Controversies in

Gynecology

Dr. Mohammed Abdalla

Egypt, Domiat G. Hospital
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. Endometrial resection and ablation versus hysterectomy ..WHICH?
3. Pre-operative endometrial thinning agents before hysteroscopic surgery ?
4. Managing patients with large symptomatic fibroids(UAE)Vs myomectomy.
5. Interventions for tubal ectopic pregnancy..Which approach and when?
6. 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 ?
• 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 color-
flow 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:
2. Menorrhagia unresponsive to (or with a
contraindication to) either:
• Hormonal therapy or other pharmacotherapy; Or
• Dilation and currettage; And

• Endometrial sampling has excluded cancer, pre-

cancer, or structural abnormalities (polyps, fibroids)
that require surgery. And
• 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 skill-
dependent 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 day-

case 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)

3. 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.
4. 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.
At the FIGO Meeting Held Year 2000 in Washington, Dr.
J.H. Ravina, Hôpital Lariboisière, 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 intra-
abdominal 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 Single dose

associated with a greater
impairment of health related
quality of life compared with
laparoscopic salpingostomy
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 5-
30 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
sub-fertility 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
 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.

• 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.