الفهرس 
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Abstract
Summary
Uterine leiomyoma are by far the commonest benign uterine tumor. It is composed mainly of smooth muscle cells and fibrous connective tissue. They are estimated to be present in at least 20 % to 30 % of all women of reproductive age and be discovered incidentally during routine annual examination.
New concepts are developed that go beyond just myomas as estrogen and progesterone responsive tumors through knowledge that these tumors are responsive to different peptide growth factors.
Tumors are present in 40 – 50 % of women older than 40 years of age. Less than one - half of uterine leiomyomas are estimated to produce symptoms. However, it is often accepted that fibroids cause a variety of female reproductive problems, such as menorrhagia, pain, infertility, pregnancy loss and pregnancy complications. The most common presenting symptoms associated with fibroids, and the one that most frequently leads to surgical intervention is, menorrhagia, which is reportedly present in one- third of women undergoing myomectomy.
In pregnancy, it is commonly believed that uterine fibroids enlarge and that they are associated with various adverse outcomes such as miscarriage, placental abruption, fetal growth restriction and Caesarean section.
Strategy of Treatment of Uterine Fibroids:
The established approach in the management of fibroids can be defined as.
1- Abdominal myomectomy: when there is a desire for future fertility.
2- Alternatives to abdominal myomectomy .
1 ) Abdominal Myomectomy:
As myomectomy is a conservative and invasive procedure performed in relatively young women, it is important to bear in mind the principles of atraumatic infertility surgery at every stage of myomectomy technique.
Laparotomy remains the most common and arguably the safest approach for the surgical management of large uterine fibroids by hysterectomy or myomectomy. Laparotomy is indicated in patients with myomas measuring over 10 cm and for multiple myoma (over 3) .
Traditional advice is to avoid posterior incisions because of a greater risk of adhesions and to remove as many fibroids as possible through a single anterior mid line incision. Good attention to haemostasis is essential . Cavities should be fully obliterated , either in layers or with large , full thickness through and through sutures. The serosa is closed separately . For very large fundal fibroids, a transverse incision can be used .
2 ) Alternatives to abdominal myomectomy:
A ) Endoscopic myomectomy:
Laparoscopic Myomectomy:
The indications for operative laparoscopy have increased greatly over the last decades as its many advantages over laparotomy have become recognized.
Only complicated myomas and /or those which give rise to persistent symptoms despite properly prescribed medical treatment, together with those, which grow rapidly, require surgery. The satisfactory results must not mask the fact that the technique is lengthy and difficult and should be carried out by experiencing surgeons thoroughly familiar with endosccopic sutures and should be restricted to specialist centers.
Under these conditions, laparoscopic myomectomy is possible, for large myomas (5cm and over) even if they are located completely intramurally. However, there are limits and it is preferable to use laparotomy for myomas measuring over 10cm and for multiple myoma (over 3). The risk of causing adhesions is minimized through out magnification, meticulous hemostasis, perfect closure of the myometrium and proper choice of the quality of the uterine suture .
Laparoscopic myomectomy as a technique is now clearly described. A monopolar hook is used for the uterine incision. After a traumatic enucleation of the myoma, myometrium and serosa are usually sutured particularly if the incision is deep or more than 2 cm long. Myomas can be removed by posterior colpotomy. However, the development of an electrical cutting device permit an easier and quicker removal of the myoma through the suprapubic puncture site .
Laser Myomectomy:
Laser myomectomy is a new method of surgery . Its advantages over conventional methods include : decrease adhesion formation , better homeostasis, direct vaporization of smaller fibroids, increased precision in destroying abnormal tissue and decreased tissue injury with subsequent improved reproductive performance.
Three types of laser are in use in gynecological surgery: the CO2 laser, argon and Nd - YAG ( neodymium – yttrium - aluminum- garnet ) lasers.
Hysteroscopic Resection of Myoma:
It is indicated in the case of small submucous fibroids using electrosurgical resection or the Nd - YAG laser . This technique is most useful for the removal of small pedunculated or sessile fibroids. Also in patients with infertility or recurrent miscarriage and having submucous fibroids to restore the normal contour of the uterine cavity.
B ) Hysterectomy:
Hysterectomy is a treatment option for women with fibroids that are giving rise to symptoms, especially menorrhagia and pressure symptoms. Increased enthusiasm for the vaginal approach to hysterectomy prompted by economic considerations, has led to arguments in favor of its greater use for the removal of large uteri, but clinical experience, common sense and patient safety must take precedence .
Traditional teaching has favoured the abdominal approach for uteri greater than a 12 - weeks gestational size , corresponding to a weight of 280 – 300 g although some would extend this up to a 14 - weeks size. General advantages of vaginal hysterectomy include less manipulation of the intestines, avoiding abdominal incisions with its complications (e.g., infection, dehiscence, discomfort, or hernia) and also patients are able to ambulate earlier and to care for themselves.
C ) Medical treatement:
For many patients, the possibility of medical treatment of their tumors is attractive. The availability of a range of medications , that can complement effective surgery , or indeed replace it completely is of great importance to many women in developed countries .
In the past decade, the utility of GnRHa in the treatment of uterine fibroids has been extensively investigated. It is indicated in all patients with fibroids prior to surgery, GnRHa could be utilize to facilitate the surgical procedure or modify the type of surgery to be used. Fibroid and myometrial shrinkage should facilitate surgery. Endometrial atrophy and a diminished hemorrhage tendency should improve vision for hysteroscopic and laparoscopic surgery and reduce fluid absorption in hysteroscopic surgery.
Studies have demonstrated a consistent and marked reduction in uterine and/or fibroid volume following treatment with GnRHa. The reduction in volume becomes maximal within 3 months treatment period for most individuals.
GnRHa therapy is of little or no benefit for patients with pedunculated or calcified myomas. In cases of non significant reduction following 2 months of GnRHa therapy, malignancy must be excluded .
Anemia related to menorrhagia can be relieved by 3 months combined treatment with GnRHa and iron therapy. Symptoms of dysmenorrhea, pelvic pain and urinary frequency can also be relieved in the majority of patients after GnRHa treatment .
GnRHa treatment produce hot sweats and flushes, vaginal dryness, reduced bone mineral density and osteoporosis due to hypoestrogenic action. In patients unsuitable for surgery GnRHa treatment and estrogen- progestogen continuous combined add back therapy could be an alternative. However, GnRHa would need to be administered for 3 months unopposed to achieve a reduction in fibroid volume prior to the commencement of add back therapy. The precise optimal add back regimen still needs further investigation.
Many patients would welcome treatments for fibroids without hypoestrogenic symptoms. Medicines that do not produce hot sweats and flushes, vaginal dryness reduced bone mineral density and the prospect of osteoporosis would be a significant option for many patients . The use of anti progesterone medications for this purpose seems particularly worthy of studies , given that these drugs have now been clinically available for nearly 20 years and are known to be clinically safe .
D ) Arterial Embolization:
Arterial embolization offers a very good option for women who are unwilling to undergo major surgery (myomectomy or hysterectomy), lose their uterus or have blood transfusion.
Uterine embolization for fibroids was used as an adjuvant to surgery. As it was used as a pre-operative technique in order to debulk and devascularize tumors, thus making the operation easier and reducing the transfusion requirements. The embolization technique is extended to include women considered high operative risks, and describe embolization as the primary treatment of fibroids as an alternative to surgery.
Embolization should be performed by radiologists experienced in diagnostic and therapeutic angiography. It is performed via percutaneous right femoral artery approach using local anesthesia and intravenous sedation. Both internal iliac arteries were in turn selectively catheterized. The aim of the embolization in patients was to effect complete occlusion of both uterine arteries and the uterine vascular bed with multiple small particulate emboli. As the uterine arteries are the major supply to the uterus, there is concern that this could result in massive necrosis and infarction of the uterus. In practice, this has not been observed in embolization of fibroids.
The advantages of angiographic embolization are that the procedure is less traumatic than the operative option, recovery is rapid with direct cost saving to the health service due to shift from in- patient to out- patient and day- case treatment, indirect cost saving to society since women return more quickly to the usual activities and, perhaps most important, that the women may preserve future fertility.
E ) Gene Therapy:
Localized gene therapy is a promising tool for medical interventions in the treatment of leiomyoma because gene therapy could be applied to women who wish to conceive in the future.
Recombinant DNA technology provides the tools to make gene therapy possible.
Cytotoxic gene therapy has been shown to successfully inhibit both tumor growth and benign cellular proliferation, and the FDA approved cytotoxic gene therapy for human treatment of brain and ovarian tumours.
Leiomyoma only become clinically relevant when they enlarge enough to elicit a size effect (pelvic pressure, urinary obstruction or frequency, and constipation) or grow in proximity to the endometrial lining, causing abnormal uterine bleeding. Uterine leiomyoma have a rare incidence of malignant transformation, so a significant reduction in tumor mass of a leiomyoma is tantamount to a cure. Cytotoxic gene therapy may provide the means to shrink leiomyoma without the need for major surgical intervention. A varity of minimally invasive techniques already exist, such as vaginal ultrasound-guided injections, laparoscopy, and hysteroscopy, that can be modified for trans gene delivery to leiomyoma.
It is though that cells that are actively dividing are more sensitive to treatment with gancicyclovir. Furthermore, it is known that human leiomyocyte are sex-steroid dependent. Therefore, it stands to reason that induction of cell division by estrogen would increase the effectiveness of this form of gene therapy. To this end, estradiol was used to supplement ELT-3 cells in vitro cells treated with gancicylovir in the presence of estradiol demonstrated a decease in cell survival.