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1.  Nonlinear analysis of biomagnetic signals recorded from uterine myomas 
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.
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).
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.
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.
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.
PMCID: PMC2855967  PMID: 19222760
electrogastrography; gastric slow wave; magnetogastrography; SQUID magnetometer
3.  Developments in Techniques for Laparoscopic Myomectomy 
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).
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.
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:
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
4.  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.
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.
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
5.  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.
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.
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.
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.
PMCID: PMC3150177  PMID: 21845062
myoma; uterine leiomyoma; DMPA; medroxyprogesterone; menstrual cycle; menstrual; depo-provera
6.  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)
7.  Multiple Layer Closure of Myoma Bed in Laparoscopic Myomectomy 
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.
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.
With proper multilayer closure of the myoma bed, laparoscopic myomectomy was feasible for moderate and even large myomas and had excellent outcomes.
PMCID: PMC3304293  PMID: 22442535
Better reproductive outcome; laparoscopic myomectomy; large myomas; multilayer closure
8.  Total Laparoscopic Hysterectomy for Large Uterus 
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.
Retrospective review (Canadian Task Force Classification II-1)
Dedicated high volume Gynecological laparoscopy centre.
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.
TLH and modifications of performing the surgery by ligating the uterine arteries prior, myomectomy followed by hysterectomy, direct morcellation after uterine artery ligation.
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).
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.
PMCID: PMC3304266  PMID: 22442509
Large uterus; multiple fibroids; total laparoscopic hysterectomy
9.  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.
PMCID: PMC3163653  PMID: 21892334
myomectomy; uterine artery embolization; pelvic tumor; hysterectomy; GnRH; leiomyoma
10.  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.
PMCID: PMC2594713  PMID: 16353656
11.  Combining Myoma Coagulation with Endometrial Ablation/Resection Reduces Subsequent Surgery Rates 
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.
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.
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).
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
12.  Physical activity and maternal-fetal circulation measured by Doppler ultrasound 
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.
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.
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.
PMCID: PMC3459289  PMID: 22678142
work; recreational activity; maternal-fetal blood flow; pregnancy; Doppler flow velocimetry waveforms; preeclampsia
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.
PMCID: PMC3917117  PMID: 24516352
Leiomyoma; Drug therapy; Gonadotropin-releasing hormone agonist; Raloxifene; Mifepristone
14.  Association between maternal anxiety in pregnancy and increased uterine artery resistance index: cohort based study 
BMJ : British Medical Journal  1999;318(7177):153-157.
To investigate whether maternal anxiety in the third trimester is associated with an increased uterine artery resistance index.
Cohort based study.
100 pregnant women, with a mean gestation of 32 weeks.
Outcome measures
Self rating Spielberger questionnaire for state anxiety and trait anxiety, and uterine blood flow waveform patterns as assessed by colour Doppler ultrasound.
A significant association was found between uterine artery resistance index and scores for both Spielberger state anxiety and trait anxiety (rs=0.31, P<0.002 and 0.28 P<0.005 respectively). Women with state anxiety scores >40 (n=15) had a higher mean uterine resistance index than those with scores ⩽40 (mean difference with mean resistance index 24%, 95% confidence interval 12% to 38%; P<0.0001). Similarly, women with trait anxiety scores >40 (n=32) had a higher mean resistance index than those with scores ⩽40, although to a lesser extent. The presence of notches in the waveform pattern produced by uterine artery blood flow was found in 4/15 (27%) women with high state anxiety scores compared with 4/85 (5%) with low anxiety scores (P<0.02).
This study shows an association between maternal anxiety in pregnancy and increased uterine artery resistance index. It suggests a mechanism by which the psychological state of the mother may affect fetal development, and may explain epidemiological associations between maternal anxiety and low birth weight. The influence of maternal anxiety may be one mechanism by which the intrauterine environment contributes to later disease in offspring.
Key messagesWomen who were anxious during pregnancy had significantly abnormal patterns of blood flow through the uterine arteriesOf the most anxious group, 27% had an increased resistance index of clinical concern, compared with 4% in the less anxious groupThe study did not establish whether the impaired blood flow was predominantly linked with state anxiety or trait anxietyThe findings may help to explain previous studies that have linked stress or anxiety in pregnancy with small for gestational age babies
PMCID: PMC27690  PMID: 9888905
15.  The safety of cesarean myomectomy in women with large myomas 
Obstetrics & Gynecology Science  2014;57(5):367-372.
To evaluate the safety of cesarean myomectomy in large myomas sized >5 cm.
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.
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.
Cesarean myomectomy in patients with large myomas is a safe and effective procedure.
PMCID: PMC4175596  PMID: 25264526
Cesarean myomectomy; Large myoma; Safety
16.  Laparoscopic Myomectomy for Very Large Myomas Using an Isobaric (Gasless) Technique 
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.
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.
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.
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
17.  Use of uterine artery Doppler ultrasonography to predict pre-eclampsia and intrauterine growth restriction: a systematic review and bivariable meta-analysis 
Alterations in waveforms in the uterine artery are associated with the development of pre-eclampsia and intrauterine growth restriction. We investigated the predictive accuracy of all uterine artery Doppler indices for both conditions in the first and second trimesters.
We identified relevant studies through searches of MEDLINE, EMBASE, the Cochrane Library and Medion databases (all records to April 2006) and by checking bibliographies of identified studies and consulting with experts. Four of us independently selected studies, extracted data and assessed study validity. We performed a bivariable meta-analysis of sensitivity and specificity and calculated likelihood ratios.
We identified 74 studies of pre-eclampsia (total 79 547 patients) and 61 studies of intrauterine growth restriction (total 41 131 patients). Uterine artery Doppler ultrasonography provided a more accurate prediction when performed in the second trimester than in the first-trimester. Most Doppler indices had poor predictive characteristics, but this varied with patient risk and outcome severity. An increased pulsatility index with notching was the best predictor of pre-eclampsia (positive likelihood ratio 21.0 among high-risk patients and 7.5 among low-risk patients). It was also the best predictor of overall (positive likelihood ratio 9.1) and severe (positive likelihood ratio 14.6) intrauterine growth restriction among low-risk patients.
Abnormal uterine artery waveforms are a better predictor of pre-eclampsia than of intrauterine growth restriction. A pulsatility index, alone or combined with notching, is the most predictive Doppler index. These indices should be used in clinical practice. Future research should also concentrate on combining uterine artery Doppler ultrasonography with other tests.
PMCID: PMC2263112  PMID: 18332385
18.  The Indications, Surgical Techniques, and Limitations of Laparoscopic Myomectomy 
To assess the indications and limits of laparoscopic myomectomies (LM).
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.
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.
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.
Case-control study
University medical center
Thirty reproductive-age women with submucosal, intramural, or no uterine myomas who underwent hysteroscopy or hysterectomy.
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.
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.
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.
PMCID: PMC3107853  PMID: 18555231
leiomyoma; fibroid; submucosal myoma; endometrium; endometrial receptivity; HOXA10
20.  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.
PMCID: PMC4163219  PMID: 25225513
Ductus venosus Doppler; Amniocentesis; Mid-cerebral artery Doppler; Uterine artery Doppler; Umbilical artery Doppler
21.  Effects of Menopausal Hormone Therapy on Uterine Myoma in Menopausal Women 
Journal of Menopausal Medicine  2013;19(3):123-129.
The aim of the present study is to evaluate the long term effects of estrogen-progestogen therapy (EPT) on uterine myomas volume in postmenopausal women.
We performed a retrospective analysis on postmenopausal women with asymptomatic uterine myoma during the period between April, 2008 and September, 2012. Postmenopause was defined as amenorrhea for longer than a year or serum follicle stimulating hormone levels higher than 40 IU/L. The volume of the myoma was assessed by transvaginal ultrasonography for every 6 months after administration of EPT.
Thirty-eight women were included in the study, with 32 in the EPT group and 6 in the control group. Overall, uterine myoma volume (mean ± standard deviation, cm3) in the EPT group was 19.5 ± 24.6 at baseline, and those at 6 and 12 months were 24.7 ± 35.1 and 28.5 ± 56.4, respectively. Myoma volume did not change significantly with EPT, and these changes were not significantly different from the control group. Myoma volume changes were not significantly different in the subgroups according to the route of estrogen administrations and the method of progestogen administrations. Clinically significant volume increases during one year of EPT was noted in 28.1% (9/32), however, only one showed transient increases.
Our results suggest that treating postmenopausal woman with EPT on a long-term basis does not increase the volume of uterine myomas.
PMCID: PMC4217555  PMID: 25371877
Estrogens; Myoma; Postmenopause; Progesterone; Uterus
22.  Uterine artery embolization immediately preceding laparoscopic myomectomy 
To determine whether performing uterine artery embolization (UAE) immediately before laparoscopic myomectomy can facilitate a minimally invasive surgical approach for larger uterine fibroids.
In a retrospective case–control study, laparoscopic myomectomy with and without preoperative UAE was examined. Data were analyzed from 26 laparoscopic myomectomies performed by a single surgeon at Northwestern University Feinberg School of Medicine between 2004 and 2010. Controls were matched for age, calendar year, surgeon, and number of fibroids removed. Surgical outcomes included preoperative clinical uterine size, operative time, operative blood loss, and postoperative myoma specimen weight. Data were analyzed via 2-tailed Student t test.
Twelve women underwent laparoscopic myomectomy within 169±16 minutes (mean±SEM) of preoperative UAE. Fourteen control patients underwent laparoscopic myomectomy alone. The UAE group had a greater mean preoperative clinical uterine size (19.7 versus 12.4 weeks, P<0.001) and a greater mean myoma specimen weight measured postoperatively (595.3 versus 153.6 grams, P<0.05). There were no significant differences in operative time or blood loss, and there were no intra-operative complications.
UAE performed immediately before laparoscopic myomectomy facilitated minimally invasive surgery for larger uteri and larger uterine myomas, with no differences in operative time or blood loss.
PMCID: PMC4034570  PMID: 22098788
Laparoscopy; Uterine artery embolization; Uterine leiomyomata
23.  Diagnostic evaluation of uterine artery Doppler sonography for the prediction of adverse pregnancy outcomes 
Increased impedance to flow in the uterine arteries assessed by value of the Doppler is associated with adverse pregnancy outcomes, especially pre-eclampsia. We investigated the predictive value of a uterine artery Doppler in the identification of adverse pregnancy outcomes such as ‘pre-eclampsia’ and ‘small fetus for gestational age’ (SGA).
Materials and Methods:
Three hundred and seventy-nine women, with singleton pregnancy, between 18 and 40 years of age, without risk factors, randomly underwent Doppler interrogation of the uterine arteries, between 16-22 weeks of gestation. Those who had a mean pulsatility index (PI) of >1.45 were considered to have an abnormal result, and were evaluated and compared with those who had normal results for adverse pregnancy outcomes, including pre-eclampsia and small for gestational age. The relationship between the variables was assessed with the use of the chi-square test.
There were 17 cases (4.5%) of abnormal uterine artery Doppler results and 15 of them (88.2%) developed pre-eclampsia and four cases (23.5%) had neonates small for gestational age. For predicting pre-eclampsia, the mean uterine artery PI had to be >1.45, had to have a specificity of 95.5% (95% CI, 70-92%), a sensitivity of 79% (95% CI, 43-82%), a negative predictive value (NPV) of 98.9% (95% CI, 72-96%), and a positive predictive value (PPV) of 88.2% (95% CI, 68-98%). In the case of ‘small for gestational age’ it had to have a specificity of 96.5% (95% CI, 42-68%), a sensitivity of 57% (95% CI, 53-76%), an NPV of 99.2% (95% CI, 70-92%), and a PPV of 23.5% (95% CI, 30-72%).
Uterine artery Doppler evaluation at 16-22 weeks of gestation might be an appropriate tool for identifying pregnancies that may be at an increased risk for development of pre-eclampsia and small fetus for gestational age.
PMCID: PMC4155705  PMID: 25197292
Adverse pregnancy outcome; pre-eclampsia; uterine artery Doppler
24.  Biomagnetic techniques for evaluating gastric emptying, peristaltic contraction and transit time 
Biomagnetic techniques were used to measure motility in various parts of the gastrointestinal (GI) tract, particularly a new technique for detecting magnetic markers and tracers. A coil was used to enhance the signal from a magnetic tracer in the GI tract and the signal was detected using a fluxgate magnetometer or a magnetoresistor in an unshielded room. Estimates of esophageal transit time were affected by the position of the subject. The reproducibility of estimates derived using the new biomagnetic technique was greater than 85% and it yielded estimates similar to those obtained using scintigraphy. This technique is suitable for studying the effect of emotional state on GI physiology and for measuring GI transit time. The biomagnetic technique can be used to evaluate digesta transit time in the esophagus, stomach and colon, peristaltic frequency and gastric emptying and is easy to use in the hospital setting.
PMCID: PMC3196621  PMID: 22025978
Biomagnetic techniques; Magnetogastrography; Gastric emptying; Scintigraphy; Peristaltic contractions
25.  Factors Influencing Endometrial Thickness in Postmenopausal Women 
Cut-off values for endometrial thickness (ET) in asymptomatic postmenopausal woman have been standardized. However, there are no comprehensive studies to document how various factors can influence the ET after the age of menopause.
To study the various factors influencing the ET in postmenopausal women.
Subjects and Methods:
This was a prospective observational study. A total of 110 postmenopausal women underwent detailed history taking, clinical examination, and transvaginal scan for uterine volume and ovarian volume. The volumes were calculated by using ellipsoid formula: Width × thickness × height × 0.523. The variation in ET with respect to the influencing factors such as age, duration of menopause, parity, body mass index (BMI), medical illness like diabetes/hypertension, drugs like tamoxifen, presence of myoma, uterine volume, ovarian volume, and serum estradiol (in selected patients) were measured. Descriptive analysis was performed using SPSS software (version 16, Chicago II, USA) to obtain mean, standard deviation (SD), 95% confidence intervals (CIs) and inter quartile ranges. Comparison of means was carried out using analysis of variance.
The mean (SD) age of the patients was 55.4 (6.91) years (95% CI, 54.1, 56.7). The mean (SD) age at menopause was 47.95 (3.90) years (95% CI, 47.2, 48.7) and the mean (SD) duration of menopause was 7.27 (6.65) years (95% CI, 6.01, 8.53). The mean (SD) ET was 3.8 (2.3) mm (95% CI, 3.36, 4.23). Medical illness like diabetes and hypertension did not alter the ET. ET increased as BMI increased and it was statistically significant. The presence of myoma increased uterine volume significantly and was associated with thick endometrial stripe. Similarly, whenever the ovaries were visualized and as the ovarian volume increased, there was an increase in ET. When ET was > 4 mm (n = 37), they were offered endocel, of which 16 agreed to undergo the procedure. None were found to have endometrial cancer.
This study suggests that parity, BMI, presence of myoma, tamoxifen usage, uterine volume, ovarian volume and serum estradiol influence the ET in postmenopausal women.
PMCID: PMC4160690  PMID: 25221714
Diabetes; Endometrial thickness; Hypertension; Ovarian and uterine volume; Postmenopause

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