Romanian Journal of Morphology and Embryology 2009, 50(4):657–662

OORRIIGGIINNAALL PPAAPPEERR

Utero-adnexal damage in septic abortion. Histopathological study on 91 cases M. BIRIŞ1), MIHAELA MOLDOVAN2), D. PĂSCUŢ1), A. MOTOC1)

1)2nd Department of Obstetrics–Gynecology, “Victor Babeş” University of Medicine and Pharmacy, Timisoara

2)Pathology Laboratory, “Dr. D. Popescu” Clinical Hospital, Timisoara

Abstract Septic abortion represents the main causes of abortion-induced maternal death. Hysterectomy may represent a beneficial therapeutic solution for septic abortion, nevertheless with irreversible effects on a woman’s reproductive condition. The study analyzes the anatomopathological damage found in ninety-one patients hospitalized for septic abortion. The patients were admitted to the “Dr. D. Popescu” Clinical Hospital, Timisoara, between 1980–1989 and 1999–2008; hysterectomy was performed in all the cases to eliminate uterine sepsis responsible for the emerging complications. Keywords: septic abortion, acute endometritis, uterine necrosis.

Introduction

Septic abortion is an abortion associated with fever, endometritis and parametritis [1–3], which remains one of the most life-threatening disorders for women all over the world [4–6]. The infection gradually involves the structure of the ovum (chorioamniotitis) and the endometrium (endometritis), subsequently spreading to the lymph and/or blood flow, or becoming generalized [7–9].

WHO defines unsafe abortion as “a procedure for terminating unwanted pregnancy either by persons lacking the necessary skills or in an environment lacking minimal medical standards or both” [10].

Septic abortion is in most cases the consequence of unsafe abortion, representing the main cause of maternal death and morbidity in pregnancy termination [3].

WHO estimates 20 million unsafe abortions in 2003, 98% of which occurring in developed countries with restrictive laws on abortion. There are 76 000 deaths/ year caused by septic abortions [11] (Table 1).

The pro-birth policy, enforced in Romania during 1966–1989, by severely restricting abortion and contra-ception, resulted in approximately 10 000 maternal deaths and the impaired fertility of about 20% of the women of reproductive age [12].

Septic abortion, once the main cause of maternal death, has nowadays become less common, mostly due to permissive legislation. Still, any abortion may be complicated by endometritis that can subsequently develop into metritis, parametritis and peritonitis [13].

During 1980–1989, when abortion was practically prohibited in Romania, the incidence of septic abortion in the “Dr. D. Popescu” Clinical Hospital, Timişoara, was 9.59 cases in 100 births, i.e. 22.18% of overall incomplete abortions, 90 women requiring hysterectomy [14]. Following the liberalization of abortion (December

1989), these figures have progressively diminished, reaching 1.35 cases in 100 births, i.e. 9.93% of overall incomplete abortions, during 1999–2008, with a single hysterectomy necessary to eliminate sepsis (Table 2).

Table 1 – WHO estimates on the incidence and mortality induced by unsafe abortion in 2003

Area

Incidence of unsafe

abortion in 1000

women, aged 15–44

Incidence of unsafe

abortion in 100 births

Mortality induced by

unsafe abortion in 100 000 live

births Developed countries 16 16 60 Eastern Europe 5 13 2 Western Europe * * * Northern Europe 0.1 0.1 * Southern Europe 3 7 1 North America * * * South America 33 38 20 *Insignificant incidence.

Table 2 – The incidence of septic abortion and of abortion-induced maternal death in the “Dr. D. Popescu” Clinical Hospital, Timişoara (complications that occurred following legal abortion have not been taken into account)

1980–1989 1999–2008 Total number of births 49 200 32 786 Incomplete abortions/100 births 43.23 13.57 Septic abortions/100 births 9.59 1.35 Septic abortions/100 incomplete abortions 22.18 9.93

Abortion-induced maternal deaths/100 000 live births 200 0

The highest incidence of septic abortion can be found in single women, aged between 15–30-year-old (Table 3).

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Table 3 – Incidence of septic abortion in the “Dr. D. Popescu” Clinical Hospital, Timişoara, per age groups and marital status, during 1980–1989

Age group [years] Married [%] Single [%] 15–20 5.7 25.7 21–30 58.3 43.4 31–35 21.8 18.6 36–40 10.9 8.8 41–45 3.3 3.5

According to the area of spreading of the infection, septic abortion can be classified in three stages:

▪ stage I: infection is limited to the endometrium and uterine contents;

▪ stage II: infection exceeds the endometrium and pervades the uterine wall (myometrium), the adnexes, the parametrium and broad ligaments;

▪ stage III: infections spreads to the lesser pelvis or to the entire peritoneal cavity (pelviperitonitis or generalized peritonitis) [15].

The aim of the study is to assess utero-adnexal damage and to establish clinical correlations in septic abortions.

In the “Dr. D. Popescu” Clinical Hospital, Timişoara, during 1980–1989, when abortion was banned in Romania, 31% of the septic abortions had a severe outcome. The most common loco-regional complications were: diffuse peritonitis (36.8%), pelvic abscesses (24.6%), uterine necrosis (17.8%), pelviperitonitis (6.8%), and metritis (3.4%). The most common general complications were: septic shock (45.8%), organ failure (kidneys, liver, lungs) (19.8%), severe anemia (19.4%), and coagulopathy (13.3%). There were 98 deaths, 6.7% of the overall septic abortions with severe outcome, 200 cases/100 000 live births.

Material and Methods

This twenty-year retrospective study analyzes the histological specimens from 91 hysterectomized patients with septic abortions during 1980–1989 and from a single patient during 1999–2008. The specimens were fixed in 10% buffered neutral paraffin-embedded forma-lin, and the slides were stained with Hematoxylin–Eosin and regular Periodic Acid Schiff.

The study assessed the incidence of the following disorders:

▪ acute cervicitis, defined by edema, hyperemia, polymorphonuclear neutrophil exudate in the mucosa and subjacent tissues, presence of microabscesses in the glands and in the superficial layers of the exocervical squamous epithelium;

▪ chronic cervicitis, defined by diffuse or nodular lymphocyte, plasmocyte or histiocyte inflammatory infiltration – follicular cervicitis [16, 17];

▪ acute endometritis, characterized by diffuse suppuration with predominant necrosis, sometimes associated with syncytial endomyometritis;

▪ syncytial endomyometritis, defined by syncitio-trophoblastic transformation of muscle fibers, lympho-plasmocyte and granulocyte inflammatory infiltration which dissociates the myometrium, hypertrophied muscle fibers [18–21];

▪ acute metritis, diagnosed by the presence of massive granulocyte inflammatory infiltration which dissociates muscle fibers, vascular ectasia, vascular thrombosis, limited areas of syncitiotrophoblastic transformation of myometrial fibers, interstitial edema [22–24];

▪ uterine necrosis, diagnosed by the presence of vascular thrombosis, hemorrhagic infiltration with tissue disorganization, cell necrosis, edema and dilaceration of muscle fibers with the impossibility of discerning the structure [25];

▪ purulent salpingitis, defined by edematous, hyperemic mucosa with leukocyte infiltration and extensive epithelial desquamation, the surface of mucosa covered with purulent exudation;

▪ pyosalpinx, characterized by purulent exudation distending the tubal lumen; massive leukocyte infiltration in the mucosa with extensive suppurative inflammatory necrosis pervading the entire thickness of the tubal wall;

▪ tubo-ovarian abscess, defined by massive leukocyte and hemorrhagic infiltration, thrombosis with septic necrobiosis and structural disorganization with inflammatory infiltration [16].

Results

Table 4 summarizes the results obtained in the study group (n=91).

Table 4 – Incidence of different types of anatomo-pathological damages

Anatomopathological damage

Incidence in the study group (n=91)

Acute cervicitis 27 (29.67%) Chronic cervicitis 61 (67.03%) Acute endometritis 91 (100%) Syncytial endometritis 23 (25.27%) Acute metritis 91 (100%) Uterine necrosis 47 (51.64%) Purulent salpingitis 3 (3.29%) Pyosalpinx 23 (25.27%) Tubo-ovarian abscess 15 (16.48%)

Thirty-four patients died despite having been hysterectomized. Death occurred because of septic shock, coagulopathy or multi-system failure. In most patients, death was correlated with uterine necrosis (Table 5).

Table 5 – Incidence of the most significant uterine damage in the deceased patients

Anatomopathological damage

Incidence in the deceased patients (n=34)

Endometritis + metritis 7 (20.58%) Endometritis + metritis + uterine necrosis 27 (79.42%)

Chronic cervicitis (Figure 1) may be considered unrelated disorders, consecutive to various vaginitis, nonetheless acute cervicitis with intraepithelial abscesses are the result of the direct action of pathogenic agents or of the spreading of the inflammatory process from septic endometritis into the blood flow.

Utero-adnexal damage in septic abortion. Histopathological study on 91 cases

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Acute endometritis is a constant characteristic in septic abortion, representing the starting point of uterine infection (Figure 2). Syncytial endometritis may some-times be associated with acute endometritis (25.27% of

the cases) (Figures 3 and 4). Acute metritis was present in all the cases, indicating that the staging of the abortion has been exceeded and confirming the necessity for hysterectomy (Figures 5 and 6).

Figure 1 – Chronic cervicitis: dilated hyperplastic glands with cysts containing seropurulent exudation; area of pavement cell metaplasia of the glandular cylindrical epithelium (HE stain, ob. ×10).

Figure 2 – Decidual plates with massive granulocyte inflammatory infiltration and suppurative inflamma-tory necrosis, decidual cells with necrobiotic alterations (HE stain, ob. ×40).

Figure 3 – Syncytial endometritis associated with extensive diffuse suppurative and hemorrhagic necrosis with irreversible loss of tissular architecture; inflammatory necrosis of vascular walls; deciduali-zation and fibrinoid thrombosis of arteriolar walls (HE stain, ob. ×20).

Figure 4 – Syncytial endometritis associated with extensive hemorrhagic necrosis; scyntiotrophoblastic transformation of muscle fibers (HE stain, ob. ×20).

Figure 5 – Syncytial metritis. Ischemic necrosis (HE stain, ob. ×20).

Figure 6 – Myometrium with extensive areas of suppu-rative inflammatory necrosis with microabscesses; massive granulocyte inflammatory infiltration; edema (HE stain, ob. ×20).

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The most severe post-abortion damage (mortality 79.42%) was uterine necrosis. The disorder has a wide-ranging macroscopical picture, from localized necrosis (21 cases) in various regions of the uterine body (most commonly in the right cornual area) or in the isthmus, to generalized uterine necrosis (26 cases), sometimes extended to the lumbo-ovarian pedicles, with utero-adnexal infarction (13 cases; 27.7%), and even to the extragenital tissue: peritoneum, mesentery (three cases), abdominal subcutaneous cell tissue (four cases). In most

cases, the uterus was enlarged, flaccid, purplish all over or only in some areas which alternated with the livid surface yielding a marble-skin aspect, while the adnexes had an edematous and bruised aspect. Microscopically, uterine necrosis is characterized by vascular thrombosis, hemorrhagic infiltration with tissue disorganization, cell necrosis, edema and microfibril dilaceration which made structure identification impossible (Figure 7).

In 58 cases, the damage had also spread to the adne-xes, thus necessitating adnexectomy (Figures 8–10).

Figure 7 – Myometrium with severe diffuse suppu-rative inflammatory necrotic damage; fibrinoid necro-sis; inflammatory disorganization of vascular system; lumen thrombosis and hyalinisation of vascular wall (HE stain, ob. ×20).

Figure 8 – Purulent acute salpingitis: the tubal mucosa has edema, hyperemia, leukocyte infiltration; extensive epithelial desquamation; purulent exudation in the lumen; thickened mucosal junctions (HE stain, ob. ×20).

Figure 9 – Ovary: extensive hemorrhagic necrosis (HE stain, ob. ×20).

Figure 10 – Ovarian abscess occurring on a corpus luteum (HE stain, ob. ×20).

Discussion

The present study, probably one of the most comprehensive ones in Romanian literature, manages to demonstrate the severity of uterine necrosis, the latter being present in 27 (79.42%) of the 34 women that died following hysterectomy.

Achim V et al. conducted an anatomopathological study on a much smaller group consisting of 30 women with septic abortion, who had undergone total hysterectomy with or without adnexectomy, and found the following uterine disorders [26]:

Macroscopic damage Macroscopic damage:

(a) endocavitary: necrosed chorial villosity, hemo-rrhagic or about to emerge; endocavitary hemorrhagic ulcer aspect; purplish color of isthmic and cervical mucosa.

(b) myometrial: pale, wilted color; dilated vessels filled with stasis liquid, thrombosed vessels or, on the contrary, vessels oozing with bright-red unclotted blood; diminished consistence, sometimes brittleness; purplish, necrotic areas pervading the depth of the wall to various degrees, predominantly in the isthmus and cervix.

(c) serous: purplish areas of the fundus or surround-ding the isthmus; false membranes on the perimeter surface.

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Microscopic damage Microscopic damage: decidua with dystrophic

processes, of necrobiosis, necrosis and granulocyte infiltration; syncytial endomyometritis; endocavitary hemorrhagic necrosis associated with extensive ulceration of the decidua, and involving variable depths of the subjacent myometrial layer; polymorphonuclear leukocyte infiltration delimiting the necrotic areas; myometrium with variable degrees of edematous dystrophy, poor and dispersed interstitial and perivascular lympho-plasmocytic infiltration, blood stasis and vascular thrombosis; location predominantly in the cervix and isthmus of blood stasis, vascular thrombosis and hemorrhagic necrosis.

Alessandrescu D et al. analyzed the data obtained from the anatomopathological exam in 32 pregnant women (pregnancies between 2nd and 4th month) who died from post-abortion septic shock, and bacterial cultures in the uterine exudate showed mixed flora, coli and perfringens [27].

Inflammatory disorders were found mainly in the uterus, the entryway for germs (25 cases). These disorders were represented by endometritis with predominant necrosis, sometimes associated with interstitial endometritis. Uterine necrosis was found in five cases, associated with massive edema, dilaceration of muscle fibers, necrosis and thrombi in several vessels. Septic foci in other organs (lung, kidney) were found in eight cases, characterized by predominant alterative damage and necrosis, the leukocyte reactive component being extremely weak.

The extension of the uterine septic process has been proved by the presence of vasculo-circulatory and dystrophic damage in parenchymal organs.

In the uterus, hemorrhage developed in the form of blood pools, mainly located in the depth of the cervical wall, and in a few cases, in the uterine body. The following disorders were found in the liver: the Diesse’ spaces and the connective tissue of the portal spaces were flooded with blood; discrete dystrophic cell alterations; these disorders developed into necrosis in patients where the damage persisted over a longer period of time (>5 days). In the lungs, interstitial hemorrhage was associated with massive interstitial and alveolar edema. These alterations gave an aspect of “heavy and damp” lung, common in every type of shock. The suprarenal glands were the sites of focal or diffuse hemorrhages. The kidneys presented: ischemic necrosis of the distal and proximal duct, and four patients had total and bilateral necrosis of the renal cortex together with bilateral suprarenal necrosis.

Our observations on the development of inflamma-tory damage, and mainly of the vasculo-circulatory damage, have proven in most cases that the damage begins in the uterus and subsequently spreads to several viscera, becoming generalized.

Conclusions

The most significant damage in septic abortion was endometritis, metritis and uterine necrosis. The occu-rrence of metritis requires hysterectomy, if possible

before septic shock sets in. It is difficult to foresee how long it takes the condition to worsen. The aggravation of uterine damage, indicated by uterine necrosis is fatal in most cases, even after the removal of the septic focus. In our study, 79.42% of the deceased patients had uterine necrosis.

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Corresponding author Marius Biriş, Teaching Assistant, MD, PhD candidate, 2nd Department of Obstetrics–Gynecology, Faculty of Medicine, “Victor Babeş” University of Medicine and Pharmacy, Timişoara, 2nd Clinic of Obstetrics–Gynecology, “Dr. D. Popescu” Clinical Hospital, 22–24 16 Decembrie 1989 Avenue, 300172 Timişoara, Romania; Phone +40744–212 410, e-mail: marius308@yahoo.com Received: September 15th, 2009

Accepted: November 15th, 2009