Endometriosis is conventionally defined as the presence of tissue lesions or nodules that are histologically similar to the endometrium, but are present at sites outside the uterus.It is a chronic, often recurring disease of complex and unclear aetiology. Endometriosis is a highly variable condition in terms of age and mode of presentation, range of symptoms, anatomical sites, response to treatment and likelihood of recurrence.

1. Evidence linked treatment for endometriosis-associated infertility

2. Apollo Medicine 2012 September
Volume 9, Number 3; pp. 184e192
Review Article
Evidence linked treatment for endometriosis-associated infertility
Sohani Verma
ABSTRACT
Endometriosis e defined as the presence of tissue similar to endometrium outside the uterine cavity, is commonly
associated with infertility. The true prevalence remains obscure due to overall lack of well-designed epidemiologic
studies. The disease has an enigmatic and multifaceted pathology which remains elusive despite decades of
investigation. Despite all the uncertainties, it is established that treatment of endometriosis can improve fertility in
some cases. Medical therapy although useful in reducing the severity of other symptoms of endometriosis such as
pain and menstrual disorders, is not efficacious to improve fertility. Laparoscopic surgery apart from establishing the
diagnosis, appears to be superior to expectant management or medical therapy. Controlled ovarian stimulation with
intrauterine insemination is recommended in early stage and surgically corrected endometriosis when pelvic anatomy
is normal. In advanced cases or moderate disease with associated tubal or male factors, in vitro fertilization is
a treatment of choice. Despite all treatments, pregnancy rates remain lower in these women compared to diseasefree controls. Further well structured randomized clinical trials are necessary to reach any conclusive answers.
Copyright © 2012, Indraprastha Medical Corporation Ltd. All rights reserved.
Keywords: Infertility, Endometriosis, Treatment, Evidence linked
Endometriosis is conventionally defined as the presence of
tissue lesions or nodules that are histologically similar to
the endometrium, but are present at sites outside the uterus.1
It is a chronic, often recurring disease of complex and
unclear aetiology. Endometriosis is a highly variable condition in terms of age and mode of presentation, range of
symptoms, anatomical sites, response to treatment and likelihood of recurrence.
Infertility is defined as failure to conceive after regular
unprotected sexual intercourse for 1e2 years.2 The incidence and prevalence of endometriosis cannot be accurately
determined due to uncertainties in making a definite diagnosis without laparoscopy. It is thought to affect upto
5e10% of women of reproductive age. Amongst those
women presenting with infertility, it can be detected in
about 30e50% of all cases.3
DOES ENDOMETRIOSIS AFFECT
INFERTILITY?
Although it is not uncommon to find varying degree of
endometriosis in parous women, there is ample evidence
in literature to implicate endometriosis contributing to infertility. When surgically investigated, infertile women have
a much larger chance of having endometriosis (21%) in
comparison to women undergoing sterilization (6%).4 If
there is associated moderate to severe dysmenorrhoea
with infertility, there is 50% of chance of women having
endometriosis.5
The most convincing evidence comes from a prospective
study of therapeutic donor insemination in which monthly
fecundity was 0.12 in women without endometriosis and
0.036 in those with minimal endometriosis.6 Similar results
Senior Consultant, Obstetrician & Gynaecologist, Infertility & ART Specialist, Clinical & Academic Coordinator, Department of IVF, Indraprastha
Apollo Hospitals, Sarita Vihar, New Delhi 110076, India.
email: sohaniverma@hotmail.com
Received: 9.6.2012; Accepted: 2.7.2012; Available online: 7.7.2012
Copyright Ó 2012, Indraprastha Medical Corporation Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.apme.2012.07.001

3. Treatment for endometriosis-associated infertility
after donor as well as husband’s sperm insemination in
women with minimal to mild endometriosis when
compared to these with a normal pelvis have been shown
in various others studies.7
Reduced pregnancy rates have been reported in women
with endometriosis undergoing In Vitro Fertilization
(IVF). Barnhart et al (2002) in a meta-analysis of 22 published studies concluded that pregnancy rate is almost
half in these women when compared with tubal factor
infertility.8
Donor oocytes from women with endometriosis have
been reported to yield lower pregnancy rates that those
from the healthy donors.9
Review Article
185
- Increased progesterone concentration in follicular
fluid
- Increased concentration of IL-6, IL-Ib, IL-8
- Increased expression of the TNFa in the cultured
granulosa cells
- Lower levels of cortisol
- Lower concentrations of IGFBP-I
- Lower levels of HCG receptors in granulosa cells
- Increased rate of apoptosis in granulosa cells mediated by elevated concentrations of soluble Fas ligand
in serum and peritoneal fluid.
EFFECT ON ENDOMETRIAL RECEPTIVITY
PATHOGENIC MECHANISM IN ENDOMETRIOSIS-ASSOCIATED INFERTILITY
The exact cause of infertility remains elusive and controversial. The possible mechanisms may be anatomical
disruption or physiological-hormonal, chemical or immunological alterations. All aspects of reproductive
process e oocyte development, ovulation process, fertilization, embryo quality and implantation have been reported to
be adversely affected by endometriosis.10 Several cytokines, interleukins, oxidative stress markers, cellular adhesion markers and immunomodulators are being
investigated to decode the mysterious role of endometriosis
in causing infertility. The current literature suggests a multifactorial mechanism.
POSSIBLE CAUSES OF REDUCED FERTILITY
IN WOMEN WITH ENDOMETRIOSIS
(i) Tubal adhesions
(ii) Impaired gamete interaction
(iii) Reduced functional ovarian tissue (ovarian reserve) by
endometriosis or surgery
(iv) Poor quality of oocytes
(v) Impaired fertilization
(vi) Lower quality embryos with a reduced ability to
implant
(vii) Impaired implantation
POOR QUALITY OF OOCYTES
Several investigators have reported altered follicular environment in women with endometriosis and linked this to
poor quality oocytes. Few of these reported markers are11,12:
Pellicer et al (2001)9 published a cross-over oocyte donation study and concluded that it is the oocyte quality and
not endometrial receptivity, that plays a role in diminished
pregnancy rates in women with endometriosis. However,
a study analyzing a cohort of 170 oocyte donors reported
no significant effects but a trend for reduced pregnancy
rates in recipient cycles if the donor had endometriosis
and a trend for reduced implantation rates in recipients
with endometriosis, suggesting a potential mild effect of
endometriosis on both the uterine environment and the
quality of the oocyte.13
There is increasing evidence to support the hypotheses
that endometriosis is primarily an “endometrial” disease.
Multiple functional and microanatomical abnormalities
have been demonstrated within endometrium. The key
functional anomalies appear to be the expression of intracellular adhesions molecules, the presence of local aromatase enzyme activity, decreased apoptosis, increased
angiogenesis and increased neurogenesis.1
The available data suggests that both-development of
oocytes & embryos and endometrial receptivity can be
compromised in women with endometriosis.
DIAGNOSIS OF ENDOMETRIOSIS IN INFERTILE WOMEN
- The most common presenting complaints include
chronic pelvic pain, dysmenorrhoea, dyspareunia, dyschezia (pain on defecation) and low back pain. On
physical examination localized pelvic tenderness with
or without a mass/nodularity is often demonstrable.
Uterus may be fixed and retroverted due to adhesions.
- Pelvic transvaginal ultrasound although limited
by its non-specificity, is very useful in detecting

4. 186
Apollo Medicine 2012 September; Vol. 9, No. 3
endometriomas (chocolate cyst) and in monitoring its
size in response to therapy.
- CT scan and MRI pelvis are other non-surgical diagnostic tools used to identify the presence and the
extent of deeply infiltrating lesions. These are especially useful in detecting bowel and ureteric
involvement.
- The “gold standard” for diagnosis remains direct visualization of endometrial lesions using laparoscopy,
ideally with histopathological confirmation by biopsy
of excised endometriotic tissue. Classic lesions are
red, blue-black powder burn appearance, white or
non-pigmented patches.
- Serum CA 125 levels may be elevated in endometriosis. However, the test’s performance in diagnosing
all disease stages is limited with an estimated sensitivity of only 28% and specificity of 90%. Compared
with laparoscopy, measuring serum CA 125 levels,
has no value as a diagnostic tool (Grade A
recommendation).
STAGING OF ENDOMETRIOSIS
Although various classification systems have been
proposed to standardise the criteria for severity of symptoms, no system so far has received universal acceptance.
Based on revised American Society for Reproductive Medicine (ASRM)14 (Fig. 1) endometriosis can be classified into
four different stages:
Stage
Stage
Stage
Stage
I (minimal)
II (mild)
III (moderate)
IV (severe)
1e5 (Revised ASRM scoring system)
6e15
16e40
>40
EVIDENCE-BASED TREATMENT OF
ENDOMETRIOSIS-ASSOCIATED
INFERTILITY
A number of treatment options are available to treat infertility in women with endometriosis.
(i) Expectant management
(ii) Medical therapy
(iii) Surgical treatment
(iv) Combined medical and surgical therapy
(v) Controlled ovarian stimulation (COS) with or without
Intrauterine Insemination (IUI)
(vi) Assisted reproduction techniques
Verma
EVIDENCE-BASED MEDICINE
Grade A recommendation is based on good evidence obtained from meta-analysis of randomized controlled trials
(RCT) e Evidence level Ia or at least one RCT e Evidence
level IB.15
Grade B recommendation is based on well controlled
clinical studies (CT, cohort, case-control) but no RCT
(Evidence levels IIa, IIb and III).
Grade C recommendation is based primarily on
consensus and expert opinion (evidence level IV).
Good practice point e Based on clinical experience of
the guideline development group.
PROBLEMS IN THE EVALUATION OF TREATMENT OPTIONS FOR ENDOMETRIOSISASSOCIATED INFERTILITY
- Any management should be compared to expectant
management
- The monthly fecundity rate (MFR) is more meaningful than the pregnancy rate (PR)
- Few studies are controlled
- Few studies report the fecundity rate
- Techniques/skills differ
- Recognition of “atypical” lesions
Expectant management in endometriosis
The fecundity defined as the probability of a woman
achieving pregnancy in a given month, ranges from 0.15
to 0.20 in normal couples and 0.02 to 0.10 in untreated
women with endometriosis.16
It is well known that monthly fecundity is lower in
women with endometriosis than in women without this
condition. The reduced fertility rates are shown in Table 1.17
As some women especially with mild to moderate endometriosis will conceive spontaneously, when comparing the
effectiveness of any therapy for infertility, this needs to
be considered.
Medical therapies
The medical treatment of endometriosis involves suppressing oestrogen/progesterone levels to prevent cyclical
changes and menstruation. Depending upon their mode of
action these agents can be classified under 3 categories
(Table 2).18 Although these medical therapies are helpful
in reducing the severity of pain and menstrual disorders

5. Treatment for endometriosis-associated infertility
Fig. 1
Review Article
187

6. 188
Apollo Medicine 2012 September; Vol. 9, No. 3
Table 1 Spontaneous
endometriosis.17
Degree of
endometriosis
Mild
Moderate
Severe
All cases
conception
in
women
Verma
with
Cumulative pregnancy rate (CPR)
Monthly fecundity
rate (MFR)
52.9%
25%
0%
24.4%
5.7%
3.2%
0%
3.1%
Table 3 Cumulative pregnancy rates following ovarian
suppression for endometriosis (CPR).5
associated with endometriosis, these are not shown to be
effective in the treatment of infertility.
The value of ovarian suppression with danazol, medroxyprogesterone acetate or gestrinone versus placebo/no treatment has been assessed in a Cochrane review.16 The odds
ratio for pregnancy following ovulation suppression versus
placebo or no treatment was 0.74 (95% CI 0.48e1.15).
These data were statistically homogeneous, despite the
use of a variety of suppression agents. The odds ratio for
pregnancy following all agents versus danazol, the most
commonly used agent prior to the advent of GnRH
agonists, was 1.3 (95% CI 0.97e1.76).
Commonly used ovulation suppression agents have been
known to cause significant adverse effects such as weight
gain, hot flushes and bone loss.
Clearly, there is no evidence to support the use of
ovarian suppression agents in the treatment of endometriosis-associated infertility (Table 3). More harm than good
may result from treatment, because of adverse effects and
the lost opportunity to conceive.
Recommendations
Suppression of ovarian function to improve fertility in minimalemild endometriosis is not effective and should not be
offered for this indication alone. There is no evidence of its
effectiveness in more severe disease either (Grade A
Recommendation).7,15
No
therapy
Thomas et al., 1987 (RCT)
(Gestrinone)
Bayer et al., 1988 (RCT)
(Danazol)
Telimaa et al., 1988 (RCT)
(Danazol)
Telimaa et al., 1988 (RCT)
(MPA)
Fedele et al., 1992 (RCT)
(Buserelin)
Ovarian
suppression
P
value
24%
25%
NS
57.4%
37.2%
NS
46%
33%
NS
46%
42%
NS
61%
37%
NS
Surgical management
When endometriosis causes mechanical distortion of the
pelvis, surgery is usually indicated to restore the normal
pelvic anatomy. However, no RCTs are available to give
a definitive answer whether surgery enhances the pregnancy rates.
Laparoscopy is the preferred surgical approach due to
40% lower risks than that of laparotomy.19 The goal of
surgery is to remove endometriotic lesions as much as
possible, restore normal anatomy with adhesiolysis and
optimize ovarian and tubal preservation and integrity. Excision or cystectomy is preferred over fenestration, drainage
or ablation of the cyst lining for the treatment of an ovarian
endometriomas.
There are several power sources used in endoscopic
surgery such as electrocautery (mono or bipolar), CO2 laser,
Fibre lasers (KTP, argon, Nd YAG), diode laser, Harmonic
scalpel or Helica thermal coagulator. No significant difference in pregnancy rates using different power source has
been reported.19 Use of adhesion-prevention adjuncts may
Table 2 Medical therapy for endometriosis.18
Suppression of ovulation/oestrogen
Oral contraceptive pill
Danazol
Gestrinone
Direct action on endometriotic deposits
Progesterone antagonists (Mifepristone, Onapristone)
SPRMs (Selective Progesterone Receptor Modulators) e
Asoprisnil
SERMs (Selective Oestrogen Receptor Modulators) e
Raloxifene
Aromatase inhibitors (Letrozole, Anastrozole)
(GnRH) Gonadotrophin releasing
hormone
agonists or antagonists
Aromatase inhibitors
ER ligands (Estrogen Receptor beta agonists)
Progestogen & (Medroxyprogesterone Angiogenesis inhibitors
etc.)
Immunomodulation
Inflammatory modulators
Matrix metallo-proteinase inhibitors
(MMP)
Anti TNF Alfa Therapy (Pentoxi-fylline
etc.)

7. Treatment for endometriosis-associated infertility
help to reduce adhesion formation but improvement in
fertility is unknown.20
Recommendations
- Ablation of endometriotic lesions plus adhesiolysis to
improve fertility in minimalemild endometriosis is
effective compared with diagnostic laparoscopy alone
(Grade A Recommendation).
- The role of surgery in improving pregnancy rates for
moderate to severe disease is uncertain (Grade B
Recommendation).
- There is no universal consensus, but generally cystectomy for ovarian endometriomas is considered better
than drainage and coagulation (Grade A recommendation) and has less chance of recurrence.
Combined medical & surgical therapy
Surgery combined with pre and postoperative medical
therapy represents a growing field of drug application.
Theoretically, preoperative medication may reduce inflammation, vascularization, and implant size, making the
surgery faster, easier and less traumatic, and the potential
for complete eradication of the disease and decreased risk
of postoperative adhesions.
However, drawbacks of combined therapy include drug
costs, side effects, and temporary regression of endometrial
foci allowing escape from laparoscopic recognition and
ablation.21
Preoperative medical therapy
The preoperative use of medication may be useful for
reducing the severity of endometriosis. A prospective
multicenter clinical trial by Audebert et al21 reported reductions in severity with preoperative compared with postoperative GnRHa treatment, although surgical feasibility did not
differ significantly. Nasal application of GnRHa has
revealed decreased inflammation, vascularization, severity,
and endometrioma growth. However, in the absence of
convincing evidence of improvements in surgical feasibility
and in fertility rate, the use of preoperative medication is
controversial.
Postoperative medical therapy
Postoperative medical therapy is another option in
combined therapy, aiming to achieve resorption of residual
deposits that cannot be surgically removed, destruction of
microscopic implants, and reduction of disease dissemination in case of endometrioma rupture. Few studies have
evaluated the use of postoperative medical therapy with
Review Article
189
GnRHa. None of these studies reported increased fertility
rates with postoperative medication. ESHRE guidelines
conclude that postoperative danazol or GnRHa treatment
is not more effective than expectant management in
improving fertility for endometriosis-associated infertility
(Grade A recommendation, Evidence level 1b).7
Sandwich therapy
d
Medical-surgical-medical therapy
Recommendations
- Cochrane review 2007 documents no benefit of
hormonal suppression before or after surgery.16
- The opinion on pre-surgical medical therapy is
controversial.21 In some reports pre-surgical medical
therapy showed a significant improvement in pregnancy rates.22,23
- Post-surgical hormonal suppression has no beneficial
effect on pregnancy rates after surgery15 (Grade A
recommendation).
Combined ovarian stimulation (COS) with or
without Intrauterine Insemination (IUI)
- Several RTCs have shown significant higher clinical
pregnancy rates with COS & IUI treatment compared
to no treatment.7 However the presence of endometriosis is shown to reduce treatment effectiveness of IUI
by approximately half (OR 0.45), when compared
with similar treatment in disease-free women.24
- In general, repetitive COS þ IUI cycles show
a plateau effect after 3e4 cycles, therefore patients
must be counselled to switch to IVF after 3e4
cycles.7
- IUI plus gonadotrophins have been shown to significantly increase live birth rates in at least two RCTs.
One RCT2 reported 29% live birth rates with IUI
and gonadotrophins in comparison to 8% with no
treatment. The other cross-over RCT2 found that
alternate cycles of gonadotrophins plus IUI had
19% pregnancy rates versus 0% with IUI alone.
Recommendation
- Treatment with IUI improves fertility in minimal to
mild endometriosis. IUI with ovarian stimulation is
effective but the role of unstimulated IUI is uncertain
(Grade A recommendation).

8. 190
Apollo Medicine 2012 September; Vol. 9, No. 3
Assisted Reproduction Techniques (ART)
In Vitro Fertilization (IVF) is appropriate treatment, especially if tubal function is compromised, if there is also
male factor infertility and/or other treatments have failed
(Grade B recommendation). It represents an effective
means to bypass the hostile peritoneal environment and
anatomic distortion associated with endometriosis.
However, a meta-analysis of published studies suggests
that IVF pregnancy rates are lower in patients with endometriosis than in those with tubal infertility.8 The review
included 22 studies, consisting of 2377 cycles in women
with endometriosis and 4383 in women without the disease.
After adjusting for confounding variables, there was a 35%
reduction in the chance of achieving pregnancy (OR 0.63).
Other outcome parameters such as fertilization rate, implantation rate, mean number of oocytes retrieved and peak oestradiol concentrations were also significantly lower in
endometriosis group.
Although both GnRH antagonist and GnRH-analogue
protocols for IVF/ICSI are equally effective in terms of
implantation and clinical pregnancy rates, GnRH-analogue
may be preferred because of the availability of more M II
oocyts and embryos.25
Use of ultralong (3e6 months) prior to IVF in a group of
patients with significantly high proportion patients classified as moderate to severe endometriosis, showed higher
pregnancy rates23 (Grade A recommendation).
Verma
endometriomas 4 cm in diameter. Women should
be counselled regarding the risks of reduced ovarian
function after surgery.
- ESHERE guidelines 2008 e laparoscopic ovarian
cystectomy in patients with unilateral endometriomas
between 3 and 6 cm in diameter before IVF/ICSI can
decrease ovarian response without improving cycle
outcome e (Evidence level IB).
- As per the evidence available, there is no significant
difference in the clinical pregnancy rate by adopting
no intervention or medical or surgical option in
women with endometriomas.27
Based on above reports, there is insufficient evidence to
recommend surgical treatment of endometriomas before
IVF/ICSI cycles.
There are exceptions e such as pelvic pain (possibility
of intensifying during COHS), presence of hydrosalpings
and large endometriomas especially when doubts exist
about their exact nature, where surgery before ART should
be undertaken.28
Large randomized trials are needed. In the meantime
decisions need to be taken on a comprehensive and individualised basis.
Aspiration of endometrioma prior to IVF remains another
controversial issue. Traditionally it has been advised to avoid
aspiration due to risk of infection, however, Suganuma et al
(2002) compared the aspiration to surgery and no treatment
and found higher fertilization rate in aspiration group.29
SUMMARY
SURGERY FOR ENDOMETRIOMA-BEFORE
ART RECOMMENDED OR NOT?
The presence of an endometriotic cyst in women undergoing ART supposedly has a negative influence on the
results although the literature is far from consistent on
this point.7 The advantage of surgery has to be weighed
against the disadvantage of the loss of ovarian tissue containing follicles close to the cyst.
Recommendations
- NICE guidelines 20042 e if endometrioma 3 cm
with reasonable amount of normal ovarian stroma
and antral follicles e it should be left alone and
IVF carried out.
- ASRM-200626 e if bilateral large endometriomas
4 cm counsel for surgical excision prior to IVF/ICSI.
- RCOG Guidelines No 2415 e laparoscopic ovarian
cystectomy before IVF is recommended for
Based on currently available evidence, the stage wise treatment of endometriosis associated with infertility can be
summarized as given below:
Management of minimal to mild endometriosis
with infertility
- Ablation of endometriotic lesions plus adhesiolysis at
the time of diagnostic laparoscopy is recommended
(Grade A Recommendation).
- Suppression of ovarian function using drugs (OC
pills, progestational agents, danazol, GnRH agonists)
is of no benefit to infertile woman and delays potential conceptions (Grade A Recommendation).
- Considering age, ovarian reserve and excluding male
and tubal factors, option to try naturally for 3e6
cycles can be offered.
- Treatment with IUI is shown to improve fertility in
minimal to mild endometriosis. Therefore controlled

9. Treatment for endometriosis-associated infertility
ovarian Stimulation and IUI is recommended for 3e4
cycles. If there is still no conception e IVF/ICSI
should be advised.
- In older patients, reduced ovarian reserve or associated male/tubal factor e early resort to IVF/ICSI is
advised.
Management of moderate to severe endometriosis with infertility
- Medical therapy alone is ineffective in restoring the
fertility in women with endometriosis (Grade A
recommendation).
- The role of surgery in improving pregnancy rates for
moderate to severe disease is uncertain (Grade B
recommendation).
- Laparoscopic cystectomy for ovarian endometrioma
is better than drainage and coagulation (Grade A
recommendation). However, loss of normal ovarian
tissue should be minimized.
- Laparoscopy surgery to assess exact extent of the
disease and surgical excision (drainage and excision
of pseudo-cyst wall) as best as possible with ablation
and adhesiolysis should be considered.
- The role of preoperative hormonal therapy is
controversial.
- Postoperative hormonal treatment has no beneficial
effect on pregnancy rates after surgery (Grade A
recommendation).
- IVF is an effective treatment of infertility in these
women and this should be offered at an early stage
while ovarian reserve is still optimal. However,
patients must be counselled for lower rate of pregnancy as compared to non-disease IVF patients.
- Young patients with good ovarian reserve and no
male or tubal factor should be offered 2e3 cycles
of COS þ IUI before proceeding to IVF/ICSI.
Management of severe/deep infiltrating endometriosis or recurrent endometriosis following
previous surgery with infertility
- GnRH agonist depot for 3e6 months followed by IVF/
ICSI (Ultralong protocol) is shown to increase the rate
of clinical pregnancy (Grade A Recommendation).
CONCLUSION
Endometriosis is commonly associated with infertility. The
exact pathogenic mechanism remains elusive and current
Review Article
191
literature suggests a multifactorial mechanism. In the
absence of any clear understanding or cure for this enigmatic
medical disorder, it is important to be flexible in diagnostic
as well as therapeutic approach. Expectant management may
be a reasonable approach in younger patients with early
stage disease and a shorter duration of infertility. The couple
should be involved in decision making at all stages and treatment must be individualized taking into account all medical
and surgical therapeutic available options. Further RCTs are
necessary to find more conclusive answers and remedies to
treat this challenging disorder.
CONFLICTS OF INTEREST
The author has none to declare.
REFERENCES
1. Fraser Ian S. Recognizing, understanding and managing endometriosis. J Hum Reprod Sci. 2008;1(2):56e64.
2. NICE Clinical GuidelinesFertility Assessment and Treatment
to People with Fertility Problems. 2004;33. 73, 77.
3. Werbrouck E, Spiessens C, Meuleman C, D’Hooghe T. Surgical
treatment of early endometriosis, unexplained infertility and
fertility treatment outcomes. Fertil Steril. 2006;86:556e571.
4. Mahmoud, Templeton. Prevalence and genesis of endometriosis. Hum Reprod. 1991;6(4):544e549.
5. D’Hooghe TM, Debrock S, Hill JA, Meuleman C. Endometriosis and subfertility: is the relationship resolved? Semin
Reprod Med. 2003;21:243e254.
6. Jansen RP. Minimal endometriosis and reduced fecundability:
prospective evidence from an artificial insemination by donor
programme. Fertil Steril. 1986;46(1):141e143.
7. Kennedy S, Bergqvist A, Chapron C, et al. ESHRE guideline
for the diagnosis and treatment of endometriosis. Hum
Reprod. 2005;20:2698e2704.
8. Barnhart K, Dunsmoor-Su R, Coutifaris C. Effect of endometriosis on in vitro fertilization. Fertil Steril. 2002;77:1148e1155.
9. Pellicer A, Navarro J, Bosch E. Endometrial quality in infertile
women with endometriosis. Ann N Y Acad Sci. 2001 Sep;943:
122e130.
10. Gupta S, Goldberg JM, Aziz N, Goldberg E, Krajcir N,
Agarwal A. Pathogenic mechanisms in endometriosis-associated infertility. Fertil Steril. 2008;90:247e257.
11. Bergquist A, Hooghe TD. Mini symposium on pathogenesis
of endometriosis and treatment of endometriosis-associated
subfertility. Hum Reprod Update. 2002;8(1):79e83.
12. Iwabe T, Harada T, Terakuwa N. Role of cytokines in endometriosis-associated infertility. Gynecol Obstet Invest.
2002;53:19e25.

10. 192
Apollo Medicine 2012 September; Vol. 9, No. 3
13. Katsoff B, Check JH, Davies E, Wilson C. Evaluation of the
effect of endometriosis on oocyte quality and endometrial
environment by comparison of donor and recipient outcomes
following embryo transfer in a shared oocyte program. Clin
Exp Obstet Gynecol. 2006;33(4):201e202. Pubmed ID:
17214020.
14. Revised American Society for Reproductive Medicine classification of endometriosis. Fertil Steril. 1997;67:817e821.
15. Royal College of Obstetrician and Gynaecologists. The Investigation and Management of Endometriosis (Green Top
Guidelines No. 24). London: RCOG; October 2008.
16. Hughes E, Fedorkow D, Collins J, Vandekerckhove P. Ovulation suppression for endometriosis. Cochrane Database Syst
Rev; 2002 (4):CD001398.
17. Olive DL, Pritis EA. Treatment of endometriosis. N Engl J
Med. 2001;345:265e275.
18. Panay N. Advances in medical management of endometriosis.
BJOG. 2008;115:814e817.
19. Marcoux S, Maheux R, Bérubé S. Laparoscopic surgery in
infertile women with minimal or mild endometriosis. Canadian Collaborative Group on Endometriosis. N Engl J Med.
1997;337:217e222.
20. DeWilde RL, Trew RG. Post operative abdominal adhesions
and their prevention in gynaecological surgery. Expert
consensus position. Part 2 e steps to reduce adhesions. Gynecol Surg. 2007;4:243e253.
21. Ozkan S, Murk W, Arici A. Endometriosis and infertility. Ann
N Y Acad Sci. 2008;1127:92e100.
Verma
22. Surrey ES, Silverberg KM, Surrey MW, Schoolcraft WB.
Effect of prolonged gonadotropin e releasing hormone
agonist therapy on the outcome in vitro fertilization-embryo
transfer in patients with endometriosis. Fertil Steril.
2002;78:699e704.
23. Sallam HN, Gar cia-Velasco JA, Dias S, Arici A. Long-term
pituitary down-regulation before in vitro fertilization (IVF) for
women with endometriosis. Cochrane Database Syst Rev.
2006 Jan 25 (1):CD004635.
24. Hughes EG. The effectiveness of ovulation induction and
intrauterine insemination in the treatment of persistent infertility: a meta-analysis. Hum Reprod. 1997;12:1865e1872.
25. Pabuccu R, Onalan G, Goktolga U, Kucuk T, Orhon E,
Ceyhan T. Aspiration of ovarian endometriomas before intracytoplasmic sperm injection. Fertil Steril. 2004;82:705e711.
26. Practice Committee of the American Society for Reproductive
Medicine. Endometriosis and infertility. Fertil Steril.
2006;86(5 suppl I):156e160.
27. Garcia-Velasco JA, Mahutte NG, Corona J, et al. Removal of
endometriomas before in vitro fertilization does not improve
fertility outcomes: a matched, case control study. Fertil Steril.
2004;81:1194e1197.
28. Somigliana E, Vercellini P, Vigano, et al. Should endometriomas be treated before IVF-ICSI cycles? Hum Reprod Update.
2006;12:57e64.
29. Suganuma N, Wakahara Y, Ishiada D, et al. Pretreatment for
ovarian endometrial cyst before in vitro fertilization. Gynecol
Obstet Invest. 2002;54:36e40.

11. A o oh s i l ht:w wa o o o p a . m/
p l o p a : t / w .p l h s i lc
l
ts p /
l
ts o
T ie: t s / ie. m/o p a A o o
wt rht :t t r o H s i l p l
t
p /w t c
ts
l
Y uu e ht:w wy uu ec m/p l h s i ln i
o tb : t / w . tb . a o o o p a i a
p/
o
o
l
ts d
F c b o : t :w wfc b o . m/h A o o o p a
a e o k ht / w . e o k o T e p l H s i l
p/
a
c
l
ts
Si s ae ht:w wsd s aen t p l _ o p a
l e h r: t / w .i h r.e/ o o H s i l
d
p/
le
A l
ts
L k d : t :w wl k d . m/ mp n /p l -o p a
i e i ht / w . e i c c a y o oh s i l
n n p/
i
n no o
a l
ts
Bo : t :w wl s l e l . /
l ht / w . t a h a hi
g p/
e tk t n