Galectin-10 Expression in Placentas of Women with Gestational Diabetes.

Galectins are known to play an important role in immunoregulatory processes and autoimmune diseases. Galectin-10 is a cytoplasmic protein of human eosinophils and is involved in various eosinophilic diseases. Since increased galectin expression is already detected in the placentas of mothers with gestational diabetes mellitus (GDM), this study focuses on the specific role of galectin-10 and hints at consequences for the diagnosis and therapeutic options of GDM. It is hypothesized that the difference in galectin-10 expression will raise the pathophysiological understanding of gestational diabetes. The study population consists of 80 women: 40 healthy mothers and 40 women suffering from gestational diabetes mellitus. The expression of galectin-10 was analyzed in the syncytiotrophoblast (SCT) and the decidua of the placenta via immunohistochemistry and immunofluorescence double staining. The immunoreactivity score (IRS) was used for evaluation. The results in this study were significant for an overexpression of galectin-10 in GDM placentas compared with the control group. The syncytiotrophoblast showed overexpression in the nucleus and the cytoplasm, whereas expression of galectin-10 in the decidua was significant in the cytoplasm only. This study identified the expression changes in galectin-10 in placental tissue between healthy and GDM mothers and intensified the understanding of gestational diabetes. Assuming that gestational diabetes mellitus is involved in inflammatory processes, galectin-10 might play a role in the development and maintenance of GDM. Further investigation is required to strengthen these findings.

Lower HLA-G levels in extravillous trophoblasts of human term placenta in gestational diabetes mellitus than in normal controls.

The non-classical human leucocyte antigen (HLA) class I molecule HLA-G is widely known to play a major role in feto-maternal tolerance. We tested the hypothesis that HLA-G expression is altered in placentas of women with gestational diabetes mellitus (GDM) in a specific pattern that depends on fetal sex. HLA-G expression was analysed in a total of 80 placentas (40 placentas from women with GDM and 40 healthy controls) by immunohistochemistry using the semi-quantitative immunoreactive score (IRS). Double immunofluorescence staining identified the cells expressing HLA-G in the decidua and allowed evaluation of the expression pattern. We found a significant (p < 0.001) reduction of HLA-G expression in extravillous cytotrophoblasts (EVTs) in the placentas of women with GDM as compared to the healthy controls and were able to demonstrate that this downregulation was not due to a loss of cell number, but to a loss of expression intensity. A special change in the cell pattern of EVTs was observed, with these cells showing an obvious decrease in HLA-G expression on their cell surface. No significant differences according to fetal sex were found. These data show a possible association between decreased HLA-G expression and presence of GDM and provide new insights into altered placental function in women with GDM.

The work and training situation for young physicians undergoing specialty training in gynecology and obstetrics in Germany: an assessment of the status quo.

PURPOSE: General conditions in the health-care system in Germany have changed dramatically in recent years. Factors affecting this include above all demographic change, rapid developments in diagnostic and therapeutic options, and the application of economic criteria to the health-care sector. This study aimed to establish the current status quo regarding conditions of work and training for young doctors in gynecology and obstetrics, analyze stress factors, and suggest potential improvements. METHODS: Between October 2015 and March 2016, a web-based survey was carried out among residents and members of the German Society for Gynecology and Obstetrics. The electronic questionnaire comprised 65 items on seven topics. Part of the survey included the short version of a validated model of professional gratification crises for analyzing psychosocial work-related stress. RESULTS: The analysis included a total of 391 complete datasets. Considerable negative findings in relation to psychosocial work pressure, time and organizational factors, quality of specialty training, and compatibility between work and family life and work and academic tasks were detected. A high level of psychosocial work pressure is associated with more frequent job changes, reduced working hours, poorer health among physicians, and a lower subjectively assessed quality of care. CONCLUSIONS: Greater efforts are needed from all the participants involved in patient care to achieve high-quality training and working conditions that allow physicians to work in a healthy and effective way. These aspects are all prerequisites for sustainably maximizing the resource "physician" and for ensuring high-quality patient care.

Cell Type- and Sex-Specific Dysregulation of Thyroid Hormone Receptors in Placentas in Gestational Diabetes Mellitus.

Thyroid hormones are essential for development of trophoblasts and the fetus. They also regulate a wide range of metabolic processes. We investigated the influence of maternal gestational diabetes mellitus (GDM) on thyroid hormone receptor (THR) isoforms THRα1, THRα2, THRß1 and THRß2 of the human placenta in a sex- and cell-type specific manner. Term placental tissue was obtained from women with (n = 40) or without GDM (control; n = 40). THRs levels were measured by semi-quantitative immunohistochemistry and real-time qRT-PCR. We localized THR immunostaining in syncytiotrophoblast (SCT), which was the tissue with the strongest signal. Double immunofluorescence identified THR in decidual cells in the stroma and in extravillous cytotrophoblasts. GDM did not change THRα1 immunolabelling intensity in decidua, but was associated with a stronger immunolabelling in SCT compared to GDM (p < 0.05). The SCT difference of GDM vs. control was strongest (p < 0.01) in female placentas. THRα2 was only weakly present and immunolabelling was weaker (p < 0.05) in SCT of only male GDM placentas in comparison to male controls. THRß1/ß2 immunostaining was weak in all cell types without changes in GDM. However, more THRß1/2 protein was present (p < 0.001) in male than female placentas. All these protein changes were paralleled by changes of THR transcript levels. The data show that THR are expressed in term trophoblast in relation to fetal sex. Maternal GDM influences predominantly THRα1 in SCT, with the strongest GDM effect in SCT of female placentas.

Placental Galectin-2 Expression in Gestational Diabetes: A Systematic, Histological Analysis.

Gestational diabetes mellitus (GDM) is the most common pregnancy-associated metabolic disorder that negatively impacts on the health of both mothers and their offspring in the long-term. The molecular mechanisms involved are not fully understood. As in other states of insulin resistance, a disproportionate immune response in GDM leads to a state of chronic low-grade inflammation. Galectin-2 exerts regulatory effects on different immune cells. This study investigated galectin-2 expression in the placenta of 40 GDM patients and 40 controls, in a sex-specific manner. Immunohistochemistry was used for semi-quantitative analysis of expression strength. The phenotypes of galectin-2 expressing cells were characterized through double immunofluorescence. We found a significant up-regulation of galectin-2 in the fetal syncytiotrophoblast, as well as in the maternal decidua of GDM placentas. Double staining showed a strong galectin-2 expression in extra villous trophoblast cells and fetal endothelial cells in GDM. These findings present the first systematic investigation of galectin-2 in GDM. The findings contribute to the emerging understanding of the role of immunomodulation and inflammation in GDM and of galectin-2 itself. This might also have implications for the long-term cardiovascular health of the offspring.

LDOC1 as Negative Prognostic Marker for Vulvar Cancer Patients.

So far, studies about targeted therapies and predictive biomarkers for vulva carcinomas are rare. The leucine zipper downregulated in cancer 1 gene (LDOC1) has been identified in various carcinomas as a tumor-relevant protein influencing patients' survival and prognosis. Due to the lack of information about LDOC1 and its exact functionality, this study focuses on the expression of LDOC1 in vulvar carcinoma cells and its surrounding immune cells as well as its correlation to clinicopathological characteristics and prognosis. Additionally, a possible regulation of LDOC1 in vulvar cancer cell lines via the NF-κB signaling pathway was analyzed. Vulvar carcinoma sections of 157 patients were immunohistochemically stained and examined regarding LDOC1 expression by using the immunoreactive score (IRS). To characterize LDOC1-positively stained immune cell subpopulations, immunofluorescence double staining was performed. The effect of the NF-κB inhibitor C-DIM 12 (3,3'-[(4-chlorophenyl)methylene]bis[1 H-indole]) on vulvar cancer cell lines A431 and SW 954 was measured according to MTT and BrdU assays. Baseline expression levels of LDOC1 in the vulvar cancer cell lines A431 and SW 954 was analyzed by real-time PCR. LDOC1 was expressed by about 90% of the cancer cells in the cytoplasm and about half of the cells in the nucleus. Cytoplasmatic expression of LDOC1 was associated with decreased ten-year overall survival of the patient, whereas nuclear staining showed a negative association with disease-free survival. Infiltrating immune cells were mainly macrophages followed by regulatory T cells. Incubation with C-DIM 12 decreased the cell viability and proliferation of vulvar cancer cell line A431, but not of cell line SW 954. LDOC1 expression on mRNA level was twice as high in the cell line A431 compared to the cell line SW 954. Overexpression of LDOC1 was associated with unfavorable overall and disease-free survival. Tumor growth could be inhibited by C-DIM 12 in vitro if the expressed LDOC1 level was high enough.

Sex Specific Expression of Interleukin 7, 8 and 15 in Placentas of Women with Gestational Diabetes.

Gestational diabetes mellitus (GDM) is known to increase the risk for feto-maternal complications during pregnancy. A state of low-grade inflammation, with elevated levels of proinflammatory molecules, similar to patients with obesity or diabetes mellitus type 2 has also been partly described in GDM. The placenta, as unique interface between mother and fetus, is not only passively affected by changes in one of these organisms, but also acts as a modulator by expressing hormones and cytokines. This study aimed to investigate the expression of the proinflammatory cytokines Interleukin (IL) 7, 8 and 15 in GDM in placental tissue. A total number of 80 placentas were included (40 GDM/40 control group). The expression of IL-7, 8 and 15 was investigated in extravillous trophoblast (EVT) and syncytiotrophoblast (SCT) by immunohistochemistry and immunofluorescence double staining. The immunohistochemical staining was evaluated with the semiquanitfied immunoreactive score (IRS). While the expression IL-15 was significantly upregulated in EVTs of women with GDM. The expression of IL-8 was significantly decreased in EVT of the GDM group. Furthermore, significant fetal sex specific differences were detectable in all three cytokines. Our findings suggest an involvement of the investigated cytokines in the maintenance of a state of chronic low-grade inflammation on placental level in patients suffering from GDM.

Validation of a new algorithm for the short-term variation of the fetal heart rate: an antepartum prospective study.

AIMS: Currently one of the most widespread systems for the computerized analysis of the fetal heart rate (FHR) is the Dawes-Redman system, where the short-term variation (STV) of the FHR is measured by dividing each minute into 16 segments (STV16). Technical progress has allowed for the development of a new algorithm, which measures the STV by dividing each minute into 240 segments (STV240), thus approximating the beat-to-beat variation. The STV240 still lacks reference values. Our aim was to develop clinically relevant reference values for the STV240 and compare them to the ones for the STV16. METHODS: In a single centre, observational study, a total of 228 cardiotocograms were registered and subsequently analyzed with both algorithms (STV240 and STV16). RESULTS: The 95% confidence interval (CI) was calculated for both algorithms. The values of the STV240 were significantly lower in comparison to the ones of the STV16. Not only the mean values but also the 95th percentile of the STV240 lay beneath the existent cut-off value for the STV16. CONCLUSIONS: Every clinician using the new algorithm must be aware that the normal values for the STV240 lie beneath the, up until now, established cut-off values for the STV16.

Biologic meshes and synthetic meshes in cancer patients: a double-edged sword: differences in production of IL-6 and IL-12 caused by acellular dermal matrices in human immune cells.

PURPOSE: In 2005, Breuing et al. first described the use of acellular dermal matrices (ADMs) in breast cancer patients. ADMs are assumed to be safe to use in an oncologic setting, but data from controlled studies are still needed. Here, we investigate the effects of ADMs on the production of interleukin (IL)-6 and IL-12, key regulators of immune suppression and activation. METHODS: Strattice (ST), CollaMend (CM), and Biodesign (BD) biologic meshes and TiLoop, a synthetic mesh (TL), were used in this study. We isolated myeloid dendritic cells (MDCs), untouched plasmacytoid dendritic cells (pDCs), naïve B cells, and CD8+ T cells and co-cultured these cells with either the biologic meshes or TL. As positive controls, we used CpG ODN 2216 or lipopolysaccharide (LPS). The cytokine concentrations of IL-12p70 and IL-6 were determined after 7 days using sandwich ELISA sets. RESULTS: There were highly significant differences between the ADMs and TL in terms of their ability to stimulate immunologic responses. IL-6 expression was significantly increased in B cells (p = 0.0006131) and T cells (p = 0.00418) when comparing TL and ADMs. We also identified significant differences in IL-12 production by B cells (p = 0.0166) and T cells (p = 0.003636) when comparing TL and ADMs. CONCLUSIONS: Despite the assumed lack of an immunological response to ADMs, in our experimental study, human immune cells reacted with significantly different cytokine profiles. These findings may have implications for the potential activation or suppression of effector cells in cancer patients and could explain some of the post clinical post surgical signs of ADMS like skin rush and seroma.

Histone H3 lysine 9 acetylation is downregulated in GDM Placentas and Calcitriol supplementation enhanced this effect.

Despite the ever-rising incidence of Gestational Diabetes Mellitus (GDM) and its implications for long-term health of mothers and offspring, the underlying molecular mechanisms remain to be elucidated. To contribute to this, the present study's objectives are to conduct a sex-specific analysis of active histone modifications in placentas affected by GDM and to investigate the effect of calcitriol on trophoblast cell's transcriptional status. The expression of Histone H3 lysine 9 acetylation (H3K9ac) and Histone H3 lysine 4 trimethylation (H3K4me3) was evaluated in 40 control and 40 GDM (20 male and 20 female each) placentas using immunohistochemistry and immunofluorescence. The choriocarcinoma cell line BeWo and primary human villous trophoblast cells were treated with calcitriol (48 h). Thereafter, western blots were used to quantify concentrations of H3K9ac and the transcription factor FOXO1. H3K9ac expression was downregulated in GDM placentas, while H3K4me3 expression was not significantly different. Cell culture experiments showed a slight downregulation of H3K9ac after calcitriol stimulation at the highest concentration. FOXO1 expression showed a dose-dependent increase. Our data supports previous research suggesting that epigenetic dysregulations play a key role in gestational diabetes mellitus. Insufficient transcriptional activity may be part of its pathophysiology and this cannot be rescued by calcitriol.

Cardiotocography and the evolution into computerised cardiotocography in the management of intrauterine growth restriction.

Timely recognition and appropriate management of high-risk pregnancies, such as intrauterine growth restriction (IUGR), are of paramount importance for every obstetrician. After the initial screening of IUGR fetuses through sonographic fetometry and Doppler, the focus is shifted to the appropriate monitoring and timing of delivery. This can, especially in cases of early IUGR, become a very difficult task. At this point, cardiotocography (CTG) is introduced as a major tool in the day-to-day monitoring of the antenatal well-being of the IUGR fetus. Since the first introduction of CTG up to the nowadays widely spreading implementation of computerised CTG in the clinical practice, there has been great progress in the recording of the fetal heart rate, as well as its interpretation. Focus of this review is to offer an understanding of the evolution of CTG from its early development to modern computerised methods and to provide an insight as to where the future of CTG is leading, especially in the monitoring of IUGR.

Part-time employment of gynecologists and obstetricians: a sub-group analysis of a Germany-wide survey of residents.

BACKGROUND: Combining family and career is increasingly taken for granted in many fields. However, the medical profession in Germany has inadequately developed structures. Little is known regarding the satisfaction of physicians working part-time (PT). METHODS: This Germany-wide on-line survey collected information on the working situation of PT employees (PTE) in gynecology. An anonymous questionnaire with 95 items, nine of which concerned PT work, was sent to 2770 residents and physicians undergoing further specialist training. RESULTS: Of the 481 participants, 104 (96 % female, 4 % male) stated they worked PT, which is greater than the national average. 94 % of all women and 60 % of all men would work PT for better compatibility between work and family life. The PTE regularly work night shifts (NS) (96 %) and weekends (98 %). The number of monthly NS (median 5-9) was not different between the full-time (FT) employees and the PTE who work >75 %. Only when the working hours are reduced by 25 % or more, there are fewer NS (median 1-4) PTE that have a desire for fewer NS. The classic PT model is seldom realized; over 70 % of PTE work whole days, while other working models do not play a major role in Germany. On-call models were subjectively declared to have the best family friendly work-life balance. OUTLOOK: The results obtained indicated that structures must be developed that to address the problem of childcare and the long working hours to ensure comprehensive medical care from specialists.

Role of Placental VDR Expression and Function in Common Late Pregnancy Disorders.

Vitamin D, besides its classical role in bone metabolism, plays a distinct role in multiple pathways of the feto-maternal unit. Calcitriol is the major active ligand of the nuclear vitamin D receptor (VDR). The vitamin D receptor (VDR) is expressed in different uteroplacental parts and exerts a variety of functions in physiologic pregnancy. It regulates decidualisation and implantation, influences hormone secretion and placental immune modulations. This review highlights the role of the vitamin D receptor in physiologic and disturbed pregnancy, as preeclampsia, fetal growth restriction, gestational diabetes and preterm birth. We discuss the existing literature regarding common VDR polymorphisms in these pregnancy disorders.

Placental Expression Patterns of Galectin-1, Galectin-2, Galectin-3 and Galectin-13 in Cases of Intrauterine Growth Restriction (IUGR).

Galectins (gal) are members of the mammalian ß-galactoside-binding proteins and recognize Galß1-4GlcNAc and Galß1-4GalNac (Thomsen-Friedenreich antigen (TF)) sequences of several cell surface oligosaccharides. In this study, gal-1, -2, -3 and -13 were investigated systematically in the trophoblast and decidua compartment of intrauterine growth restriction (IUGR) placentas and normal third trimester control placentas and stratified by fetal gender and gestational age. Within this study, 29 third trimester placentas after delivery were analyzed. Fetal gender was equally divided within both groups, and immunohistochemical staining was analyzed according to fetal gender and gestational age. Double immune-fluorescence with trophoblast-specific markers was used to identify galectin-expressing cells at the feto-maternal interface in the decidua. Gal-3 was significantly downregulated only in the extravillous trophoblast of IUGR placentas. In contrast, expressions of gal-2 and gal-13 were downregulated in both villous and extravillous trophoblast cells of IUGR placentas. In addition, gal-2 and gal-13 showed a highly correlated expression scheme in the placenta. There are significant gender-specific expression patterns for single prototype galectins with downregulation of gal-2 and gal-13 of male gender placentas in cases of IUGR. Gal-3 as the chimera type galectin shows only little gender-specific differences in expression, which disappear in IUGR cases.

Cervical conisation and the risk of preterm delivery: a retrospective matched pair analysis of a German cohort.

PURPOSE: Since the routine screening program for cervical dysplasia by Pap smear was established in the early 1970s, the rate of cervical cancer has continually dropped. Even if a high percentage of cervical dysplasia shows spontaneous restitution, the only effective therapy for persisting cervical dysplasia is local ablation or excision which might be associated with an increased risk of preterm delivery in subsequent pregnancies. However, data from German patients are missing, so the aim of this study was to evaluate the risk of preterm delivery and associated risks in a cohort of patients who had undergone cervical conisation previous to their pregnancies. METHODS: A total of 144 patients with conisation and subsequent pregnancy were identified. They were compared regarding week of delivery and preterm birth, fetal birth weight, fetal outcome and birth procedure (spontaneous delivery, vacuum extraction, primary and secondary cesarean section) with their matched partners. RESULTS: 135 patients with singleton pregnancies and their matched partners were evaluated in the final analysis. The mean age was 33.5 years. Comparing the case and control group we reached significant different results for week of delivery, but not preterm birth defined as birth prior to 37 weeks of gestation. CONCLUSIONS: Within this German cohort cervical conisation did not increase the risk for preterm birth, cesarean section or poor fetal outcome. We therefore conclude that cervical conisation is an appropriate method to treat women with cervical dysplasia also at childbearing age when prevention of cervical cancer is needed.

Getting too sweet: galectin-1 dysregulation in gestational diabetes mellitus.

Galectin-1 (gal-1) is a prototype carbohydrate-binding protein, whose dysregulation is associated with adverse pregnancy outcomes such as spontaneous abortion and pre-eclampsia. Furthermore, it is known that faulty gal-1 protein production or gene regulation can be caused by single-nucleotide polymorphisms in the LGALS1 gene. Gestational diabetes mellitus (GDM) is also an adverse pregnancy outcome and the most common metabolic disorder during gestation. However, gal-1 expression patterns during GDM remain largely unknown. Our aims were to define local and peripheral gal-1 expression patterns during pregnancy, and to investigate LGALS1 gene polymorphisms in GDM patients. Circulating gal-1 levels were determined by ELISA in GDM patients and normal pregnant controls, and LGALS1 gene polymorphisms were assessed for association with GDM. Placental tissues were collected from control and GDM term pregnancies to evaluate local gal-1 expression by immunofluorescence. Our results show that GDM is associated with a failure to increase circulating gal-1 levels during the second and third trimester, as well as overexpression of gal-1 in placental tissue. Additionally, the LGALS1 polymorphism rs4820294 was associated with the development of GDM. In pregnancies complicated by GDM, we observed gal-1 dysregulation both locally in the placenta and peripherally in the circulation. Furthermore, the association between the LGALS1 polymorphism and GDM may indicate a genetic contribution to this adverse pregnancy outcome.

Reversal of pathological pain through specific spinal GABAA receptor subtypes.

Inflammatory diseases and neuropathic insults are frequently accompanied by severe and debilitating pain, which can become chronic and often unresponsive to conventional analgesic treatment. A loss of synaptic inhibition in the spinal dorsal horn is considered to contribute significantly to this pain pathology. Facilitation of spinal gamma-aminobutyric acid (GABA)ergic neurotransmission through modulation of GABA(A) receptors should be able to compensate for this loss. With the use of GABA(A)-receptor point-mutated knock-in mice in which specific GABA(A) receptor subtypes have been selectively rendered insensitive to benzodiazepine-site ligands, we show here that pronounced analgesia can be achieved by specifically targeting spinal GABA(A) receptors containing the alpha2 and/or alpha3 subunits. We show that their selective activation by the non-sedative ('alpha1-sparing') benzodiazepine-site ligand L-838,417 (ref. 13) is highly effective against inflammatory and neuropathic pain yet devoid of unwanted sedation, motor impairment and tolerance development. L-838,417 not only diminished the nociceptive input to the brain but also reduced the activity of brain areas related to the associative-emotional components of pain, as shown by functional magnetic resonance imaging in rats. These results provide a rational basis for the development of subtype-selective GABAergic drugs for the treatment of chronic pain, which is often refractory to classical analgesics.

Peroxisome proliferator-activated receptor-gamma (PPARγ) is down regulated in trophoblast cells of gestational diabetes mellitus (GDM) and in trophoblast tumour cells BeWo in vitro after stimulation with PPARγ agonists.

AIMS: Peroxisome proliferator-activated receptor-gamma (PPARγ) plays an important role in insulin metabolism, trophoblast differentiation and anti-inflammatory circuits. The aim of this study was to investigate the expression of PPARγ in the placenta of patients with gestational diabetes mellitus (GDM) and the regulation of PPARγ by its agonists in trophoblast tumour cells BeWo in vitro. METHODS: PPARγ expression in a total of 80 placentas (40 GDM/40 controls) was analysed by immunohistochemistry using the semi-quantitative immunoreactive score. Furthermore, a quantitative reverse transcription-polymerase chain reaction (PCR) was performed to determine the PPARγ mRNA-expression in both groups. We used a fused and a non-fused BeWo cell culture model for the stimulation with arachidonic acid and 15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2). Afterwards PPARγ mRNA-expression was analysed by quantitative real-time PCR (RT-PCR) (TaqMan). RESULTS: Using immunohistochemistry we identified a decreased expression of PPARγ in the syncytiotrophoblast and the extravillous trophoblast of GDM placentas compared to normal controls. Furthermore, PPARγ mRNA-expression was reduced in GDM placentas. Stimulation of BeWo cells with arachidonic acid and 15d-PGJ2 caused a downregulation of PPARγ expression. CONCLUSION: As PPARγ is down regulated by arachidonic acid and 15d-PGJ2, the reduced PPARγ expression in GDM placentas may be due to an altered concentration of fatty acid derivates.

Association of oestrogen-containing contraceptives with pulmonary lymphangioleiomyomatosis in women with tuberous sclerosis complex--findings from a survey.

OBJECTIVES About 30-40% of women with tuberous sclerosis complex (TSC) develop pulmonary lymphangioleiomyomatosis (LAM). Oestrogen seems to be involved in LAM pathogenesis and oestrogen-containing contraception should be avoided in women with known LAM. However, there is very little data on the use of contraceptives in TSC patients. METHODS We conducted a survey on the use of contraception and disease characteristics. The questionnaire was forwarded to all adult female TSC patients listed in the database of a German patient organisation. RESULTS Data from 39 such patients could be analysed. Of these, 15 were diagnosed with LAM. Twenty-five patients (65%) confirmed current or past use of oestrogen-containing contraceptives. We found a suggestive correlation between the history of oestrogen-containing contraception, and LAM (Odds ratio: 6.500; 95% confidence interval: 1.199-35.230). However, oestrogen use was not associated with LAM complications. CONCLUSIONS Based on our findings, oestrogen-containing contraceptives should be resorted to by these patients only with great caution, and avoided whenever possible.