The Rising Phoenix-Progesterone as the Main Target of the Medical Therapy for Leiomyoma.

Leiomyomas, also known as uterine fibroids, are a common benign tumor in women of reproductive age. These lesions disrupt the function of the uterus causing menorrhagia and pelvic pressure as well as reproductive disorders. These women pose a true challenge for clinicians in the attempt of choosing the suitable treatment for each patient. Patient's age, interest in fertility preservation, and leiomyoma location and size are all factors to be taken into account when deciding upon the preferable therapeutic option. For the past few decades, surgical treatment was the only reliable long-term treatment available. A variety of surgical approaches have been developed over the years but these developments have come at the expense of other treatment options. The classical medical treatment includes gonadotropin-releasing hormone (GnRH) agonists and antagonists. These agents are well known for their limited clinical effect as well as their broad spectrum of side effects, inspiring a need for new pharmacological treatments. In recent years, promising results have been reported with the use of selective progesterone receptor modulators (SPRM). Long-term clinical trials have shown a reduction in bleeding and shrinkage of leiomyoma mass. These results instill hope for women suffering from symptomatic leiomyomas seeking an effective, long-term medical option for their condition.

Does hysteroscopy affect prognosis in apparent early-stage endometrial cancer?

The objective of the study was to compare the outcome measures of patients with endometrial adenocarcinoma diagnosed by endometrial biopsy, uterine curettage, or hysteroscopy. Medical records of 392 women diagnosed with apparent early-stage endometrial adenocarcinoma were reviewed. Data concerning the mode of diagnosis, histologic type and grade, surgical stage, peritoneal washings and lymph nodes status, and patient's outcome were retrieved. During the study period, 99 (25.3%) cases were diagnosed by endometrial biopsy, 193 (49.2%) by uterine curettage, and 100 (25.5%) by hysteroscopy. There were 347 (88.5%) cases of endometrioid adenocarcinoma and 45 (11.5%) of poor histologic types, including serous papillary, clear cell, and small cell cancer. Three hundred and sixteen (80.6%) patients had stage I disease, 8 (2.0%) stage II, and 68 (17.4%) stage III. Peritoneal cytology was positive in only one case. Recurrent disease occurred in 6.9% patients, of which 50% had local recurrence and 50% had distant. Recurrent disease was found in 15.2% patients diagnosed by endometrial biopsy, in 4.7% where uterine curettage was used, and in 5% when hysteroscopy was applied. No statistically significant difference in the survival rate between the different diagnostic methods applied was found, although a higher recurrence rate was noted following endometrial biopsy. After a median follow-up time of 25 months for patients undergoing hysteroscopy, there was no difference in recurrence rates and/or overall survival compared to other diagnostic procedures implying that hysteroscopy can be safely used in the diagnosis of endometrial cancer.

Maternal morbidity following routine second trimester genetic amniocentesis.

Two cases of septic complications of routine second trimester amniocentesis are presented. The first case is a 37-year-old gravida suffering from ulcerative colitis who was admitted for amniocentesis in the 18th week of her third pregnancy. An uncomplicated transabdominal amniocentesis was performed using a sterile technique and ultrasound guidance. Twenty-eight hours later the patient had a septic abortion and sepsis. The second case is a 34-year-old gravida in the 24th week of her pregnancy who was admitted with amnionitis 10 h after an uncomplicated amniocentesis, and subsequently had a septic abortion. A high index of suspicion and rapid intervention were crucial in both cases.

Infertility, ovulation induction treatments and the incidence of breast cancer--a historical prospective cohort of Israeli women.

CONTEXT: Ovulation induction drugs may be associated with increased breast cancer risk. Results so far have been inconclusive. OBJECTIVE: To evaluate the association between infertility, exposure to ovulation induction drugs and the incidence of breast cancer. DESIGN: Historical prospective cohort and nested case-control study. SETTING: Institutional practice PATIENTS: About 5,788 women attending five infertility centers in Israel between 1964 and 1984. INTENTION: Abstracting of medical records and telephone interviews. MAIN OUTCOME MEASURE: Breast cancer incidence was determined through linkage with the National Cancer Registry database. Standardized incidence ratios (SIRs) and 95% confidence intervals were computed by comparing the observed to the expected cancer rates in the general population. In addition, a nested case-control study within the cohort was performed with interviews of breast cancer cases and two matched controls. RESULTS: The study cohort included 120,895 women years of follow-up. Compared to 115.2 expected breast cancer cases, 131 cases were observed (SIR = 1.1; 95% CI 0.9-1.4). Risk for breast cancer was significantly higher for women treated with clomiphene citrate (SIR = 1.4; 95% CI 1.0-1.8). Similar results were noted when comparisons were carried out between treated and untreated women, and when multivariate models were applied. In the nested case-control study, higher cycle index (OR = 2.2; 95% CI 1.0-4.8) and treatment with clomiphene citrate (OR=2.7; 95% CI 1.3-5.7) were associated with higher risk for breast cancer. CONCLUSION: Infertility and usage of infertility drugs in general are not associated with increased risk for breast cancer. However, for infertile women treated with clomiphene citrate, breast cancer risk is elevated.

In vitro maturation and fertilization of oocytes from an intact ovary of a surgically treated patient with endometrial carcinoma: case report.

Polycystic ovary syndrome (PCOS) with prolonged anovulation had resulted in endometrial carcinoma in a 43-year-old woman. Since she and her husband did not share common biological children, they requested fertility preservation. Due to the woman's age, high dose progesterone and postponing surgery were both considered inappropriate. We therefore proposed oocyte retrieval from the ovaries removed by staging laparotomy followed by in vitro maturation and ICSI. Surrogacy could then enable a future pregnancy. Fourteen of 17 (82%) retrieved oocytes matured in vitro. Following ICSI, eight embryos (two at the pronuclear stage and six cleaved) were cryopreserved. To the best of our knowledge, this is the first report of oocyte aspiration, maturation and fertilization from an ovary removed by laparotomy.

Diagnostic and therapeutic advantages of hysteroscopic surgery in management of intrauterine lesions in postmenopausal women.

STUDY OBJECTIVE: To determine the value of hysteroscopic surgery in the management of intrauterine lesions in postmenopausal women. DESIGN: Descriptive study (Canadian Task Force classification II-2). SETTING: Tertiary care university hospital. Patients. Fifty postmenopausal women, most with vaginal bleeding, all with intrauterine lesions (leiomyomas, polyps, adhesions) on hysteroscopy or ultrasound. INTERVENTION: Hysteroscopic operations consisting of myomectomy, polypectomy, and adhesiolysis. MEASUREMENTS AND MAIN RESULTS: Forty-seven procedures were completed successfully by hysteroscopy; partial myomectomies were performed in three women for large or deeply embedded leiomyomas. The only complication was one case of fluid overload. Median operating time was 20.0 minutes (range 5.0-60.0 min) and median postoperative hospital stay was zero days (range 0-2 days). Eight patients (16%) subsequently underwent hysterectomy, mostly for uterine malignancy or premalignancy. In two cases, the operative specimen included malignant elements that were not evident on preoperative endometrial biopsy. During mean follow-up of 33.1 months (range 6-72 mo), 95.2% of women without hysterectomy were free of symptoms. CONCLUSION: Hysteroscopic surgery is an effective and safe option for postmenopausal women with intrauterine lesions. It allows the correct diagnosis to be made, reduces the need for major and unnecessary surgery, and is therapeutic in most patients. (J Am Assoc Gynecol Laparosc 8(1):87-91, 2001)

Laparoscopic 'oophorectomy-in-a bag'--an alternative to laparotomy for the evaluation of suspicious ovarian masses.

A prospective observational study was performed to assess the feasibility of the technique of laparoscopic 'oophorectomy-ina bag' for the safe removal of ovarian masses that do not meet the standard guidelines for laparoscopic management of adnexal pathology. Ovarian lesions were selected preoperatively by: age of the patient, ultrasound appearance, bilaterality and size. None of the women had ascites or matted bowel on ultrasound, and all had normal serum tumour markers. There were no stigmata of malignant disease in any of the cases at the time of surgery. Twenty women were recruited. Eighteen procedures (90.0%) were completed successfully laparoscopically. In two cases the bag could not be removed laparoscopically and minilaparotomy was performed. Nineteen of the tumours (95.0%) were removed without intra-abdominal spillage; the bag ruptured in one case. There were no major complications. One case of borderline ovarian tumour (stage Ia) was discovered. We conclude that laparoscopic 'oophorectomy-in-a bag' allows for the safe removal of suspicious ovarian tumours. The advantages of this approach are that women can be treated locally, a laparotomy is avoided, and the subgroup with ovarian malignancy can be identified to be referred to an oncological centre.

[Residents training in gynecologic operative endoscopy: a review of Israeli and world experience].

Two decades ago, Gynecologic procedures performed by endoscopy were basically limited to diagnostic procedures. Since 1990, operative endoscopy is increasingly used to treat a growing variety of gynecologic conditions, resulting in shorter hospital stay and smaller, less painful incisions. One of the greatest tasks facing today's academic gynecologic surgeons is training residents and attendant physicians to perform endoscopic surgery adequately and safely. Clearly, there is a need to provide basic knowledge of endosurgical principles, and understanding of equipment and technologies used in operative endoscopy. Also, information on minimization, early recognition and treatment of endoscopic complications is of great importance as well as hands-on experience in these new procedures. We have reviewed the world as well as the Israeli experience in the field and out of this growing base of knowledge we have tried to delineate and forge guidelines for adequate teaching, training and accreditation.

Truncation of a mammalian myosin I results in loss of Ca2+-sensitive motility.

MYR-1, a mammalian class I myosin, consisting of a heavy chain and 4-6 associated calmodulins, is represented by the 130-kDa myosin I (or MI(130)) from rat liver. MI(130) translocates actin filaments in vitro in a Ca(2+)-regulated manner. A decrease in motility observed at higher Ca(2+) concentrations has been attributed to calmodulin dissociation. To investigate mammalian myosin I regulation, we have coexpressed in baculovirus calmodulin and an epitope-tagged 85-kDa fragment representing the amino-terminal catalytic "motor" domain and the first calmodulin-binding IQ domain of rat myr-1; we refer to this truncated molecule here as MI(1IQ). Association of calmodulin to MI(1IQ) is Ca(2+)-insensitive. MI(1IQ) translocates actin filaments in vitro at a rate resembling MI(130), but unlike MI(130), does not exhibit sensitivity to 0.1-100 micrometer Ca(2+). In addition to demonstrating successful expression of a functional truncated mammalian myosin I in vitro, these results indicate that: 1) Ca(2+)-induced calmodulin dissociation from MI(130) in the presence of actin is not from the first IQ domain, 2) velocity is not affected by the length of the IQ region, and 3) the Ca(2+) sensitivity of actin translocation exhibited by MI(130) involves 1 or more of the other 5 IQ domains and/or the carboxyl tail.

Induction of ovulation and borderline ovarian cancer--the hormonal connection?

While the data regarding the possible association between fertility drugs and invasive ovarian cancer are inconclusive, there is evidence to suggest an association between induction of ovulation and borderline ovarian tumors. The plausibility of these results is heightened by the finding that estrogen receptor expression is a common feature of ovarian borderline tumors. On the other hand, recent data indicate that in contrast to the crucial role of germline mutations in the pathogenesis of invasive ovarian cancer, these mutations play a minor role, if any, in the pathogenesis of borderline ovarian tumors. This evidence suggests that the differences between invasive and borderline ovarian tumors are not based on minor morphological criteria, but that, most probably these represent two different entities, with different clinical behavior, and that borderline tumors might be associated with hormonal factors rather than genetic mutations.

A case-control study to compare the variability of operating time in laparoscopic and open surgery.

The purpose of this study was to compare the variability of operating times for some of the most common gynaecological procedures performed laparoscopically and by open surgery. The case notes of 60 women randomly selected from a cohort of 600 who had undergone laparoscopic surgery for ectopic pregnancy, ovarian cysts, leiomyoma and hysterectomy were reviewed. These patients were matched with an equal number of women who had been treated by open surgery for similar indications. Additional matching criteria included age (+/-2 years), size of the lesion in cases of ovarian cysts and fibroids (+/-3 cm), the period of amenorrhoea in ectopic pregnancies, and uterine size and pelvic pathology in women undergoing hysterectomy. Comparison of laparoscopy and laparotomy showed that the mean procedure times were similar for the two routes of surgery, with the exception of hysterectomy which took significantly longer if done laparoscopically. The duration of laparoscopic surgery for ectopic pregnancy, ovarian cystectomy and hysterectomy was significantly less predictable than at laparotomy. These data indicate that with the exception of hysterectomy, the average operating time for laparoscopic procedures is comparable to that for laparotomy. In contrast, the variability of duration of laparoscopic surgery tends to be much greater than with laparotomy for all procedures considered.

How long does laparoscopic surgery really take? Lessons learned from 1000 operative laparoscopies.

The purpose of this study was to assess the operating time of the most common gynaecological laparoscopic procedures. We analysed retrospectively 1000 consecutive operative laparoscopies on a procedure-by-procedure basis. Diagnostic laparoscopy and laparoscopic sterilization were specifically excluded from the analysis. The various laparoscopic procedures were grouped and analysed under six major categories. The average operating time for all cases was 76.9 min (range 10-400). In 38 cases (3.8%) the laparoscopic procedure was converted to laparotomy. The average operating time for treating ectopic pregnancy and tubal disease was approximately 60 min (range 13-240). Surgery for endometriosis and ovarian cysts averaged 72 min (range 10-240). Laparoscopic myomectomy and hysterectomy averaged 113 and 131 min respectively (range 25-400). Our results show that while the operating time for most operative laparoscopies is less than 75 min, the range of operating times is great. The relative lack of predictability in procedure times means that the efficient utilization of fixed theatre sessions is difficult.

Myometrial scoring: a new technique for the management of severe Asherman's syndrome.

OBJECTIVE: To describe a new hysteroscopic technique for the management of severe Asherman's syndrome. DESIGN: Prospective observational study. SETTING: Volunteers in an academic research environment. PATIENT(S): Seven patients with secondary infertility associated with amenorrhea or oligomenorrhea secondary to severe Asherman's syndrome. INTERVENTION(S): Six to eight longitudinal incisions were made into the myometrium extending from the uterine fundus to the isthmus with a resectoscope fitted with a Collins knife electrode. MAIN OUTCOME MEASURE(S): Restoration of menses, symptomatic relief, and postoperative reproductive performance. RESULT(S): The amount of menstrual bleeding increased in all cases, including two women who were amenorrheic before their surgery. Pelvic pain decreased in two of the four symptomatic cases. Three to four months after surgery, hysteroscopy showed a normal sized uterine cavity in five cases. After a median follow-up of 12 months, three women conceived four pregnancies, including a missed abortion, a tubal abortion, an ongoing pregnancy currently at 7 weeks' gestation, and one child delivered at 36 weeks gestation after premature rupture of the membranes. CONCLUSION(S): Hysteroscopic myometrial scoring enlarges uterine cavity size in cases of severe Asherman's syndrome and improves menstrual function. Reproductive performance seems to be improved also, but longer follow-up is required.