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Missed Abortion

Missed abortion is characterized by clinically unapparent embryonic death. Causes most commonly include genetic abnormalities and infections. It is often asymptomatic, but spotting may be reported. The diagnosis is made by ultrasonography, which shows the disappearance of fetal cardiac activity, while the estimation of β-hCG is also helpful. Treatment includes evacuation of remaining tissue, usually with the help of cervical dilators such as misoprostol and mifepristone.


Presentation

Like all other types of miscarriage, the clinical presentation of missed abortion usually involves bleeding [12], with spotting encountered in the majority of cases [13]. However, missed abortion may develop without apparent bleeding and have an asymptomatic course, because unlike the majority of miscarriages, the expulsion of pregnancy tissue does not occur. Pelvic pain, which is commonly mentioned as one of the possible symptoms, has not shown significant association with missed abortion [12].

Absence of Fetal Heart Tones
  • Clinical manifestations of missed abortion include absence of fetal heart tone, discharge from the breasts and diminution of their size, general fatigue, fever, and sometimes skin itch.[ncbi.nlm.nih.gov]
  • They include the absence of fetal heart tones on an ultrasound, vaginal discharge that turns from brown to bright red, and a reduction of pregnancy symptoms .[checkpregnancy.com]
First Trimester Bleeding
  • First-trimester bleeding in a pregnant woman has an extensive differential diagnosis ( Table 2 ) and should be evaluated with a full history and physical examination.[aafp.org]
Meningism
  • A selective tissue biopsy specimen of the cystic lesion demonstrated meningeal tissue such as a meningocele.[ncbi.nlm.nih.gov]

Workup

Physical examination of women with suspected missed abortion reveals the absence of cervical dilation and given the fact that symptoms may not be present in this type of miscarriage, the diagnosis must be established through laboratory tests and imaging studies. β-hCG levels should be measured, usually from urine, which will reveal very low values for appropriate gestational age. Certain studies have established that progesterone levels from serum can be indicators of nonviable pregnancy [14], which indicates that levels of this hormone could be evaluated during the diagnostic workup as well. A definite diagnosis, however, is made by ultrasonography, usually vaginal, which can reveal several key findings [1]. The absence of previously established cardiac activity of the fetus, usually in a fetus that has a crown-rump length > 5 mm and absence of a fetal pole are described as diagnostic criteria.

Treatment

Since the pregnancy tissues remain in the uterus, removal of these products is the mainstay of managing patients with missed abortion. The approach depends on gestational age, with suction curettage being performed for fetuses that were < 12 weeks old, while cervical dilation and evacuation are performed for fetuses between 12 and 23 weeks [1]. Because cervical dilation in women with missed abortion does not occur, the use of pharmacologic agents to facilitate dilation has been recommended [15]. Misoprostol, a synthetic analog of prostaglandin E1, directly stimulates dilation of the cervix and is usually combined with mifepristone, a prostaglandin receptor antagonist which prevents progesterone from binding and exerting its effects. Treatment is effective and does not pose a risk for the patient in terms of future pregnancies.

Prognosis

Missed abortion poses little risk, as it very rarely causes complications. However, the risk of subsequent miscarriage is shown to be increased according to certain studies, with the risk of subsequent miscarriage in twin pregnancies increasing up to ten times [3]. For these reasons, potential causes and factors that led to miscarriage should be determined, if possible.

Etiology

Various causes have been implicated in missed abortion and include:

  • Infections - Viral pathogens, such as cytomegalovirus (CMV), herpesvirus, parvovirus and rubella [1].
  • Genetic abnormalities - Cytogenetic analysis has shown that karyotypic anomalies are frequent in missed abortions, with isolated studies reported that up to 75% of cases had chromosomal defects [5].
  • Idiopathic - In about 60% of missed abortions, the cause is not determined, which implies other factors may be responsible [2].

Various conditions, including hereditary thrombophilias, trauma, and autoimmune diseases have also been implicated as potential causes [1].

Epidemiology

Overall incidence rates indicate that about 10-20% of all pregnancies end in miscarriage, with the majority occurring during early pregnancy (up to 12 weeks). When it comes to missed abortion, epidemiological surveys established a prevalence rate of about 2%, while the rate of this type of miscarriage was almost double among twin pregnancies [3]. Various risk factors have been established, such as age extremes (more commonly > 35 years), prior miscarriage, prolonged exposure to stress, abnormalities in uterine anatomy (presence of adhesions or tumors) and use of substances like cigarettes, alcohol, and certain drugs [6]. Lower progesterone levels prior to miscarriage, low body mass index but also obesity have shown to be significant risk factors as well [7] [8].

Sex distribution
Age distribution

Pathophysiology

Various factors have been incorporated into the pathogenesis model of spontaneous abortion, including genetic, endocrine, environmental and embryologic. One of the theories includes an increased inflammatory reaction involving the Th1 subset of CD4+ T-helper cells [9], as well as involvement of natural killer (NK) cells and various other cytokines during embryo implantation, which illustrates that immune-mediated mechanisms are thought to play a significant role [10]. Numerous morphologic abnormalities have been observed in women where the pregnancy was terminated as a missed abortion, which showed significant karyotypic changes, as well as numerous mutations [9], suggesting that genetics are important factors in the pathogenesis of missed abortion. In addition, the process of differentiation of endometrial stromal cells into decidual cells is hypothesized to be impaired in women who experience one or more miscarriages. Under physiological circumstances, decidual cells are pivotal during the process of implantation and provide the growing embryo nutritional support that will eventually aid in the formation of the placenta [11]. They also perform the function of eliminating other "flawed" embryos that may potentially implant, thus performing the process of selection. If endometrial cells do not differentiate properly into decidual cells, the entire process may be compromised. Embryos that would otherwise be destroyed can attach, placental development is not adequate and eventually, the embryo is not able to grow further, leading to miscarriage.

Prevention

To reduce the risk of miscarriage, in general, attempts can be made through several strategies. Cessation or reduced exposure to cigarettes and alcohol, as well as maintaining proper dietary habits are vital, while genetic counseling could be beneficial for women with recurrent miscarriages. In fact, it is established that supportive care shows benefit in women with recurrent miscarriages [16]. In terms of reducing the risk of missed abortion once pregnancy has started, regular follow-ups and ensuring good general health is key.

Summary

Missed abortion is a type of miscarriage which implies undetected embryonic death without its expulsion before the 20th week of gestation [1]. Like any form of miscarriage, it may be caused by diverse factors, including infections such as cytomegalovirus, parvovirus, and herpesvirus, as well as genetic abnormalities including chromosomal aberrations and various mutations [1]. However, the causes of more than 60% of miscarriages remain undisclosed [2]. Overall epidemiological data indicate that between 10-20% of all pregnancies end in spontaneous abortion, while missed abortion is established to occur in around 2%, with numbers almost doubling in twin pregnancies [3]. Most important risk factors include advanced age, uterine abnormalities and previous history of miscarriage. Environmental factors, such as cigarette smoking and drug abuse are also established as important risk factors. The pathogenesis of missed abortion is incompletely understood, but it is thought that various immune mechanisms contribute to inflammatory and thrombotic events, principally the CD4+ T-helper cells and the Th1 subset that secretes interferon gamma (IFN-γ). Additionally, the process of differentiation of endometrial cells into specialized decidual cells, which should provide nutritional support during the process of implantation and further embryonic growth, is shown to be impaired. A substantial number of missed abortions were shown to have karyotypic abnormalities, which indicates that genetic factors are also important constituents of the pathogenesis model. Clinical presentation of patients with missed abortion may not include any symptoms, but in most cases, vaginal bleeding or spotting is reported. To make the diagnosis, ultrasonography is the optimal method and can show the disappearance of fetal cardiac activity, while levels of beta-human chorionic gonadotropin (β-hCG) are also measured [4]. Treatment principles include evacuation of fetal content, which is recommended early on. Various principles exist depending on which stage miscarriage occurred, while the use of cervical dilators such as misoprostol to reduce complications from these procedures is frequently used. The prognosis is good, very few complications from this type of abortion may occur, but women who experience one missed abortion are at a substantially higher risk for developing recurrent miscarriages.

Patient Information

Missed abortion is a type of miscarriage in which obvious signs or symptoms may not appear, and thus the death of the fetus may be "missed". Like with all types of abortion, it may occur due to genetic abnormalities, infections (most likely viral) and a plethora of diseases that have shown to interfere with normal fetal development. It is estimated that about 2% of pregnancies will end as missed abortions. Several risk factors have been determined and include extremes of age (below 25, but more commonly over 35 years), cigarette smoking, alcohol and drug abuse and previous miscarriages. Although the exact cause and mechanism of abortion remain unclear, it is hypothesized that the process of embryonic binding to the uterus (implantation) is impaired, which leads to insufficient nutritional support of the fetus, prevention of "natural selection" of viable embryos and subsequent fetal death. Certain components of the immune system are also targets of research since one of the main theories includes increased inflammation and blood vessel activity due to overactivation of these cells, but the exact mechanism remains unclear. Women with missed abortion may report bleeding during pregnancy, but bleeding may not occur and no other symptoms may be present. Moreover, physical examination will reveal a normal diameter of the cervix, which differs from other types of abortion in which cervical dilation is observed. To make the definite diagnosis, levels of beta-human chorionic gonadotropin (β-hCG) should be measured and levels will not fit the appropriate gestational age. Ultrasound is the imaging technique of choice to confirm missed abortion, which will reveal the absence of normal cardiac function of the fetus that was determined on prior examinations. Once the diagnosis is made, treatment is based on the removal of the remaining products in the uterus, usually with the aid of drugs that dilate the cervix. Misoprostol and mifepristone are used with good efficacy. This condition has a good prognosis, but some studies have established an increased risk of recurrent miscarriage. For these reasons, all factors which can be influenced upon should be handled, such as cigarette smoking and alcohol consumption and reduction of all possible risk factors.

References

Article

  1. Porter RS, Kaplan JL. Merck Manual of Diagnosis and Therapy. 19th Edition. Merck Sharp & Dohme Corp. Whitehouse Station, N.J; 2011.
  2. Kwak-Kim JY, Chung-Bang HS, Ng SC, et al. Increased T helper 1 cytokine responses by circulating T cells are present in women with recurrent pregnancy losses, and infertile women with multiple implantation failure after IVF. Hum Reprod. 2003;18:767-773.
  3. Sebire NJ, Thornton S, Hughes K, Snijders RJ, Nicolaides KH. The prevalence and consequences of missed abortion in twin pregnancies at 10 to 14 weeks of gestation. Br J Obstet Gynaecol. 1997;07:847–848.
  4. Boue A, Boue J. Cytogenetics of pregnancy wastage. Adv Hum Genet. 1985;14:1–57.
  5. Philipp T, Philipp K, Reiner A, Beer F, Kalousek DK. Embryoscopic and cytogenetic analysis of 233 missed abortions: factors involved in the pathogenesis of developmental defects of early failed pregnancies. Hum Reprod. 2003;18(8):1724-1732.
  6. Maconochie N, Doyle P, Prior S, Simmons R. Risk factors for first trimester miscarriage--results from a UK-population-based case-control study. BJOG. 2007;114(2):170-186.
  7. Arck PC, Rucke M, Rose M, et al. Early risk factors for miscarriage: a prospective cohort study in pregnant women. Reprod Biomed Online. 2008;17(1):101-113.
  8. Jauniaux E, Farquharson RG, Christiansen OB, Exalto N. Evidence-based guidelines for the investigation and medical treatment of recurrent miscarriage. Hum Reprod 2006;21:2216-2222.
  9. Calleja-Agius J, Jauniaux E, Pizzey AR, Muttukrishna S. Investigation of systemic inflammatory response in first trimester pregnancy failure. Hum Reprod. 2012;27(2):349-357.
  10. King K, Smith S, Chapman M, et al. Detailed analysis of peripheral blood natural killer (NK) cells in women with recurrent miscarriage. Hum Reprod. 2010;25:52-58.
  11. Teklenburg G, Salker M, Heijnen C, et al. The molecular basis of recurrent pregnancy loss: impaired natural embryo selection. Mol Hum Reprod. 2010;16:886-895.
  12. Gracia CR, Sammel MD, Chittams J, Hummel AC, Shaunik A, Barnhart KT. Risk factors for spontaneous abortion in early symptomatic first-trimester pregnancies. Obstet Gynecol. 2005;106(5 Pt 1):993-999.
  13. Baszak E, Sikorski R, Milart P, Wójcik D. Clinical features of missed abortion. [Article in Polish] Ginekol Pol. 2001;72(12):1069-1072.
  14. Verhaegen J, Gallos ID, van Mello NM, et al. Accuracy of single progesterone test to predict early pregnancy outcome in women with pain or bleeding: meta-analysis of cohort studies. BMJ. 2012;345:e6077.
  15. Grønlund A, Grønlund L, Clevin L, Andersen B, Palmgren N, Lidegaard Ø. Management of missed abortion: comparison of medical treatment with either mifepristone + misoprostol or misoprostol alone with surgical evacuation. A multi-center trial in Copenhagen county, Denmark. Acta Obstet Gynecol Scand. 2002;81(11):1060-1065.
  16. Clifford K, Rai R, Regan L. Future pregnancy outcome in unexplained recurrent first trimester miscarriage. Hum Reprod. 1997;12(2):387-389.

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Last updated: 2018-06-22 09:04