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Surgical removal of adhesions may be most effective when done in a specific time period after surgery. Adhesions are common at the site of an abdominal surgical scar and some doctors use laparoscopy some time after the operation to remove them. Researchers deliberately injured the uteruses of mice during surgery and then examined them again for adhesions 5, 7, 14, or 21 days later. If adhesions were found they were removed and 14 days later the animals were examined again. The rate of recurring adhesions was lowest in the animals who were examined 14 days after the injury.

Background. Recent studies have shown that multiple cytokines are secreted by ovarian epithelial cancer cells. Previous studies have shown that the cancer cell lines secrete macrophage colony-stimulating factor (M-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-1 (IL-1), interleukin-6 (IL-6), and transforming growth factor-alpha (TGF-[alpha]). Concomitantly, the serum levels of one of the growth factors (M-CSF) was found to be significantly elevated in patients with primary ovarian cancer and in second-look patients. The authors evaluated the serum levels of IL-1 [alpha], IL-1 [beta], IL-6, and tumor necrosis factor-alpha (TNF-[alpha]) in patients with primary ovarian epithelial cancer. These levels were then compared with cytokine concentration found in normal peritoneal fluid. Methods. Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of cytokines in normal peritoneal fluid, ascites, and serum. Results. In serum, TNF-[alpha] and IL-6 were significantly increased in primary ovarian cancer patients when compared with control subjects (P < 0.0001 for both cytokines). TNF-[alpha] and IL-6 were also significantly higher than the levels found in second-look patients (P < 0.007 for TNF-[alpha], and P = 0.0002 for IL-6). The levels of IL-1 [alpha] and [beta] were not elevated in ovarian cancer. TNF-[alpha] in the ascites was higher when compared with normal peritoneal fluid and was statistically significantly different when a cut-off point between 71-110 pg was selected (P < 0.005). The levels of IL-6 in ascites from patients with primary ovarian cancer also showed a marked increase (P < 0.0001) when compared with peritoneal fluid from control subjects. Conclusions. Levels of IL-1, IL-6, and TNF-[alpha] were determined in normal peritoneal fluid, ovarian malignant ascites, normal serum, and serum from patients with ovarian cancer. This study showed that the patients with ovarian cancer have elevated levels of IL-6 and TNF-[alpha] in serum and ascitic fluid. A larger study would help in evaluating the potential use of cytokines as tumor markers in ovarian cancer.

OBJECTIVE: The peritoneal fluid cell responses to the available barriers used to prevent postoperative adhesions, oxidized regenerated cellulose (Interceed), and expanded polytetrafluoroethylene (Gore-Tex Surgical Membrane), were compared. STUDY DESIGN: Oxidized regenerated cellulose and expanded polytetrafluoroethylene were inserted into the peritoneal cavity on mice and the peritoneal fluid cell number, differential cell count, morphologic type, adherence to plastic, and phorbol-12, 13-myristate acetate-stimulated hydrogen peroxide production evaluated. Peritoneal fluid cell attachment to oxidized regenerated cellulose and expanded polytetrafluoroethylene was evaluated by electron microscopy. RESULTS: Oxidized regenerated cellulose promptly elicited increased numbers of large, morphologically activated peritoneal fluid macrophages that adhered more rapidly and produced more hydrogen peroxide than controls. Expanded polytetrafluoroethylene gradually increased the number of normal-appearing peritoneal fluid macrophages with increased hydrogen peroxide production but normal adherence. Macrophages rapidly attached to both materials in vivo, with oxidized regenerated cellulose being rapidly degraded. CONCLUSION: Oxidized regenerated cellulose, to a greater extent than expanded polytetrafluoroethylene, elicits an acute peritoneal fluid inflammatory exudate in the mouse, which may contribute to the oxidized regenerated cellulose-induced peritoneal injury and de novo adhesions observed in this model. (Am J Obstet Gynecol 1992;166:1137-49.)

Genital warts (condylomata acuminata) are caused by the same virus that results in hand or finger warts, but are transmitted sexually. In two cases, vaginal condylomata were diagnosed in young women who had undergone the creation of a semi-artificial vagina. The operation, called a McIndoe neovagina creation, is a rare procedure used for women with congenitally malformed vaginas. A split-thickness skin graft is used to create a new vagina, but the grafted tissue has different mucosal characteristics than vaginal tissue. The first case was remarkable in that the woman had an identical twin with a normal genital tract. In both cases, the patients became sexually active soon after the operation. Several years after the surgery, both women developed vaginal growths that were surgically removed, and then chemically treated. It is uncertain whether the lesions resulted from the relocation of previously infected skin, or were acquired through coitus. However, considering the rarity of the operation, it seems unusual that condylomata acuminata occurred in both women; another similar case has been reported in the literature. These cases also illustrate that, although women with neovaginas do not need contraception, they are not immune to serious sexually transmitted disease. (Consumer Summary produced by Reliance Medical Information, Inc.)

Highlights current needs facing clinical decision making regarding leiomyomata in the 3rd millennium. Effective prevention strategy in genetically predisposed individuals; Slowing the growth of leiomyomata; Mechanisms of infertility; Early detection; Better surgical techniques; Recurrences after myomectomy.

This study investigated changes in peripheral serum estrogen (E), progesterone (P), luteinizing hormone (LH), follicle-stimulating hormone, and prolactin (PRL) in 11 women of reproductive age undergoing a variety of operations under general anesthesia without compromise of ovarian vasculature. All hormone determinations were plotted in relation to the midcycle LH peak; eight women with cyclic ovulatory menses served as controls.

A primary “empty” sella may be associated with significant hypothalamic-pituitary dysfunction. This report characterizes the endocrinologic and radiographic findings in six patients with hyperprolactinemia (range 34.3 to 1,170 ng/ml) ultimately found to have an enlarged empty sella. Lateral skull x-ray films and thin-section tomograms were suggestive of pituitary tumors in all patients. Four patients underwent transphenoidal sellar exploration after pneumoencephalography (PEG) failed to demonstrate air within the sella. The inability of PEG to demonstrate an empty sella in two patients was explainable on the basis of an intact diaphragma sellae with previous transient intrasellar pathology responsible for the sellar enlargement. Dynamic hypothalamic-pituitary testing yielded no consistent pattern of response. These studies suggest that an empty sella: (1) may be associated with hyperprolactinemia, regardless of etiology, (2) is not diagnosable by dynamic hormonal testing, and (3) may be indistinguishable from a pituitary tumor by current radiographic techniques.

The mechanism by which antisperm antibodies inhibit fertility is not completely understood. Macrophages may play a role in mediating infertility by interacting with sperm and destroying gametes. Experiments were conducted evaluating the effect of antisperm antibody on the phagocytosis and lysis of sperm by human peritoneal macrophages in vitro. Sperm from a fertile man treated with sera from normal men and women or medium alone had 5 to 280 molecules of IgG/sperm, as determined by a 125I-labeled anti-human IgG monoclonal antibody assay. By contrast, sperm treated with sera containing antisperm antibodies had 310 to 1240 molecules of IgG/sperm. Peritoneal macrophages harvested from infertile women with tubal/adhesive problems mediated phagocytosis and lysis of 111In-labeled sperm which was enhanced by treatment of the sperm with sera containing antisperm antibodies (39.0%±1.5% versus 76.3%±3.2% phagocytosis, and 3.3%±0.3% versus 23.3%±2.3% lysis of sperm [control versus antibody-treated]). The likelihood of fertilization in couples with antisperm antibody may be determined not only by the antibody but also by the presence of genital tract macrophages capable of destroying the antibody-coated sperm.

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.

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.

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<0.05), PF leukocyte number (P<0.05), and total PF lysozyme (P<0.05). Significant correlations were found between total PF lysozyme and PF volume (r=0.72, P<0.0001) and leukocyte number (r=0.67, P<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.

To evaluate the impact of the materials contained in the available adhesion prevention barriers on the peritoneum.

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 (GnRH-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.

Objective:To evaluate the hypothesis that a postcoital test, optimally performed in the periovulatory period of cycles in which gonadotropin-induced superovulation was used, correlates with cycle fecundity.

Nitric oxide (NO) is produced by numerous different cell types, and it is an important regulator and mediator of many processes including smooth muscle relaxation, neurotransmission, and murine macrophage-mediated cytotoxicity for microbes and tumor cells. Although murine macrophages produce NO readily after activation, human monocytes and tissue macrophages have been reported to produce only low levels of NO in vitro. The purpose of this study was to determine if stimulated human mononuclear phagocytes produce inducible nitric oxide synthase (iNOS) mRNA, protein, and enzymatic activity. By reverse transcriptase-polymerase chain reaction (RT-PCR) analysis, we show that human monocytes can be induced to express iNOS mRNA after treatment with lipopolysaccharide (LPS) and/or interferon- γ (IFN-γ). By immunofluorescence and immunoblot analyses, we show monocytes and peritoneal macrophages contain detectable levels of iNOS antigen after stimulations with cytokines in vitro. Control monocytes or those cultured with LPS and/or various cytokines have low levels of NOS functional activity as measured by the ability of cell extracts to convert L-arginine to L-citrulline, and they produce low levels of the NO catabolites nitrite and nitrate. Peritoneal macrophages have significantly enhanced nitrite/nitrate production and NOS activity after treatment with LPS and/ or IFN-γ, whereas monocyte nitrite/nitrate production and NOS activity are not altered by the treatments. Monocytes cultured with various live or heat-killed bacteria, fungi, or human immunodeficiency virus (HIV)-1 do not produce high levels of nitrite/nitrate. Antibodies against transforming growth factor-β (TGF-β), a factor known to inhibit iNOS expression and NO production in mouse macrophages, do not enhance NO production in human monocytes or macrophages. Biopterin, an obligate cofactor of iNOS enzymatic activity, is undetectable in freshly isolated or cultured human monocytes and peritoneal macrophages. However, replenishment of intracellular levels of tetrahydrobiopterin by culture with the cell-permeable, nontoxic precursor sepiapterin does not enhance the abilities of the human mononuclear phagocytes to produce NO in vitro. Mixing experiments show no evidence of a functional NOS inhibitor in human mononuclear phagocytes. Thus, we demonstrate that human mononuclear phagocytes can produce iNOS mRNA and protein, and (despite this) their abilities to generate NO are very low.

The mechanism of infertility in women with endometriosis is unknown, but it is independent of mechanical factors that affect fallopian tube function. Increased numbers of peritoneal macrophages are present in women with endometriosis and have access to the female reproductive tract via the oviducts. To determine whether peritoneal macrophages might phagocytize sperm and thereby contribute to infertility in women with endometriosis, we examined peritoneal macrophages from 32 fertile and infertile women; the infertile group was separated into those with and those without visible endometriosis. Peritoneal macrophages from infertile patients with endometriosis phagocytized more normal sperm in vitro (84% ± 4%) than did those from fertile women (43% ± 4%) or infertile women without endometriosis (46% ± 8%) (p < 0.002). The sperm phagocytosis occurred rapidly and reached a peak by approximately 6 hours. Incubation at 0° C, lysing the macrophages by freezing and thawing, or fixing the macrophages with glutaraldehyde inhibited the sperm uptake by macrophages. The process occurred in cultures with or without serum, thereby indicating that the sperm phagocytosis was not dependent on sperm opsonization with a serum factor. Electron microscopy showed internalization of the spermatozoa into phagosomes with subsequent intravacuolar degradation. These data demonstrate that: (1) peritoneal macrophages phagocytize and degrade sperm in vitro and (2) peritoneal macrophages isolated from women with endometriosis exhibit greater phagocytosis in vitro than do macrophages from fertile women or infertile women without endometriosis. These results suggest that, if peritoneal macrophages from women with endometriosis enter the reproductive tract via the oviducts, they might adversely influence fertilization by phagocytizing sperm.

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.