 2000 at Vincent Memorial Andrology Laboratory of Massachusetts General Hospital. After age adjustment, semen pH and motility significantly increased 0.05 units/year and 2.33%/year, respectively, while sperm with normal morphology decreased 0.33%/year. Sperm concentration showed a small upward trend. The year of birth in the present study ranged from 1932 to 1981; 2% were born between 1932 and 1941, 13% between 1942 and 1951, 48% between 1952 and 1961, 36% between 1962 and 1971, and 1% were born between 1972 and 1981. There were significant positive relationships between year of birth and semen volume (0.04 mL/1-year interval increase in year of birth) and motility (0.61 percent/1-year interval increase in year of birth), as well as with sperm concentration and morphology. Overall, there were temporal and year of birth trends in several human semen parameters.

Adult↗