Uterine Fibroids and Infertility

Infertility is a disease of the reproductive system defined by the failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse. Uterine fibroids are the most common tumor in women, and their prevalence is high in patients with infertility. Fibroids may be the sole cause of infertility in 2-3% of women. Depending on their location in the uterus, fibroids have been implicated in recurrent pregnancy loss as well as infertility. Pregnancy and live birth rates appear to be low in women with submucosal fibroids; their resection has been shown to improve pregnancy rates. In contrast, subserosal fibroids do not affect fertility outcomes and their removal does not confer any benefit. Intramural fibroids appear to reduce fertility, but recommendations concerning their treatment remain unclear. Myomectomy should be discussed individually with the patient; other potential symptoms such as dysmenorrhea or bleeding disorders should be included in the indication for surgery

Impact of nicotine and maternal BMI on fetal birth weight

Data from 110.047 singleton pregnancies, achieved from the German Perinatal Survey in Schleswig-Holstein and registered between 2010 and 2017 were analyzed in August 2018 concerning maternal BMI and smoking. The BMI was taken from the maternity log. Information concerning the smoking status were self-reported and further subdivided into the following four categories: a) non-smokers; b) 1-7 cigarettes/day; c) 8-14 cigarettes/ day; and d) ≥ 15 cigarettes/ day. Furthermore, we classified women by their BMI into underweight, normal weight, overweight and obese. Comparisons between non-smokers and the respective smoking group, and their relationship with maternal BMI were performed by the t-test (birth weight). A number of 97.092 women (88.2%) were non-smokers and 12.955 (11.8%) were smokers. Furthermore 10.3% of women of normal weight smoked during pregnancy, but both high and low BMI were associated with a high prevalence of smoking. The proportion of smokers was highest (18.1%) among underweight women (BMI ≤ 18.5 kg/m2). A large number of smokers (15.5%) were registered in the obesity group (BMI ≥ 30 kg/m2). Mean birth weight (≥ 37 + 0 gestational age) increased with increasing maternal BMI, and was reduced by smoking for every BMI category. The differences between smokers and non-smokers were always highly significant (p < 0.001). Mean birth weight varied between 2995 g in underweight frequent smokers and 3607 g in obese non-smokers. Conclusion Both maternal BMI and smoking during pregnancy influences the birth weight and therefore pregnancy outcome. Smoking during pregnancy was significantly associated with low birth weight. Pregnant women should be advised to cease or at least reduce smoking in order to improve the birth weight of the newborn and to minimize child morbidities

Live Birth Rates after Active Immunization with Partner Lymphocytes

Although many potential causes have been established for recurrent implantation failure (RIF) and recurrent miscarriage (RM), about 50% of these remain idiopathic. Scientific research is focused on immunological risk factors. In the present study, we aim to evaluate live birth rates after immunization with paternal lymphocytes (lymphocyte immunotherapy (LIT)). This retrospective study consisted of 148 couples with a history of RM and/or RIF. The women underwent immunization with lymphocytes of their respective partners from November 2017 to August 2019. Fifty-five patients (43%) had live births. Stratified by indication (RM, RIF, combined), live birth rates in the RM and the combined group were significantly higher than that in the RIF group (53%, 59% and 33%, respectively, p = 0.02). The difference was especially noticeable during the first 90 days after immunization (conception rate leading to live births: 31%, 23% and 8% for RM, the combined group and RIF, respectively; p = 0.005), while there was no difference between groups during the later follow-up. LIT was associated with high live birth rates, especially in women with recurrent miscarriage. In view of the limited data from randomized studies, LIT cannot be recommended as routine therapy. However, it may be considered in individual cases

Ectopic pregnancy in noncommunicating horn of unicornuate uterus: 3D-ultrasound and primary laparoscopic management.

Unicornuate uterus with pregnancy in the noncommunicating rudimentary horn is extremely rare. Diagnosis requires awareness, high suspicion index, 3D ultrasound, and MRI. If missed, it can be catastrophic. Treatment varies across literature. We present a case where detection was done by 3D ultrasound and primary laparoscopic surgery done for treatment

Video Feedback and Video Modeling in Teaching Laparoscopic Surgery: A Visionary Concept from Kiel

Learning curves for endoscopic surgery are long and flat. Various techniques and methods are now available for surgical endoscopic training, such as pelvitrainers, virtual trainers, and body donor surgery. Video modeling and video feedback are commonly used in professional training. We report, for the first time, the application of video modeling and video feedback for endoscopic training in gynecology. The purpose is to present an innovative method of training. Attendees (residents and specialists) of minimally invasive surgery courses were asked to perform specific tasks, which were video recorded in a multimodular concept. Feedback was given later by an expert at a joint meeting. The attendees were asked to fill a questionnaire in order to assess video feedback given by the expert. The advantages of video feedback and video modeling for the development of surgical skills were given a high rating (median 84%, interquartile ranges (IQR) 72.5-97.5%, n = 37). The question as to whether the attendees would recommend such training was also answered very positively (median 100%, IQR 89.5-100%, n = 37). We noted a clear difference between subjective perception and objective feedback (58%, IQR 40.5-76%, n = 37). Video feedback and video modeling are easy to implement in surgical training setups, and help trainees at all levels of education

Endogenous TRAIL-R4 critically impacts apoptotic and non-apoptotic TRAIL-induced signaling in cancer cells

Binding of TRAIL to its death domain-containing receptors TRAIL-R1 and TRAIL-R2 can induce cell death and/or pro-inflammatory signaling. The importance of TRAIL and TRAIL-R1/R2 in tumor immune surveillance and cancer biology has meanwhile been well documented. In addition, TRAIL has been shown to preferentially kill tumor cells, raising hope for the development of targeted anti-cancer therapies. Apart from death-inducing receptors, TRAIL also binds to TRAIL-R3 and TRAIL-R4. Whereas TRAIL-R3 is lacking an intracellular domain entirely, TRAIL-R4 contains a truncated death domain but still a signaling-competent intracellular part. It is assumed that these receptors have anti-apoptotic, yet still not well understood regulatory functions. To analyze the significance of the endogenous levels of TRAIL-R4 for TRAIL-induced signaling in cancer cells, we stably knocked down this receptor in Colo357 and MDA-MB-231 cells and analyzed the activation of apoptotic and non-apoptotic pathways in response to treatment with TRAIL. We found that TRAIL-R4 affects a plethora of signaling pathways, partly in an opposite way. While knockdown of TRAIL-R4 in Colo357 strongly increased apoptosis and reduced clonogenic survival, it inhibited cell death and improved clonogenic survival of MDA-MB-231 cells after TRAIL treatment. Furthermore, TRAIL-R4 turned out to be an important regulator of the expression of a variety of anti-apoptotic proteins in MDA-MB-231 cells since TRAIL-R4-KD reduced the cellular levels of FLIPs, XIAP and cIAP2 but upregulated the levels of Bcl-xL. By inhibiting Bcl-xL with Navitoclax, we could finally show that this protein mainly accounts for the acquired resistance of MDA-MB-231 TRAIL-R4-KD cells to TRAIL-induced apoptosis. Analyses of non-apoptotic signaling pathways revealed that in both cell lines TRAIL-R4-KD resulted in a constitutively increased activity of AKT and ERK, while it reduced AKT activity after TRAIL treatment

Mucinous Cystic Neoplasm of Pancreas in a Pregnant Woman Presenting with Severe Anemia and Gastric Bleeding: Case Report and Review of the Literature

Mucinous cystic neoplasms of the pancreas are uncommon and especially their occurrence during pregnancy is an extremely rare event which necessitates an individualized and interdisciplinary management. A 33-year old woman was referred to our department during her third trimester of pregnancy (34th week of gestation) with severe anemia and tarry stools. Based on gastroscopic findings, our interdisciplinary team suspected a gastrointestinal stromal tumor and therefore indicated a prompt delivery via cesarean section completed with an oncological resection of the neoplasm. Histological examination subsequently showed a mucinous cystic neoplasm of the pancreas with no evidence of malignancy. To review the prevalence of mucinous cystic neoplasms and to discuss diagnosis and treatment during pregnancy. Moreover, we critically value the indication of preterm delivery and the oncological procedure in the perspective of outcome for mother and infant. A bleeding gastrointestinal tumor during pregnancy represents a life-threatening risk for mother and infant and requires an immediate interdisciplinary treatment. The urgency and radicality of the therapy should be adapted according to individual findings. As our patient&#39;s tumor was suspected of having a malignant progression, an extensive surgical intervention was necessary

ADAM17 Inhibition Increases the Impact of Cisplatin Treatment in Ovarian Cancer Spheroids

Chemotherapy resistance is a major challenge in ovarian cancer (OvCa). Thus, novel treatment combinations are highly warranted. However, many promising drug candidates tested in two-dimensional (2D) cell culture have not proved successful in the clinic. For this reason, we analyzed our drug combination not only in monolayers but also in three-dimensional (3D) tumor spheroids. One potential therapeutic target for OvCa is A disintegrin and metalloprotease 17 (ADAM17). ADAM17 can be activated by chemotherapeutics, which leads to enhanced tumor growth due to concomitant substrate cleavage. Therefore, blocking ADAM17 during chemotherapy may overcome resistance. Here, we tested the effect of the ADAM17 inhibitor GW280264X in combination with cisplatin on ovarian cancer cells in 2D and 3D. In 2D, the effect on five cell lines was analyzed with two readouts. Three of these cell lines formed dense aggregates or spheroids (HEY, SKOV-3, and OVCAR-8) in 3D and the treatment effect was analyzed with a multicontent readout (cytotoxicity, viability, and caspase3/7 activation). We tested the combined therapy on tumor spheroids derived from primary patient cells. In 2D, we found a significant reduction in the half minimal (50%) inhibitory concentration (IC50) value of the combined treatment (GW280264X plus cisplatin) in comparison with cisplatin monotherapy in all five cell lines with both 2D readout assays (viability and caspase activation). In contrast, the combined treatment only showed an IC50 reduction in HEY and OVCAR-8 3D tumor spheroid models using caspase3/7 activity or CelltoxTM Green as the readout. Finally, we found an improved effect of GW280264X with cisplatin in tumor spheroids derived from patient samples. In summary, we demonstrate that ADAM17 inhibition is a promising treatment strategy in ovarian cancer