Seminal plasma (SP) induces a rapid transforming growth factor beta 1 (TGFß1)-independent up-regulation of epithelial-mesenchymal transdifferentiation (EMT) and myofibroblastic metaplasia-markers in endometriotic (EM) and endometrial cells.

PURPOSE: To study if short-term exposure (2 h and 6 h) of endometrial/endometriotic tissues and cells to 10% seminal plasma (SP) can induce EMT/metaplasia. METHODS: Basic research experimental study was carried out in a University hospital-based fertility center. Semen samples, peritoneal fluid (PF) from endometriosis patients, endometrial biopsy from premenopausal women, immortalized endometriotic epithelial cell line (12Z), and immortalized endometrial stromal cell line (St-T1b) were studied. Rapid stain identification test (RSID), TGFß1 immunofluorescence of washed sperms, TGFß1-ELISA of SP and PF, in vitro study (2 h and 6 h incubation) and real-time PCR of endometrial tissue and cell lines to analyze gene expression of EMT/metaplasia markers and mediators were done. RESULTS: SP is still detectable in washed semen. TGFß1 was expressed on the plasma membrane of the sperms and was significantly more concentrated in SP (88.17 ng/ml) than PF. 10% SP induced an up-regulation of alpha smooth muscle actin expression in endometrial tissue (p = 0.008) and in 12Z cells (p = 0.05), mostly TGFß1-independent. TWIST expression was persistently significantly down-regulated while Snail1 and 2 were up-regulated, though insignificant. CONCLUSION: Our results provide novel evidence to support that even in semen washed twice, SP is still detectable. The changes in EMT/metaplasia markers and mediators give a new insight into a possible effect of SP on the pathogenesis of endometriosis.

Practical recommendations for fertility preservation in women by the FertiPROTEKT network. Part I: Indications for fertility preservation.

PURPOSE: Most guidelines about fertility preservation are predominantly focused on scientific evidence, but are less practically orientated. Therefore, practically oriented recommendations are needed to support the clinician in daily practice. METHODS: A selective literature search was performed based on the clinical and scientific experience of the authors, focussing on the most relevant diseases and gynaecological cancers. This article (Part I) provides information on topics that are essential for the fertility preservation indication, such as disease prognosis, disease therapy and its associated risks to fertility, recommending disease-specific fertility preservation measures. Part II specifically focusses on fertility preservation techniques. RESULTS: In breast cancer patients, fertility preservation such as ovarian tissue and oocyte cryopreservation is especially recommended in low-stage cancer and in women < 35 years of age. In Hodgkin's lymphoma, the indication is mainly based on the chemotherapy regime as some therapies have very low, others very high gonadotoxicity. In borderline ovarian tumours, preservation of fertility usually is achieved through fertility sparing surgery, ovarian stimulation may also be considered. In cervical cancer, endometrial cancer, rheumatic diseases and other malignancies such as Ewing sarcoma, colorectal carcinoma, non-Hodgkin lymphoma, leukaemia etc., several other factors must be considered to enable an individual, stage-dependent decision. CONCLUSION: The decision for or against fertility preservation depends on the prognosis, the risks to fertility and individual factors such as prospective family planning.

Moiré patterns as a probe of interplanar interactions for graphene on h-BN.

By atomistic modeling of moiré patterns of graphene on a substrate with a small lattice mismatch, we find qualitatively different strain distributions for small and large misorientation angles, corresponding to the commensurate-incommensurate transition recently observed in graphene on hexagonal BN. We find that the ratio of C-N and C-B interactions is the main parameter determining the different bond lengths in the center and edges of the moiré pattern. Agreement with experimental data is obtained only by assuming that the C-B interactions are at least twice weaker than the C-N interactions. The correspondence between the strain distribution in the nanoscale moiré pattern and the potential energy surface at the atomic scale found in our calculations makes the moiré pattern a tool to study details of dispersive forces in van der Waals heterostructures.

Importance of transvaginal ultrasound applying elastography for identifying deep infiltrating endometriosis - a feasibility study.

PURPOSE: To evaluate the presence of a lesion indicative of endometriosis with transvaginal elastography. MATERIALS AND METHODS: Transvaginal ultrasound and clinical examination were carried out in 48 women with clinical symptoms indicative of endometriosis. In 31 cases strain values were measured at two regions of interest (ROIs) in the Douglas's cul-de-sac during a cycle of compression and decompression with a vaginal probe. RESULTS: A significant difference was found for the ratio of the ROI measuring points in the Douglas' cul-de-sacs of women with a palpable nodule in examination compared to women without a palpable nodule (p = 0.002). CONCLUSION: The ratio of strain values between two ROIs in the Douglas' s cul-de-sac is associated with the presence of an endometriotic lesion. In the future, these findings could allow for a more detailed pre-surgical evaluation and possibly serve as a novel diagnostic tool for predicting deep infiltrating endometriosis.

mRNA-expression of ERα, ERß, and PR in clonal stem cell cultures obtained from human endometrial biopsies.

Background. Proliferation and differentiation of the endometrium are regulated by estrogen and progesterone. The enormous regenerative capacity of the endometrium is thought to be based on the activity of adult stem cells. However, information on endocrine regulatory mechanisms in human endometrial stem cells is scarce. In the present study, we investigated the expression of ERα, ERß, and PR in clonal cultures of human endometrial stem cells derived from transcervical biopsies. Methods. Endometrial tissue of 11 patients was obtained by transcervical biopsy. Stromal cell suspensions were plated at clonal density and incubated for 15 days. Expression of ERα, ERß and PR was determined by qPCR prior to and after one cloning round, and normalized to 18 S rRNA expression. Results. Expression of ERα and ERß was downregulated by 64% and 89%, respectively (P = 0.002 and P < 0.001). In contrast, PR was not significantly downregulated, due to a more heterogenous expression pattern. Conclusions. Culture of human endometrial stroma cells results in a downregulation of ERα and ERß, while expression of PR remained unchanged in our patient collective. These results support the hypothesis that stem cells may not be subject to direct stimulation by sex steroids, but rather by paracrine mechanisms within the stem cell niche.

Fertility preservation and management of pregnancy in melanoma patients requiring systemic therapy.

Melanoma is one of the most common cancers in adolescents and adults at fertile age, especially in women. With novel and more effective systemic therapies that began to profoundly change the dismal outcome of melanoma by prolonging overall survival, the wish for fertility preservation or even parenthood has to be considered for a growing portion of melanoma patients-from the patients' as well as from the physicians' perspective. The dual blockade of the mitogen-activated protein kinase pathway by B-Raf proto-oncogene serine/threonine kinase and mitogen-activated protein kinase inhibitors and the immune checkpoint inhibition by anti-programmed cell death protein 1 and anti-cytotoxic T-lymphocyte-associated protein-4 monoclonal antibodies constitute the current standard systemic approaches to combat locally advanced or metastatic melanoma. Here, the preclinical data and clinical evidence of these systemic therapies are reviewed in terms of their potential gonadotoxicity, teratogenicity, embryotoxicity and fetotoxicity. Recommendations for routine fertility and contraception counseling of melanoma patients at fertile age are provided in line with interdisciplinary recommendations for the diagnostic work-up of these patients and for fertility-protective measures. Differentiated recommendations for the systemic therapy in both the adjuvant and the advanced, metastatic treatment situation are given. In addition, the challenges of pregnancy during systemic melanoma therapy are discussed.

Relevance of anti-Mullerian hormone measurement in a routine IVF program.

BACKGROUND: Diminished ovarian reserve has become a major cause of infertility. Anti-Mullerian hormone (AMH) seems to be a promising candidate to assess ovarian reserve and predict the response to controlled ovarian hyperstimulation (COH). This prospective study was conducted to evaluate the relevance of AMH in a routine IVF program. METHODS: Three hundred and sixteen patients were prospectively enrolled to enter their first IVF/ICSI-cycle. Age, FSH-, inhibin B- and AMH-levels and their predictive values for ovarian response and clinical pregnancy rate were compared by discriminant analyses. RESULTS: A total of 132 oocyte retrievals were performed. A calculated cut-off level < or =1.26 ng/ml AMH alone detected poor responders (< or =4 oocytes) with a sensitivity of 97%, and there was a 98% correct prediction of normal response in COH if levels were above this threshold. With levels <0.5 ng/ml, a correct prediction of very poor response (< or =2 oocytes) was possible in 88% of cases. Levels of AMH > or =0.5 ng/ml were not significantly correlated with clinical pregnancy rates. CONCLUSIONS: AMH is a predictor of ovarian response and suitable for screening. Levels < or =1.26 ng/ml are highly predictive of reduced ovarian reserve and should be confirmed by a second line antral follicle count. Measurement of AMH supports clinical decisions, but alone it is not a suitable predictor of IVF success.

Optimal binding site of a methane molecule on the silanol covered (010) surface of silicalite-1: ONIOM calculations.

The binding energies and the corresponding structures of a methane molecule on the silanol covered (010) surface of silicalite-1 have been investigated using ab initio methods. Different levels of calculations, HF/6-31G(d), MP2/6-31G(d) and ONIOM (MP2/6-31G(d):HF/6-31G(d)) including the correction of an error due to an unbalance of the basis set, known as basis set super position error (BSSE), as well as the size of the cluster representing the silicalite-1 surface, were systematically examined to validate the model used. The ONIOM method with the BSSE correction was found to be a compromise between accuracy and computer time required. The optimal binding site on the silicalite-1 surface was observed at the configuration where the methane molecule points one H atom toward the O atom of the silanol group. The corresponding binding energy is -1.71 kJ/mol. This value is significantly higher than that of -5.65 kJ/mol when the methane molecule approaches the center of the straight channel. At this configuration, the C atom of methane was observed to locate exactly at the center of the channel. This leads to the conclusion that the methane molecule will relatively seldom be adsorbed on the silanol covered (010) surface of silicalite-1. Instead, the adsorption process will take place directly at the center of the straight channel.

Treatment strategies for severe oligoasthenoteratozoospermia (OAT) (<0.1 million/mL) patients.

Intracytoplasmic sperm injection (ICSI) using spermatozoa from patients with severe oligoasthenoteratozoospermia is still a challenge. Although spermatozoa are available, lower fertilisation rates as well as compromised pregnancy rates are observed after ICSI. We aimed at identifying respective parameters in the pre-values of ejaculate samples used for couple counselling. The clinical pre-values of 121 patients and their corresponding 228 ICSI cycles performed between 2002 and 2010 were retrospectively analysed. Patients were divided into three groups: (i) group 1 (G1, n = 51) where all patients showed at least once <0.1 million/mL and ICSI was performed using ejaculate alone; (ii) group 2 (G2, n = 14) patients had once <0.1 Mill/mL or azoospermia and a testicular biopsy before start of ICSI; (iii) group 3 (G3, n = 56) patients were azoospermic and directed immediately to testicular sperm extraction (TESE). The pre-values of G2 differed significantly from G1 in terms of volume and motility. Lutenizing hormone (LH) and follicle-stimulating hormone (FSH) values were equal in G1 and G2, but showed significant differences in comparison to G3. Testis volume was significantly higher in G3. In the corresponding ICSI cycles, the percentage of cancelled embryo transfers was highest in G3. We did not find any correlations of hormonal markers or sperm pre-values with the success rates of ICSI. In our patient cohort, spermatozoa retrieved either from ejaculate or testicular biopsies have nearly identical chances in achieving pregnancies. Patients in need of TESE before ICSI have significantly lower sperm counts. However, it is not possible to calculate threshold values as indicator for TESE.

Solving ossicular problems in stapedectomy.

Three unusual ossicular problems encountered in stapedectomy are: floating stapes footplate, partial absence of the incus long process, and otosclerosis combined with a fixed malleus. The surgical techniques advocated in solving these problems are: placing a Robinson prosthesis on the floating footplate, utilizing the Lippy modification of the Robinson prosthesis for the problem incus, and performing only a stapedectomy for malleus fixation and otosclerosis. The hearing results in 242 cases were quite satisfactory and no patient had a further sensorineural loss.

Solving ossicular problems in tympanoplasty.

Four troublesome problems encountered in ossicular reconstruction are: low profile stapes, lateral tympanic membrane, remaining stapes crura, and absent stapes capitulum. The design advantages and modifications of the semibiological ossicle cup and ossicle columella prostheses are given to solve these problems. The hearing results are completely satisfactory.

Reconstructing the absent lenticular process.

When a surgeon encounters an absent lenticular process of the incus, he must either reposition the incus or attempt to bridge the small gap between the remaining incus long process and the stapes capitulum. Our solution to this problem is to place a Lippy modified Robinson stapes prosthesis on the stapes footplate and attach it to the remaining long process, thus bypassing the stapes superstructure. This modified Robinson prosthesis has a portion of the well removed allowing the eroded long process to enter from the side. The hearing results of 63 cases at 6 months (two-thirds of which had a concurrent tympanoplasty) are 67% within 10 dB and 91% within 20 dB of the preoperative bone hearing level. The use of an existing and proven prosthesis provides both stability and, to date, the most successful hearing results for reconstructing the absent lenticular process.

Stapedectomy in patients with small air-bone gaps.

Controversy exists concerning stapedectomy for patients with small air-bone gaps. The purpose of this study was to examine the results for patients who had a stapedectomy to correct a small (10 dB or less) air-bone gap. One hundred fifty-four patients with suspected otosclerosis were explored and a stapedectomy was performed in 136 (88.3%) of these cases. The mean pure-tone average (PTA) improved 16.7 dB and overdosed the preoperative bone conduction PTA by 8.1 dB. The majority of the stapedectomy patients (89.7%) had a PTA closure greater than or equal to 0 dB. These results showed that stapedectomy can be an effective procedure for eliminating and overdosing even small air-bone gaps due to otosclerosis.

Short- and long-term results of stapedectomy in children.

Studies have indicated that stapedectomy can be an effective procedure in children for correcting conductive hearing losses due to juvenile otosclerosis. However, because childhood otosclerosis is rare and children commonly choose to use hearing aids in lieu of undergoing surgery, little outcome data are available. The purpose of this retrospective study was to provide additional outcome data in both the short and the long term. Stapedectomies were performed on 47 children. Preoperative hearing results were compared with 6-month postoperative hearing results. Hearing results for the children who had long-term follow-up (5 years or more) were compared with the 6-month postoperative results. Stapedectomy was successful (postoperative air conduction pure-tone average [PTA] within 10 dB of the preoperative bone conduction PTA) in 91.7% of the cases. The mean overclosure of the preoperative bone conduction PTA by the postoperative air conduction PTA was 0.2 dB. The mean PTA hearing improvement was 32.8 dB. Results from the 21 children (28 ears) who had long-term follow-up indicated an average 0.7 dB/year PTA worsening from the 6-month postoperative PTA. Results from this study provide additional evidence that stapedectomy can be an effective procedure for correcting conductive hearing losses due to juvenile otosclerosis.

Acoustic reflexes, auditory brainstem response, and MRI in the evaluation of acoustic neuromas.

Patient records were reviewed to determine whether persons with absent acoustic reflexes have a higher incidence of abnormal auditory brainstem response (ABR) results in the absence of a cerebellopontine angle (CPA) tumor than those with normal acoustic reflexes. Results showed patients with absent reflexes to have borderline or abnormal ABR results in 45.2% of the cases. Patients with normal reflexes had borderline or abnormal ABR results in 14.2% of the cases. Results indicate that magnetic resonance imaging is a more appropriate test for patients with absent reflexes, since ABR was often nondiagnostic for a CPA tumor in this group.

Partial ossicular reconstruction in children: a review of 62 operations.

OBJECTIVE/HYPOTHESIS: The published experience and audiometric results with ossicular reconstruction in children are limited. To better understand the role of ossiculoplasty in children, audiometric results were examined for partial ossicular reconstructions performed on a pediatric population. STUDY DESIGN: Retrospective. METHODS: Sixty-two partial ossicular reconstructions performed on a pediatric population were reviewed for audiometric results, prosthesis extrusion rates, and mechanisms of failure at revision. Comparison of techniques and prosthesis types: porous polyethylene partial ossicular replacement prosthesis (POP), Schuring ossicle cup (SOC), and modified Robinson prosthesis (MRP) were also evaluated. Follow-up ranged from 6 to 72 months. RESULTS: Six-month hearing results showed postoperative airbone gaps less than or equal to 20 dB in 77% of cases. Successful results at 1 and 2 years were retained in 66% and 63% of cases, respectively. Results for POPs at 1 and 2 years were 78% and 89%. Results for SOCs at 1 and 2 years were 61% and 55%. The overall extrusion rate was approximately 3%. CONCLUSIONS: These results compare favorably with those from other, mostly adult, studies. Comparison of prosthesis types revealed generally stable long-term results with few significant differences. Success with ossiculoplasty in children can be obtained by applying the same principles and approach to ossicular reconstruction as used in adults. Ossicular reconstruction in children remains a secondary goal after establishing a safe, dry, and stable ear. A discussion of techniques and comparative literature review are presented.

Practical use of total and partial ossicular replacement prostheses in ossiculoplasty.

The use of porous polyethylene total and partial ossicular replacement prostheses (TOPs and POPs) for ossicular reconstruction in middle ear surgery was retrospectively reviewed at the Warren Otologic Group, a tertiary referral center for otologic problems. Extrusion rates, lower than those previously reported, and improvement in hearing results were found in 250 cases. Follow-up ranged from 6 months to 8 years. This paper details the optimal placement and relationships of the prosthesis, the interposed tragal cartilage, and the drum. Modifications to the prosthesis have increased stability and ease of reconstruction. The hearing results of both TOP and POP reconstruction, and comparison with the literature, will be presented. With TOPs, the air-bone gap was closed to within 20 dB in 67% of cases. With POPs, similar results were obtained in 81% of cases.

Stapedectomy revision following sensorineural hearing loss.

This study analyzes 71 stapedectomies that resulted in a sensorineural hearing loss, followed by a revision stapedectomy on the suspicion of an oval window fistula. The cases were divided between two primary stapedectomy techniques: a stainless steel Robinson prosthesis on a vein graft and a wire prosthesis with Gelfoam. The major differences between the surgical findings of the two groups were the fistula rate with the wire prosthesis was 10 times that with the Robinson prosthesis; the wire prosthesis was longer than necessary in 21% of the cases in which it was used; there was no finding of excess length with the Robinson prosthesis; and after revision stapedectomy, dizziness was lessened in 20% of the patients in the Robinson prosthesis group, in 60% of those in the wire prosthesis group, and in 75% of those with fistula. Surgical directions are given for revision stapedectomy following a sensorineural hearing loss.

The ossicle-cup prosthesis: five years later.

The ossicle-cup prosthesis is a semibiologic prosthesis that incorporates a synthetic portion into the remaining (or transplant) ossicle. This assembly is positioned on the stapes capitulum, with the synthetic cup forming a dynamic joint. During 1978, 114 patients underwent surgical procedures in which an ossicle cup prosthesis was used. After 1 year 84% of these patients were within 20 dB of their preoperative bone hearing levels. Patients with a concurrent mastoidectomy did worse than those who underwent only a tympanoossiculoplasty. Five years later, 74% of the successful cases were still within 20 dB of the preoperative hearing levels. Eighteen patients underwent a revision surgical procedure to regain hearing. The postoperative hearing results at 1 year were 50% within 20 dB. The causes of failure included further ossicle necrosis (28%), a laterally healed tympanic membrane (39%), and fixation of the prosthesis (33%). Extrusion of the prosthesis during the 5-year period was between 1% and 2%. Overall, the ossicle cup prosthesis has proved to be a stable assembly, easy to revise, and longlasting. Once successful, three of four cases will retain successful hearing for more than 5 years.

Validating the excision of cholesteatoma.

In lieu of a radical mastoidectomy, 138 patients underwent a closed tympanomastoidectomy with subsequent staged surgical procedures until the excision of cholesteatoma could be validated. All the patients underwent two surgical procedures, 29% underwent three procedures, and 4% underwent four procedures. The surgical findings at the second procedure were: negative, 41.5%; retraction pockets, 7%; squamous pearls, 14%; recurrent cholesteatoma, 12%; and residual cholesteatoma, 25.5%. At each stage the likelihood of finding any form of cholesteatoma lessens. A conversion from a closed to an open mastoidectomy was necessary for 9% of the patients, and 4% were lost to follow-up. The opportunity to adjust the reconstructed ossicular assembly exists at each stage. With the use of semibiologic prostheses (ossicle cup and columella), the hearing results were: first stage, 67% within 20 dB, 84% within 30 dB; second stage, 77% and 90%; third stage, 77% and 96%.