Effect of perceptions of menstrual blood loss and menstrual pain on women's quality of life.

OBJECTIVES: The aim of the study was to explore Australian women's experiences of menstruation and effect on quality of life (QoL). METHODS: A representative sample of women recruited through a commercial social research sampling organisation completed a detailed online questionnaire about menstruation. Specific detailed questions were asked about perceptions of heavy menstrual bleeding (HMB) and menstrual pain. RESULTS: The questionnaire was completed by 1575 women aged 20-39 years. Most perceived their bleeding to be light (11.6%) or moderate (60.5%); 363 (22.5%) perceived it to be heavy and 86 (5.3%) very heavy. Women who experienced severe or very severe menstrual pain were significantly more likely to report periods as heavy or very heavy (p < .001). The prevalence ratios for being confined to bed during menstruation for women experiencing severe or very severe menstrual pain were 12.02 (95% CI: 5.71-25.31) and 15.93 (95% CI: 7.51-33.78), respectively, compared with women experiencing no pain. The prevalence ratios for being confined to bed were 1.58 (95% CI: 1.11-2.24) and 1.53 (95% CI: 1.04-2.25) for women with heavy or very heavy bleeding, respectively. Women who experienced severe or very severe menstrual pain associated with their HMB were >12 times more likely to be confined to bed for 0.5-1 day during menstruation than if they reported HMB without pain. CONCLUSION: Severe menstrual pain with HMB has a much more profound effect on all aspects of women's QoL than HMB alone; it accounts for more days in bed and for loss of productivity.

Use of hormonal therapy is associated with reduced nerve fiber density in deep infiltrating, rectovaginal endometriosis.

OBJECTIVE: To study the density of nerve fibers in cases of deep infiltrating endometriosis (DIE) of the rectovaginal septum in relation to various clinical factors. DESIGN: A research laboratory-based study. SETTING: A tertiary center together with a research laboratory. METHODS: Archived DIE tissue samples from 45 women operated upon for rectovaginal septum DIE were re-examined histologically, and by immunohistochemistry. MAIN OUTCOME MEASURES: The effect of progestogens or combined oral contraceptives on the density of nerve fibers, and the expression of nerve growth factor (NGF) and its high-affinity receptor (tyrosine kinase receptor A, Trk-A). RESULTS: The use of hormonal therapy was associated with reduced densities of sympathetic, parasympathetic and sensory nerve fibers in DIE lesions. Density of total nerve fibers (with pan-neuronal marker PGP9.5) was significantly lower (p < 0.05) in lesions collected from hormone-treated women (8.6/mm², 4.2-20.8/mm²; median density, from 25th to 75th quartiles) compared with that in lesions from untreated women (24.9/mm², 11.2-34.9/mm²). DIE lesions stained strongly for NGF and its receptor Trk-A. Expression of NGF, but not of Trk-A, was significantly reduced during use of hormonal therapy. CONCLUSIONS: Use of hormonal therapy was associated with significantly reduced nerve fiber density in DIE lesions. This may be an important mechanism of action of hormonal therapy for controlling DIE pain symptoms. The expression of estrogen-regulated NGF and its receptor was only partially suppressed during the use of hormonal therapy, suggesting that local estrogen action is often maintained during conventional hormonal therapy in cases of DIE.

Detection of the pan neuronal marker PGP9.5 by immuno-histochemistry and quantitative PCR in eutopic endometrium from women with and without endometriosis.

PURPOSE: To assess endometrial gene as well as protein expression of neuroendocrine and supposedly endometriosis-associated product PGP9.5 and pain symptoms in women with endometriosis and controls undergoing laparoscopy, using molecular biological and immuno-histochemical approaches in the same patients. METHODS: Biopsy of eutopic endometrium from 29 patients by sharp curettage, and preparation of paraffin blocks. Determination of PGP9.5 gene expression and protein abundance using qPCR and immuno-histochemistry. RESULTS: qPCR; The PGP9.5 mRNA expression level between women with (N = 16) and without (N = 13) endometriosis was not different, regardless of pain symptoms or menstrual cycle phase. PGP9.5 expression was higher in women who reported pain compared to those who did not; however, this association was not statistically significant. The expression of PGP9.5 mRNA was higher in women with endometriosis and pain during the proliferative than in the secretory phase (P = 0.03). Furthermore, in the first half of the cycle, the abundance of the PGP9.5 transcript was also significantly higher in endometriosis patients compared to those without (P = 0.03). Immuno-histochemistry; Thirteen of the 16 endometriosis patients showed positive PGP9.5 immuno-reactivity in the endometrium, whereas no such signal was observed in women without endometriosis. The absolute number of nerve fibres per mm(2) in women with endometriosis was similar, regardless of the pain symptoms. CONCLUSIONS: PGP9.5 mRNA expression is increased in the proliferative phase of endometriotic women with pain. The presence of nerve fibres was demonstrated by a PGP9.5 protein signal in immuno-histochemistry and restricted to patients with endometriosis. Based on these results, however, there did not appear to be a direct association between the gene expression and protein abundance in women with and without endometriosis or those that experienced pain.

Abnormal uterine bleeding: advantages of formal classification to patients, clinicians and researchers.

OBJECTIVE: To highlight the advantages of formal classification of causes of abnormal uterine bleeding from a clinical and scientific perspective. DESIGN: Review and recommendations for local implementation. SETTING: In the past, research in the field of menstrual disorders has not been funded adequately with respect to the impact of symptoms on individuals, healthcare systems and society. This was confounded by a diverse terminology, which lead to confusion between clinical and scientific groups, ultimately harming the underlying evidence base. To address this, a formal classification system (PALM-COEIN) for the causes of abnormal uterine bleeding has been published for worldwide use by FIGO (International Federation of Gynecology and Obstetrics). POPULATION AND MAIN OUTCOME MEASURES: This commentary explains problems created by the prior absence of such a system, the potential advantages stemming from its use, and practical suggestions for local implementation. RESULTS AND CONCLUSIONS: The PALM-COEIN classification is applicable globally and, as momentum gathers, will ameliorate recurrence of historic problems, and harmonise reporting of clinical and scientific research to facilitate future progress in women's health.

Female genital mutilation/cutting--towards abandonment of a harmful cultural practice.

Globally, the prevalence of, and support for, female genital mutilation/cutting (FGM/C) is declining. However, the entrenched sense of social obligation that propagates the continuation of this practice and the lack of open communication between men and women on this sensitive issue are two important barriers to abandonment. There is limited evidence on the role of men and their experiences in FGM/C. Marriageability of girls is considered to be one of the main driving forces for the continuation of this practice. In some countries, more men than women are advocating to end FGM/C. Moreover, men, as partners to women with FGM/C, also report physical and psychosexual problems. The abandonment process involves expanding a range of successful programs, addressing the human rights priorities of communities and providing power over their own development processes. Anecdotal evidence exists that FGM/C is practised amongst African migrant populations in Australia. The Australian Government supports a taskforce to improve community awareness and education, workforce training and evidence building. Internationally, an African Coordinating Centre for abandonment of FGM/C has been established in Kenya with a major global support group to share research, promote solidarity, advocacy and implement a coordinated and integrated response to abandon FGM/C.

The FIGO systems for nomenclature and classification of causes of abnormal uterine bleeding in the reproductive years: who needs them?

In November 2010, the International Federation of Gynecology and Obstetrics formally accepted a new classification system for causes of abnormal uterine bleeding in the reproductive years. The system, based on the acronym PALM-COEIN (polyps, adenomyosis, leiomyoma, malignancy and hyperplasia-coagulopathy, ovulatory disorders, endometrial causes, iatrogenic, not classified) was developed in response to concerns about the design and interpretation of basic science and clinical investigation that relates to the problem of abnormal uterine bleeding. A system of nomenclature for the description of normal uterine bleeding and the various symptoms that comprise abnormal bleeding has also been included. This article describes the rationale, the structured methods that involved stakeholders worldwide, and the suggested use of the International Federation of Gynecology and Obstetrics system for research, education, and clinical care. Investigators in the field are encouraged to use the system in the design of their abnormal uterine bleeding-related research because it is an approach that should improve our understanding and management of this often perplexing clinical condition.

Pregnancy rates in older poor responders who achieve embryo transfer in long down-regulated ART cycles are comparable to those in younger poor responders.

OBJECTIVE: To determine whether older women with a poor response to follicular stimulation achieve pregnancy results that are comparable to those of younger poor responders. METHODS: Two hundred five women undergoing in vitro fertilization treatment at the Fertility Unit in the Royal Prince Alfred Hospital in Sydney, Australia were selected for retrospective cohort analysis. The outcomes in women > 38 years of age with < 5 oocytes retrieved were compared with those in women ≤ 38 years who also had < 5 oocytes retrieved. Clinical and ongoing pregnancy rates were compared. RESULTS: Implantation rates (21.01 ± 0.38 % vs. 12.82 ± 0.27%, P = 0.11) and clinical pregnancy rates (25.71 ± 0.44% vs. 20.21 ± 0.40%, P = 0.41) were similar in the two groups following cleavage stage embryo transfer. The same was true for blastocyst stage embryo transfer (implantation rates 16.67 ± 0.33% vs. 13.89 ± 0.33%, P = 0.80, and clinical pregnancy rates 23.81 ± 0.44% vs. 16.67 ± 0.38%, P = 0.59). Ongoing pregnancies beyond the 12th week of gestation were also comparable between cleavage stage (24.28 ± 0.43% vs. 16.84 ± 0.34%, P = 0.24) and blastocyst stage embryo transfers (23.81 ± 0.44% vs. 11.11 ± 0.32%, P = 0.32). CONCLUSION: If older poor responders reach the stage of embryo transfer, they can achieve pregnancy rates similar to those of younger poor responders when matched numbers of embryos are transferred.

Effective treatment of heavy and/or prolonged menstrual bleeding without organic cause: pooled analysis of two multinational, randomised, double-blind, placebo-controlled trials of oestradiol valerate and dienogest.

OBJECTIVES: To evaluate the efficacy of oestradiol valerate/dienogest (E2V/DNG) for the treatment of heavy and/or prolonged menstrual bleeding without organic pathology based on the analysis of data from two identically designed double-blind, randomised studies. METHODS: Women aged ≥ 18 years with heavy and/or prolonged menstrual bleeding were randomised to E2V/DNG (n = 269) or placebo (n = 152) for 196 days. Objective changes in menstrual blood loss (MBL) volume were assessed using the alkaline haematin method. RESULTS: After six months of treatment, median MBL decreased by 88% with E2V/DNG compared with 24% with placebo. The greatest reduction was achieved at the first withdrawal bleed after treatment initiation and it was sustained with no loss of effect throughout treatment. CONCLUSION: E2V/DNG was more effective than placebo in reducing MBL in women with heavy and/or prolonged menstrual bleeding without organic pathology. The reduction was largely achieved as early as the first withdrawal bleed, with further gradual improvement throughout treatment.

Neuroendocrine cells in eutopic endometrium of women with endometriosis.

BACKGROUND: Endometriosis is a common gynaecological disease, but the pathogenesis of endometriosis and pathophysiological basis for endometriosis-associated painful symptoms are still uncertain. Little is known about neuroendocrine (NE) cells in the uterus. METHODS: For this study, 38 premenopausal women with histologically diagnosed ovarian endometrioma or peritoneal endometriosis and 24 women without endometriosis were selected. Biopsy samples from eutopic endometrium were used for immunohistochemical staining to detect synaptophysin (SYN) and neuron-specific enolase (NSE) expression in women with and without endometriosis. RESULTS: There were substantially more NE cells of eutopic endometrium stained with SYN and NSE in women with endometriosis than in those without endometriosis (3.8 +/- 1.8 versus 0.5 +/- 0.7/mm2, P < 0.001, and 2.8 +/- 2.1 versus 0.4 +/- 0.6/mm2, respectively, P < 0.001). These cells were scattered in the epithelium of endometrial glands. At all stages of the menstrual cycle, the densities of NE cells stained with SYN and NSE were greater in women with endometriosis than in those without endometriosis (P < 0.05). CONCLUSIONS: These results suggest that NE cells in eutopic endometrium probably play some role in the pathogenesis or symptoms of endometriosis.

A cost-effectiveness analysis of in-vitro fertilization by maternal age and number of treatment attempts.

BACKGROUND: The increase in use and costs of assisted reproductive therapies including in-vitro fertilization (IVF) has led to debate over public funding. A decision analytic model was designed to estimate the incremental cost-effectiveness of IVF by additional treatment programmes and maternal age. METHODS: Data from the Australian and New Zealand Assisted Reproductive Database were used to estimate incremental effects (live birth and other pregnancy outcomes) and costs for cohorts of women attempting up to three treatment programmes. A treatment programme included one fresh cycle and a variable number of frozen cycles dependent on maternal age. RESULTS: The incremental cost per live birth ranged from AU dollars 27 373 and AU dollars 31 986 for women aged 30-33 on their first and third programmes to AU dollars 130 951 and AU dollars 187 515 for 42-45-year-old women on their first and second attempts. Overall, these trends were not affected by inclusions of costs associated with ovarian hyperstimulation syndrome or multiple births. CONCLUSIONS: This study suggests that cost per live birth from IVF increases with maternal age and treatment programme number and indicates that maternal age has the much greater effect. This evidence may help decisionmakers target the use of IVF services conditional on societal willingness to pay for live births and equity considerations.

The role of Foxp3+ regulatory T-cells in endometriosis: a potential controlling mechanism for a complex, chronic immunological condition.

BACKGROUND: Endometriosis is an inflammatory condition, associated with highly dysregulated immune response at both uterine and peritoneal levels. Surprisingly, Foxp3+ regulatory T-cells, which control and suppress a range of immune responses, have not previously been investigated in endometriosis. METHODS AND RESULTS: Immunohistochemical analysis of Foxp3+ cells in 127 eutopic endometrial samples and 59 ectopic peritoneal lesions revealed that these immune cell populations are highly disturbed in women suffering from endometriosis. We showed that Foxp3+ cells remained highly up-regulated during the secretory phase of the menstrual cycle, while at this time their expression is significantly down-regulated in women without endometriosis (P < 0.001). Foxp3+ cells were detected in the stroma of 18 of the 59 peritoneal endometriotic lesions, but not in the surrounding or control peritoneal tissue. CONCLUSIONS: We propose that in eutopic endometrium in women with endometriosis Foxp3+ cells decrease the ability of newly recruited immune cell populations to effectively recognize and target endometrial antigens shed during menstruation, allowing their survival and ability to implant in ectopic sites. At these ectopic sites, variable expression of Foxp3+ cells within some peritoneal endometriotic lesions is likely to be linked to the characteristics and stage of individual lesion development and be playing key roles in pathogenesis and progression of this unique condition.

A historical overview of the study and representation of uterine microvascular structures.

The concept of anatomical modelling of the internal vascular structures of organs dates back to the Middle Ages by way of corrosion casting. The first to apply this classic injection technique in the reproductive arena was John Hunter (1754), who undertook to establish the independence of the maternal and fetal circulations in the placenta. The first detailed microscopic study of the endometrial vessels was undertaken a century later. Endometrial inoculation studies in the 1930s with coloured fluids such as India ink have provided the basis of our current understanding of the complex sequence of morphological vascular changes which occur in the endometrial tissue leading up to and during the process of menstruation. Classic injection techniques were limited in that they were often associated with artefacts due to injection-induced vessel breakages and variability in size of the suspended particles in the injection material. Following this, the smallest blood vessels were better demonstrated using Gomori's alkaline phosphate method. An adaptation of this method in the early 1960s demonstrated the uterine vasculature in a more detailed way than ever before. In the early 1970s, novel microradiography studies involved the injection of warmed radio-opaque medium into both arterial and venous microvasculature of the human uterus. Early 1980s investigators also utilized corrosion casting of uterine microvessels combined with scanning electron microscopy. The last 20 years have seen the dawn of the computer age, immunohistochemistry, advanced microscopy (laser scanning confocal and multiphoton emission), and stereological methods to obtain quantitative measurements of 3-dimensional endometrial vascular structures. This review article contains a historical overview of uterine microanatomical vascular visualisation from the early beginnings to the latest computerised techniques.

Mysteries of endometriosis pain: Chien-Tien Hsu Memorial Lecture 2009.

The more that one looks at the condition endometriosis, the more one realises that it is a unique and complex condition exhibiting a bizarre range of deviations from normal endometrial and myometrial physiology, and presenting with a challenging range of pain-related symptoms. The changing nature of the pain is not well defined, and the molecular mechanisms leading to pain generation are far from clear. Recent research has begun to reveal some of these links between expression of unusual molecules in the eutopic endometrium and ectopic lesions, microanatomical changes in the pelvic nervous system, neuronal dysfunction and the later development of neuropathic pain. A better understanding of these mechanisms will undoubtedly lead to improved use of current medical and surgical treatments, and to the development of novel treatments in the future.

The effect of retrieved oocyte count on pregnancy outcomes in an assisted reproduction program.

OBJECTIVE: To determine if women with less than five eggs retrieved do as well as women with more eggs retrieved in terms of pregnancy outcomes in our assisted reproduction program. METHOD: Two hundred one women undergoing in vitro fertilization treatment at Fertility Unit in Royal Prince Alfred Hospital, University of Sydney, Australia were selected for retrospective evaluation. The women were grouped according to the number of oocytes retrieved at ovum pick-up. Group A consisted of women with less than 5 oocytes, group B with 5 to 10 oocytes and group C with 11 to 15 oocytes collected. Clinical and ongoing pregnancy rates were compared. RESULTS: There was no difference between the groups in terms of clinical and ongoing pregnancy rates. CONCLUSION: With good IVF lab conditions, if a patient reaches embryo transfer, the number of eggs retrieved should not affect the likelihood of pregnancy outcome in an assisted reproductive technology treatment.

Best Practices for Counseling Adolescents about the Etonogestrel Implant.

Among young persons, ease of use, high efficacy, and high acceptability makes the etonogestrel contraceptive implant an important choice for this age group. Adolescent-friendly, patient-centered counseling considers the patient's cognitive development, the influence of friends and family, as well as their own preferences and values. Age-appropriate language, graphics, and models are useful to explain contraceptive options and relevant side effects. Effectiveness, reversibility, safety, noncontraceptive benefits, and side effects are important attributes and should be discussed when teens are choosing a contraceptive method. In this review we describe suggested best practices for counseling adolescents about the etonogestrel implant so they can make informed, prudent decisions about using this contraceptive method.

Diagnosing adenomyosis: an integrated clinical and imaging approach.

BACKGROUND: Adenomyosis is a benign uterine disorder where endometrial glands and stroma are pathologically demonstrated within the uterine myometrium. The pathogenesis involves sex steroid hormone abnormalities, inflammation, fibrosis and neuroangiogenesis, even though the proposed mechanisms are not fully understood. For many years, adenomyosis has been considered a histopathological diagnosis made after hysterectomy, classically performed in perimenopausal women with abnormal uterine bleeding (AUB) or pelvic pain. Until recently, adenomyosis was a clinically neglected condition. Nowadays, adenomyosis may also be diagnosed by non-invasive techniques, because of imaging advancements. Thus, a new epidemiological scenario has developed with an increasing number of women of reproductive age with ultrasound (US) or magnetic resonance imaging (MRI) diagnosis of adenomyosis. This condition is associated with a wide variety of symptoms (pelvic pain, AUB and/or infertility), but it is also recognised that some women are asymptomatic. Furthermore, adenomyosis often coexists with other gynecological comorbidities, such as endometriosis and uterine fibroids, and the diagnostic criteria are still not universally agreed. Therefore, the diagnostic process for adenomyosis is challenging. OBJECTIVE AND RATIONALE: We present a comprehensive review on the diagnostic criteria of adenomyosis, including clinical signs and symptoms, ultrasound and MRI features and histopathological aspects of adenomyotic lesions. We also briefly summarise the relevant theories on adenomyosis pathogenesis, in order to provide the pathophysiological background to understand the different phenotypes and clinical presentation. The review highlights the controversies of multiple existing criteria, summarising all of the available evidences on adenomyosis diagnosis. The review aims also to underline the future perspective for diagnosis, stressing the importance of an integrated clinical and imaging approach, in order to identify this gynecological disease, so often underdiagnosed. SEARCH METHODS: PubMed and Google Scholar were searched for all original and review articles related to diagnosis of adenomyosis published in English until October 2018. OUTCOMES: The challenge in diagnosing adenomyosis starts with the controversies in the available pathogenic theories. The difficulties in understanding the way the disease arises and progresses have an impact also on the specific diagnostic criteria to use for a correct identification. Currently, the diagnosis of adenomyosis may be performed by non-invasive methods and the clinical signs and symptoms, despite their heterogeneity and poor specificity, may guide the clinician for a suspicion of the disease. Imaging techniques, including 2D and 3D US as well as MRI, allow the proper identification of the different phenotypes of adenomyosis (diffuse and/or focal). From a histological point of view, if the diagnosis of diffuse adenomyosis is straightforward, in more limited disease, the diagnosis has poor inter-observer reproducibility, leading to extreme variations in the prevalence of disease. Therefore, an integrated non-invasive diagnostic approach, considering risk factors profile, clinical symptoms, clinical examination and imaging, is proposed to adequately identify and characterise adenomyosis. WIDER IMPLICATIONS: The development of the diagnostic tools allows the physicians to make an accurate diagnosis of adenomyosis by means of non-invasive techniques, representing a major breakthrough, in the light of the clinical consequences of this disease. Furthermore, this technological improvement will open a new epidemiological scenario, identifying different groups of women, with a dissimilar clinical and/or imaging phenotypes of adenomyosis, and this should be object of future research.

Interrelationships between ovarian and pituitary hormones in ovulatory menstrual cycles across reproductive age.

CONTEXT: Ovarian hormones regulate pituitary gonadotropin secretion across the menstrual cycle via negative and positive feedback mechanisms. The contribution of individual hormones is complex and is a continuing area of research. OBJECTIVE: The aim of the study was to identify relationships between LH/FSH and estradiol, progesterone, inhibin A, inhibin B, and anti-Mullerian hormone (AMH) in ovulatory menstrual cycles across reproductive age. DESIGN: Serum ovarian and pituitary hormones were studied in a group of young (<35 yr; n = 21) and older (>45 yr; n = 55) women. The slopes of the regression lines relating the ovarian and pituitary hormones were determined by multiple linear regression analysis and expressed with 95% confidence intervals for each ovarian hormone, with FSH and LH as independent variables. Both simultaneous and delayed (time lagged) relationships were examined. RESULTS: Clear associations were evident for the lagged prediction of FSH, with significant negative associations being evident with inhibin B and AMH in the follicular phase and with estradiol, inhibin B, progesterone, and AMH in the luteal phase. For the lagged prediction of LH, significant positive and negative associations were observed with estradiol and inhibin B, respectively, in the follicular phase and a negative association with progesterone and inhibin B in the luteal phase. CONCLUSIONS: It is concluded that in the follicular phase, inhibin B is a major feedback regulator of FSH and may also be a negative feedback regulator of LH. AMH may be indirectly involved in FSH regulation.

Rich innervation of deep infiltrating endometriosis.

BACKGROUND: Deep infiltrating endometriosis (DIE) is a specific type of endometriosis, which can be associated with more severe pelvic pain than other forms of endometriotic lesions. However, the mechanisms by which pain is generated are not well understood. METHODS: DIE (n = 31) and peritoneal endometriotic (n = 40) lesions were sectioned and stained immunohistochemically with antibodies against protein gene product 9.5, neurofilament, nerve growth factor (NGF), NGF receptors tyrosine kinase receptor-A (Trk-A) and p75, substance P, calcitonin gene-related peptide, vesicular acetylcholine transporter, neuropeptide Y, vasoactive intestinal peptide and tyrosine hydroxylase to demonstrate myelinated, unmyelinated, sensory and autonomic nerve fibres. RESULTS: There were significantly more nerve fibres in DIE (67.6 +/- 65.1/mm(2)) than in peritoneal endometriotic lesions (16.3 +/- 10.0/mm(2)) (P < 0.01). DIE was innervated abundantly by sensory Adelta, sensory C, cholinergic and adrenergic nerve fibres; NGF, Trk-A and p75 were strongly expressed in endometriotic glands and stroma of DIE. CONCLUSIONS: The rich innervation of DIE may help to explain why patients with this type of lesion have severe pelvic pain.

Dendritic cell populations in the eutopic and ectopic endometrium of women with endometriosis.

BACKGROUND: Immune alterations may be involved in the pathogenesis and progression of endometriosis. Dendritic cells (DCs) are potent antigen presenting cells that are highly involved in the initiation of the immune response. The aim of this study was to investigate DC populations in the eutopic and ectopic endometrium of women with endometriosis compared with controls. METHODS: Hysterectomy samples were obtained from premenopausal women with (n = 33) and without (n = 28) endometriosis. In addition, paired peritoneal endometriotic lesions and uterine curettings were collected from 32 women with endometriosis. Specimen sections were stained immunohistochemically using antibodies for monoclonal mouse antibodies directed against human CD1a and CD83, which are specific for immature and mature DCs, respectively. RESULTS: The mean density of endometrial CD1a+ DCs in the basal layer was significantly increased in women with endometriosis compared with controls during the proliferative phase only (P = 0.001). There was a highly significant decrease in the density of endometrial CD83+ DCs in women with endometriosis compared with controls in both layers of the endometrium across all phases of the menstrual cycle (P = 0.001). The density of CD1a+ DCs was significantly increased in peritoneal endometriotic lesions (P = 0.003) and in the surrounding peritoneum (P = 0.001) compared with paired uterine curettings and peritoneum distant from the lesion. CONCLUSIONS: Both CD1a+ and CD83+ DC populations were altered in the eutopic and ectopic endometrium of women with endometriosis compared with controls. Alterations in these cells, which play a crucial role in the coordination of the immune response, may be involved in pain generation and the pathogenesis of endometriosis.

Macrophages and nerve fibres in peritoneal endometriosis.

BACKGROUND: Endometriosis is considered to be an inflammatory disease, and macrophages are the most numerous immune cells in endometriotic lesions. However, the mechanisms underlying the elevation of macrophages and their role in the pathogenesis and manifestations of endometriosis still remain unclear. METHODS: The number of macrophages stained for CD68 in endometriotic lesions (n = 24) and in peritoneum distant from the lesions (n = 14) from women with endometriosis was compared with the number of macrophages in normal peritoneum from women without endometriosis (n = 18). Peritoneal lesions were also double-stained for CD68 and protein gene product 9.5 to study the relationship between macrophages and nerve fibres. RESULTS: The densities of macrophages in peritoneal endometriotic lesions and unaffected peritoneum from women with endometriosis were both significantly higher than that in normal peritoneum from women without endometriosis (P < 0.001). More nerve fibres were also found in the areas where increased numbers of macrophages were identified. CONCLUSIONS: There was a significant elevation of macrophages in both normal peritoneum and peritoneal lesions from women with endometriosis compared with normal peritoneum from women without endometriosis. These cells may well play roles in the growth and development of endometriotic lesions and in the generation of pain through interaction with nerve fibres.