Dr.Mohammed Abdalla Egypt. Domiat G.

Hospital

Controversies in Gynecology

there are often

serious disagreements

And over the years, the prevailing medical wisdom can swing as dramatically as clothing fashions and gasoline prices.

Some Items Of Controversy

1. Screening for ovarian cancer..Yes or no ?

2.
3. 4. 5. 6.

Endometrial resection and ablation versus hysterectomy ..WHICH?

Pre-operative endometrial thinning agents before hysteroscopic surgery ? Managing patients with large symptomatic fibroids(UAE)Vs myomectomy. Interventions for tubal ectopic pregnancy..Which approach and when? Evaluation of abnormal uterine bleedingOffice Hysteroscopy vs saline infusion Sonography (SIS) Therapeutic conization .Is there a necessity of removing the entire endocervical canal, including the internal os, in all cases ?

7.

8. 9.

Clomiphene citrate for unexplained subfertility in women. Metformin as a treatment option in PCO patients.

1
Screening for Ovarian Cancer..Yes Or No ?

Screening for Ovarian Cancer..Yes Or No ?

Increased risk: Women who have never been pregnant. Women who have had breast, intestinal, or rectal cancer. Women with close relatives who have had ovarian cancer.

Pelvic Examination
is of unknown sensitivity in detecting ovarian cancer. Ovarian cancers detected by pelvic examination are generally advanced

Tumor markers
Carcinoembryonic antigen, ovarian cystadenocarcinoma antigen CA125 The reported sensitivities of CA-125 in detecting stage I and stage II cancers are 29- 75% and 67-100%, respectively Tumor markers may have limited specificity. It has been reported that CA- 125 is elevated in 1% of healthy women, 6-40% of women with benign masses it may be possible to improve the specificity of CA-125 measurement by selective screening of postmenopausal women

Ultrasound imaging
detect masses as small as 1 cm, and distinguish solid lesions from cysts. Transvaginal colorflow Doppler ultrasound can also identify vascular patterns associated with tumors. sensitivity50-100% specificity76-97%,

Ultrasound imaging cont.

THIS MEAN that to detect 40 cases of ovarian cancer you must do ultrasound screening of 100,000 women but at a cost of 5,398 false positives and over 160 complications from diagnostic laparoscopy.

Ultrasound imaging cont.

It may be possible to improve accuracy by combining ultrasound with other screening tests, such as the measurement of CA-125.
Further research is needed, however, to determine the sensitivity, specificity, and positive predictive value of performing these tests in combination to screen symptomatic women.

Key Recommendations
There are no official recommendations to screen routinely for ovarian cancer in asymptomatic women by performing ultrasound or serum tumor marker measurements

Key Recommendations
A national institutes of health consensus conference on ovarian cancer recommended taking a careful family history and performing an annual pelvic examination on all women

Key Recommendations
American college of obstetricians and gynecologists the pelvic examination (and pap smear) is recommended annually for all women who are or have been sexually active

Key Recommendations
The NIH consensus conference concluded that women with presumed hereditary cancer syndrome should undergo annual pelvic examinations, CA-125 measurements, and transvaginal ultrasound until childbearing is completed or at age 35, at which time prophylactic bilateral oopherectomy was recommended

Routine Screening for Ovarian Cancer Cannot Be Recommended.

2
Endometrial Resection and Ablation Versus Hysterectomy ..

Endometrial ablation for women when ALL of the following criteria are met: 1. Menorrhagia unresponsive to (or with a contraindication to) either: a. Hormonal therapy or other pharmacotherapy; Or b. Dilation and currettage; And

2. Endometrial sampling has excluded cancer, precancer, or structural abnormalities (polyps, fibroids) that require surgery. And 3. Pap smear and gynecologic examination have excluded significant cervical disease.

There was a significant advantage in favour of hysterectomy in the improvement in HMB and satisfaction rates (up to 4 years post surgery) compared with endometrial destruction techniques.

although many quality of life scales reported no differences between surgery

groups, there was some evidence of a greater improvement in general health for hysterectomy patients.

The total coast of endometrial destruction was significantly lower than the
cost of hysterectomy but the difference between the two procedures narrowed over time because of the high cost of re-treatment in the endometrial destruction group.

But if a proportion of women treated initially by ablation will require further

surgery, the initial procedure may provide sufficient control until menopause for many patients and may enable others to avoid or defer major surgery

Ablation
yes
Although a subsequent hysterectomy rate of 20% after endometrial ablation may seem high, 80% of women who otherwise would have had a hysterectomy will avoid it with an endometrial ablation. * ablation technology is becoming less expensive, more user friendly, requires less anesthesia and analgesia, and is producing about 85% patient satisfaction.

No
Hysterectomy remains a skilldependent procedure with 100% effectiveness. However, its safety record for death and injury compares unfavorably with ablation. Its costs are higher and recovery is longer. The long term problems with ablation are failure before menopause requiring a repeat procedure, and the unknown rate of post ablation endometrial cancer.

Cochrane Reviewers' Conclusions

Endometrial destruction offers an alternative to hysterectomy as a surgical treatment for heavy menstrual bleeding. Both procedures are effective and satisfaction rates are high. Although hysterectomy is associated with a longer operating time, a longer recovery period and higher rates of post-operative complications, it offers permanent relief from heavy menstrual bleeding. The cost of endometrial destruction is significantly lower than hysterectomy but since re-treatment is often necessary the cost difference narrows ISSUE 1,2003

3
Pre-operative endometrial thinning agents before hysteroscopic surgery ?

Pre-operative endometrial thinning agents before hysteroscopic surgery ?

Endometrial ablation or resection offers a daycase surgical alternative to hysterectomy for these women. Complete endometrial removal or destruction is one of the most important determinants of treatment success

Pre-operative endometrial thinning agents before hysteroscopic surgery ?

Therefore surgery will be most effective if undertaken when endometrial thickness is less than 4mm, in the immediate post-menstrual phase. IF it is difficult to arrange surgery for this time ,the other option is the use of hormonal agents which induce endometrial thinning or atrophy prior to surgery. The most commonly evaluated agents have been goserelin (a GnRH analogue) and danazol.

A double-blind, randomized study that compared the use of goserelin acetate with placebo. Injections were given every 28 days for 8 weeks; endometrial ablation was performed 6 weeks after the first injection. At 3 years, 337 of 350 women were evaluated. Patients who had received goserelin acetate had an amenorrhea rate of 21%, as compared with 14% in the placebo group.**

**Vilos GA, Donnez J, Gannon MJ, et al. Goserelin acetate plus endometrial ablation for dysfunctional uterine bleeding. The journal of the American association of gynecologic Laparoscopists. 2000;7(suppl):s65.

 Many of the more experienced hysteroscopy's were not convinced that the additional cost, especially of multiple injections, warranted its use over simple mechanical preparation at the time of endometrial ablation. It is not believe that use of birth control pills or medroxyprogesterone acetate (MPA) was good for preparation, because they can lead to an edematous stroma.

The global congress on gynecologic EndoscopyOrlando, Florida -- November 15-19, 2000.

 Administration of MPA immediately postoperatively would improve endometrial ablation results in patients with submucosal myomas or adenomyosis. He noted a higher amenorrhea rate and lower failure rate in the treated group.

Goldrath MH. Does medroxyprogesterone acetate immediately postoperatively improve results of adenomyosis and endometrial ablation? The Journal of the American Association of Gynecologic Laparoscopists. 2000;7(suppl):S21.

Cochrane Reviewers' Conclusions

Endometrial thinning prior to hysteroscopic surgery for menorrhagia improves both the operating conditions for the surgeon and short term post-operative outcome. Gonadotrophin-releasing hormone analogues produce slightly more consistent endometrial thinning than danazol, though both agents produce satisfactory results. The effect of these agents on longer term post-operative outcomes and the need for further surgical intervention has not been considered in the studies included in this review. ISSUE 1.2003

4
Managing Patients With Large Symptomatic Fibroids

(UAE) Vs myomectomy

 Transient uterine ischemia by uterine artery occlusion has been shown to be effective in treating the primary symptoms of myomas, namely menorrhagia and bulk symptoms

 surgical uterine artery ligation for

myomas allows for management of the myomas by the gynecologist without involvement of interventional radiologists. Furthermore, it allows for visualization of the entire pelvis and treatment of any concomitant pathology. This does require the ability to isolate the uterine arteries, however, and, as seen in one of the series, does entail a risk of ureteric injuries(1) The results seem to be comparable to those seen with UAE, although decrease in bulk may be slower.(2)
1. Lee PI, Yoon JB, Joo KY. Uterine artery ligation for symptomatic leiomyomas. The Journal of the American Association of Gynecologic Laparoscopists. 2000;7(suppl):S32. Park KH, Kim JY, Chung JE. New treatment of myomas: angioblock and uterine artery ligation. The Journal of the American Association of Gynecologic Laparoscopists. 2000;7(suppl):S46.

2.

At the FIGO Meeting Held Year 2000 in Washington, Dr. J.H. Ravina, Hpital Lariboisire, Paris, France, Has Suggested That Possible Myomectomy After embolization, Especially of Dominant subserosal myomas, May Be Warranted. Furthermore, the Large submucosal myoma May Be Prone to Infection As Well As prolapse.

 Those who support myomectomy rely on a large body of evidence showing improvement in patients receiving fertility treatment whose only etiology for infertility is fibroids. Pregnancies in such patients are relatively uncomplicated except for the possible need for cesarean section for delivery, and there is a slight increase in risk of uterine rupture when the endometrial integrity is compromised. Information regarding fertility and pregnancy post-UAE is much more limited. While successful pregnancies have been reported, some questions of increased pregnancy loss have been raised. Furthermore, the risk of premature ovarian failure must be considered in these patients.

5
Interventions for Tubal Ectopic Pregnancy..Which Approach and When?

 The hCG level should rise at least 66% in 48 hours, and at least double in 72 hours. By 5.5-6 weeks of pregnancy (1.5-2 weeks after the missed period) all normal pregnancies should be seen by vaginal ultrasound.
The discriminatory zone is the level of serum beta-subunit human chorionic gonadotropin above which a gestational sac can be consistently visualized. With transabdominal sonography, this value is 6,500 mIU per ml; With transvaginal sonography, it is a level greater than 2000 mIU per ml.

Interventions for Tubal Ectopic Pregnancy..Which Approach and When?

As a consequence, the clinical presentation of ectopic pregnancy has changed from a life threatening disease to a more benign condition. This in turn has resulted in major changes in the options available for therapeutic management. Many treatment options are now available to the clinician in the treatment of tubal pregnancy:

Interventions for tubal ectopic pregnancy..which approach and when?

The choice of a treatment modality should be based on : 1-primary treatment success and reinterventions for clinical symptoms or persistent trophoblast (short term outcome) 2- tubal patency and future fertility.(Long term outcome)

Interventions for tubal ectopic pregnancy..which approach and when?

Incidence of persistent ectopic: After laparotomy: 3-5% of cases After laparoscopy: 3-20% of cases (most reports at 5-10%)
Best approach is to follow the woman with weekly hCG levels until negative. If a persistent ectopic is diagnosed, methotrexate therapy is usually the treatment of choice.

Interventions for Tubal Ectopic Pregnancy..Which Approach and When?

Selection criteria for methotrexate: 1. Hemodynamically stable 2. No evidence of tubal rupture or significant intraabdominal hemorrhage 3. Tube < 3-4 cm diameter 4. No contraindications to MTX 5. Informed consent 6. Patient will be available for protracted follow-up.

Local methotrexate is not a treatment option. Injection of this drug, both under laparoscopic guidance and under ultrasound guidance, is significantly less successful in the elimination of tubal pregnancy. Systemic methotrexate

Multiple dose
associated with a greater impairment of health related quality of life compared with laparoscopic salpingostomy

Single dose
is not effective enough in eliminating the tubal pregnancy compared to laparoscopic salpingostomy. This as a result of inadequately declining serum hCG concentrations after one single dose of methotrexate necessitating additional methotrexate injections or surgical interventions.

Prophylactic methotrexate after linear salpingostomy reduced the risk of persistent ectopic pregnancy.

Drawbacks of this kind of prophylactic therapy are that many patients will be treated unnecessarily with a chemotherapeutic agent which may produce severe side-effects.
hCG is estimated once seven days after surgery and if the level is higher than expected the patient should be given a single IM dose of methotrexate

Cochrane Reviewers' Conclusions

Laparoscopic surgery is the cornerstone of treatment in the majority of women with tubal pregnancy. If the diagnosis of tubal pregnancy can be made noninvasively, medical treatment with systemic methotrexate in a multiple dose intramuscular regimen is an alternative treatment option but only in hemodynamically stable women with an unruptured tubal pregnancy and no signs of active bleeding presenting with low initial serum hCG concentrations, after properly informing them about the risks and benefits of the available treatment options.
Citation: Hajenius PJ, mol BWJ, Bossuyt PMM, Ankum WM, van der Veen F. Interventions for tubal ectopic pregnancy (Cochrane review). In: the Cochrane library, issue 1 2003. Oxford: update software.

6
Evaluation of abnormal uterine bleeding
Office hysteroscopy vs saline infusion Sonography (SIS)

Sampling of the endometrium should be considered in all women over 40 ys. Of age with abnormal bleeding and in women who are at higher risk of

endometrial cancer including : nulliparity with a history of infertility obesity ( 90 kg)

polycystic ovaries
family history of endometrial and colonic cancer tamoxifen therapy.
Ballard-Barbash R, Swanson CA. Body weight: Estimation of risk for breast and endometrial cancer.Am J Clinical Nutrition 1996;63:437-41. Gibson M. Reproductive health and polycystic ovary syndrome.Am J Med 1995;98:67-75. Morgan RW. Risk of endometrial cancer after tamoxifen treatment. Oncology 1997;11: 25-33. Barakat RR. Benign and hyperplastic endmetrial changes associated with tamoxifen use. Oncology 1997;1:35-7.

Blind sampling of the endometrial cavity is relatively accurate for detecting cancer but are not sensitive for detecting structural abnormalities such as polyps or fibroids. Office hysteroscopy has become part of the gynecologist's armamentarium for the evaluation of abnormal uterine bleeding. It is well tolerated by patients and enables direct visualization and sampling

Given the fact that most gynecologists perform diagnostic hysteroscopies in the operating room and that the office equipment for hysteroscopy is expensive, hysteroscopy will be used as a purely operative procedure, for directed biopsies of focal lesions, or when the SIS is equivocal.

Transvaginal ultrasound is especially useful in postmenopausal patients to determine endometrial thickness. In a large multicenter study of postmenopausal women with an endometrial echo of less than 4 mm, the sensitivity and specificity of this technique for detecting endometrial pathology were 96% and 68%, respectively. *Of note is that if 5 mm was used as a cutoff limit, 2 endometrial carcinomas would have been missed in 1168 women with postmenopausal bleeding.
*Karlsson B, Granberg S, Wikland M, et al. Transvaginal ultrasonography of the endometrium in women with postmenopausal bleeding - a Nordic multicenter study. Am J Obstet Gynecol 1995;172:1488-1494.

The problem with transvaginal ultrasound is that it is not sensitive for diagnosing such intracavitary lesions as polyps or fibroids. In such cases,
the addition of SIS has helped. Polyps and fibroids within the endometrial lining are easily delineated with the installation of 530 cc of saline
Goldstein SR, Zeltser I, Horan CK, Et Al. Ultrasonography-based Triage for Perimenopausal Patients With Abnormal Uterine Bleeding. Am J Obstet Gynecol. 1997;177:102-108.

The introduction of five to 15 mL of saline into the uterine cavity using a saline primed catheter or a pediatric feeding tube may improve the diagnosis of intrauterine masses during TVS
*Spencer CP,Whitehead MI. Endometrial assessment re-visited (a review). Br J Obstet Gynecol 1999;106:623-32. Farquhar CM, Lethaby A, Sowter M,Verry J, Baranyai J.An evaluation of **Widrich T, Bradley LD, Mitchinson AR, Colins RI. Comparison of saline infusion sonography with office hysteroscopy for the evaluation of the endometrium.Am J Obstet Gynecol 1996;174:1327-34. Wolman I, Jaffa A, Hartoov J, Bar-Am A, David M. Sensitivity and

Key Recommendation
SIS made by skilled operators allows an accurate evaluation of uterine cavity and malformations, particularly in young women, reaching a diagnostic accuracy similar to that of hysteroscopy, improving the examination compliance and lowering both risks and side effects.
F.M. Severi, C. Bocchi, P. Florio, L. Cobellis, R. La Rosa, M.G. Ricci and F. Petraglia Chair of Obstetrics and Gynecology, University of Siena, Siena, Italy

7
Therapeutic Conization .Is There a Necessity of Removing the Entire endocervical canal in all cases

Therapeutic conization .is there a necessity of removing the entire

Therapeutic conization is currently the preferred modality to treat CIN grades 2 and 3. All described approaches (cold-knife, laser, and LEEP conizations) are equally effective, as found by Mitchell and colleagues. Controversies exist as to the necessity of removing the entire endocervical canal, including the internal os, in all cases. This approach, recommended by at least 2 studies, may increase the risk of cervical incompetence in women who desire posttreatment pregnancy

Therapeutic conization .is there a necessity of removing the entire

Since destructive methods such as cryotherapy yield no specimen for histologic studies, their use should be limited to those women in whom an accurate preoperative diagnosis has been established by directed biopsies.

By performing endocervical curettage or by obtaining cytology with an endocervical brush. If these tests are negative for CIN or glandular atypia, and if the patient wishes to preserve her childbearing potential, we preserve the cranial extremity of the endocervical canal.

8
Clomiphene citrate for unexplained subfertility in women

Clomiphene citrate for unexplained subfertility in women

The effectiveness of clomiphene citrate has been clearly demonstrated in the treatment of subfertility associated with oligo-ovulation. The multiple pregnancy rate associated with clomiphene, however, is elevated at approximately 10%. Additional side effects associated with clomiphene use also include hot flashes, mood swings, headaches and visual disturbances.

Clomiphene citrate for unexplained subfertility in women

A variety of publications have raised the question of increased ovarian cancer risks associated with clomiphene use. Understanding the effectiveness of clomiphene in this patient group is therefore, extremely important.

Cochrane Reviewers' conclusions

Although the absolute treatment effect is small, given the low cost and ease of administration, clomiphene citrate appears to be a sensible first choice treatment for women with unexplained infertility. However, in making this treatment choice, concerns of long-term use and ovarian cancer risk, multiple pregnancy risk and minor symptoms should be discussed. Given the extensive use of clomiphene in ovulatory women and recent concerns associated with long term use, a definitive trial with adequate power is warranted to establish effectiveness in women with unexplained subfertility.

9
Metformin as a treatment option in PCO patients.

Metformin As a Treatment Option in PCO Patients.

Fortunately, when given to non_diabetic patients, Metformin does not lower blood sugar while appears to be very safe

 It has been shown to increase levels of sex hormone binding globulin, thought to be a secondary response of reducing hyperinsulinaemia and thus reducing free testosterone levels in circulation* . It also reduces luteinising hormone concentrations and ovarian sensitivity to luteinising hormone. Over 90% of women with oligomenorrhoea or amenorrhoea are reported to return to normal cycles with treatment, with 20% conceiving within six months.**
*Pirwany IR, Yates RW, Cameron IT, Fleming R. Effects of the insulin
sensitizing drug metformin on ovarian function, follicular growth and ovulation rate in obese women with oligomenorrhoea. Hum Reprod 1999; 14: 2963-296826.

**Nestler JE, Jakubowicz DJ, Evans WS, Pasquali R. Effects of metformin

on spontaneous and clomiphene-induced ovulation in the polycystic ovary syndrome. N Engl J Med 1998; 338: 1876-1880

Metformin As a Treatment Option in PCO Patients.

Four trials (two controlled and two uncontrolled) of metformin, a diabetes medication that reduces insulin resistance, have demonstrated a fall in serum androgens, luteinising hormone and weight and an improvement in fertility and fibrinolysis in both obese and lean women with polycystic ovary syndrome.*,**
*Legro R, Finegood D, Dunaif A. A fasting glucose to insulin ratio is a useful measure of insulin sensitivity in women with polycystic ovary syndrome. J Clin Endocrinol Metabol 1998; 83: 2694-2698. **Nestler JE, Jakubowicz DJ. Lean women with polycystic ovary syndrome respond to insulin reduction with decreases in ovarian P450c170 activity and serum androgens. J Clin Endocrinol Metab 1997; 82: 4075-4079

Metformin As a Treatment Option in PCO Patients.

Two studies have shown no improvement with metformin. The women in the first of these two studies were Turkish, which may have influenced the result as it is known that many intracellular enzyme defects can lead to insulin resistance and that the nature of insulin resistance can vary between racial groups. In the second negative study, the diet of the subjects was modified to prevent weight loss during metformin therapy.
Acbay O, Gundogdu S. Can metformin reduce insulin resistance in polycystic ovary syndrome? Fertil Steril 1996; 65: 946-949. Ehrmann DA, Cavaghan MK, Imperial J, et al. Effects of metformin on insulin secretion, insulin action and ovarian steroidogenesis in women with polycystic ovary syndrome. J Clin Endocrinol Metab 1997; 82: 524-530.

Metformin As a Treatment Option in PCO Patients.

A recent controlled trial was performed in the united states, Venezuela and Italy in which obese women with polycystic ovary syndrome were given either metformin or placebo. Within 53 days only 7% of women treated with metformin or metformin plus clomiphene had not ovulated, compared with 88% of women treated with clomiphene alone.
1. Nestler J, Jakubowicz D, Evans W, et al. Effects of metformin on spontaneous and clomiphene-induced ovulation in the polycystic ovary syndrome. N Engl J Med 1998; 338: 1876-1880.

Metformin as a treatment option in PCO patients.

Side effects are rare. . In the first week of taking the medication, people will often experience upset stomach or diarrhea which usually resolves after the first week. For those on metformin, this side effect can be minimized by starting with one pill 850 mg.Daily the first week and increasing to twice a day during the second week.

Metformin As a Treatment Option in PCO Patients.

Patients with reduced renal function are at a higher risk for a rare side effect of metformin therapy called lactic acidosis, and the drug should be given cautiously, if at all, to such patients.

Metformin as a treatment option in PCO patients.

While safety during pregnancy has not yet been established ,this drug is considered class B meaning that insufficient human data is available but no credible animal data suggests a teratogenic risk.