Ovarian reserve may influence the outcome of bone mineral density in patients with long-term use of dienogest.

OBJECTIVE: Long-term administration of dienogest, which is known to have effect on bone mineral density, is frequently done in patients with endometriosis and adenomyosis, but a few studies focused on the bone mineral density changes after finishing the long-term therapy. This study aimed to reveal the factors that adversely affect lumbar bone mineral density. METHOD: Fifty-seven premenopausal women who visited our hospital were diagnosed as either endometriosis or adenomyosis, and they were treated by dienogest for more than 115 weeks (26.5 months). Based on a previous report, bone mineral density changes less than 2% was categorized as the osteopenic group (n = 30), and the others were assigned to the unchanged group (n = 27). Bone mineral density was measured at the lumbar spine using dual-energy X-ray absorptiometry. A representative ovarian reserve marker, endogenous estradiol levels, and follicle-stimulating hormone levels were measured over time and were compared between the osteopenic and unchanged groups. RESULT: Duration of dienogest intake was 59.5 months (osteopenic group) versus 57.5 months (unchanged group). These patients experienced ovarian surgeries in a similar frequency, but the ovarian reserve in osteopenic group was impaired as suggested by the decline of endogenous estradiol level during intake of dienogest compared to that of unchanged group (p = 0.0146). Endogenous follicle-stimulating hormone level between osteopenic group and unchanged group did not reach statistically significant difference, although the osteopenic group showed relatively higher level. CONCLUSION: This study might suggest that decreased ovarian reserve as judged by endogenous estradiol level is a factor that negatively affect bone mineral density, and measurement of endogenous estradiol level during intake of dienogest could have a predictive meaning of future decreased bone mineral density level.

Peripartum type B aortic dissection in patients with Marfan syndrome who underwent aortic root replacement: a case series study.

OBJECTIVE: To investigate pregnancy outcomes, especially the risk of pregnancy-related aortic dissection (AD), in patients with Marfan syndrome (MFS) after prophylactic aortic root replacement (ARR). DESIGN: Retrospective case series study. SETTING: Tertiary perinatal care centre at a university hospital. POPULATION: Pregnant women fulfilling the revised Ghent nosology (2010) criteria for MFS who were managed at our institute. METHODS: The pregnancy outcomes of all patients with MFS managed at our institute between 1982 and September 2016 were reviewed retrospectively based on medical records. MAIN OUTCOME MEASURES: Obstetrical management and complication including the incidence of AD throughout the peripartum period. RESULTS: Among 22 patients (28 pregnancies) who had been managed as potential MFS or related disorders, 14 (17 pregnancies) fulfilled the revised Ghent nosology (2010) criteria for MFS and were enrolled in this study. Five patients (five pregnancies) had received ARR before conception: three (60%) developed type B aortic dissection [AD(B)] during the peripartum period, compared with only one of 10 patients (12 pregnancies) without ARR (P < 0.05, Chi-square test). CONCLUSIONS: Our study results suggest that MFS patients after prophylactic ARR are still at high risk of AD(B) during the peripartum period. Careful pre-pregnancy counselling and multidisciplinary care throughout the peripartum period are essential for the management of MFS, even after surgical repair of an ascending aortic aneurysm. TWEETABLE ABSTRACT: MFS patients after prophylactic ARR are still at high risk of type B aortic dissection during the peripartum period.

Bradykinin system is involved in endometriosis-related pain through endothelin-1 production.

BACKGROUND: Endometriosis is a gynaecological disease exhibiting severe pelvic pain, but the mechanism of pain production remains unknown. Bradykinin (BK) is known as an inflammatory mediator, and shows elevated levels in inflammatory diseases such as rheumatoid arthritis. In the present study, we evaluated whether BK is involved in endometriosis-related pain. METHODS: Endometriotic lesions were used for immunohistochemistry. Primary cultures of endometriotic stromal cells (ESC) were stimulated with IL-1ß and/or BK. Quantitative RT-PCR was used to evaluate the mRNA expressions of BK receptors (BKR) and endothelin-1 in ESC. The concentration of endothelin-1 in cystic fluid of endometrioma or non-endometrioma was measured with ELISA. The conditioned medium of ESC stimulated with IL-1ß and/or BK was injected intraplantarly in mice, and evaluated whether pain-related licking behaviour was elicited. RESULTS: The expressions of BK and BKR in endometriotic lesions were observed by immunohistochemistry. In vitro experiments showed that IL-1ß induced BKR-B1 and B2 on ESC. Activation of these receptors by BK significantly induced endothelin-1 expression in ESC, which was negated completely by HOE-140, a BKR-B2 antagonist. The cystic fluid of endometrioma contained higher amount of endothelin-1 compared to non-endometrioma. Intraplantar injection of the conditioned medium of ESC treated with IL-1ß and BK significantly induced licking behaviour, which was suppressed with BQ-123, an endothelin type-A receptor antagonist. CONCLUSIONS: The present study demonstrated the presence and the function of the BK axis in endometriosis, and established a potential new therapy target for endometriosis-related pain. SIGNIFICANCE: The present study demonstrated (1) the presence and the function of the BK system in endometriosis, (2) activation of BKR induced endothelin-1 in endometriotic lesion and (3) blocking endothelin-1 was effective to decrease pain.

Systematic approach to sonographic evaluation of the pelvis in women with suspected endometriosis, including terms, definitions and measurements: a consensus opinion from the International Deep Endometriosis Analysis (IDEA) group.

The IDEA (International Deep Endometriosis Analysis group) statement is a consensus opinion on terms, definitions and measurements that may be used to describe the sonographic features of the different phenotypes of endometriosis. Currently, it is difficult to compare results between published studies because authors use different terms when describing the same structures and anatomical locations. We hope that the terms and definitions suggested herein will be adopted in centers around the world. This would result in consistent use of nomenclature when describing the ultrasound location and extent of endometriosis. We believe that the standardization of terminology will allow meaningful comparisons between future studies in women with an ultrasound diagnosis of endometriosis and should facilitate multicenter research. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Viperin is induced following toll-like receptor 3 (TLR3) ligation and has a virus-responsive function in human trophoblast cells.

INTRODUCTION: Viperin, a virus-inducible antiviral protein, has been reported to inhibit the replication of a variety of viruses. However, its expression and function in trophoblast cells remains unclear. Toll-like receptor 3 (TLR3) is a key component of the innate immune system that recognizes viral double-stranded RNA and triggers immune reactions by producing type I interferon. We hypothesized that viperin inhibits the replication of human cytomegalovirus (HCMV) in trophoblast cells. METHODS: In situ examinations of viperin expression was conducted in the human first-trimester placenta by immunohistochemical staining. Using a human trophoblast cell culture system, we studied the effect of TLR-3 ligation on viperin expression by treating trophoblasts with polyinosinic-polycytidylic acid [Poly (I: C)] (a synthetic double-stranded RNA, which mimics viral RNA). Viperin mRNA and protein expression were evaluated by real-time PCR and Western blot analysis. In a HCMV infected Swan 71 cell model, HCMV immediate early 1 (IE1) protein mRNA expression was evaluated by real-time PCR after viperin RNA interference. RESULTS: Viperin was localized in trophoblast cells. Poly (I: C) induced viperin expression in a dosage and time-dependent manner. Blocking of TLR3 signaling by neutralizing antibody against IFN-ß abolished the stimulation of viperin expression. After HCMV infection, expression of viperin mRNA and protein was unregulated. HCMV IE1 mRNA expression was significantly inhibited by viperin RNA interference. DISCUSSION: Viperin is a virus-responsive protein that is constitutively expressed in human trophoblast cells. However, contrary to our hypothesis, viperin facilitates HCMV replication post infection.

Role of multifunctional transcription factor TFII-I and putative tumour suppressor DBC1 in cell cycle and DNA double strand damage repair.

BACKGROUND: In multicellular organisms, precise control of cell cycle and the maintenance of genomic stability are crucial to prevent chromosomal alterations. The accurate function of the DNA damage pathway is maintained by DNA repair mechanisms including homologous recombination (HR). Herein, we show that both TFII-I and DBC1 mediate cellular mechanisms of cell-cycle regulation and DNA double strand damage repair. METHODS: Regulation of cell cycle by TFII-I and DBC1 was investigated using Trypan blue dye exclusion test, luciferase assay, and flow cytometry analysis. We also analysed the role of TFII-I and DBC1 in DNA double strand damage repair after irradiation by immunofluorescence study, clonogenicity assay, and HR assay. RESULTS: Flow cytometry analysis revealed a novel function that siRNA-mediated knockdown of endogenous DBC1 resulted in G2/M phase arrest. We also have shown that both endogenous TFII-I and DBC1 activate DNA repair mechanisms after irradiation because irradiation-induced foci formation of TFII-I-γH2AX was observed, and the depletion of endogenous TFII-I or DBC1 resulted in the inhibition of normal HR efficiency. CONCLUSION: These results reveal novel mechanisms by which TFII-I and DBC1 can modulate cellular fate by affecting cell-cycle control as well as HR pathway.

Introducing HPV vaccine and scaling up screening procedures to prevent deaths from cervical cancer in Japan: a cost-effectiveness analysis.

OBJECTIVE: To assess the cost-effectiveness of universal vaccination of 11-year-old girls against human papillomavirus (HPV) infection and increased screening coverage to prevent cervical cancer in Japan where the coverage of Papanicolaou smears is very low. DESIGN: A cost-utility analysis from a societal perspective. SETTING: Japan, 2010. POPULATION: The female Japanese population aged 11 years or older. METHODS: A Markov model of the natural history of cervical cancer was constructed to compare six strategies: i.e. a screening coverage rate of 20, 50 and 80% with and without routine vaccination at age 11. MAIN OUTCOME MEASURES: Cervical cancer incidence, quality-adjusted life years (QALYs), costs and incremental cost-effectiveness ratios. RESULTS: Expanding the coverage of Papanicolaou smears from the current level of 20-50 and 80% yields a 45.5 and 63.1% reduction in cervical cancer incidence, respectively. Impact of combined strategies increases with coverage. Coverages of 20, 50 and 80% showed a 66.1, 80.9 and 86.8% reduction in disease, respectively. The costs of strategies with vaccination are four times higher than the cost of strategies without vaccination. Vaccinating all 11-year-old girls with bivalent vaccines with a Papanicolaou smear coverage rate of 50% is likely to be the most cost-effective option among the six strategies. CONCLUSIONS: The introduction of HPV vaccination in Japan is cost-effective as in other countries. It is more cost-effective to increase the coverage of the Papanicolaou smear along with the universal administration of HPV vaccine.

Decreased pregnancy rate is linked to abnormal uterine peristalsis caused by intramural fibroids.

BACKGROUND: The relationship between fibroids and infertility remains an unsolved question, and management of intramural fibroids is controversial. During the implantation phase, uterine peristalsis is dramatically reduced, which is thought to facilitate embryo implantation. Our aims were to evaluate (i) the occurrence and frequency of uterine peristalsis in infertile women with intramural fibroids and (ii) whether the presence of uterine peristalsis decreases the pregnancy rate. METHODS: Ninety-five infertile patients with uterine fibroids were examined using magnetic resonance imaging (MRI). Inclusion criteria were as follows: (i) presence of intramural fibroids, excluding submucosal type; (ii) no other significant infertility factors (excluding endometriosis); and (iii) regular menstrual cycles, and MRI performed at the time of implantation (luteal phase day 5-9). The frequency of junctional zone movement was evaluated using cine-mode-display MRI. After MRI, patients underwent infertility treatment for up to 4 months, and the pregnancy rate was evaluated prospectively. RESULTS: Fifty-one patients fulfilled the inclusion criteria, and 29 (57%) and 22 (43%) patients were assigned to the low (0 or 1 time/3 min) or high frequency (≥ 2 times/3 min) uterine peristalsis group, respectively. Endometriosis incidence was the same in both groups. Ten out of the 29 patients (34%) in the low-frequency group achieved pregnancy, compared with none of the 22 patients (0%) in the high-frequency group (P< 0.005). Comparing pregnant and non-pregnant cases, 4 of 10 patients (40%) and 9 of 41 patients (22%), respectively, had endometriosis (not significant). CONCLUSIONS: A higher frequency of uterine peristalsis during the mid-luteal phase might be one of the causes of infertility associated with intramural-type fibroids.

Post-operative oral contraceptive use reduces the risk of ovarian endometrioma recurrence after laparoscopic excision.

BACKGROUND: The aim of this study was to evaluate the impact of post-operative oral contraceptives (OCs) use on the rate of recurrence after laparoscopic excision of ovarian endometrioma. METHODS: In May 2005, we introduced a 'post-operative OC recommendation' for patients treated with laparoscopic excision of endometrioma. That is, at the time of the operation, we provided each patient with information about OC, known and possible benefits and risks and let her decide whether to take OC. A retrospective cohort study included 87 patients who underwent a laparoscopy after May 2005. The endometrioma recurrence rate at 24 months was compared between those who used OC for the entire follow-up period OC (n = 34) and all of the others (n = 53). We also performed logistic regression analysis to identify variables associated with recurrence. A before-after study included another 224 patients who underwent a laparoscopy before May 2005 and compared the recurrence rate before and after introduction of the 'post-operative OC recommendation'. RESULTS: The recurrence rate in those who used OC for the entire period was significantly lower than in the 'others' group (2.9 versus 35.8%, relative risk 0.082, 95% CI 0.012-0.58, P < 0.001). Post-operative OC was determined as an independent variable associated with lower recurrence (OR 0.054, 95% CI 0.007-0.429, P < 0.001). The overall recurrence rate in patients who underwent laparoscopy after the introduction of the 'post-operative OC recommendation' was significantly lower than that in patients who received laparoscopy before the introduction (18.6 versus 33.1%, relative risk 0.56, 95% CI 0.32-0.97, P < 0.05). CONCLUSIONS: Post-operative OC use reduces the risk of ovarian endometrioma recurrence after laparoscopic excision. This information will help in appropriate planning of pre- and post-operative management.

Recurrence of ovarian endometrioma after laparoscopic excision.

BACKGROUND: To analyse risk factors that influence the recurrence of endometrioma after laparoscopic excision. METHODS: A total of 224 patients who had a minimum of 2 years of post-operative follow-up after laparoscopic ovarian endometrioma excision were studied retrospectively. Recurrence was defined as the presence of endometrioma more than 2 cm in size, detected by ultrasonography within 2 years of surgery. Fourteen variables (age, presence of infertility, pain, uterine myoma, adenomyosis, previous medical treatment of endometriosis, previous surgery for ovarian endometriosis, single or multiple cysts, the size of the largest cyst at laparoscopy, unilateral or bilateral involvement, co-existence of deep endometriosis, revised American Society for Reproductive Medicine (ASRM) score, post-operative medical treatment and post-operative pregnancy) were evaluated to assess their independent effects on the recurrence using logistic regression analysis. RESULTS: The overall rate of recurrence was 30.4% (68/224). Significant factors that were independently associated with higher recurrence were previous medical treatment of endometriosis [odds ratio (OR) = 2.324, 95% confidence interval (95% CI) = 1.232-4.383, P = 0.0092) and larger diameter of the largest cyst (OR = 1.182, 95% CI = 1.004-1.391, P = 0.0442). Post-operative pregnancy was associated with lower recurrence (OR = 0.292, 95% CI = 0.028-0.317, P = 0.0181). CONCLUSIONS: Previous medical treatment of endometriosis or large cyst size was a significant factor that was associated with higher recurrence of the disease. Post-operative pregnancy is a favourable prognostic factor.

Usefulness of epidural anesthesia in gynecologic laparoscopic surgery for infertility in comparison to general anesthesia.

BACKGROUND: Although the advantages of epidural anesthesia in open surgery have been established, its usefulness in the setting of laparoscopic surgery remains to be studied. METHODS: Patients undergoing laparoscopic surgery for infertility were randomly administered epidural anesthesia (group A, n = 11) or general anesthesia (group B, n = 9). The operation was performed under 4 mmHg pneumoperitoneum and in the 20 degrees Trendelenburg position. Respiratory function tests using a spirometer and blood gas analysis were performed during the intra- or perioperative period. Pain status was evaluated with visual analog scale scoring. The number of postoperative recovery days needed to resume daily activities was obtained by a questionnaire. RESULTS: Respiratory rate, minute volume, P(a)CO2, % vital capacity (VC), and forced expiratory volume in 1 s (FEV1) % were virtually constant throughout the study period in group A, whereas %VC was decreased immediately after operation in group B (p < 0.05). Minute volume immediately after operation was significantly increased in group B compared with group A (p < 0.01), suggesting shallow respiration in women undergoing general anesthesia. Observed pain scores on abdominal pain, shoulder pain, and dyspnea were very low during operation in group A. Pain scores immediately and 3 h after operation were also minimal in group A, whereas abdominal pain scores at these points were significantly higher in group B than those in group A (both p < 0.01). The number of days required for a half reduction in wound pain, trotting, and full recuperation for group A were less than those for group B (p < 0.05). CONCLUSIONS: Epidural anesthesia, when used in laparoscopic surgery for infertility treatment, has advantages over general anesthesia in terms of analgesic effects, postoperative respiratory function, and a return to preoperative daily activities.

A primary cell culture system for human cytotrophoblasts of proximal cytotrophoblast cell columns enabling in vitro acquisition of the extra-villous phenotype.

Cytotrophoblast (CT) differentiation into the extra-villous phenotype is a crucial process in initiating their invasion into the decidua and thereby developing the placenta. However, how CTs differentiate into extra-villous CTs (EVCTs) is not fully elucidated. To address this, a suitable culture model for CTs has been long-sought. But this has been hampered by annoying problems such as; cell aggregation, in vitro syncytialization, low plating efficiency, etc. The aim of this study is to develop a culture system in which CTs differentiate into EVCTs. CTs were isolated from the first trimester placenta using density gradient separation and immuno-depletion using anti-CD9 antibody to remove contaminating fibroblasts and EVCTs. The resultant isolated CTs were found to have the character similar to poorly differentiated CTs comprising proximal cytotrophoblastic cell columns as confirmed by immunocytochemical and flowcytometric analyses. When cultured on type 4 collagen-coated plates in culture media containing low calcium concentration, CTs neither aggregated nor syncytialized, remaining mononuclear and monolayer state. Interestingly, cultured CTs gradually upregulated integrin alpha1, CD9, and human leukocyte antigen (HLA)-G; the known markers specific for EVCTs invading into the decidua diffusely. Hence, the CT culture system provides a sophisticated experimental model in which highly purified CTs acquire the extra-villous phenotype without syncytialization.

Effects of gonadotropin-releasing hormone analog treatment on skin condition.

The skin is a target organ of estrogens. Thus, theoretically, a hypoestrogenic state induced by gonadotropin-releasing hormone analog (GnRHa) treatment may have effects on skin condition. The aim of this study was to evaluate skin condition during GnRHa treatment. Sixteen premenopausal women undergoing GnRHa treatment for 16 weeks, as a presurgical treatment for uterine leiomyomas, were studied. Measurement of serum estradiol levels and epidermal hydration, and evaluation of subjective findings on skin condition using a questionnaire, were performed every 4 weeks during the treatment period. Serum estradiol levels were significantly suppressed at 4 weeks of treatment, and remained low afterwards. Epidermal hydration measured by corneometer did not show any significant difference at any time point examined, compared with that before treatment. No particular subjective findings relating to the skin (dryness, wrinkling, roughness, pigmentation, itching, formication, reaction to cosmetics) were reported during treatment, whereas complaints about hot flushes and sweating were notable. The results of this preliminary study support the notion that GnRHa treatment for 16 weeks is unassociated with apparent changes in skin condition.

Demonstration of angiogenin in human endometrium and its enhanced expression in endometrial tissues in the secretory phase and the decidua.

Angiogenesis is thought to be crucial for normal physiology of the endometrium, where dynamic vascular remodeling occurs during the menstrual cycle and pregnancy. We investigated the presence of angiogenin, a potent inducer of angiogenesis, and the regulatory mechanisms of its production in the human endometrium. Western blot analysis demonstrated that angiogenin protein expression increased by 3- to 4-fold in the endometrium in the mid and late secretory phases and in early gestation relative to that during the proliferative phase. Quantitative mRNA analysis showed the similar tendency in the expression of angiogenin mRNA in the endometrium, with the highest levels observed in the mid and late secretory phases and early gestation. An immunohistochemical study showed that angiogenin was expressed in both stromal cells and epithelial cells, with indistinguishable intensity between these cells regardless of phases of the menstrual cycle. In support of the Western blot analysis, the intensity of staining appeared to be highest in the mid to late secretory phases relative to other phases. Consistent with these in vivo results, decidualized cultured stromal cells, after treatment with progesterone or progesterone plus E2, exhibited the capacity to secrete significantly increased amounts of angiogenin compared with untreated or E2 alone-treated control group. Both the treatment with (Bu)2cAMP and hypoxic conditions stimulated angiogenin secretion by stromal cells. For isolated epithelial cells, hypoxia stimulated angiogenin secretion, whereas (Bu)2cAMP had no appreciable effect. In summary, we demonstrated the presence of angiogenin in human endometrium and its possible local regulatory factors, such as progesterone, cAMP, and hypoxia. These findings along with its enhanced expression in the endometrium in the secretory phase and in decidual tissues raise the possibility that angiogenin may play a role in establishing pregnancy.

Successful laparoscopic treatment of ileo-cecal endometriosis producing bowel obstruction.

Bowel endometriosis manifesting with ileus is difficult to diagnose, often requiring laparotomy for diagnosis and treatment. We report here a case of ileo-cecal endometriosis causing bowel obstruction. A diagnosis of intestinal endometriosis with menstruation-associated bowel symptoms was made, and the patient was successfully treated by laparoscopic ileo-cecal resection.

Usefulness of long-jaw forceps in laparoscopic cornual resection of interstitial pregnancies.

Although laparoscopic surgery could be an option for treating interstitial pregnancies, it has not gained wide acceptance largely because of difficulty achieving hemostasis. To overcome this, we employed long-jaw forceps in three cases of interstitial pregnancy that were successfully treated by laparoscopic cornual resection. The forceps grasped a relatively large portion of pregnant myometrium without slipping, thus securing hemostasis and facilitating suturing.

Successful emergency endometrial ablation for intractable uterine bleeding in a postmenopausal woman complicated with liver cirrhosis and morbid obesity.

Life-threatening intractable uterine bleeding is difficult to treat when concurrent medical complications contraindicate invasive surgery. We present a case of heavy uterine bleeding in a postmenopausal woman that was complicated by liver cirrhosis and morbid obesity. The bleeding was successfully halted through emergency endometrial ablation after failure of uterine artery embolization.

Evidence for the presence of keratinocyte growth factor (KGF) in human ovarian follicles.

The presence of keratinocyte growth factor (KGF) in human follicular fluid (FF) was investigated in a total of 145 FFs obtained during oocyte retrieval for in vitro fertilization (IVF) from 29 patients with no apparent endocrine disorders. The concentrations of KGF, estradiol, progesterone, testosterone and human chorionic gonadotropin (hCG) in FF were measured by enzyme-linked immunosorbent assay. FF samples contained relatively higher amounts of KGF (2194+/-87 pg/ml), whereas its concentrations in serum were below assay limit (<31.2 pg/ml). Concentrations of KGF in FF were positively correlated with both progesterone (r=0.311, p<0.0005) and testosterone (r=0.230, p<0.01) concentrations in FF. However, KGF concentrations were not significantly correlated with estradiol and hCG concentrations. KGF in FF was detected as a broad band (26-29 kD) by immunoblotting, the size being reduced by 7kD after N-glycosidase treatment. In an in vitro experiment, KGF suppressed the basal and hCG-stimulated progesterone production by cultured human luteinized granulosa cells. summary, we demonstrated the presence of KGF in human ovarian follicles, suggesting its possible role as a local factor in regulating human ovarian functions.

Evidence for the expression of interleukin (IL)-18, IL-18 receptor and IL-18 binding protein in the human endometrium.

To see whether the interleukin (IL)-18 system is operative in the endometrium, we examined the expression of IL-18, IL-18 receptor (IL-18R) and IL-18 binding protein (IL-18BP), the substance known to neutralize IL-18 activity, in this tissue. Reverse transcription-polymerase chain reaction analyses showed that IL-18, IL-18R and IL-18BP mRNA were constitutively expressed without significant fluctuation throughout the menstrual cycle. When epithelial cells and stromal cells were cultured separately, the expression levels of IL-18 mRNA in epithelial cells were about 18-fold higher compared to those in stromal cells. Furthermore, the IL-18 precursor protein was detected by Western blot analysis in cultured epithelial cells but not in stromal cells. Recombinant human IL-18 stimulated the secretion of interferon (IFN)-gamma by resident bone marrow-derived cells in the endometrium. On the other hand, IFN-gamma up-regulated the IL-18BP expression both in cultured epithelial cells and stromal cells. Thus, we have presented evidence for the presence of the IL-18 system in the human endometrium. In light of its immunomodulatory roles in a variety of tissues, this system may afford protection against pathogenic micro-organisms and provide a regulatory mechanism for controlled trophoblast invasion by modulating a local cytokine network.