Recurrent Pregnancy Loss

Recurrent pregnancy loss (RPL) is a common clinical problem. Other terms for RPL include recurrent spontaneous abortion, miscarriage, or recurrent early pregnancy loss. A definite cause is established in no more than 50% of couples, and several alleged causes of RPL are controversial. There are also many unproven hypotheses and poorly designed clinical studies, resulting in various treatments for RPL, many of which are without proven benefit. The following is a contemporary approach to RPL, based on medical studies through 2002. Some of these involve newer identified causes of early pregnancy loss.

Broadly defined, pregnancy loss includes any type of loss of the Conceptus from fertilized ovum to neonate. The early pre-embryonic stage is <6 menstrual weeks of gestation, and the embryonic stage is 6-9 menstrual weeks. RPL must be distinguished from sporadic spontaneous abortions that are losses occurring randomly during a woman’s reproductive years. Sporadic pregnancy loss occurs in about 15% of all clinically recognized pregnancies in women under age 35, and the frequency of spontaneous pregnancy loss increases as a woman’s age increases.

Causes of Recurrent Pregnancy Loss

Uterine Anatomic Abnormalities
Ten to fifteen percent of women with RPL have congenital uterine abnormalities. The majority of these women have a septum in their uterine cavity, or adhesions (Ascherman’s Syndrome). The presence of a submucosal fibroid(s) or large endometrial polyps may also cause recurrent pregnancy loss.

Diagnosis: Saline sonohysterogram, hysteroscopy or hysterosalpingogram (dye study).
Treatment: Outpatient Hysteroscopic resection (removal) of abnormal tissue. In severe cases, use of a surrogate to carry a future pregnancy.

Genetic Abnormalities
In 2-4% of couples with RPL, one partner will have a genetically balanced structural chromosome rearrangement (balanced translocation). Studies using preimplantation genetic diagnosis in women with RPL have shown that more than 50% of embryos were found to have aneuploidy (any deviation in the normal haploid number of chromosomes).

Diagnosis: Parental Karyotypes (a blood test) which measures chromosomes.
Treatment: Donor sperm or donor egg, or in some cases, preimplantation genetic diagnosis using IVF technology.

Ovarian Reserve
As a woman ages, so does her eggs, and each woman’s ovaries age at a unique rate. Ongoing research has shown that as the quality of a woman’s egg(s) declines, the quality of the embryo produced is less, and thus the chances of a spontaneous abortion in the first 3 months of pregnancy increases. Thus in some women with RPL, this may be an indication of a decline in the quality of their remaining eggs. Fortunately, there is a simple, safe and easily performed method for measuring your remaining ovarian reserve, and this is called a “Clomid Challenge Test”

Diagnosis: Clomid Challenge Test (CCT).
Treatment: Depending upon results of CCT, gonadotropins/WIUI, IVF, or possible Egg Donation IVF.

Infectious
While accounting for a smaller number of pregnancy losses, some studies have demonstrated that reproductive tract infections with myocoplasma appear to be associated with RPL. Cultures are frequently recommended at the time of initial consultation.

Treatment: Doxycycline 100 mg. twice daily for 7 days for both partners, taken simultaneously.

Autoimmune and Clotting Disorders
Probably less than 5% of women with RPL have an immunologic cause. We do frequently recommend testing for selected blood tests to rule-out autoimmune or inherited thrombophilia.

Diagnosis: ACA (anticardiolipin antibody), Lupus Anticoagulant test, Leiden Factor V mutation and Methylenetetrahydrofol Reductase (MTHFR) mutation
Treatment: Low dose Heparin therapy, Aspirin (ASA).

Endocrine
Evaluation of the luteal phase of a woman’s cycle, and the resulting effect on the development and thickness of her uterine lining. Several easy methods for testing are available, and treatment is simple and generally effective.

Diagnosis: Endometrial thickness on transvaginal ultrasound, timed endometrial biopsy, short luteal phase duration, Prolactin and TSH (thyroid stimulating hormone).
Treatment: Supplementation of cycle with vaginal or injectable progesterone, or HCG injections; correction of other hormonal or medical abnormalities.

Environmental
This is best assessed with a careful history. Studies have shown, for example, that women exposed to certain volatile anesthetic agents in the first 3 months of pregnancy have a higher miscarriage rate. Smoking has also been associated with a higher rate of infertility and pregnancy loss.