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Endometriosis-related
Infertility

A Comprehensive Manual
Simone Ferrero
Editor

123
Endometriosis-related Infertility
Simone Ferrero
Editor

Endometriosis-related
Infertility
A Comprehensive Manual
Editor
Simone Ferrero
Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal and Child
Health (DINOGMI)
IRCCS Ospedale Policlinico San Martino, University of Genoa
Genova, Italy

ISBN 978-3-031-50661-1    ISBN 978-3-031-50662-8 (eBook)

https://doi.org/10.1007/978-3-031-50662-8

© The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature
Switzerland AG 2024
This work is subject to copyright. All rights are solely and exclusively licensed by the Publisher, whether
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Preface

In addition to the distressing pain symptoms, individuals afflicted with endometrio-

sis often face the challenge of infertility, a condition that necessitates precise diag-
nosis and adept management to optimize their chances of conception. The intricate
nature of endometriosis-related infertility, stemming from the distortion of pelvic
anatomy, inflammatory processes within the pelvic cavity, and adverse effects on
ovarian follicles and ovulation, remains only partially understood. This book delves
into the nuanced impact of various manifestations of endometriosis, including ovar-
ian endometriomas and deep infiltrating endometriosis, on reproductive potential.
A significant emphasis is placed on the utilization of ultrasonography for the
diagnosis of endometriosis in individuals struggling with infertility, alongside
advanced imaging techniques to evaluate tubal patency. The therapeutic landscape,
encompassing intrauterine insemination and in vitro fertilization, will be explored
in depth to illuminate their roles in overcoming endometriosis-induced reproductive
hurdles. Furthermore, the consequences of surgical intervention for endometriosis
on natural fertility and the efficacy of assisted reproductive technologies will be
thoroughly examined.
Additionally, this volume sheds light on the influence of endometriosis on endo-
metrial receptivity and introduces the critical concept of fertility preservation for
women diagnosed with this condition. Designed as an essential resource, this book
aims to equip reproductive surgeons, sonographers, and IVF specialists with com-
prehensive insights into the multifaceted relationship between endometriosis and
infertility.
I extend my heartfelt gratitude to the esteemed international experts whose con-
tributions have enriched this work, making it an indispensable tool for healthcare
professionals dedicated to the care of those affected by endometriosis.

Genova, Italy Simone Ferrero

v
Contents


The Epidemiology of Infertility in Women with Endometriosis������������������    1
Nicola Berlanda, Francesca Chiaffarino, Elena Roncella, Giovanna
Esposito, and Fabio Parazzini

Endometriosis and Infertility: The Comorbidities ��������������������������������������    9
Tommaso Capezzuoli, Flavia Sorbi, Silvia Vannuccini, Roberto Clarizia,
Marcello Ceccaroni, and Felice Petraglia

Impact of the Endometriomas on the Ovarian Follicles������������������������������   19
Paul J. Yong and Mohamed A. Bedaiwy
Fertility Prediction in Patients with Endometriosis (Endometriosis
Fertility Index)�������������������������������������������������������������������������������������������������   31
Tingfeng Fang and Wenjun Wang

Spontaneous Ovulation in Patients with Endometriosis������������������������������   41
Simone Ferrero, Fabio Barra, Marco Crosa, Umberto Leone Roberti
Maggiore, and Herut Attar

Endometrial Receptivity in Women with Endometriosis ����������������������������   49
Eva Vargas, Irene Leones-Baños, Nerea M. Molina, and Signe Altmäe

Assessment of Ovarian Reserve in Women with Endometriosis�����������������   81
Baris Ata, Engin Turkgeldi, and Uzeyir Kalkan

Assessment of Tubal Patency in Women with Endometriosis����������������������   93
Fabio Barra, Marco Crosa, Francesco Rosato, Giulio Evangelisti, and
Simone Ferrero

Role of Fallopian Tubes in Endometriosis-­Related Infertility �������������������� 103
Simone Ferrero, Michele Paudice, Umberto Leone Roberti Maggiore,
Francesco Rosato, and Ertan Saridogan

vii
viii Contents


Role of Ultrasonography in the Diagnosis of Endometriosis in Infertile
Women: Ovarian Endometrioma, Deep Endometriosis, and Superficial
Endometriosis�������������������������������������������������������������������������������������������������� 113
Rodrigo Manieri Rocha, Mathew Leonardi, and George Condous

Surgical Treatment of Endometriomas: Impact on Ovarian Reserve�������� 131
Sabrina K. Rangi, Natalia C. Llarena, and Tommaso Falcone
Surgical Treatment of Deep Endometriosis: Impact on
Spontaneous Conception �������������������������������������������������������������������������������� 149
Simone Ferrero, Umberto Perrone, Chiara Sertoli, Francesca Falcone,
and Mario Malzoni

Intrauterine Insemination in Women with Endometriosis�������������������������� 163
Simone Ferrero, Umberto Leone Roberti Maggiore, and Luca Bernardini
Hormonal Therapies before In-Vitro Fertilization in Women
with Endometriosis������������������������������������������������������������������������������������������ 171
Antoine Naem and Antonio Simone Laganà
IVF Stimulation Protocols and Outcomes in Women with
Endometriosis�������������������������������������������������������������������������������������������������� 199
Jwal Banker, Henrique D’Allagnol, and Juan A. Garcia-Velasco

The Effect of Endometriosis on the Quality of Oocytes and Embryos
Obtained by IVF���������������������������������������������������������������������������������������������� 209
Loukia Vassilopoulou, Michail Matalliotakis, Charoula Matalliotaki,
Konstantinos Krithinakis, and Ioannis Matalliotakis

Impact of Surgery for Deep Endometriosis on the Outcomes of In Vitro
Fertilization������������������������������������������������������������������������������������������������������ 223
Simone Ferrero, Giovanni Camerini, and Emad Mikhail
Impact of Surgery for Ovarian Endometriomas on the Outcomes
of In Vitro Fertilization������������������������������������������������������������������������������������ 229
Mauro Cozzolino, Daniela Galliano, and Antonio Pellicer

Endometriosis Progression and In Vitro Fertilization���������������������������������� 249
Ginevra Mills and Michael H. Dahan
Endometriosis-Related Complications in Women Undergoing
In Vitro Fertilization���������������������������������������������������������������������������������������� 269
Gaetano Riemma, Salvatore Giovanni Vitale, and Stefano Angioni

Fertility Preservation in Endometriosis �������������������������������������������������������� 279
Simone Ferrero, Umberto Leone Roberti Maggiore, Irene Gazzo,
and Annalisa Racca
Index������������������������������������������������������������������������������������������������������������������ 291
The Epidemiology of Infertility in Women
with Endometriosis

Nicola Berlanda, Francesca Chiaffarino, Elena Roncella, Giovanna Esposito,

and Fabio Parazzini

Endometriosis is a common disease, affecting about 10% of women of reproductive

age. The main symptoms are pelvic pain, menorrhagia, dysmenorrhea; further,
endometriosis may reduce fertility. Frequently cited statistics report that about 30%
of women with endometriosis have a diagnosis of infertility [1]. Other studies have
reported a frequency of endometriosis among infertile women ranging from 20 to
50% [2, 3]. The strength of the association between endometriosis and infertility is
variable; it has been suggested that the extent of disease impacts the degree of
reduced spontaneous fertility [4].
The causes of infertility in women with endometriosis are not completely under-
stood, but distorted pelvic anatomy, endocrine and ovulatory abnormalities, altered
peritoneal function, and hormonal and cell-mediated functions in the endometrium
are factors that can explain the association.
In this chapter, we have briefly reviewed the main epidemiological data on the
relationship between endometriosis and infertility, focusing on data on the fre-
quency of infertility among women with endometriosis, the frequency of endome-
triosis among women with infertility, and finally the determinants of infertility
among women with endometriosis. Further, a brief paragraph will address the
impact of infertility on the quality of life of women with endometriosis.

N. Berlanda · F. Chiaffarino
Gynaecology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico,
Milan, Italy
E. Roncella
Gynaecology Unit, Ospedale di Melzo, Asst Melegnano-Martesana, Milan, Italy
G. Esposito · F. Parazzini (*)
Department of Clinical Sciences and Community Health, Università degli Studi di Milano,
Milan, Italy
e-mail: [email protected]

© The Author(s), under exclusive license to Springer Nature 1

Switzerland AG 2024
S. Ferrero (ed.), Endometriosis-related Infertility,
https://doi.org/10.1007/978-3-031-50662-8_1
2 N. Berlanda et al.

1 Frequency of Infertility among Women with Endometriosis

In the “normal” couples, the monthly probability of conception, i.e. fecundability, is

about 0.15–0.20. This value decreases to 0.02–0.1 per month in women with endo-
metriosis [5–7] and this disease is also associated with a lower live birth rate [8].
The more simple way to analyze the relationship between infertility and endome-
triosis is to investigate the frequency of infertility among women with endometrio-
sis. However, despite the impressive number of papers published every year on
endometriosis, only a few epidemiological studies offer information on this issue.
The most quoted data are from the Nurses’ Health Study II prospective cohort study.
This study reported 1721 cases of laparoscopically confirmed endometriosis among
women with no past infertility during a 10-year follow up. Among these, 1340
women were never infertile whereas 361 (21%) women reported an infertility evalu-
ation as well as a laparoscopic confirmation of endometriosis. The overall incidence
rate of endometriosis was 237/100,000 person-years and did not begin to decrease
significantly until women were in their late 30 s to early 40 s. The corresponding
values of age-adjusted incidence rate of diagnosis of laparoscopically confirmed
endometriosis among women with a history of infertility were 1380/100,000
person-­years [9].
In a prospective study conducted by Prescott et al., among the 58,427 eligible
women included in the analysis, 3537 (6%) reported a diagnosis of laparoscopically
confirmed endometriosis. Among them, 83% were parous by the age of 40 and, of
these, 15% reported ever use of clomiphene or gonadotrophin to stimulate ovula-
tion, and 2% reported ever use of IVF. In that cohort study, women with a history of
endometriosis have a higher risk for incident infertility compared with women with-
out a history of endometriosis [hazard ratio (HR) 2.12, 95% confidence interval
(CI): 1.76–2.56] [10].
In line with these findings, recently in Canada, Singh et al. conducted a cross-­
sectional online survey of women aged 18–49. Out of about 2000 women with
endometriosis, 22% reported infertility [11].

2 Frequency of Endometriosis among Infertile Women

Another way for quantifying the association between endometriosis and infertility
is to analyze the frequency of endometriosis among infertile women. We have
recently conducted a systematic review of the frequency of endometriosis in infer-
tile populations [12]. We included studies that reported incidence or prevalence
rates or ratios for infertile women. On the whole, 14 papers were included for a total
of more than 6000 women [13–26] (Table 1).
The pooled estimated prevalence of endometriosis was 23.8% (95%CI:
16.1–31.5) in infertile women. However, this estimation has some limitations. First,
since surgical visualization has been traditionally considered the gold standard for a
diagnosis of endometriosis, it is possible that only a proportion of infertile women
had laparoscopy. Second, large differences emerged in the prevalence among
The Epidemiology of Infertility in Women with Endometriosis 3

Table 1 Main results of References, country Frequency of endometriosis (%)

studies on the prevalence of [15], USA 43 (43/100)a
endometriosis in women with
infertility [20], Spain 34.5 (259/750)
[25], Nepal 2.5 (5/200)
[16], Pakistan 16.8 (134/796)
[21], Belgium 47 (104/221)
[13], Poland 9.6 (145/1517)
[14]. Malta 23 (74/437)
[22], India 48.4 (180/372)
[24], Australia 6.6 (5/76)
[26], Nigeria 24 (33/141)
[18], Pakistan 11 (9/80)
[19], USA 9.5 (68/717)b
[23], USA 55 (276/502)
[17], Pakistan 11 (11/100)
a
Cases with endometriosis/total cases
b
Endometriomas are not included

studies ranging from 2.5% to 55%. These differences can be at least in part explained
by different study designs. Some studies have recruited selected women and other
studies had a small sample size. The direction of these biases is unclear, but in gen-
eral, we can consider that about one out of three to four women with clinically evi-
dent endometriosis experiences infertility problems.

3 Risk Factors

Frequency of the disease apart, the goal of epidemiological studies is also to analyze
the factors associated with a condition. A few studies have considered the factors
associated with infertility among women with endometriosis. Similarly, very few
data are available on the risk factors for endometriosis among infertile women.

4 Factors Associated with Infertility among Women

with Endometriosis

4.1 Stage and Site of Endometriosis

The Revised American Fertility Society (AFS) scoring system is widely used to
staging the endometriotic disease. Clinical data, however, have consistently shown
that there is no clear relationship between the AFS staging and the infertility [27, 28].
It is a common thought that pelvic anatomy distortion can explain infertility in
patients with severe forms of endometriosis. Further, pelvic/peritubal adhesions
4 N. Berlanda et al.

could affect tube patency, oocyte release and capture by the fimbriae, ovum pickup,
and ovum transport. Moreover, it has been suggested that women diagnosed with
advanced endometriosis have a smaller follicle count, maybe due to surgical treat-
ment damaging the ovarian tissue [29]. In this perspective, Adamson and Pasta pro-
posed the use of the “Endometriosis fertility index” that takes into account, with the
ASRM score, the functional status of the fallopian tubes, ovaries, and fimbriae and
some clinical characteristics such as woman’s age, duration of infertility, and previ-
ous pregnancies [30]. This index has been shown to be a useful tool for predicting
reproductive prognosis after ASRM staging, underlining the role of tubal status on
the risk of infertility [30, 31].
However, infertility in women with early endometriosis, where pelvic anatomi-
cal distortions are not present, involves other mechanisms, such as the alteration of
the peritoneal, follicular, and endometrial microenvironments which can cause
damage to folliculogenesis, ovulation, oocyte quality, endometrial receptivity, and,
even, sperm function [32, 33]. Due to the plurality of the possible mechanisms lead-
ing to infertility and to the frequent coexistence of different phenotypes of endome-
triosis, it is difficult to assess the risk of infertility specifically for deep, ovarian, and
peritoneal disease. Recently, a specific mechanism for ovarian endometriosis to
cause infertility has been demonstrated in a mice model, consisting in an iron-­
mediated oxidative stress of ovarian follicles [34]. Further studies are advisable to
assess whether ovarian endometriosis is more frequently associated with infertility
as compared to the other locations of the disease.
A risk factor for infertility in women with endometriosis may be represented by
adenomyosis. In a recent study by Decter et al. [35], among women undergoing
surgery for endometriosis, those presenting five or more ultrasonographic features
of adenomyosis had a two-fold risk of infertility as compared to those who did not
[odds ratio (OR) 2.31, 95%CI:1.20–4.45, p = 0.012].

4.2 General Characteristics of the Woman

In the previously quoted cohort study by Prescott et al., the increased risk of
endometriosis-­associated infertility was apparent only among women <35 years of
age and those of normal weight (BMI < 25 kg/m2) [10].

5 Risk Factors for the Endometriosis Associated

with Infertility

The main recognized risk factors for endometriosis are nulliparity, never oral con-
traceptive use, and regular menstrual cycles [36]. A few studies have analyzed the
role of these factors on the risk of endometriosis associated with infertility in com-
parison with asymptomatic endometriosis or endometriosis associated with pain.
The Epidemiology of Infertility in Women with Endometriosis 5

In two case–control studies conducted in Italy during the last decade of the previ-
ous century, regular menstrual cycles and oral contraceptive use increased the risk
of endometriosis associated with infertility and the estimated ORs were largely
similar to those associated with the risk of painful endometriosis [37–39]. Calhaz-­
Jorge et al., among 1079 subfertile women, reported that risk factors for the pres-
ence of endometriosis were race, obesity, irregular menstrual cycles, intensity of
menstrual flow, dysmenorrhea, chronic pelvic pain, obstetric history, oral contra-
ceptive pill use, and smoking habits, i.e. the general risk factors for endometriosis
[40]. These findings suggest that the epidemiological profile of endometriosis asso-
ciated with infertility is similar to that of endometriosis associated with pain.

5.1 Impact of Infertility on the Quality of Life of Women

with Endometriosis

Another important aspect of the relationship between endometriosis and fertility is

the impact of infertility on the quality of life of women with endometriosis. Recently,
Missmer et al. have published a narrative review. The authors have identified seven
studies that address the impact of endometriosis on the fertility component of the
life course [41]. The authors reported that “the experience of infertility adds to the
burden of endometriosis, negatively affecting psychological health, marital relation-
ships, social interactions (e.g. avoiding friends and relatives with children), and
financial status (due to fertility treatment) as well as causing feelings of stigmatiza-
tion and hopelessness.” Moreover, some young women with endometriosis worry
about finding a significant other who will be accepting a possible infertility [42]. In
particular, the potential risk of infertility associated with endometriosis impacts the
family planning [43]. Some couples may be pushed to search for a pregnancy earlier
than they had planned, inducing anxiety.

6 Conclusion

Infertility is a condition commonly associated with endometriosis. Epidemiological

data suggest that the risk of infertility is about two times or more higher among
women with endometriosis in comparison with the general population. However,
not all women with endometriosis had infertility: about 25% of women with clini-
cally evident endometriosis will experience infertility during their life, and con-
versely about 25% of infertile women will be diagnosed with endometriosis.
If we are able to quantify the relationship between endometriosis and infertility,
the mechanisms of this relationship are poorly understood. The functional status of
the fallopian tubes, ovaries, and fimbriae is probably the most important determi-
nant of the reproductive prognosis in women with endometriosis, but this evaluation
6 N. Berlanda et al.

requires invasive procedures. Older age and no previous births (primary infertility)
are clinical determinants of poor prognosis, but their clinical impact is limited due
to the large proportion of “old,” nulliparous women among women with an incident
diagnosis of endometriosis or infertile women.
Fertility preservation (e.g. egg freezing) among reproductive-age women with
endometriosis has been suggested [44]. A more clearer understanding of the relation
between endometriosis and infertility and, in particular, the identification of risk
factors of poor reproductive prognosis among women with a diagnosis of endome-
triosis may be useful to offering personalized counseling and therapeutic options to
women with endometriosis.

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25883035
Endometriosis and Infertility:
The Comorbidities

Tommaso Capezzuoli, Flavia Sorbi, Silvia Vannuccini, Roberto Clarizia,

Marcello Ceccaroni, and Felice Petraglia

1 Introduction

Infertility is one of the most important symptoms in women with endometriosis.

Endometriosis-related infertility is associated with ovarian damage, altered endo-
metrium, alteration of the pelvic cavity due to inflammation, and adhesions with
distortion of pelvic architecture and inflammatory changes in peritoneal fluid [1].
The prevalence of infertility in women with endometriosis is very high and the dis-
ease is one of the main causes of female infertility. The monthly fecundity rate in
endometriosis is reduced from 15–20% to 2–10%; an advanced stage of disease
correlates with a greater decline of this rate. In patients undergoing laparoscopy for
infertility, the prevalence of endometriosis is at least 30%, confirming the relevant
impact on women’s reproductive life [2].
The present chapter will review the coexistence of gynecological [adenomyosis,
uterine fibroids, and polycystic ovarian syndrome (PCOS)] or systemic (immune,
inflammatory, and psychiatric and neurological disorders) comorbidities (Fig. 1)

T. Capezzuoli · F. Sorbi · F. Petragli (*)

Department of Clinical Experimental and Biomedical Sciences, University of Florence,
Florence, Italy
e-mail: [email protected]; [email protected]
S. Vannuccini
Obstetrics and Gynecology, Department of Maternity and Infancy, AOU Careggi,
Florence, Italy
e-mail: [email protected]
R. Clarizia · M. Ceccaroni
Department of Obstetrics & Gynecology, Gynecologic Oncology and Minimally Invasive
Pelvic Surgery, International School of Surgical Anatomy, IRCCS Sacro Cuore Don Calabria
Hospital, Negrar, Verona, Italy
e-mail: [email protected]

© The Author(s), under exclusive license to Springer Nature 9

Switzerland AG 2024
S. Ferrero (ed.), Endometriosis-related Infertility,
https://doi.org/10.1007/978-3-031-50662-8_2
10 T. Capezzuoli et al.

Fig. 1 Gynecological and systemic comorbidities of endometriosis

which may influence fertility and reduce the chance of onception in women with
endometriosis.
The coexistence of gynecological and systemic comorbidities can in fact contrib-
ute in different ways to associated infertility. Therefore, the evaluation of these
comorbidities is crucial in the management of endometriosis-associated infertil-
ity [3, 4].

1.1 Gynecological Comorbidities

1.1.1 Adenomyosis

Adenomyosis is characterized by the presence of endometrial glands and stroma in

the myometrium and dysmenorrhea and heavy menstrual bleeding (HMB) are the
main symptoms [5]. In the past few years, several studies have shown the presence
of adenomyosis in patients with endometriosis.
Trans-vaginal ultrasound (TVUS) evaluation of women before undergoing lapa-
roscopic surgery for pelvic pain highlights a strong association between uterine
Endometriosis and Infertility: The Comorbidities 11

adenomyosis and stage IV endometriosis [6]. Naftalin et al. observed a 20.9% prev-
alence of adenomyosis by using TVUS in a general population of patients attending
a gynecological clinic; adenomyosis was associated with an older age, higher gra-
vidity and parity, and presence of pelvic endometriosis [7].
Di Donato et al. showed a prevalence of 21.8% in patients undergoing surgery
for endometriosis, detecting a statistically significant association with parity, age,
dysmenorrhea intensity, and the presence of deep infiltrating endometriosis (DIE)
[8]. A higher prevalence of adenomyosis was found by Eisemberg et al., who
observed an 89.4% prevalence of TVUS signs of adenomyosis in women with a
history of surgery for endometriosis [9]. Lazzeri et al. found a 47.8% prevalence of
adenomyosis in women with DIE, influencing significantly the pre- and post-­
surgical dysmenorrhea severity [10]. A similar prevalence of adenomyosis (59.9%)
was detected by using magnetic resonance imaging (MRI) in symptomatic women
younger than 42 years, undergoing surgery for endometriosis [11]. Capezzuoli et al.
evaluated the coexistence of uterine disorders by TVUS in patients with endome-
triosis and history of infertility, with a prevalence of adenomyosis in 21.2% of
patients [3].
Adenomyosis-related infertility is caused by aberrant uterine contractility, abnor-
mal myometrial activity, and deranged endometrial milieu with altered expression
of implantation factors [5, 12]. Adenomyosis affects fertility in a very strong way by
reducing the fertility rate and increasing the abortion rate, as described by a pioneer
study in baboons [13] and recently confirmed [14].

1.1.2 Uterine Fibroids

Uterine fibroids are present in 5–10% of infertile women, but they represent the
unique cause of infertility only in 2–3% and, in particular, when determining distor-
tion of the uterine cavity, alteration to the endometrial and myometrial blood supply,
deviation or obstruction of the tubal ostia, and impaired implantation [15, 16].
The association between uterine fibroids and endometriosis is less clear and most
of the studies showed histological prevalence of uterine fibroids in women with
endometriosis undergoing surgery. Uimari et al. [17] detected uterine fibroids in
25.8% of patients undergoing surgery for endometriosis and, conversely, in 19.6%
of patients operated for uterine fibroids. According to another surgical report, pre-
menopausal women requiring a hysterectomy for benign uterine disorders had
endometriosis and adenomyosis in 40.4%, endometriosis and uterine fibroids in
22.7%, and both conditions in 34.1% [18]. In a similar report on women undergoing
surgery for benign gynecological disease, the coexistence of endometriosis with
uterine fibroids, adenomyosis, and benign ovarian cysts was 28%, 43.5%, and 50%,
respectively [19].
Coexisting uterine fibroids and endometriosis were identified in 21.2% of
patients undergoing laparoscopy myomectomy [20].
12 T. Capezzuoli et al.

When evaluated by TVUS in infertile endometriotic patients [3], the prevalence

of uterine fibroids in women with endometriosis was 3.1%, while the prevalence of
uterine fibroids associated with adenomyosis was 14.6%.

1.1.3 PCOS

PCOS results from a vicious circle of androgen excess favoring abdominal and vis-
ceral adipose tissue deposition that induces insulin resistance and compensatory
hyperinsulinemia, further facilitating androgen secretion by the ovaries and adrenal
glands. This cyclical pathogenetic interaction between insulin resistance, hyperin-
sulinemia, and hyperandrogenism, in combination with hypothalamic-pituitary dys-
function, leads to further ovarian dysfunction that can result in anovulation and
infertility. Similar mechanisms are involved in infertility related to metabolic syn-
drome [21].
The association between endometriosis and PCOS is less studied. In a recent
retrospective cohort study and meta-analysis [22], the prevalence of asymptomatic
endometriosis in women undergoing laparoscopic ovarian drilling for Clomiphene-­
resistant polycystic ovary syndrome was 7.7%. PCOS is associated with lower
endometriosis stages (I and II) at the American Society for Reproductive Medicine
(ASRM) classification [23].

1.2 Systemic Comorbidities

Endometriosis is a benign endocrine disorder but inflammation and immune factors

should be considered in the pathogenetic mechanisms. Epidemiological studies
show that women with endometriosis are often affected by systemic comorbidities,
including immune, inflammatory, psychiatric, and neurological disorders [24–27].

1.2.1 Autoimmune Diseases

Systemic autoimmune diseases can interfere in several ways with female fertility,
with general and specific mechanisms. Patients with systemic autoimmune diseases
have less children than expected in the general population. Some of these women do
not have children, some others report a prolonged time to pregnancy resulting in
smaller family size than they expected. The disease itself and the musculoskeletal
limitations linked to it can impair sexual function and psychologically impact
woman desire. In addition, in several systemic autoimmune diseases, also the poor
body image, the related to poor self-esteem, and depression can influence the per-
sonal and sexual relationships of these women [28].
Women affected by endometriosis present an increased prevalence of several auto-
immune diseases. The presence and the growth of endometrial cells in the peritoneal
cavity promote oxidative stress and inflammation. Endometriosis is in fact
Endometriosis and Infertility: The Comorbidities 13

characterized by an inflammation milieu with an increased production of metallopro-

teinases, prostaglandins, and cytokines, such as interlukein-6 and tumor necrosis fac-
tor (TNF) that promote the adhesion of endometrial tissue on ectopic surfaces.
Moreover, women with endometriosis exhibit altered immune surveillance with
depressed cell-mediated immunity and higher humoral immune response. Moreover,
a genetic predisposition HLA DQ7-related is suggested for endometriosis and several
gene polymorphisms are found both in endometriosis and autoimmune diseases as
well as some genetic alleles involved in the release of autoantibodies [29].
Altered cell-mediated immunity is also involved in the development of the Celiac
disease because the disease pathogenesis is characterized by a critical role of inter-
leukin-­18 (IL-18) and interferon-c (IFN-c) in inducing and maintaining Th1
responses after gluten exposure. Similarly, a Th1 imbalance with involvement of
IL-18 and IFN-c has been reported in endometriosis and it has been shown that
IL-18 is a key cytokine in developing the pathogenesis of endometriosis [29].
The relationship between systemic lupus erythematosus (SLE) and endometrio-
sis could be related to ANA autoantibodies production, detected also in endometrio-
sis [24]. Moreover, the similarities between the underlying humoral immune
dysfunction observed in SLE and endometriosis and the similar direction of asso-
ciations between hormonal risk factors in these two diseases may explain the strong
concomitancy [30]. The premature ovarian failure observed in SLE patients is
linked to immunosuppressive drug treatment but also the associated autoantibodies
can directly affect the male and female gonads. In women, anti-ovarian antibodies
described as linked to ovarian aging and autoimmune oophoritis leading to impaired
ovarian function were reported in SLE patients and linked to premature menopause.
Moreover, menstrual irregularity and ovulatory cycles are reported in SLE patients
with high disease activity [28].
Humoral immunity can explain the correlation with autoimmune thyroid dis-
eases. A higher reactivity of some autoantibodies (e.g., anti-thyroid peroxidase anti-
bodies) in patients with endometriosis has been found. Another possible link
between endometriosis and autoimmune thyroiditis (in this case Grave’s disease)
could be identified in an alteration in the expression of the estrogen receptor beta
gene (ESR2), which is an important modulator of the immune system as an regula-
tor of cytokine expression, antigen presentation, and B-cell lymphopoiesis [29, 31,
32]. Hypothyroidism associated with autoimmune thyroiditis can impair fertility by
decreasing levels of sex-hormone-binding globulin and increasing the secretion of
prolactin (ovulatory dysfunction from inadequate corpus luteal progesterone secre-
tion associated to the altered secretion of gonadotrophin-releasing hormone) [28].

1.2.2 Inflammatory Diseases

Women with endometriosis have an increased risk of inflammatory bowel diseases,

even after 20 years from diagnosis. In a large Danish cohort study, women with
endometriosis had an increased risk of Chron’s disease and ulcerative colitis with a
standardized incidence ratio of 1.5 (95% CI 1.3–1.7) and 1.6 (95% CI 1.3–2.0),
respectively [33]. In epidemiological studies with a control group, the proportion of
14 T. Capezzuoli et al.

inflammatory bowel diseases in patients with endometriosis varied from 2% to

3.4%, compared to 0%–1% of the control group. Endometriosis and inflammatory
bowel diseases are characterized by similar features and symptoms. In the case of
concomitancy, this results in an increased risk of delayed or indeterminate diagno-
sis. Inflammatory cytokines and dysregulation of the immune system are key fea-
tures of endometriosis and inflammatory bowel diseases. Both conditions overlap
not only in symptoms but also in the potential mechanism of disease pathogenesis.
In patients where endometriosis and inflammatory bowel diseases coexist, the
symptoms can be atypical and cyclic, and fibrosis, caused by chronic inflammation,
can contribute to obstruction of the intestinal lumen [34]. Women with Crohn’s
disease have normal or only slightly reduced fertility, whereas those with ulcerative
colitis have normal fertility [35]. The low fertility rate is rather because of voluntary
childlessness than severe disease, perianal involvement, and ileal pouch-anal anas-
tomosis surgery [36].
Women with endometriosis are at a 1.4–1.6 higher risk of myocardial infarction/
coronary disease. The data may be correlated with high levels of oxidative stress
markers, elevated inflammatory factors, and oxidative stress markers in affected
women. Part of the associations was found to be statistically accounted for by endo-
metriosis treatments that are risk factors for cardiovascular diseases, such as hyster-
ectomy/oophorectomy and earlier age at surgery following endometriosis diagnosis
[24, 37, 38]. Moreover, women with endometriosis present a higher risk of hyper-
cholesterolemia with RR 1.25 (95% CI, 1.21–1.30) and hypertension with RR 1.14
(95% CI, 1.09–1.18) [38, 39]. These data may be associated with the altered hor-
monal and chronic systemic inflammatory milieu typical of endometriosis.
Conversely, elevated low-density lipoprotein in hypercholesterolemia and chronic
systemic inflammation resulting from hypertension may increase the risk of endo-
metriosis [39].
Considering intra-pelvic inflammation conditions, superficial endometriosis
prevalence is increased in women undergoing emergency surgery for appendectomy
[40]. Moreover, endometriosis patients seem to present a higher prevalence of pel-
vic inflammatory disease (PID), above all, in the case of high-stage disease [41].
Infertility can result from PID because the infection can cause severe damage to the
fallopian tubes, including loss of the ciliary epithelial cells of the fallopian tube and
occlusion of the tube [41]. Finally, also bladder pain syndrome and recurrent inter-
stitial cystitis (BPS/IC) seems to be associated with endometriosis. BPS/IC and
endometriosis share common pathogenetic mechanisms including inflammatory
changes through several potential mediators such as chemokines or cytokines [42].

1.2.3 Mental Health Disorders and Migraine

A great vulnerability to psychiatric disorders is described in endometriosis patients.

There is, in particular, a tendency to contract affective or anxiety disorders as well
as panic–agoraphobic, somatoform, and substance use disorders. Endometriosis
with pelvic pain, infertility, and psychic vulnerability usually leads to disability and
Endometriosis and Infertility: The Comorbidities 15

a markedly lower quality of life for women of reproductive age. Thus, the burden of
endometriosis is not limited to the symptoms and dysfunctions of the disease; it
extends to the social, working, and emotional spheres, leading to severe impairment
of global functioning and significant disruption of daily life [26, 43]. Finally, endo-
metriosis seems to be associated with a higher risk of migraine. In a recent study,
adolescents with endometriosis were more likely to experience migraine (69.3%)
than those without endometriosis (30.7%) [44].

2 Conclusions

Endometriosis is a complex disease and it is often associated with various gyneco-

logical and systemic comorbidities. The concomitant presence of these disorders
has a synergistic effect in determining the worst quality of life in affected women
and interferes with fertility. A common pathogenesis between endometriosis and
some of these diseases (adenomyosis or systemic autoimmune diseases) supports
the concept of infertility as a syndrome with various clinical aspects.
The diagnosis of concomitant gynecological and systemic conditions affecting
fertility is critical to define a more comprehensive counseling and a better plan for
fertility desire. The identification of coexistent gynecological diseases allows to
plan a medical or surgical pretreatment. The association of endometriosis with sys-
temic autoimmune conditions is a well-known cause of infertility and/or subfertility
that needs to be taken into consideration when difficulties in conception are reported.

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Impact of the Endometriomas
on the Ovarian Follicles

Paul J. Yong and Mohamed A. Bedaiwy

1 Introduction

This chapter will focus on the biological impact of ovarian endometriomas on ovar-
ian structure and function, which may lead to infertility. We will begin with a brief
overview of the etiology of ovarian endometriomas, and then review potential bio-
logical mechanisms including (a) anatomical distortion and other non-ovarian
mechanisms; (b) endometrioma fluid and cyst wall; (c) iron metabolism, oxidative
stress, and local inflammation, and their relation to abnormalities in granulosa cells
and follicular fluid; and (d) pathways leading to a reduction in oocyte quantity.
There will be a focus on the published literature specific to ovarian endometriomas,
rather than endometriosis in general. These mechanisms are illustrated in Fig. 1.

2 Etiology of Ovarian Endometriomas

There are several hypotheses for the genes of the endometrioma cyst wall [1]. One
hypothesis is metaplasia of invaginated mesothelial inclusions, where mesothelium
covering the ovary invaginates into the cortex and subsequently undergoes coelomic
metaplasia. A second hypothesis is that superficial implants invaginate into the
ovarian cortex, for example, where the ovary becomes attached to adjacent non-­
ovarian endometriosis, followed by invagination into the ovarian cortex. A third
hypothesis is that adjacent non-ovarian endometriosis invades a corpus luteum.
Regardless, the resulting endometrioma has a mean cyst wall thickness of 1.4 mm,

P. J. Yong (*) · M. A. Bedaiwy

Department of Obstetrics and Gynaecology, University of British Columbia, BC Women’s
Centre for Pelvic Pain and Endometriosis, Vancouver, BC, Canada
e-mail: [email protected]

© The Author(s), under exclusive license to Springer Nature 19

Switzerland AG 2024
S. Ferrero (ed.), Endometriosis-related Infertility,
https://doi.org/10.1007/978-3-031-50662-8_3
20 P. J. Yong and M. A. Bedaiwy

Fig. 1 Biological effects of ovarian endometriomas on ovarian follicles. Ovarian endometriomas

are associated with increased iron, oxidative stress, and inflammation, which can diffuse to sur-
rounding follicles and reduce oocyte quality. Granulosa cells demonstrate higher rates of senes-
cence, apoptosis, and autophagy, which can lead to decreased estradiol production. Endometriomas
also induce surrounding ovarian fibrosis and decreased vascularization, as well as stretch-induced
hyperactivation of primordial follicles, which reduces oocyte quantity. Around endometrioma-­
affected ovaries, the presence of non-ovarian endometriosis, tubo-ovarian adhesions, and perito-
neal inflammation also reduce fertility. It should be noted that this is a simplified diagram only; for
example, the ovarian endometrioma would consist of chocolate fluid, endometrial epithelium/
stroma cyst wall, as well as fibrosis. Created with BioRender

with the endometriosis epithelium/stroma penetrating the cyst wall only 0.6 mm on
average [2].
While a full account of the biological studies of ovarian endometriomas is
beyond the scope of this chapter, a brief review of recent novel methodological
approaches will be provided. In a review of epigenetic studies of endometriomas
[3], epigenetic alterations were noted in histones H3 and H4, and notably hypo-
methylation of steroidogenic factor-1 (SF-1) that binds promoters of steroidogenic
acute regulatory protein (STAR) and aromatase. The latter was replicated in a
genome-wide methylation study of endometrial stromal cells from endometriomas
[4]. Other genes have been found to be hypomethylated or hypermethylated in ovar-
ian endometriomas in another genome-wide analysis by Borghese et al. [5], although
only a specific subset of epigenetic events were correlated to nearby gene expression.
Furthermore, somatic cancer driver mutations and other somatic genomic events
in the epithelium of endometriosis (without cancer), including endometriomas,
were recently reviewed [6]. In ovarian endometriomas, a variety of abnormalities
Impact of the Endometriomas on the Ovarian Follicles 21

have been noted such as chromosome abnormalities (e.g. chromosome 17 aneu-

ploidy, as well as a variety of chromosome arm gains or losses using comparative
genomic hybridization), areas of loss of heterozygosity (e.g. 10q23.3), loss of
BAF250 (ARID1A) immunohistochemistry expression in a proportion (8–19%) of
endometriomas, and recurrent somatic cancer driver mutations in endometriosis
epithelium in work done by Suda et al. (e.g. in KRAS and PIK3CA) [7, 8]. The bio-
logical implications of these somatic genomic events remain unclear, but as they are
characteristic of malignancies, they may promote invasion or invagination of endo-
metriosis cells into the ovary.
Sanchez et al. [3] reviewed the literature for microarray gene expression studies
on ovarian endometriomas specifically in comparison to the eutopic uterine endo-
metrium. They found that endometriomas had comparatively higher expression of
hydroxysteroid 11beta-dehydrogenase that converts cortisone to cortisol; phospho-
lipase A2 group II and group V that produce arachidonic acid precursor for prosta-
glandins; apolipoprotein E expressed by macrophages; peroxisome
proliferator-activated receptor gamma that regulates cytokine transcription; as well
as complement proteins (C1R, C3, and C7), cytoskeletal components actin alpha2
and myosin 11, and various major histocompatibility complex molecules.
Finally, Hayashi et al. [9] generated a mouse model of ovarian endometriomas,
where uterine tissue was implanted in the ovaries of syngeneic mice. They found
that the endometrioma-affected ovaries had elevated iron levels and more oxidative
stress in follicles, accompanied by a reduction in FSH expression. The role of iron
and oxidative stress in endometriomas and surrounding follicles will be explained
in more detail below.

3 Anatomic Distortion and Other Non-ovarian Mechanisms

Endometriomas may be associated with tubo-ovarian adhesions and non-ovarian

endometriosis (particularly, deep endometriosis), resulting in anatomic distortion
that negatively affects the ability of the tubal fimbriae to capture the ovulated oocyte.
Endometriomas and endometriosis, in general, are also associated with peritoneal
inflammation (e.g. elevated IL-1beta, IL-6, and tumor necrosis factor) that may
affect tubo-ovarian function and also hinder sperm motility and oocyte–sperm inter-
action [10]. The increase in peritoneal inflammation may also potentially impair
oocyte quality [11]. Moreover, the peritoneal fluid has evidence of oxidative stress
due to iron from shed blood from endometriosis lesions and from retrograde men-
struation, which contributes to the inflammation in the peritoneal fluid that sur-
rounds the ovary [10]. If macrophages take up the iron, then the iron not be accessible
to ferritin, which further increases oxidative stress [12]. In addition, it is also plau-
sible that endometriosis (and endometriomas) may affect endometrial receptivity
and implantation, if there is an increase in eutopic endometrial inflammation in
endometriosis (e.g. related to increased aromatase producing higher estradiol) [13],
22 P. J. Yong and M. A. Bedaiwy

with perhaps another mechanism being anterograde flow of endometriosis-­

associated inflammatory peritoneal fluid into the endometrial cavity.

4 Endometrioma Fluid and Cyst Wall

Cellular and molecular features of endometriomas were extensively reviewed by

Sanchez et al. [1], who divided their review into the endometriosis fluid, the cyst
wall and other cellular elements lining the inside of the endometrioma, and the local
environment around the endometrioma. One hypothesis is that the endometrioma
fluid itself, which arises from repeated bleeding into the cyst from the endometri-
oma cyst wall, is toxic to surrounding ovarian tissue. Similar to peritoneal fluid, the
endometrioma fluid may have an increase in iron that can mediate an increase in
oxidative stress and subsequent inflammation (e.g. IL-8). There may also be an
imbalance among activins, inhibins, and follistatin, as well as changes in soluble
adhesion molecules, in endometrioma cyst fluid. Unlike other cysts, endometriomas
are not surrounded by a true capsule such that there is less of the barrier of diffusion
from the endometrioma to surrounding ovarian tissue and follicles [14]. This local
diffusion of molecules from the endometrioma is supported by the observation of an
increase in total iron and ferritin in the follicular fluid of follicles proximal to the
endometrioma compared to follicles distal to the endometrioma and from the con-
tralateral ovary [15].
For the cyst wall, there are regions of endometriosis epithelium/stroma, but there
can also be the presence of metaplasia and regions of the cyst wall being replaced
with fibrotic tissue, as well as surrounding hemosiderin macrophages (particularly
M2 macrophages) that may support endometriosis lesion growth [1]. It has been
postulated that iron-mediated oxidative stress, such as in the endometrioma fluid, is
one mechanism that can predispose to the somatic cancer driver mutations seen in
ovarian endometrioma epithelium [1].

5 Iron, Oxidative Stress, and Inflammation

Before moving on to a discussion of changes in granulosa cells and follicular fluid,

the relationship among iron metabolism, oxidative stress, and inflammation will be
reviewed. Gupta et al. reviewed proteomic studies of the role of oxidative stress in
infertility, including in endometriosis [12]. Reactive oxygen species arise from
mitochondrial respiration (electron transport chain), and when antioxidants cannot
clear these reactive oxygen species, the result is oxidative stress. Reactive oxygen
species lack electrons which makes them reactive with surrounding molecules, with
examples being hydrogen peroxide, hydroxyl radicals, and superoxide anion. Iron
can be a cause of reactive oxygen species, due to its ability to shift between Fe2+
Impact of the Endometriomas on the Ovarian Follicles 23

and Fe3+ forms [16], and is important in endometriosis due to shed blood in endo-
metrioma fluid, in peritoneal fluid and via retrograde menstruation.
Anti-oxidants can be enzymatic (e.g. superoxide dismutase and glutathione oxi-
dase) and non-enzymatic (e.g. Vitamins A and E, zinc, and selenium) [12]. There is
a balance between reactive oxygen species and anti-oxidants: a homeostatic level of
reactive oxygen species being important for physiological processes during ovula-
tion such as resumption of meiosis I and formation of the dominant follicle, while
anti-oxidants promote resumption of meiosis II. Thus, either excessive or inade-
quate reactive oxygen species may negatively affect reproduction. Specifically, oxi-
dative stress results when reactive oxygen species exceed anti-oxidant activities,
with the oxidative stress in endometriomas then resulting in an increase in pro-­
inflammatory cytokines [1].

6 Granulosa Cell Abnormalities

Huo studied granulosa cells with associated endometriomas for evidence of mito-
chondrial abnormalities [17]. They found evidence that endometrioma-associated
granulosa cells had fewer mitochondria, more abnormal morphology, and lower
ATPase and proteins involved in oxidative phosphorylation. There was also a higher
level of cell-free mitochondrial DNA in follicular fluid in endometriosis cases com-
pared to controls that were in turn inversely associated with cell-free mitochondrial
DNA in granulosa cells. The authors interpreted these findings as suggesting a nega-
tive impact on oocyte quality, particularly as mitochondrial DNA has been corre-
lated with embryo quality. Urs et al. [18] found that endometrioma-affected ovarian
granulosa cells had less mitochondrial mass and membrane potential and less
expression of STAR and 3beta-hydroxysteroid dehydrogenase (which together were
correlated with decreased follicular estradiol), in comparison to different control
groups. There was also an increase in apoptosis of cumulus cells in the endometri-
oma group.
Another study examined granulosa cells from patients with endometrioma and
studied the role of endoplasmic reticulum stress [19]. There was evidence of endo-
plasmic reticulum stress (e.g. increased expression of unfolded protein response and
phosphorylated endoplasmic reticulum stress sensor proteins). In functional culture
studies, hydrogen peroxide (a feature of oxidative stress) promoted the expression
of unfolded protein response in cultured granulosa cells, as well as apoptosis-­
associated caspase 8 and caspase 3. Therefore, oxidative stress in the ovary due to
endometrioma may lead to endoplasmic reticulum stress and apoptosis in granulosa
cells. Similarly, lipidomic profiling showed an increase in sphingolipids and phos-
phatidylcholines in endometrioma-affected follicular fluid, which could also be
involved in apoptosis [20].
Recently the role of autophagy (catabolic process to recycle cell components) in
granulosa cells with endometrioma was investigated [21]. They found that these
granulosa cells had increased autophagy and expression of Beclin-1 (a mediator of
24 P. J. Yong and M. A. Bedaiwy

autophagy) and that these patients had an increase in serum progesterone in the late
follicular phase that may be a marker of poorer oocyte quality. In functional studies,
they showed that Beclin-1 promoted progesterone expression through the degrada-
tion of low-density lipoprotein.
Li et al. [22] examined the nuclear factor-ĸB (NF-ĸB) pathway and found that
granulosa cells in patients with endometriomas had higher NF-ĸB binding activity.
They also examined telomerase activity, which was inversely related to NF-ĸB
binding levels. In cultured granulosa cells, tumor necrosis factor-alpha (TNF-alpha)
reduced human telomerase reverse transcriptase (hTERT) and telomerase. The
authors hypothesized that in the presence of ovarian endometriomas, there may be
higher TNF-alpha that increases NF-ĸB pathway activation and reduces telomerase
activity in granulosa cells, resulting in increased granulosa cell senescence. Given
the importance of granulosa cells in promoting aromatase, this granulosa cell senes-
cence, apoptosis, and autophagy may together account in part for the observation of
decreased estradiol concentrations in endometriosis [11].
Recent studies have utilized innovative technologies to study granulosa cells in
the presence of endometriomas. Notarstefano et al. [23] used infrared and Raman
microspectroscopy on luteinized granulosa cells and found indirect evidence for
oxidative stress and lipid/carbohydrate metabolism abnormalities, both in the
endometrioma-­affected ovary and in the normal contralateral ovary, in comparison
to control ovaries. Da Luz et al. examined the transcriptome of cumulus cells from
endometriosis patients with or without endometrioma, compared to controls, using
RNA sequencing [24]. There were 461 differentially expressed genes between
endometrioma cases and control, and 66 between endometriosis (non-­endometrioma)
cases and controls. These differentially expressed genes were involved in oocyte
competence including oxidative phosphorylation, mitochondrial functioning, and
steroid metabolism. Interestingly, there were no differentially expressed genes com-
paring endometriosis cases with or without endometrioma. Another study [25]
involved microRNA profiling in cumulus cells and found that miR-532-3p was sig-
nificantly lower in stage III/IV endometriosis compared to stage I/II and to the infer-
tile control group (only five cases per group). The authors noted that this
microRNA-regulated pathway is involved in oocyte competence and oocyte meiosis.

7 Follicular Fluid Abnormalities

In general, there is evidence that the follicular fluid in ovaries affected by endome-
triomas may be associated with increased oxidative stress (e.g. mediated by iron)
and inflammation (e.g. IL-8 and IL-12) that lead to decreased oocyte quality [11]. It
should be noted that one study did not find a difference in oxidative stress in endo-
metriomas [26], while another did find evidence for an increase in ferritin and reac-
tive oxygen species pathways using a proteomic tandem mass spectrometry
approach in endometriomas [27]. Li et al. [28] also sampled follicular fluid in
patients with stage III and IV endometriosis (anatomic subtypes not specified) and
Impact of the Endometriomas on the Ovarian Follicles 25

found the endometriosis group to have decreased transferrin and iron overload and,
using a mouse model, demonstrated that this may contribute to abnormal oocyte
maturation. Another study found increased ferritin in the affected ovary compared
to the contralateral normal ovary, but no difference in iron [29].
This iron overload and subsequent oxidative stress leads to local inflammation.
Mao et al. [30] found that the follicular fluid cytokine profile in patients with a his-
tory of endometriosis compared to controls showed some that were elevated (e.g.
IL-14, IL-13, IL-3, and IL-1alpha) and some were decreased (e.g. IFN-gamma).
Yland et al. [31] recently profiled cytokines in follicular fluid in patients with endo-
metriomas compared to controls. They found that a set of cytokines that were
hypothesized to be abnormal in endometriosis (e.g. IL-6, IL-8, and IL-1beta) were
generally elevated in endometrioma-affected ovaries (and, in some cases, the con-
tralateral normal ovary in the same patient) compared to control ovaries. Toll-like
receptors (TLRs) and associated inflammation have also been investigated in ovar-
ian endometriosis [32]. In follicular fluid of endometrioma-affected ovaries, there
was an increase in cytokines such as IL-6 and IL-8, and, in cell pellets from the
follicular fluid, there was an increase in TLR1, 5, 6, 7, 8, 10, as well as NF-ĸB,
IL-10 and transforming growth factor-beta (TGF-β).
It should be noted that mitochondrial superoxide dismutase (SOD2) is an anti-­
oxidant that converts superoxide to hydrogen peroxide that is subsequently detoxi-
fied [33]. Imbalances between enzymes may result in imbalances in reactive oxygen
species, and, in fact, the accumulation of hydrogen peroxide may promote cell pro-
liferation. Thus, while SOD2 has an anti-oxidant effect, there is some evidence that
it can promote tumor cell proliferation and progression perhaps via hydrogen per-
oxide. In this study [33], endometriomas had increased expression of SOD2 (in
response to increased oxidative stress), and, in endometrial primary cell cultures,
there was evidence of SOD2-promoting cell proliferation and migration.
Finally, a microRNA profiling study was done on follicular fluid from 30 patients
with ovarian endometriomas compared to controls [34]. The authors found that
miR-451 was decreased in endometriosis, and, in functional studies, inhibiting
miR-451 in human and mouse oocytes negatively affected oocyte and embryonic
development with possible involvement of the Wnt pathway.

8 Reduction in Oocyte Quantity

The above mechanisms can reduce oocyte quality, as evidenced by changes in mor-
phology, the spindle apparatus, and the mitochondrial content of the cytoplasm [11].
For example, Ferrero et al. [35] examined metaphase II oocytes from patients with
ovarian endometriomas compared to healthy egg donors. Single-cell RNA sequenc-
ing was performed. They found numerous differentially expressed genes, typically
overexpression, for oocytes from both the affected ovary and the normal contralat-
eral ovary, in comparison to the egg donors. These genes were involved in a variety
26 P. J. Yong and M. A. Bedaiwy

of processes such as cell growth, oxidative stress, and steroid metabolism, with
particular enrichment for the mitochondria.
However, endometriomas may also reduce oocyte quantity [36]; for example, a
prospective longitudinal study found that a larger reduction in markers of ovarian
reserve in women with endometrioma-affected ovaries compared to controls [37].
As well, follicle density is lower in ovaries with endometriomas compared to the
unaffected contralateral ovary [38], and, more so, in comparison to other non-­
endometriosis benign cysts [39].
Both oxidative stress and fibrosis induced by the associated local inflammation
in endometriomas may lead to follicular depletion and decreased oocyte quantity
[10]. A reduction in ovarian cortical stromal vascularization may also contribute
[10]. In the presence of endometriomas, there may also be an increase in early fol-
licular development and subsequent atresia [10]. Di Nisio et al. found that the ovar-
ian cortex adjacent to an ovarian endometrioma had higher expression of
apoptosis-associated caspase 8, and also of p53 that is involved in the regulation of
oxidative stress response and apoptosis [40]. Altogether these mechanisms may lead
to a “burnout” of follicles and decreased ovarian reserve [10].
Notably, Takeuchi et al. utilized a mouse model of endometriosis and oocytes
from ovaries with endometriomas [41]. In the mouse model, there was a decrease in
primordial follicles and an increase in primary, secondary, and antral follicles, sug-
gesting elevated primordial follicle activation. In human oocytes from ovaries with
endometriomas, there was an activation of the phosphoinositide 3-kinase (PI3K)–
protein kinase B (Akt) pathway that when inhibited in a mouse model, increased the
primordial follicles. Therefore, endometriomas may be associated with over-­
activation of primordial follicles mediated via the PI3K-Akt pathway, leading to
“burnout” and a decrease in ovarian reserve.
The decrease in primordial follicles in endometrioma-affected ovaries may
involve the Yes-associated protein (YAP) and transcriptional co-activator with PDZ-­
binding motif (TAZ) pathway known to be involved in primordial follicle activation
[42]. In particular, YAP/TAZ are regulated by tissue stiffness and stretching. Thus,
the stretching caused by an ovarian endometrioma may mechanotransduce YAP/
TAZ that leads to the hyperactivation of primordial follicles, although the authors
note that there are likely multiple pathways involved than just simple stretching of
ovarian tissue. For example, they hypothesize that endometriomas may release reac-
tive oxygen species and inflammatory factors that can promote the PI3K/Akt path-
way, which can lead to hyperactivation of primordial follicles that further promote
a reduction in ovarian reserve.
Regarding the environment around the endometrioma, reactive oxygen species
may promote local tissue fibrosis, a change in follicular pattern, and vascular altera-
tions [1]. Fibrosis results in a reduction in follicles and cortex-specific stroma and
may also negatively affect follicular development. The loss of stroma is also impor-
tant due to its role in providing blood supply to primordial follicles. This fibrosis
and reduction in vascularization further compound the decrease in oocyte quantity.
Impact of the Endometriomas on the Ovarian Follicles 27

9 Conclusion

In conclusion, endometrioma-affected ovaries are characterized by anatomic distor-

tion and several pathophysiological changes including increased iron-mediated oxi-
dative stress and inflammation. Together, these pathways may impair oocyte quality
and quantity (Fig. 1). These biological observations have potential implications for
clinical management, in terms of the potential long-term ongoing effects of an un-­
operated endometrioma on ovarian structure and function (due to oxidative stress
and inflammation), and whether these effects can be attenuated by hormonal ther-
apy or are in any way altered by surgical removal.

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Fertility Prediction in Patients
with Endometriosis (Endometriosis
Fertility Index)

Tingfeng Fang and Wenjun Wang

1 Introduction

Endometriosis remains an enigmatic disease. Pain and infertility are the primary
presenting symptoms in the patient with endometriosis. The incidence rate of endo-
metriosis is 6–10% in reproductive-aged women and 21–47% of them are subfertil-
ity [1]. The average incidence rate of endometriosis in infertile women is about 30%
(if surgically investigated), and it rises to roughly 50% if these women have
moderate-­to-severe dysmenorrhea [2].
In terms of fertility, four factors are required for conception: the male sperm, the
female oocyte, the functional uterine cavity and the patent tube. The prediction of a
women’s future fertility usually needs to be taken into account, including appropri-
ate ovarian reserve, a patent tube, and a functional uterine cavity. Multi-factors
potentially lead to the infertility of women with endometriosis: anovulation, ana-
tomical changes in the pelvic floor, the adhesions in fallopian tubes that impair its
transport function, and it has been demonstrated that the endometrioma intrinsic
presence is correlated with decreased ovarian reserve (a decreasing quality and
quantity of oocytes), especially in bilateral endometriomas [3, 4].
To date, four endometriosis classifications have been built up to provide a mea-
sure of the severity of the endometriosis, a prediction for future fertility, and a
degree of pain. The earliest one is the revised American Fertility Society (r-AFS) or
the revised American Society for Reproductive Medicine (r-ASRM) classification
in 1996 [5], which is longevity and universal familiarity. The following is the Enzian
classification for deep infiltrating endometriosis (DIE) in 2005 [6]. The third is the
American Association of Gynecological Laparoscopists (AAGL) classification in
2007, which is more focused on pain and surgical difficulty [7]. The latest one is the

T. Fang · W. Wang (*)

Department of Obstetrics & Gynecology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen
University, Guangzhou, Guangdong, China

© The Author(s), under exclusive license to Springer Nature 31

Switzerland AG 2024
S. Ferrero (ed.), Endometriosis-related Infertility,
https://doi.org/10.1007/978-3-031-50662-8_4
32 T. Fang and W. Wang

endometriosis fertility index (EFI), which is used to predict pregnancy rates (PRs)
after endometriosis surgical staging [8]. However, it has been demonstrated that,
except for the EFI, the current classification systems have little prognostic value [9].
They rely on sole surgical findings while the EFI includes more important clinical
variables which may reflect the probability of infertility.

2 The Current Commonly Used Endometriosis

Classification Introduction

The Consensus of World Endometriosis Society (WES) in 2014 advised that “until
better classification systems are validated, all women with endometriosis undergo-
ing surgery should have an r-ASRM (or possibly, when published, AAGL) score
and stage completed, women with deep endometriosis should have an Enzian clas-
sification completed, and women for whose fertility is a future concern should have
an EFI score completed, and documented in the medical/surgical records” [9].
However, this consensus also indicated that “the classification systems in current
use continue to attract criticism from women with endometriosis and those provid-
ing care for them because of the poor correlation with disease symptoms as well as
a lack of predictive prognosis and, to date, unclear pathways of treating pelvic pain
and infertility based on its classification” [9].

3 The American Society for Reproductive Medicine

(r-ASRM) Classification Background

The first version of the AFS classification was established in 1979, as several authors
had demonstrated that no correlation existed between PRs and the severity follow-
ing treatment in this classification, further recommendations were then created to
revise the AFS classification [7]. It was revised in 1985 [10]; the revised version
presented more detail in observing and documenting the number of lesions, extent,
size, and severity of adhesion. This version was republished in 1996 adding instruc-
tions and color illustrations to ensure consistency in describing the appearance of
the disease. It was mainly set to predict the pregnancy chance after treatment. The
DIE was not considered in this scoring system [5].

4 Limitations of the r-ARSM Classification

Despite several revisions in the current r-ARSM system, some limitations still have
been found in this classification. Four different stages are pronounced (stage
I:minimal, 1–5 points; stage II, mild, 6–15 points; stage III, moderate, 16–40 points;
Fertility Prediction in Patients with Endometriosis (Endometriosis Fertility Index) 33

stage IV, severe, >40 points) in this classification, but information on the lesion
location is not provided. Moreover, the r-ARSM classification mainly depends on
morphological descriptions with the arbitrary stage demarcation by point score and
the wide score range [7]. Potential observer errors may exist resulting from the
observer’s subjective scoring [11]. It cannot effectively predict PRs in infertile
patients [12] and pelvic pain [13]. To date, the r-ASRM staging system is still the
most commonly used classification for endometriosis, which is still the best tool for
physicians and surgeons to communicate the severity of the disease. Because of its
widespread clinical use and prevalence in describing the surgical appearance of
endometriosis, it is retained in the endometriosis classification [9].

5 The EFI Background

As a complement to r-AFS classification that can better diagnose the fertility status
associated with endometriosis, the EFI, first proposed by Adamson and Pasta in
2010, can be used to accurately predict the probability of natural pregnancy for
women following the surgical staging of endometriosis. This simple scoring system
was established by prospectively collecting detailed clinical and surgical data of
579 infertile patients with endometriosis and then testing its predictive value on a
cohort of 222 patients. The result revealed that the EFI is a simple, robust, and vali-
dated clinical tool for PRs prediction in women with a surgical documented endo-
metriosis [8]. The EFI score combines historical factors and surgical factors, and the
score ranges from 0 to 10, with a score of 0 indicating the poorest prognosis and a
score of 10 indicating the best prognosis. The historical factors account for five
scores based on patient’s characteristics including age, years infertile, and history of
a prior pregnancy. The surgical factors account for another five scores based on
calculating the least function (LF) score of adnexa (fallopian tubes, fimbria, and
ovaries) by the surgeon, the endometriosis lesion score, and total score in r-ASRM
classification (Fig. 1).
It was found that the LF score was the most important contributor among all the
EFI score variables [14]. The LF score of the bilateral tube, fimbria, and ovary was
performed by the surgeon, where a score of 0 representing absent or nonfunctional;
a score of 1 representing severe; a score of 2 representing moderate; a score of 3
representing mild dysfunction; and a score of 4 representing normal. If an ovary is
absent on the one side, the lowest score on the other side with the ovary is doubled
to obtain an LF score [8], a detailed description is shown in Table 1.
The EFI has been externally validated for its predictive value of endometriosis-­
associated fertility by over 24 studies [15]. The type, duration, and cost of treatment
can be decided based on EFI for a patient before considering assisted reproductive
technology (ART) procedures after endometriosis surgery. EFI also provides a guar-
antee for the patient with a good prognosis and avoids waste of time and treatment
for the patient with a poor prognosis [7]. As only a part of patients enable attempts
at ART therapy after endometriosis, the EFI can bring great benefit to most patients
34 T. Fang and W. Wang

Fig. 1 Endometriosis fertility index surgery form. Reprinted fromAdamson, G.D., & Pasta, D.J. (2010)
Endometriosis fertility index: the new, validated endometriosis staging system. Fertility and
Sterility, 94(5):1609–1615, with permission from Elsevier

with fertility desire. To date, none of the other endometriosis classifications except
the EFI shows any correlation with PRs after surgery [7, 9]. Clinicians should man-
age postoperative fertility in women with endometriosis according to EFI score (i.e.
women with lower EFI score should be timely offered ART treatment as an option
after surgery) [16]. A recent meta-analysis has also confirmed that the EFI score has
a good performance in predicting the pregnancy rate beyond in vitro fertilization
(IVF) [11]. The EFI comprehensively analyzes the multi-factors of endometriosis-­
related infertility, guides clinicians in making individualized treatment, and subse-
quently prompts to improve outcomes of endometriosis. Although the LF score may
be differences in interpretations by different observers, a recent study has confirmed
that EFI can be reliably reproduced by independent observers, further supporting its
use in routine clinical practice for postoperative fertility counseling/management in
a patient with endometriosis [17]. Ferrier et al. evaluated a cost-effectiveness per-
spective for surgically documented endometriosis-associated infertility with the
stratification of the EFI score. The results indicated that immediate IVF/ICSI in
women with EFI scores 0–3 was much costly and more effective. After one-year
natural conception attempts failed, continuing natural conception attempts in
Fertility Prediction in Patients with Endometriosis (Endometriosis Fertility Index) 35

Table 1 Descriptions of least function terms

Structure Dysfunction Description
Tube Mild Slight injury to serosa of the fallopian tube
Moderate Moderate injury to serosa or muscularis of the fallopian tube;
moderate limitation in mobility
Severe Fallopian tube fibrosis or mild/moderate salpingitis isthmica nodosa;
severe limitation in mobility
Nonfunctional Complete tubal obstruction, extensive fibrosis, or salpingitis isthmica
nodosa
Fimbria Mild Slight injury to fimbria with minimal scarring
Moderate Moderate injury to fimbria, with moderate scarring, moderate loss of
fimbrial architecture, and minimal intrafimbrial fibrosis
Severe Severe injury to fimbria, with severe scarring, severe loss of fimbrial
architecture, and moderate intrafimbrial fibrosis
Nonfunctional Severe injury to fimbria, with extensive scarring, complete loss of
fimbrial architecture, complete tubal occlusion or hydrosalpinx
Ovary Mild Normal or almost normal ovarian size; minimal or mild injury to
ovarian serosa
Moderate Ovarian size reduced by one-third or more; moderate injury to
ovarian surface
Severe Ovarian size reduced by two-thirds or more; severe injury to ovarian
surface
Nonfunctional Ovary absent or completely encased in adhesions
Note: 0 = absent or nonfunctional; 1 = severe; 2 = moderate; 3 = mild dysfunction; 4 = normal. If
the ovary is absent on the one side, all the ovulation will occur from the ovary on the other side. In
this situation, the LF score is obtained by determining the function score on the side with the ovary
and then doubling it. Reprinted from Adamson, G.D., & Pasta, D.J. (2010) Endometriosis fertility
index: the new, validated endometriosis staging system. Fertility and Sterility, 94(5):1609–1615,
with permission from Elsevier

women with EFI scores 9–10 was strongly dominant; delayed IVF/ICSI was more
costly and more effective in women with EFI scores 0–7. They concluded that the
EFI is a useful score to help a couple decide on different care pathways—natural
conception, immediate or delayed IVF/ICSI after considering the healthcare cost
[18]. In China, young women (age ≤ 30 years) with r-ASRM stages I and II and EFI
score ≥5 were recommended to expectant management for 6 months under the
guidance of the Chinese Medical Association; women with EFI score ≤4 and high-­
risk infertile factor (age > 35 years, infertile years >3 years, especially primary
infertility, serve endometriosis, pelvic adhesion, incomplete lesion excision, and
oviduct obstruction) were recommended to treat aggressively with IVF-ET [19].
36 T. Fang and W. Wang

6 Limitations of the EFI

First, the importance of adnexal function has been emphasized in endometriosis by

the ESHRE and NICE guidelines [20, 21]. A possible limitation of EFI is the lack
of ovarian reserve parameters. Studies have demonstrated that unilateral or bilater-
ality endometrioma sizes are significantly correlated with ovarian reserve [22, 23].
As the EFI serves as a reference for guiding the post-surgery patients about their
fertility prognosis counseling, the time to ART treatment should take into the ovar-
ian reserve. Serum anti-­Müllerian hormone (AMH) as an effective marker for ovar-
ian reserve has been proven by numerous studies [24–26]. It deserves further
discussion whether adding serum AMH as a variable into the EFI score predicts
reproductive capability more accurately. Second, the uterine abnormality is a factor
of pregnancy prediction which is not included in the EFI. As clinically significant
severe uterine abnormality is uncommon in endometriosis patients, Adamson pro-
posed that “deficiencies in the reproductive function of the gametes or uterus will
obviously affect the prognosis and must be considered separately as fertility factors,
just as they would with any patient with any other type of disease” [7].

7 The Enzian Classification Background

The Enzian classification was established in 2005 to supplement the r-AFS score
concerning the description of DIE, especially the retroperitoneal structures [6].
Advantages of the Enzian stage system include that it provides precise morphologi-
cal description (e.g. anatomical location) of involved retroperitoneal structures; and
suspected involvement of DIE can be well described preoperatively by using the
Enzian classification [27]. Recent studies have shown a strong correlation between
the MRI-based Enzian score for Deep Infiltrating Endometriosis (DIE) and intraop-
erative findings [28, 29]. This correlation is valuable for effective communication
between radiologists and gynecologists when assessing surgical complexity and
estimating the operating time.

8 Limitations of the Enzian Classification

Since the Enzian staging system is seen as more complicated to use compared with
the r-ASRM score, it is mainly used in German-speaking countries with a poor level
of international acceptance [15]. Only a few studies on the classification have been
published in international journals. No current data exist to study whether the
Enzian classification is associated with clinical symptoms [27].
Fertility Prediction in Patients with Endometriosis (Endometriosis Fertility Index) 37

9 Predicting Non-IVF Pregnancy Rate in Women

with Endometriosis

As mentioned above, over 24 studies have demonstrated that EFI is an effective tool
in predicting non-IVF pregnancy after endometriosis surgery. Some studies revealed
that the cut-off of the EFI score for predicting a non-IVF pregnancy ranged from 5
to 7 [30, 31]. The cumulative non-IVF pregnancy rate of women with EFI ≥ 5 in the
first 2 and 3 years after surgery was 50–66% versus 26–33% in women with EFI < 5
[31, 32]. The cumulative pregnancy rates (PRs) at 12 months after surgery ranged
from 17% to 46% for EFI scores 0–3 and were 63% for EFI scores 9–10 in cases of
Endometriosis Fertility Index (EFI) [14]. The EFI can also accurately predict the
live birth of endometriosis in r-ASRM stages III and IV. The estimated cumulative
non-IVF live birth rate at 5 years was 0% at an EFI score of 0–2, rising steadily to
91% at an EFI score of 9–10; while among women receiving ART treatment, the
live birth rate increased steadily from 38% to 71% in the same EFI score strata [33].
Cook and Adamson’s study presented additional information to assist the physi-
cians and patients in understanding prognosis after endometriosis diagnosis at lapa-
roscopy. As shown in Tables 2 and 3, they defined EFI score as four treatment levels
(I–IV) based on monthly fecundity data, with treatment levels and recommenda-
tions ranging from “attempt non-IVF conception for at least 1 year” to “refer to
ART center for IVF” [34]. Although EFI aims to predict PRs in infertile patients
with laparoscopic surgery, a recent new study attempted to estimate EFI before
surgery, the necessary information was obtained through clinical examination,
gynecological ultrasound, and hysterosalpingo-foam sonography for tubal patency
testing, and the results revealed that the EFI can be estimated accurately according
to mere clinical and ultrasound information, this means that the EFI could be used
as a tool to guide doctors and patients to make individualized treatment among sur-
gery, ART, or other fertility management options [35].

Table 2 Treatment levels and recommendations

Treatment Monthly
level fecundity Treatment recommendation
I >3% Attempt non-ART conception for at least 1 year
II 2–3% Probable attempt non-ART conception, consider role of IVF
III 1–2% Probable IVF, refer to a reproductive endocrinologist for
fertility management
IV <1% Refer to ART center for IVF
Note: reprinted from Cook, A.S., & Adamson, G.D. (2013) The Role of the Endometriosis Fertility
Index (EFI) and Endometriosis Scoring Systems in Predicting Infertility Outcomes. Current
Obstetrics and Gynecology Reports, 2(3):186–194, with permission from Springer Nature
38 T. Fang and W. Wang

Table 3 EFI score and treatment level

EFI Treatment level
Year 1 Year 2 Year 3
0–3 IV IV IV
4 III IV IV
5 III III IV
6 II II III
7 I II II
8 I II III
9 and 10 I I IV
Note: Cook, A.S., & Adamson, G.D. (2013) The Role of the Endometriosis Fertility Index (EFI)
and Endometriosis Scoring Systems in Predicting Infertility Outcomes. Current Obstetrics and
Gynecology Reports, 2(3):186–194, with permission from Springer Nature

10 Predicting ART Pregnancy Rate in Women

with Endometriosis

Although the EFI does not consider to predict the PRs in women who underwent
ART treatment after endometriosis surgery, two studies attempted to analyze the
predictive value of EFI in IVF pregnancy, the results still revealed a good correla-
tion between EFI and IVF pregnancy [36, 37]. One study in China analyzed 199
consecutive women with surgically documented endometriosis receiving IVF treat-
ment. The results showed the cut-off EFI score for predicting IVF pregnancy was 6.
The clinical pregnancy rate was 28.6% in women with an EFI score of ≤5, which
was significantly increased to 53% in women with an EFI score ≥ 6. A higher num-
ber of antral follicle count, oocytes retrieved, and implantation rate were found in
women with an EFI score ≥6 than women with an EFI score ≤5 [37]. Garavaglia
et al. evaluated the predictive value of the EFI score for cumulative ART cycles
pregnancy outcome in 44 women with previous attempts to obtain a natural preg-
nancy after surgery, the result showed the best cut-off point for ART pregnancy was
5.5, and the clinical pregnancy rate in women with an EFI score ≤5 was 5.6% [36].

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24. Fleming R, Seifer DB, Frattarelli JL, Ruman J. Assessing ovarian response: antral follicle
count versus anti-Müllerian hormone. Reprod Biomed Online. 2015;31(4):486–96. https://doi.
org/10.1016/j.rbmo.2015.06.015.
25. Iwase A, Osuka S, Goto M, Murase T, Nakamura T, Takikawa S, et al. Clinical application
of serum anti-Mullerian hormone as an ovarian reserve marker: a review of recent studies. J
Obstet Gynaecol Res. 2018;44(6):998–1006. https://doi.org/10.1111/jog.13633.
26. Younis JS, Shapso N, Fleming R, Ben-Shlomo I, Izhaki I. Impact of unilateral versus bilateral
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Hum Reprod Update. 2019;25(3):375–91. https://doi.org/10.1093/humupd/dmy049.
27. Haas D, Shebl O, Shamiyeh A, Oppelt P. The rASRM score and the Enzian classification for
endometriosis: their strengths and weaknesses. Acta Obstet Gynecol Scand. 2013;92(1):3–7.
https://doi.org/10.1111/aogs.12026.
28. Burla L, Scheiner D, Samartzis EP, Seidel S, Eberhard M, Fink D, et al. The ENZIAN score as
a preoperative MRI-based classification instrument for deep infiltrating endometriosis. Arch
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29. Di Paola V, Manfredi R, Castelli F, Negrelli R, Mehrabi S, Pozzi MR. Detection and localiza-
tion of deep endometriosis by means of MRI and correlation with the ENZIAN score. Eur J
Radiol. 2015;84(4):568–74. https://doi.org/10.1016/j.ejrad.2014.12.017.
30. Hobo R, Nakagawa K, Usui C, Sugiyama R, Ino N, Motoyama H, et al. The endometriosis
fertility index is useful for predicting the ability to conceive without assisted reproductive
technology treatment after laparoscopic surgery, regardless of endometriosis. Gynecol Obstet
Investig. 2018;83(5):493–8. https://doi.org/10.1159/000480454.
31. Zhou Y, Lin L, Chen Z, Wang Y, Chen C, Li E, et al. Fertility performance and the predictive
value of the endometriosis fertility index staging system in women with recurrent endometrio-
sis: a retrospective study. Medicine (Baltimore). 2019;98(39):e16965. https://doi.org/10.1097/
MD.0000000000016965.
32. Zeng C, Xu JN, Zhou Y, Zhou YF, Zhu SN, Xue Q. Reproductive performance after surgery
for endometriosis: predictive value of the revised American fertility society classification and
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org/10.1159/000358390.
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humrep/dex291.
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metriosis scoring Systems in Predicting Infertility Outcomes. Curr Obstet Gynecol Rep.
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Estimation of the endometriosis fertility index prior to operative laparoscopy. Hum Reprod.
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doi.org/10.1159/000366443.
37. Wang W, Li R, Fang T, Huang L, Ouyang N, Wang L, et al. Endometriosis fertility index score
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Spontaneous Ovulation in Patients
with Endometriosis

Simone Ferrero, Fabio Barra, Marco Crosa,

Umberto Leone Roberti Maggiore, and Herut Attar

1 Introduction

The establishment and the progression of endometriosis are associated with ovula-
tion and ensuing menses. Exposure to menses and associated retrograde bleeding is
one of the critical factors related to an increased risk of endometriosis. Therefore,
oligo-anovulation (as encountered in women suffering polycystic ovary syndrome,
PCOS) might theoretically lessen the likelihood of developing endometriosis. Based
on this background, some studies investigated the prevalence of oligo-anovulation
in patients with endometriosis.

S. Ferrero (*)
Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal and Child
Health (DINOGMI), IRCCS Ospedale Policlinico San Martino, University of Genoa,
Genova, Genova, Italy
e-mail: [email protected]
F. Barra
Department of Health Sciences (DISSAL), University of Genova, Genova, Italy
IRCCS Ospedale Policlinico San Martino, Genova, Italy
M. Crosa
DINOGMI, University of Genova, Genova, Italy
e-mail: [email protected]
U. Leone Roberti Maggiore
Unit of Gynecologic Oncology, Fondazione IRCCS Istituto Nazionale Dei Tumori,
Milan, Italy
e-mail: [email protected]
H. Attar
Department of Obstetrics and Gynecology, Yeditepe University Medical School,
Istanbul, Turkey

© The Author(s), under exclusive license to Springer Nature 41

Switzerland AG 2024
S. Ferrero (ed.), Endometriosis-related Infertility,
https://doi.org/10.1007/978-3-031-50662-8_5
42 S. Ferrero et al.

Endometriomas are among the most common manifestations of endometriosis,

affecting between 17% and 44% of women suffering from this disease [1]. These
cysts contain “chocolate” fluid that is generally thought to arise from the accumula-
tion of menstrual debris deriving from the shedding of the active implants inside the
cyst. The cysts contain a high concentration of cellular damage-mediating factors,
proteolytic enzymes, inflammatory molecules, reactive oxygen species, and iron
[2]. These molecules could be a potential source of toxicity for the surrounding
healthy tissue and, therefore, have detrimental effects on ovarian physiology. It has
been hypothesized that endometriomas may interfere with ovulation. Therefore,
several studies investigated whether endometriomas influence the rate of ovulation
in the affected ovary.
This chapter will summarize the available data on ovulation characteristics in
women with endometriosis.

2 Ovulation in the Animal Models of Endometriosis

Studies on the effects of experimental endometriosis on infertility have used ani-

mals with endometrial autografts placed throughout the pelvic peritoneum [3, 4]. In
these studies, infertility was associated with failure of ovulation. Schenken and
Asch investigated the effect of surgically induced endometriosis on the reproductive
performance of New Zealand White rabbits [3]. Endometrium obtained from one
uterine horn was surgically implanted into the peritoneum. Adipose tissue was
implanted in another group of animals which served as a control. The induction of
endometriosis significantly impaired fertility rates (25%) compared with the control
group (75%). The primary cause of infertility in the endometriotic group was the
failure to ovulate since only four of the eight animals showed stigmata of ovulation.
However, because only two of the four ovulatory animals became pregnant, an
effect on ovum transport, luteolysis, or induced abortion after implantation cannot
be excluded.
Another study investigated the effect of endometriosis on follicular rupture [5].
Endometrial tissue was **autografted to New Zealand White rabbits. Endometrium
was surgically implanted into the peritoneal cavity or the rectus muscle. Human
chorionic gonadotropin was administered to induce ovulation. The viability of the
implants was demonstrated histologically. The number of corpora lutea and stig-
mata was counted during three subsequent laparotomies. Ovaries were removed
during the last laparotomy, and ovarian serial sections were examined. In rabbits
with peritoneal-induced endometriosis, the percentage of stigmata/corpora lutea
was significantly decreased. The macroscopic study was confirmed by histological
examination. Indeed, a high incidence of entrapped oocytes was found in rabbits
with peritoneal endometriosis. Extraperitoneal endometriosis did not affect ovula-
tion. These data suggested that endometriosis induces a failure of follicular rupture.
After the excision of endometriosis, no failure to ovulate was observed, suggesting
Spontaneous Ovulation in Patients with Endometriosis 43

that the effect of endometriosis on the ovulation disappeared with the removal of
endometriotic implants.
Another study performed in the animal model investigated whether ovarian
endometriosis impairs ovulation [6]. The authors induced ovarian endometriosis in
Virgin New Zealand White rabbits. Endometrial tissue was placed in one ovary, and
adipose tissue was placed in the contralateral ovary as a control in a randomized
fashion. Ovulation was induced with human chorionic gonadotropin, and ovulation
points were counted before and after induction of endometriosis. Periovarian adhe-
sions were graded according to their density and the extent of ovarian surface
affected. A significant decrease in ovulation points was observed in ovaries with
endometrial tissue but not in ovaries that contained adipose tissue. Periovarian
adhesions decreased the number of ovulation points in ovaries with adipose or
endometrial tissues. In the absence of adhesions, a near-significant decrease in the
number of ovulation points was observed in ovaries with endometrial tissue. Still,
no change was evident in ovaries with adipose tissue. Multivariate analysis demon-
strated that an increase in adhesion severity was correlated with a decrease in the
number of ovulation points, but endometrial tissue was not. In the rabbit model, the
authors concluded that minimal ovarian endometriosis impairs ovulation primarily
through a mechanism related to periovarian adhesions.

3 Oligo-Anovulation in Women with Endometriosis

In a study published more than 40 years ago, Soules et al. investigated the incidence
of anovulation in women with endometriosis [7]. In a series of 350 women with
endometriosis (77% of whom were confirmed by histology), these authors found
that 17% exhibited anovulation or oligo-ovulation patterns. Among women with
endometriosis and oligo-anovulation, the distribution according to disease severity
was as follows: 39% had mild endometriosis, 59% moderate, and 2% severe endo-
metriosis. These authors concluded that endometriosis and anovulation could
coexist.
A study including 21 infertile women with laparoscopically documented
minimal-­mild endometriosis investigated follicular development and ovulation [8].
Of the 27 cycles studies, 24 (89%) appeared to be endocrinologically normal and
ovulatory. Luteinized unruptured follicle (LUF) occurred in one cycle (4%). One
further patient exhibited abnormal endocrinology with evidence of premature ovu-
lation over two (8%) consecutive cycles. This study indicated that most women with
minimal-mild endometriosis have endocrinologically regular menstrual cycles and
that luteinized unruptured follicles occur infrequently.
Some studies investigated the prevalence of endometriosis in women with
PCOS. An American retrospective study reported that among 102 infertile patients
with PCOS diagnosed according to the Rotterdam criteria, 73 (71.5%) had endome-
triosis at laparoscopy [9]. About 40% had ASRM stage I endometriosis, 41% stage
44 S. Ferrero et al.

II, 12% stage III, and 7% stage IV. A more recent retrospective cohort study inves-
tigated the prevalence of endometriosis in PCOS patients who did not suffer pain
symptoms and underwent laparoscopic ovarian drilling for clomiphene citrate resis-
tance [10]. Endometriosis was present in 16.9% of the patients. Around 86.6% of
the patients had ASRM stage I endometriosis, and the remaining patients (13.2%)
had stage II endometriosis. In a meta-analysis, the pooled prevalence of endome-
triosis in clomiphene citrate-resistant PCOS patients was 7.7% [10]. These data
suggest that the prevalence of endometriosis in anovulatory women with PCOS is
similar to that of the general population.
More recently, a French cross-sectional study investigated the prevalence of
oligo-anovulation in women with and without endometriosis [11]. The study
included 354 women with histologically proven endometriosis and 474 women in
whom endometriosis was surgically ruled out. There was no difference in the rate of
oligo-anovulation between women with endometriosis (15.0%) and controls
(11.2%). Oligo-anovulation was observed in 18.2% of patients with superficial peri-
toneal endometriosis, 10.6% with ovarian endometrioma, and 16.6% with deep
infiltrating endometriosis.

4 Impact of Endometriomas on Spontaneous Ovulation

Ovarian endometrioma may affect ovulation by several mechanisms. The inflamma-

tory reaction caused by the endometrioma may have a negative effect on ovulation.
In addition, the presence of an ovarian cyst may cause mechanical damage to the
growing follicle by thinning and stretching the cortical tissue and disturbing the
vascularization of the ovary.
Maneschi et al. [12] investigated the functional morphologic features of the ovar-
ian cortex surrounding benign cysts. The study included 48 women who underwent
surgical excision of benign ovarian cysts. The ovarian cortex was not morphologi-
cally altered in the presence of mature teratomas (n = 13) and benign cystadenomas
(n = 9). In contrast, endometriomas (n = 32) were associated with microscopic stro-
mal implants and reduced follicular number and activity. Follicular maturation up to
the antral stage was observed less frequently in the cortical tissue surrounding the
endometriomas than in that surrounding mature teratoma and benign cystadenomas.
Moreover, there was no evidence of follicles in 16% of the specimens obtained from
women with endometriomas.
Over the last 15 years, several studies investigated the impact of ovarian endome-
triomas on spontaneous ovulation and reported contradictory results. A retrospec-
tive study including 28 infertile women with unilateral endometriomas showed that
the rate of ovulation (mean ± standard error of the mean, SEM) in the affected ovary
was 34.4% (±6.6%) [13]. When the endometriomas had the largest diameter < 4 cm,
the rate of ovulation in the affected ovary was 41.0% (± 8.0%). In contrast, when the
endometriomas had the largest diameter ≥ 4 cm, the rate of ovulation in the affected
ovary was 26.8% (±10.9%). All the patients included in the study underwent
Spontaneous Ovulation in Patients with Endometriosis 45

laparoscopic cystectomy. After surgery, there was a significant decrease in the ovu-
lation rate in the affected ovary (16.9 ± 4.5%). This decrease was observed when the
endometriomas had the largest diameter < 4 cm but not when it was ≥4 cm.
An Italian prospective single-center study including women with unilateral
endometriomas investigated the rate of ovulation in the affected ovaries [14]. The
criteria for inclusion in the study were the presence of one or more endometriomas
(with largest diameter ≥ 10 mm), no previous adnexal surgery, and regular men-
strual cycles (24–35 days). Study patients underwent serial transvaginal ultrasono-
graphic examination starting on days 6–10 of the menstrual cycle. Ovulation was
defined as the presence of a growing leading follicle and subsequent development of
a corpus luteum. The study included 70 women, and the mean age (± SD) of the
patients was 35.0 (±4.5) years. Ovulation occurred in the affected ovary in only 31%
of the cases. When the side of the endometrioma was considered, the study showed
that the left ovary was less vulnerable than the right one; in fact, the ovulation rate
was reduced only when the endometrioma was located on the right ovary. The sig-
nificant limitations of the study were that patients were recruited only for one men-
strual cycle and that the sample size was relatively small.
An Italian single-center prospective study investigated if ovarian endometriotic
cysts influence the rate of spontaneous ovulation in the affected ovary [15]. The
study included women of reproductive age desiring to conceive, with an ultrasono-
graphic diagnosis of a unilateral ovarian endometriotic cyst with a diameter of
≥2 cm. The patients included in the study had no history of infertility. Study patients
had regular menstrual cycles, and male partners had a normal semen analysis. Study
patients underwent serial transvaginal ultrasounds to assess the side of ovulation
starting on days 6–8 of the menstrual cycle for up to six ovulatory cycles. The ovu-
lation was defined by the presence of a growing leading follicle and the subsequent
development of the corpus luteum. Two hundred forty-four women were included in
the study. The mean (± SD) age of the study population was 34.3 (±4.9) years. One
hundred and ninety-eight (81.1%) patients had single endometrioma, 37 (15.2%)
had two endometriomas, and 9 (3.7%) had three endometriomas. At baseline, 166
patients (55.5%) had endometriomas with a largest diameter of ≥40 mm, and 45
(15.1%) had endometriomas with a largest diameter of ≥60 mm. A total of
1311 cycles were evaluated. It was impossible to identify the ovulation in 112 cycles
(8.5%). There was no significant difference in ovulation rate between the healthy
(50.3%) and the affected ovary (49.7%). The ovulation rate between the affected
and the healthy ovary was not affected by endometriomas’ laterality, number, and
size. The rate of ovulation in the affected and the healthy ovary was not affected by
deep endometriosis. Following the six spontaneous ovulations monitored during the
study, 105 patients conceived (43.2%). There was no significant difference in the
side of ovulation (healthy or affected ovary) when the patients conceived. The high
pregnancy rate observed in the current study may be explained by the fact that the
patients had unilateral endometriomas, no history of infertility, no risk factors for
tubal disease (such as a history of pelvic inflammatory disease), and their male part-
ners had a regular semen analysis.
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Les considérations relatives à la courtisane peuvent, jusqu'à un certain
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humeur; en effet, il n'y a ici rien de trivial; c'est plutôt le débordement
d'une nature énergique, qui verse dans le mal toutes les forces dues à la
culture du bien; c'est l'amour effréné, immense, chaotique, élevé jusqu'à
la hauteur d'une contre-religion, d'une religion satanique. Ainsi, le
compositeur, dans la traduction musicale, a échappé à cette vulgarité qui
accompagne trop souvent la peinture du sentiment le plus populaire,—
j'allais dire populacier,—et pour cela il lui a suffi de peindre l'excès dans le
désir et dans l'énergie, l'ambition indomptable, immodérée, d'une âme
sensible qui s'est trompée de voie. De même dans la représentation
plastique de l'idée, il s'est dégagé heureusement de la fastidieuse foule
des victimes, des Elvires innombrables. L'idée pure, incarnée dans l'unique
Vénus, parle bien plus haut et avec bien plus d'éloquence. Nous ne
voyons pas ici un libertin ordinaire, voltigeant de belle en belle, mais
l'homme général, universel, vivant morganatiquement avec l'idéal absolu
de la volupté, avec la reine de toutes les diablesses, de toutes les
faunesses et de toutes les satyresses, reléguées sous terre depuis la mort
du grand Pan, c'est à dire avec l'indestructible et irrésistible Vénus.

Que les hommes qui peuvent se donner le luxe d'une maîtresse parmi les
danseuses de l'Opéra désirent qu'on mette le plus souvent possible en
lumière les talents et les beautés de leur emplette, c'est là certes un
sentiment presque paternel que tout le monde comprend et excuse
facilement; mais que ces mêmes hommes, sans se soucier de la curiosité
publique et des plaisirs d'autrui, rendent impossible l'exécution d'un
ouvrage qui leur déplaît parce qu'il ne satisfait pas aux exigences de leur
protectorat, voilà ce qui est intolérable. Gardez votre harem et conservez-
en religieusement les traditions; mais faites-nous donner un théâtre où
ceux qui ne pensent pas comme vous pourront trouver d'autres plaisirs
mieux accommodés à leur goût. Ainsi nous serons débarrassés de vous et
vous de nous, et chacun sera content.

"DES MAÎTRESSES. Si je veux observer la loi des contrastes, qui gouverne

l'ordre moral et l'ordre physique, je suis obligé de ranger dans la classe
des femmes dangereuses aux gens de lettres, la femme honnête, le bas-
bleu et l'actrice;—la femme honnête, parce qu'elle appartient
nécessairement à deux hommes et qu'elle est une médiocre pâture pour
l'âme despotique d'un poète;—le bas-bleu, parce que c'est un homme
manqué;—l'actrice, parce qu'elle est frottée de littérature et qu'elle parle
argot,—bref, parce que ce n'est pas une femme dans toute l'acception du
mot,—le public lui étant une chose plus précieuse que l'amour.
Vous figurez-vous un poète amoureux de sa femme et contraint de lui voir
jouer un travesti? Il me semble qu'il doive mettre le feu au théâtre.
Vous figurez-vous celui-ci obligé d'écrire un rôle pour sa femme qui n'a
pas de talent?
Et cet autre suant à rendre par des épigrammes au public de l'avant-
scène les douleurs que ce public lui a faites dans l'être le plus cher,—cet
être que les Orientaux enfermaient sous triple clef, avant qu'ils ne
vinssent étudier le droit à Paris? C'est parce que tous les vrais littérateurs
ont horreur de la littérature à de certains moments que je n'admets pour
eux âmes libres et fières, esprits fatigués, qui ont toujours besoin de se
reposer leur septième jour,—que deux classes de femmes possibles: les
filles ou les femmes bêtes, l'amour ou le pot-au-feu.—Frères est-il besoin
d'en expliquer les raisons?
15 Avril 1846.
Deux exemples me sautent déjà à la mémoire. L'un des plus orgueilleux
soutiens de l'honnêteté bourgeoise, l'un des chevaliers du bon sens, M.
Émile Augier, a fait une pièce, La Ciguë, où l'on voit un jeune homme
tapageur, viveur et buveur, un parfait épicurien, s'éprendre à la fin des
yeux purs d'une jeune fille. On a vu de grands débauchés jeter tout d'un
coup tout leur luxe par la fenêtre et chercher dans l'ascétisme et le
dénûment d'amères voluptés inconnues. Cela serait beau, quoique assez
commun. Mais cela dépasserait les forces vertueuses du public de M.
Augier. Je crois qu'il a voulu prouver qu'à la fin il faut toujours se ranger,
et que la vertu est bien heureuse d'accepter les restes de la débauche.
Écoutons Gabrielle, la vertueuse Gabrielle, supputer avec son vertueux
mari combien il leur faut de temps de vertueuse avarice, en supposant les
intérêts ajoutés au capital et portant intérêt, pour jouir de dix ou vingt
mille livres de rente. Cinq ans, dix ans, peu importe, je ne me rappelle
pas les chiffres du poète. Alors, disent les deux honnêtes époux:
NOUS POURRONS NOUS DONNER LE LUXE D'UN GARÇON!
Par les cornes de tous les diables de l'impureté! par l'âme de Tibère et du
marquis de Sade! que feront-ils donc pendant tout ce temps-là? Faut-il
salir ma plume avec les noms de tous les vices auxquels ils seront obligés
de s'adonner pour accomplir leur vertueux programme? Ou bien le poète
espère-t-il persuader à ce gros public de petites gens que les deux époux
vivront dans une chasteté parfaite? Voudrait-il par hasard les induire à
prendre des leçons des Chinois économes et de M. Malthus?

Ainsi il y a une cohue de poètes abrutis par la volupté païenne, et qui

emploient sans cesse les mots de saint, sainte, extase, prière, etc..., pour
qualifier des choses et des êtres qui n'ont rien de saint ni d'extatique,
bien au contraire, poussant ainsi l'adoration de la femme jusqu'à l'impiété
la plus dégoûtante. L'un d'eux, dans un accès d'érotisme saint, a été
jusqu'à s'écrier: ô ma belle catholique! Autant salir d'excréments un autel.
Tout cela est d'autant plus ridicule que généralement les maîtresses des
poètes sont d'assez vilaines gaupes, dont les moins mauvaises sont celles
qui font la soupe et ne payent pas un autre amant.
À côté de l'école du bon sens et de ses types de bourgeois corrects et
vaniteux, a grandi et pullulé tout un peuple malsain de grisettes
sentimentales, qui, elles aussi, mêlent Dieu à leurs affaires, de Disettes
qui se font tout pardonner par la gaieté française, de filles publiques qui
ont gardé je ne sais où une pureté angélique, etc... Autre genre
d'hypocrisie.

Le vice est séduisant, il faut le peindre séduisant; mais il traîne avec lui
des maladies et des douleurs morales singulières; il faut les décrire.

Exprimez-vous la crainte, la tristesse de voir l'espèce humaine s'amoindrir,

la santé publique dégénérer par une mauvaise hygiène, il y aura à côté de
vous un poète pour répondre: «Comment voulez-vous que les femmes
fassent de beaux enfants dans un pays où elles adorent un vilain
pendu!»—Le joli fanatisme!

...Et la brûlante Sapho, cette patronne des hystériques.

Est-ce Vénus Aphrodite ou Vénus Mercenaire qui soulagera les maux

qu'elle vous aura causés? Toutes ces statues de marbre seront-elles des
femmes dévouées au jour de l'agonie, au jour du remords, au jour de
l'impuissance?

J'admets tous les remords de saint Augustin sur le trop grand plaisir des
yeux. Le danger est si grand que j'excuse la suppression de l'objet.

HÉGÉSIPPE MOREAU.—Ce n'est pas la volupté de l'épicurien, c'est plutôt la

sensualité claustrale, échauffée, du cuistre, sensualité de prison et de
dortoir. Ses badinages amoureux ont la grossièreté d'un collégien en
vacances. Lieux communs de morale lubrique, rogatons du dernier siècle
qu'il réchauffe et qu'il débite avec la naïveté scélérate d'un enfant ou d'un
gamin.

La femme est non seulement un être d'une beauté suprême, comparable

à celle d'Ève ou de Vénus; non seulement, pour exprimer la pureté de ses
yeux, le poète empruntera des comparaisons à tous les meilleurs
réflecteurs et à toutes les plus belles cristallisations de la nature, mais
encore faudra-t-il doter la femme d'un genre de beauté tel que l'esprit ne
peut le concevoir que comme existant dans un monde supérieur. Or, si je
me souviens qu'en trois ou quatre endroits de ses poésies Banville,
voulant orner des femmes d'une beauté non comparable et non égalable,
dit qu'elles ont des têtes d'enfant. C'est là une espèce de trait de génie
particulièrement lyrique, c'est à dire amoureux du surhumain. Il est
évident que cette expression contient implicitement cette pensée que le
plus beau des visages humains est celui dont l'usage de la vie, passion,
colère, péché, angoisse, souci, n'a jamais terni la clarté ni ridé la surface.
Tout poète lyrique, en vertu de sa nature, opère fatalement un retour vers
l'Eden perdu.

La nauséabonde niaiserie de la femme, etc...

Phèdre en paniers a ravi les esprits les plus délicats de l'Europe; à plus
forte raison, Vénus, qui est immortelle, peut bien, quand elle veut visiter
Paris, faire descendre son char dans les bosquets du Luxembourg.

...La grâce éternelle qui coule des lèvres et du regard de la femme...

Grâce à une opération d'esprit toute particulière aux amoureux quand ils
sont poètes, ou aux poètes quand ils sont amoureux, la femme s'embellit
de toutes les grâces du paysage, et le paysage profite occasionnellement
des grâces que la femme aimée verse à son insu sur le ciel, sur la terre et
sur les flots.

Quelle est la donnée la plus usée, la plus prostituée, l'orgue de Barbarie le

plus éreinté?
L'Adultère.

L'imagination, faculté suprême et tyrannique, substituée au cœur, ou à ce

qu'on appelle le cœur, d'où le raisonnement est d'ordinaire exclu, et qui
domine généralement dans la femme comme dans l'animal.
L'hystérie! Pourquoi ce mystère physiologique ne ferait-il pas le fond et le
tuf d'une œuvre littéraire, ce mystère que l'Académie de médecine n'a pas
encore résolu, et qui, s'exprimant dans les femmes par la sensation d'une
boule ascendante et asphyxiante (je ne parle que du symptôme
principal), se traduit chez les hommes nerveux par toutes les
impuissances et aussi par l'aptitude à tous les excès?

En somme, Madame Bovary est vraiment grande, elle est surtout

pitoyable, et, malgré la dureté systématique de Flaubert, qui a fait tous
ses efforts pour être absent de son œuvre et pour jouer la fonction d'un
montreur de marionnettes, toutes les femmes intellectuelles lui sauront
gré d'avoir élevé la femelle à une si haute puissance, si loin de l'animal
pur et si près de l'homme idéal, et de l'avoir fait participer à ce double
caractère de calcul et de rêverie qui constitue l'être parfait.

Je ne dirai certainement pas comme le Lycanthrope d'insurrectionnelle

mémoire, ce révolté qui a abdiqué: «En face de toutes les platitudes et de
toutes les sottises du temps présent, ne nous reste-t-il pas le papier à
cigarettes et l'adultère?» Mais j'affirmerai qu'après tout, tout compte fait,
même avec des balances de précision, notre monde est bien dur pour
avoir été engendré par le Christ, qu'il n'a guère qualité pour jeter la pierre
à l'adultère; et que quelques minotaurisés de plus ou de moins
n'accéléreront pas la vitesse rotatoire des sphères et n'avanceront pas
d'une seconde la destruction finale des univers.—Il est temps qu'un terme
soit mis à l'hypocrisie de plus en plus contagieuse, et qu'il soit réputé
ridicule pour des hommes et des femmes, pervertis jusqu'à la trivialité, de
crier: haro! sur un malheureux auteur qui a daigné avec une chasteté de
rhéteur jeter un voile de gloire sur des aventures de table de nuit,
toujours répugnantes et grotesques, quand la poésie ne les caresse pas
de sa clarté de veilleuse opaline.

...Si remarquable, si plein de désolation, si véritablement moderne, où la

future adultère—car elle n'est encore qu'au commencement du plan
incliné, la malheureuse!—va demander secours à l'Église, à la divine Mère,
à celle qui n'a pas d'excuses pour n'être pas toujours prête, à cette
Pharmacie où nul n'a le droit de sommeiller! Le bon curé Bournisien,
uniquement préoccupé des polissons du catéchisme qui font de la
gymnastique à travers les stalles et les chaises de l'église, répond avec
candeur: «Puisque vous êtes malade, Madame, et puisque M. Bovary est
médecin, pourquoi n'allez-vous pas trouver votre mari?»
Quelle est la femme qui, devant cette insuffisance du curé, n'irait pas,
folle amnistiée, plonger sa tête dans les eaux tourbillonnantes de
l'adultère, et quel est celui de nous qui, dans un âge plus naïf et dans des
circonstances troublées, n'a pas fait forcément connaissance avec le
prêtre incompétent?

Dans cette terre lointaine il a d'ailleurs trouvé l'amour, qui, comme une
médecine énergique, remet chaque faculté à son rang, et pacifie tous ses
organes troublés. «Le péché d'orgueil a été racheté par l'amour.»

Les femmes, une à qui sa douceur animale, sa nullité peut-être, donne

aux yeux de son amant ensorcelé un faux air de sphinx, une autre,
modiste prétentieuse, qui a fouaillé son imagination avec toutes les orties
de George Sand, se font des révérences d'un autre monde et se traitent
de Madame! gros comme le bras.

...Car sainte Thérèse était brûlante d'un si grand amour de Dieu, que la
violence de ce feu lui faisait jeter des cris... Et cette douleur n'était pas
corporelle, mais spirituelle, quoique le corps ne laissât pas d'y avoir
beaucoup de part.

Vous est-il arrivé, comme à moi, de tomber dans de grandes mélancolies,

après avoir passé de longues heures à feuilleter des estampes libertines?
Vous êtes-vous demandé la raison du charme qu'on trouve parfois à
fouiller ces annales de la luxure, enfouies dans les bibliothèques ou
perdues dans les cartons des marchands, et parfois aussi de la mauvaise
humeur qu'elles vous donnent? Plaisir et douleur mêlés, amertume dont la
lèvre a toujours soif!—Le plaisir est de voir représenté sous toutes ses
formes le sentiment le plus important de la nature,—et la colère, de le
trouver souvent si mal imité ou si sottement calomnié. Soit dans les
interminables soirées d'hiver au coin du feu, soit dans les lourds loisirs de
la canicule, au coin des boutiques de vitrier, la vue de ces dessins m'a mis
sur des pentes de rêverie immenses, à peu près comme un livre obscène
nous précipite vers les océans mystiques du bleu. Bien des fois je me suis
pris à désirer, devant ces innombrables échantillons du sentiment de
chacun, que le poète, le curieux, le philosophe, pussent se donner la
jouissance d'un musée de l'amour, où tout aurait sa place, depuis la
tendresse inappliquée de sainte Thérèse jusqu'aux débauches sérieuses
des siècles ennuyés. Sans doute la distance est immense qui sépare Le
Départ pour l'île de Cythère des misérables coloriages suspendus dans les
chambres des filles, au-dessus d'un pot fêlé et d'une console branlante;
mais dans un sujet aussi important rien n'est à négliger. Et puis le génie
sanctifie toutes choses, et, si ces sujets étaient traités avec le soin et le
recueillement nécessaires, ils ne seraient point souillés par cette obscénité
révoltante, qui est plutôt une fanfaronnade qu'une vérité.

Que le moraliste ne s'effraye pas trop; je saurai garder les justes

mesures, et mon rêve d'ailleurs se bornait à désirer ce poème immense
de l'amour crayonné par les mains les plus pures, par Ingres, par
Watteau, par Rubens, par Delacroix! Les folâtres et élégantes princesses
de Watteau, à côté des Vénus sérieuses et reposées de M. Ingres; les
splendides blancheurs de Rubens et de Jordaens, et les mornes beautés
de Delacroix, telles qu'on peut se les figurer: de grandes femmes pâles,
noyées dans le satin! (On m'a dit qu'il avait fait autrefois pour son
Sardanapale une foule d'études merveilleuses de femmes, dans les
attitudes les plus voluptueuses).
Ainsi pour rassurer complètement la chasteté effarouchée du lecteur, je
dirai que je rangerais dans les sujets amoureux, non seulement tous les
tableaux qui traitent spécialement de l'amour, mais encore tout tableau
qui respire l'amour, fût-ce un portrait. (Deux tableaux essentiellement
amoureux, et admirables du reste, composés dans ce temps-ci, sont La
Grande Odalisque et La Petite Odalisque, de M. Ingres).

Dans cette immense exposition, je me figure la beauté et l'amour de tous

les climats exprimés par les premiers artistes; depuis les folles, évaporées
et merveilleuses créatures que nous a laissées Watteau fils dans ses
gravures de mode, jusqu'à ces Vénus de Rembrandt qui se font faire les
ongles, comme de simples mortelles, et peigner avec un gros peigne de
buis.
Les sujets de cette nature sont chose si importante, qu'il n'est point
d'artiste, petit ou grand, qui ne s'y soit appliqué, secrètement ou
publiquement, depuis Jules Romain jusqu'à Devéria et Gavarni.

Leur grand défaut, en général, est de manquer de naïveté et de sincérité.

Je me rappelle pourtant une lithographie qui exprime,—sans trop de
délicatesse malheureusement,—une des grandes vérités de l'amour
libertin. Un jeune homme déguisé en femme et sa maîtresse habillée en
homme sont assis à côté l'un de l'autre, sur un sopha,—le sopha que vous
savez, le sopha de l'hôtel garni et du cabinet particulier. La jeune femme
veut relever les jupes de son amant. Sedebant in fornicibus pueri
puellæve sub titulis et lychnis, illi femineo compti mundo sub stola, hæ
parum comptæ sub puerorum veste, ore ad puerilem formant composito.
Alter venibat sexus sub altero sexu. Corruperat omni caro viam suam.—
Meursius.

Ainsi, devant le portrait bleu de M. Amaury-Duval et bien d'autres

portraits de femmes ingristes ou ingrisées, j'ai senti passer dans mon
esprit, amenées par je ne sais quelle association d'idées, ces sages
paroles du chien Berganza, qui fuyait les bas-bleus aussi ardemment que
ces messieurs les recherchent: «Corinne ne t'a-t-elle jamais paru
insupportable?
...............................................
À l'idée de la voir s'approcher de moi, animée d'une vie véritable, je me
sentais comme oppressé par une sensation pénible, et incapable de
conserver auprès d'elle ma sérénité et ma liberté d'esprit
...............................................
Quelque beaux que pussent être son bras ou sa main, jamais je n'aurais
pu supporter ses caresses sans une certaine répugnance, un certain
frémissement intérieur qui m'ôte ordinairement l'appétit.—Je ne parle ici
qu'en ma qualité de chien!»
J'ai éprouvé la même sensation que le spirituel Berganza devant presque
tous les portraits de femmes, anciens ou présents... Dulcinée de Toboso
elle-même, en passant par l'atelier, en sortirait diaphane et bégueule
comme une élégie, et amaigrie par le thé et le beurre esthétiques.

J'ai entendu dire à un poète ordinaire de la Comédie-Française qu'il ne

concevait pas que des amoureux vécussent d'autre chose que du parfum
des fleurs et des pleurs de l'aurore.

À propos des Adieux de Roméo et Juliette, j'ai une remarque à faire que
je crois fort importante. J'ai tant entendu plaisanter de la laideur des
femmes de Delacroix, sans pouvoir comprendre ce genre de plaisanterie,
que je saisis l'occasion pour protester contre ce préjugé. M. Victor Hugo le
partageait, à ce qu'on m'a dit. Il déplorait,—c'était dans les beaux temps
du Romantisme,—que celui à qui l'opinion publique faisait une gloire
parallèle à la sienne commît de si monstrueuses erreurs à l'endroit de la
beauté. Il lui est arrivé d'appeler les femmes de Delacroix des grenouilles.
Mais M. Victor Hugo est un grand poète sculptural qui a l'œil fermé à la
spiritualité.
Je suis fâché que le Sardanapale n'ait pas reparu cette année. On y aurait
vu de très belles femmes, claires, lumineuses, roses, autant qu'il m'en
souvient du moins. Sardanapale lui-même était beau comme une femme.
Généralement les femmes de Delacroix peuvent se diviser en deux
classes: les unes, faciles à comprendre, souvent mythologiques, sont
nécessairement belles (la Nymphe couchée et vue de dos, dans le plafond
de la galerie d'Apollon). Elles sont riches, très fortes, plantureuses,
abondantes, et jouissent d'une transparence de chair merveilleuse et de
chevelures admirables.
Quant aux autres, quelquefois des femmes historiques (la Cléopâtre
regardant l'aspic), plus souvent des femmes de caprice, de tableaux de
genre, tantôt des Marguerite, tantôt des Ophélia, des Desdémone, des
Sainte-Vierge même, des Madeleine, je les appellerais volontiers des
femmes d'intimité. On dirait qu'elles portent dans les yeux un secret
douloureux, impossible à enfouir dans les profondeurs de la dissimulation.
Leur pâleur est comme une révélation de batailles intérieures. Qu'elles se
distinguent par le charme du crime ou par l'odeur de la sainteté, que leurs
gestes soient alanguis ou violents, ces femmes malades du cœur ou de
l'esprit ont dans les yeux le plombé de la fièvre ou la nitescence anormale
et bizarre de leur mal, dans le regard, l'intensité du surnaturalisme.
Mais toujours, et quand même, ce sont des femmes distinguées,
essentiellement distinguées; et enfin, pour tout dire en un seul mot, M.
Delacroix me paraît être l'artiste le mieux doué pour exprimer la femme
moderne, surtout la femme moderne dans sa manifestation héroïque,
dans le sens infernal ou divin. Ces femmes ont même la beauté physique
moderne, l'air de rêverie, mais la gorge abondante, avec une poitrine un
peu étroite, le bassin ample, et des bras et des jambes charmants.

L'Amour, l'inévitable Amour, l'immortel Cupidon des confiseurs, joue dans

l'école néogrecque, que je nommerai l'école des pointus, un rôle
dominateur et universel. Il est le président de cette république galante et
minaudière. C'est un poisson qui s'accommode à toutes les sauces. Ne
sommes-nous pas cependant bien las de voir la couleur et le marbre
prodigués en faveur de ce vieux polisson, ailé comme un insecte, ou
comme un canard, que Thomas Hood nous montre accroupi, et, comme
un impotent, écrasant de sa molle obésité le nuage qui lui sert de
coussin? De sa main gauche il tient en manière de sabre son arc appuyé
contre sa cuisse; de la droite il exécute avec sa flèche le commandement:
Portez armes! sa chevelure est frisée drue comme une perruque de
cocher; ses joues rebondissantes oppriment ses narines et ses yeux; sa
chair, ou plutôt sa viande, capitonnée, tubuleuse et soufflée, comme les
graisses suspendues aux crochets des bouchers, est sans doute distendue
par les soupirs de l'idylle universelle; à son dos montagneux sont
accrochées deux ailes de papillon. «Est-ce bien là l'incube qui oppresse le
sein des belles?... Ce personnage est-il le partenaire disproportionné pour
lequel soupire Pastorella, dans la plus étroite des couchettes virginales?
La platonique Amanda (qui est tout âme) fait-elle donc, quand elle
disserte sur l'Amour, allusion à cet être trop palpable, qui est tout corps?
Et Bélinda croit-elle, en vérité, que ce Sagittaire ultra-substantiel puisse
être embusqué dans son dangereux œil bleu?

«La légende raconte qu'une fille de Provence s'amouracha de la statue

d'Apollon et en mourut. Mais demoiselle passionnée délira-t-elle jamais et
se dessécha-t-elle devant le piédestal de cette monstrueuse figure? ou
plutôt ne serait-ce pas un emblème indécent qui servirait à expliquer la
timidité et la résistance proverbiale des filles à l'approche de l'Amour?
«Je crois facilement qu'il lui faut tout un cœur pour lui tout seul; car il
doit le bourrer jusqu'à la réplétion. Je crois à sa confiance; car il a l'air
sédentaire et peu propre à la marche. Qu'il soit prompt à fondre, cela
tient à sa graisse, et, s'il brûle avec flamme, il en est de même de tous les
corps gras. Il a des langueurs comme tous les corps d'un pareil tonnage,
et il est naturel qu'un si gros soufflet soupire.
«Je ne nie pas qu'il s'agenouille aux pieds des dames, puisque c'est la
posture des éléphants; qu'il jure que cet hommage sera éternel; certes il
serait malaisé de concevoir qu'il en fût autrement. Qu'il meure, je n'en
fais aucun doute, avec une pareille corpulence et un cou si court! S'il est
aveugle, c'est l'enflure de sa joue de cochon qui lui bouche la vue. Mais
qu'il loge dans l'œil bleu de Bélinda, ah! je me sens hérétique, je ne le
croirai jamais; car elle n'a jamais eu une étable dans l'œil!»—Une étable
contient plusieurs cochons, et, de plus, il y a calembour; on peut deviner
quel est le sens du mot sty au figuré.
Cela est doux à lire, n'est-ce pas? et cela nous venge un peu de ce gros
poupard troué de fossettes qui représente l'idée populaire de l'Amour.
Pour moi, si j'étais invité à représenter l'Amour, il me semble que je le
peindrais sous la forme d'un cheval enragé qui dévore son maître, ou bien
d'un démon aux yeux cernés par la débauche et l'insomnie, traînant,
comme un spectre ou un galérien, des chaînes bruyantes à ses chevilles,
et secouant d'une main une fiole de poison, de l'autre le poignard
sanglant du crime.

...La gouge qui, je crois, n'est pas là, mais qui pouvait y être, cette fille
peinte du moyen âge, qui suivait les soldats avec l'autorisation du prince
et de l'Église, comme la courtisane du Canada accompagnait les guerriers
au manteau de castor.

Quant aux figures grotesques que nous a laissées l'antiquité, les

masques, les figurines de bronze, les Hercules tout en muscles, les petits
Priapes à la langue recourbée en l'air, aux oreilles pointues, tout en
cervelet et en phallus,—quant à ces phallus prodigieux sur lesquels les
blanches filles de Romulus montent innocemment à cheval, ces
monstrueux appareils de la génération armée de sonnettes et d'ailes, je
crois que toutes ces choses sont pleines de sérieux. Vénus, Pan, Hercule,
n'étaient pas des personnages risibles. On en a ri après la venue de
Jésus, Platon et Sénèque aidant.

Gavarni a créé la Lorette. Elle existait bien un peu avant lui, mais il l'a
complétée. Je crois même que c'est lui qui a inventé le mot. La Lorette,
on l'a déjà dit, n'est pas la fille entretenue, cette chose de l'Empire,
condamnée à vivre en tête-à-tête funèbre avec le cadavre métallique dont
elle vivait, général ou banquier. La Lorette est une personne libre. Elle va
et elle vient. Elle tient maison ouverte. Elle n'a pas de maître; elle
fréquente les artistes et les journalistes. Elle fait ce qu'elle peut pour avoir
de l'esprit. J'ai dit que Gavarni l'avait complétée; et, en effet, entraîné par
son imagination littéraire, il invente au moins autant qu'il voit, et, pour
cette raison, il a beaucoup agi sur les mœurs. Paul de Kock a créé la
Grisette, et Gavarni, la Lorette; et quelques-unes de ces filles se sont
perfectionnées en se l'assimilant, comme la jeunesse du quartier latin
avait subi l'influence de ses étudiants, comme beaucoup de gens
s'efforcent de ressembler aux gravures de mode.

L'amour, c'est le goût de la prostitution. Il n'est même pas de plaisir noble

qui ne puisse être ramené à la prostitution.
Dans un spectacle, dans un bal, chacun jouit de tous.
............................................................
L'amour peut dériver d'un sentiment généreux: le goût de la prostitution;
mais il est bientôt corrompu par le goût de la propriété.
L'amour veut sortir de soi, se confondre avec sa victime, comme le
vainqueur avec le vaincu, et cependant conserver des privilèges de
conquérant.
Les voluptés de l'entreteneur tiennent à la fois de l'ange et du
propriétaire. Charité et férocité. Elles sont même indépendantes du sexe,
de la beauté et du genre animal.
............................................................
Anecdote du chasseur, relative à la liaison intime de la férocité et de
l'amour.

De la couleur violette (amour contenu, mystérieux, voilé, couleur de

chanoinesse).

Je crois que j'ai déjà dans mes notes écrit que l'amour ressemblait fort à
une torture ou à une opération chirurgicale. Mais cette idée peut être
développée de la manière la plus amère. Quand même les deux amants
seraient très épris et très pleins de désirs réciproques, l'un des deux sera
toujours plus calme, ou moins possédé que l'autre. Celui-là ou celle-là,
c'est l'opérateur ou le bourreau; l'autre, c'est le sujet, la victime.
Entendez-vous ces soupirs, préludes d'une tragédie de déshonneur, ces
gémissements, ces cris, ces râles? Qui ne les a proférés, qui ne les a
irrésistiblement extorqués? Et que trouvez-vous de pire dans la question
appliquée par de soigneux tortionnaires? ces yeux de somnambule
révulsés, ces membres dont les muscles jaillissent et se roidissent comme
sous l'action d'une pile galvanique, l'ivresse, le délire, l'opium, dans leurs
plus furieux résultats, ne vous en donneront certes pas d'aussi affreux,
d'aussi curieux exemples. Et le visage humain, qu'Ovide croyait façonné
pour refléter les astres, le voilà qui ne parle plus qu'une expression de
férocité folle, ou qui se détend dans une espèce de mort. Car, certes, je
croirais faire un sacrilège en appliquant le mot: extase à cette sorte de
décomposition.
—Épouvantable jeu, où il faut que l'un des joueurs perde le
gouvernement de soi-même!
Une fois, il fut demandé, devant moi, en quoi consistait le plus grand
plaisir de l'amour. Quelqu'un répondit naturellement: à recevoir, et un
autre: à se donner.—Celui-ci dit: plaisir d'orgueil;—et celui-là: volupté
d'humilité. Tous ces orduriers parlaient comme L'Imitation de Jésus-Christ.
Enfin, il se trouva un impudent utopiste qui affirma que le plus grand
plaisir de l'amour était de former des citoyens pour la Patrie.
Moi, je dis: la volupté unique et suprême de l'amour gît dans la certitude
de faire le mal. Et l'homme et la femme savent, de naissance, que dans le
mal se trouve toute volupté.
Nous aimons les femmes à proportion qu'elles nous sont plus étrangères.
Aimer les femmes intelligentes est un plaisir de pédéraste. Ainsi la
bestialité exclut la pédérastie.

La maigreur est plus nue, plus indécente que la graisse.

...Le plaisir viendrait après, à bien plus juste titre qu'on ne dit: l'amour
vient après le mariage.

J'ai trouvé la définition du Beau, de mon Beau.

C'est quelque chose d'ardent et de triste, quelque chose d'un peu vague,
laissant carrière à la conjecture. Je vais, si l'on veut, appliquer mes idées
à un objet sensible, à l'objet par exemple le plus intéressant dans la
société, à un visage de femme. Une tête séduisante et belle, une tête de
femme, veux-je dire, c'est une tête qui fait rêver à la fois, mais d'une
manière confuse, de volupté et de tristesse; qui comporte une idée de
mélancolie, de lassitude, même de satiété,—soit une idée contraire, c'est-
à-dire une ardeur, un désir de vivre, associés avec une amertume
refluante, comme venant de privation ou de désespérance. Le mystère, le
regret sont aussi des caractères du Beau.
Une belle tête d'homme n'a pas besoin de comporter, excepté peut-être
aux yeux d'une femme, cette idée de volupté, qui, dans un visage de
femme, est une provocation d'autant plus attirante que le visage est
généralement plus mélancolique.

DE L'AIR DANS LA FEMME.—Les airs charmants, et qui font la beauté, sont:

l'air blasé, l'air ennuyé, l'air évaporé, l'air impudent, l'air froid, l'air de
regarder en dedans, l'air de domination, l'air de volonté, l'air méchant,
l'air malade, l'air chat, enfantillage, nonchalance et malice mêlés.

Du culte de soi-même dans l'amour, au point de vue de la santé, de

l'hygiène, de la toilette, de la noblesse spirituelle et de l'éloquence.
Il y a dans l'acte de l'amour une grande ressemblance avec la torture ou
avec une opération chirurgicale.

Tantôt il lui demandait la permission de lui baiser la jambe, et il profitait

de la circonstance pour baiser cette belle jambe dans telle position qu'elle
dessinât nettement son contour sur le soleil couchant.

«Minette, minoutte, minouille, mon chat, mon loup, mon petit singe,
grand singe, grand serpent, mon petit singe mélancolique». De pareils
caprices de langue trop répétés, de trop fréquentes appellations bestiales
témoignent d'un côté satanique dans l'amour. Les satans n'ont-ils pas des
formes de bêtes? Le chameau de Cazotte, chameau, diable et femme.

Un homme va au tir au pistolet, accompagné de sa femme. Il ajuste une

poupée, et dit à sa femme: Je me figure que c'est toi.—Il ferme les yeux
et abat la poupée.—Puis il dit, en baisant les mains de sa compagne: Cher
ange, que je te remercie de mon adresse.

Il n'y a que deux endroits où l'on paye pour avoir le droit de dépenser: les
latrines publiques et les femmes.

Par un concubinage ardent, on peut deviner les jouissances d'un jeune

ménage.
Le goût précoce des femmes. Je confondais l'odeur de la fourrure avec
l'odeur de la femme. Je me souviens... Enfin, j'aimais ma mère pour son
élégance. J'étais donc un dandy précoce.
.......................................
Les pays protestants manquent de deux éléments indispensables au
bonheur d'un homme bien élevé, la galanterie et la dévotion.
.......................................
L'Espagne met dans la religion la férocité naturelle de l'amour.
Le ton fille entretenue (ma toute-belle! sexe volage!)... La prima-donna et
le garçon boucher.

Ému au contact de ces voluptés qui ressemblaient à des souvenirs,

attendri par la pensée d'un passé mal rempli, de tant de fautes, de tant
de querelles, de tant de choses à se cacher réciproquement, il se mit à
pleurer; et ses larmes chaudes coulèrent, dans les ténèbres, sur l'épaule
nue de sa chère et toujours attirante maîtresse.
Elle tressaillit, elle se sentit, elle aussi, attendrie, et remuée. Les ténèbres
rassuraient sa vanité et son dandysme de femme froide. Ces deux êtres
déchus, mais souffrant encore de leur reste de noblesse, s'enlacèrent
spontanément, confondant, dans la pluie de leurs larmes et de leurs
baisers, les tristesses de leur passé avec leurs espérances bien incertaines
d'avenir. Il est présumable que jamais, pour eux, la volupté ne fut si
douce que dans cette nuit de mélancolie et de charité;—volupté saturée
de douleur et de remords.
À travers la noirceur de la nuit, il avait regardé derrière lui dans les
années profondes, puis il s'était jeté dans les bras de sa coupable amie,
pour y retrouver le pardon qu'il lui accordait.

Alors, les errantes, les déclassées, celles qui ont eu quelques amants et
qu'on appelle parfois des anges, en raison et en remerciement de
l'étourderie qui brille, lumière de hasard, dans leur existence logique
comme le mal,—alors celles-là, dis-je, ne seront plus qu'impitoyable
sagesse, sagesse qui condamnera tout, fors l'argent, tout, même les
erreurs des sens! Alors, ce qui ressemblera à la vertu, que dis-je, tout ce
qui ne sera pas l'ardeur vers Plutus sera réputé un immense ridicule. La
justice, si, à cette époque fortunée, il peut encore exister une justice, fera
interdire les citoyens qui ne sauront pas faire fortune. Ton épouse, ô
Bourgeois! ta chaste moitié, dont la légitimité fait pour toi la poésie,
introduisant désormais dans la légalité une infamie irréprochable,
gardienne vigilante et amoureuse de ton coffre-fort, ne sera plus que
l'idéal parfait de la femme entretenue. Ta fille, avec une nubilité
enfantine, rêvera, dans son berceau, qu'elle se vend un million.
La femme est le contraire du dandy. Donc elle doit faire horreur. La
femme a faim, et elle veut manger; soif, et elle veut boire. Elle est en rut,
et elle veut être f***.
Le beau mérite!
La femme est naturelle, c'est à dire abominable.
Aussi est-elle toujours vulgaire, c'est là dire le contraire du dandy.

Dans Les Oreilles du Comte de Chesterfield, Voltaire plaisante sur cette

âme immortelle qui a résidé, pendant neuf mois, entre des excréments et
des urines. Voltaire, comme tous les paresseux, haïssait le mystère.
Ne pouvant pas supprimer l'amour, l'Église a voulu au moins le
désinfecter, et elle a fait le mariage.

[En marge]. Au moins aurait-il pu deviner dans cette localisation une

malice ou une satire de la Providence contre l'amour, et, dans le mode de
la génération, un signe du péché originel. De fait, nous ne pouvons faire
l'amour qu'avec des organes excrémentiels.

Pourquoi l'homme d'esprit aime les filles plus que les femmes du monde,
malgré qu'elles soient également bêtes? À trouver.

Il y a de certaines femmes qui ressemblent au ruban de la Légion

d'honneur. On n'en veut plus parce qu'elles se sont salies à de certains
hommes. C'est par la même raison que je ne chausserais pas les culottes
d'un galeux.
Ce qu'il y a d'ennuyeux dans l'amour, c'est que c'est un crime où l'on ne
peut pas se passer d'un complice.

Le goût du plaisir nous attache au présent. Le soin de notre salut nous

suspend à l'avenir.
Celui qui s'attache au plaisir, c'est a dire au présent, me fait l'effet d'un
homme roulant sur une pente, et qui, voulant se raccrocher aux arbustes,
les arracherait et les emporterait dans sa chute.

Avant tout, être un grand homme et un saint pour soi-même.

Qu'est-ce que l'amour? Le besoin de sortir de soi.

L'homme est un animal adorateur. Adorer, c'est se sacrifier et se
prostituer.
Aussi tout amour est-il prostitution.
L'être le plus prostitué, c'est l'être par excellence, c'est Dieu, puisqu'il est
l'ami suprême pour chaque individu, puisqu'il est le réservoir commun,
inépuisable, de l'amour.

J'ai toujours été étonné qu'on laissât les femmes entrer dans les églises.
Quelle conversation peuvent-elles avoir avec Dieu?
L'éternelle Vénus (caprice, hystérie, fantaisie) est une des formes
séduisantes du diable.

La femme ne sait pas séparer l'âme du corps. Elle est simpliste, comme
les animaux.—Un satirique dirait que c'est parce qu'elle n'a que le corps.
Un chapitre sur la toilette.—Moralité de la toilette, les bonheurs de la
toilette.

Musique. De l'esclavage.—Des femmes du monde.—Des filles.

Dans l'amour, comme dans presque toutes les affaires humaines, l'entente
cordiale est le résultat d'un malentendu. Ce malentendu, c'est le plaisir.
L'homme crie: O mon ange! La femme roucoule: Maman! maman! Et ces
deux imbéciles sont persuadés qu'ils pensent de concert.—Le gouffre
infranchissable, qui fait l'incommunicabilité, reste infranchi.
La jeune fille des éditeurs. La jeune fille des rédacteurs en chef. La jeune
fille épouvantail, monstre, assassin de l'art.
La jeune fille, ce qu'elle est en réalité. Une petite sotte et une petite
salope; la plus grande imbécillité unie à la plus grande dépravation.
Il y a dans la jeune fille toute l'abjection du voyou et du collégien.

Goût inamovible de la prostitution dans le cœur de l'homme, d'où naît son

horreur de la solitude.—Il veut être deux. L'homme de génie veut être un,
donc solitaire. La gloire, c'est rester un, et se prostituer d'une manière
particulière.
C'est cette horreur de la solitude, le besoin d'oublier son moi dans la chair
extérieure, que l'homme appelle noblement besoin d'aimer.
Deux belles religions, immortelles sur les murs, éternelles obsessions du
peuple: le phallus antique, et «Vive Barbés!» ou «À bas Philippe!» ou
«Vive la République»!

De la nécessité de battre les femmes.

On peut châtier ce que l'on aime. Ainsi, les enfants. Mais cela implique la
douleur de mépriser ce que l'on aime.
Du cocuage et des cocus. La douleur du cocu. Elle naît de son orgueil,
d'un raisonnement faux sur l'honneur et sur le bonheur, et d'un amour
niaisement détourné de Dieu pour être attribué aux créatures. C'est
toujours l'animal adorateur se trompant d'idole.

Plus l'homme cultive les arts, moins il b***.

Il se fait un divorce de plus en plus sensible entre l'esprit et la brute.
La brute seule b*** bien et la fouterie est le lyrisme du peuple.
F***, c'est aspirer à entrer dans un autre, et l'artiste ne sort jamais de
lui-même.
J'ai oublié le nom de cette salope... Ah! bah! je le retrouverai au jugement
dernier.
Tous les imbéciles de la Bourgeoisie qui prononcent sans cesse les mots:
immoral, immoralité, moralité dans l'art et autres bêtises me font penser à
Louise Villedieu, putain à cinq francs, qui, m'accompagnant une fois au
Louvre, où elle n'était jamais allée, se mit à rougir, à se couvrir le visage,
et, me tirant à chaque instant par la manche, me demandait devant les
statues et les tableaux immortels comment on pouvait étaler
publiquement de pareilles indécences.

Chronique locale. J'ai appris par des ouvriers, qui travaillaient au jardin,
qu'on avait surpris, il y a déjà longtemps, la femme du ***, se faisant
f*** dans un confessionnal. Cela m'a été révélé, parce que je demandais
pourquoi l'église Sainte-Catherine était fermée aux heures où il n'y a pas
d'offices. Il paraît que le curé a pris depuis lors ses précautions contre le
sacrilège. C'est une femme insupportable, qui me disait dernièrement
qu'elle avait connu le peintre qui a peint le fronton du Panthéon, mais qui
doit avoir un c*** superbe (elle). Cette histoire de f*** provinciale, dans
un lieu sacré, n'a-t-elle pas tout le sel classique des vieilles saletés
françaises? Gardez-vous bien de raconter cette histoire à des gens qui
pourraient dire à Honfleur que vous la tenez de moi, alors il me faudrait
fuir mon lieu de repos.

C'est depuis ce temps que est obligé d'effacer des cornes que l'on dessine
sur sa porte.
Pour le curé, que tout le monde appelle ici un brave homme, c'est
presque un homme remarquable, et même érudit.

Nerciat (utilité de ses livres).

Au moment où la Révolution française éclata, la noblesse française était
une race physiquement diminuée (de Maistre).
Les livres libertins commentent donc et expliquent la Révolution.

La fouterie et la gloire de la fouterie étaient-elles plus immorales que

cette manière moderne d'adorer et de mêler le saint au profane?
On se donnait alors beaucoup de mal pour ce qu'on avouait être une
bagatelle, et on ne se damnait pas plus qu'aujourd'hui.
Mais on se damnait moins bêtement, on ne se pipait pas.

Comment on faisait l'amour sous l'ancien régime.

Plus gaiement, il est vrai.

Ce n'était pas l'extase, comme aujourd'hui, c'était le délire.

C'était toujours le mensonge, mais on n'adorait pas son semblable. On le
trompait, mais on se trompait soi-même.

Ici, comme dans la vie, la palme de la perversité reste à la femme.

Laufeia. Fæmina simplex dans sa petite maison.

Manœuvres de l'Amour.
Belleroche. Machines à plaisir.

Cécile, dans Les Liaisons dangereuses, type parfait de la détestable jeune

fille, niaise et sensuelle.
Son portrait, par la Merteuil, qui excelle aux portraits.

La jeune fille. La niaise, stupide et sensuelle. Tout près de l'ordure

originelle.
La Merteuil: Tartuffe femelle, tartuffe de mœurs, tartuffe du XVIIIe siècle.

J'ai bien besoin d'avoir cette femme pour me sauver du ridicule d'en être
amoureux... J'ai, dans ce moment, un sentiment de reconnaissance pour
les femmes faciles, qui me ramène naturellement à vos pieds.
Lettre IV: Les Liaisons dangereuses.
Cet entier abandon de soi-même, ce délire de la volupté, où le plaisir
s'épure par son excès, ces biens de l'amour ne sont pas connus d'elle...
Votre présidente croira avoir tout fait pour vous en vous traitant comme
son mari, et, dans le tête-à-tête conjugal le plus tendre, on est toujours
deux.
Lettre V: Les Liaisons dangereuses.

(Source de la sensualité mystique et des sottises amoureuses du XIXe

siècle.)

J'aurai cette femme. Je l'enlèverai au mari, qui la profane (G. Sand).

J'oserai la ravir au Dieu même qu'elle adore (Valmont Satan, rival de
Dieu). Quel délice d'être tour à tour l'objet et le vainqueur de ses
remords! Loin de moi l'idée de détruire les préjugés qui l'assiègent. Ils
ajouteront à mon bonheur et à ma gloire. Qu'elle croie à la vertu, mais
qu'elle me la sacrifie... Qu'alors, si j'y consens, elle me dise: «Je t'adore!»
Lettre VI: Les Liaisons dangereuses.

(La femme qui veut toujours faire l'homme, signe de grande dépravation).
Imprudentes qui, dans leur amant actuel, ne savent pas voir leur ennemi
futur.
.......................................
Je n'avais pas quinze ans... La tête seule fermentait. Je ne désirais pas de
jouir, je voulais savoir. (Georges Sand et autres).
Lettre LXXXI: Les Liaisons dangereuses.

Encore une touche au portrait de la petite Volanges par la Merteuil:

Tandis que nous nous occuperions à former cette petite fille pour l'intrigue
[nous n'en ferions qu'une femme facile]... Ces sortes de femmes ne sont
absolument que des machines à plaisir.
Lettre CVI: Les Liaisons dangereuses.
Valmont se glorifie et chante son futur triomphe.
Je la montrerai, dis-je, oubliant ses devoirs... Je ferai plus, je la quitterai...
Voyez mon ouvrage et cherchez-en dans le siècle un second exemple!...
Lettre CXV: Les Liaisons dangereuses.

Quant aux femmes, leur éducation informe, leur incompétence politique

et littéraire empêchent beaucoup d'auteurs de voir en elles autre chose
que des ustensiles de ménage ou des objets de luxure. Le dîner absorbé
et l'animal satisfait, le poète entre dans la vaste solitude de sa pensée.

Les femmes écrivent, écrivent avec une rapidité débordante, leur cœur
bavarde à la rame. Elles ne connaissent généralement ni l'art, ni la
mesure, ni la logique; leur style traîne et ondoie comme leurs vêtements.
Un très grand et très justement illustre écrivain, George Sand and elle-
même, n'a pas tout à fait, malgré sa supériorité, échappé à cette loi du
tempérament; elle jette ses chefs-d'œuvre à la poste comme des lettres.
Ne dit-on pas qu'elle écrit ses livres sur du papier à lettres?

...Je pense qu'une littérature sévère serait chez nous une protestation
utile contre l'envahissante fatuité des femmes, de plus en plus surexcitée
par la dégoûtante idolâtrie des hommes; et je suis très indulgent pour
Voltaire, trouvant bon dans sa préface de La Mort de César, tragédie sans
femme, sous de feintes excuses de son impertinence, de bien faire
remarquer son glorieux tour de force: «...Aucun de ces auteurs n'a avili ce
grand sujet par une intrigue de galanterie. Mais il y a environ trente-cinq
ans qu'un des plus beaux génies de France [Fontenelle] s'étant associé
avec Mlle Barbier pour composer un Jules César, il ne manqua pas de
représenter César et Brutus amoureux et jaloux. Cette petitesse ridicule
est un des plus grands exemples de la force de l'habitude; personne n'ose
guérir le théâtre français de cette contagion. Il a fallu que, dans Racine,
Mithridate, Alexandre, Porus, aient été galants. Corneille n'a jamais évité
cette faiblesse: il n'a fait aucune pièce sans amour, et il faut avouer que,
dans ses tragédies, si vous exceptez Le Cid et Polyeucte, cette passion est
aussi mal peinte qu'elle y est étrangère.»
SUR LA BELGIQUE.—MŒURS. LES FEMMES ET L'AMOUR.

Pas de femmes; pas d'amour.

Pourquoi?

Pas de galanterie chez l'homme, pas de pudeur chez la femme. La pudeur,

objet prohibé, ou dont on ne sent pas le besoin. Portrait général de la
Flamande, ou du moins de la Brabançonne. (La Wallonne, mise de côté,
provisoirement.) Type général de physionomie, analogue à celui du
mouton et du bélier.—Le sourire, impossible à cause de la récalcitrante
des muscles et de la structure des dents et des mâchoires.
Le teint, en général, blafard, quelquefois vineux. Les cheveux, jaunes. Les
jambes, les gorges, énormes, pleines de suif, les pieds, horreur!!!
En général, une précocité d'embonpoint monstrueux, un gonflement
marécageux, conséquence de l'humidité de l'atmosphère et de la
goinfrerie des femmes.
La puanteur des femmes. Anecdotes.
Obscénité des dames belges. Anecdotes de latrines et de coins de rues.
Quant à l'amour, en référer aux ordures des anciens Flamands. Amour de
sexagénaires. Ce peuple n'a pas changé, et les peintres flamands sont
encore vrais.
Ici, il y a des femelles. Il n'y a pas de femmes.
—Prostitution belge. Haute et basse prostitution. Contrefaçon des biches
françaises. Prostitution française à Bruxelles.
Extraits du règlement sur la prostitution.

Nous avons tous la vérole dans les os, nous nous sommes démocratisés
et syphilisés.
Il y avait en Allemagne un duché de quatre sous, grand comme la main,
qui s'appelait le duché de Cobourg-Gotha. C'était pour ainsi dire un haras
royal, une écurie de beaux hommes, tous taillés en tambours-majors qui
étaient destinés aux princesses de l'Europe.
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