Contralateral Ovary Research Articles

Safety of transient abdominal ovariopexy in patients with severe endometriosis

ObjectiveTo evaluate complications of transient ovariopexy performed to reduce adhesions in patients with severe endometriosis. MethodsA bicentric retrospective study involved 193 consecutive patients who underwent laparoscopic surgery for severe endometriosis at 2 French university hospitals from 1997 to 2009. At the end of surgery, unilateral or bilateral transient ovariopexy was performed on 297 ovaries. Immediate (e.g. reproducibility, tolerance, and hospital stay) and long-term (evaluated via vaginal access to the ovaries, ovarian function, and ovarian vascularization) complications were assessed. ResultsThe technique, which was easy and reproducible, did not increase hospital stay and was well tolerated. There were 2 (0.7%) immediate complications. There was no difference in ovarian accessibility before and after surgery (177/183 [96.7%] vs 176/183 [96.1%]). Potential vaginal oocyte retrieval for in vitro fertilization was possible for all patients. The antral follicle count and the pulsatility index of suspended ovaries were not different from those of contralateral unsuspended ovaries. Endometrioma excision did not modify these results. ConclusionThe short- and long-term safety results of transient ovariopexy for adnexal adhesions in patients with severe endometriosis were encouraging.

Giant Endometrioma associated with Serous Cystadenoma: A Case Report

Background Giant endometriomas are a rare condition and the association with cystadenomas has not been reported previously. Case A 37-year-old woman without any previous medical history of disease presented to the emergency department because of dyspnea. During physical examination the patient presented a considerably sized abdominal growth when a tomography was performed; this revealed a large mass which was presumably dependent on the pelvic cavity. Surgery was performed to remove the tumor, during which another cyst was found in the contra-lateral ovary. Conculsions The histopathologic report showed that the tumor found on the left ovary corresponded to a giant endometriosic cyst and on the right ovary, a papillary serous cystadenoma.

Ovarian Sertoli-Leydig cell tumors. A retrospective MITO study

ObjectiveTo evaluate clinicopathologic features and to investigate the outcome of patients with ovarian Sertoli-Leydig cell tumors (SLCTs). MethodsData concerning 21 patients treated in 11 MITO centers were retrospectively reviewed. ResultsMedian age was 37 (range 16–76). FIGO stage was: 17 (81%) IA, 1 (4.8%) IC, 1 (4.8%) IIB and 2 (9.5%) IIIC. Five patients (23.8%) had G1 tumor, ten (47.6%) had G2, and six (28.6%) had G3. Fertility-sparing operation was performed in 11 patients, while hysterectomy with bilateral salpingo-oophorectomy was executed in 10 patients; five patients received adjuvant chemotherapy (G2–3). Seven patients (33.3%) relapsed with a median time to recurrence of 14months. Six recurrent patients had G2–3 disease, while one had G1. Four patients had stage IA disease, one IC and 2 stage IIIC. Patients with stage IA disease did not receive adjuvant chemotherapy. Two patients had pelvic recurrence, 4 abdominal (one with lymph nodal involvement), one on the contralateral ovary and the trocar access. Five patients underwent salvage surgery plus chemotherapy, while one received only salvage chemotherapy and one palliation.Five patients died of disease, four had received first treatment not in a MITO center. 5year overall survival was 100% for patients with G1 disease and 77.8% for G2–3. 5year overall survival was 92.3% for stage I and 33.3% for stage>I. ConclusionsThe prognosis of patients with grade 1 SLCT is excellent without adjuvant chemotherapy. Patients with advanced stage or grade 2–3 tumors appear to benefit from postoperative chemotherapy.

MRI Features of Ovarian Fibroma and Fibrothecoma With Histopathologic Correlation

The purpose of this article is to evaluate MRI features of ovarian fibroma and fibrothecoma with histopathologic correlation. In this retrospective study, preoperative MRI examinations of 35 women (mean age, 49 years; range, 24-86 years) with pathologically proven ovarian fibroma (n = 25) or fibrothecoma (n = 10) were reviewed by two radiologists in consensus. MRI features, including visibility of ovaries, presence of capsule, degeneration, T1 and T2 signal, and enhancement pattern, were recorded and correlated with histopathologic features. After administration of gadopentetate dimeglumine, the maximum percentages of enhancement of fibroma or fibrothecoma, myometrium, and, if present, uterine fibroids (11/35 patients) were compared. All fibromas and fibrothecomas appeared well defined, with a mean size of 6.36 × 4.81 cm. Ipsilateral and contralateral ovaries were each seen in 89% (31/35) of patients. Most fibromas and fibrothecomas were isointense to hypointense compared with myometrium on T1-weighted (91% [32/35]) and T2-weighted (77% [27/35]) images. Capsule was noted in 63% (22/35) and degenerative changes were noted in 66% (23/35) of patients. Fibromas and fibrothecomas larger than 6 cm more likely showed capsule (p < 0.0001, Fisher exact probability test), degenerative changes (p = 0.003), peripheral subcapsular cystic areas (p < 0.0001), heterogeneous T2 signal (p = 0.001), and heterogeneous enhancement (p = 0.005). At least four of the above five characteristics were present in 93% (14/15) of fibromas and fibrothecomas larger than 6 cm (p < 0.0001). The maximum percentage of enhancement for fibromas and fibrothecomas (63%) was significantly lower than those for myometrium (131%; p < 0.0001) and fibroids (103%; p < 0.0001), without a statistically significant difference between the maximum percentage enhancement of myometrium and fibroids. A maximum percentage of enhancement less than 75% yielded 92% positive predictive value in differentiating fibromas and fibrothecomas from fibroids. Fibrothecomas had a higher maximum percentage of enhancement than did fibromas (p = 0.01). MRI features of ovarian fibromas and fibrothecomas depend on size, with capsule and degenerative changes common with fibromas and fibrothecomas larger than 6 cm. Fibromas and fibrothecomas enhance less than myometrium and fibroids do, and less than 75% maximum percentage enhancement can help in differentiating fibromas and fibrothecomas from fibroids.

Unilateral ablation of follicles ≥ 4 mm leads to compensatory follicle response from the contralateral ovary in heifers

In each of two experiments, heifers were assigned to a control group and a unilaterally ablated (UA) group (n = 6/group). In the UA group, follicles ≥ 4 mm in the left ovary were ablated by transvaginal ultrasound-guided technique at Hour 0 (8:00 AM) on the day of ovulation. Follicles in the CL-bearing right ovary remained intact. In Experiment 1, ablations continued until the next ovulation, and new follicles emerged in the right ovary in 9 of 14 (64%) waves. The number of follicles/wave (combined, 6.4 ± 0.4) did not differ between groups. In Experiment 2, follicles were counted at Hours 0, 4, 8, 12, and 24; the resistance index (RI) for blood flow in the ovarian pedicle was determined at Hours 0 and 12; and blood samples were collected every hour from Hours 0 to 12 and at Hour 24. An increase (P < 0.05) in the number of follicles in the follicle-intact ovary began at Hour 4 with complete compensation by Hour 24. Concentrations of FSH did not change between Hours 0 and 24 in the UA group but decreased (P < 0.05) in the controls by Hour 7. At Hour 12, RI to the right ovary approached being lower (P < 0.06) in the UA group than in the control group. Results indicated that unilateral ablation of follicles ≥ 4 mm led to compensatory follicle response in the follicle-intact ovary, and initially circulatory FSH concentrations were maintained and blood flow to the follicle-intact ovary increased.

Granulosa cell tumour: An interesting case in a pregnant mare

Summary This report describes the successful management of a pregnant 14-year-old seven-eighths Thoroughbred mare with an ovarian granulosa cell tumour. The mare initially presented with unilateral ovarian enlargement whilst being managed for artificial insemination, demonstrating normal ovarian function with ovulation from the contralateral ovary leading to conception. The mare subsequently re-presented with stallion-like behaviour at 3.5 months gestation and ovarian suppression was evident. The mare maintained her pregnancy and delivered a live colt foal at term. Ovariectomy was performed 3 months post foaling and the mare regained cyclic activity 9 months post surgery. The mare then conceived and became pregnant once more. The diagnostic and therapeutic challenges during pregnancy are discussed.

A primary ovarian pregnancy with a contralateral ruptured corpus luteum: a case report.

A primary ovarian pregnancy is one of the rarest varieties of ectopic pregnancies. The conditions which are most commonly confused with an ovarian pregnancy are, a ruptured corpus luteal cyst, a haemorrhagic corpus luteum and a ruptured endometriotic cyst. This case presents the clinical and the histological findings of a ruptured ovarian pregnancy, along with a ruptured corpus luteal cyst in the contralateral ovary.

The impact of in situ methotrexate injection after transvaginal ultrasound-guided aspiration of ovarian endometriomas on ovarian response and reproductive outcomes during IVF-cycles

The primary aim of the present study is to evaluate prospectively whether in situ methotrexate (MTX) injection as alternative treatment of unilateral ovarian endometrioma compromises ovarian response. The secondary aim is to estimate the short term effect of exposure to MXT on reproductive outcomes and fetal congenital anomalies during IVF-cycles. Case controlled study. El-Menya infertility research and treatment center (MRTC), Egypt. 65 patients during their reproductive age complained of a unilateral symptomatic ovarian endometrioma and infertility problem. Ovarian endometrioma was successfully treated by transvaginal ultrasound aspiration with in situ methotrexate followed by ICSI. Oocytes retrieved, M II oocytes, quality of embryos, clinical pregnancy rates and reproductive outcomes were prospectively evaluated from the aspirated and contralateral normal ovary. There was no statistically significant difference between mean number of oocytes retrieved (6.1 ± 1.5 vs 7.2 ± 0.5), M II oocytes, fertilization rate (67.5% ± 1.32 in the aspirated ovary versus 70% ± 0.55 in the normal ovary), and quality of the embryos obtained from the aspirated ovary and the normal contralateral one ( P > 0.05). The mean endometrial thickness was (11.3 ± 1.33 mm) and the quality of the endometrium was homogenous in 54/65 (83.07%). Implantation rate was 30.7% and the clinical pregnancy rate was 21/65 (32.30%). Nine patients (42.85%) have full term deliveries. The total living birth was 14/21 (66.6%) and cumulative pregnancy rate was 48%. In situ methotrexate injection after transvaginal ultrasound-guided aspiration was a simple, safe and successful method for treating ovarian endometriomas with minimal effects on ovarian response. Short term effects on reproductive outcomes, risk of fetal loss or anomaly were minimal. Six months was enough as washout period of the drug prior to conception and was advisable to prevent the small chance of chromosomal abnormalities in the offspring.

Évaluation par échographie tridimensionnelle de la réduction du volume des ovaires après kystectomie des endométriomes

Objective The aim of our study was to assess ovarian tissue loss related to endometrioma cystectomy by 3D-ultrasonography. Patients and methods We have retrospectively included 15 women with no previous ovarian surgery who benefited from cystectomy of an unilateral endometrioma the diameter of which was superior to 30 mm. Cystectomy has been performed using an ovarian tissue-sparing procedure with no incision of the ovarian cortex. Patients underwent ultrasonography at least 9 months after the surgery. Several ovarian parameters, such as the area on longitudinal cross-section, the volume and the antral follicles count (AFC), were measured on both operated and contra lateral ovary, and then were compared using Mann and Whitney test. The relationship between the reduction of operated ovary volume and preoperative endometrioma diameter was evaluated by multiple regression. Results Operated ovary presented a significant reduction in area (mean reduction 229.8 mm 2 ± 47.6; P < 0.0001), volume (mean reduction 5.8 cm 3 ± 1.16; P < 0.0001) and AFC (mean reduction 5.1 ± 3.8, P = 0.002). No statistically significant correlation was found between operated ovary volume reduction and preoperative endometrioma diameter. Discussion and conclusion Endometrioma cystectomy leads to significant reduction in ovarian parenchyma volume and AFC, when compared to contra lateral ovary. This event must be taken into account in the choice of treatment strategy, especially in the case of enlarged, bilateral and recurrent endometriomas, recurrence, as well as in women presenting with other risk factor for ovarian failure.

Ovarian Radiation Dose During Heterotopic Ossification Radiation Prophylaxis

To evaluate the impact of different photon energies and techniques in the total dose of radiation received by ovaries after radiation prophylaxis RT) of heterotopic ossification (HO) around the hip joint. This is a single-institution, retrospective study investigating the dose of radiation to the ovaries during RT for HO prophylaxis. From January (2008 - 2010), 32 patients, all had traumatic acetabular fractures (TAF) underwent surgery followed by RT. Postoperative RT was delivered within 72 hours in a single fraction of 700 cGy, prescribed to the mid-plane, using MV photons. The fields included the soft tissues around the proximal femur and acetabulum without bone shielding. All patients underwent CT simulation and 2 portal images prior to treatment. In all patients, the ipsilateral (IL OV) and contralateral (CL OV) ovaries were contoured separately as a region of interest and dose volume histograms (DVH) generated. Additional planning trials were created for each patient by utilizing a beam split technique medially and by using different photon energies (6 - 18 MV) to investigate the effects of these maneuvers on the delivered dose to the ovaries. 32 female patients, with median age 41 years (range 18 - 85). In reviewing the DVH for all patients, it was noted that the median Mean dose) delivered to the (IL OV) was 59 cGy (range 6 - 262) and the median Max.dose) was 177 cGy (range 7 - 650). (CL OV) median Mean dose) was 6 cGy (range 1 - 11) and median Max.dose) was 10 cGy (range 1 - 21). When a beam split was applied at the medial edge of the field, (27%, 22%) dose reduction in the mean and max.dose, respectively, delivered to the (IL OV) while (9%, 5%) reduction in the mean and maximum dose, respectively, to the (CL OV). When higher energies (10 - 18 MV) were compared to 6 MV, additional 28%, 16 % reduction in mean and max.doses, respectively, of the (IL OV) were achieved. The (CL OV) mean dose was reduced by 18% and the maximum dose was reduced by 12%. A biologically meaningful radiation dose is delivered to the ovaries during RT HO prophylaxis around the hip. This dose could be reduced to the IL Ov by half and the CL Ov by one-quarter by using simple technical adjustments (medial beam split technique and photon energies above 6 MV). All female patients especially those in the childbearing age should be informed and consented with ovarian radiation exposure and possible temporary alteration in ova production and morphology.Tabled 1ResultsBoth Ovaries DVHIL OV Mean DoseIL OV Max DoseCL OV Mean DoseCL OV Max DoseDelivered Median59 cGy177 cGy6 cGy10 cGyBeam Split Reduction27%22%9%5%10 - 18 MV Reduction28%16%18%12%Total Reduction65%38%27%17% Open table in a new tab

Unicornuate uteri associated with contralateral renal agenesis and ovarian anomalies

Our findings regarding two cases of unicornuate uterus validate that conventional transvaginal ultrasound is helpful in diagnosing uterine anomalies. Moreover, anomalies of the urinary system and the contralateral ovary should always be considered.

Poorly Differentiated Ovarian Adenocarcinoma Developing in a Case of Well-Differentiated Endometrioid Carcinoma of the Contralateral Ovary

Abstract Background: Endometrioid carcinoma and undifferentiated carcinoma in the ovary have not been reported together or in the same patient. Case: The case of a young woman who developed undifferentiated carcinoma ovary within 3 months of contralateral adnexectomy for well-differentiated endometrioid carcinoma stage I is presented. The probable etiopathogenesis and management are discussed. Total hysterectomy, right adnexectomy, and infracolic omentectomy with peritoneal sampling were performed. There was no grossly apparent residual disease and histology revealed a poorly differentiated ovarian adenocarcinoma and metastatic implants on the uterus and omentum. Combination chemotherapy was given. Results: The patient was disease free after 6 months. Conclusions: Both kinds of epithelial malignancies arose independently. A possible molecular mechanism could be operating at the genetic level to predispose women with low-grade epithelial tumors of low malignant potential to develop other epithelial tumors ...

Ovarian surgery for bilateral endometriomas influences age at menopause

Questions remain as to whether surgical excision of ovarian endometriomas might cause damage to ovarian function. To test the hypothesis that ovarian surgery for endometrioma compromises ovarian function and accelerates ovarian failure. In a tertiary university Clinic, longitudinal prospective cohort study. Patients who underwent laparoscopy for endometriosis between March 1993 and November 2007 were assessed for inclusion in the study. A prospective follow-up at 3, 6 and 12 months then yearly was conducted. Evolution of menstrual pattern, symptoms and reproductive outcomes were investigated. From over the 14-year period, 302 patients were included in the study. The mean age (±SD) of patients was 32.6 ± 5.6 years; the median duration of follow-up was 8.5 years (range 2-17 years). Menopause was documented in 43 women (14.3%) at a mean age of 45.3 ± 4.3 years (range 32-52 years). Women previously submitted to bilateral cystectomy were younger at menopause than those with monolateral endometrioma (42.1 ± 5.1 years versus 47.1 ± 3.5 years, P = 0.003). Premature ovarian failure (POF) was observed in 7 of 43 (16.3%) menopausal patients; the majority (4, 57.1%) after bilateral cystectomy. The relationship between the preoperative ovarian endometriomas total diameter and menopausal age was significant in case of surgery for bilateral endometriomas (R(2) = 0.754, P = 0.002). Patients who had been operated on for bilateral endometriomas have an increased risk of POF. Ovarian parenchyma loss at the time of surgery seems related to cyst diameter. In the case of unilateral ovarian endometrioma, the contralateral intact ovary might adequately compensate.

Do Hormonal Characteristics of the Luteal Phase Affect the Conception Rate of Women Undergoing IUI Treatment in the Following Menstrual Cycle?

Objective: The present study was performed to evaluate whether the hormone profiles of the mid-luteal phase impact on the chances of conceiving during the following menstrual cycle in connection with intrauterine insemination (IUI) treatment. Design: Observational clinical study. Setting: Infertility clinic. Patient(s): 92 women underwent a total of 288 IUI treatment cycles, without use of exogenous hormones. Intervention(s): The mid-luteal hormone profiles including levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin, oestradiol, progesterone, androstenedione and testosterone, were measured in the preceding cycle of IUI treatment. Main outcome measure(s): The mid-luteal hormone profiles were correlated to whether the women conceived in the following natural menstrual cycle in which IUI treatment was performed and to whether ovulation occurred on the same ovary in two consecutive cycles (ipsilateral ovulation) or jumped from one ovary to the other (contralateral ovulation). Result(s): When ovulation occurred from the same ovary in two consecutive cycles mid-luteal levels of progesterone of the preceeding cycle were significantly lower in conceptional than non-conceptional cycles. No significant differences of LH, FSH, estradiol, androstendione and testosterone were observed when correlating the different parameters. Conclusion(s): Lower mid-luteal progesterone levels seem to enhance chances of conception when ovulation occurs in the same ovary for two consecutive cycles.

Review of seven cases of granulosa cell tumour of the equine ovary

This paper reviews the equine granulosa cell tumour (GCT) and describes the clinicopathological features, treatment and outcome in seven cases of GCT in mares. Mares were presented with unilateral ovarian...

Endometriomas as a possible cause of reduced ovarian reserve in women with endometriosis

To evaluate the adverse effects of endometriomas on ovarian reserve. Analysis of prospectively collected biopsy samples. Gynecology research unit in a university hospital. Women younger than age 35 years with endometriomas. Biopsy of normal cortex from ovaries affected by endometriomas (≤4 cm) and contralateral ovaries without cysts. Presence of cortex-specific stroma, observation of superficial endometriosis, follicular density, and presence of fibrosis. Twenty samples of cortical tissue from ovaries with endometriomas and 11 from contralateral ovaries without cysts were analyzed. Follicular density was significantly lower in cortex from ovaries with endometriomas than in cortex from contralateral ovaries without cysts (mean ± SD = 6.3 ± 4.1/mm(3) vs 25.1 ± 15.0/mm(3)). Eleven (55%) cortical samples from ovaries with endometriomas showed fibrosis and concomitant loss of cortex-specific stroma, not observed in contralateral normal ovaries. Multivariate analysis revealed that the presence of endometrioma and fibrosis were significantly and independently associated with follicular density. Endometriotic cyst formation and associated structural tissue alterations in apparently normal ovarian cortex may be a cause of reduced ovarian reserve. Early diagnosis and intervention may be beneficial in women with endometriomas to protect their ovarian function.

Novel approaches to quantify estradiol-induced loss of ERβ1 protein in older mouse ovarian surface epithelium: new tools to assess the role of ER protein subtypes in predisposing to ovarian epithelial cancer?

Loss of estrogen receptor-beta (ERβ) occurs in ovarian epithelial cancer (OEC), a cancer of mainly older women. OEC is linked epidemiologically to hormone replacement therapy, predominantly with estrogen-only formulations. This study introduces a novel, non-biased method to quantify levels of estradiol-induced loss of ERβ1 protein, and defines, for the first time, normal OSE expression patterns for ERα and ERβ1 with advancing age. Older (7-10months) Swiss Webster mice were injected with estradiol valerate (EV) while age-matched diestrous controls received oil. Mice were culled after 48h, and blood and one ovary were frozen for estradiol RIA. Contralateral ovaries were paraffin-embedded for immunohistochemistry. Subsets of serial sections, triple-labeled with immunofluroescent tags, were imaged with confocal microscopy to provide optimal visualization of ER protein subtype expression in OSE. Immunofluorescence emission profiles distinct to ERβ1 in OSE were standardized and quantified in control mice then compared to profiles from EV-exposed mice. Estradiol levels were significantly elevated in EV-treated mice, both in blood (p < 0.0001) and ovarian tissue (p < 0.001), resulting in 11-fold reduction in OSE expression of ERβ1 protein (p < 0.0001). In aging OSE, expression patterns of both ER subtypes varied within cells and with cell shape. ER co-localization appeared predominantly cytoplasmic and was infrequent in columnar compared to cuboidal-shaped OSE cells. Immunofluorescence emission profiling and multiple-label immunofluorescent tagging of ER using confocal microscopy, provides sharp definition of ER locus enabling concurrent qualitative and quantitative analysis of ER protein. It offers significant potential for assessing ER protein subtype status in predisposition to OEC.

Incomplete ovariosalpingectomy and subsequent malignant granulosa cell tumor in a female green iguana (Iguana iguana)

A 9-year-old spayed female green iguana (Iguana iguana) was evaluated because of a distended coelom and weight loss. History included a single episode of egg binding and subsequent bilateral ovariosalpingectomy. Physical examination revealed a mass within the coelomic cavity. Ultrasonography revealed a large, irregular mass with hypoechoic regions and coelomic effusion. Clinicopathologic derangements included heterophilia, monocytosis, lymphopenia, basophilia, hypocholesterolemia, hypoproteinemia, and hypercalcemia. Results of cytologic evaluation of the mass were suggestive of malignant epithelial neoplasia, but neoplastic cells were not found in the effusion. An ovarian tumor was suspected on the basis of clinical signs, clinicopathologic findings, and results of cytologic evaluation of the mass. Surgical exploration revealed a large left ovary, a normal-appearing contralateral ovary, and a mass in the fat body, all of which were removed and submitted for histologic examination. The histologic diagnosis was granulosa cell tumor with metastasis to the fat body. The patient died 11 months after evaluation, and disseminated granulosa cell tumor was confirmed at necropsy; histologic examination at that time also identified systemic mastocytosis. Granulosa cell tumors are uncommon in reptiles, and this was the first granulosa cell tumor described antemortem cytologically, histologically, and ultrastructurally in an iguana. Findings in this iguana underscored concerns associated with incomplete oophorectomy of iguanas; cytologic and histopathologic findings were similar to those observed in other domestic animals. Oophorectomy should be considered as an alternative to standard ovariosalpingectomy to avoid potential complications in pet reptiles, and use of microsurgical instruments and vascular clips is advised.

Ultrasound ovarian assessments after endometrioma ablation using plasma energy

We performed a retrospective three-dimensional ultrasound evaluation of the ovarian features in ten women with no previous ovarian surgery who benefited from ablation by plasma energy for unilateral endometriomas greater than to 30 mm in diameter. Values of ovarian volume and antral follicle count in operated ovaries were decreased by an average 12% and 18%, respectively, suggesting that endometrioma ablation using plasma energy spares the underlying ovarian parenchyma.

Bilateral ovarian squamous cell carcinoma with an antecedent dermoid cyst in the left ovary

Ovarian squamous cell carcinoma is a rare malignancy and its occurrence is commonly attributed to malignant transformation of a pre-existing mature cystic teratoma. The de novo occurrence of primary squamous cell carcinoma is extremely rare. Malignant transformation in a mature cystic teratoma is almost always unilateral; however, there have been isolated reports of an uncomplicated mature cystic teratoma in the contralateral ovary. We report here a case of a 40-year-old woman presenting with squamous cell carcinoma of both ovaries with antecedent dermoid cyst in the left ovary, along with involvement of the fallopian tubes, cervix and omentum.