Abraham Tsur1, Antonio Malvasi2, 3 , Ughetta Vergari4 and Howard Carp1
Department of Obstetrics and Gynecology, Sheba Medical Center, Tel Hashomer, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
Department of Obstetrics and Gynecology, Santa Maria Hospital, G.V.M. Care and Research, Bari, Italy
International Translational Medicine and Biomodelling Research Group, Department of Applied Mathematics, Moscow Institute of Physics and Technology (State University), Moscow Region, Russia
Department of Classical Philology and Philosophical Sciences, International Center of Bioethics and Human Rights, University of Salento, Lecce, Italy
Howard Carp (Corresponding author)
MiscarriageAbortionUterine perforationPregnancy complications
Miscarriage, the most common complication of pregnancy, is the loss of a pregnancy before fetal viability (Fig. 2.1). The term therefore includes all pregnancy losses from conception up to 20 weeks in North America and 24 weeks of gestation in Europe (Fig. 2.2). Although 15 % of clinical pregnancies miscarry, up to 50 % of conceptuses may be lost . The causes of miscarriage are numerous, but include the presence of an abnormal embryo which is incompatible with life or a hostile maternal environment which does not support life (Fig. 2.3). The fetal causes include chromosomal aberrations which may account for up to 60 % of miscarriages or lethal structural malformations. However, whatever the cause, there is a final common pathway which includes uterine contractions, placental separation, and expulsion of the uterine contents. Fetal demise may precede expulsion, in a “missed miscarriage”; alternatively contractions may occur in the presence of a live embryo. Expulsion of the embryo and placenta is accompanied by varying degrees of bleeding, which may vary from a few drops of blood to torrential hemorrhage. Expulsion of the contents may be complete or incomplete (with only partial expulsion of the gestational products). If incomplete, intervention may be required such as curettage. Each of the above may have complications which may compromise the mother’s well-being and future fertility. Some of the complications are described in this chapter.
The abortion is the loss of a pregnancy before fetal viability
Prostaglandins are often used to induce abortion after fetal demise to soften or dilate the cervix. BCF, fetal heartbeat stopped
Severe fetal anomalies or chromosomal aberrations may lead to fetal demise presenting as abortion. BCF, fetal heartbeat stopped
2.2 Early Complications
2.2.1 Excessive Blood Loss and Disseminated Intravascular Coagulation
Incomplete miscarriage, with heavy bleeding, should be treated with surgical evacuation promptly. Risks of delayed intervention include excessive blood loss subsequently requiring transfusion of blood products or DIC (disseminated intravascular coagulation). Obstetrical DIC (Fig. 2.4a, b) is relatively rare in first-trimester miscarriages but can occur in midtrimester losses, especially if there are fetal demise and retention in utero for a long period. DIC can follow placental abruption or septic abortion and may lead to severe hemorrhage  and possibly amniotic fluid embolism. Severe DIC can lead to multiple organ failure and even mortality . In extreme cases even hysterectomy may be required. These can be prevented by prompt diagnosis and treatment. The clinical presentation of DIC is acute bleeding combined with the following laboratory changes: decreased platelet count, prothrombin time prolongation, decreased fibrinogen levels, and increased markers of fibrin breakdown such as D-dimer. In order to facilitate early diagnosis and standardize assessment and treatment, several DIC scoring systems have been introduced . Recently Erez et al. have introduced a new scoring system adjusted to pregnancy .
Venous vein thrombosis and Diffuse Intravascular Coagulation may be a consequence of fetal death particularly in the second trimester, as thromboplastin is released into the maternal circulation from the degenerating placenta DIC with hepatic vein thrombosis (a) and fetal death (b)
Management of DIC related to incomplete abortion or septic abortion includes the following four steps:
Tranexamic acid is widely used for the treatment and prevention of obstetrical hemorrhage. However, there is no evidence regarding its safety and efficacy in the scenario of incomplete or septic abortion. There is an ongoing international randomized, double-blind placebo-controlled trial aiming to determine the effect of early administration of tranexamic acid on mortality, hysterectomy, and other complications in women with postpartum hemorrhage (The WOMAN Trial ). The results are eagerly awaited and may have implications for the use of tranexamic acid in other conditions such as septic and incomplete abortions.
Recombinant activated factor VII (rFVIIa) was originally developed for the treatment of hemophilia. Similarly to tranexamic acid, there is lack of high-quality evidence regarding its efficacy and safety in the setting of DIC complicating incomplete or septic abortion. There is concern regarding the possibility of arterial thrombosis. Recent guidelines for the treatment of PPH stated that rFVIIa may be used as an adjunct to other surgical treatments .
220.127.116.11 Role of Oxytocin During Surgical Evacuation of the Uterus
Oxytocin is often used to enhance uterine contraction at the time of curettage. However, a randomized controlled blinded trial comparing the impact of 5 IU (international unit) of oxytocin and no oxytocin on bleeding, pain, and nausea after surgical termination of first-trimester pregnancies found oxytocin injection to confer no significant advantage .
However, in the Sheba Medical Center, we do administer oxytocin (in a dose of 5–10 IU depending on gestational age and size of the fetus) to most women undergoing surgical evacuation of the uterus as the contraction of the myometrium facilitates the procedure by clearly identifying the uterine border with the curette.
2.2.2 Infection and Septic Abortion
Septic abortion (Fig. 2.5) is defined as infection of the products of conception of a provable pregnancy. If not treated promptly, the infection can spread to the uterus and pelvis. Further spread may lead to systemic infection presenting as bacteremia, sepsis, septic shock, and potential failure of distal vital organs. Sepsis can spread rapidly if infected tissue is retained in the uterus . The organisms involved are usually common vaginal bacteria. However clinicians should be alert to potentially lethal infection by bacteria that produce toxins, such as Staphylococcus aureus, that may be resistant to some penicillin: Clostridium perfringens and Clostridium sordellii; group A streptococcus; and also some toxin-producing strains of E. coli [8, 9].
A septic abortion
The treatment of septic abortion includes fluid replacement, culture collection, and antibiotic therapy, followed promptly with curettage in order to evacuate the infected products of conception. A common feature in reported cases of death from septic abortion is delayed treatment .
18.104.22.168 The Role of Prophylactic Antibiotics
The role of antibiotic cover at curettage (Fig. 2.6) has been controversial; supporters of antibiotic cover have argued that antibiotics prevent infection. However, the counterargument is that if an infection occurs under antibiotic cover, it will be resistant to the simple antibiotics and therefore much harder to treat. However, a meta-analysis of 12 randomized trials by Sawaya et al.  reported that prophylactic antibiotics have a significant protective effect in preventing postaborted infections and can prevent up to one half of postaborted infection cases. This effect was found to be significant even in low-risk women. The choice of antibiotic regimen is less evidence based. In Sawaya et al.’s  meta-analysis, both the tetracycline and metronidazole (Fig. 2.7) were found to have significant and comparable protection against upper genital tract infection. An American College of Obstetrics and Gynecology Practice Bulletin (No. 104) states that the choice of doxycycline 100 mg orally a few hours before the procedure followed by 200mg after the procedure is effective and inexpensive .
The metronidazole chemical formulation
In the developed world, death is rarely associated with spontaneous or induced abortion. The incidence is less than 1 per 100,000 procedures in the United States, whether spontaneous or induced . In the recently published data regarding pregnancy-related mortality in the United States between the years 2006–2013 – the pregnancy-related mortality was 16 deaths per 100,000 women. Only 2.7 % of pregnancy-related deaths were attributed to induced or spontaneous abortion . However, worldwide the percentage of maternal death attributed to abortion is higher, and it is estimated that complications of abortion are responsible for 7–14 % of maternal deaths [15, 16]. The lower mortality in the developed world may be due to better prevention of infection, aseptic techniques, and better availability of blood products and antibiotics. Unsafe and illegal abortions (Fig. 2.8) are still taking place in many parts of the world utilizing unsterile instruments, lack of appropriate conditions, and procedures being performed by individuals lacking the necessary skills as defined by the WHO .
The risk of septic abortion using nonsterile instrument
2.3 Complications of Intervention
2.3.1 Uterine Perforation and Pelvic Organ Damage
Uterine perforation has been reported to occur in less than 0.5 % of patients in both first- and second-trimester procedures [18, 19]. The most common site of perforation is the uterine fundus. The uterine perforation can be by hysterometer (Fig. 2.9) or curette (Fig. 2.10) or forceps (Fig. 2.11) or Karman cannula (Fig. 2.12) . An analysis of 67,175 curettage abortions performed at 13 institutions in the United States from 1975 to 1978 showed that if curettage were performed by an attending physician, the risk of uterine perforation was considerably lowered (Fig. 2.13). There are also many possibilities to perforate uterine cavity during a surgical abortion removal, while clinician measures by hysterometer the uterine length. It can be linked to uterine fibroids (Fig. 2.14), malformations, and post-cesarean section scar, with stenotic inner uterine orifice, uterine deep retroversion (Fig. 2.15), adhesions (Fig. 2.16), and the uterine niche (Fig. 2.17).
The figure shows a uterine perforation by hysterometer in a complete abortion during excessive and wrong hysterometry
Uterine fundal perforation by curette
Uterine fundal perforation by forceps, complicated by omental clamping
Uterine fundal perforation by Karman cannula, complicated by bowel clamping
Prior to cervical dilatation or curettage, it is mandatory to carefully measure the uterine length by hysterometry, and to compare it to the curette length, especially in cases of second-trimester abortion
Uterine fundal perforation by hysterometer in incomplete abortion for intramural anterior multiple fibroids
Maneuver to avoid uterine perforation: uterus is clamped and pulled by clinicians and checked by ultrasonography during hysterometry (echo-guided abortion removal)
A fixed uterus for deep and strong adhesions, perforated by hysterometer that penetrates into the bladder
Uterine perforation through the niche by hysterometer
Dilatation of the cervix by laminaria also has a protective effect in preventing perforation, but the trend was not statistically significant (RR, 0.17; 95 % CI, 0.02–1.2) . Darney et al.  have reviewed 15 cases of uterine perforations during second-trimester dilatation and evacuation (D&E). Two thirds of patients suffered concomitant bowel injuries and two patients required hysterectomy. These cases were characterized by errors in estimation of gestational age, failure to use sonography for dating, and inadequate cervical dilatation (Fig. 2.18) . Traditionally, complications of uterine perforation were treated with laparotomy. However, today, with improved expertise in endoscopy, laparoscopy has been reported as a safe and effective option for treating these complications . If perforation occurs prior to completing uterine evacuation, evacuation can be completed transcervically under direct visualization of the perforation site using laparotomy or laparoscopy .
Uterine perforation for inadequate cervical dilatation with Hegar dilator: (a) uterus with a large posterior myoma deforming the uterine cavity, (b) uterus in hyperanteversion, (c) uterus with anterior perforation
22.214.171.124 Failure to Diagnose Uterine Perforation
Some believe that perforation may be more common than diagnosed and that many patients may go undiagnosed without sequela. Perforation should be suspected if the instrument is passed to a greater depth than the measured size of the uterine cavity. If the perforation is not diagnosed, the patient may complain of excessive pain on awakening. There may be bleeding from the perforation site which may present as hemorrhage (Fig. 2.19). However, hemorrhage may not be apparent if bleeding occurs into the abdominal cavity or into the broad ligament in the case of a lateral perforation. Sometimes the perforation could be in the posterior part of the cervix (Fig. 2.20), without passing through the uterine cavity. Therefore, the vital signs should be monitored if perforation is suspected. The question arises as to when further intervention such as laparoscopy is indicated (Fig. 2.21). If fat or other extrauterine tissue is removed, it is our opinion that exploratory laparoscopy is mandatory. Laparoscopy is also indicated if the patient becomes hemodynamically unstable. If perforation is diagnosed prior to completion of curettage, the procedure can be completed either under laparoscopic or ultrasound control (Fig. 2.22). If there are no complications of perforation, the patient can be discharged home after 24–48 h. If there is organ damage (Fig. 2.23), this should be repaired appropriately. In cases of broad ligament hematoma, ultrasound should be used to demarcate the size of the hematoma and subsequent resolution.
Uterine perforation by a curette, suspected since the instrument passed to a greater depth than the measured size of the uterine cavity; it caused uterine bleeding in the Douglas pouch
Uterine perforation could be in the posterior part of the cervix
Laparoscopic extraction of an embryo sac through the omentum attached to anterior uterine body, after uterine perforation
A posterior uterine body perforation by Karman cannula: clinician checks by transabdominal ultrasound the gestational sac and the posterior perforation
Uterine perforation by Karman cannula and omental stripping
Failure to diagnose uterine perforation either during or after the uterine revision, it can lead to further complications (Fig. 2.24). Su et al. described a 31-year-old woman with the ovary incarcerated into the uterine perforation , while Shulman et al. described incarcerated small bowel inside the uterus following uterine perforation  (Fig. 2.25).
Uterine perforation by Karman cannula and bowel clamping with enterobacteria release in the abdominal cavity (high risk of successive peritonitis)
An incarcerated small bowel inside the uterus following uterine perforation
2.3.2 Cervical Lacerations and Future Cervical Incompetence
Although cervical lacerations can occur during the spontaneous expulsion of gestational products at abortion, most lacerations arise during dilatation and curettage (D&C) or dilatation and evacuation (D&E). Lacerations can be due to the traction applied to the cervix with a tenaculum (Fig. 2.26), from trauma during dilatation of the cervix (Fig. 2.27) or from trauma during the curettage itself.
Care should be taken not to traumatise the cervix with excessive dilatation due to the risk of subsequent cervical incompetence. Cervical dilatation can be facilitated with prior preparation with misoprostol or laminaria
A cervical trauma for excessive dilatation of the cervix with Hegar dilator n° 13
Cervical injury can be significantly reduced with the use of osmotic dilators such as Laminaria japonica and Dilapan-S  or cervical softening with misoprostol (Fig. 2.28) .
Cervical dilatation after prostaglandin administration
A large, retrospective study, analyzing 15,438 suction curettage procedures carried out at 12 or less gestational weeks, demonstrated that the use of laminaria had a strong protective effect on cervical injury compared to rigid dilators (RR = 0.19 CI 0.07–0.52), whereas if the operator was a resident rather than an attending physician, the RR was 2.0 (CI 1.3–2.9). It is interesting that the use of general rather than local anesthesia had a detrimental effect on the occurrence of cervical injury (RR = 2.6 CI 1.8–3.9). The use of laminaria, local anesthesia, and performance by experienced physicians showed a 27-fold protective effect .
Bleeding from cervical lacerations can be managed with direct pressure or cautery to the bleeding site and in some cases suturing. An important long-term consequence of cervical injury during dilatation and curettage is cervical incompetence leading to subsequent late miscarriage, premature rupture of the membranes, and preterm birth. It has been shown that women with a history of termination of pregnancy have a significantly greater risk for preterm birth, and the risk increases as the number of terminations of pregnancy increases. However, other mechanisms may contribute to the increase in preterm births in women undergoing termination of pregnancy in addition to cervical injury, such as uterine scarring, that can lead to faulty placental implantation and socioeconomic status .
2.3.3 Cervical Stenosis and Hematometra
Hematometra also known as uterine distension syndrome usually presents immediately or soon after surgical evacuation of the uterus (Fig. 2.29). The classic presentation is pain without vaginal bleeding. The condition is caused by accumulation of blood within the uterus and lack of drainage through the cervix. An ultrasound examination will demonstrate the blood accumulated inside the uterine cavity (Fig. 2.30). The condition can be alleviated by passing a uterine sound through the cervix in order to release the blood. Another alternative is to use a curette (Fig. 2.31), or a pipette, and aspirate the blood. However, pipette aspiration is often painful. The use of methylergonovine maleate given either intramuscularly or orally may assist by contracting the uterus. However, neither aspiration nor uterine stimulants will prevent cervical stenosis. If there is stenosis, hematometra may reoccur at subsequent menstruation. Adequate cervical dilatation usually overcomes the problem of cervical stenosis (Fig. 2.32) and prevents further stenosis.
Hematometra is accumulation of blood in the uterine cavity, causing distension immediately or soon after surgical evacuation of the uterus
Ultrasound image showing blood retained within the uterine cavity
Hematometra can be evacuated by curettage, or by suction applied through a pipelle of small diameter feeding tube. Feeding tube is illustrated
Cervical stenosis at the level of the canal or internal os. Dilatation can be performed by passing a Foley catheter, inflating the balloon, and applying gentle traction
Numerous anesthetic agents can be used for D&C: general, neuraxial (spinal or epidural), or local (paracervical block) which is usually combined with intravenous sedation. In cases of excessive blood loss, neuraxial anesthesia is contraindicated due to the risk of worsening hypotension. General anesthesia is preferred if the patient is emotionally upset or the gestational age is 13 weeks or above . If local anesthesia is used, vasovagal syncope may occur (known as “cervical shock”). Cervical shock is self-limiting and can be treated or prevented with the use of atropine.
The complications of neuraxial anesthesia can be immediate, intermediate, or long term.
Immediate sequela includes high or prolonged blockade, motor blockade, and seizures after unintentional intravenous injection of local anesthetic. Intermediate complications include epidural hematoma and infection such as epidural abscess and meningitis . The long-term neurologic sequela is clearly of most importance but is beyond the scope of this chapter. Grimes et al.  compared the safety of local versus general anesthesia. Local anesthesia was associated with higher rates of febrile and convulsive morbidity, while general anesthesia was associated with higher rates of hemorrhage, uterine perforation, and cervical injury. The authors concluded that both techniques appear to be safe although each is associated with a different spectrum of complications . However, it should be noted that as the rate or abortion-related mortality decreases, the percentage of death related to general anesthesia increases. Using CDC data, it has been shown that the death-to-case rate for abortions at less than or equal to 12 weeks’ gestation associated with general anesthesia was 0.37/100,000 – more than twice the rate with local anesthesia was 0.15/100,000 .
2.4 Late Complications
2.4.1 Pain and Bleeding
Pain and cramps may persist in some women for the first few days or even weeks after miscarriage. Additionally vaginal bleeding may be normal in the first few weeks after miscarriage and is usually heavier and of longer duration after medical treatment with misoprostol than curettage . The clinical challenge is to identify the women that require further investigation. Clearly worsening or heavy bleeding and worsening pain or additional symptoms such as fever should alert the physician to search for the complications described in this chapter such as retained products of conception and endometritis.
2.4.2 Retained Products of Conception (RPOC)
The clinical presentation of retained products of conception may include irregular uterine bleeding, pelvic pain, uterine tenderness, and fever. The ultrasound findings indicative of RPOC are a hyperechoic endometrial thickness combined with abundant low-resistance flow in the myometrium or just beneath the endometrium. Diagnostic confirmation may be necessary depending on the expertise of the ultrasonographer. Repeat curettage, suction evacuation, removal by clamp ring (Fig. 2.33), or hysteroscopic resection can be employed. Hysteroscopic excision is probably the treatment of choice as hysteroscopic excision allows the retained placental products to be excised under direct vision, possibly leading to fewer uterine adhesions and avoidance of incomplete evacuation . Women preferring to avoid surgical intervention can be treated with misoprostol (Fig. 2.34) in order to induce uterine contractions. Complete evacuation rates have been reported to lie between 53 and 87 % . It has been suggested that the progesterone receptor modulator mifepristone should be added to misoprostol in order to enhance the effect. However there is insufficient evidence to draw firm conclusion about the added value of mifepristone . In our clinical experience, the efficacy of misoprostol in leading to evacuation of the uterus decreases as the time from the primary abortion increases.
Removal of retained products of conception in the uterus using a clamp ring
2.4.3 Asherman Syndrome
Asherman originally defined the syndrome bearing his name as intrauterine adhesions accompanied by amenorrhea or infertility . The condition is mainly caused by intrauterine trauma associated with surgical procedures, especially curettage after missed abortion or puerperal curettage (Fig. 2.35) . If excessive pressure is applied at curettage, the stratum basale and even the myometrium may be excised, leaving a raw area, and denudation of the endometrium may adhere. Infection may also have a role in the pathogenesis, but the role of infection is controversial. Sometimes Asherman syndrome was suspected in patient treated by Foley catheter insertion after uterine cavity revision for abortion and massive bleeding (Fig. 2.36a, b).
Uterine cavity revision by Karman curette. Some operators prefer the Karman curette, as it is flexible, and my carry less risk of perforation, than a hard metal instrument
Foley catheter insertion in the uterine cavity after uterine cavity suction (a) and balloon insufflation (b)
Polishuk et al.  found no difference in the occurrence of intrauterine adhesions between patients who developed endometritis (Fig. 2.37) when compared to a control group of women that did not develop infection.
Uterine cavity revision by curette in a patient with puerperal endometritis
Asherman syndrome can be prevented by minimizing the trauma to the uterus, by avoiding postpartum or postabortion, and by repeat curettage for residual placental tissue. Suction curettage is probably much less traumatic than sharp curettage, as the suction curette does not allow excess pressure to be applied. The treatment of choice for removing residual placental tissue is probable hysteroscopic excision . Hysteroscopy allows direct vision of Asherman syndrome (Fig. 2.3a, b) and of residual tissue and shows the plane of demarcation between the placental tissue and endometrium. A diathermy loop can then be used to excise the retained products of conception under direct vision (without using diathermy).
Subsequent pregnancy after Asherman syndrome is at a higher risk for spontaneous abortion, intrauterine growth restriction, preterm delivery, placenta previa or accreta, and even uterine rupture .
2.4.4 Rhesus (Rh) Alloimmunization
Rh-D-negative women who are pregnant with an Rh-D-positive fetus and who are exposed to fetal blood cells are at risk of developing anti-D antibodies. In a subsequent pregnancy, if the fetus is Rh-D positive, maternal antibodies may cross the placenta causing hydrops fetalis and hemolytic disease of the fetus and newborn (HDN). HDN can be associated with severe morbidity and mortality. Alloimmunization can be prevented by administration of anti-D immune globulin within 72 h of suspected maternal exposure to fetal blood cells. The Rh-D antigen has been detected in embryos from 38 days of gestation . Spontaneous abortions are associated with a 1.5 % risk of alloimmunization. This risk rises up to 5 % if a D&C is required . Because the red cell mass of the first-trimester fetus is small, the dose of anti-D administered can be adjusted, and 50 μg (microgram) is adequate for first-trimester abortions. Spontaneous or induced abortion in the second trimester onward requires the standard 300 μg dose .
2.4.5 Recurrent Miscarriage
Recurrent miscarriage is defined in North America as two or more miscarriages, but in Europe as three or more consecutive miscarriages. If the incidence of miscarriage is 15 % of all pregnancies, three losses would be expected to occur in 0.03 % of women. In fact the incidence of three consecutive miscarriages is 1 % , which suggests an underlying recurrent cause rather than a repetition of chance events. Additionally the cause of miscarriage is chromosomal rearrangements in approximately 60–70 % of cases (such as 16 trisomy, triploidy, monosomy X, etc.) . There is at present no known cause of recurrent aneuploidy. However, recurrent aneuploidy is known to exist in approximately 15 % of women with recurrent miscarriage due to fetal aneuploidy [44, 45]. Hence there is little reason to consider recurrent miscarriage as a complication of spontaneous miscarriage.
2.4.6 Psychological Complications
The reaction to miscarriage varies greatly among different couples: some exhibit little or no reaction, whereas others show a significant decline in their coping ability [46, 47]. There may be feelings of emptiness and guilt, increased anxiety, and depressive symptoms [47, 48]. These depressive symptoms can include staying in bed and doing nothing, difficulty in performing daily tasks, and a feeling of a physical illness. One month after miscarriage, approximately half of the women are still depressed, and for some depression may persist up to half a year after the miscarriage .
Many couples experiencing a miscarriage undergo a process of grieving . They mourn the lost child and their unaccomplished parenthood. Unfortunately, these couples do not generally receive social support, particularly if the miscarriage occurs before the couple share the news of the pregnancy. It is crucial to understand that even if the embryo was lost at a very early gestational week, many couples already regard their embryo as a baby, name or nickname him, talk to him, ascribe him with a specific personality, and imagine his future. However, the psychological consequences of pregnancy loss are usually reversible. While psychological treatment is not necessary for all women after miscarriage, an empathetic and respectful attitude of all medical teams is associated with better psychological experience and outcomes . In some couples, however, psychological support may be helpful. Psychological support can take numerous forms including group therapy, which allows couples to share their experience of pregnancy loss; educating couples about the grieving process, so that they understand that grieving is one of the normal coping mechanisms; and reducing anxiety with physical activity, art, meditation yoga, etc., all of which are not specific and are dependent on the patients particular interests and cognitive restructuring (Fig. 2.38).
(a, b) Typical hysteroscopic image of the uterine cavity with Asherman syndrome (a) and other four hysteroscopic images of Asherman syndrome (b)
Text contributed by Abraham Tzur and Howard Carp. Illustrations contributed by Antonio Malvasi and Ughetta Vergari.
Chard T (1991) Frequency of implantation and early pregnancy loss in natural cycles. Baillieres Clin Obstet Gynaecol 5(1):179–189CrossRefPubMed
Berg CJ, Callaghan WM, Syverson C, Henderson Z (2010) Pregnancy-related mortality in the United States, 1998 to 2005. Obstet Gynecol 116(6):1302–1309CrossRefPubMed
Taylor FB, Toh CH, Hoots WK, Wada H, Levi M (2001) (ISTH) SSoDICDotISoTaH. Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation. Thromb Haemost 86(5):1327–1330PubMed
Erez O, Novack L, Beer-Weisel R, Dukler D, Press F, Zlotnik A et al (2014) DIC score in pregnant women--a population based modification of the International Society on Thrombosis and Hemostasis score. PLoS One 9(4):e93240CrossRefPubMedPubMedCentral
Shakur H, Elbourne D, Gülmezoglu M, Alfirevic Z, Ronsmans C, Allen E et al (2010) The WOMAN Trial (World Maternal Antifibrinolytic Trial): tranexamic acid for the treatment of postpartum haemorrhage: an international randomised, double blind placebo controlled trial. Trials 11:40CrossRefPubMedPubMedCentral
Abdul-Kadir R, McLintock C, Ducloy AS, El-Refaey H, England A, Federici AB et al (2014) Evaluation and management of postpartum hemorrhage: consensus from an international expert panel. Transfusion 54(7):1756–1768CrossRefPubMed
Nygaard IH, Valbø A, Heide HC, Kresovic M (2011) Is oxytocin given during surgical termination of first trimester pregnancy useful? A randomized controlled trial. Acta Obstet Gynecol Scand 90(2):174–178CrossRefPubMed
Eschenbach DA (2015) Treating spontaneous and induced septic abortions. Obstet Gynecol 125(5):1042–1048CrossRefPubMed
Finkielman JD, De Feo FD, Heller PG, Afessa B (2004) The clinical course of patients with septic abortion admitted to an intensive care unit. Intensive Care Med 30(6):1097–1102CrossRefPubMed
Stubblefield PG, Grimes DA (1994) Septic abortion. N Engl J Med 331(5):310–314CrossRefPubMed
Sawaya GF, Grady D, Kerlikowske K, Grimes DA (1996) Antibiotics at the time of induced abortion: the case for universal prophylaxis based on a meta-analysis. Obstet Gynecol 87(5 Pt 2):884–890PubMed
Bulletins--Gynecology ACoP (2009) ACOG practice bulletin No, 104: antibiotic prophylaxis for gynecologic procedures. Obstet Gynecol 113(5):1180–1189CrossRef
Zane S, Creanga AA, Berg CJ, Pazol K, Suchdev DB, Jamieson DJ et al (2015) Abortion-Related Mortality in the United States: 1998–2010. Obstet Gynecol 126(2):258–265CrossRefPubMedPubMedCentral
Creanga AA, Berg CJ, Syverson C, Seed K, Bruce FC, Callaghan WM (2015) Pregnancy-related mortality in the United States, 2006–2010. Obstet Gynecol 125(1):5–12CrossRefPubMed
Say L, Chou D, Gemmill A, Tunçalp Ö, Moller AB, Daniels J et al (2014) Global causes of maternal death: a WHO systematic analysis. Lancet Glob Health 2(6):e323–e333CrossRefPubMed
Kassebaum NJ, Bertozzi-Villa A, Coggeshall MS, Shackelford KA, Steiner C, Heuton KR et al (2014) Global, regional, and national levels and causes of maternal mortality during 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 384(9947):980–1004CrossRefPubMedPubMedCentral
Rasch V (2011) Unsafe abortion and postabortion care - an overview. Acta Obstet Gynecol Scand 90(7):692–700CrossRefPubMed
Peterson WF, Berry FN, Grace MR, Gulbranson CL (1983) Second-trimester abortion by dilatation and evacuation: an analysis of 11,747 cases. Obstet Gynecol 62(2):185–190PubMed
Ben-Baruch G, Menczer J, Shalev J, Romem Y, Serr DM (1980) Uterine perforation during curettage: perforation rates and postperforation management. Isr J Med Sci 16(12):821–824PubMed
Grimes DA, Schulz KF, Cates WJ (1984) Prevention of uterine perforation during curettage abortion. JAMA 251(16):2108–2111CrossRefPubMed
Darney PD, Atkinson E, Hirabayashi K (1990) Uterine perforation during second-trimester abortion by cervical dilation and instrumental extraction: a review of 15 cases. Obstet Gynecol 75(3 Pt 1):441–444PubMed
Lawin-O’Brien A, Olowu O, Shahid A, Odejinmi F (2013) Complex organ injuries after mid-trimester termination of pregnancy: pushing boundaries in laparoscopic management. J Minim Invasive Gynecol 20(6):899–902CrossRefPubMed
Chen MJ, York S, Hammond C, Gawron L (2015) Uterine perforation during dilation and evacuation prior to fetal extraction–now what? A case report. J Reprod Med 60(5–6):254–256PubMed
Su S, Tao G, Dong B, Shi L, Dong J (2015) Delayed presentation of uterine perforation with ovary migration after dilatation and curettage. Int J Clin Exp Med 8(4):6311–6314PubMedPubMedCentral
Shulman SG, Bell CL, Hampf FE (2006) Uterine perforation and small bowel incarceration: sonographic and surgical findings. Emerg Radiol 13(1):43–45CrossRefPubMed
Schulz KF, Grimes DA, Cates W (1983) Measures to prevent cervical injury during suction curettage abortion. Lancet 1(8335):1182–1185CrossRefPubMed
Meirik O, My Huong NT, Piaggio G, Bergel E, von Hertzen H (2012) Regulation WRGoPMoF. Complications of first-trimester abortion by vacuum aspiration after cervical preparation with and without misoprostol: a multicentre randomised trial. Lancet 379(9828):1817–1824CrossRefPubMed
Shah PS, Zao J (2009) births KSGoDopL. Induced termination of pregnancy and low birthweight and preterm birth: a systematic review and meta-analyses. BJOG 116(11):1425–1442CrossRefPubMed
Reynolds F. (2014) Neurologic complications of pregnancy and neuraxial anesthesia. In: Chestnut’s obstetric anesthesia: principles and practice [Internet]. Elsevier/Saunders, Philadelphia, PA
Grimes DA, Schulz KF, Cates W, Tyler CW (1979) Local versus general anesthesia: which is safer for performing suction curettage abortions? Am J Obstet Gynecol 135(8):1030–1035CrossRefPubMed
Peterson HB, Grimes DA, Cates W, Rubin GL (1981) Comparative risk of death from induced abortion at less than or equal to 12 weeks’ gestation performed with local versus general anesthesia. Am J Obstet Gynecol 141(7):763–768CrossRefPubMed
Davis AR, Hendlish SK, Westhoff C, Frederick MM, Zhang J, Gilles JM et al (2007) Bleeding patterns after misoprostol vs surgical treatment of early pregnancy failure: results from a randomized trial. Am J Obstet Gynecol 196(1):31.e1–7CrossRef
Hooker AB, Aydin H, Brölmann HA, Huirne JA (2015) Long-term complications and reproductive outcome after the management of retained products of conception: a systematic review. Fertil Steril
Neilson JP, Hickey M, Vazquez J. Medical treatment for early fetal death (less than 24 weeks). Cochrane Database Syst Rev. 2006(3):CD002253.
van den Berg J, Gordon BB, Snijders MP, Vandenbussche FP, Coppus SF (2015) The added value of mifepristone to non-surgical treatment regimens for uterine evacuation in case of early pregnancy failure: a systematic review of the literature. Eur J Obstet Gynecol Reprod Biol 195:18–26CrossRefPubMed
Yu D, Wong YM, Cheong Y, Xia E, Li TC (2008) Asherman syndrome--one century later. Fertil Steril 89(4):759–779CrossRefPubMed
Schenker JG (1996) Etiology of and therapeutic approach to synechia uteri. Eur J Obstet Gynecol Reprod Biol 65(1):109–113CrossRefPubMed
Polishuk WZ, Anteby SO, Weinstein D (1975) Puerperal endometritis and intrauterine adhesions. Int Surg 60(8):418–420PubMed
Goldenberg M, Schiff E, Achiron R, Lipitz S, Mashiach S (1997) Managing residual trophoblastic tissue. Hysteroscopy for directing curettage. J Reprod Med 42(1):26–28PubMed
Bergström H, Nilsson LA, Nilsson L, Ryttinger L (1967) Demonstration of Rh antigens in a 38-day-old fetus. Am J Obstet Gynecol 99(1):130–133PubMed
ACOG practice bulletin. (1999) Prevention of Rh D alloimmunization. Number 4, May 1999 (replaces educational bulletin Number 147, October 1990). Clinical management guidelines for obstetrician-gynecologists. Am Coll Obstetr Gynecol Int J Gynaecol Obstet. 66(1):63–70
Salat-Baroux J (1988) Recurrent spontaneous abortions. Reprod Nutr Dev 28:1555–1568CrossRefPubMed
Stein Z (1981) Early fetal loss. Birth Defects Orig Artic Ser 17:95–99PubMed
Carp H, Guetta E, Dorf H, Soriano D, Barkai G, Schiff E (2006) Embryonic karyotype in recurrent miscarriage with parental karyotypic aberrations. Fertil Steril 85(2):446–450CrossRefPubMed
Sullivan AE, Silver RM, LaCoursiere DY, Porter TF, Branch DW (2004) Recurrent fetal aneuploidy and recurrent miscarriage. Obstet Gynecol 104:784–788CrossRefPubMed
Lee C, Slade P (1996) Miscarriage as a traumatic event: a review of the literature and new implications for intervention. J Psychosom Res 40:235–244CrossRefPubMed
Athey J, Spielvogel AM (2000) Risk factors and interventions for psychological sequelae in women after miscarriage. Prim Care Update Ob Gyns 7:64–69CrossRefPubMed
Nikcevic AV, Tunkel SA, Nicolaides KH (1998) Psychological outcomes following missed abortions and provision of follow-up care. Ultrasound Obstet Gynecol 11:123–128CrossRefPubMed
Legendre G, Gicquel M, Lejeune V, Iraola E, Deffieux X, Séjourné N et al (2014) Psychology and pregnancy loss. J Gynecol Obstet Biol Reprod (Paris) 43(10):908–917CrossRef