Probably no aspect of infertility is more traumatic than becoming pregnant and then losing the baby to miscarriage. And while most women who miscarry do go on to give birth to a healthy baby in the next pregnancy, infertility specialists are often called in to find out the cause for the recurrent pregnancy loss and recommend treatment.
The incidence of pregnancy loss among all women is about 20%. Statistics show that if the first pregnancy ended in miscarriage, the second has similar possibility - 20% - of the same outcome. After two miscarriages, however, the risk rises to 25%-30%. So, only about 4% of women will experience two consecutive pregnancy losses and less than 1% will experience 3 or more consecutive miscarriages. For this reason, most experts recommend that a woman see a fertility specialist if she has experienced two miscarriages in a row. For a woman who has had three consecutive miscarriages but no history of live birth, the next pregnancy has a 30-45% chance of ending in miscarriage. Keep in mind, however, that this means she still has better than 60% odds of carrying the next pregnancy to term!
It had long been believed that - unlike "first" miscarriages, of which a little over half are caused by chromosomal abnormalities - recurrent pregnancy loss had other causes. However, recent research has demonstrated that about 60% of recurrent miscarriages are also caused by chromosomal abnormalities. Researchers are still debating what causes the remainder. Possibilities include immune system malfunction, hormone imbalances, distortions of the uterine cavity, and pelvic infections. Studies have also linked the use of alcohol, cigarettes, and excessive caffeine consumption to an increased risk of miscarriage.

The risk of miscarriage increases with age, and, in many cases, can be attributed to an abnormal egg. As a woman gets older, the quality of her eggs diminishes resulting, not only in more miscarriages, but also in an increased infertility and genetic abnormalities (such as Down’s syndrome) rates. When a woman seeks medical care for recurrent miscarriages, her doctor will first seek to diagnose the cause for her problem.

What causes recurrent miscarriage?

A cause for the miscarriage can be identified in only 50 % of the cases.

• Cervical factor – Incompetent cervix is associated with second trimester pregnancy loss as a result of weakening of the cervical tissue. The treatment involves placing stitches to strengthen the cervix and prevent it from dilating prematurely.

• Advanced reproductive age  has been associated with diminished ovarian reserve  and increased rates of miscarriage. After age 40, 30-40% of pregnancies end in miscarriage, most often as a result of an abnormal number of chromosomes in the embryo (aneuploidy).
• Infectious causes - In some patients a miscarriage can be associated with the presence of an organism called "Ureaplasma", which can be detected by a simple cervical culture and treated with an antibiotic, such as, Doxycycline.
• Immunologic factors - such as Antiphospholipid antibodies (APA) or Factor V. In these types of cases, aspirin therapy (81mg daily) may be prescribed during pregnancy. Low dose Heparin therapy has also been demonstrated to be successful in about 80% of patients with recurrent pregnancy losses. Recent studies demonstrated both aspirin and heparin therapy to be equally effective in treating recurrent pregnancy loss with about 80% live birth rate.
• Unexplained recurrent miscarriages - In women with unexplained or unknown cause for the recurrent miscarriages, no specific treatment has been found to be helpful.
  In a recent randomized placebo-controlled study (2/2010) of 364 women with unexplained recurrent miscarriages, Aspirin and low-molecular weight heparin treatment did not improve live birth rates. 54.5% of women given aspirin and heparin had live births. 50.8% of women given aspirin alone and 57% of women given only placebo (sugar pill) had live births.
  Most importantly, aspirin and heparin therapy can increase the risk of placental abruption and pregnancy loss. The take home message is that there is no proven benefit to this treatment in women with recurrent miscarriages and that such treatment may increase the risk of pregnancy loss. Treatment with aspirin and heparin should, therefore, be reserved for patient with recurrent miscarriages caused by inherited thrombophilia or antiphospholipid syndrome.

Leukocyte immunization and Immunoglobulin (IVIG) therapy have been evaluated in patients with recurrent miscarriages. The treatment is expensive and has been shown to provide no significant benefit in preventing further miscarriages. Similarly, natural killer cells (NK) have been implicated in recurrent pregnancy loss, but it is still not certain that NK are necessarily bad in humans.

Evaluation for recurrent pregnancy loss

An evaluation for known causes of recurrent pregnancy loss is most often initiated after 2 or 3 consecutive pregnancy losses and may include the following:

• Hysterosalpingogram (HSG), Saline Infusion Sonography  (SIS) and hysteroscopy  to make sure that there are no uterine abnormalities.
• Progesterone level or endometrial biopsy to see if an ovulatory disorder, such as corpus luteum defect, is causing the problem.
• Chromosomal analysis (karyotype) for the husband and wife.
• Culture for Ureaplasma organism.
• Immunologic workup (anticardiolipin antibodies, thrombophilia panel).
• Day 3 FSH and Estrogen (E2) levels to evaluate the ovarian reserve.
• Thyroid, prolactin, blood sugar and insulin levels (in PCOS  patients).

Looking for sperm defects (Sperm DNA fragmentation) has not been proven to be helpful for patients with recurrent pregnancy loss.

What can I do to prevent another miscarriage?

• Keep in mind that even if the cause for your miscarriages is unknown, you have about 60 - 70% chance of having a successful outcome with your next pregnancy.
• If the cause for your miscarriage is known, specific treatment can improve your chances for a successful pregnancy. 
• Maintain healthy weight and exercise regularly; avoid caffeine, alcohol and smoking. Consider folic acid supplementation and baby aspirin therapy. Seek support from professionals or family members to help you cope with the emotional difficulties often experienced after a miscarriage.
• Some patients consider gestational surrogacy  (patient’s embryos generated from IVF treatment-implanted into another woman’s womb) in cases of unexplained high order recurrent pregnancy loss.
• If you are over 40  with recurrent pregnancy loss, the problem may be attributed to poor egg quality. In such cases, Donor egg IVF  can be considered.