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Causes and Treatment of Recurrent Pregnancy Loss (RPL)
- Anatomic
Distortion of the uterine cavity may be found in approximately 10% to 15% of women with recurrent pregnancy losses. Inborn (congenital) abnormalities of uterine shape are relatively common. Septate uterus contains 2 small cavities within a unified uterine body (see images below). Other uterine abnormalities include scarring (Asherman’s syndrome), submucous fibroids and endometrial polyps.
Ultrasound of septate uterus (S=septum, C=cavities)
Hysteroscopic view of septum at arrow and 2 cavities in upper panel; unified uterine cavity after incision of septum in lower panel
Diagnostic tests: HSG (hystero-salpingogram or dye study), SIS (saline infusion sono-hysterogram), trans-vaginal ultrasound, MRI (magnetic resonance imaging).
Treatment: Hysteroscopy with removal of the abnormality usually succeeds. Rarely a gestational surrogate is necessary (What is Surrogacy?).
- Genetic
In 2-4% of couples with RPL, one partner will have a genetically balanced chromosome rearrangement (balanced translocation). When eggs and sperm are formed in such an individual they frequently exhibit an unbalanced state since eggs and sperm contain only half of the chromosomes compared to the other cells in the would-be parents.
Other couples with RPL may have an increased frequency of forming embryos with an abnormal number of chromosomes (aneuploidy). In fact, 60% or more of all early miscarriages may be caused by a random chromosomal abnormality, usually a missing or duplicated chromosome. The chance of a miscarriage increases as a woman ages. After age 40, more than one-third of all pregnancies end in miscarriage. Most of these embryos have an abnormal number of chromosomes.
Diagnostic Tests: Karyotype on the parents and pregnancy tissue at D&C (if available).
Treatment: IVF with pre-implantation genetic diagnosis (What is PGD?) or the use of donor sperm or donor egg.
- Hormonal
Disorders of thyroid hormones and prolactin may result in RPL. Progesterone secretion in the luteal phase and in early pregnancy is important for successful implantation and development. Reduced ovarian reserve, which is associated with aging, is a major cause of pregnancy losses and must be evaluated in detail (How Do We Test Ovarian Reserve? What is Age Factor?)
Diagnostic tests: Serum TSH, prolactin and progesterone. Cycle day 3 FSH/Estradiol, AFC (antral follicle count) on transvaginal ultrasound and clomiphene citrate challenge test (CCCT).
Treatments: Hormonal supplementation with thyroid hormone or suppression of excess prolactin secretion. Supplemental progesterone and/or hCG, and ovulation augmentation are relatively simple and effective approaches. While no replenishment of ovarian reserve is currently possible, early diagnosis and aggressive therapies with FSH/IUI or IVF may increase the chance of a successful pregnancy. In more extreme cases of diminished ovarian reserve, donor egg IVF may be necessary (Donor Egg Program).
- Autoimmune and Clotting Disorders
A complex and highly controversial area of research and therapy, immunologic factors cause about 3-15% of recurrent miscarriages. While each condition is rare, as a group, congenital clotting disorders (thrombophilias) may lead to RPL, poor reproductive outcomes and obstetrical complications.
Diagnostic tests: ACA (anticardiolipin antibody), Lupus Anticoagulant, Anti-Phospholipid Antibodies; Factor II, Factor V(Leiden) and MTHFR mutations and multiple other tests.
Treatments include: low dose aspirin and heparin; high dose folic acid; in rare cases. IVIG (intravenous immunoglobulin) infusions may be appropriate under supervision of a reproductive immunology consultant.
- Infections
While unlikely to cause symptoms, Myocoplasma and Ureoplasma appear to be associated with RPL. Bacterial vaginosis (BV) may be associated with premature rupture of membranes and untoward pregnancy outcomes.
Diagnostic tests: Cervical swab.
Treatment: Antibiotics.
- Male factor
Increasing evidence suggests that abnormalities of sperm DNA may affect embryo development and increase miscarriage risk.
However, these data are still very preliminary, and it is not known how often sperm defects contribute to recurrent miscarriage.
- Toxic Exposure
Women exposed to anesthetic agents, specifically nitrous oxide, in the first 3 months of pregnancy have a higher miscarriage rate. Smoking is associated with both infertility and increased pregnancy loss rate.
If you have suffered two or more early pregnancy losses, you may wish to contact us to schedule a consultation with Dr. Chetkowski who takes special interest in the evaluation and treatment of RPL. Thorough evaluation and targeted therapy usually result in favorable outcomes.