Search PubMed⌕ Search

Biomedical subjects

A F Haney

Publications and source records attributed to A F Haney.

At least 73 records · Page 4Linked to original sources

Endometriosis: etiology and pathophysiology of infertility.

The risk for developing endometriosis begins at puberty and extends to menopause in women of all races. The major pathway in the pathogenesis of this disease is the transplantation of endometrial cells to the pelvis and other abdominal organs via retrograde menstruation. Although retrograde menstruation appears to be a near universal occurrence, those women who are at particular risk for developing the disease have menstrual characteristics that increase the amount and duration of menstrual contamination of the pelvis. The ability of the body's immune system to remove this debris may play a significant independent role. In spite of the apparent association of infertility and endometriosis, there is a paucity of evidence to identify a clear cause-and-effect relationship or to clarify the specific mechanism(s) of infertility due to this enigmatic disease. Areas that warrant additional attention include the effect of endometriosis on ovulation, the impact of the immune system on the development of endometriosis, and the effect of peritoneal inflammation on reproduction. A better understanding of these areas will lead to more efficacious and specific therapies for endometriosis-associated infertility.

Endometriosis↗

Immunohistochemical analysis of human uterine estrogen and progesterone receptors throughout the menstrual cycle.

Estrogen receptors (ER) and progesterone receptors (PgR) were studied immunohistochemically using specific antireceptor monoclonal antibodies in uterine tissue samples from 33 women in various stages of the menstrual cycle. Immunohistochemical localization was quantified as to intensity of staining and tissue distribution in glandular epithelium, stroma, and myometrium, and the results were compared with those of standard ligand binding assays. In all samples ER and PgR localized within the nuclei of target cells. The maximal concentrations of ER and PgR occurred in the mid- to late proliferative phase of the menstrual cycle. ER content declined throughout the secretory phase. In contrast, PgR content underwent unexpectedly complex and dyssynchronous fluctuations during the secretory phase of the menstrual cycle. Specifically, the glandular epithelium had diminished PgR content, while the stroma and myometrium maintained a significant PgR content. PgR and perhaps ER are not concordant in different cell types within the uterus. Segregation of function through alteration of receptor content may be an important mechanism in steroid-dependent growth and differentiation of target tissues.

Adult↗

Treatment-independent, treatment-associated, and pregnancies after additional therapy in a program of in vitro fertilization and embryo transfer.

Although the technique of in vitro fertilization and embryo transfer (IVF-ET) was developed for couples with untreatable tubal factor infertility, IVF-ET is now being applied to women with other causes of infertility and normal pelvic anatomy. In an effort to determine the treatment-independent pregnancy rate, we retrospectively reviewed the first 245 couples enrolled in the IVF-ET program at Duke University Medical Center. There were 19 treatment-independent pregnancies in 18 women and 3 treatment-associated pregnancies in cycles in which the oocyte retrieval was canceled (in 2 women washed intrauterine insemination was substituted for oocyte retrieval). Six pregnancies were established after an unsuccessful attempt at IVF-ET with additional non-IVF-ET therapy, including washed intrauterine insemination in three couples, and donor insemination in two couples. These observations suggest that a significant number of treatment-independent pregnancies will occur in couples clinically deemed appropriate for IVF-ET, pregnancies can be established in cycles of controlled hyperstimulation without oocyte retrieval, and additional non-IVF-ET therapy can result in pregnancy despite failure of IVF-ET in selected couples.

Adult↗

Superovulation with intrauterine insemination in the treatment of infertility: a possible alternative to gamete intrafallopian transfer and in vitro fertilization.

In vitro fertilization and embryo transfer (IVF-ET) and gamete intrafallopian transfer (GIFT) are used to treat intractable infertility in women with no distortion of the pelvic viscera, despite the lack of controlled trials demonstrating efficacy. The mechanism of any purportedly enhanced cycle fecundity in ovulatory women without significant distortion of the pelvic viscera is unclear, but both GIFT and IVF-ET increase the number of male and female gametes at the site of fertilization. Intrauterine insemination (IUI) during human menopausal gonadotropin (hMG)-stimulated superovulatory cycles has similar potential but does not require oocyte retrieval. To evaluate the possibility that simply increasing the number of gametes at the site of fertilization might account for pregnancies attributed to IVF-ET and GIFT, the authors retrospectively analyzed the outcome of couples undergoing IUI during hMG cycles between 1983 and 1986 in women with normal pelvic anatomy. IUI during hMG-stimulated cycles yielded a cycle fecundity (f) of 0.17 for endometriosis, 0.29 for cervical factor, and 0.19 for idiopathic infertility, which approaches the fecundity of normal women and equals or exceeds that reported for IVF-ET and GIFT. The authors conclude that treatment with IUI in hMG cycles, alleviating the need for invasive oocyte retrieval, should be considered for inclusion in a randomized, controlled trial in comparison with IVF-ET and GIFT.

Cervix Mucus↗

Are we exploiting the infertile couple?

We hope that this article brings into focus some problems that merit consideration and debate. These thoughts come from a group of individuals who are actively engaged in reproductive endocrine/infertility practices with special interests ranging from ovulation induction to IVF to laser surgery. As a group, we practice in all parts of the country, and the problems mentioned are not restricted to any individual or region. We urge that all of us be candid with ourselves and our colleagues about what we can and cannot do for the infertile couple. We suggest that gynecologists ask themselves this question and proceed when the answer is affirmative: "Is this procedure really in the patient's best interest?"

Advertising↗

Sperm-macrophage interaction in the mouse: a quantitative assay in vitro using 111indium oxine-labeled sperm.

The role of reproductive tract macrophages in contraception and reproductive failure has become widely recognized. However, in vitro analysis of sperm phagocytosis by macrophages has relied upon a semi-quantitative method of sperm counting that is of limited accuracy and reproducibility. We have developed an assay using murine sperm labeled with 111indium oxine, and results indicate the labeling to be rapid and efficient. Incorporation of 111indium into sperm increased the dose and sperm concentration and reached 90% maximal uptake after 15 min incubation, with maximal uptake occurring at 30 min. No decrease in sperm motility was noted with levels of oxine in excess of those required for significant labeling. Maximal labeling efficiency occurred in phosphate-buffered saline (PBS), with Dulbecco's modified Eagle's medium (DMEM) + 10% adult bovine serum (ABS) producing significantly less uptake. Label dissociation was detectable in PBS at room temperature, but at 37 degrees C in DMEM + 10% ABS, loss of label occurred at a rate of 23.5%/h. Addition of labeled sperm to murine macrophage monolayers under optimal conditions resulted in uptake of 111indium by macrophages, while free label was unincorporated. Results indicated assay specificity for macrophage-limited uptake, with insignificant label uptake by nonphagocytic murine fibroblasts and better sensitivity than sperm counting. Macrophages from Bacillus Calmette-Guerin (BCG)-infected mice resulted in a decrease in sperm uptake. Female macrophages showed greater capacity for sperm uptake than those of the male mouse. These initial studies demonstrated the utility of this model system in enhancing the understanding of sperm-macrophage interaction in the female reproductive tract.

Animals↗

Estrogen and progesterone production by granulosa cell monolayers derived from in vitro fertilization procedures: lack of evidence for modulation by androgen.

The role(s) of androgens in the steroidogenic regulation of human granulosa cell production of estrogen and progesterone during monolayer culture was studied. These cells were exposed in vivo to human menopausal gonadotropin and hCG gonadotropin with or without clomiphene citrate. Steroid production rates were compared between cells cultured in control medium and those cultured in medium containing a nonaromatizable androgen [dihydrotestosterone (DHT)] or an aromatizable androgen [androstenedione (A'D)]. Some cultures received A'D from 3-12 days; other cultures received DHT alone for 3, 6, or 9 days before the addition of A'D for 3 days. The effect on steroid production during the culture interval before the addition of A'D also was evaluated. Exposure to A'D increased estrogen production over 50-fold compared with that in control cells or those treated with DHT (P less than 0.001). DHT also failed to alter estrogen production when A'D was added to cultures. Furthermore, the delay in introducing A'D to the cultures for up to 9 days did not decrease subsequent estrogen production compared with that in cultures continually exposed to A'D or DHT plus A'D. Progesterone production was substantial for at least 12 days of culture and was unaffected by the presence of androgen. These results do not confirm previous studies using murine or porcine granulosa cells, which suggested that androgen receptor-dependent mechanisms were involved in increasing estrogen and/or progesterone production in vitro. Rather, they indicate that androgen may not be required to maintain aromatase capability per se in human granulosa-luteal cells previously exposed to ovulation-inducing quantities of gonadotropin.

Adult↗

The effect of leuprolide acetate on ovulation induction with human menopausal gonadotropins in polycystic ovary syndrome.

The use of exogenous gonadotropins for treatment of clomiphene-resistant chronic anovulation in women with the polycystic ovary syndrome (PCO) is hazardous and often ineffective, possibly because of the abnormal endogenous gonadotropin secretion characteristic of PCO. We evaluated the effect of leuprolide acetate, a long-acting GnRH agonist, on serum gonadotropin and sex steroid concentrations before and during human menopausal gonadotropin (hMG) induction of ovulation in women with PCO. In this controlled prospective randomized study, leuprolide was administered daily for 4 weeks, followed by concomitant hMG administration. Gonadotropin and steroid hormone concentrations were compared with those during ovulation induction cycles in women with PCO receiving hMG only. Daily administration of leuprolide for 4 weeks resulted in significantly decreased serum LH, estradiol, and testosterone concentrations, but no change in serum progesterone, FSH, and dehydroepiandrosterone sulfate. Compared to ovulation induction using hMG alone, leuprolide administration before and during hMG treatment prevented preovulatory rises in serum LH and P concentrations, while having no effect on serum FSH, testosterone, estradiol, and dehydroepiandrosterone sulfate. We conclude that leuprolide administered to women with PCO decreases gonadal steroid production and is capable of preventing premature luteinization during hMG induction of ovulation.

Adult↗

Endocrine and anatomical correlations in human ovarian pathology.

Knowledge of normal gonadal hormone production and function provides the basis for understanding the ovarian pathologic effects resulting from perturbations in endocrine balance and feedback. A precisely timed, complex, and well-coordinated cascade of ovarian steroidogenesis accompanies normal cyclical follicular function. This cascade involves both estrogens and androgens. Alterations in the hormonal milieu are associated with specific morphological changes in the ovary. While predictable hormonal changes accompany commencement of menopause, several disease states are associated with ovarian dysfunction. These diseases include polycystic ovarian syndrome and hyperthecosis, both associated with androgenization. Ovarian tumors may also be associated with morphological and clinical alterations. While endocrinologically inert ovarian tumors are associated with morphologic evidence of stromal activation, endocrinologically active ovarian tumors may cause differentiation along either male or female lines as a consequence of differential productions of androgens and estrogens.

Aging↗

The nature of the intraperitoneal exudate associated with infertility: peritoneal fluid and serum lysozyme activity.

An intraperitoneal inflammatory process has been associated with infertility in women without anatomic distortion of the pelvic viscera, particularly with endometriosis. This phenomenon was investigated by measuring peritoneal fluid (PF) and serum levels of a major secretory product of the macrophage, lysozyme, in fertile and infertile women undergoing laparoscopy. Serum lysozyme levels were in the normal range and did not correlate with total PF lysozyme. Regression analysis revealed a negative correlation between adnexal adhesions and PF volume (P less than 0.05), PF leukocyte number (P less than 0.05), and total PF lysozyme (P less than 0.05). Significant correlations were found between total PF lysozyme and PF volume (r = 0.72, P less than 0.0001) and leukocyte number (r = 0.67, P less than 0.0001). These results suggest that a localized intraperitoneal inflammatory reaction is associated with infertility in the absence of anatomic distortion of the pelvic viscera.

Adnexal Diseases↗

The "physiology" of the climacterium.

The climacteric represents both a time of declining gonadal function and general aging with subsequent alterations in those organs responsive to sex hormones. Men and women differ in that in women sex hormone production is intimately linked to the presence of gametes. As the number of oocytes is fixed at birth and oocytes are lost at a relatively constant rate, gonadal failure is the inevitable result. When the human life expectancy did not exceed the age of the climacteric, this was not a clinical problem for our species. With our rapidly lengthening life span, however, the medical impact of an extended life span without reproductive hormones becomes significant. In order to address these clinical problems in a humane and cost-effective manner to improve the quality of life for our increasingly aging population, a thorough understanding of the climacteric is mandatory for any physician treating women. Like most concepts in medicine, this one is not new. Borner stated in 1887: The climacteric, or so-called change of life in women, presents, without question, one of the most interesting subjects offered to the physician, and especially to the gynecologist, in the practice of his profession. The phenomena of this period are so varied and changeable, that he must certainly have had a wide experience who has observed and learned to estimate them all....it is desirable in the interest of our patients of the other sex, that the greatest possible light should be thrown upon this question. The modern practitioner will need to apply all the skills and resources available to adequately deal with the multitude of interrelated problems that beset women beyond the climacteric.

Aged↗

Bilateral tubal occlusion secondary to asymptomatic ectopic pregnancies.

An infertile woman with normal pelvic anatomy apparently underwent two consecutive asymptomatic tubal pregnancies without surgical intervention. Bilateral tubal obstruction resulted from destruction of the proximal segments of the fallopian tubes. These findings suggest that unrecognized ectopic pregnancies may cause destruction of segments of the fallopian tube and should be considered as an etiology of the rarely noted absence of tubal segments.

Adult↗

Compartmental ovarian steroidogenesis in polycystic ovary syndrome.

Compartmental ovarian steroidogenesis in vitro was investigated in polycystic ovary syndrome. Basal estrogen secretion by granulosa cells ranged from 60 to 284 pg/micrograms cell protein for 24 hours and progesterone secretion from 24 to 1646 pg/micrograms cell protein for 24 hours. In three of four specimens, the addition of either 10(-5)M testosterone or androstenedione significantly increased estrogen production, demonstrating the presence of aromatase activity. Treatment with human follicle-stimulating hormone (100 ng/mL) or human chorionic gonadotropin (100 ng/mL) significantly increased the progesterone production in three of four specimens. The thecal compartment of every patient secreted significantly more testosterone and androstenedione than the capsule and stroma and more estrogen in tissue from two of the four women. The androgen/estrogen ratio was significantly greater for the theca (16.9) than the capsule (1.1) or stroma (1.7). These data demonstrate that in polycystic ovary syndrome a portion of the follicles possess the qualitative characteristics of developing follicles, granulosa cell aromatase activity and gonadotropin responsiveness, and that the theca is likely the principal site of ovarian androgen synthesis. These findings suggest that the small follicles characteristic of polycystic ovary syndrome consist of a mixed population of developing and atretic follicles and that the peripheral androgen excess is attributable to the large mass of the thecal compartment from both follicle populations.

Adult↗

Paraovarian cysts associated with prenatal diethylstilbestrol exposure. Comparison of the human with a mouse model.

The association of prenatal exposure to diethylstilbestrol (DES) and abnormalities in structures of müllerian (paramesonephric) origin has been well documented. In a murine model, exposure to DES in utero results in persistent mesonephric remnants in adult female mice. Six women exposed prenatally to DES had paraovarian cysts excised during routine gynecologic surgery; and in 4, histologic abnormalities were observed, including thickened fibromuscular walls with tall columnar epithelium in a papillary or pseudoglandular configuration. Four of 25 nonexposed and 8 of 9 DES-exposed infertile women undergoing surgery for infertility had paraovarian cysts, and the difference was statistically significant (P less than 0.02). These findings raise the possibility that structures derived from the mesonephric ducts or tubules may also be affected in women exposed in utero to DES.

Animals↗

Endometriosis: pathogenetic implications of the anatomic distribution.

The authors have reassessed the anatomic distribution of ectopic endometrium by the laparoscopic study of the location of implants, adhesions, and uterine position in 182 consecutive patients with infertility and endometriosis. The ovary was the most common site of implants with 54.9% having either unilateral or bilateral involvement. This was followed, in order of frequency, by the posterior broad ligament (35.2%), the anterior cul-de-sac (34.6%), the posterior cul-de-sac (34.0%), and the uterosacral ligament (28.0%). Adhesion formation followed the same anatomic distribution. No patients were noted to have endometriosis of the cervix and vagina. Endometriosis of the anterior compartment (anterior cul-de-sac, anterior broad ligament, and anterior uterine serosa) was significantly more common in patients with anterior uteri (40.7%) versus patients with posterior uteri (11.8%, P less than .0005). Exclusive anterior compartment disease was found only in patients with anterior uteri, and significantly more commonly in patients with severely anteflexed uteri (P less than .005). These data suggest that factors influencing implantation of retrograde menstrual debris include: the dependent pooling of peritoneal fluid as affected by uterine position; epithelial cell type at the site of implantation; unique ovarian susceptibility; route of entry; and mobility of the pelvic structures. The data support the Sampson hypothesis of retrograde menstruation as the primary model of development of endometriosis.

Broad Ligament↗

Peritoneal macrophages and infertility: the association between cell number and pelvic pathology.

Increased numbers of peritoneal macrophages have been repeatedly associated with infertility. Because the factors contributing to this intraperitoneal exudate are unknown, this study was carried out to determine which anatomic or endocrinologic abnormalities in infertile women might be associated with an increase in leukocyte numbers. The peritoneal fluid from 103 women was analyzed. Nonparametric data analysis demonstrated significantly greater cell counts in infertile women with endometriosis, compared with other infertile women (P less than 0.01) or fertile control subjects (P less than 0.005). Multiple regression analysis was then used to determine the relationship of individual variables to cell number without the influence of confounding factors. These data demonstrate that the best correlation with elevated macrophage number is in women who have infertility and no mechanical fertility factors (of which mild endometriosis is a subgroup). Thus, an increase in peritoneal macrophage number is not restricted to women with endometriosis but, rather, is seen in a subset of infertile women generally without mechanical or endocrinologic infertility factors.

Ascitic Fluid↗