Guidelines for goals of care discussions in patients with gynecologic cancer.

This article represents a distillation of literature to provide guidance for goals of care discussions with patients who have gynecologic malignancies. As clinicians who provide surgical care, chemotherapy, and targeted therapeutics, gynecologic oncology clinicians are uniquely positioned to form longitudinal relationships with patients that can enable patient-centered decision making. In this review, we describe optimal timing, components, and best practices for goals of care discussions in gynecologic oncology.

Association of Genomic Instability Score, Tumor Mutational Burden, and Tumor-Infiltrating Lymphocytes as Biomarkers in Uterine Serous Carcinoma.

Background: Uterine serous carcinomas represent 10% of uterine carcinomas but account for nearly 40% of deaths from the disease. Improved molecular characterization of these tumors is instrumental in guiding targeted treatment and improving outcomes. This study assessed the genomic instability score (GIS), tumor mutational burden (TMB), and tumor-infiltrating lymphocytes (TILs) in patients with USC. Methods: A retrospective cohort study evaluated patients with USC following staging surgery. The GIS and TMB were determined from archived specimens. We evaluated the tumoral expression of CD3, CD4, CD8, FOXP3, and CD68 using immunohistochemistry. T-tests were used to assess associations of TILs with the GIS. Results: We evaluated 53 patients with USC. The median GIS was 31 (range: 0−52) and a higher GIS was not associated with progression-free (PFS) or overall survival (OS). The median TMB was 1.35 mt/Mb; patients with TMB > 1.35 mt/Mb had improved PFS and OS (p = 0.005; p = 0.002, respectively). Tumors with increased CD3+ and CD4+ immune cells had a higher mean GIS (p = 0.013, p = 0.002). Conclusions: TMB > 1.35 mt/Mb was associated with improved survival in USC patients, whereas the GIS was not. Lower TMB thresholds may provide prognostic value for less immunogenic tumors such as USC. In this limited cohort, we observed that increased TIL populations were correlated with a higher GIS.

Cost-effectiveness of management strategies for patients with recurrent ovarian cancer and inoperable malignant bowel obstruction.

OBJECTIVES: Patients with recurrent platinum-resistant ovarian cancer often present with inoperable malignant bowel obstruction (MBO) from a large burden of abdominal disease. Interventions such as total parenteral nutrition (TPN) and chemotherapy may be used in this setting. We aim to describe the relative cost-effectiveness of these interventions to inform clinical decision making. METHODS: Four strategies for management of platinum-resistant recurrent ovarian cancer with inoperable MBO were compared from a societal perspective using a Monte Carlo simulation: (1) hospice, (2) TPN, (3) chemotherapy, and (4) TPN + chemotherapy. Survival, hospitalization rates, end-of-life (EOL) setting, and MBO-related utilities were obtained from literature review: hospice (survival 38 days, 6% hospitalization), chemotherapy (42 days, 29%), TPN (55 days, 25%), TPN + chemotherapy (74 days, 47%). Outcomes were the average cost per strategy and incremental cost-effectiveness ratios (ICERs) in US dollars per quality-adjusted life year (QALY) gained. RESULTS: In the base case scenario, TPN + chemotherapy was the most costly strategy (mean; 95% CI) ($49,741; $49,329-$50,162) and provided the highest QALYs (0.089; 0.089-0.090). The lowest cost strategy was hospice ($14,591; $14,527-$14,654). The TPN alone and chemotherapy alone strategies were dominated by a combination of hospice and TPN + chemotherapy. The ICER of TPN + chemotherapy was $918,538/QALY compared to hospice. With a societal willingness to pay threshold of $150,000/QALY, hospice was the strategy of choice in 71.6% of cases, chemotherapy alone in 28.4%, and TPN-containing strategies in 0%. CONCLUSIONS: TPN with or without chemotherapy is not cost-effective in management of inoperable malignant bowel obstruction and platinum-resistant ovarian cancer.

Development and Characterization of a Luciferase Labeled, Syngeneic Murine Model of Ovarian Cancer.

Despite advances in surgery and targeted therapies, the prognosis for women with high-grade serous ovarian cancer remains poor. Moreover, unlike other cancers, immunotherapy has minimally impacted outcomes in patients with ovarian cancer. Progress in this regard has been hindered by the lack of relevant syngeneic ovarian cancer models to study tumor immunity and evaluate immunotherapies. To address this problem, we developed a luciferase labeled murine model of high-grade serous ovarian cancer, STOSE.M1 luc. We defined its growth characteristics, immune cell repertoire, and response to anti PD-L1 immunotherapy. As with human ovarian cancer, we demonstrated that this model is poorly sensitive to immune checkpoint modulators. By developing the STOSE.M1 luc model, it will be possible to probe the mechanisms underlying resistance to immunotherapies and evaluate new therapeutic approaches to treat ovarian cancer.

Novel Therapies in Gynecologic Cancer.

During the past decade, considerable strides have been made in the understanding and treatment of gynecologic cancers. The advent of PARP inhibitors, antiangiogenic therapies, immunotherapy combinations, and targeted agents have altered the standard of care in ovarian, endometrial, and cervical cancers. However, continued advancement in the treatment of gynecologic cancers is critical. Fortunately, exciting work defining new therapeutic targets and novel treatment strategies is on the horizon. Here, we discuss emerging treatments for gynecologic cancers, including endometrial, cervical, ovarian, and rare gynecologic cancers. We highlight research that has deepened our understanding of the unique biology and molecular underpinnings of these cancers and is being translated into powerful new treatment approaches. We particularly highlight the advent of immunotherapy in endometrial cancer; radiosensitizers in cervical, vaginal, and vulvar cancers; targeted therapies in ovarian cancer; and molecularly driven approaches to treat rare gynecologic cancers. Continued basic, translational, and clinical research holds the promise to change the landscape of gynecologic cancer and improve the lives of all women impacted by these diseases.

Opioid Use in Patients With Cervical Cancer at Two Urban Medical Centers.

Purpose: Patients with cervical cancer are at high risk for opioid use. This study aimed to characterize opioid prescribing patterns at 2 urban hospitals. Methods and Materials: Data from patients with cervical cancer treated with curative intent from 2011 to 2018 were retrospectively collected. Women with unrelated chronic opioid use before diagnosis, persistent/recurrent disease at 3 months after initiation of treatment, or initiation of opioids >6 months after treatment were excluded. Demographics, disease characteristics, treatment, and outpatient prescription practices were collected. Endpoints included duration of opioid use ≥6 and ≥12 months. Results: There were 106 women included, of whom 83% received definitive radiation. Most patients (n = 91, 85.8%) received outpatient opioids. Most common timing of prescriptions were before cancer therapy (35.9%), postprocedure (26.4%), and during radiation therapy (17.0%). Median duration was 3 (interquartile range, 1-11) months; 35.2% of these patients received opioids ≥6 months and 22% received opioids ≥12 months. Greater International Federation of Gynaecology and Obstetrics (FIGO) stage, recurrent/residual disease, initiation of opioids before treatment, history of depression or anxiety, and use of gabapentin or steroids were associated with long-term opioid use. Conclusions: Most patients were prescribed outpatient opioids, many of whom used opioids for 12 months. Improvement in provider communication and education, increased posttreatment monitoring, and further evaluation of nonopioid therapies are needed in this patient population to reduce long-term opioid use.

Local Control and Use of External Beam Parametrial Boost in the Era of Image-Guided Brachytherapy for Locally Advanced Cervical Cancer.

OBJECTIVE: Historically, external beam parametrial boost (EBPB) has been used in locally advanced cervical cancers to supplement radiation dose. However, it has become controversial in the era of image-guided brachytherapy. Modern 3D imaging and brachytherapy techniques have improved delineation and coverage of tumor. Outcomes with and without parametrial boost were analyzed. METHODS: Women with cervical cancer involving the parametria (clinically or radiographically) diagnosed between 2001 and 2017 were identified. Clinicopathologic and treatment features, survival and patterns of failure data were collected. Univariate and multivariable data analysis was performed to evaluate association of these variables, including parametrial boost, with local failure-free survival and overall survival. Competing risks analysis was performed for cumulative incidence of local failure, with death and other failures treated as competing events. RESULTS: A total of 100 women were identified (median follow-up 26.8 mo). Forty-one (41%) received EBPB; these patients were less likely to have received magnetic resonance imaging, positron emission tomography, interstitial, or high-dose rate brachytherapy. Magnetic resonance imaging, positron emission tomography, dose rate, and treatment era were highly correlated (Cramer's V: 0.43 to 0.68, P<0.01). Two-year overall survival and local failure were 78% and 12% for the entire cohort. While the use of EBPB was not associated with any outcome on multivariable analysis, treatment year after 2009 was highly associated with improved outcomes in all models. CONCLUSIONS: In this study, omission of EBPB did not compromise local control or survival in the modern era, supporting a decreased need for standardized use of parametrial boost.

Primary treatment of advanced ovarian cancer: how does the 'real world' practice?

Aims: This study evaluated primary treatment modalities in advanced ovarian cancer according to sociodemographic characteristics and characterized chemotherapy regimens used. Methods: This was a retrospective study of newly diagnosed advanced ovarian, tubal or peritoneal cancer patients at two hospitals from 2011 to 2016. Results: Of 175 women, 41% received neoadjuvant chemotherapy and 59% received primary cytoreductive surgery. Within the neoadjuvant chemotherapy group, 23% did not have a surgical consultation prior to initiating treatment. Women receiving neoadjuvant chemotherapy lived closer to an academic center and more frequently received carboplatin/paclitaxel every 3 weeks. Cytoreductive surgery patients more frequently received intraperitoneal chemotherapy. Conclusion: The authors identified disparities in age, insurance, distance from treatment center and chemotherapy choice in the primary treatment for ovarian cancer.

Lay abstract Aims: This study evaluated surgery versus chemotherapy in stage III or IV ovarian cancer and whether differences exist between different groups of patients. Methods: This study looked at newly diagnosed stage III/IV ovarian, tubal or peritoneal cancer patients at two hospitals from 2011 to 2016. Results: Of 175 women, 41% received neoadjuvant chemotherapy and 59% received primary cytoreductive surgery. Within the neoadjuvant chemotherapy group, 23% did not see a gynecologic oncologist prior to initiating treatment. Women receiving neoadjuvant chemotherapy lived closer to an academic center and more frequently received carboplatin/paclitaxel every 3 weeks. Cytoreductive surgery patients more frequently received intraperitoneal chemotherapy. Conclusion: The authors identified differences in age, insurance, distance from treatment center and chemotherapy choice in the treatment for ovarian cancer.

PET-detected asymptomatic recurrence is associated with improved survival in recurrent cervical cancer.

PURPOSE: We aimed to examine utilization patterns of positron emission tomography scans (PET or PET/CT) beyond 6 months after cervical cancer treatment. We investigated survival outcomes of asymptomatic patients with PET-detected recurrence. METHODS: We performed a retrospective review of 283 patients with stage IA-IVA cervical cancer treated with primary chemoradiation. The 107 patients (37.8%) with recurrence were categorized as "asymptomatic PET-detected recurrence" (n = 23) or "standard detection" (n = 84) and we compared clinical characteristics and outcomes using multivariate logistic regression analysis. RESULTS: Late post-treatment PET (≥ 6 months after treatment) was performed in 35.3% (n = 100). Indications for late post-treatment PET included restaging in setting of known recurrence (23.6%), follow up of prior ambiguous imaging findings (9.7%), and new symptoms or exam findings (6.7%). However, late post-treatment PET was most commonly performed outside of current imaging guidelines, in asymptomatic patients without suspicion for recurrence (60.0%), presumably for surveillance. The median time to recurrence was 12.1 months (IQR 7.3-26.6). 23 patients (21.5%) had recurrence detected late post-treatment PET while asymptomatic (n = 23/107). Patients with asymptomatic PET-detected recurrence had improved survival by 26.3 months compared to the standard detection cohort (50.3 vs 24.0 months, p = 0.0015). On multivariate analysis, predictors of survival after recurrence were presence of distant metastases at diagnosis (p = 0.010) and asymptomatic PET-detected recurrence (p = 0.039). CONCLUSIONS: PET imaging in asymptomatic patients beyond 6 months after treatment may have clinical benefit and warrants further study. Detection of recurrence by PET in asymptomatic patients ≥ 6 months after chemoradiation was associated with prolonged survival by more than   2 years.

An integrated molecular profile of endometrioid ovarian cancer.

OBJECTIVE: Endometrioid ovarian carcinoma (EOVC) is an uncommon subtype of epithelial ovarian carcinoma and its molecular characteristics have been incompletely described. Prior sequencing investigations have been limited to targeted gene panels. We performed whole-exome sequencing to build an unbiased genetic profile of molecular alterations in endometrioid ovarian tumors with a goal to better understand this disease in the context of epithelial ovarian cancer and endometrioid uterine cancers. METHODS: Whole-exome sequencing was performed on EOVC samples (n = 26) and matched normals (n = 15). Gene mutations, mutational signatures and copy number variations (CNVs) informed a multi-dimensional regression classifier allowing for comparison to endometrial carcinoma (UCEC) and high grade serous ovarian carcinoma (HGSC). RESULTS: EOVC has a distinct and heterogeneous genomic profile. Identified significantly mutated genes in EOVC (PTEN, CTNNB1, PIK3CA, KMT2D, KMT2B, PIK3R1, ARID1A and TP53) occurred at similar frequencies in UCEC. Hypermutation, resulting from both mismatch repair deficiency (MMRd) and POLE mutation, was observed in EOVC at a frequency similar to UCEC. Like UCEC, a subset of EOVC cases closely resembled HGSC, harboring TP53 mutations, homologous recombination deficiency (HRd) mutation signatures and widespread CNVs. A machine-learning classifier confirmed the heterogeneous composition of EOVC. Potential therapeutic targets were identified in 62% of EOVC cases. We validated our findings in an orthogonal clinical sequencing registry of EOVC cases. CONCLUSIONS: We identified that EOVC are a molecularly heterogeneous group of epithelial ovarian cancers with distinct mutational signatures. In an age of precision oncology, there is a pressing need to understand the unique molecular drivers in uncommon histologic subtypes to facilitate genomically driven oncologic treatments.

Malignant bowel obstruction due to uterine or ovarian cancer: Are there differences in outcome?

OBJECTIVES: To describe and compare treatments and outcomes of patients with malignant bowel obstructions (MBO) due to uterine or ovarian cancer. METHODS: Retrospective chart review from two institutions of women admitted 1/1/2005-12/31/2016 with a MBO from recurrent/progressive uterine or ovarian cancer. Data collected includes patient characteristics, cancer-directed treatments before and after MBO, MBO management strategies, and survival after MBO. RESULTS: Women with MBO from uterine cancer (n = 46) and ovarian cancer (n = 130) underwent similar inpatient interventions such as inpatient chemotherapy and surgery. Median overall survival (OS) after admission for MBO for all patients was 105 days and was shorter for uterine cancer patients (57 vs 131 days, p = 0.0013). Uterine and ovarian cancer patients who had surgery had similar survival (182 vs 210 days, p = 0.6), as did those discharged on hospice from their first admission for MBO (26 vs 38 days, p = 0.1). Uterine and ovarian cancer patients had similar rates of post-discharge chemotherapy (37% vs 50%, p = 0.12), but uterine cancer patients who had chemotherapy still had shorter survival (151 vs 225 days, p = 0.03). CONCLUSIONS: MBO has a relatively poor prognosis. Ovarian and uterine cancer patients whose interventions included surgery or hospice had similar outcomes. Among patients managed medically without hospice, uterine cancer patients experienced worse survival, even when candidates for subsequent chemotherapy. Patient counseling regarding goals of care at this difficult juncture can be informed by these findings and will be enhanced by patient-reported and qualitative data on the patient experience with MBO.

Fertility treatment is associated with multiple meningiomas and younger age at diagnosis.

PURPOSE: Meningiomas are more common in females and 70-80% express the progesterone receptor, raising the possibility that high-dose exogenous estrogen/progesterone exposure, such as occurs during fertility treatments, may increase the risk of developing a meningioma. The goal of this study was to report the incidence of prior fertility treatment in a consecutive series of female meningioma patients. METHODS: A retrospective review (2015-2018) was performed of female patients with meningioma, and those with prior fertility treatment were compared to those without fertility treatment using standard statistical methods. RESULTS: Of 206 female patients with meningioma, 26 (12.6%) had a history of fertility treatments. Patients underwent various forms of assisted reproductive technology including: in vitro fertilization (50.0%), clomiphene with or without intrauterine insemination (34.6%), and unspecified (19.2%). Median follow up was 1.8 years. Tumors were WHO grade I (78.6%) or grade II (21.4%). Patients who underwent fertility treatments presented at significantly younger mean age compared to those who had not (51.8 vs. 57.3 years, p = 0.0135, 2-tailed T-test), and on multivariate analysis were more likely to have multiple meningiomas (OR 4.97, 95% CI 1.4-18.1, p = 0.0154) and convexity/falx meningiomas (OR 4.45, 95% CI 1.7-11.5, p = 0.0021). CONCLUSIONS: Patients in this cohort with a history of fertility treatment were more likely to present at a younger age and have multiple and convexity/falx meningiomas, emphasizing the importance of taking estrogen/progesterone exposure history when evaluating patients with meningioma. Future clinical studies at other centers in larger populations and laboratory investigations are needed to determine the role of fertility treatment in meningioma development.

Mutant p53 regulates LPA signaling through lysophosphatidic acid phosphatase type 6.

Emerging evidence has indicated that high-grade serous ovarian cancer (HGSOC) originates in the fallopian tube, where the earliest known genetic lesion is the mutation of TP53. In addition to such genetic changes, HGSOC is characterized by altered metabolism, including the production of oncogenic lipids such as lysophosphatidic acid (LPA). To understand the crosstalk between TP53 mutations and LPA signaling, we utilized primary fallopian tube epithelial cells (FTEC) engineered to overexpress mutant p53. We found that gain-of-function (GOF) p53 mutations downregulated the LPA-degrading enzyme lysophosphatidic acid phosphatase type 6 (ACP6), leading to upregulation of focal adhesion signaling in an LPA-dependent manner. Although highly expressed in normal fallopian tube epithelium, ACP6 expression was significantly reduced in ovarian cancer tumors and early in situ lesions. Downregulation of ACP6 in ovarian cancer cells was necessary and sufficient to support HGSOC proliferation, adhesion, migration, and invasion. Using mouse models of metastasis, we established that attenuation of ACP6 expression was associated with increased tumor burden. Conversely, overexpression of ACP6 suppressed invasive behavior. These data identify an involvement of oncogenic p53 mutations in LPA signaling and HGSOC progression through regulation of ACP6 expression.

Measuring and Improving Physician Knowledge of Safety Risks Using Traditional and Online Methods in Pharmacovigilance.

BACKGROUND: Traditional methods for assessing prescriber knowledge can take several years to deliver results. This study was undertaken to obtain insights into the potential for using existing online communities to educate prescribers on therapy-related safety risks. OBJECTIVE: The aim of this study was to describe approaches to measuring prescribers' knowledge of safety risk (osteonecrosis of the jaw) outlined in the European Medicine Agency's summary of product characteristics for denosumab (XGEVA®). METHODS: Short multiple-choice online instruments were administered as (1) a two-round cross-sectional survey fielded in January 2013-May 2015 (traditional, nine European countries, study duration: 3 years), (2) a survey targeting the online Medscape community (seven European countries, study duration: 3 weeks), and (3) a continuing medical education module with pre-/post-assessment in an online Medscape community (Medscape Education, USA). All respondents were oncologists; treated five or more patients with bone metastases from solid tumours in the previous 3 months; and prescribed denosumab within the previous 12 months. Medscape (a WebMD company, New York, NY, USA) is the leading online medical information resource, serving approximately 3 million physicians worldwide and 400,000 within Europe. RESULTS: In the traditional 29-month study, 420 (n = 210 per round; 14% of screened physicians) individuals participated. Knowledge levels exceeded 75% correct on five questions (incidence of osteonecrosis of the jaw, concomitant risk factors and prevention of osteonecrosis of the jaw during denosumab treatment, importance of ensuring oral hygiene, and care for patients who have or develop osteonecrosis of the jaw) with less awareness of optimal osteonecrosis of the jaw treatment. The Medscape survey (n = 207; 32.1% of 645 eligible) provided similar results in a 3-week post-survey launch. The Medscape Education study (n = 264) documented knowledge acquisition. CONCLUSIONS: Assessments that target physicians through online platforms where they seek information about drug-related safety risks may result in increased efficiencies, informing regulators about prescribers' knowledge of safe use within weeks rather than years. Online communities or professional societies may provide venues in which to implement knowledge-acquisition surveys tied to training/education modules that address safety topics.

Educational outcomes in the era of the Affordable Care Act: impact of personalized education about non-small cell lung cancer.

INTRODUCTION: The Affordable Care Act is moving medical care-and medical education-toward a quality-driven environment. Quality medical education must be available when the health care provider is ready to learn, provide feedback, and maximize translation of knowledge from desk to clinic. To best accomplish these goals, medical education must be personalized to clinicians' needs. Research has defined multiple knowledge/performance gaps among oncologists who manage advanced non-small cell lung cancer (NSCLC). A study was conducted to determine the effectiveness with which a personalized learning approach for oncologists will diminish these gaps. METHODS: The authors undertook development, online distribution, and impact measurement of an NSCLC curriculum in which learners' responses to a preeducation self-assessment of knowledge, skills, and attitudes resulted in receipt of a personalized curriculum. Upon completion of the assessment, each learner received a personalized curriculum, which included up to 5 distinct activities selected to address identified knowledge and practice gaps. Feedback was provided at the completion of each activity. RESULTS: Ninety-two oncologists completed an individualized learning plan. Analysis shows that completion of the learning plan was associated with a high effect size (d = .70). Significant increases were seen in oncologists' ability to correctly identify the rationale for determining histological subtype (13% increase), prevalence of genetic abnormalities (21% increase, p = .04), appropriate use of maintenance therapy (31% increase, p = .01), and appropriate treatment regimens for squamous cell carcinoma (19% increase, p = .003) and of adenocarcinoma (44% increase, p < .001). DISCUSSION: This study demonstrates the feasibility and impact of a personalized targeted curriculum for improving the competence of oncologists treating patients with advanced NSCLC.

Modeling the Early Steps of Ovarian Cancer Dissemination in an Organotypic Culture of the Human Peritoneal Cavity.

The pattern of ovarian cancer metastasis is markedly different from that of most other epithelial tumors, because it rarely spreads hematogenously. Instead, ovarian cancer cells exfoliated from the primary tumor are carried by peritoneal fluid to metastatic sites within the peritoneal cavity. These sites, most notably the abdominal peritoneum and omentum, are organs covered by a mesothelium-lined surface. To investigate the processes of ovarian cancer dissemination, we assembled a complex three-dimensional culture system that reconstructs the lining of the peritoneal cavity in vitro. Primary human fibroblasts and mesothelial cells were isolated from human omentum. The fibroblasts were then mixed with extracellular matrix and covered with a layer of the primary human mesothelial cells to mimic the peritoneal and omental surfaces encountered by metastasizing ovarian cancer cells. The resulting organotypic model is, as shown, used to examine the early steps of ovarian cancer dissemination, including cancer cell adhesion, invasion, and proliferation. This model has been used in a number of studies to investigate the role of the microenvironment (cellular and acellular) in early ovarian cancer dissemination. It has also been successfully adapted to high throughput screening and used to identify and test inhibitors of ovarian cancer metastasis.

Iodixanol density gradient centrifugation for selecting stallion sperm for cold storage and cryopreservation.

Density gradient centrifugation can be used for selection of sperm of superior quality and removal of seminal plasma for use in artificial insemination. In this study, the use of two-layer iodixanol density gradient centrifugation was evaluated for processing of stallion semen. The protocol includes centrifugation through a 16% iodixanol top layer of 1.090 g mL(-1) and collection of motile and intact sperm on a 30% iodixanol bottom layer of 1.165 g mL(-1). Sperm recovery and effects on sperm quality were determined during cold storage as well as after cryopreservation and compared with ordinary dilution and centrifugation. Two-layer iodixanol density gradient centrifugation allows for selection of greater percentages of morphologically normal and progressively motile sperm compared to ordinary centrifugation. This likely results from collecting sperm on the bottom layer that functions as cushion fluid, which prevents mechanical forces as occur when sperm are packed in a pellet. In addition, percentages of membrane and chromatin integrity are increased when cells are selected based on their density via centrifugation through the top and bottom layers. Removal of seminal plasma and increased initial percentages of motile and membrane intact sperm after iodixanol density gradient centrifugation also result in greater percentages of progressively motile and membrane intact sperm during cold storage as well as after freezing and thawing. In conclusion, the two-layer iodixanol density gradient centrifugation protocol described in this manuscript allows for selection of stallion sperm with greater survival rates for cold storage and cryopreservation.

Quality and fertility of cooled-shipped stallion semen at the time of insemination.

Stallion semen processing is far from standardized and differs substantially between AI centers. Suboptimal pregnancy rates in equine AI may primarily result from breeding with low quality semen not adequately processed for shipment. It was the aim of the study to evaluate quality and fertility of cooled-shipped equine semen provided for breeding of client mares by commercial semen collection centers in Europe. Cooled shipped semen (n = 201 doses) from 67 stallions and 36 different EU-approved semen collection centers was evaluated. At arrival, semen temperature was 9.8 ± 0.2 °C, mean sperm concentration of AI doses was 68 ± 3 x 10(6)/ml), mean total sperm count was 1.0 ± 0.1 x 10(9), total motility averaged 83 ± 1% and morphological defects 45 ± 2%. A total of 86 mares were inseminated, overall per season-pregnancy rate in these mares was 67%. Sperm concentration significantly influenced semen motility and morphology at arrival of the shipped semen. Significant effects of month of the year on volume, sperm concentration and total sperm count of the insemination dose were found. The collection center significantly influenced all semen parameters evaluated. Semen doses used to inseminate mares that became pregnant had significantly higher total and progressive motility of spermatozoa and a significantly lower percentage of morphological semen defects than insemination doses used for mares failing to get pregnant. Results demonstrate that insemination with semen of better quality provides a higher chance to achieve pregnancy. Besides the use of stallions with good semen quality, appropriate semen processing is an important factor for satisfying results in artificial insemination with cooled-shipped horse semen.