Biomedical subjects

A F Haney

Publications and source records attributed to A F Haney.

At least 55 records · Page 3Linked to original sources

PubMed1991

Hormone-resistant endometriosis following total abdominal hysterectomy and bilateral salpingo-oophorectomy: correlation with histology and steroid receptor content.

Endometriosis is rare after hysterectomy and oophorectomy for conditions unrelated to endometriosis. We present a case of delayed development of aggressive, hormone-resistant endometriosis temporally remote from hysterectomy and oophorectomy performed for chronic pelvic inflammatory disease. Treatment with depo-medroxyprogesterone acetate resulted in continued growth of the retroperitoneal endometrioma and necessitated posterior exenteration because of the endometrioma's location. Estrogen and progesterone receptor levels were measured to clarify why this woman's endometriosis was resistant to hormone therapy. Despite administration of large amounts of depo-medroxyprogesterone acetate, the progesterone receptor content was elevated while the estrogen receptor content was undetectable. Why this patient developed this particular type of aggressive endometriosis is unclear, but the lack of down-regulation of progesterone receptors in response to high-dose progestin therapy may indicate an alteration in basic regulatory and cellular processes within the endometriotic implant.

Adult↗

PubMed1991

Adjunctive leuprolide therapy does not improve cycle fecundity in controlled ovarian hyperstimulation and intrauterine insemination of subfertile women.

Problems arising from controlled ovarian hyperstimulation for intrauterine insemination, such as premature luteinization and asynchronous ovarian follicular development, are identical to those encountered with controlled ovarian hyperstimulation for in vitro fertilization (IVF) and gamete intrafallopian transfer (GIFT). It has been suggested that the adjunctive use of GnRH agonists for controlled ovarian hyperstimulation improves the efficiency of GIFT and IVF cycles. We hypothesized that adjunctive use of leuprolide acetate, a GnRH agonist, would have a similarly beneficial effect on cycle quality and cycle fecundity in subfertile women treated with controlled ovarian hyperstimulation and intrauterine insemination. We randomly assigned the first cycle of controlled ovarian hyperstimulation and intrauterine insemination for each of 97 subfertile women to include either human menopausal gonadotropins (hMGs) alone or hMGs following midluteal pre-treatment with leuprolide. If a pregnancy did not occur in the first cycle, the woman was given the other treatment in the second cycle. Although the cycles that included leuprolide required a larger amount of hMGs and more days of stimulation per cycle, the mean estradiol concentrations and numbers of follicles were not different. Despite prevention of premature luteinization with leuprolide, the cycle fecundity was not different between groups (0.11 with adjunctive leuprolide treatment and 0.22 with hMGs alone). We conclude that in unselected subfertile patients, the adjunctive use of leuprolide for controlled ovarian hyperstimulation and intrauterine insemination does not improve cycle fecundity compared with treatment cycles that do not include adjunctive leuprolide therapy.

Adult↗

PubMed1990

CA 125 in peritoneal fluid and serum from patients with benign gynecologic conditions and ovarian cancer.

CA 125 was measured in peritoneal fluid from 200 patients with primary ovarian malignancies (35) and benign gynecologic conditions (165). In 86 patients CA 125 was measured both in peritoneal fluid and in serum. Patients with ovarian cancer had markedly greater serum CA 125 levels compared to patients with benign disease. CA 125 levels in peritoneal fluid were usually higher than serum levels. Twenty-six (93%) of 28 patients with ovarian cancer had peritoneal fluid levels which exceeded serum levels in paired samples. peritoneal fluid CA 125 values greater than 200 U/ml identified ovarian cancer patients with 96% sensitivity and 99% specificity. Serum CA 125 values greater than 35 U/ml identified ovarian cancer patients bearing ascites with a sensitivity of 99% and specificity of 94%. Only 2 of 165 patients with benign gynecological conditions had peritoneal fluid values above 200 U/ml. By contrast, only two values below 200 U/ml were found in ascitic fluids from 35 patients with ovarian cancer. CA 125 levels in peritoneal fluid deserve further evaluation for follow-up of patients with ovarian cancer.

Animals↗

PubMed1990

Synthetic estrogens suppress granulosa cell progesterone production in vitro.

We evaluated the effect of commonly used pharmaceutical estrogens and zeranol, an estrogenic growth-promoting agent used in livestock, on progesterone (P) production by cultures of highly differentiated porcine granulosa cells (GC). The compounds were added to GC cultures over a dose range of 10(-8) to 10(-5) M with P and cell protein measured after 24 h. P production was suppressed by estradiol (minimal suppressive dose: 10(-7) M; maximal suppression to 11% of control), ethinyl estradiol (10(-7) M, 15%), diethylstilbestrol (10(-5) M, 72%), clomiphene citrate (10(-6) M, 30%), nafoxidine (10(-7) M, 33%), tamoxifen (10(-6) M, 37%), and zeranol (10(-5) M, 83%). P production was not suppressed by mestranol. GC protein was suppressed by estradiol, ethinyl estradiol, nafoxidine, and zeranol. These data suggest that synthetic estrogens have the potential to suppress luteal P production by a mechanism unrelated to the usual measures of estrogenicity.

Animals↗

PubMed1990

Use of human cumulus granulosa cells for in vitro screening of reproductive toxicants.

We investigated the possibility that human granulosa cells from the cumulus mass obtained during human in vitro fertilization/embryo transfer (IVF/ET) might be useful for screening of potential reproductive toxicants in vitro. The cumulus granulosa cells detached from the zona pellucida after fertilization were allowed to spontaneously adhere to the incubation dish following transfer (removal) of the embryo. These cumulus cells survived in culture for at least four additional days, appeared on simple inspection to be morphologically normal luteinized granulosa cells, and produced large amounts of progesterone (P) over the culture interval. Production gradually declined during culture in the absence of human chorionic gonadotropin (hCG); however, inclusion of hCG (100 ng/mL) in the medium maintained P production at control (day 1) levels. Introduction of estrogenic agents previously shown to suppress P production in porcine or human culture systems using mural granulosa cells showed comparable effects in this human cumulus cell system. 17 beta-estradiol (10(-5) M), clomiphene citrate (10(-5) M), and o,p-DDT (10(-5)) significantly inhibited hCG-supported P production by human cumulus cells in vitro. This system has the advantages that (1) human cumulus granulosa cells are readily available from IVF/ET programs, (2) the techniques for maintaining the cells in culture are extremely simple, (3) a marker of highly differentiated granulosa cell function (P production) can be reliably measured, and (4) the cells respond predictably like other comparable granulosa cell systems. We conclude that human cumulus cells are a readily available and useful resource for in vitro screening of potential female reproductive toxicants.

Chorionic Gonadotropin↗

PubMed1990

The luteal phase in polycystic ovary syndrome during ovulation induction with human menopausal gonadotropin with and without leuprolide acetate.

Little data exist on the effects of adjunctive therapy with leuprolide acetate (LA) in the luteal phase of women with polycystic ovary syndrome (PCOS) undergoing ovulation induction with human menopausal gonadotropin (hMG). Additionally, it is not known whether gonadal steroid concentrations in the luteal phase of induced cycles in PCOS are predictive of pregnancy. In this prospective, randomized study comparing cycles using hMG alone (n = 26) with cycles using hMG with LA (n = 33), no differences were noted between treatment groups in progesterone (P), estradiol (E2), and P:E2 ratios on luteal days 3, 6, and 9. When all treatment cycles were pooled, there were no differences in P, E2, or P:E2 ratios, comparing conception and nonconception cycles. We conclude that adjunctive therapy with LA in PCOS patients undergoing ovulation induction with hMG does not alter the luteal phase concentrations of P, E2, and P:E2. Furthermore, no correlation was found between the serum concentrations of these luteal phase steroids and cycle fecundity.

Drug Therapy, Combination↗

PubMed1990

Effect of age on response to human menopausal gonadotropin stimulation.

Conception rates decline in the latter part of the reproductive years. To examine which ovarian parameters are altered with aging, 486 cycles from 225 ovulatory infertile women undergoing human menopausal gonadotropin (hMG) superovulation and washed intrauterine insemination were analyzed. Infertility factors included endometriosis (68%), unexplained infertility (8.4%), male factor (12.9%), and ovulatory dysfunction (10.7%). Parameters that demonstrated a linear relationship with increasing age included numbers of ampules of hMG required per cycle (r = 0.79; P less than 0.05), days of stimulation (r = 0.73; P less than 0.01), estradiol level at the time of hCG (r = -0.92; P less than 0.0001), number of follicles larger than 15 mm (r = -0.61; P less than 0.05), and rate of rise of estradiol (r = -0.92; P less than 0.0001). These same age-dependent changes were observed in women receiving a standard stimulation protocol (3 ampules hMG beginning on cycle day 2). When standard cycles were limited to the first cycle only, the preovulatory estradiol (r = -0.92; P less than 0.005), slope of estradiol rise (r = -0.92; P less than 0.005), and number of preovulatory follicles (r = -0.92; P less than 0.005) still showed a significant decrease with age. Although the mean estradiol level per preovulatory follicle showed a slight decrease with maternal age, no statistically significant trend was noted. In addition, the cycle day of hCG administration was unaffected by age. With advancing age, there appears to be a decreased ovarian response to an increased amount of stimulation, as measured by steroidogenesis and follicular recruitment; yet the estradiol/follicle remains unaltered, indicating continued health of the follicle. These observations may explain in part the observed decrease in fecundity in older women.

Adult↗

PubMed1990

Etiology and histogenesis of endometriosis.

Based on the available scientific evidence, the mechanism of developing endometriosis appears to be transplantation of viable endometrial cell fragments shed during menses and regurgitated through the fallopian tubes under the influence of prostaglandin-mediated uterine contractions. As all women apparently retrograde menstruate to some extent, it is not surprising that circumstances which increase the total number of menstrual days experienced have been clinically associated with endometriosis. Similarly, factors which lead to relative uterine outflow obstruction have been associated with a higher incidence of endometriosis. There is virtually no other scientific evidence supporting alternate mechanisms of development of endometriosis. There are many unanswered questions regarding endometriosis including: 1) Are all women equally susceptible to development of the disease? 2) As the clinical presentation and course is extremely variable, what factors influence these events? 3) Does medical suppression of ovulation with oral contraceptives or continuous progestins provide a protective effect? 4) Are there systemic immunologic changes associated with endometriosis? Hopefully, this manuscript will help stimulate the next generation of clinical investigators to address these questions, as they are of paramount importance with this apparently increasingly devastating and frequent clinical disease.

Endometriosis↗

PubMed1989

Ovarian hyperstimulation in polycystic ovary syndrome during therapy with leuprolide acetate.

Continuous exposure to GnRH eliminates the pituitary as a source of gonadotropins and may have direct suppressive effects on the ovary. A woman with PCO syndrome received leuprolide acetate (1 mg/d SC) for 4 weeks before and simultaneously with hMG stimulation. Human chorionic gonadotropin (5,000 IU) was administered IM on the 8th day of hMG therapy. There were 10 follicles greater than 15 mm and a polycystic appearance to the ovaries with 25 follicles measuring less than 10 mm. The serum E2 concentration was 2,280 pg/mL. She developed severe ovarian hyperstimulation and required hospitalization for 12 days for fluid management. A viable intrauterine pregnancy was present. Four weeks of pretreatment with leuprolide did not prevent hyperstimulation in the presence of an intrauterine pregnancy.

Adult↗

PubMed1989

Clinical characteristics of ovulation induction with human menopausal gonadotropins with and without leuprolide acetate in polycystic ovary syndrome.

Ovulation induction in polycystic ovary syndrome (PCOS) with human menopausal gonadotropins (hMG) results in suboptimal cycle fecundity and frequently is complicated by ovarian hyperstimulation. The use of a gonadotropin releasing-hormone agonist (Gn-RH-a) with hMG induction of ovulation may improve the therapeutic outcome. In this prospective, randomized trial, 27 women with PCOS underwent a total of 25 cycles of hMG alone and 33 cycles with adjunctive GnRH-a (leuprolide) treatment. Premature luteinization was seen less frequently in the leuprolide-treated cycles than in cycles treated with hMG alone. There were no differences between the treatments in ovarian sensitivity to hMG. Cycle fecundity was 0.16 for hMG alone cycles, and 0.27 for leuprolide with hMG cycles, which were not statistically different. We conclude that the sensitivity of the PCOS ovary to hMG is not affected by 4 weeks of leuprolide pretreatment.

Drug Therapy, Combination↗

PubMed1989

Immunohistochemical analysis of estrogen and progesterone receptors in endometriosis: comparison with normal endometrium during the menstrual cycle and the effect of medical therapy.

Estrogen receptors (ER) and progesterone receptors (PgR) in 19 endometriotic implants from 16 normally cycling and hormonally treated women were measured using immunohistochemical techniques and compared with 34 samples of normal intrauterine endometrium. Endometriotic implants contained specific ER and PgR in both glandular epithelium and stroma. In contrast to intrauterine endometrium, receptor content among implants was noted to be more heterogeneous, and did not undergo predictable changes in response to endogenous hormones. In the endometriotic implants of patients treated with hormonal therapy, there were significant decreases in ER and PgR in both the glands and stroma relative to untreated patients. These data imply that endometriosis is unpredictable in its response to the cyclic hormonal milieu in terms of ER and PgR, but retains the ability to respond to hormonal suppression over a prolonged interval.

Adult↗

PubMed1989

Bovine cervical mucus penetration by human spermatozoa: lack of association with conception.

Penetration of bovine cervical mucus (BCMP) by human spermatozoa has been reported to be a test that may aid in assessment of male fertility. We determined the predictive value of BCMP for conception in 127 infertile couples. Fresh semen and swim-up specimens were tested with the Penetrak assay. Out of 127 patients 16 (13%) achieved pregnancy with 6 months to 2 years of follow-up. In the 62 men with sperm counts of greater than 20 million/ml and motility of greater than 60%, 55 (89%) had adequate BCMP while adequate penetration was found in only eight of 24 (33%) with both sperm count and motility below these values (p less than 0.001). A normal BCMP did not predict pregnancy, and a reduced BCMP had no prognostic value in designating couples not likely to conceive. The comparison of penetration values for semen following swim-up suggests that this preparation may improve the correlation of BCMP with fertility. These results indicate that the semen parameters of sperm density and percent motility predicted spermatozoal performance in the BCMP assay, and that the assessment of BCMP did not predict the likelihood of pregnancy.

Animals↗

PubMed1989

Etiology of endometriosis.

The likelihood of developing endometriosis can thus be viewed as a quantitative phenomenon--that is, the probability of having large amounts of endometrium delivered to the peritoneal cavity and the inherent ability of the pelvic tissues to support transplantation, or a combination of the two. What part immunologic, genetic, and menstrual factors contribute to an individual woman's susceptibility to develop the disease has yet to be explored in detail. A substantial amount of research will be required to evaluate these areas to devise methods of preventing the development of endometriosis.

Endometriosis↗

PubMed1988

Clinical trials with human tumor necrosis factor: in vivo and in vitro effects on human mononuclear phagocyte function.

The purpose of this investigation was to understand the biological effects of recombinant human tumor necrosis factor used as therapy for cancer. We studied changes in mononuclear phagocyte function following exposure to this cytokine in vitro or in vivo. Tumor necrosis factor increased phorbol myristate acetate-induced hydrogen peroxide production 8- to 20-fold in peripheral blood monocytes and peritoneal macrophages in vitro in a dose-dependent manner. Similarly, tumor necrosis factor increased phorbol myristate acetate-induced peroxide production 2.3-fold in monocytes isolated from nine patients following an i.v. infusion of this cytokine (40 to 200 micrograms/m2). In addition, tumor necrosis factor induced a 2.3-fold increase in tissue factor-like activity in mononuclear phagocytes in vitro. In vivo, tumor necrosis factor induced a trend toward higher procoagulant activity in monocytes, although this change was not statistically significant. We also noted a trend toward increased activated partial thromboplastin times and the presence of fibrin D-dimer in patients treated with tumor necrosis factor, demonstrating activation of the coagulation and fibrinolytic systems. Thus, in vivo treatment of humans with i.v. recombinant human tumor necrosis factor induced functional changes in mononuclear phagocytes similar to those noted with in vitro treatment.

Blood Coagulation Factors↗

PubMed1988

Multiple pregnancies conceived with intrauterine insemination during superovulation: an evaluation of clinical characteristics and monitored parameters of conception cycles.

The use of human menopausal gonadotropins to induce superovulation in conjunction with intrauterine insemination as treatment for infertility is associated with an increased incidence of multiple gestation. Identification of clinical characteristics and/or monitored parameters of the stimulation cycles highly associated with multiple gestation would enable cancellation of these cycles. We retrospectively evaluated the clinical profiles and conception cycle characteristics of 48 infertile women undergoing the induction of superovulation and intrauterine insemination. We compared 14 of these women who conceived multiple gestations (eight twins and six triplets) with 34 who conceived singleton gestations. We found no differences between the groups in age, parity, cause or duration of infertility, duration or amount of human menopausal gonadotropin administration, serum estradiol concentrations on the day of human chorionic gonadotropin injection, number of preovulatory-sized follicles, or number of motile sperm inseminated. We conclude that neither the patients' clinical characteristics nor the parameters evaluated in monitoring human menopausal gonadotropin cycles provide information helpful in predicting which superovulation cycles will result in multiple pregnancy.

Adult↗

PubMed1988

Reduction of the intraperitoneal inflammation associated with endometriosis by treatment with medroxyprogesterone acetate.

An intraperitoneal inflammatory exudate has been repeatedly observed in infertile women without mechanical compromise of the pelvic viscera, particularly with endometriosis. This is manifested by increases in the peritoneal fluid volume, leukocyte number, and proteolytic enzyme concentrations. We tested the hypothesis that the stimulus responsible for eliciting this intraperitoneal inflammation is retrograde menstruation by measuring the peritoneal fluid volume and leukocyte count in 16 infertile women with endometriosis before and after ovulation suppression with medroxyprogesterone acetate, 30 mg/day for 4 months. Medroxyprogesterone acetate therapy significantly reduced the peritoneal fluid volume (22.5 +/- 4.1 versus 6.8 +/- 0.9 ml mean +/- SE, p less than 0.0001), the peritoneal fluid leukocyte count (30.7 +/- 6.5 versus 7.1 +/- 0.7 x 10(6) cells per patient, p less than 0.0001), and American Fertility Society score (23.2 +/- 5.1 versus 15.4 +/- 4.1, p less than 0.0002). We conclude that medroxyprogesterone acetate treatment reduces the intraperitoneal exudate associated with endometriosis. These results support the contention that the stimulus eliciting the intraperitoneal inflammation in infertile women with endometriosis is retrograde menstruation.

Adult↗

PubMed1988

Reduced trypsin-binding capacity of alpha 2-macroglobulin in the peritoneal fluid of women with endometriosis: possible relevance to alterations in macrophase function.

Alpha 2-macroglobulin (alpha 2M) is a plasma protein with proteinase inhibitor and immune modulatory capabilities. The amounts of alpha 2M in peritoneal fluid (PF) from women with endometriosis and women with noninflammatory gynecologic conditions were analyzed by functional (trypsin binding) and immunologic assays. The most important finding of this study was that a significant amount of the alpha 2M in the peritoneal fluid of patients with endometriosis had been inactivated by an as yet undetermined mechanism. The concentration and total amount of immunologically reactive alpha 2M in the samples varied widely and was not significantly different between the groups. However, women with endometriosis had significantly lower amounts of functional alpha 2M than did women without endometriosis. There was no significant difference between functional and immunologic measurements of alpha 2M in samples from women without endometriosis. Women with endometriosis, however, had less functional than immunologically reactive alpha 2M. This discrepancy was not due to inactivation of alpha 2M by having previously bound proteinase. Alpha 2M-proteinase complexes can down-regulate macrophase functions. It is possible that decreased proteinase-binding ability of alpha 2M may play a role in the pathogenesis of endometriosis and associated infertility by decreasing negative feedback control of macrophage activities.

Ascitic Fluid↗

PubMed1988

Limited hormonal responsiveness of ectopic endometrium: histologic correlation with intrauterine endometrium.

In order to assess the hormonal responsiveness of ectopic endometrium, 438 unselected endometrial implants and corresponding intrauterine endometrium from 196 patients were evaluated and classified by standard endometrial dating criteria. Only 13% of the endometrial implants were histologically synchronous with the corresponding intrauterine endometrium. Both proliferative and secretory implants were present in relatively constant proportions throughout the menstrual cycle, demonstrating a lack of correlation with cyclic endogenous hormones. A significant percentage (range, 25% to 49%) of endometrial implants displayed some form of local hemorrhage irrespective of the menstrual cycle timing. Sixty percent of the patients had evidence of hemorrhage in at least one implant. In women receiving hormonal therapy at the time of surgery, the proportion of endometrial implants that were histologically in concert with the corresponding endometrium ranged from 0% to 33%. In early pregnancy and menopause, 50% and 31% of endometrial implants were histologically similar, respectively. These data indicate that the hormonal responsiveness of endometrial implants is unpredictable and inconsistent.

Adolescent↗