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1.  Nonlinear analysis of biomagnetic signals recorded from uterine myomas 
Objective
To determine if there is any non-linearity in the biomagnetic recordings of uterine myomas and to find any differences that may be present in the mechanisms underlying their signal dynamics.
Methods
Twenty-four women were included in the study. Sixteen of them were characterised with large myomas and 8 with small ones. Uterine artery waveform measurements were evaluated by use of Pulsatility Index (PI) (normal value PI<1.45).
Results
Applying nonlinear analysis to the biomagnetic signals of the uterine myomas, we observed a clear saturation value for the group of large ones (mean = 11.35 ± 1.49) and no saturation for the small ones.
Conclusion
The comparison of the saturation values in the biomagnetic recordings of large and small myomas may be a valuable tool in the evaluation of functional changes in their dynamic behavior.
doi:10.1186/1477-044X-4-2
PMCID: PMC1484479  PMID: 16571144
2.  Biomagnetic signatures of uncoupled gastric musculature 
Gastric slow waves propagate in the electrical syncytium of the healthy stomach, being generated at a rate of approximately three times per minute in a pacemaker region along the greater curvature of the antrum and propagating distally towards the pylorus. Disease states are known to alter the normal gastric slow wave. Recent studies have suggested the use of biomagnetic techniques for assessing parameters of the gastric slow wave that have potential diagnostic significance. We present a study in which the gastric syncytium was uncoupled by mechanical division as we recorded serosal electric potentials along with multichannel biomagnetic signals and cutaneous potentials. By computing the surface current density (SCD) from multichannel biomagnetic recordings, we were able to quantify gastric slow wave propagation as well as the frequency and amplitude of the slow wave and to show that these correlate well with similar parameters from serosal electrodes. We found the dominant slow wave frequency to be an unreliable indicator of gastric uncoupling as uncoupling results in the appearance of multiple slow wave sources at various frequencies in external recordings. The percentage of power distributed in specific frequency ranges exhibited significant postdivision changes. Propagation velocity determined from SCD maps was a weak indicator of uncoupling in this work; we believe that the relatively low spatial resolution of our 19-channel biomagnetometer confounds the characterization of spatial variations in slow wave propagation velocities. Nonetheless, the biomagnetic technique represents a non-invasive method for accurate determination of clinically significant parameters of the gastric slow wave.
doi:10.1111/j.1365-2982.2009.01265.x
PMCID: PMC2855967  PMID: 19222760
electrogastrography; gastric slow wave; magnetogastrography; SQUID magnetometer
3.  Real-time Measurement of Biomagnetic Vector Fields in Functional Syncytium Using Amorphous Metal 
Scientific Reports  2015;5:8837.
Magnetic field detection of biological electric activities would provide a non-invasive and aseptic estimate of the functional state of cellular organization, namely a syncytium constructed with cell-to-cell electric coupling. In this study, we investigated the properties of biomagnetic waves which occur spontaneously in gut musculature as a typical functional syncytium, by applying an amorphous metal-based gradio-magneto sensor operated at ambient temperature without a magnetic shield. The performance of differentiation was improved by using a single amorphous wire with a pair of transducer coils. Biomagnetic waves of up to several nT were recorded ~1 mm below the sample in a real-time manner. Tetraethyl ammonium (TEA) facilitated magnetic waves reflected electric activity in smooth muscle. The direction of magnetic waves altered depending on the relative angle of the muscle layer and magneto sensor, indicating the existence of propagating intercellular currents. The magnitude of magnetic waves rapidly decreased to ~30% by the initial and subsequent 1 mm separations between sample and sensor. The large distance effect was attributed to the feature of bioelectric circuits constructed by two reverse currents separated by a small distance. This study provides a method for detecting characteristic features of biomagnetic fields arising from a syncytial current.
doi:10.1038/srep08837
PMCID: PMC4351545  PMID: 25744476
4.  Uterine leiomyoma and its association with menstrual pattern and history of depo-medroxyprogesterone acetate injections 
Background and aim:
Despite the high prevalence of uterine leiomyoma, according to recent review studies there is uncertainty and a paucity of information regarding its predisposing or protective factors. The aim of this study was to assess the possible association between menstrual cycle pattern and occurrence of surgically treated myomas and also to check if depo-medroxyprogesterone acetate (DMPA) injection earlier in reproductive life can affect the later occurrence of myomas needing surgical treatment.
Methods:
In a case–control study in Ardabil, 85 women with definite diagnosis of surgically treated uterine leiomyoma and 154 community controls were enrolled. Possible predictors of myoma including menstrual cycle and menstrual bleeding patterns were assessed. Data were analyzed using SPSS software (SPSS, IBM, Somers, NY). Odds ratios were used as the main statistic in assessing the strength of observed associations.
Results:
Mean age of the participants was 41.8 ± 8.5 years. Length of menstrual cycle was associated with myoma and a higher likelihood of myoma was observed among those having shorter menstrual cycles (P < 0.05). Number of menstrual bleeding days was also associated with surgically treated myoma and longer bleeding periods increased the likelihood of myoma (P < 0.05). Only one of the eight women who had a history of depo-medroxyprogesterone acetate injections had developed surgically treated uterine leiomyoma and the others belonged to the control group without a history of surgical treatment for uterine leiomyoma.
Conclusion:
Menstrual cycle pattern is associated with developing leiomyomas requiring surgical treatment. DMPA, other than its role in myoma treatment, is also assumed to have a role in preventing myomas, but due to the small sample size in this study, larger scale prospective trials are needed in the future.
doi:10.2147/IJGM.S23337
PMCID: PMC3150177  PMID: 21845062
myoma; uterine leiomyoma; DMPA; medroxyprogesterone; menstrual cycle; menstrual; depo-provera
5.  CA 125 and other tumor markers in uterine leiomyomas and their association with lesion characteristics 
The aim of this study was to investigate the factors associated with serum levels of several tumor markers in a group of patients operated for uterine myoma. One hundred thirty-seven female patients operated for uterine myoma were included. Serum samples were examined for CA 125, CA 19-9, CA 15-3, carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP) levels as part of routine workup. Pathological and morphological characteristics of the patients were retrieved from medical records. The mean age was 46.7 ± 8.8 years (range, 22-85 y). Abnormally high levels of CA 125, CA 19-9, CA 15-3, CEA, and AFP were found in 19.7%, 6.6%, 5.1%, 3.7%, and 1.5% of the patients, respectively. Patients with additional adenomyosis and patients with at least one large myoma (≥ 5 cm diameter) had significantly higher levels of CA 125. Multivariate analysis identified coexistence of adenomyosis (OR 7.7 [95% CI, 2.6-23.0], p < 0.001) and presence of at least one large myoma (OR 5.6 [1.4-22.8], p = 0.016) as independent predictors of abnormally high CA 125 levels. CA 125 levels are affected by the tumor size and coexistence of adenomyosis in uterine leiomyomas. Indirect mechanisms caused by large myoma size such as peritoneal irritation may be responsible for CA 125 elevations.
PMCID: PMC4057864  PMID: 24955185
Uterine leiomyoma; uterine fibroma; tumor marker; CA 125; CA 19-9; CA 15-3; carcinoembryonic antigen (CEA); alpha fetoprotein (AFP)
6.  Total Laparoscopic Hysterectomy for Large Uterus 
Aim:
In this review, we assessed the feasibility of total laparoscopic hysterectomy (TLH) in cases of very large uteri weighing more than 500 grams. We have analyzed whether it is possible for an experienced laparoscopic surgeon to perform efficient total laparoscopic hysterectomy for large myomatous uteri regardless of the size, number and location of the myomas.
Design:
Retrospective review (Canadian Task Force Classification II-1)
Setting:
Dedicated high volume Gynecological laparoscopy centre.
Patients:
173 women with symptomatic myomas who underwent total laparoscopic hysterectomy at our center. There were no exclusion criteria based on the size number or location of myomas.
Intervention:
TLH and modifications of performing the surgery by ligating the uterine arteries prior, myomectomy followed by hysterectomy, direct morcellation after uterine artery ligation.
Results:
72% of patients had previous normal vaginal delivery and 28% had previous cesarean section. Average clinical size of the uterus was 18 weeks (10, 32). The average weight of the specimen was 700 grams (500, 2240). The average duration of surgery was 107 min (40, 300) and the average blood loss was 228 ml (10, 3200).
Conclusion:
Total laparoscopic hysterectomy is a technically feasible procedure. It can be performed by experienced surgeons for large uteri regardless of the size, number or location of the myomas.
doi:10.4103/0974-1216.51908
PMCID: PMC3304266  PMID: 22442509
Large uterus; multiple fibroids; total laparoscopic hysterectomy
7.  Developments in Techniques for Laparoscopic Myomectomy 
Objectives:
Conflicting opinions about laparoscopic myomectomy (LM) are still present regarding indications and risks related to reproductive outcome. We reviewed our 13-year experience (1) to identify risk factors or changes in methods that have improved our myomectomy technique and (2) to evaluate how the learning curve and improved surgical devices influenced our procedures, and (3) to study the myomectomy scar with a power color Doppler ultrasound (US).
Methods:
From January 1991 to December 2003, we studied 332 patients who underwent laparoscopic myomectomy. We analyzed, as the learning curve, how the introduction of the Steiner morcellator, the use of vasoconstrictive agents, and different techniques of suturing have influenced parameters such as operating time and blood loss.
Results:
We performed 332 single or multiple myomectomies for symptomatic myomas. Most patients (47%) had more than one myoma, with a maximum of 8 per patient (average myomas removed for patients: 2.23, range 1 to 8). Myoma size ranged from 1cm to 20 cm (mean, 60.20±SD27.1 mm). Myomas <4cm were removed during myomectomy for larger ones. The conversion rate to laparotomy was 1.51%. The average drop in hemoglobin concentration was 1.06±SD0.86 g/100 mL (range, 0.7 to 2.2 g/100 mL). No blood transfusions were required. No major intraoperative complications occurred. The duration of the procedure ranged from 30 minutes to 360 minutes (mean, 124±SD52.6). The dimensions of the myomas removed increased with experience (4.91±SD2.2 cm of the earlier cases to 6.76±SD2.7 of the latest group, P<0.000). The learning curve positively influenced the length of the procedures in the first cases. The introduction of electromechanical morcellation in 1996 reduced the procedure time. Data showed significantly reduced Hb drop after the introduction in 1998 of vasoconstrictive agents (ΔHb 1.62 g/100 mL versus 0.95; P<0.001). The running suture offered few advantages in terms of procedure time. However, the drop in hemoglobin was advantageous (ΔHb 1.1 g/100mL vs 0.61, P<0.01). The overall rate of intrauterine pregnancy following LM was 65.5%. No uterine ruptures occurred. We had 2 serious postoperative complications:
Conclusions:
With increased experience, the technical improvements and clinical results have changed our approach and decision making regarding laparoscopic myomectomy. Our results and extremely low conversion rate suggest that laparoscopic myomectomy is a safe and reliable procedure even in the presence of multiple or enlarged myomas.
PMCID: PMC3015797  PMID: 17651554
Laparoscopic myomectomy; Morcellator; Learning curve; Vasoconstrictive agents
8.  Transient Occlusion of Uterine Arteries in Laparoscopic Uterine Surgery 
Background and Objectives:
This study was conducted to determine the feasibility and effectiveness of transient occlusion of the uterine arteries (TOUA) during laparoscopic surgery for benign uterine tumors, with preservation of fertility.
Methods:
Patients with uterine myoma or adenomyoma underwent laparoscopic uterine surgery, with or without TOUA, performed by a single surgeon (Y.-S.K.). Surgical outcomes included operative time; occurrence of intraoperative injury of blood vessels, nerves, and pelvic organs; and intraoperative blood loss.
Results:
Of the 168 surgical patients included in this study, 144 were enrolled consecutively during the study period, and 24 had undergone adenomectomy before the study period. A total of 104 women (70 with myoma; 34 with adenomyoma) seeking uterine preservation underwent laparoscopic surgery with TOUA for benign uterine tumors. Sixty-four women (40 with myoma; 24 with adenomyoma) underwent surgery without TOUA. The mean total surgical time of the TOUA groups was 74.85 minutes for uterine myoma and 84.09 minutes for uterine adenomyoma. The mean estimated blood loss during laparoscopic myomectomy and adenomyomectomy was less in the TOUA groups than in the non-TOUA groups (109 vs. 203.4 mL in myomectomy, P < .05; 148.1 vs. 158.9 mL in adenomyomectomy; P < .05). Time to perform TOUA was 13.9 minutes in laparoscopic myomectomy and 7.33 minutes in laparoscopic adenomyomectomy. The hospital stay of the TOUA groups was 3.32 days for uterine myoma and 3.82 days for uterine adenomyoma. No intraoperative conversion to laparotomy was necessary, and no major complications occurred during any of the procedures.
Conclusion:
Laparoscopic uterine surgery with TOUA could be a safe and effective surgical method for women with symptomatic benign uterine tumors who wish to preserve fertility.
doi:10.4293/JSLS.2014.00189
PMCID: PMC4376212  PMID: 25848179
Benign uterine tumor; Laparoscopic uterine surgery; Uterus preservation; Transient occlusion of uterine arteries
9.  Low dose mifepristone in medical management of uterine leiomyoma - An experience from a tertiary care hospital from north India 
The Indian Journal of Medical Research  2013;137(6):1154-1162.
Background & objectives:
Uterine myoma is a common indication for hysterectomy in India. An effective medical treatment option may reduce hysterectomy associated morbidity. This study was undertaken to evaluate efficacy and safety of low dose mifepristone in medical management of myoma and to compare two doses - 10 vs. 25 mg/day.
Methods:
In this randomized clinical trial, women with symptomatic myoma or myoma>5cm were included. Uterine size >20 wk, fibroids >15 cm were excluded. Pictorial blood loss assessment chart (PBAC) score was used to assess menstrual-blood-loss and visual analog scale (VAS) for other symptoms. Haemogram, liver function test, ultrasound with doppler and endometrial histology was performed. Patients were randomized and were given oral mifepristone as 25 mg/day in group 1 and 10 mg/day in group 2 for 3 months. Patients were followed at 1, 3 and 6 months.
Results:
Seventy patients in group 1 and 73 in group 2 completed treatment. Mean PBAC score reduced from 253 to 19.8 and from 289.2 to 10.4 at 1 and 3 months in groups 1 and 2, respectively. At 3 months, 67 of 70 (95.7%) patients of group 1 and 66 of 73 (90.4%) of group 2 developed amenorrhoea which reverted after median 34 (range 4-85) days. Mean myoma volume decreased by 35.7 per cent (from 176.8 to 113.7cm3) and 22.5 per cent (from 147.6 to 114.4 cm3) at 3 months in groups 1 and 2, respectively. Side effects seen were leg cramps in 7 of 70 (10%) and 5 of 73 (6.8%) and hot-flushes in 5 of 70 (7.1%) and 5 of 73 (6.8%) in groups 1 and 2, respectively. Repeat endometrial-histopathology did not reveal any complex hyperplasia or atypia in either group.
Interpretation & conclusions:
Mifepristone (10 and 25 mg) caused symptomatic relief with more than 90 per cent reduction in menstrual blood. Greater myoma size reduction occured with 25 mg dose. Amenorrhoea was developed in 90-95 per cent patients which was reversible. It can be a reasonable choice for management of uterine leiomyoma as it is administered orally, cost-effective and has mild side effects.
PMCID: PMC3734720  PMID: 23852296
Amenorrhoea; fibroid; leiomyoma; mifepristone; medical management; uterine
10.  Current and emerging treatments for uterine myoma – an update 
Uterine myomas, the most common benign, solid, pelvic tumors in women, occur in 20%–40% of women in their reproductive years and form the most common indication for hysterectomy. Various factors affect the choice of the best treatment modality for a given patient. Asymptomatic myomas may be managed by reassurance and careful follow up. Medical therapy should be tried as a first line of treatment for symptomatic myomas, while surgical treatment should be reserved only for appropriate indications. Hysterectomy has its place in myoma management in its definitiveness. However, myomectomy, rather than hysterectomy, should be performed when subsequent childbearing is a consideration. Preoperative gonadotropin-releasing hormone analog treatment before myomectomy decreases the size and vascularity of the myoma but may render the capsule more fibrous and difficult to resect. Uterine artery embolization is an effective standard alternative for women with large symptomatic myomas who are poor surgical risks or wish to avoid major surgery. Its effects on future fertility need further evaluation in larger studies. Serial follow-up without surgery for growth and/or development of symptoms is advisable for asymptomatic women, particularly those approaching menopause. The present article is incorporated with multiple clear clinical photographs and simplified elaboration of the available management options for these tumors of uterine smooth muscle to facilitate clear understanding.
doi:10.2147/IJWH.S15710
PMCID: PMC3163653  PMID: 21892334
myomectomy; uterine artery embolization; pelvic tumor; hysterectomy; GnRH; leiomyoma
11.  Fertility outcomes following myomectomy in an urban hospital setting. 
OBJECTIVE: Infertility is rarely a consequence of myomas. However, a causal relationship may be suspected when other causes of infertility have been excluded. Uterine myomas have been reported in 27% of infertile women; 50% of women with unexplained infertility become pregnant after myomectomy. The objective of this study was to establish the impact of the surgical removal of myomas on fertility outcomes in women experiencing recurrent pregnancy loss or unexplained infertility. Fallopian tube, anovulatory disorders and male fertility factors had been appropriately excluded. DESIGN: This was a retrospective study in which we compiled data from the medical records of eight patients from 2003-2004 who underwent abdominal myomectomy for infertility or recurrent pregnancy loss. We calculated rates for subsequent spontaneous abortion, preterm delivery, cesarean delivery, malpresentation and postpartum hemorrhage. RESULTS: There were two patients who were nulliparous premyomectomy, and six had recurrent pregnancy losses. There was a cumulative success rate of 75% (six live births in eight patients) following myomectomy. One had two subsequent pregnancies. There were no spontaneous abortions. Three (37.5%) patients failed to conceive postmyomectomy, one of which was found to have bilateral tubal occlusion. Of the six pregnancies achieved, two (33%, 95% CI 2.06, 3.14) were preterm deliveries, six (100%, 95% CI 1.74, 3.50) were delivered by cesarean section and three (50%, 95% CI 3.50, 1.73) were malpresentations (two breech, one transverse lie). One patient (16%, 95% CI 2.06, 3.30) had abruptio placentae and two patients (33%, 95% CI 2.06, 3.14) experienced postpartum hemorrhage. CONCLUSION: This study suggests that there may be a beneficial effect of surgical removal of myomas on enhancing fertility and successful pregnancy outcome. However, the sample was too small to achieve statistical significance.
Images
PMCID: PMC2594713  PMID: 16353656
12.  Combining Myoma Coagulation with Endometrial Ablation/Resection Reduces Subsequent Surgery Rates 
Background:
This study compares results of endometrial ablation alone and in combination with myoma coagulation. Subsequent surgery rates were 38% for ablation alone and 12% for combined therapy.
Objective:
The purpose of this study was to compare hysterectomy rates following various surgical procedures to treat profuse uterine bleeding as well as myomatous uteri.
Study Design:
This is a descriptive study of women who underwent endometrial ablation alone, endometrial ablation with myoma coagulation, or endometrial resection with myoma coagulation to treat profuse uterine bleeding as well as myomatous uterus. From 1986 to 1995, the author performed 52 endometrial ablation procedures; 88 myoma coagulation and endometrial ablation procedures; and 28 myoma coagulations with resection of submucous myomas in patients who were subsequently available for follow-up. Patients were followed up for up to ten years.
Results:
Of the patients undergoing ablation alone, 20 (38%) of 52 required a second surgery for continued symptoms during a mean follow-up of 47 months. Five of these patients (9.6%) underwent hysterectomy. Of the patients who underwent endometrial ablation plus myoma coagulation (myolysis), 11 (12.5%) of 88 required a repeat surgical procedure during a mean follow-up of 25 months. Five of these patients (5.7%) underwent hysterectomy. Volumetric measurements revealed an average reduction in fibroid volume of 54.5% in this patient group following treatment with a gonadotropin-releasing hormone (GnRH) agonist and combined myoma coagulation and endometrial ablation surgery. Of the 28 patients who underwent myoma coagulation plus resection, five (18%) required a repeat procedure. Of these five, one (4%) required hysterectomy. Fibroid volume in this group was reduced by a mean of 72.6% following administration of a GnRH agonist and combined laparoscopic and hysteroscopic surgery as described. The rate of reoperation was significantly lower among patients receiving endometrial ablation with myoma lysis with or without resection compared with those undergoing endometrial ablation alone (P<0.01).
Conclusions:
Myoma coagulation (myolysis), when combined with endometrial ablation among women with symptomatic fibroids and bleeding, reduces all subsequent surgery rates compared with endometrial ablation alone. Myolysis with endometrial resection also results in a reduced need for hysterectomy.
PMCID: PMC3015361  PMID: 10694070
Fibroids; Uterine bleeding; Endometrial ablation; Myoma coagulation; Endometrial resection; Hysterectomy
13.  Comparison of the Inhibitory Effect of Gonadotropin Releasing Hormone (GnRH) Agonist, Selective Estrogen Receptor Modulator (SERM), Antiprogesterone on Myoma Cell Proliferation In Vitro 
Uterine myomas are the most common gynecologic tumor in women of reproductive age. Treatment options of uterine myomas consist of surgical, medical and interventional therapy such as uterine artery embolization or myolysis. Given that it is the most common type of tumor in women of reproductive age, the treatment of uterine myomas must prioritize uterine conservation. There are several drugs for medical treatment of uterine myoma such as gonadotropin releasing hormone (GnRH) agonist, selective estrogen receptor modulator (SERM) and antiprogesterone. The objective of this study was to compare the effect of GnRH agonist, SERM, and antiprogesterone in the treatment of uterine myomas in vitro. The effect of drugs was evaluated through the cell viability assay in cultured leiomyoma cells, western blot analysis of proliferating cell nuclear antigen (PCNA), and BCL-2 protein expression. As a result, mifepristone single-treated group represents the most significant reduction in myoma cell viability and proliferation. When pretreated with leuprolide acetate, raloxifene shows more significant reduction in myoma cell viability and proliferation than mifepristone. This study suggests one of the possible mechanisms how medications act on uterine myoma, especially at the molecular level.
doi:10.7150/ijms.7627
PMCID: PMC3917117  PMID: 24516352
Leiomyoma; Drug therapy; Gonadotropin-releasing hormone agonist; Raloxifene; Mifepristone
14.  Office Hysteroscopic Laser Enucleation of Submucous Myomas without Mass Extraction: A Case Series Study 
BioMed Research International  2015;2015:905204.
Background and Objectives. A new two-step hysteroscopic myomectomy carried out in the office setting and without anesthesia was feasible for the excision of submucous myomas. The objective of this study was to assess whether removal of submucous myomas from the uterine cavity after hysteroscopic laser enucleation is necessary. Methods. Between June 2009 and April 2013, all outpatients with symptomatic myomatosis (bleeding, pelvic pain, and infertility) assessed ultrasonographically were eligible to participate in a prospective study. All patients underwent office hysteroscopic enucleation of submucous myomas. Enucleated myomas were left in the uterine cavity. Neither anesthesia nor antibiotic prophylaxis was used. Results. Sixty-one women (mean age: 47.3 years) were included. Regardless of hysteroscopic localization and grading, all myomas were enucleated. The mean (standard deviation, SD) diameter of the myoma as measured by the ultrasound scan was 22.6 (8.5) mm. In 29 cases (47.5%), the diameter of the resected myoma was >20 mm and in 10 cases (16.4%) >30 mm. After a mean follow-up of 68.2 (16.5) days, none of the patients showed a residual myoma inside the uterine cavity. Conclusions. The present results indicate that leaving laser-enucleated submucous myoma in the uterine cavity is a feasible and safe therapeutic option.
doi:10.1155/2015/905204
PMCID: PMC4450281  PMID: 26090457
15.  Physical activity and maternal-fetal circulation measured by Doppler ultrasound 
Objective
To examine the association of physical activity on maternal-fetal circulation measured by uterine and umbilical artery Doppler flow velocimetry waveforms.
Study Design
Participants included 781 pregnant women with Doppler ultrasounds of the uterine and umbilical artery and who self-reported past week physical activity. Linear and generalized estimating equation regression models were used to examine these associations.
Results
Moderate-to-vigorous total and recreational activity were associated with higher uterine artery pulsatility index (PI) and an increased risk of uterine artery notching as compared to reporting no total or recreational physical activity, respectively. Moderate-to-vigorous work activity was associated with lower uterine artery PI and a reduced risk of uterine artery notching as compared to no work activity. No associations were identified with the umbilical circulation measured by the resistance index.
Conclusion
In this epidemiologic study, recreational and work activity were associated with opposite effects on uterine artery PI and uterine artery notching, though associations were modest in magnitude.
doi:10.1038/jp.2012.68
PMCID: PMC3459289  PMID: 22678142
work; recreational activity; maternal-fetal blood flow; pregnancy; Doppler flow velocimetry waveforms; preeclampsia
16.  The safety of cesarean myomectomy in women with large myomas 
Obstetrics & Gynecology Science  2014;57(5):367-372.
Objective
To evaluate the safety of cesarean myomectomy in large myomas sized >5 cm.
Methods
One hundred sixty-five pregnant women with myomas who delivered via cesarean section were identified. Ninety-six women had cesarean section without myomectomy, and 65 women underwent cesarean myomectomy. We compared the maternal characteristics, neonatal weight, myoma types, and operative outcomes between two groups. We further analyzed cesarean myomectomy group according to myoma size. The large myoma was defined as myoma >5 cm in size. The maternal characteristics, neonatal weight, and myoma types were compared between two groups. We also compared the operative outcomes such as preoperative and postoperative hemoglobin, operative time, and hospitalized days between two groups.
Results
There were no significant differences in the maternal characteristics, myoma types, neonatal weight and operative outcomes between cesarean section without myomectomy and cesarean myomectomy. The subgroup analysis according to myoma size (>5 cm or not) in cesarean myomectomy group revealed that there were no significant differences in the mean hemoglobin change (1.2 vs. 1.3 mg/dL, P=0.6), operative time (90.5 vs. 93.1 minutes, P=0.46), and the length of hospital stay (4.7 vs. 5.2 days, P=0.15) between two groups. The comparison of maternal characteristics, neonatal weight, and myoma types between two groups also showed no statistical significance.
Conclusion
Cesarean myomectomy in patients with large myomas is a safe and effective procedure.
doi:10.5468/ogs.2014.57.5.367
PMCID: PMC4175596  PMID: 25264526
Cesarean myomectomy; Large myoma; Safety
17.  Laparoscopic Myomectomy for Very Large Myomas Using an Isobaric (Gasless) Technique 
Objectives:
Laparoscopic myomectomy using pneumoperitoneum for large myomas (≥8 cm) is hindered by several factors, such as the increased operative time, the risk of perioperative bleeding, and the risk of conversion to laparotomy. With the introduction of isobaric laparoscopy using abdominal wall lifting, this procedure can be performed using conventional surgical instruments introduced through small abdominal incisions. The aim of this study was to evaluate the feasibility, reproducibility, and safety of isobaric laparoscopic myomectomy for very large myomas ≥10 cm using a subcutaneous abdominal wall-lifting device.
Methods:
A series of 24 consecutive patients with at least 1 symptomatic myoma ≥10 cm underwent a gasless laparoscopic myomectomy with the Laparotenser device. Conventional long laparotomy instruments were used.
Results:
Gasless laparoscopic myomectomy was successful in all 24 consecutive patients. The size of the dominant myoma varied from 10 cm to 20 cm. The median operating time was 93 minutes. The median postoperative drop in hemoglobin was 2.8 g/dL. No surgical complications occurred. The median hospital stay was 2.8 days.
Conclusion:
Gasless laparoscopic myomectomy is feasible, reproducible, and safe for removing very large myomas. Therefore, it can represent an excellent option for the minimally invasive removal of very large myomas.
PMCID: PMC3015631  PMID: 16381362
Very large myomas; Isobaric gasless laparoscopy; Myomectomy; Subcutaneous abdominal wall lifting device
18.  The Indications, Surgical Techniques, and Limitations of Laparoscopic Myomectomy 
Objective:
To assess the indications and limits of laparoscopic myomectomies (LM).
Methods:
We conducted a retrospective analysis of 89 consecutive cases of LM. Our LM procedures were as follows: Diluted vasopressin was injected into the myoma capsule, and a transverse incision was made by fine monopolar electrode. Traction was applied to the myoma with a myoma screw. The uterine wall was sutured with a curved needle. Fibrin glue spray was applied to prevent adhesion formation. Enucleated myomas were removed via trocar by using an electric morcellator.
Results:
We enucleated 195 nodules with diameters > 2 cm; the mean size of the dominant myomas was 5.3 cm. The mean number of myomas removed from each patient was 2. The uterine wall was sutured in all cases with a mean of 9 sutures. The mean blood loss was 102 mL, and the mean operating time was 111 minutes. No patients were converted to laparotomy. The average hospital stay was 2.4 days. When the myomas were larger than 10 cm, the blood loss and operating time were increased. However, the number of myomas did not correlate with blood loss.
Conclusion:
LM appears to offer a number of advantages if the myoma is not larger than 10 cm.
PMCID: PMC3015481  PMID: 12856836
Laparoscopic myomectomy; Surgical technique; Indication; Limitation
19.  Submucosal uterine leiomyomas have a global effect on molecular determinants of endometrial receptivity 
Fertility and sterility  2008;93(6):2027-2034.
Study objective
To evaluate the effect of uterine leiomyomas on the endometrium using molecular markers of endometrial receptivity: HOXA10, HOXA11, LIF, and BTEB1.
Design
Case-control study
Setting
University medical center
Patients
Thirty reproductive-age women with submucosal, intramural, or no uterine myomas who underwent hysteroscopy or hysterectomy.
Interventions
Proliferative phase endometrial sampling was performed at the time of surgery. In uteri with a submucosal myoma, directed endometrial biopsies were obtained over the myoma and over normal myometrium.
Main outcome measures
Endometrial HOXA10 expression was evaluated as a primary end point using quantitative real time RT-PCR and immunohistochemistry. HOXA11, BTEB1, and LIF were evaluated using real time RT-PCR.
Results
Endometrial HOXA10 and HOXA11 mRNA expression were significantly decreased in uteri with submucosal myomas compared to controls and to uteri with intramural myomas. A similar trend was seen in BTEB1 mRNA expression, however no difference was found in LIF mRNA expression. Immunohistochemistry localized the decrease in endometrial HOXA10 protein expression to stroma. In the presence of a submucosal myoma, there were no regional differences in gene expression.
Conclusions
The molecular mechanism by which submucosal myomas adversely affect reproduction includes a global decrease in endometrial HOX gene expression, not simply a focal change over the myoma. This may explain the reproductive dysfunction observed with submucosal myomas.
doi:10.1016/j.fertnstert.2008.03.029
PMCID: PMC3107853  PMID: 18555231
leiomyoma; fibroid; submucosal myoma; endometrium; endometrial receptivity; HOXA10
20.  Innervation in women with uterine myoma and adenomyosis 
Obstetrics & Gynecology Science  2015;58(2):150-156.
Objective
To determine if neurofilament (NF) is expressed in the endometrium and the lesions of myomas and adenomyosis, and to determine their correlation.
Methods
Histologic sections were prepared from hysterectomies performed on women with adenomyosis (n=21), uterine myoma (n=31), and carcinoma in situ of the uterine cervix. Full-thickness uterine paraffin blocks, which included the endometrium and myometrium histologic sections, were stained immunohistochemically using the antibodies for monoclonal mouse antihuman NF protein.
Results
NF-positive cells were found in the endometrium and myometrium in 11 women with myoma and in 7 with adenomyosis, but not in patients with carcinoma in situ of uterine cervix, although the difference was statistically not significant. There was no significant difference between the existence of NF-positive cells and menstrual pain or phases. The NF-positive nerve fibers were in direct contact with the lesions in nine cases (29.0%) of myoma and in five cases (23.8%) of adenomyosis. It was analyzed if there was a statistical significance between the existence of NF positive cells in the endometrium and the expression of NF-positive cells in the uterine myoma/adenomyosis lesions. When NF-positive cell were detected in the myoma lesions, the incidence of NF-positive nerve cells in the eutopic endometrium was significantly high. When NF-positive cell were detected in the basal layer, the incidence of NF-positive nerve cells in the myoma lesions and adenomyosis lesions was significantly high.
Conclusion
We assume that NF-positive cells in the endometrium and the myoma and adenomyosis lesions might play a role in pathogenesis. Therefore, more studies may be needed on the mechanisms of nerve fiber growth in estrogen-dependent diseases.
doi:10.5468/ogs.2015.58.2.150
PMCID: PMC4366868  PMID: 25798429
Adenomyosis; Endometrium; Myoma; Nerve fibers; Neurofilament
21.  Sonohysterographic Predictors of Successful Hysteroscopic Myomectomies 
Background and Objectives:
The purpose of this study is to assess the rate of persistent submucosal myomas and intrauterine scarring after hysteroscopic myomectomy, as well as to evaluate the preoperative and intraoperative sonohysterographic findings that will predict persistence of myomas, scarring, and the need for repeat surgery.
Methods:
Charts from all hysteroscopic myomectomies performed by a single surgeon between 2003 and 2011 were reviewed for preoperative, intraoperative, and postoperative sonohysterographic findings. Predictors included myoma number, diameter and percent extension into the cavity of the largest fibroid, and percent surgically resected. These predictors were assessed with postoperative sonohysterography. Statistics included t test, logistic regression, χ2 test, and Fisher exact test.
Results:
Among the 79 cases with postoperative sonohysterograms, 17 (21.5%) had persistent submucosal myoma, and 9 (11.4%) had intrauterine scarring on postoperative sonohysterogram. Repeat hysteroscopic myomectomy was required in 11 (13.9%), but none required lysis of adhesions. The myoma number was not a significant predictor. A higher percentage of myoma within the cavity (63.35% vs 44.89%, P < .05) and smaller myoma size (2.22 cm vs 3.31 cm, P < .01) were significant predictors of a complete resection, a normal postoperative sonohysterogram, and avoidance of repeat surgery. On regression analysis, the percent of the myoma resected was the most significant outcome predictor (P < .001).
Conclusion:
Larger myomas with a lower percent found within the uterine cavity are less likely to be completely resected. Percent resection at the time of surgery is the most significant predictor of a normal postoperative sonohysterogram, as well as the best predictor of the need for repeat surgery.
doi:10.4293/JSLS.2014.00105
PMCID: PMC4379864  PMID: 25848194
Hysteroscopic myomectomy; Submucosal fibroid; Sonohysterography
22.  Ductus Venosus Doppler Flow Velocity after Transplacental and Non-transplacental Amniocentesis during Midtrimester 
Objective: We aimed to evaluate ductus venosus Doppler waveforms before and after amniocentesis in order to investigate any effect of amniocentesis on fetal myocardial hemodynamics. We also evaluated the umbilical artery, uterine artery and fetal mid-cerebral artery Doppler waveforms in order to investigate any relationship with ductus venosus Doppler changes.
Methods: The study population consisted of 56 singleton pregnancies having genetic amniocentesis. Twenty seven of them had transplacental needle insertion; whereas 29 of them had non-transplacental amniocentesis. Uterine artery, umbilical artery, mid-cerebral artery and ductus venosus pulsatiliy index and resistance index were measured just before and after amniocentesis.
Results: Amniocentesis does not cause any significant changes in fetal ductus venosus Doppler waveforms. There is also no significant changes in uterine artery, umbilical artery, mid-cerebral artery pulsatility and resistance index.
Conclusion: Amniocentesis-whether transplacental or not- does not cause any significant effect on fetal myocardial hemodynamics.
doi:10.12669/pjms.305.5065
PMCID: PMC4163219  PMID: 25225513
Ductus venosus Doppler; Amniocentesis; Mid-cerebral artery Doppler; Uterine artery Doppler; Umbilical artery Doppler
23.  First-Trimester Uterine Artery Doppler Analysis in the Prediction of Later Pregnancy Complications 
Disease Markers  2015;2015:679730.
Uterine artery Doppler waveform analysis has been extensively studied in the second trimester of pregnancy as a predictive marker for the later development of preeclampsia and fetal growth restriction. The use of Doppler interrogation of this vessel in the first trimester has gained momentum in recent years. Various measurement techniques and impedance indices have been used to evaluate the relationship between uterine artery Doppler velocimetry and adverse pregnancy outcomes. Overall, first-trimester Doppler interrogation of the uterine artery performs better in the prediction of early-onset than late-onset preeclampsia. As an isolated marker of future disease, its sensitivity in predicting preeclampsia and fetal growth restriction in low risk pregnant women is moderate, at 40–70%. Multiparametric predictive models, combining first-trimester uterine artery pulsatility index with maternal characteristics and biochemical markers, can achieve a detection rate for early-onset preeclampsia of over 90%. The ideal combination of these tests and validation of them in various patient populations will be the focus of future research.
doi:10.1155/2015/679730
PMCID: PMC4418013  PMID: 25972623
24.  Multiple Layer Closure of Myoma Bed in Laparoscopic Myomectomy 
Objective:
To assess the feasibility and outcome of laparoscopic myomectomy and multiple layer closure of the myoma bed, for management of myomas, at a tertiary care hospital.
Materials and Methods:
From September 2005 to September 2010, 417 patients, with large and moderate size myomas, were managed by laparoscopic myomectomy. Indications were subfertility, menorrhagia, and abdominal mass. Preoperative evaluation included history, clinical examination, and sonographic mapping. The myomas were enucleated and retrieved laparoscopically. Myoma beds were sutured in multiple layers by endoscopic intracorporeal suturing.
Results:
Three hundred and fifteen patients presented with subfertility, 45 with menorrhagia, and 57 with abdominal mass. The average maximum diameter of a myoma was 9 cm. The mean duration of surgery was 120 minutes. The mean postoperative stay was 24 hours. No intraoperative complication occurred and the hospital course was uncomplicated. In one case, a minilap incision was performed for retrieval of the myoma with suturing of the bed. Two patients had minor delayed wound healing of the morcellator port site. The patients did not report any complaints during the follow-up, except one patient who developed omental hernia at the morcellator port site. There was no rupture of the scar and very low adhesion scores in the subsequent cesarean sections or second-look scopies.
Conclusion:
With proper multilayer closure of the myoma bed, laparoscopic myomectomy was feasible for moderate and even large myomas and had excellent outcomes.
doi:10.4103/0974-1216.85281
PMCID: PMC3304293  PMID: 22442535
Better reproductive outcome; laparoscopic myomectomy; large myomas; multilayer closure
25.  Multiple Layer Closure of Myoma Bed in Laparoscopic Myomectomy 
Objective:
To assess the feasibility and outcome of laparoscopic Myomectomy and multiple layer closure of myoma bed for management of myomas at a tertiary care hospital.
Materials and Methods:
Four hundred and seventeen patients from September 2005 to September 2010 with large and moderate size myomas were managed by laparoscopic Myomectomy. Indications were subfertility, menorrhagia and abdominal mass. Pre-operative evaluation included history, clinical examination and sonographic mapping. Myomas were enucleated and retrieved laparoscopically. Myoma beds were sutured in multiple layers by endoscopic intracorporeal suturing.
Results:
Three hundred and fifteen patients presented with subfertility, 45 with menorrhagia and 57 with abdominal mass. The average maximum diameter of myoma was 9 cm. The mean duration of surgery was 120 min. The mean post-operative stay was 24 h. No intra-operative complication occurred and hospital course was uncomplicated. In one case, minilap incision was given for retrieval of myoma and suturing of the bed. Two patients had minor delayed wound healing of the morcellator port site. The patients did not report any complaints during follow-up except one patient who developed omental hernia at morcellator port site. There was no rupture of scar and very low adhesion scores in subsequent caesarian sections or second look scopies.
Conclusion:
With proper multilayer closure of the myoma bed, laparoscopic Myomectomy is feasible for moderate and even large myomas and has excellent outcomes.
doi:10.4103/0974-1216.114079
PMCID: PMC4453202  PMID: 26085750
Better reproductive outcome; laparoscopic myomectomy; large myomas; multilayer closure

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