Habitual abortion
Encyclopedia
Habitual abortion, recurrent miscarriage or recurrent pregnancy loss (RPL) is the occurrence of three or more pregnancies
that end in miscarriage
of the fetus
, usually before 20 weeks of gestation
. RPL affects about 0.34% of women who conceive.
is considered to cause about 15% of recurrent miscarriages. The most common abnormality is a uterine septum
, a partition of the uterine cavity. The diagnosis is made by MRI or a combined laparoscopy hysteroscopy of the uterus. Also uterine leiomyoma
ta could result in pregnancy loss.
can become a recurrent problem. Such cervical incompetence
leads to premature pregnancy loss resulting in miscarriages or preterm deliveries.
or Robertsonian translocation
in one of the partners leads to unviable fetuses that are aborted spontaneously. This explains why a karyogram is often performed in both partners if a woman has experienced repeated abortions.
About 3% of the time a chromosomal problem of one or both partners can lead to recurrent pregnancy loss. Although patients with such a chromosomal problem are more likely to miscarry, they may also deliver normal or abnormal babies.
may be a cause of a random spontaneous as well as recurrent pregnancy loss. Aneuploidy is more common with advanced reproductive age reflecting decreased germ cell
quality.
are at increased risk for pregnancy losses. Unrecognized or poorly treated diabetes mellitus
leads to increased miscarriages. Women with polycystic ovary syndrome
also have higher loss rates possibly related to hyperinsulinemia or excess androgens. Inadequate production of progesterone
in the luteal phase may set the stage for RPL (see below).
(propensity for blood clots
). The most common problem is the factor V Leiden
and prothrombin G20210A mutation
. Some preliminary studies suggest that anticoagulant
medication may improve the chances of carrying pregnancy to term but these studies need to be confirmed before they are adopted in clinical practice. Note that many women with thrombophilia go through one or more pregnancies with no difficulties, while others may have pregnancy complications. Thrombophilia may explain up to 15% of recurrent miscarriages.
is a generally accepted cause of recurrent pregnancy loss. High levels of antiphospholipid antibodies may account for 3%-15% of recurrent miscarriages. In these cases, pregnancy outcomes are improved by the use of aspirin or heparin.
are associated with an increased risk of recurrent miscarriage with an odds ratio
of 2.3 with a 95% confidence interval
of 1.5–3.5.
s in the uterus
. It is poorly understood whether these cells actually inhibit the formation of a placenta
, and it has been noted that they might be essential for this process. A 2004 paper (Moffett et al.) warned that determination of NK cells in peripheral blood does not predict uterine NK cell numbers, because they are a different class of lymphocyte
s, and state that immunosuppressive
treatments are not warranted.
genes would be associated with increased pregnancy loss have not been confirmed.
are prone to higher risk of repeated miscarriages. Such miscarriages are due to decreased egg quality .
is produced by the corpus luteum
to maintain the early pregnancy. Assessment of this situation was traditionally carried out by an endometrial biopsy
, however recent studies have not confirmed that such assessment is valid. Studies about the value of progesterone supplementation remain deficient, however, such supplementation is commonly carried out on an empirical basis.
, alcohol
, and drugs
.
, and certain viral infections (rubella
, herpes simplex
, measles
, cytomegalo virus, coxsackie
virus). However, there are no confirmed studies to suggest that specific infections will lead to recurrent pregnancy loss in humans. Malaria, syphilis and brucellosis can also cause recurrent abortion.
In non-pregnant patients who are evaluated for RPL the following tests are usually performed.
Parental chromosome testing (karyogram) is generally recommended after 2 or 3 pregnancy losses. Blood test
s for thrombophilia
, ovarian function, thyroid
function and diabetes are performed.
may be able to identify embryos with a reduced risk of another pregnancy loss which then would be transferred
. Close surveillance during pregnancy is generally recommended for pregnant patients with a history of recurrent pregnancy loss.
Even with appropriate and correct treatment another pregnancy loss may occur as each pregnancy develops its own risks and problems.
However, there is currently no drug that has evidence of preventing recurrent pregnancy loss by boosting maternal immune tolerance; aspirin has no effect in this case.
Pregnancy
Pregnancy refers to the fertilization and development of one or more offspring, known as a fetus or embryo, in a woman's uterus. In a pregnancy, there can be multiple gestations, as in the case of twins or triplets...
that end in miscarriage
Miscarriage
Miscarriage or spontaneous abortion is the spontaneous end of a pregnancy at a stage where the embryo or fetus is incapable of surviving independently, generally defined in humans at prior to 20 weeks of gestation...
of the fetus
Fetus
A fetus is a developing mammal or other viviparous vertebrate after the embryonic stage and before birth.In humans, the fetal stage of prenatal development starts at the beginning of the 11th week in gestational age, which is the 9th week after fertilization.-Etymology and spelling variations:The...
, usually before 20 weeks of gestation
Gestation
Gestation is the carrying of an embryo or fetus inside a female viviparous animal. Mammals during pregnancy can have one or more gestations at the same time ....
. RPL affects about 0.34% of women who conceive.
Epidemiology
The majority (85%) of women who have had two miscarriages will conceive and carry normally afterwards, so statistically the occurrence of three abortions at 0.34% is regarded as "habitual".Causes
There are various causes for habitual abortions, and some are treatable. Some couples never have a cause identified, often after extensive investigations.Uterine conditions
An uterine malformationUterine malformation
A uterine malformation is a type of female genital malformation resulting from an abnormal development of the Müllerian duct during embryogenesis...
is considered to cause about 15% of recurrent miscarriages. The most common abnormality is a uterine septum
Uterine septum
A uterine septum is a form of a congenital malformation where the uterine cavity is partitioned by a longitudinal septum; the outside of the uterus has a normal typical shape...
, a partition of the uterine cavity. The diagnosis is made by MRI or a combined laparoscopy hysteroscopy of the uterus. Also uterine leiomyoma
Leiomyoma
A leiomyoma is a benign smooth muscle neoplasm that is not premalignant. They can occur in any organ, but the most common forms occur in the uterus, small bowel and the esophagus.- Etymology:* Greek:** λεῖος leios "smooth"...
ta could result in pregnancy loss.
Cervical conditions
In the second trimester a weak cervixCervix
The cervix is the lower, narrow portion of the uterus where it joins with the top end of the vagina. It is cylindrical or conical in shape and protrudes through the upper anterior vaginal wall...
can become a recurrent problem. Such cervical incompetence
Cervical incompetence
Cervical incompetence is a medical condition in which a pregnant woman's cervix begins to dilate and efface before her pregnancy has reached term. Internal os opening more than 1 cm is abnormal and cervical length less than 2 cm is considered diagnostic...
leads to premature pregnancy loss resulting in miscarriages or preterm deliveries.
Translocations
A balanced translocationChromosomal translocation
In genetics, a chromosome translocation is a chromosome abnormality caused by rearrangement of parts between nonhomologous chromosomes. A gene fusion may be created when the translocation joins two otherwise separated genes, the occurrence of which is common in cancer. It is detected on...
or Robertsonian translocation
Robertsonian translocation
Robertsonian translocation is a common form of chromosomal rearrangement that in humans occurs in the five acrocentric chromosome pairs, namely 13, 14, 15, 21, and 22. Other translocations occur but do not lead to a viable fetus. They are named after the American biologist William Rees Brebner...
in one of the partners leads to unviable fetuses that are aborted spontaneously. This explains why a karyogram is often performed in both partners if a woman has experienced repeated abortions.
About 3% of the time a chromosomal problem of one or both partners can lead to recurrent pregnancy loss. Although patients with such a chromosomal problem are more likely to miscarry, they may also deliver normal or abnormal babies.
Aneuploidy
AneuploidyAneuploidy
Aneuploidy is an abnormal number of chromosomes, and is a type of chromosome abnormality. An extra or missing chromosome is a common cause of genetic disorders . Some cancer cells also have abnormal numbers of chromosomes. Aneuploidy occurs during cell division when the chromosomes do not separate...
may be a cause of a random spontaneous as well as recurrent pregnancy loss. Aneuploidy is more common with advanced reproductive age reflecting decreased germ cell
Germ cell
A germ cell is any biological cell that gives rise to the gametes of an organism that reproduces sexually. In many animals, the germ cells originate near the gut of an embryo and migrate to the developing gonads. There, they undergo cell division of two types, mitosis and meiosis, followed by...
quality.
Endocrine disorders
Women with hypothyroidismHypothyroidism
Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone.Iodine deficiency is the most common cause of hypothyroidism worldwide but it can be caused by other causes such as several conditions of the thyroid gland or, less commonly, the pituitary gland or...
are at increased risk for pregnancy losses. Unrecognized or poorly treated diabetes mellitus
Diabetes mellitus
Diabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...
leads to increased miscarriages. Women with polycystic ovary syndrome
Polycystic ovary syndrome
Polycystic ovary syndrome is one of the most common female endocrine disorders. PCOS is a complex, heterogeneous disorder of uncertain aetiology, but there is strong evidence that it can to a large degree be classified as a genetic disease....
also have higher loss rates possibly related to hyperinsulinemia or excess androgens. Inadequate production of progesterone
Progesterone
Progesterone also known as P4 is a C-21 steroid hormone involved in the female menstrual cycle, pregnancy and embryogenesis of humans and other species...
in the luteal phase may set the stage for RPL (see below).
Thrombophilia
An important example is the possible increased risk of abortion in women with thrombophiliaThrombophilia
Thrombophilia is an abnormality of blood coagulation that increases the risk of thrombosis . Such abnormalities can be identified in 50% of people who have an episode of thrombosis that was not provoked by other causes...
(propensity for blood clots
Thrombosis
Thrombosis is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets and fibrin to form a blood clot to prevent blood loss...
). The most common problem is the factor V Leiden
Factor V Leiden
Factor V Leiden is the name given to a variant of human factor V that causes a hypercoagulability disorder. In this disorder the Leiden variant of factor V cannot be inactivated by activated protein C. Factor V Leiden is the most common hereditary hypercoagulability disorder amongst Eurasians...
and prothrombin G20210A mutation
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
. Some preliminary studies suggest that anticoagulant
Anticoagulant
An anticoagulant is a substance that prevents coagulation of blood. A group of pharmaceuticals called anticoagulants can be used in vivo as a medication for thrombotic disorders. Some anticoagulants are used in medical equipment, such as test tubes, blood transfusion bags, and renal dialysis...
medication may improve the chances of carrying pregnancy to term but these studies need to be confirmed before they are adopted in clinical practice. Note that many women with thrombophilia go through one or more pregnancies with no difficulties, while others may have pregnancy complications. Thrombophilia may explain up to 15% of recurrent miscarriages.
Immune factors
A common feature of immune factors in causing recurrent pregnancy loss appears to be a decreased maternal immune tolerance towards the fetus.Antiphospholipid syndrome
The antiphospholipid syndromeAntiphospholipid syndrome
Antiphospholipid syndrome or antiphospholipid antibody syndrome , often also Hughes syndrome, is an autoimmune, hypercoagulable state caused by antibodies against cell-membrane phospholipids that provokes blood clots in both arteries and veins as well as pregnancy-related complications such as...
is a generally accepted cause of recurrent pregnancy loss. High levels of antiphospholipid antibodies may account for 3%-15% of recurrent miscarriages. In these cases, pregnancy outcomes are improved by the use of aspirin or heparin.
Thyroid antibodies
Anti-thyroid autoantibodiesAnti-thyroid autoantibodies
Anti-thyroid autoantibodies are autoantibodies targeted against one or more components of the thyroid. The main types of anti-thyroid autoantibodies are anti-thyroid peroxidase antibodies and stimulating autoantibodies that are associated with Grave's disease.-Anti-TPO antibodies:Aanti-thyroid...
are associated with an increased risk of recurrent miscarriage with an odds ratio
Odds ratio
The odds ratio is a measure of effect size, describing the strength of association or non-independence between two binary data values. It is used as a descriptive statistic, and plays an important role in logistic regression...
of 2.3 with a 95% confidence interval
Confidence interval
In statistics, a confidence interval is a particular kind of interval estimate of a population parameter and is used to indicate the reliability of an estimate. It is an observed interval , in principle different from sample to sample, that frequently includes the parameter of interest, if the...
of 1.5–3.5.
Increased uterine NK cells
A controversial area is the presence of increased natural killer cellNatural killer cell
Natural killer cells are a type of cytotoxic lymphocyte that constitute a major component of the innate immune system. NK cells play a major role in the rejection of tumors and cells infected by viruses...
s in the uterus
Uterus
The uterus or womb is a major female hormone-responsive reproductive sex organ of most mammals including humans. One end, the cervix, opens into the vagina, while the other is connected to one or both fallopian tubes, depending on the species...
. It is poorly understood whether these cells actually inhibit the formation of a placenta
Placenta
The placenta is an organ that connects the developing fetus to the uterine wall to allow nutrient uptake, waste elimination, and gas exchange via the mother's blood supply. "True" placentas are a defining characteristic of eutherian or "placental" mammals, but are also found in some snakes and...
, and it has been noted that they might be essential for this process. A 2004 paper (Moffett et al.) warned that determination of NK cells in peripheral blood does not predict uterine NK cell numbers, because they are a different class of lymphocyte
Lymphocyte
A lymphocyte is a type of white blood cell in the vertebrate immune system.Under the microscope, lymphocytes can be divided into large lymphocytes and small lymphocytes. Large granular lymphocytes include natural killer cells...
s, and state that immunosuppressive
Immunosuppression
Immunosuppression involves an act that reduces the activation or efficacy of the immune system. Some portions of the immune system itself have immuno-suppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reaction to treatment of other...
treatments are not warranted.
Parental HLA sharing
Earlier studies that perhaps paternal sharing of HLAHuman leukocyte antigen
The human leukocyte antigen system is the name of the major histocompatibility complex in humans. The super locus contains a large number of genes related to immune system function in humans. This group of genes resides on chromosome 6, and encodes cell-surface antigen-presenting proteins and...
genes would be associated with increased pregnancy loss have not been confirmed.
Male-specific minor histocompatibility
Immunization of mothers against male-specific minor histocompatibility (H-Y) antigens has a pathogenic role in many cases of secondary recurrent miscarriage, that is, recurrent miscarriage in pregnancies succeeding a previous live birth. An example of this effect is that the male:female ratio of children born prior and subsequent to secondary recurrent miscarriage is 1.49 and 0.76 respectively.Reduced ovarian reserve
The risk for miscarriage increases with age, and women in the advanced reproductive age who have a reduced ovarian reserveOvarian reserve
Ovarian reserve is a term that is used to determine the capacity of the ovary to provide eggs that are capable of fertilization resulting in a healthy and successful pregnancy...
are prone to higher risk of repeated miscarriages. Such miscarriages are due to decreased egg quality .
Luteal phase defect
The issue of a luteal phase defect is complex. The theory behind the concept suggests that an inadequate amount of progesteroneProgesterone
Progesterone also known as P4 is a C-21 steroid hormone involved in the female menstrual cycle, pregnancy and embryogenesis of humans and other species...
is produced by the corpus luteum
Corpus luteum
The corpus luteum is a temporary endocrine structure in mammals, involved in production of relatively high levels of progesterone and moderate levels of estradiol and inhibin A...
to maintain the early pregnancy. Assessment of this situation was traditionally carried out by an endometrial biopsy
Endometrial biopsy
The endometrial biopsy is a medical office procedure that is used to remove a sample of the lining of the uterus. The tissue subsequently undergoes a histologic evaluation which is supplied to the physician to aid in the diagnosis.-Indications:...
, however recent studies have not confirmed that such assessment is valid. Studies about the value of progesterone supplementation remain deficient, however, such supplementation is commonly carried out on an empirical basis.
Lifestyle factors
While lifestyle factors have been associated with increased risk for miscarriage in general, and are usually not listed as specific causes for RPL, every effort should be made to address these issues in patients with RPL. Of specific concern are chronic exposures to toxins including smokingTobacco smoking
Tobacco smoking is the practice where tobacco is burned and the resulting smoke is inhaled. The practice may have begun as early as 5000–3000 BCE. Tobacco was introduced to Eurasia in the late 16th century where it followed common trade routes...
, alcohol
Ethanol
Ethanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug and one of the oldest recreational drugs. Best known as the type of alcohol found in alcoholic beverages, it is also used in thermometers, as a...
, and drugs
DRUGS
Destroy Rebuild Until God Shows are an American post-hardcore band formed in 2010. They released their debut self-titled album on February 22, 2011.- Formation :...
.
Infection
A number of maternal infections can lead to a single pregnancy loss, including listeriosis, toxoplasmosisToxoplasmosis
Toxoplasmosis is a parasitic disease caused by the protozoan Toxoplasma gondii. The parasite infects most genera of warm-blooded animals, including humans, but the primary host is the felid family. Animals are infected by eating infected meat, by ingestion of feces of a cat that has itself...
, and certain viral infections (rubella
Rubella
Rubella, commonly known as German measles, is a disease caused by the rubella virus. The name "rubella" is derived from the Latin, meaning little red. Rubella is also known as German measles because the disease was first described by German physicians in the mid-eighteenth century. This disease is...
, herpes simplex
Herpes simplex
Herpes simplex is a viral disease caused by both Herpes simplex virus type 1 and type 2 . Infection with the herpes virus is categorized into one of several distinct disorders based on the site of infection. Oral herpes, the visible symptoms of which are colloquially called cold sores or fever...
, measles
Measles
Measles, also known as rubeola or morbilli, is an infection of the respiratory system caused by a virus, specifically a paramyxovirus of the genus Morbillivirus. Morbilliviruses, like other paramyxoviruses, are enveloped, single-stranded, negative-sense RNA viruses...
, cytomegalo virus, coxsackie
Coxsackie
Coxsackie may refer to:* Coxsackie , New York* Coxsackie , New York* Coxsackievirus -- any of a group of 23 Coxsackie A viruses and 6 Coxsackie B viruses....
virus). However, there are no confirmed studies to suggest that specific infections will lead to recurrent pregnancy loss in humans. Malaria, syphilis and brucellosis can also cause recurrent abortion.
Assessment
Transvaginal ultrasonography has become the primary method of assessment of the health of an early pregnancy.In non-pregnant patients who are evaluated for RPL the following tests are usually performed.
Parental chromosome testing (karyogram) is generally recommended after 2 or 3 pregnancy losses. Blood test
Blood test
A blood test is a laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a needle, or via fingerprick....
s for thrombophilia
Thrombophilia
Thrombophilia is an abnormality of blood coagulation that increases the risk of thrombosis . Such abnormalities can be identified in 50% of people who have an episode of thrombosis that was not provoked by other causes...
, ovarian function, thyroid
Thyroid
The thyroid gland or simply, the thyroid , in vertebrate anatomy, is one of the largest endocrine glands. The thyroid gland is found in the neck, below the thyroid cartilage...
function and diabetes are performed.
Treatment
If the likely cause of recurrent pregnancy loss can be determined treatment is to be directed accordingly. In patients with unexplained RPL chances are about 60-70% that the next pregnancy is successful without treatment. In certain chromosomal situations, while treatment may not be available, IVF with preimplantation genetic diagnosisPreimplantation genetic diagnosis
In medicine and genetics pre-implantation genetic diagnosis refers to procedures that are performed on embryos prior to implantation, sometimes even on oocytes prior to fertilization. PGD is considered another way to prenatal diagnosis...
may be able to identify embryos with a reduced risk of another pregnancy loss which then would be transferred
Embryo transfer
Embryo transfer refers to a step in the process of assisted reproduction in which embryos are placed into the uterus of a female with the intent to establish a pregnancy...
. Close surveillance during pregnancy is generally recommended for pregnant patients with a history of recurrent pregnancy loss.
Even with appropriate and correct treatment another pregnancy loss may occur as each pregnancy develops its own risks and problems.
However, there is currently no drug that has evidence of preventing recurrent pregnancy loss by boosting maternal immune tolerance; aspirin has no effect in this case.