After Fibroids Surgery Open Mymectomy They Grow Again

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Open Access

Peer-reviewed

Research Article

Reoperation rates for recurrence of fibroids after abdominal myomectomy in women with large uterus

• Katherine J. Kramer,
• Sarah Ottum,
• Damla Gonullu,
• Capricia Bell,
• Hanna Ozbeki,
• Jay Thou. Berman,
• Maurice-Andre Recanati

x

• Published: December nine, 2021
• https://doi.org/10.1371/journal.pone.0261085

Figures

Abstract

Background

The population of women undergoing abdominal myomectomy for symptomatic large coarse uterus is unique. Nosotros seek to narrate the timing, risk factors too as the presenting symptoms which led patients to undergo repeat surgery in this patient population.

Methods and findings

We followed 592 patients who underwent an abdominal myomectomy from March 1998 to June 2010 at St. Vincent'southward Catholic Medical Heart and presented later during the study period with a recurrence of symptoms attributable to a reemergence of fibroids and who chose to undergo repeat surgical management. Twelve percent of patients exhibited symptoms of fibroid uterus which led to reoperation within the study period. The hateful age at repeat surgery was 44.1 ± 0.vi years sometime (n = 69) and the mean time betwixt operations was vii.9 ± 0.3 years. Presentation was variable merely included bleeding, pain and infertility. Patients presented for surgery with a significantly smaller sized uterus than at their initial surgery. Timing betwixt surgeries correlated with age at initial surgery and uterine size but race, number of fibroids, amass weight of fibroids removed, operative time or blood loss at the initial surgery did non correlate. Data is suggestive that intraperitoneal triamcinolone may reduce reoperation rates but non timing of recurrence.

Conclusion

These results may assistance in counseling patients, especially younger women, on the risks of coarse recurrence necessitating echo surgery. Farther inquiry is necessary to assess if triamcinolone can change fibroid reurrence in patients who undergo uterus sparing procedures.

Commendation: Kramer KJ, Ottum S, Gonullu D, Bell C, Ozbeki H, Berman JM, et al. (2021) Reoperation rates for recurrence of fibroids after abdominal myomectomy in women with large uterus. PLoS 1 sixteen(12): e0261085. https://doi.org/x.1371/periodical.pone.0261085

Editor: Robert Jeenchen Chen, Ohio State University Wexner Medical Center Department of Surgery, Usa

Received: July 25, 2021; Accustomed: November 23, 2021; Published: Dec 9, 2021

Copyright: © 2021 Kramer et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted utilise, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are inside the manuscript and its S1 File files.

Funding: This research was supported under NIH-Women'due south Reproductive Wellness Research Career Development Award (Thou-12HD001254). The funders had no role in study design, data collection and assay, decision to publish, or preparation of the manuscript.

Competing interests: The authors declare no conflict of interest.

1. Introduction

Uterine fibroids, or leiomyomas, are the most mutual benign tumors in premenopausal women. They are normally discovered incidentally by imaging in asymptomatic women, simply twenty%-50% of women develop symptoms such as abnormal uterine bleeding, pelvic pressure level, pain or urinary or bowel complaints [1]. Some chance factors for the formation of these benign tumors include: Black race, historic period, family unit history, premenopausal country and hypertension, while use of hormonal contraception, smoking in depression BMI women and low parity are protective [2]. Black women have the highest lifetime risk of having fibroids and suffer from more severe symptoms, which interfere with daily functioning [3].

Not-surgical handling of uterine fibroids include expectant management [4] and medical therapy, which include estrogen-progestin contraceptives, progestins [v, 6], levonorgesterel releasing intrauterine devices [7] and implants, progesterone receptor modulators [8] such as ulipristal acetate [9], mifepristone [10], and GnRH agonists [11], aromatase inhibitors [12] and selective estrogen receptor modulators such every bit raloxifene [xiii]. These approaches may provide symptom relief, peculiarly in situations where bleeding is the primary complaint. Although well-nigh three quarters of women study brusk-term improvement over the start yr of treatment, long-term failure rates are high [14], and about 50% volition have surgery within 24 months [fifteen]. The surgical approach is the main treatment of fibroids, peculiarly in cases where majority-symptoms are the dominant issue or if infertility is attributable to the presence of myomas. Hysterectomy also as modern surgical approaches such equally uterine artery embolization, radio frequency ablation and magnetic resonance-guided focused ultrasound can provide a cure for symptoms. Myomectomy, which may exist performed laparoscopically or hysteroscopically, is recommended for women, who wish to maintain fertility. With any uterine conserving approach, still, the risk of fibroid recurrence remains.

Around xv–33% of fibroids recur afterwards myomectomy, and around ten%-21% of women undergo a hysterectomy within five to 10 years [xvi, 17]. Published rates and time to recurrence vary widely and include 12–xv%, 31–43%, 51–62%, and 84% at 1, 3, 5, and 8 years respectively [18–22]. In this written report, nosotros focus on a group of 64 women, who were admitted for uterine surgery after having previously undergone an open myomectomy for a big symptomatic fibroid uterus with a mean size equivalent to 20.9 ±0.5 weeks gestation (range: 12–30 week-size). While the recurrence rates published in the literature address recurrence of fibroids in general [23] or the rates of reoperation following myomectomy [17], our report specifically addresses reoperation rates in patients, who have undergone myomectomy using an open approach for an initial diagnosis of big symptomatic fibroid uterus. The electric current literature also does not typically address the reasons underlying the demand for echo surgery. We seek to characterize the timing, gamble factors as well as the presenting symptoms which led patients to undergo echo surgery in this patient population.

ii. Materials and methods

ii.i Patient selection

Admissions for uterine surgery later previous myomectomy from March ane, 1998 to June 2010 were identified past the St. Vincent's Catholic Medical Centre Manhattan medical records function and through role charts under IRB approval (#0104191MX). A subset of this deidentified dataset was previously queried for a separate unrelated report evaluating postoperative adhesions. Tabulated fields included, information from the initial surgery (age, uterine size, number and aggregate weight of fibroids removed, surgical time and estimated claret loss and initial surgeon name). Uterus size was determined clinically via bimanual test performed past the attending surgeon and described in menstrual weeks as with the gravid uterus besides as by abdominal and transvaginal ultrasound. All women were continuously enrolled and followed during the report period (range: 1 to 12 years). Fields from the office visit when the surgeon evaluated the patient with new complaints included: symptoms, alternate treatments received thus far as well as uterine size. Patients were evaluated preoperatively with pelvic exam, transvaginal ultrasound, endometrial biopsy, liquid-based cervical smear, complete blood count, type and screen, coagulation studies, thyroid role tests, follicular stimulating hormone and serum human chorionic gonadotropin (hCG). Nautical chart review documented that patients were accordingly counselled on alternative approaches including watchful waiting, medical management and minimally invasive surgical approaches including repeat myomectomy and hysterectomy. Data nerveless from the electronic hospital chart at reoperation included age, uterine size, surgical complications and proper noun of surgeon performing the procedure. Total number of myomectomies performed besides as total number which involved the instillation of the intraperitoneal steroid triamcinolone, during a previous study at the establishment, were obtained from medical records.

2.2 Surgical methods

We recorded, from the operative note, if any anti-adhesive methods were employed at all at the initial surgery or if the patient received no such treatment. This conclusion is left to the surgeon at our institution. Such methods potentially included either the employ of adhesion barriers: principally at our establishment Interceed (Johnson&Johnson, New Brunswick, NJ) or Seprafilm (Baxter, Deerfield, IL); or the instillation of intraperitoneal steroids. This latter method consisted of intraperitoneal placement of 200 mg triamcinolone acetonide intermission (Bristol-Myers-Squibb Pharmaceutical, Princeton NJ) in 500 mL dextran in the peritoneal crenel at the time of closure as previously published past our group [24].

Operative technique consisted of a Pfannenstiel incision, pitressin (20U in threescore mL normal saline) was slowly injected into the eye of each myoma using an xviii-guage spinal needle. Uterine incisions were made using electrocautery in a transverse direction to avoid the arcuate vessels and were carried through the serosa, myometrium and pseudocapsule using needlepoint electrode. The myoma was grasped with a tenaculum and the overlying myometrium and pseudocapsule were bluntly dissected off the myoma. Care was taken not to enter the uterine cavity unless the coarse was classified as International Federation of Gynecology and Obstetrics (FIGO) type 2, 3 or 2–5, in which instance removing the entire fibroid was prioritized. The defect was closed in multiple layers using running 0-polyglactin (Vicryl, Johnson&Johnson) suture.

2.3 Data analysis

Data previously collected in an Excel Spreadsheet was analyzed using Prism (Graphpad, San Diego, CA) and Magician Pro for Mac. Descriptive statistics were used to characterize the dataset. Pearson correlation was performed to test for correlation, Student t-examination was used to compare groups bold unequal variance (F-examination) and two tails. Pearson Chi-squared test was performed on chiselled data. Significance was set with p<0.05.

2.4 Ethics statement

This study was approved by the institutional review board (IRB) at St. Vincent's Catholic Medical Centers Manhattan, (IRB# 010419M1X), and involved a retrospective chart review. All data was de-identified and informed consent was waved by the IRB for this retrospective chart review. All procedures performed in studies involving man participants were in accord with the ethical standards of the institutional and national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

3. Results

iii.1. Sample population

During the study period, 592 primary open myomectomies for large symptomatic fibroid uterus were performed and these patients were followed. Out of this group, 72 uterine surgeries were performed in patients who had previously undergone myomectomy. Mean historic period at reoperation was 44.1 ± 0.six years (range 33–53) and racial limerick was as follows: Non-Hispanic White: 29.0%, African American: 52.2%, Hispanic: 10.1%, Other: 8.7%. The mean time from initial surgery to second surgery was vii.9 ±0.3 years (range: 5–15 years).

3.ii. Rates of reoperation

Five hundred and ninety-two patients were followed and 70-two patients (12%) from this group chose to undergo uterine surgery for their symptoms at a later engagement. Information was available for n = 69 patients (Fig 1).

Fig 1. Summary of study cohort.

Our cohort consisted of 72 patients who underwent reoperation for a recurrence of symptoms attributable to fibroid uterus after having undergone a primary abdominal myomectomy for large myomas. Data was available on north = 69 patients.

https://doi.org/ten.1371/journal.pone.0261085.g001

3.3. Indication for repeat uterine surgery

Indications for uterine surgery after previous myomectomy in our sample consisted of: aberrant uterine bleeding secondary to fibroids (37.vii%), dyspareunia/dysmenorrhea refractory to medical management (24.6%), pelvic pressure (xiii.0%), infertility (17.four%), also equally other symptoms, such as urinary issues, attributed to fibroid uterus (7.viii%). Although patients were extensively counselled on alternatives, including hysterectomy, to repeat open up myomectomy, patients cited the following reasons for uterine conserving surgery: want to maintain fertility (40%), belief that having a uterus/cervix enhances sexual pleasure (50%), conventionalities that having a neck prevents prolapse (10%).

3.iv. Time to reoperation

The fourth dimension between the kickoff surgery and the patient presenting for her second uterine surgery was, in this study, not correlated with race, the number of fibroids or the aggregate weight of fibroids removed during the initial surgery nor with the operative time or EBL at initial process, unlike reported in other studies [25]. Time to reoperation was, all the same, significantly correlated with both age at initial surgery (correlation = -0.twoscore, R2 = 0.16, p<0.001) and uterine size at reoperation (correlation = 0.42, R2 = 0.eighteen, p<0.001) (Fig 2A and 2B). Published not-modifiable adventure factors for recurrence include uterine size, premenopausal status and age [26], which our results confirmed. Reoperation a decade or more after the initial surgery was significantly correlated with younger age at the initial surgery (p = 0.031) and a larger uterus (p<0.008) (Fig 2C and 2D).

Fig ii. Timing of reoperation.

Time between get-go surgery and patient presenting for echo uterine surgery was correlated with (A) historic period at initial surgery (correlation = -0.46, R2 = 0.21, p<0.001) and (B) uterine size at reoperation (correlation = 0.41, R2 = 0.16, p<0.001). Reoperation a decade or more after initial surgery was significantly correlated with (C) younger historic period at the initial surgery(* p<0.031) and (D) larger uterus (* p<0.008).

https://doi.org/10.1371/journal.pone.0261085.g002

3.five Uterine size at reoperation

When presenting for echo surgery, mean uterine size was 12.2 ±0.2 weeks (range: 10–20 weeks) consistent with ultrasound. This was a significantly (p<0.001) smaller than when they presented for their initial surgery, which had a mean uterine size of 20.8 ±0.5 weeks (range: 12–xxx weeks). Presentation at recurrence of fibroids was highly variable and included haemorrhage, pelvic pressure and pain with a considerable number of patients complaining of a combination of these symptoms. Indication for pain was associated with older ages, while infertility was associated with younger ages (mean age of 46.seven vs 38.9 respectively, p<0.001). Uterine size at reoperation was establish to be contained of race.

3.six. Apply of adhesion-reducing methods at the fourth dimension of myomectomy

The Triamcinolone group (north = 348) was compared to the "other method grouping" (northward = 244) and no significant differences were found regarding age, number of fibroids removed, aggregate weight of fibroids, blood loss at surgery and initial uterine size. Data was analyzed to determine if the use of intraperitoneal triamcinolone with dextran (northward = 36) or adhesion barriers such as Seprafilm (n = 2) or Interceed (north = ten) at the time of the initial myomectomy influenced timing of fibroid recurrence over untreated patients (n = 21). Neither steroids nor adhesion barriers significantly delayed timing for reoperation.

Data was analyzed to make up one's mind if the utilise of triamcinolone would alter the rate of patients with symptoms necessitating repeat uterine surgery. Data from a previous written report on postoperative adhesions consisted of a group of 348 patients in the arm receiving triamcinolone. These patients were followed longitudinally and 36 patients (10%) underwent subsequent uterine surgery during the study period. For comparison, 33 women, out of the 244 primary myomectomies that were performed using either no adhesion barriers or commercially available products as described previously, underwent echo surgery with all but two choosing echo myomectomy. This difference (10% vs xiii%) was statistically meaning (p<0.001).

four. Discussion

Uterine fibroids are a common condition and, in the U.s., incur an estimated annual direct cost of $four.1 to $9.iv billion [27]. Despite counseling on the risks of recurrence, many women prefer to opt for uterine sparing procedures citing concerns regarding fertility and sexual pleasance. Recurrence of the symptoms of fibroids is associated with increased costs, hospital admissions, transfusions, and pain for the patient.

In this written report, we accept examined the recurrence rates of uterine leiomyomas leading to reoperation after open myomectomy on a big fibroid uterus. Our charge per unit of reoperation of about 12% seems lower than the boilerplate, with some studies citing recurrence rates of 23%, following open myomectomy, and slightly higher rates post-obit laparoscopic procedures [21, 28]. 1 well-synthetic study which followed patients afterwards myomectomy [17] determined that about 21% of women had a second surgery, 75% of which were hysterectomies. Our results were significantly lower. It is unclear if this is because of the use of a more than meticulous open up technique where even small palpable fibroids are removed before they take time to grow larger while in comparison to that study, the type of initial myomectomy was performed through a combination of approaches. In minimally invasive myomectomies, where the surgeon can't palpate pocket-size fibroids, preoperative investigations (ultrasound and magnetic resonance imaging) and intraoperative laparoscopic ultrasound [29] are of import to identify and remove small "occult" fibroids, thus preventing them from growing to a size that may in some menstruum of time later crusade symptoms. Additionally, such modalities can help place if other pathologies, such every bit adenomyosis, are present (potentially contributing to symptoms) and ensure that the patient receives appropriate management. Our approach in counselling patients with recurrence of symptoms was individualized and also emphasized watchful waiting or medical management, particularly in older women. Every bit a middle for myomectomy, possible bias in counselling may accept resulted in a greater ratio of repeat myomectomy over hysterectomy. Ultimately, in a shared decision-making approach, the patient made the pick of handling, weighing risks, benefits and alternatives as it applied to her.

Our study found no correlation between the time to reoperation and race, number of fibroids, or amass weight. This contrasts with previous studies that established a correlation between reoperation rates and number of fibroids: recurrence rates with a single fibroid was nine.5% vs 24.9% with multiple myomectomy [18, 26]. Since we accept shown that historic period is tightly correlated with timing of recurrence, this result may be due to the departure in average historic period of women in their study (29.8 ± 3.eight) compared to our study (36.1 ± 0.6 years old). Additionally, our myomectomies were performed in larger uteri via laparotomy, which may likewise influence recurrence rates as one of the limitations of minimally invasive surgery is the lack of tactile sensation, making it difficult to detect smaller fibroids embedded in the myometrium.

Still, we did find a significant correlation between fourth dimension to reoperation and both historic period at initial diagnosis and uterine size at reoperation, which is consistent with the data sets of other studies [21, 25, 26]. This suggests that longer time spans allow fibroids to grow more; all the same, this may be a bias introduced past patients, who presented for surgical management. Patients, who were older at the fourth dimension of initial myomectomy, who returned with symptomatic coarse uterus, may take been counselled on watchful waiting until menopause or alternative (not-surgical) treatment methods.

Patients presented once more primarily with complaints of abnormal uterine bleeding and pain (dyspareunia/dysmenorrhea) and surgery performed for indication of "pain" were significantly associated with older ages. Younger patients, all the same, presented again for infertility and were counselled on pregnancy outcomes following repeat myomectomy [30]. The subsequent presentation was associated with a smaller burden of fibroid tumor than at initial presentation, suggesting that either patients tended to recognize these symptoms earlier or that emergence of symptoms occurred at a smaller uterine size. Thus, patients presented with uterus sizes significantly smaller than when they presented for their original myomectomy and may opt to repeat an approach which previously worked for them instead of delaying care until symptoms worsen significantly.

One of the weaknesses of this study, is that it consists of a retrospective assay of women, who elected to undergo surgical management. This self-selected group of patients may non reflect entirely the cohort of patients, who have a recurrence of symptoms but cull an alternative approach. For instance, this study did non include women with ultrasound findings of recurrent fibroids, who are asymptomatic, women, who are symptomatic but cull watchful waiting or a bourgeois approach or women, who choose other surgical approaches such as embolization. Thus, in this written report, the recurrence rates are cogitating of patients with recurrence of symptoms, who elected to have a repeat surgery. Some other weakness involves the utilise of bimanual exam to determine, in conjunction with ultrasound, clinical uterine size. This type of exam yields important pre-surgical information (such equally mobility of the uterus), laxity in the tissues, presence of other gynecological pathology and helps with surgical planning, particularly when fibroids are shut to the cervix. Additionally, bimanual sizing is highly reproducible among gynecologists.

In this written report, the use of intraperitoneal triamcinolone and dextran equally an arroyo to limit postoperative adhesion germination [24] was associated with significantly lower rates of recurrence requiring repeat surgery (10% vs 13%, p<0.001) when compared to not using anti-adhesion measures or using barrier methods besides as to recurrence rates from other published studies cited herewith. It is unclear if this departure is from steroid assistants or surgical technique. Analysis of the fourth dimension to recurrence as a role of patients having received either no treatment or steroids or the adhesion barriers Seprafilm or Interceed found no significant correlations. Further assay may be necessary equally "fourth dimension to recurrence" (and presenting for surgery) and "recurrence rates" are related just distinct quantities.

The cellular origin of uterine fibroids remains unknown [31] but genetic studies support that they are monoclonal tumors [32]. A mutation in MED12 or HMGA2 [33] in myometrial stem cells [34] may be the precipitating event. Under estrogen and progesterone stimulation, mature myometrial cells secrete paracrine factors, such equally WNT ligands, which actuate the β-catenin-T-cell transcription factor pathway through the Frizzled receptor [35] and inducing TGF-B production [36]. In mutated cells this triggers proliferation through the smad pathway. Thus, afterward an open up myomectomy, information technology is possible that some mutated fibroid stalk cells, which were too small-scale to be seen or palpated, were left behind. With time, as well every bit through de-novo transformation of myometrial cells, these fibroids can proliferate in an exponential fashion, and become symptomatic.

At the cellular level, we hypothesize that triamcinolone may abate fibroid recurrence past downregulating fibroid growth factors, principally TGF-β3 [37, 38], which is one of the primary drivers of uterine shine musculus and extracellular matrix proliferation. Our group has shown that intraperitoneal steroids decrease adhesion formation through a reduction in TGF-β at hypoxia levels typically found in the peritoneum. As a next stride, blocking the TGF-β pathway through an ALK5 blockade, such every bit by using SB525334/SB 505124 [39], may decrease activation of smad 2/3 and the transcription factors involved in smooth musculus proliferation.

five. Conclusion

This study followed a grouping of women who chose to undergo repeat surgery for recurrence of symptomatic fibroid uterus after an initial open myomectomy for large size myomatous uterus. Time to reoperation was correlated to historic period and to fibroid size only not to race or number of fibroids removed, which may be an of import office of patient counselling, particularly in younger women. Further research is necessary to assess how gynecologists tin prevent the recurrence of fibroids in patients who undergo uterus sparing procedures. Novel interventions, such equally intraperitoneal triamcinolone at the time of initial surgery, may potentially play a role in reducing reoperation rates.

Supporting information

Acknowledgments

As a former resident of St. Vincent'due south Hospital (Manhattan), MR wishes to thank the mentor, Dr. Stanley West, for his help and support.

References

1. ane. Vilos GA, Allaire C, Laberge PY, Leyland N, Special C. The management of uterine leiomyomas. J Obstet Gynaecol Can. 2015;37(2):157–78. pmid:25767949
   • View Article
   • PubMed/NCBI
   • Google Scholar
2. 2. Stewart EA, Cookson CL, Gandolfo RA, Schulze-Rath R. Epidemiology of uterine fibroids: a systematic review. BJOG. 2017;124(10):1501–12. pmid:28296146
   • View Commodity
   • PubMed/NCBI
   • Google Scholar
3. 3. Stewart EA, Nicholson WK, Bradley L, Borah BJ. The burden of uterine fibroids for African-American women: results of a national survey. Journal of women's health (2002). 2013;22(10):807–16. pmid:24033092
   • View Commodity
   • PubMed/NCBI
   • Google Scholar
4. four. Parker WH. Uterine myomas: management. Fertil Steril. 2007;88(2):255–71. pmid:17658523
   • View Article
   • PubMed/NCBI
   • Google Scholar
5. 5. Dean J, Kramer KJ, Akbary F, Wade S, Huttemann M, Berman JM, et al. Norethindrone is superior to combined oral contraceptive pills in curt-term delay of menstruum and onset of breakthrough bleeding: a randomized trial. BMC Womens Health. 2019;nineteen(1):lxx. pmid:31138184
   • View Commodity
   • PubMed/NCBI
   • Google Scholar
6. half-dozen. Venkatachalam S, Bagratee JS, Moodley J. Medical direction of uterine fibroids with medroxyprogesterone acetate (Depo Provera): a pilot study. J Obstet Gynaecol. 2004;24(7):798–800. pmid:15763792
   • View Article
   • PubMed/NCBI
   • Google Scholar
7. 7. Grigorieva V, Chen-Mok M, Tarasova G, Mikhailov A. Utilise of a levonorgestrel-releasing intrauterine system to treat bleeding related to uterine leiomyomas. Fertil Steril. 2003;79(5):1194–8. pmid:12738516
   • View Commodity
   • PubMed/NCBI
   • Google Scholar
8. 8. Murji A, Whitaker L, Chow TL, Sobel ML. Selective progesterone receptor modulators (SPRMs) for uterine fibroids. The Cochrane database of systematic reviews. 2017;iv:CD010770. pmid:28444736
   • View Article
   • PubMed/NCBI
   • Google Scholar
9. 9. Liu JH, Soper D, Lukes A, Gee P, Kimble T, Kroll R, et al. Ulipristal Acetate for Handling of Uterine Leiomyomas: A Randomized Controlled Trial. Obstet Gynecol. 2018;132(five):1241–51. pmid:30303900
   • View Article
   • PubMed/NCBI
   • Google Scholar
10. x. Steinauer J, Pritts EA, Jackson R, Jacoby AF. Systematic review of mifepristone for the treatment of uterine leiomyomata. Obstet Gynecol. 2004;103(6):1331–6. pmid:15172874
    • View Commodity
    • PubMed/NCBI
    • Google Scholar
11. 11. Friedman AJ, Barbieri RL, Doubilet PM, Fine C, Schiff I. A randomized, double-blind trial of a gonadotropin releasing-hormone agonist (leuprolide) with or without medroxyprogesterone acetate in the treatment of leiomyomata uteri. Fertil Steril. 1988;49(three):404–nine. pmid:2963759
    • View Article
    • PubMed/NCBI
    • Google Scholar
12. 12. Varelas FK, Papanicolaou AN, Vavatsi-Christaki N, Makedos GA, Vlassis GD. The effect of anastrazole on symptomatic uterine leiomyomata. Obstet Gynecol. 2007;110(iii):643–9. pmid:17766612
    • View Article
    • PubMed/NCBI
    • Google Scholar
13. 13. Jirecek S, Lee A, Pavo I, Crans K, Eppel Westward, Wenzl R. Raloxifene prevents the growth of uterine leiomyomas in premenopausal women. Fertil Steril. 2004;81(ane):132–six. pmid:14711556
    • View Article
    • PubMed/NCBI
    • Google Scholar
14. 14. Carlson KJ, Miller BA, Fowler FJ Jr. The Maine Women'southward Health Report: 2. Outcomes of nonsurgical management of leiomyomas, abnormal bleeding, and chronic pelvic pain. Obstet Gynecol. 1994;83(4):566–72. pmid:8134067
    • View Article
    • PubMed/NCBI
    • Google Scholar
15. 15. Marjoribanks J, Lethaby A, Farquhar C. Surgery versus medical therapy for heavy menstrual haemorrhage. The Cochrane database of systematic reviews. 2006(2):CD003855. pmid:16625593
    • View Commodity
    • PubMed/NCBI
    • Google Scholar
16. xvi. Singh SS, Belland L. Contemporary management of uterine fibroids: focus on emerging medical treatments. Curr Med Res Opin. 2015;31(i):1–12. pmid:25365466
    • View Article
    • PubMed/NCBI
    • Google Scholar
17. 17. Reed SD, Newton KM, Thompson LB, McCrummen BA, Warolin AK. The incidence of repeat uterine surgery following myomectomy. Journal of women's health (2002). 2006;xv(9):1046–52. pmid:17125423
    • View Article
    • PubMed/NCBI
    • Google Scholar
18. 18. Yoo EH, Lee PI, Huh CY, Kim DH, Lee BS, Lee JK, et al. Predictors of leiomyoma recurrence after laparoscopic myomectomy. J Minim Invasive Gynecol. 2007;14(vi):690–7. pmid:17980328
    • View Article
    • PubMed/NCBI
    • Google Scholar
19. 19. Nezhat FR, Roemisch Grand, Nezhat CH, Seidman DS, Nezhat CR. Recurrence rate after laparoscopic myomectomy. J Am Assoc Gynecol Laparosc. 1998;v(3):237–40. pmid:9668143
    • View Article
    • PubMed/NCBI
    • Google Scholar
20. twenty. Fedele Fifty, Parazzini F, Luchini Fifty, Mezzopane R, Tozzi Fifty, Villa L. Recurrence of fibroids after myomectomy: a transvaginal ultrasonographic study. Hum Reprod. 1995;ten(seven):1795–6. pmid:8582982
    • View Commodity
    • PubMed/NCBI
    • Google Scholar
21. 21. Kotani Y, Tobiume T, Fujishima R, Shigeta Thousand, Takaya H, Nakai H, et al. Recurrence of uterine myoma after myomectomy: Open up myomectomy versus laparoscopic myomectomy. J Obstet Gynaecol Res. 2018;44(2):298–302. pmid:29227004
    • View Article
    • PubMed/NCBI
    • Google Scholar
22. 22. Rossetti A, Sizzi O, Soranna L, Cucinelli F, Mancuso S, Lanzone A. Long-term results of laparoscopic myomectomy: recurrence charge per unit in comparing with abdominal myomectomy. Hum Reprod. 2001;xvi(4):770–4. pmid:11278231
    • View Article
    • PubMed/NCBI
    • Google Scholar
23. 23. Nishiyama S, Saito Grand, Sato 1000, Kurishita M, Itasaka T, Shioda Yard. High recurrence rate of uterine fibroids on transvaginal ultrasound later on intestinal myomectomy in Japanese women. Gynecol Obstet Invest. 2006;61(3):155–9. pmid:16391486
    • View Article
    • PubMed/NCBI
    • Google Scholar
24. 24. Westward S, Ruiz R, Parker WH. Abdominal myomectomy in women with very large uterine size. Fertil Steril. 2006;85(1):36–9. pmid:16412723
    • View Article
    • PubMed/NCBI
    • Google Scholar
25. 25. Shiota Chiliad, Kotani Y, Umemoto Chiliad, Tobiume T, Hoshiai H. Recurrence of uterine myoma afterwards laparoscopic myomectomy: What are the risk factors? Gyn and Mini Invasive Therapy. 2012;1(i):34–half-dozen.
    • View Article
    • Google Scholar
26. 26. Obed JY, Bako B, Usman JD, Moruppa JY, Kadas S. Uterine fibroids: risk of recurrence after myomectomy in a Nigerian population. Curvation Gynecol Obstet. 2011;283(2):311–5. pmid:20098994
    • View Commodity
    • PubMed/NCBI
    • Google Scholar
27. 27. Cardozo ER, Clark Advertising, Banks NK, Henne MB, Stegmann BJ, Segars JH. The estimated annual cost of uterine leiomyomata in the United States. Am J Obstet Gynecol. 2012;206(3):211 e1–9. pmid:22244472
    • View Article
    • PubMed/NCBI
    • Google Scholar
28. 28. Fauconnier A, Chapron C, Babaki-Fard K, Dubuisson JB. Recurrence of leiomyomata afterward myomectomy. Hum Reprod Update. 2000;6(vi):595–602. pmid:11129693
    • View Article
    • PubMed/NCBI
    • Google Scholar
29. 29. Levine DJ, Berman JM, Harris M, Chudnoff SG, Whaley FS, Palmer SL. Sensitivity of myoma imaging using laparoscopic ultrasound compared with magnetic resonance imaging and transvaginal ultrasound. J Minim Invasive Gynecol. 2013;xx(6):770–four. pmid:24021910
    • View Article
    • PubMed/NCBI
    • Google Scholar
30. 30. Teo UL, Kopeika J, Pundir J, El-Toukhy T. Peri-operative morbidity and fertility outcome after echo abdominal myomectomy for large fibroid uterus. J Obstet Gynaecol. 2020;40(v):673–7. pmid:31462123
    • View Article
    • PubMed/NCBI
    • Google Scholar
31. 31. Bulun SE. Uterine fibroids. N Engl J Med. 2013;369(14):1344–55. pmid:24088094
    • View Article
    • PubMed/NCBI
    • Google Scholar
32. 32. Linder D, Gartler SM. Glucose-6-phosphate dehydrogenase mosaicism: utilization as a cell marker in the written report of leiomyomas. Science. 1965;150(3692):67–ix. pmid:5833538
    • View Article
    • PubMed/NCBI
    • Google Scholar
33. 33. Makinen N, Mehine M, Tolvanen J, Kaasinen E, Li Y, Lehtonen HJ, et al. MED12, the mediator complex subunit 12 gene, is mutated at loftier frequency in uterine leiomyomas. Science. 2011;334(6053):252–v. pmid:21868628
    • View Article
    • PubMed/NCBI
    • Google Scholar
34. 34. Ono G, Qiang W, Serna VA, Yin P, Coon JSt, Navarro A, et al. Role of stem cells in human uterine leiomyoma growth. PLoS I. 2012;7(5):e36935. pmid:22570742
    • View Article
    • PubMed/NCBI
    • Google Scholar
35. 35. Tanwar PS, Lee HJ, Zhang L, Zukerberg LR, Taketo MM, Rueda BR, et al. Constitutive activation of Beta-catenin in uterine stroma and smooth musculus leads to the development of mesenchymal tumors in mice. Biol Reprod. 2009;81(3):545–52. pmid:19403928
    • View Article
    • PubMed/NCBI
    • Google Scholar
36. 36. Arici A, Sozen I. Transforming growth factor-beta3 is expressed at loftier levels in leiomyoma where it stimulates fibronectin expression and cell proliferation. Fertil Steril. 2000;73(5):1006–11. pmid:10785229
    • View Article
    • PubMed/NCBI
    • Google Scholar
37. 37. Joseph DS, Malik M, Nurudeen Southward, Catherino WH. Myometrial cells undergo fibrotic transformation under the influence of transforming growth cistron beta-3. Fertil Steril. 2010;93(5):1500–8. pmid:19328471
    • View Article
    • PubMed/NCBI
    • Google Scholar
38. 38. Lee BS, Nowak RA. Human leiomyoma smooth musculus cells prove increased expression of transforming growth gene-beta 3 (TGF beta 3) and altered responses to the antiproliferative effects of TGF beta. J Clin Endocrinol Metab. 2001;86(2):913–20. pmid:11158066
    • View Article
    • PubMed/NCBI
    • Google Scholar
39. 39. Grygielko ET, Martin WM, Tweed C, Thornton P, Harling J, Brooks DP, et al. Inhibition of cistron markers of fibrosis with a novel inhibitor of transforming growth factor-beta blazon I receptor kinase in puromycin-induced nephritis. J Pharmacol Exp Ther. 2005;313(three):943–51. pmid:15769863
    • View Article
    • PubMed/NCBI
    • Google Scholar

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