Laparoscopic Ablation For Minimal Or Mild Lesions In Endometriosis Associated Subfertility

1
Laparoscopic Ablation For Minimal Or Mild Lesions
In Endometriosis Associated Subfertility
Hesham Al-Inany, M.D kaainih_at_link.net
2
Dr Al-Inany is a Senior Lecturer at Cairo
University and IVF specialist at the Egyptian
IVF-ET Center. He has conducted the first
prospective meta-analysis in the entire filed of
gynecology comparing GnRH agonist vs antagonist
in assisted conception. Dr.Al-Inany is
responsible for "Evidence Based Medicine" corner
in the Middle East Fertility Society Journal for
more than 3 years, explaining the values of
evidence based medicine and it tools. He has
published over 25 scientific articles since he
obtained his medical qualification in Obstetrics
Gynecology in 1998.
3
Definition

• Endometriosis, defined as the presence of
  endometrial glands and stroma at ectopic sites,
  is still not yet fully understood

4
Prevalence

• Endometriosis prevalence varies widely being seen
  more frequently among women investigated for
  infertility (21) than among those undergoing
  sterilisation (6).
• Among those being investigated for chronic
  abdominal pain, the incidence of endometriosis is
  15, while among those undergoing abdominal
  hysterectomy, it can be as high as 25.

5

• The relation of minimal or mild endometriosis to
  subfertility is not established. The association
  is not necessarily cause and effect.

6

• Hence, the concept that minimal or mild
  endometriosis should always be treated to avoid
  worsening of the condition is controversial
  (Buyalos RP, Agarwal SK,2000)

7

• Minimal/mild endometriosis could represent a
  temporary phase in an on-going process that
  usually results in cytolysis of recently
  implanted endometrial cells, whereas in a few
  immunologically 'tolerant' subjects, nodular,
  cystic and infiltrating lesions develop

8
Diagnosis

• The gold standard test to diagnose endometriosis
  is the direct visualisation of classical or
  subtle lesions at laparoscopy.

9
Is it progressive!!!

• In the medical literaturer, there is one small
  randomised controlled trial (RCT) in which repeat
  laparoscopy was performed in the women treated
  with placebo.

10

• Over 12 months, endometrial deposits resolved
  spontaneously in a quarter, deteriorated in
  nearly half, and were unchanged in the remainder.
  (Cooke,1989)

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Where we stand?

• Whether minimal endometriosis is a condition that
  is frequently self-limited or resolves
  spontaneously or not, we still face a problem.
  Could ablation of minimal or mild endometriosis
  be associated with an increase in pregnancy rate.
  This is the hypothesis to be tested.

12
Treatment modalities

• Conventional treatments for endometriosis aim to
  remove or decrease deposits of ectopic
  endometrium. They achieve this either by inducing
  atrophy within the hormonally dependent ectopic
  endometrium, or by destroying the endometriotic
  implant.

13

• Medical treatment options for endometriosis
  include hormonal drugs such as the combined oral
  contraceptive, progestogens, danazol, gestrinone
  or gonadotrophin releasing hormone analogues for
  pain relief.

14

• The aim of therapy is to "switch off ovarian
  function". Their role in infertility treatment
  has been reviewed in a Cochrane systematic review
  which concluded that there is no evidence to
  support their use in women with endometriosis
  who wish to conceive. (Hughes,1999)

15

• While these approaches continue to be useful for
  the management of endometriosis associated pain,
  they may do more harm than good in women whose
  major concern is fertility. For the six months or
  more of treatment, women are forced to contracept.

16

• The other option for women with endometriosis who
  wish to conceive is surgical ablation of deposits
  of endometriosis. The surgery may be performed
  laparoscopically including excision, laser or
  diathermy ablation and adhesiolysis.

17
Where is the evidence?

• A prospective cohort analysis was conducted to
  analyze results from 579 women with
  endometriosis to evaluate the role of surgery in
  the treatment of endometriosis associated with
  infertility. Adamson GD, Pasta DJ ,1994)

18

• Interventions consisted of no treatment, medical
  treatment, or surgical treatment by laparoscopy
  or laparotomy. The main outcome measure was
  pregnancy rates.

19

• For minimal and mild disease, no treatment,
  laparoscopy, and laparotomy had equivalent 3-year
  estimated cumulative life-table pregnancy rates
  (67 /- 12, 68 /- 4, and 74 /- 8,
  respectively) that were higher than medical
  treatment pregnancy rates (p 0.003).

20
The authors urged for prospective randomized
trials to be performed to confirm these findings.
21
RCTs

• Marcaux et al, 1997 conducted a randomized
  controlled trial to reach a clear evidence on
  ablation of minimal or mild endometriosis. They
  studied 341 infertile women 20 to 39 years of age
  with minimal or mild endometriosis.

22

• During diagnostic laparoscopy the women were
  randomly assigned to undergo resection or
  ablation of visible endometriosis or diagnostic
  laparoscopy only. They were followed for 36
  weeks after the laparoscopy

23

• The corresponding rates of fecundity were 4.7 and
  2.4 per 100 woman-months (rate ratio, 1.9 95
  confidence interval, 1.2-3.1).

24

• Fetal losses occurred in 20.6 of all the
  recognized pregnancies in the laparoscopic-surgery
  group and in 21.6 of all those in the
  diagnostic-laparoscopy group (P0.91). The
  authors concluded that Laparoscopic resection or
  ablation of minimal and mild endometriosis
  enhances fecundity in infertile women.

25

• Two years later, a group from Italy have
  conducted another randomized controlled trial to
  evaluate the available evidence. Eligible women
  were randomly assigned to resection or ablation
  of visible endometriosis (54 patients) or
  diagnostic laparoscopy only (47 patients).

26

• Follow up for one year showed that 12 (24) in
  the resection/ablation group and 13 (29) in the
  no treatment group conceived the difference was
  not significant.

27
Comments

• Two points should be noticed in these two trials.
  First, in order to be able to conclude that
  removing endometriosis is effective, then it
  would be better not to do the adhesiolysis which
  can be considered as a co-intervention. However,
  this was not done.

28

• The second point is that the patients were
  informed about the result of procedure done
  (ablation or no ablation) immediately after
  laparoscopy at their postoperative appointments.
  This could have a possible negative placebo
  effect on those in expectant group or a positive
  placebo effect in those who had ablation.

29

• If we consider only late pregnancies in the these
  two trials (50/172 in the ablation group versus
  29/169 in the no surgery group in the Canadian
  study and 10/54 versus 10/47 respectively in the
  Italian study), the O.R would be 1.64 (95 CI,
  1.022.67) noticing that the lower confidence
  interval limit is too close to unity

30
NNT

• If we express the results more practically in
  terms of number of women to undergo surgery to
  achieve an additional pregnancy. In this case,
  even taking into account only the results of the
  Canadian trial, the benefit of laparoscopic
  ablation appears less encouraging.

31

• The net result is that eight women with minimal
  to mild endometriosis need to undergo
  laparoscopic ablation to achieve an additional
  late pregnancy.

32

• However, considering that we cannot identify
  women with endometriosis preoperatively, and that
  the proportion of subjects with endometriosis in
  the Canadian series of patients undergoing
  laparoscopy for unexplained infertility was a
  little lt50, the number needed to be treated
  doubles at least

33
More Over

• Interestingly, the Canadian group has also
  conducted a well designed prospective cohort
  study (1998) to assess whether infertile women
  with minimal or mild endometriosis have lower
  fecundity than women with unexplained
  infertility.

34

• Infertile women with minimal or mild
  endometriosis (n 168) were compared with women
  with unexplained infertility (n 263). Both
  groups were managed expectantly. The women were
  followed up for 36 weeks after the laparoscopy
  or, for those who became pregnant, for up to 20
  weeks of the pregnancy.

35

• Fecundity was 18.2 in infertile women with
  minimal or mild endometriosis and 23.7 in women
  without endometriosis. The fecundity rate was
  2.52 per 100 person-months in women with
  endometriosis and 3.48 per 100 person-months in
  women with unexplained infertility.

36

• The crude and adjusted fecundity rate ratios
  were 0.72 and 0.83 (95 confidence interval
  0.53-1.32), respectively. Thus, The fecundity of
  infertile women with minimal or mild
  endometriosis is not significantly lower than
  that of women with unexplained infertility.

37

• Many investigators are wondering if minimal or
  mild endometriosis is really a disease that needs
  treatment.

38
Conclusion

• Laparoscopic ablation for minimal or mild
  endometriosis associated subfertility seems to be
  of very limited efficacy. Exposing those women to
  unnecessary anaesthesia and laparoscopic
  manipulations should not be done except in the
  context of randomized controlled trial

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Recommendations(if you decide to do ablation)

• Exclude all other causes of subfertility
• Estimate the probability of pregancy with and
  without treatment.
• Counsel the couple.

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• Decide on the most appropriate ablation modality
  available (laser, diathermy)
• Assess the potential for harm with this treatment
  (e.g.pelvic adhesions)
• If ablation is still to be done, ensure that it
  is provided optimally.