Couples with Recurrent Pregnancy Losses

Recurrent pregnancy loss (RPL) is defined as two or more consecutive pregnancy losses in which an appropriately rising quantitative hCG level was documented during each pregnancy that ultimately fails. This excludes pregnancies that are confirmed to be located outside of the uterus, most commonly in the fallopian tube, called ectopic pregnancies. Based on this definition, RPL affects 1-2% of all fertile couples.

Although some physicians would recommend there be three losses before evaluation, given the emotional and physical pain of miscarriage, who would want to wait for a third loss before seeking a solution?

Please make an appointment with our physicians to learn more about evaluation and treatment of recurrent pregnancy loss to assist you in having a healthy baby.

Potential Detectable Causes and Remedies Can Be:

Genetic Abnormalities

A genetic abnormality unique to the egg, sperm, embryo or parent.

Remedies may include:

• In-vitro fertilization with pre-implantation genetic testing by comprehensive chromosome screening.
• Donor egg or sperm.

Uterine Abnormalities

A uterus abnormality caused by being born with an abnormal uterine formation, developing fibroid tumors, or scarring from previous surgery of the uterus.

Remedies may include:

• Surgical repair of the uterus.
• In-vitro fertilization with transfer of your embryo into another woman’s uterus to serve as a gestational carrier.

Hormonal Disorders

Hormonal disorders related to advanced female reproductive age, thyroid conditions and polycystic ovary syndrome. These conditions result in a greater chance of a genetically abnormal embryo.

Remedies may include:

• Restore normal thyroid balance with medication.
• Improve hormone and sugar metabolism imbalance of polycystic ovary syndrome with metformin, low carbohydrate diet, exercise and weight loss if overweight.
• In-vitro fertilization with pre-implantation genetic testing by comprehensive chromosome screening to select a single embryo among many that is more likely to have the normal number and distribution of chromosomes (euploid) for a single embryo transfer.

Immune and Blood Clotting Disorders

Conditions such as anti-phospholipid antibody syndrome and genetic mutations affecting the blood clotting ability, such as Leiden Factor V, can cause recurrent pregnancy losses at any time during pregnancy. However, these conditions are unlikely to cause extremely early losses before a gestational sac can be seen by vaginal ultrasound. Women with these abnormal conditions have babies without intervention. We just don’t know which women with these conditions will experience the problem of recurrent pregnancy losses. Although the collective scientific understanding is in agreement that a woman’s immune system is an essential part of pregnancy, this area of science is not well understood and the remedies are vague and inconsistent with regard to preventing miscarriage. There are many theories, but few are well supported by reproducible science. It is often said in sports, “records are made to be broken.” The same is true for theories in science.

Remedies may include:

• Anti-clotting medication Lovenox and baby aspirin on a daily basis throughout pregnancy.

Environmental Toxins

Smoking, alcohol and recreational drug abuse have all been associated with increased miscarriage rates. Smoking hurts eggs. Other drugs may impair the body’s metabolism or affect the embryo and fetus directly, leading to miscarriage or substantial birth defects that impair baby’s body and mind.

Remedies may include:

• Cessation of exposure to such toxic substances is imperative.

Genetic Causes

We have expanded the review of genetic causes on this webpage because the most common cause of miscarriage, about 2 in 3, is an abnormal number or distribution of chromosomes in the embryo or fetus.The increasing influence and role of genetic testing is beginning to unveil the true causes where, without such insight, speculation has often led to endless and expensive tests for unproven causes and treatments that pose potential harm and no benefit.

Genetic Evaluation of the Products of Conception

Often a pregnancy loss is discovered by ultrasound tests before bleeding or passing of tissue occurs. A D&C can be safely performed removing the products of conception tissue from the uterus providing an opportunity to perform genetic testing on the tissue itself. Genetic testing of the tissue, called a karyotype, can be done. A karyotype test can evaluate the number, size and distribution of chromosomes. If there is a chromosome abnormality found, called aneuploidy, then the root cause and most common cause of miscarriage has been confirmed. Once this is known, testing for many other rare causes of miscarriage can be avoided.

Age of the Egg

Advancing female reproductive age is closely related to random miscarriage due to an abnormal number of chromosomes, called “aneuploidy”, in the egg. The resulting embryo can cause miscarriage or die before implanting in the uterus, and this can happen without knowing conception occurred.

Translocations

A less common genetic cause of RPL is when the mother or the father has a preexisting genetic irregularity known as a translocation that is unrelated to their age. Some genes have been rearranged to be present on different chromosomes. An analogy is to consider a deck of cards carefully arranged by suits and in progressive order within each suit from “2s” to “Aces”. Rearrangement is like cutting the deck. You still have the same number of cards, but now they are out of order. Although they are out of order, if you have all of your cards (genes), you are fine and live.

However, this describes a parent who is a “carrier of a balanced rearrangement.” When you want to have a child, each parent cuts their deck evenly in half and shares it with the other, uniting them to create a new full deck for their baby. If one parent has a rearranged deck, that parent is providing an out-of-order half deck and combining it with the ordered half deck of the other parent. You will wind up with a new deck that may have too many or too few cards of any given suit. This rearrangement of genes and chromosomes is not compatible with life, and a miscarriage can result much more frequently and lead to recurrent pregnancy losses.

Sometimes you get lucky and have all the right cards in the new deck, and a healthy child is created similar to the parent with the rearranged deck.  However, this happens less often than if both parents had a normal organized deck. The chance of having a normal child depends on the type of rearrangement. We will recommend a consultation with a genetic counselor expert in providing as clear an assessment as possible. Translocations within a parent are the most common parental, non-random cause of recurrent miscarriage. About 1 in 20 couples with recurrent pregnancy losses have this problem as the cause.

What We Don’t Know

Immunology

Although the embryo resides in the mother, an embryo has some genetics from the father and is thus not identical to the mother. It is clearly different in genetic makeup from the mother, and yet the mother’s immune system is normally permissive, allowing the fetus to grow and survive to birth. In the absence of a clear scientific explanation for why a mother’s body generally does not reject the fetus, there are several theories to explain the breakdown of immune permissiveness to the developing fetus that can result in recurrent pregnancy losses, and these include:

• Similarities in human leukocyte antigens (HLA)
• Generation of toxic factors to the embryo
• The presence of natural killer cells (NK)

To date, none of these theories have clearly been shown to be true. Despite the lack of evidence, several tests have been developed intended to help in the evaluation of recurrent pregnancy losses and include:

• Embryo toxic factors
• Natural killer cell assays
• T-helper cell 1 and 2 cytokine ratios

Unfortunately, none of these tests have clearly been shown to differentiate women with recurrent pregnancy loss from women in the general population who lack this problem. For these reasons, our physicians do not recommend these tests or proposed treatments:

• White blood cell immunotherapy (currently banned by the US FDA)
• Intravenous gamma globulin immunotherapy
• Intralipid therapy.

These treatments are both controversial and experimental, requiring further research. They require using blood products from other people that are collected and processed. Use of blood products carries the risk of adverse immune allergic reactions and infectious disease by viruses.  Some of these viruses are undetectable with current technology, such as slow viruses called prions that cause diseases including Mad Cow disease, Kuru and Jabob-Creutzfeldt disease. At this time, the risks outweigh the benefits of such theoretical treatments.

Please make an appointment with our physicians to learn more about evaluation and treatment of recurrent pregnancy loss to assist you in having a healthy baby.