Recurrent Miscarriage: Mysteries & Facts
Posted on June 6, 2005 by Inception Fertility
 Many people who get pregnant easily but have experienced recurrent miscarriages may not realize that they may actually have an "infertility" problem. The rubric of infertility includes not only helping couples establish a pregnancy but also achieving a **viable** pregnancy, which will grow to full term. So the diagnosis and treatment of recurrent miscarriages is indeed an area that is managed by infertility experts. Recurrent Miscarriages, also called recurrent pregnancy loss (RPL), is diagnosed after at least 2 or 3, or more, consecutive pregnancy losses in the first or early second trimester (less than 15 weeks gestation). It is one of the most common clinical problems in reproduction, yet a definite cause can be established in only about 50% of the cases, often leaving patients distraught and frustrated. Consequently, some patients will turn to alternative therapies of unproven benefit. Medically known causes and treatments are described in this article. **Egg Quality Factor** The normal biological aging process of the egg causes the egg to function less accurately during the fertilization process at the critical time of chromosomal duplication and pairing. The resulting chromosomally abnormal embryos have a lower chance of implanting in the uterine lining. If implantation does occur, these embryos have a higher chance of leading to a first trimester miscarriage. We test for egg quality by performing a blood test for the **FSH** and **Estradiol** hormones on menstrual cycle day 2 or 3. For some patients we may recommend a more extensive test called a **Clomid Challenge Test**. **Other Hormonal Factors** Other hormonal abnormalities that result in miscarriage must be very subtle because the cycle is normal enough to allow egg development, ovulation, fertilization, and implantation, yet the pregnancy is lost at a later time. The amount of progesterone produced by the follicle after ovulation and the effect of that progesterone on the lining of the uterus may be of importance. **A low progesterone level or an inadequate maturation of the uterine lining is called a luteal phase defect.** Abnormalities of other metabolic hormones can cause a luteal phase defect. If the **prolactin** level is elevated, it is important to evaluate for prolactin-elevating drugs, hypothyroidism (check the **TSH**), and pituitary tumors. The prolactin level can be lowered to a normal range with medications. **Women who have polycystic ovary syndrome (PCOS) are at higher risk of miscarriages** because of an intraovarian hormonal imbalance. If PCOS is suspected, checking for LH, androgens and insulin resistance can be helpful in discussing treatment with insulin-sensitizing agents (metformin). **Anatomical factors** The anatomical factors are a variety of structural abnormalities of the cervix and uterus that are found in about 15% of women with recurrent pregnancy loss. These factors are diagnosed by performing a **hysterosalpingogram** (HSG), **mid-cycle ultrasound** or **saline hysterogram**, with attention directed to the shape or contour of the uterine cavity. **Potential abnormalities that may be found and associated with recurrent miscarriages are polyps, fibroids, and uterine septums.** These anatomical abnormalities can lead to an unfavorable uterine environment for the embryo at the time of implantation and early embryo development. These can lead to early pregnancy loss. All of these abnormalities can usually be corrected with minor surgery. **Chromosomal Factor** **There are 2 types of chromosomal factors. One is a random event; the other is genetically inherited by the fetus.** At least 60% of all miscarriages are chromosomally abnormal embryos that arose from sporadic, random genetic defects in the sperm or the egg. These are defects that would not have been detected by analysis of the couple's chromosomes (karyotype). However, these defects become more common as the woman ages. **The miscarriage risk increases from about 15% of pregnancies before age 35, to 35% by age 40 and to 50% by age 45.** About 99% of the time a chromosomally abnormal embryo will be miscarried. Because perhaps 1% will continue to develop, amniocentesis or chorionic villus sampling, which determine the genetic makeup of the fetus, is suggested for women over 35. When the genetic makeup of the fertilized egg is very abnormal, no embryo forms. On ultrasound examination an empty sac or a "blighted ovum" is seen in the uterus. Some patients have chromosomal abnormalities in each cell, including eggs and sperm, which place them at greater risk of making a larger proportion of abnormal embryos. The fetus then genetically inherits this abnormality. Every cell in our body other than eggs and sperm has 46 chromosomes arranged in 23 pairs. It is possible that between the two chromosomes of a designated pair there could be a mix-up in the sequence of genes that make up these chromosomes, but the total number of genes is still normal. This mix-up is called a **"balanced translocation"** and causes no symptoms, diseases, or abnormalities in the patient or partner. However, if this genetic rearrangement occurs in a sperm or egg, the embryo will be chromosomally abnormal, and a miscarriage will follow. Balanced translocations can be detected by performing a chromosomal analysis. Chromosomal analysis requires a blood sample from both partners. The white blood cells are cultured to produce an analysis, or **karyotype**, of the chromosome pairs. The karyotype will be abnormal in about 5% of cases of couples that have suffered from three or more miscarriages. It is difficult to say what the risk of repeated miscarriages will be with a balanced translocation, however a normal full term pregnancy is still possible. **Immunologic factors** The immune system protects our bodies against foreign micro-organisms by recognizing any cells that are different from our own and making antibodies that attack and destroy those cells. Some women with recurrent pregnancy loss have **autoantibodies**. These are antibodies in their blood vessels that are made to attack their own tissues (e.g., **antiphospholipid (anticardiolipin)**, **antinuclear**, or **antithyroid antibodies**). Antiphospholipid antibodies, along with **lupus anticoagulant**, may interfere with the formation of a normal placenta early in pregnancy and increase the risk of abnormal blood clotting in the placenta later in the pregnancy. This compromised placenta will lead to compromised growth of the fetus and an eventual miscarriage. If one has a positive antibody test, the test should be repeated 6-8 weeks later. If both sets of tests are positive, the recommended treatment may include one **"baby" aspirin** tablet per day, and sometimes the addition of daily **heparin**. **Thrombophilia Factors** Various enzymes regulate effective flow and clotting of blood. If there is a deficiency in some of the clotting enzymes, then small blood vessels of the placenta may be at greater risk of forming clots. Clots of the placenta will compromise blood flow to the growing embryo, placing the pregnancy at greater risk of a miscarriage. There are now a number of clotting enzymes that are recommended to be tested for in patients with recurrent miscarriages. If specific combinations of these enzymes are found to be in an abnormal range, then recommended treatment is a "Baby" aspirin per day with the possible addition of heparin. Most miscarriages are the result of a **random** genetic defect leading to abnormal chromosomes for that particular fetus. This random event is unlikely to recur. For patients who have had three consecutive first-trimester miscarriages, and normal results after full evaluation, the chance of the next pregnancy leading to the delivery of a child is approximately 65%. Therefore, despite having had three recurrent miscarriages, the odds are still in favor of the next pregnancy being a normal pregnancy. While it can be incredibly frustrating both for patient and physician, to face repetitive failed pregnancies, it is still important to understand that the odds are still in the patient's favor of eventual success. This may require fertility treatment, from low-tech intervention such as Clomid to high tech intervention such as IVF with preimplantation genetic screening (PGS), but in general, success is in our favor. If you are, or know someone who is experiencing recurrent miscarriages, please discuss this with a fertility specialist who may be able to recommend treatment options. **-- Isabelle Ryan MD** Categories
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