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Pathophysiology of cyclic hemorrhagic ascites and endometriosis
Pathophysiology of Cyclic Hemorrhagic Ascites and Endometriosis
Anastasia Ussia, MD, George Betsas, MD, Roberta Corona, MD, Carlo De Cicco, MD,and Philippe R. Koninckx, MD*From the Department of Obstetrics and Gynecology, Villa Giose, Crotone, Italy (Dr. Ussia); Department of Obstetrics and Gynecology, UZ Gasthuisberg,Katholieke Universiteit Leuven, Belgium (Drs. Betsas, Corona, De Cicco, and Koninckx); University of Thessaloniki, Greece (Dr. Betsas); University ofCagliari, Italy (Dr. Corona); and University Cattolica, Rome, Italy (Drs. De Cicco and Koninckx).
Massive hemorrhagic ascites (4470 mL, range 1–10 L) in women with endometriosis is a rare condition occurring predomi-nantly in black women. Of the 43 case reports published, 42 are compatible with the hypothesis that the hemorrhagic ascitesis predominantly a consequence of excessive ovarian transudation similar to a Meigs syndrome. Indeed, bilateral ovariectomycures the condition without recurrences, whereas after unilateral ovariectomy or cystectomy recurrence rate is more than 50%;during ovarian suppression by luteinizing hormone-releasing hormone agonist ascites disappears, but reappears after treatment.
Superficial pelvic endometriosis also contributes to the ascites because after superficial endometriosis destruction the recur-rence rate is only 4 in 14. Based on these data, it is suggested, to scrutinize the ovaries for tumors given the analogy with Meigssyndrome. In women desiring fertility, conservative treatment with destruction of endometriosis only can be attempted giventhe cure rate of some 20%. It is unknown what the effect of ovulation induction would be. Journal of Minimally Invasive Gy-necology (2008) 15, 677–681 Ó 2008 AAGL. All rights reserved.
Endometriosis; Ascites; Meigs syndrome; Cystic ovarian endometriosis
Peritoneal fluid during the normal menstrual cycle was de-
tions of blood proteins are lower in peritoneal fluid. For
scribed to be predominantly formed as an ovarian exudate.
example, albumin concentration being some 70% of the
Women without ovarian activity have less than 5 mL of
plasma concentration whereas the concentration of larger
peritoneal fluid whereas in cyclic women the volume of
molecules such as gammaglobulins and fibrinogen is even
peritoneal fluid increases progressively up to a few hundred
lower This also is the reason that locally secreted large
milliliters during ovulation The increased vascular per-
molecular–weight proteins, such as CA 125 and PP14, accu-
meability around the developing follicle was postulated as
mulate and their concentrations can be very high in peritoneal
the underlying mechanism, explaining the high steroid hor-
mone concentrations in peritoneal fluid mediated by local
Inflammation, either locally after a mechanical trauma
factors such as the extremely high estrogen concentrations,
such as surgery or more generalized during peritonitis, also
and other factors such as angiogenic factors, prostaglandins,
increases the volume of peritoneal fluid by a mechanism of
histamine, and cytokines. The massive ascites in women with
exudation. This fluid typically contains similar protein con-
ovarian hyperstimulation syndrome have been explained by
centrations as in blood, with high fibrinogen content and
similar mechanisms . The mesothelial cells of the perito-
neum actively regulate the exchange between peritoneal fluid
The Meigs syndrome is well known as the association of an
and the bloodstream, and the transport rate is much slower for
ovarian fibroma, massive ascites, and hydrothorax . The
larger molecules. This explains the fact that the concentra-
mechanism of the increased ovarian exudation is, to our knowl-edge, not yet identified. After the excision of the ovarian tumoror after adnexectomy, the ascites disappears. By analogy, a ma-
The authors have no commercial, proprietary, or financial interest in the
lignant ovarian tumor, or a metastasis in the ovary together
products or companies described in this article.
with ascites and hydrothorax is called a pseudo-Meigs syn-
Corresponding author: Philippe R. Koninckx, MD, Department of Obstetricsand Gynecology, UZ Gasthuisberg, Katholieke Universiteit Leuven, B3000-
drome. Other rare causes of pseudo-Meigs syndrome are the
struma ovarii and rare cases of uterine fibroma .
Pelvic endometriosis is known to constitute a low-grade
pelvic inflammation and the peritoneal fluid volume
Submitted July 15, 2008. Accepted for publication August 20, 2008.
Available at and
is only slightly higher than in women without endometriosis
1553-4650/$ - see front matter Ó 2008 AAGL. All rights reserved.
Journal of Minimally Invasive Gynecology, Vol 15, No 6, November/December 2008
. In addition, in women with severe bilateral cystic
She is symptom free without ascites, dysmenorrhea, or pelvic
ovarian endometriosis and with extensive superficial endo-
pain and with an excellent quality of life. Because the patient
metriosis, the volume of peritoneal fluid is hardly increased.
wants to continue this treatment we do not know whether stop-
Occasionally, some women with endometriosis have an im-
ping the treatment would cause a recurrence. In vitro
portant hemorrhagic ascites as described in 43 case reports.
fertilization will be considered in the near future.
The pathophysiology of this hemorrhagic ascites is unknown,but the widely held belief that the ascites is a consequence of
the superficial endometriosis, similar to peritoneal metasta-ses, remains speculative.
A 26-year-old, Caucasian, nulliparous woman had an
Two cases of massive hemorrhagic ascites together with
emergency laparoscopy and more than 1 L of hemorrhagic
endometriosis in women with mechanical fertility prompted
ascites was evacuated. One year later a second laparoscopy
us to review the literature in detail, to evaluate whether the
was performed for acute pain. Again, more than 1 L of hem-
pathophysiology could be similar to Meigs syndrome, and
orrhagic ascites was drained. Severe superficial endometri-
to decide whether ovulation induction for in vitro fertilization
osis involving the bowel, peritoneum, and omentum was
excised. Two years later an ultrasound-guided evacuationof 2 L of hemorrhagic ascites was performed for recurringpain. Two months later a third laparoscopy was performed
because of severe pain, massive ascites, and increased con-
centrations of white blood cell count, increased concentrationof C-reactive protein, and slight fever. Ascites was drained,
A 23-year-old nulligravida woman had severe dysmenor-
and an adhesiolysis together with the excision of an endo-
rhea and menstrual right shoulder pain. A hydrothorax was
metriotic rectovaginal nodule was performed. Less than 1
drained twice, confirming the diagnosis of endometriosis.
year later the patient again had acute pain, important ascites,
During treatment with luteinizing hormone-releasing hor-
and signs of an inflammatory reaction. Another paracentesis
mone agonists symptoms disappeared, but 3 months later
was performed and 1.5 L of hemorrhagic fluid evacuated.
symptoms recurred. A pleurectomy was performed with re-
Some 2 months later, the ascites had returned and pain was
moval of many small endometriotic lesions on the pleura,
intolerable. Because at magnetic resonance imaging a 2-cm
a 2-cm nodule in the right diaphragm, a 4-cm nodule in the up-
ovarian cyst was found, a laparotomy was performed. Mas-
per part, and a 3.5-cm nodule in the middle part of the right
sive adhesions were lysed, and an appendicectomy, an omen-
lung. Four months later, she was readmitted with severe pelvic
tectomy, and a unilateral adnexectomy were performed. One
pain and ascites. At laparoscopy, massive hemorrhagic ascites
year later symptoms and ascites had returned, and after another
was found together with a frozen pelvis, bowel adhesions, and
paracentesis to evacuate hemorrhagic fluid, gonadotropin-
multiple spots of endometriosis on the peritoneum and the
releasing hormone therapy was started. With this therapy,
patient is still symptom free after 3 years.
releasing hormone agonists the patient was free of symptomsbut 1 year after stopping the treatment, she was readmitted
with symptoms of subocclusion, ascites, and pain. A large sig-moid nodule was diagnosed on contrast enema. At laparos-
All original case reports (n 5 44) written since 1980 were
copy, 1.5 L of hemorrhagic ascites was found together with
reviewed in detail except 2 articles we could not retrieve
severe adhesions and 2 big nodules of deep endometriosis.
We looked specifically for pathophysiology, volume
A low rectovaginal nodule of 5-cm diameter attached to the
of peritoneal fluid, presence of hematothorax, CA 125 con-
right spine was excised with a carbon-dioxide laser, together
centrations, age, parity, race, whether a tumor or mass was
with ureterolysis over a double J because of hydronephrosis
detected in the ovaries before or during surgery, and the
of the left ureter. For a sigmoid nodule of some 4-cm diameter
outcome of ovarian suppression therapy, adnexectomy, and
with more than 50% occlusion of the bowel, a resection anas-
other therapies. For volume we recorded the original volumes
tomosis was performed. A liver lesion was biopsied but re-
vealed fibrosis only. Thorough inspection of the ovariesduring surgery and by ultrasound failed to identify any tumor.
After surgery she received 6 months of gonadotropin-releasinghormone agonists, followed by intermittent administration of
Statistics were performed with the SAS system (SAS
corticosteroids (Fiorenzo De Cicco) for unclear reasons.
Institute, Inc., Cary, NC), using Spearman correlation.
With this treatment she remained symptom free. Because ofpersisting primary infertility, a second-look laparoscopy was
performed 1 year later showing few adhesions, no residualendometriosis, and no ascites. Two years later, the patient is
The age of the women reported in the literature ranged
without medical treatment except intermittent corticosteroids.
from 20 to 50 years with a mean age of 31.9 6 8.8 years
Table 1Literature review of hemorrhagic ascites in endometriosis
A 5 Asian; B 5 black; BSO 5 bilateral salpingo-oophorectomy; DB 5 dark brown; GnRH 5 gonadotropin-releasing hormone; H 5 hemorrhagic; TAH 5
total abdominal hysterectomy; USO 5 unilateral salpingo-oophorectomy; W 5 white.
(Surprisingly, during this 27-year period, the age of
dark brown in 17 and as hemorrhagic in 15 (9 missing). Peri-
the women published increased significantly (p 5 .001). The
toneal fluid was liquid without clots in all cases.
volume of the ascites was high at 4470 6 2625 L. CA 125, if
Race distribution was 21 black, 5 Asian, 1 Hispanic, 3
reported, was elevated. Color of the fluid was described as
white, and 13 not reported (p 5 .001 for black).
Journal of Minimally Invasive Gynecology, Vol 15, No 6, November/December 2008
An endometrioma was described in 25 women with 2 rup-
leaking from the ovary is associated with active endometri-
turing. All other ovaries were reported as normal at inspec-
otic lesions or an open cystic ovarian endometriosis, some
tion. In none of the reports nor in our 2 cases was an
blood staining will occur, resulting by accumulation of red
ovarian tumor or mass identified by preoperative computer
blood cells in dark brown ascites fluid, with some red blood
aided tomography scan (n 5 17) magnetic resonance imag-
cells in all cases when reported. The 50% recurrence rate after
ing (n 5 1), ultrasound (n 5 16), during surgery or by pathol-
unilateral ovariectomy or cystectomy also is compatible with
the concept that the ovary is the source of the fluid.
Surgical treatment consisted of bilateral salpingo-
The pathology clearly is acquired and not congenital.
oophorectomy (with or without hysterectomy) in 14 women
Symptoms start many years after menarche, and are unrelated
followed by ovarian suppression in 2. Unilateral oophorec-
to a pregnancy. No explanation exists as to why the preva-
tomy was performed in 6 followed by medical treatment in
lence is higher in black women than in white, as observed
3; cystectomy in 5 with medical treatment in all 5; and de-
before, nor for the observation that the age of the women in
struction of peritoneal endometriosis and adhesiolysis in 10
the case reports increases over time.
followed by ovarian suppression in 8. In all 14 women treated
In conclusion, the pathophysiology of the hemorrhagic as-
by bilateral salpingo-oophorectomy, ascites disappeared
cites is suggested to be similar to Meigs syndrome (i.e., a local
without recurrence. In all 26 patients receiving ovarian sup-
intraovarian factor). Whether this is related to the endometri-
pression, the ascites disappeared during treatment of up to
osis is unknown, although the deep brown color of the ascites
5 years. After unilateral oophorectomy, ascites redeveloped
suggests a causal relationship. Unfortunately we do not yet
in 2 of 6. After excision of ovarian endometriosis only, the
have any conclusive evidence for this, as we do not know
recurrence rate was 2 of 3 and after destruction of superficial
the pathophysiology of Meigs syndrome. Superficial pelvic
endometriosis is suggested to be a cofactor, contributing tothe ascites and to the dark brown color. Ovulation inductionor in vitro fertilization was not reported yet.
Hemorrhagic ascites together with endometriosis belongs
to the rare but seemingly well-known pathologies, with mas-sive ascites, either dark brown or hemorrhagic, but without
Fiorenzo De Cicco, Universita` Cattolica del Sacro Cuore
clots. The pathophysiology repetitively was suggested to be
Roma, Italy, and G. Melis and A. Angioni, University of
caused by rupture of an endometrioma or by exudation
Cagliari, Italy, are thanked for reviewing the manuscripts.
from widespread pelvic endometriosis. The available evi-
We thank the University of Leuven, Belgium, and the Uni-
dence suggests, however, that both suggestions are either er-
versita` Cattolica, Rome, Italy, for supporting the collabora-
roneous or insufficient. An endometrioma was found in only
tion between both universities in deep endometriosis surgery.
65%. Rupture of an endometrioma is a well-known pathol-ogy, with acute pain, slight fever, and less than 500 mL of
fluid at laparoscopy/laparotomy Very extensive pel-vic superficial endometriosis can be associated with a slight
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