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Recurrent Pregnancy Loss

Recurrent miscarriages or as it is known medically, “recurrent pregnancy loss” (RPL), can be a difficult problem. When a woman is faced with multiple losses in the first trimester of her pregnancy, it can be very disheartening. Some may even have had one successful pregnancy and then experience multiple losses when trying for another. Keep in mind, there is an overall risk of miscarriage in 40% of pregnancies just due to random abnormalities.

The American Society of Reproductive Medicine  (ASRM) considers that, “Recurrent pregnancy loss is a disease distinct from infertility, defined by two or more failed pregnancies. When the cause is unknown, each pregnancy loss merits careful review to determine whether specific evaluation may be appropriate. After three or more losses, a thorough evaluation is warranted. Although approximately 25% of all recognized pregnancies result in miscarriage, less than 5% of women will experience two consecutive miscarriages, and only 1% experience three or more. Couples who experience recurrent pregnancy loss may benefit from a medical evaluation and psychological support.” ASRM “Recurrent Pregnancy Loss Fact Sheet” 8/2008

A basic workup for RPL may take one to two months. While treatment doesn’t guarantee a successful pregnancy, a comprehensive evaluation should result in success rates approaching 85% for most women. If conventional treatment fails, genetic testing of the embryos prior to an IVF transfer, called preimplantation genetic screening (PGS) is usually recommended. Please see our page on “Genetic Testing and Diagnosis” for more information.

The following are some of the possible factors that may be contributing to a woman suffering from multiple miscarriages:

Genetic/Chromosomal Causes

The most common reason for RPL is because of a spontaneous chromosomal abnormality. This occurs when the egg is dividing. The risk of miscarriage increases with a woman’s age:

  • 10 – 15% between the ages of 20 – 30 years
  • 15 – 30% between the ages of 30 – 40 years
  • 30 – 60% between the ages of 40 – 45 years

After age 40, more than one-third of all pregnancies end in miscarriage. Most of these embryos have an abnormal number of chromosomes. A numerical abnormality in the chromosomes of the embryo are thought to be the main cause. Between 70 – 90% of all miscarriages in the first trimester are due to the chromosomal abnormalities such as trisomy (extra chromosome), monosomy (lacking one chromosome) and a few others.

Chromosomal translocation (relocation of a segment of genes from one chromosome to another) may be found in up to 4% of couples. This rare anomoly can be identified through a blood test on both partners. The benefit of genetic testing is that if an abnormality is identified, then IVF with genetic testing (PGD) could prevent another miscarriage.

Polyps, Fibroids and Uterine Disorders

As part of his infertility evaluation, Dr. Ramirez typically requires a pelvic ultrasound, a hysterosalpingogram and a hysteroscopy to diagnose any distortions or congenital abnormalities in the uterus, such as a uterine septum. Surgical correction by operative hysteroscopy may restore fertility in these patients. These diagnostic screenings can also help to identify scar tissue (from Asherman’s syndrome), uterine fibroids, and uterine polyps that may also cause recurrent miscarriages.

In general, the current recommendation by ASRM is that only fibroids that invade into the uterine cavity need to be removed (because they can interfere with implantation). A 7 cm or larger fibroid may need to be removed through an open surgical procedure. Smaller fibroids can be removed laparoscopically.

Hematologic Disorders

Abnormal blood clotting in the small placental blood vessels can also cause RPL. Factor V Leiden, a genetically determined factor, causes recurrent miscarriage through an increased risk of blood clots at the tiny vessels feeding the pregnancy.  Antiphospholipid syndrome causes the production of antibodies to phospholipids, important components of blood vessel walls. Thrombophilia is a tendency for increased blood clotting. A comprehensive blood test must be done to ensure that any one of these disorders is present. The key to treatment is to use anticoagulant medications that decrease this clotting. At our center the preferred treatment is to use low dose heparin or Lovenox beginning at the start of the menstrual cycle or treatment cycle, in addition to aspirin.

Ovarian Cycle With Luteal Phase

Hormonal

Thyroid disease or pituitary dysfunction can be responsible for RPL. Women with PCOS that have an elevated LH on cycle day 9 or 10 may also be at increased risk.

In addition, luteal phase defect, an insufficiency of progesterone after ovulation could play a role. Progesterone is a hormone produced by the ovary and is necessary for a healthy pregnancy. If a woman has suffered from bleeding at odd times during the month this may be a possible cause. The luteal phase is one of the most exact parts of a woman’s cycle, if she is ovulatory. It is the second half of the menstrual cycle after ovulation. The corpus luteum secretes progesterone which prepares the endometrium for the implantation of an embryo. A normal luteal phase is 14 days. However, there is a disorder of the luteal phase whereby this part is short. It is called a luteal phase defect, caused by hormonal asynchrony. The uterine lining (endometrium) is very dependant on appropriate hormonal synchrony to keep it stable. If it is unstable, it breaks apart, hence the bleeding at odd times during the month. Treatment for this defect may include ovulation induction, progesterone supplementation or injections of hCG.

Infectious, Genetic and Immune Factors

Infection has been associated with pregnancy loss. Chlamydia and Gonorrhea contribute to infections and scarring within the uterus and fallopian tubes. The CDC (see their website) has been urging all sexually active women under 26 years old to be tested for STDs annually, as well as older women who have had a change of sexual partner. Yet fewer than 40 % of women in those categories are being screened.  Chlamydia can be detected with a simple urine test and can be treated with a single dose of antibiotics preventing future infertility in these women.

In addition, chronic vaginal infections can certainly kill the sperm, thereby preventing pregnancy. When you have Bacterial Vaginosis, there are changes to the acid environment of your vagina. Many factors can contribute to BV including: use of highly scented soaps, douches and bubble baths; use of an IUD or the coil; or because of certain types of sexual acts. It can also happen when the pH level of the vagina alters during the menstrual cycle. But it can also happen without any of these factors in place. It is, after all, the most common form of odorless bacterial discharge.

Genetic mutations such as MTFHR (Methylenetetrahydrofolate reductase) can cause an increased risk of miscarriage. The association of MTHFR and recurrent pregnancy loss is debatable. Some feel that the mutations can cause blood clots between the developing placenta and uterine wall, thus preventing transport of vital nutrition to the developing fetus. This usually occurs early in pregnancy when the embryo or fetus is most vulnerable. The treatment at our center for MTHFR is increased Folic acid (for more information see MTHFR.net).

Immune factors play a role in miscarriage as well. Treatment for these factors include prednisone and estrogen as well as some of the other medications listed below. There are other controversial treatments which we do not use. Immunotherapy (IVIG) is quite expensive and should be considered experimental. Until proven effective as a result of well-run clinical trials, it is our policy to be cautious in our approach to this therapy.

Treatment For Recurrent Pregnancy Loss

Undoubtedly, the goal is not to leave recurrent miscarriages undiagnosed and untreated. With a history of recurrent pregnancy loss or RPL, Dr. Ramirez will usually add the following anti-clotting and supportive medications during and after each ovulatory cycle:

1. Low dose aspirin 81 mg (baby aspirin) starting with the start of the cycle
2. Low dose heparin starting with the beginning of the cycle (you can substitute Lovenox but it is more expensive).
3. Medrol starting with the beginning of the cycle until ovulation then a decreased dosage
4. Increase progesterone supplementation of either Crinone 8% per day or Endometrin 100 mg three times per day starting after ovulation.

A Note Of Caution For PCOS Patients

Over the years Dr. Ramirez has gotten numerous letters and patients who come to him after being prescribed Metformin for recurrent miscarriage. Unless prescribed for diabetes, Metformin will do nothing to help with the continuation of the pregnancy. A quote from a 2011 blog post :

Metformin does nothing to help with a continuation of pregnancy and does not need to be continued once pregnant unless it was prescribed for diabetes. It is a pregnancy category B medication so is safe in pregnancy if your doctor insists that you continue it. If you were my patient, you would not be on it now. Metformin, given to help some PCO patients ovulate, is for that specific reason only. Once pregnant, the Metformin has done its job and is no longer required. If it is causing side effects, which it usually does, then I think I would recommend that you stop. There are absolutely NO recent studies that show that continuation of Metformin in PCO patients helps the pregnancy to survive or continue. Pregnancies continue or miscarry for many other reasons.”