Reproductive BioMedicine Online (2010) 21, 179 185

www.sciencedirect.com
www.rbmonl i ne.com
ELSEVIER
ARTICLE
Endometriosis-associated infertility: surgery and
IVF, a comprehensive therapeutic approach
Pedro N Barri *, Buenaventura Coroleu, Rosa Tur, Pedro N Barri-Soldevila,
Ignacio Rodriguez
Service of Reproductive Medicine, Department of Obstetrics, Gynecology and Reproduction, Institut Universitari Dexeus,
Gran Via Carles III 71-75, 08028 Barcelona, Spain
* Corresponding author. E-mail address: pbarri@dexeus.com (PN Barri).
Dr Pedro N Barri was born in Barcelona in 1949. He graduated from the Faculty of Medicine in Barcelona in 1971
and completed his doctorate in 1993 with a thesis entitled "Respuesta Anmala a la Estimulacin de la
Maduracin Folicular en Fecundacin In Vitro" with qualification Cum Laude. He is Director of the Department
of Obstetrics, Gynaecology and Reproductive Medicine at USP Institut Universitari Dexeus, Honorary President
of the Spanish Fertility Society, Honorary member of the Argentina Society of Sterility and Fertility, emeritus
member of the Executive Committee of the ISGE since 1998, member of the French Society of Sterility and
member of the ASRM.
Abstract Infertility is a common problem presented by patients with endometriosis. At present, whichever treatment is chosen,
half of patients with advanced stages of the disease will remain infertile afterwards. This observational study looked at the repro-
ductive outcome achieved after treating a group of 825 patients aged between 20 and 40 years with endometriosis-associated infer-
tility during the period 2001 2008. Of the 483 patients who had surgery as the primary option, 262 became pregnant (54.2%). Among
the patients who did not become pregnant, 144 underwent 184 IVF cycles and 56 additional pregnancies were obtained (30.4% clin-
ical pregnancy rate per retrieval). It is notable that, before any treatment, patients with endometriosis had a poorer ovarian reserve
than the control group. The combined strategy of endoscopie surgery and subsequent IVF led to a total of 318 pregnancies, which
represents a combined clinical pregnancy rate of 65.8%. This percentage is significantly higher than that obtained with surgery alone
(P .. 0.0001), with 173 patients who were not operated on and who went to IVF as the primary option (P v 0.0001) and with 169
patients who had no treatment and achieved 20 spontaneous pregnancies (P< 0.0001). (W
lo 2010, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.
KEYWORDS: endometriosis, endoscopie surgery, infertility, in-vitro fertilization, ovarian reserve
Introduction
It is difficult to establish the real prevalence of endome-
triosis as it depends on the population under study. How-
ever, an estimate of data from women of childbearing age
shows that around 10% may be affected by endometriosis,
and the figure rises to above 40% among patients with
symptoms such as dysmenorrhoea, intermenstrual bleed-
ing and dyspareunia (Meuleman et al., 2009; Practice
Committee of the American Society of Reproductive Med-
icine, 2004). Nevertheless, in most studies, there is great
heterogeneity relating to variables such as age and
duration of infertility that makes it difficult to establish
absolute figures for prevalence (Guo and Wang, 2006).
1472-6483/$ - see front matter c 2010, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved,
doi: 10.1016/j.rbmo.2010.04.026
180 PN Barri et al.
Epidemiological data suggest that the hypothesis of men-
strual reux is the origin of most cases of endometriosis
(Vigano et al., 2004).
The association between endometriosis and infertility
is especially evident for advanced stages of the disease.
There are many reasons why endometriosis might com-
promise fertility but they are basically connected with
ovulatory abnormalities and distorted pelvic anatomy
(Gupta et al ., 2008). Autoimmune disorders have also
been implicated in the pathogenesis and possible associa-
tion between endometriosis and periodontal disease
(Kavoussi et al ., 2009). A number of studies have shown
the possibility of spontaneous pregnancy after 1 year of
follow-up; in cases of mild endometriosis, this varies be-
tween 17% and 22% (Marcoux et al ., 1997; Parazzini,
1999) and does not exceed 3% in severe cases (Adamson
and Pasta, 1994).
For definitive diagnosis of endometriosis, laparoscopy
has become the gold standard (Practice Committee of the
American Society of Reproductive Medicine, 2004; Royal
College of Obstetricians and Gynecologists, 2006), although,
in the last decade, ultrasound diagnosis has made consider-
able progress and now plays an important role in the diagno-
sis of this disease (Alczar et al ., 1997). In fact, there are
many studies that show that an accurate ultrasound diagno-
sis can be made, both of the ovarian affectation (Eskenazi
et al ., 2001; Pascual et al ., 2000) and of lesions that affect
the rectum, bladder and other pelvic structures (Hudelist
et al ., 2009a,b). Now, the remaining indications where a
laparoscopy must be practised are cases in which the painful
symptoms and the clinical examination provide strong evi-
dence of an endometriosis needing surgical treatment
(Pouly et al., 2007).
The infertility that these patients suffer has classically
been treated with surgery or a combination of medical
and surgical treatment. It is currently accepted that the re-
sults from surgery are superior to those from medical treat-
ment and, of course, from abstaining from therapeutic
treatment (Pouly et al ., 2007). New combinations of surgi-
cal and immunomodulation treatment with pentoxifylline
with interesting preliminary results have been published
(Creuset al., 2008).
Nowadays, IVF techniques represent a new therapeutic
strategy for these patients. Although there are suggestions
of worse results from IVF for cases of endometriosis than
for other indications (Barnhart et al., 2002), there are many
articles and national registries, such as the French National
IVF Register (FIVNAT) and the US Society for Assisted Repro-
ductive Technology Registry, that show the same results
from IVF for endometriosis (Pouly and Larue, 2007; SART-
ASRM, 2007).
Assisted reproduction treatment should be seen not as
competing with surgical treatment of endometriosis-asso-
ciated infertility but as a complementary therapeutic
strategy. Depending on the stage of the disease, the pa-
tient's age and the duration of the infertility, physicians
have to take the right decision for each case. In this re-
gard, the aim here was to study final outcomes of
obtaining a pregnancy following a holistic therapeutic ap-
proach to endometriosis-associated infertility in a large
number of patients treated in the same private university
centre.
Materials and methods
This is an observational study of reproductive outcome ob-
tained by applying a holistic treatment that combined sur-
gery and/or IVF to treat a population of 825 patients
suffering from endometriosis-associated infertility, with a
mean age of 35.3 3.1 years (range 20-40) and mean length
of infertility 3.2 2.3 years. These patients were diagnosed
with stage III-IV cystic endometriosis with endometriomas
with a mean size of 5.8 2.1 cm by means of ultrasound
and/or laparoscopy in the study department during the per-
iod 2001-2005. In all cases, endometriosis was the major
factor for infertility. Endoscopie surgery was used to treat
483 patients (group l a), usually using cystectomy whenever
possible, removing the whole capsule of the cyst, with later
histological analysis to confirm its endometriotic origin. The
follow-up of these patients continued until the end of 2008.
Apart from being infertile, the majority of the study group
complained of dysmenorrhoea and/or dyspareunia. The
variables evaluated were the clinical pregnancies obtained
directly after surgery as primary therapeutic strategy and
the time interval elapsed to achieving the pregnancy, as
well as other parameters such as a previous operation, the
presence of unilateral or bilateral lesions and the recur-
rence of the disease.
Patients who did not become pregnant after surgery had
the option of having IVF treatment (group 1b). There were
also 173 patients who, although having endometriosis as
the only factor, preferred to refrain from surgery and went
directly to IVF (group 2). As a treatment control group (group
3), the study used 169 infertile patients who, in spite of being
diagnosed with endometriosis, did not undergo any treat-
ment. To study ovarian reserve in patients with endometri-
osis, the control group of patients with infertility unrelated
to endometriosis consisted of 334 patients who underwent
IVF for male factor infertility, mean age 34.3 4 years and
mean duration of infertility 2.9 3.2 years. The endometri-
osis group and the male factor infertility group were compa-
rable for age and duration of infertility.
Stati sti cal analysis
The Student's i-test was used to compare quantitative vari-
ables and chi-squared Pearson test or Fisher's exact test
were used to compare qualitative variables. A Kaplan-Meier
survival analysis was applied to compare the pregnancy
rates by time. All the tests were bilateral and with a level
of significance of P = 0.05.
Results
Laparoscopic treatment was the first therapeutic choice in
483 patients (group l a; 58.5%) and 262 achieved spontane-
ous pregnancies after surgery (54.2%). The mean time to
pregnancy was 11.2 months (1-66 months). Of the 221 pa-
tients who did not become pregnant after surgery, 144 went
on to IVF (group 1b) and underwent 184 oocyte retrievals
and 56 additional pregnancies were obtained (30.4% clinical
pregnancy/retrieval).
IVF was chosen as the primary therapeutic option by 173
patients who rejected surgery (group 2) diagnosed with
Combined surgery and IVF with endometriosis-associated infertility 181
advanced endometriosis with endometriomas with a mean
size of 5.4 3.2 cm. This group was comparable with the
group of 483 patients who had a laparoscopic treatment as
far as the age of the patients and duration of infertility were
concerned. In these patients, 211 oocyte retrievals were
performed, 68 of which achieved pregnancy (32.2% clinical
pregnancy/retrieval).
It is interesting to see the effect of age on the final out-
come of the two therapeutic options. In group 1a, 61.6%
(229/372) of patients aged <35 years became pregnant,
doing so in a mean time of 12.5 months (1-66) and only
29.7% (33/111) of patients aged 35 years or over became
pregnant (P < 0.05), in a mean time of 6.6 months (1-14)
(Table 1, Figure 1 ). In group 2, with IVF as the primary op-
tion, patients aged 35 years achieved rates for clinical
pregnancy/retrieval of 35.7% (51/143), which was signifi-
cantly higher than the 25.0% (17/68) obtained in the pa-
tients aged 35 years or over (P < 0.05; Table 1 ).
For the treatment control group (group 3), patients with
endometriosis who did not undergo any treatment, it was
found by means of personal or telephone interviews,
11.8% (20/169) of patient had a spontaneous pregnancy dur-
ing the period 2001 -2008.
It is interesting to note the yield from the combined
strategy of surgical treatment plus IVF if they did not be-
come pregnant 1 year after surgery, which made it possible
to achieve 318 pregnancies in 483 patients, a rate of 65.8%,
which is significantly higher than the 54.2% for surgery-only
patients (P < 0.0001), the 32.2% achieved by the patients
who did not undergo surgery and went to IVF as the primary
option (P 0.0001 ) and the 11.8% of spontaneous pregnancy
observed in patients who underwent no treatment
(P 0.0001; Table 2).
An analysis of the results obtained from treating patients
suffering from endometriosis-associated infertility with sur-
gical treatment and/or IVF gives rise to a series of contro-
versial points. In light of this data, therefore, additional
analyses were performed.
Ovarian reserve and response to stimulation
The ovarian reserve of the whole population of 825 patients
before undergoing any treatment was compared with that
observed in a simultaneous control group, made up of 334
patients who were going to have IVF for male factor infertil-
ity and adjusted for age. Patients with endometriosis had
basal follicle-stimulating hormone concentrations on cycle
days 3-5 of 8. 86. 3U/ l , which was significantly higher
than those observed in the control group 7. 53U/ l
(P < 0.001). Also, the antral follicle count in these patients
was 7.3 4 antral follicles, which was significantly lower
than the 10.2 5.1 antral follicles observed in the control
group (P < 0.004).
Comparing IVF treatments between patients with endo-
metriosis (group 1b, n = 144; group 2, n = 173; total
n = 317) and patients with male factor infertility, those with
endometriosis had a poorer response to ovarian stimulation,
needed larger doses of gonadotrophins and produced a low-
er number of follicles and mature oocytes. For this reason,
the total numbers of embryos and of embryos frozen per pa-
tient in the study group were significantly lower than in the
patients in the control group (P < 0.000 and P < 0.000,
respectively). No significant differences were found be-
tween the live-birth rates in the study and control groups
(Table 3).
Does surgery for endometriosis have any effect on
the final outcome of an IVF cycle?
Comparing the yield from the IVF cycles in group 2 (no sur-
gery) with that obtained in group 1b (after surgery), the
only differences found were that group-2 patients produced
more follicles >16mm (7.8 5.1 versus 5.9 6. 1; P<0.03)
and more mature oocytes (10.1 2.2 versus 7.3 5;
P < 0.03) than those in group 1b.
Is there any difference between the IVF results
obtained in patients operated on for bilateral or
unilateral endometriosis?
This study showed that the 51 patients who came to an IVF
cycle with an endometriosis that affected both ovaries pro-
duced fewer follicles >16mm. (3.0 2.8 versus 7.1 6;
P < 0.03) and fewer mature oocytes (4.1 2 versus 8.7 6;
P<0.03) than the 93 patients suffering from unilateral
affection.
Can IVF be attempted in a patient previously
operated on for endometriosis who has a '
recurrence?
Among the 144 patients who went on to IVF after not
becoming pregnant post surgery, 32 presented recurrence
Table 1 Endometriosis-associated infertility: pregnancy rates after surgery and/or IVF.
Age
< 35 years
>35 years
Total
Group la (surgery)
(n = 483)
Pregnancy^
229/372 (61.6)
33/111 (29.7)
262/483 (54.2)
Values are number/total (%) or mean
"184 IVF cycles.
"211 IVF cycles.
Time (Months)
12.5 12 (1-66)
6.6 7.2 (1-14)
11.8 12.1 (1-66)
SD (range).
Group 1b (surgery and IVF)
(n = 144)^
Pregnanc)/^
34/99 (34.3)
22/85 (25.9)
56/184 (30.4)
Group 2 (IVF first option)
(n = 173)"
Pregnancy
51/143 (35.7)
17/68 (25.0)
68/211 (32.2)
182 PN Barri et al.
1.0-
0.8-
><
i
n
O)
0.6-
0.4-
0.2-
0.0-
AGE
. - - K 35 years
..;--' >.35 years
J "
..I
20 40
Months
60 80
Figure 1 Age influence on pregnancy rate after surgery for endometriosis.
Table 2 Endometriosis-associated i nferti l i ty: pregnancy rate according to different treatment strategies.
Pregnancies after surgery (n)
Pregnancies after IVF (n)
Total pregnancies
Final clinical pregnancy
rate {%)
Group la
(surgery)
(n = 483)
262
-
262
54.2
Group 1b
(surgery and IVF)
(n = 483)
262
56
318
65.8
Group 2
(IVF first option)
(n = 173)

68
68
32.2
Group 3
(no treatment)
(n = 169)

-
20 (spontaneous)
11.8
Group l-a versus Group l-b: P < 0.0001.
Group I (a-b) versus Group II: P < 0.0001.
Group I (a-b) versus Group III: P < 0.0001.
Group II versus Group III: P< 0.0001.
Table 3 IVF outcomes in patients wi th endometriosis or male factor i nferti l i ty after IVF
treatment.
HCG on day of oestradiol (pg/ml)
Follicles
Mil oocytes
Total embryos
Embryos frozen
Live births per patient
Endometriosis
(n = 317)
1843.2 1368
8.3 5. 8
6.7 5. 2
4.0 3. 4
1.9 3
97/317 (30.6)
Male factor infertility
(n = 334)
1889 981
11.23.1
10.36
4.5 3.8
2.7 1
112/334(33.5)
P-value
NS
< 0.001
< 0.001
< 0.001
< 0.001
NS
Values are mean SD or number/total {%).
HCG, human chorionic gonadotrophin; MM, metaphase I NS, not statistically significant.
Combined surgery and IVF with endometriosis-associated infertility 183
of the endometriosis. These patients had a worse ovarian
reserve, as shown by the basal follicle-stimulating hormone
concentrations of 12.5 5.9 U/l being significantly higher
than the values of 7.7 3.3 U/l observed in the 112 patients
who did not present any recurrence (P < 0.01). However,
the clinical pregnancy rate obtained in the two groups
showed no significant differences.
Discussion
There are a number of options in the therapeutic arsenal that
are available to treat endometriosis-associated infertility
and there is now sufficient information to clarify the best op-
tion for treatment. Primary-option medical treatment would
be restricted to very painful cases and would be adminis-
tered only in the pre-operative period (Daraiet al ., 2007).
It is accepted that surgery should be the primary thera-
peutic option because of its efficacy (Chapron et al .,
2002; Marcoux et al., 1997; Moayeri et al., 2009; Ouahba
et al ., 2004; Pouly et al ., 2007; Vercellini et al ., 2009a,b)
and also for its safety (Nezhat et al ., 2005). The surgical
indication is greater when there is intestinal affectation.
In these cases, laparoscopic resection of the affected intes-
tinal segment improves subsequent reproductive perfor-
mance (Dara et al ., 2008; Ferrero et al., 2009;
Stepniewska et al ., 2009), although the improvement is
not so evident in younger patients (Vercellini et al ., 2006).
As for recurrence, the current study observed a recurrence
rate after surgery of 22%, which agrees with recurrence
rates of 20-30% at 2 years in most studies, with greater fre-
quency in younger patients presenting larger cysts, receiv-
ing additional medical treatment and not becoming
pregnant (Guo, 2009; Koga et al ., 2006). In these cases,
the efficacy of IVF seems to be greater than that of a second
surgical intervention (Aboulghar et al ., 2003; Fedele et al.,
2006; Vercellini et al., 2009a,b). There is one alternative
that must be borne in mind for cases of repeated endome-
triomas; evacuating aspiration combined with ethanol scle-
rotherapy may contribute both to achieving spontaneous
pregnancies and to protecting the ovary for later IVF at-
tempts (Noma and Yoshida, 2001; Pabuccu et al ., 2004;
Yazbecket al., 2009).
An additional advantage of surgical treatment derives
from the possibility that an early diagnosis of a neoplastic
affectation of the ovary could be missed otherwise
(Somigliana et al ., 2006b,c; Vigan et al., 2006). There
are studies that suggest that endometriosis could be a risk
factor for ovarian cancer (Brinton et al ., 2004; Melin
et al., 2006) and that the association of infertility and endo-
metriosis could also increase the risk of other neoplasias
such as melanomas and thyroid cancer (Brinton et al.,
2005). For this reason, some authors suggest that a proper
diagnosis, which is key in avoiding confusion between possi-
ble endometriosis and a neoplastic affectation at the pelvic
level (Banz et al ., 2009; Goumenou et al ., 2006), and com-
plete surgical treatment are fundamental in reducing the
risk of an ovarian neoplasia appearing in these patients
(Nezhat et al ., 2008).
Nevertheless, it would seem that, in treating infertility,
the efficacy of surgery itself is less than that obtained in
combination with IVF (this study; Coccia et al., 2008).
One important aspect to bear in mind is the ovarian re-
serve of patients with endometriosis. This study has shown
that these patients have a poorer reserve even before sur-
gery. The same observation has been published in patients
presenting unilateral ovarian endometriomas who did not
undergo previous ovarian surgery (Gupta et al ., 2006;
Somigliana et al ., 2006a). Controversy surrounds the effect
of endometriosis surgery on the ovarian reserve; some
authors have shown that ovarian response in patients with
severe endometriosis and surgical excision is lower than
that of patients with minimal or mild endometriosis without
ovarian surgery (Busacca et al., 2006; Horikawa et al., 2008;
Matalliotakis et al ., 2007; Yazbeck et al ., 2006) while others
have shown that laparoscopic ovarian cystectomy of
endometriomas does not affect ovarian reserve and re-
sponse to stimulation (Marconi et al., 2002; Tsolakidis
et al ., in press). The same findings have been published in
a recent systematic review and meta-analysis of five studies
that compared surgery with non-treatment of endometrio-
mas before IVF (Tsoumpou et al ., 2009). There is contro-
versy as to whether response to stimulation after an
operation to treat endometrioma is better (Somigliana
et al ., 2006a), worse (Esinler et al ., 2006; Somigliana
et al ., 2008) or not affected (Garcia-Velasco et al., 2004).
It is important to point out that it seems that unoperated
endometriomas will not grow from the effect of the stimu-
lation of the IVF cycle (Benaglia et al ., 2009).
With the results from this study, IVF should be proposed
as the primary option only in cases where there are addi-
tional infertility factors or where there is some contraindi-
cation to surgery. All studies agree that IVF should be
recommended to infertile patients who have not become
pregnant after operation for endometriosis. However, the
question of when remain. From this study's results, the an-
swer varies with the patient's age. Patients younger than
35 years of age can wait for up to 1 year post surgery to
go for IVF while older patients are recommended to have
IVF 6 months post surgery. With regard to the ovarian stim-
ulation protocol, the usual protocols that combine gonado-
trophins and gonadotrophin-releasing hormone agonists or
antagonists obtain good responses if the ovarian reserve is
normal (Zikopoulos et al ., 2004). Accepting that the possi-
bility of a low response is higher in these patients, whether
or not they have been operated on, the yield of the IVF cycle
is usually good, with pregnancy rates in the expected ranges
and comparable with those attained in IVF cycles carried
out for other indications. For patients who resort to IVF as
their primary treatment option and do not become preg-
nant, laparoscopic surgery could be suggested to help to im-
prove their chances of pregnancy, either spontaneously or
before a new IVF attempt (Littman et al ., 2005).
This study agrees with other reports that the progression
of pregnancy with endometriosis presents no greater prob-
lems than pregnancies obtained with other indications (Kor-
telahti et al., 2003). However, some authors suggest that
the pregnancies of patients suffering from endometriosis
should be considered as high risk for preterm birth, antepar-
tum haemorrhage, placental complications, pre-eclampsia
and Caesarean section (Omland et al., 2005; Stephansson
et al., 2009).
In conclusion, infertile patients with endometriosis
should undergo surgical treatment as the primary option.
184 PN Barri et al.
Those who do not become pregnant after surgery must be
treated with IVF and their possibilities of pregnancy will
be identical to those of patients who come to IVF for other
indications. The combination of surgery and IVF offers the
best chance of pregnancy for these patients.
Acknowledgements
This work was performed under the auspices of 'Ctedra
d'Investigaci en Obstetricia i Ginecologia' of the Depart-
ment of Obstetrics, Gynecology and Reproduction, Institut
Universitt Autnoma de Barcelona.
References
Aboulghar, M.A., Mansour, R.T., Serour, G.I., et al ., 2003. The
outcome of in vitro fertilization in advanced endometriosis with
previous surgery: a case-controlled study. Am. J. Obstet.
Gynecol. 188, 371-375.
Adamson, G.D., Pasta, D.J., 1994. Surgical treatment of endome-
triosis-associated infertility: meta-analysis compared with sur-
vival analysis. Am. J. Obstet. Gynecol. 171, 1488-1504.
Alczar, J.L., Laparte, C, Jurado, M., et al ., 1997. The role of
transvaginal ultrasonography combined with color velocity
imaging and pulsed Doppler in the diagnosis of endometrioma.
Frtil. Steril. 67,487-491.
Banz, C, von Otte, S., Noack, F., et al ., 2009. Primary peritoneal
carcinoma in a young woman with suspected endometriosis.
Frtil. Steril. 92, 39O.e5-39O.e7.
Barnhart, K., Dunsmoor-Su, R., Coutifaris, C, 2002. Effect of
endometriosis on in vitro Fertilization. Frtil. Steril. 77, 1148
1155.
Benaglia, L., Somigliana, E., Vighi, V., et al ., 2009. Is the
dimension of ovarian endometriomas significantly modified by
IVF-ICSI cycles? Reprod. Biomed. Online 18, 401-406.
Brinton, L.A., Lamb, E.J., Moghissi, K.S., et al ., 2004. Ovarian
cancer risk associated with varying causes of infertility. Frtil.
Steril. 82, 405-414.
Brinton, L.A., Westhoff, CL. , Scoccia, B., et al ., 2005. Causes of
infertility as predictors of subsequent cancer risk. Epidemiology
16, 500-507.
Busacca, M., Riparini, J., Somigliana, E., et al ., 2006. Postsurgical
ovarian failure after laparoscopic excision of bilateral endome-
triomas. Am. J. Obstet. Gynecol. 195, 421-425.
Chapron, C, Vercellini, P., Barakat, H., et al ., 2002. Management of
ovarian endometriomas. Rev. Hum. Reprod. update 8, 591-597.
Coccia, M.E., Rizzello, F., Cammilli, F., et al ., 2008. Endometriosis
and infertility Surgery and ART: an integrated approach for
successful management. Eur. J. Obstet. Gynecol. Reprod. Biol.
138, 54-59.
Creus, M., Fbregues, F., Carmona, F., et al ., 2008. Combined
laparoscopic surgery and pentoxifylline therapy for treatment of
endometriosis-associated infertility: a preliminary trial. Hum.
Reprod. 23, 1910-1916.
Darai, E., Azoulay, C, Dubernard, G., 2007. Indications for GnRH
analogs in the treatment of genital endometriosis. Gynecol.
Obstet. Frtil. 35 (Suppl. 1), S14-S16.
Darai, E., Bazot, M., Rouzier, R., et al ., 2008. Colorectal endome-
triosis and fertility. Gynecol. Obstet. Frtil. 36, 1214-1217.
Esinler, I., Bozdag, G., Aybar, F., et al ., 2006. Outcome of in vitro
fertilization/intracytoplasmic sperm injection after laparo-
scopic cystectomy for endometriomas. Frtil. Steril. 85, 1730-
1735.
Eskenazi, B., Warner, M., Bonsignore, L., et al ., 2001. Validation
study of nonsurgical diagnosis of endometriosis. Frtil. Steril.
76, 929-935.
Fedele, L., Bianchi, S., Zanconato, G., et al ., 2006. Laparoscopic
excision of recurrent endometriomas: long-term outcome and
comparison with primary surgery. Frtil. Steril. 85, 694 699.
Ferrero, S., Anserini, P., Abbamonte, L.H., et al ., 2009. Fertility
after bowel resection for endometriosis. Frtil. Steril. 92, 4 1 -
46.
Garcia-Velasco, J.A., Mahutte, N.G., Corona, J., et al ., 2004.
Removal of endometriomas before in vitro fertilization does not
improve fertility outcomes: a matched, case-control study.
Frtil. Steril. 81, 1194-1197.
Goumenou, A., Matalliotakis, I., Mahutte, N., et al ., 2006. Endo-
metriosis mimicking advanced ovarian cancer. Frtil. Steril. 86,
219.e23-219.e25.
Guo, S.W., 2009. Recurrence of endometriosis and its control. Hum.
Reprod. Update 15, 441-461.
Guo, S.W., Wang, Y., 2006. Sources of heterogeneities in estimating
the prevalence of endometriosis in infertile and previously
fertile women. Frtil. Steril. 86, 1584-1595.
Gupta, S., Agarwal, A., Agarwal, R., et al ., 2006. Impact of ovarian
endometrioma on assisted reproduction outcomes. Reprod.
Biomed. Online 13, 349-360.
Gupta, S., Goldberg, J.M., Aziz, N., et al ., 2008. Pathogenic
mechanisms in endometriosis-associated infertility. Frtil.
Steril. 90, 141-1^7.
Horikawa, T., Nakagawa, K., Ohgi, S., et al ., 2008. The frequency
of ovulation from the affected ovary decreases following
laparoscopic cystectomy in infertile women with unilateral
endometrioma during a natural cycle. J. Assist. Reprod. Genet.
25, 239-244.
Hudelist, G., Tuttlies, F., Rauter, G., et al ., 2009a. Can transvag-
inal sonography predict infiltration depth in patients with deep
infiltrating endometriosis of the rectum? Hum. Reprod. 24,
1012-1017.
Hudelist, G., Oberwinkler, K.H., Singer, CF. , et al ., 2009b.
Combination of transvaginal sonography and clinical examina-
tion for preoperative diagnosis of pelvic endometriosis. Hum.
Reprod. 24, 1018-1024.
Kavoussi, S.K., West, B.T., Taylor, G.W., et al ., 2009. Periodontal
disease and endometriosis: analysis of the National Health and
Nutrition Examination Survey. Frtil. Steril. 91, 335-342.
Koga, K., Takemura, Y., Osuga, Y., et al ., 2006. Recurrence of
ovarian endometrioma after laparoscopic excision. Hum.
Reprod. 21, 2171-2174.
Kortelahti, M., Anttila, M.A., Hippelainen, M.I., et al ., 2003.
Obstetric outcome in women with endometriosis a matched
case-control study. Gynecol. Obstet. Invest. 56, 207 212.
Littman, E., Giudice, L., Lathi, R., et al ., 2005. Role of laparo-
scopic treatment of endometriosis in patients with failed in vitro
fertilization cycles. Frtil. Steril. 84, 1574-1578.
Marconi, G., Vilela, M., Quintana, R., et al ., 2002. Laparoscopic
ovarian cystectomy of endometriomas does not affect the
ovarian response to gonadotropin stimulation. Frtil. Steril.
78, 876-878.
Marcoux, S., Maheux, R., Brub, S., 1997. Laparoscopic surgery in
infertile women with minimal or mild endometriosis. Canadian
Collaborative Group on Endometriosis. N. Engl. J. Med. 337,
lM-111, lA.
Matalliotakis, I.M., Cakmak, H., Mahutte, N., et al ., 2007. Women
with advanced-stage endometriosis and previous surgery
respond less well to gonadotropin stimulation, but have similar
IVF implantation and delivery rates compared with women with
tubal factor infertility. Frtil. Steril. 88, 1568-1572.
Melin, A., Sparen, P., Persson, I., et al ., 2006. Endometriosis and
the risk of cancer with special emphasis on ovarian cancer. Hum.
Reprod. 21, 1237-1242.
Meuleman, C, Vandenabeele, B., Fieuws, S., et al ., 2009. High
prevalence of endometriosis in infertile women with normal
ovulation and normospermic partners. Frtil. Steril. 92, 68-74.
Combined surgery and IVF with endometriosis-associated infertility 185
Moayeri, S.E., Lee, H.C., Lathi, R.B., et al ., 2009. Laparoscopy in
women with unexplained infertility: a cost-effectiveness anal-
ysis. Frtil. Steril. 92, 471-480.
Nezhat, C, Littman, E.D., Lathi, R.B., et al ., 2005. The dilemma of
endometriosis: is consensus possible with an enigma? Frtil.
Steril. 84, 1587 1588.
Nezhat, F., Datta, M.S., Hanson, V., et al ., 2008. The relationship
of endometriosis and ovarian malignancy: a review. Frtil.
Steril. 90, 1559-1570.
Noma, J., Yoshida, N., 2001. Efficacy of ethanol sclerotherapy for
ovarian endometriomas. Int. J. Gynaecol. Obstet. 72, 35-39.
Omland, A.K., Abyholm, T., Fedorcsk, P., et al ., 2005. Pregnancy
outcome after IVF and ICSI in unexplained, endometriosis-
associated and tubal factor infertility. Hum. Reprod. 20, 722-
727.
Ouahba, J., Madelenat, P., Poncelet, C, 2004. Transient abdominal
ovariopexy for adhesion prevention in patients who underwent
surgery for severe pelvic endometriosis. Frtil. Steril. 82, 1407-
1411.
Pabuccu, R., Onalan, G., Goktolga, U., et al ., 2004. Aspiration of
ovarian endometriomas before intracytoplasmic sperm injec-
tion. Frtil. Steril. 82, 705 711.
Parazzini, F., 1999. Ablation of lesions or no treatment in minimal-
mild endometriosis in infertile women: a randomized trial.
Gruppo Italiano per lo Studio dell'Endometriosi. Hum. Reprod.
14, 1332-1334.
Pascual, M.A., Tresserra, F., Lpez-Marin, L., et al ., 2000. Role of
color Doppier ultrasonography in the diagnosis of endometriotic
cyst. J. Ultrasound Med. 19, 695-699.
Pouly, J.L., Canis, M., Velemir, L., et al ., 2007. Endometriosis
related infertility. J. Gynecol. Obstet. Biol. Reprod. 36, 151-
161.
Pouly, J.L., Larue, L., 2007. Are French results in assisted
reproductive techniques so bad? Gynecol. Obstet. Frtil. 35,
30-37.
Practice Committee of the American Society for Reproductive
Medicine. 2004. Endometriosis and infertility. Frtil. Steril. 81,
1441-1446.
Royal College of Obstetricians and Gynecologists. 2006. The
investigation and management of endometriosis London: RCOG.
Green Top Guideline No. 24.
Society for Assisted Reproductive Technology; American Society for
Reproductive Medicine. 2007. Assisted reproductive technology
in the United States: 2001 results generated from the American
Society for Reproductive Medicine/Society for Assisted Repro-
ductive Technology registry. Frtil. Steril. 87, 1253-1266.
Somigliana, E., Infantino, M., Benedetti, F., et al ., 2006a. The
presence of ovarian endometriomas is associated with a reduced
responsiveness to gonadotropins. Frtil. Steril. 86, 192-196.
Somigliana, E., Vigano', P., Parazzini, F., et al ., 2006b. Association
between endometriosis and cancer: a comprehensive review and
a critical analysis of clinical and epidemiological evidence.
Gynecol. Oncol. 101, 331-341.
Somigliana, E., Vercellini, P., Vigano, P., et al ., 2006c. Should
endometriomas be treated before IVF-ICSI cycles? Hum. Reprod.
Update 12, 57-64.
Somigliana, E., Arnoldi, M., Benaglia, L., et al ., 2008. IVFICSI
outcome in women operated on for bilateral endometriomas.
Hum. Reprod. 23, 1526-1530.
Stephansson, 0. , Kieler, H., Granath, F., et al ., 2009. Endometri-
osis, assisted reproduction technology, and risk of adverse
pregnancy outcome. Hum. Reprod. 24, 2341-2347.
Stepniewska, A., Pomini, P., Bruni, F., et al ., 2009. Laparoscopic
treatment of bowel endometriosis in infertile women. Hum.
Reprod. 24, 1619-1625.
Tsolakidis, D., Pados, G., Vavilis, D., et al ., in press. The impact on
ovarian reserve after laparoscopic ovarian cystectomy versus
three-stage management in patients with endometriomas: a
prospective randomized study. Frtil. Steril. 24.
Tsoumpou, I., Kyrgiou, M., Gelbaya, T.A., et al ., 2009. The effect
of surgical treatment for endometrioma on in vitro fertilization
outcomes: a systematic review and meta-analysis. Frtil. Steril.
92, 75-87.
Vercellini, P., Pietropaolo, G., De Giorgi, 0. , et al ., 2006. Repro-
ductive performance in infertile women with rectovaginal
endometriosis: is surgery worthwhile? Am. J. Obstet. Gynecol.
195, 1303-1310.
Vercellini, P., Somigliana, E., Daguati, R., et al ., 2009b. The
second time around: reproductive performance after repetitive
versus primary surgery for endometriosis. Frtil. Steril. 92,
1253-1255.
Vercellini, P., Somigliana, E., Vigano, P., et al ., 2009a. Surgery for
endometriosis-associated infertility: a pragmatic approach.
Hum. Reprod. 24, 254-269.
Vigano, P., Parazzini, F., Somigliana, E., et al ., 2004. Endometri-
osis: epidemiology and aetiological factors. Best Pract. Res.
Clin. Obstet. Gynaecol. 18, 177-200.
Vigano, P., Somigliana, E., Chiodo, I., et al ., 2006. Molecular
mechanisms and biological plausibility underlying the malignant
transformation of endometriosis: a critical analysis. Hum.
Reprod. Update 12, 77-89.
Yazbeck, C, Madelenat, P., Ayel, J.P., et al ., 2009. Ethanol
sclerotherapy: a treatment option for ovarian endometriomas
before ovarian stimulation. Reprod. Biomed. Online 19,121-125.
Yazbeck, C, Madelenat, P., Sifer, C, et al ., 2006. Ovarian
endometriomas: effect of laparoscopic cystectomy on ovarian
response in IVF-ET cycles. Gynecol. Obstet. Frtil. 34, 808-812.
Zikopoulos, K., Kolibianakis, E.M., Devroey, P., 2004. Ovarian
stimulation for in vitro fertilization in patients with endometri-
osis. Acta Obstet. Gynecol. Scand. 83, 651-655.
Declaration: The authors report no financial or commercial
conflicts of interest.
Received 2 October 2009; refereed 26 November 2009; accepted 23
March 2010.
Copyright of Reproductive BioMedicine Online is the property of Reproductive Healthcare Limited and its
content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's
express written permission. However, users may print, download, or email articles for individual use.