Causes and Treatments
Miscarriage is one of the most difficult conditions couples have to face and it is magnified in those who have recurrent miscarriage, also known as spontaneous abortion. Miscarriage is especially painful in those couples who underwent months of fertility therapy in order to become pregnant. Recurrent miscarriage is typically defined as three or more consecutive pregnancy losses that occur prior to 24 weeks of gestation. First trimester losses are the most common and occur prior to 12 weeks of gestation.
A woman’s reproductive history influences the chances for miscarriage and includes factors such as previous miscarriage, female age, presence of a condition such as PCOS, and many others. When a couple has had two or more miscarriages the chances for future miscarriage is increased.
Miscarriage is more common than many people believe and occurs in 15-20% of clinical pregnancies in women under the age of 30; 20-30% for women in their 30’s and often occurs greater than 50% of the time for women over the age of 40. In approximately 50% (some feel that perhaps as high as 80%) or more of the cases, miscarriage is the body’s way of “screening for” an abnormal fetus that will not be able to survive. One of the major causes of miscarriage is an abnormal number of chromosomes in the embryo. This condition is known as aneuploidy and increases as women age.
Currently preimplantation genetic diagnosis (PGD) technology combined with IVF can screen embryos for aneuploidy. Currently up to 12 of the 23 pairs of chromosomes can be tested on each embryo. Many aneuploidies such as Trisomies 13 and 18 are universally fatal. There can also be broken or dislocated chromosomes. In women over the age of 40, it is common to find more than 50% of the embryos are chromosomally abnormal. Women should be evaluated for “ovarian reserve” using a day 3 estradiol and FSH level. Abnormal FSH levels would suggest a significant increased risk of aneuploid embryos.
One cause of repetitive miscarriages due to genetic problems in the fetus is the situation where the husband or the wife has a balanced chromosomal translocation. This is found in 3-4% of couples who have had 3 or more miscarriages. Genetic testing consists of obtaining a blood test for high resolution/definition peripheral blood karyotype (chromosome analysis). If a balanced translocation is found, the affected person usually has the normal amount of DNA material but when eggs or sperm are made there may be either too much DNA or not enough. This may increase the risk for miscarriage.
Some medical conditions, including PCOS, increase the chances of miscarriage. Pretreatment prior to conception with insulin sensitizing agents such as Glucophage (Metformin®) may decrease this risk for some patients.
There may also be uterine abnormalities such as congenital or acquired malformations. Congenital malformations include double uterus (uterus didelphysis), a singled sided uterus (unicornuate uterus), a heart shaped uterus (bicornuate uterus) and a septate uterus (midline muscle growth in the uterine cavity). Most of these abnormalities decrease the chance of pregnancy, increase the risk of miscarriage and also increase the risk of pre term labor.
A uterine septum is especially amenable to outpatient hysteroscopic surgical repair using modern methods such as the Versapoint® bipolar coagulator. Acquired abnormalities include uterine fibroids and intrauterine adhesions. Fibroids (uterine leiomyoma) are usually benign muscle growths that arise from the wall of the uterus.
There are three types of fibroids: 1) submucosal (fibroid is in or impinging into the uterine cavity, 2) intramural where the fibroid is within the wall of the uterus and, 3) subserosal where the fibroid is primarily on the outside (serosal surface) of the uterine wall. Typically, submucosal fibroids are thought to significantly decrease the likelihood of conception by 50-80% and significantly increase the likelihood of miscarriage. Intramural fibroids have less of an impact unless they are greater than 2 cm in size. Submucosal fibroids probably do not have a major impact on miscarriage rates. A skilled reproductive surgeon can usually surgically remove fibroids.
Uterine adhesions are usually the result of prior uterine surgery. This is primarily a complication of postpartum D&C (dilation and curettage) procedures but can also occur after intrauterine surgery for fibroids or polyps. Uterine abnormalities are best evaluated using a hysterosalpingogram (HSG), 3D saline sonogram or hysteroscopy.
A luteal phase defect occurs when there is insufficient progesterone after ovulation. Progesterone is produced by the leftover follicular structure known as the corpus luteum. Adequate progesterone is needed to support preparation of the endometrium needed to support an embryo and developing fetus. A luteal phase defect is usually the result of suboptimal or poor ovulation.
Treatment to improve ovulatory function with oral, such as clomiphene citrate (Clomid®), or injectable agents (FSH) can often help correct this problem. It can also be treated by administering supplemental progesterone. Other hormonal defects that affect ovulatory function including hypo- or hyperthyroidism or hyperprolactinemia can increase miscarriage rates. This can usually be corrected by treating the specific endocrine abnormality.
Thrombophilic (blood-clotting) tendencies may impair the development or function of the placenta. Abnormal blood clotting in the placental blood vessels may result in recurrent miscarriage. This may be due to antibodies to phospholipids (antiphospholipid antibodies) which are important components of the membrane that surrounds all cells and small blood vessels. For this reason, aspirin and/or heparin may be used in some cases of recurrent abortion. Dr. Ware Branch, a maternal fetal medicine expert at the University of Utah, is one of the world’s experts on this particular syndrome.
Some specialists believe that miscarriage can result because of abnormal autoimmune responses. When this happens, the body “mistakes” the fetus for an invading pathogen and creates antibodies to destroy it. This type of evaluation can be expensive and treatments that have been recommended in the past have often been proven ineffective. Most of these conditions are identified in the workup for infertility.
A hysterosalpingogram involves injecting dye into the uterus and following its flow via x-ray back through the tubes. Abnormalities appear as shadows or collections of fluid. The hysteroscope is a “telescope like” device that allows the physician to directly view the inside of the uterus. A 3D office saline sonogram is often the best noninvasive way to evaluate the uterine cavity and the wall of the uterus.
Hormonal testing for ovarian reserve (day 3 FSH and estradiol), ovulatory function (TSH, prolactin), androgen excess and insulin resistance testing may be helpful in the evaluation.
Successful pregnancy can often be achieved when hormonal problems are medically corrected, uterine abnormalities are surgically corrected, immunologic or thrombophilia abnormalities are treated with aspirin or heparin and embryo genetic abnormalities are screened through preimplantation genetic diagnosis (PGD) testing. When the uterus is severely damaged, gestational surrogacy may be the only treatment option. A gestational surrogate carries the embryo created from an IVF cycle between the mother and father.
Patients should be aware that even after careful screening a specific etiology of recurrent miscarriage is not found in up to 50% of the cases. However, due to the emotionally traumatic nature of these pregnancy losses consideration should be given to evaluation after two successive losses.
If a D&C procedure is performed after the fetus has stopped developing, patients should ask their obstetrician to analyze the products of conception (fetal material) for chromosome abnormalities to help in the delineation of the etiology of the loss.