Pregnancy losses occur in about 15% of pregnancies in women under the age of 35 years but their frequency rises sharply with advancing age. Most of these losses are “sporadic” inasmuch they occur in different women rather than over and over again in the same woman. About half of sporadic pregnancy losses are due to chromosomal abnormalities which are not compatible with normal development.
Recurrent pregnancy loss (RPL), on the other hand, is an uncommon condition which is currently defined by two or more failed consecutive pregnancies. RPL is distinct from infertility and warrants an extensive evaluation to detect specific abnormalities. Most couples with RPL will eventually achieve a live birth of a healthy infant. Close monitoring of early pregnancy, judicious use of the many tests and treatments as well as emotional support, all play an important role in a comprehensive approach to this complex condition.
Causes and Treatments of Recurrent Pregnancy Loss
Distortion of the uterine cavity may be found in approximately 10% to 15% of women with recurrent pregnancy losses. Septate uterus is the most common of congenital uterine anomalies with 2 small cavities within a unified uterine body (see images below). Acquired uterine abnormalities include submucous fibroids, polyps and scarring (Asherman’s syndrome).
Diagnostic tests: HSG (hystero-salpingogram or dye study), SIS (saline infusion sono-hysterogram), trans-vaginal ultrasound, MRI (magnetic resonance imaging).
Treatment: Hysteroscopy to correct the abnormality. In some cases a gestational surrogate is advisable.
Ultrasound of a 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
In 2-4% of couples, one partner will have a genetic rearrangement (balanced translocation) which is transmitted to the eggs or sperm.
Other couples with RPL may have a tendency to form embryos with an abnormal number of chromosomes (aneuploidy) without directly transmitting any abnormality. 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: Chromosomal analysis on the parents and/or pregnancy tissue (if available).
Treatment: IVF with genetic testing of embryos (PGS), or the use of donor sperm or egg donor eggs.
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.
Diagnostic tests: Serum TSH, prolactin and progesterone. AMH, FSH/Estradiol and antral follicle count on ultrasound.
Treatments: Hormonal supplementation or suppression as appropriate. Ovulation augmentation, FSH/IUI or IVF. Donor egg IVF.
IV. Immune Disorders
A complex and controversial area of reproductive medicines, immune factors cause about 3-15% of recurrent losses. Immune abnormalities fall into 2 categories: 1. Auto-immune conditions in which abnormal antibodies are present; 2. Dysregulation of natural killer (NK) cell number and/or activity.
Diagnostic tests: ACA (anti-cardiolipin antibody), Lupus Anticoagulant, Anti Beta II Glycoprotein, Anti-Phospholipid Antibodies, Anti-Thyroid Antibodies. Assays for NK-cell activity and frequency in blood and in endometrial biopsy.
Treatments: Aspirin and heparin for autoimmune disorder. Intralipid infusion for NK-cell dysregulation; steroids.
V. Other Conditions
Prolonged toxic exposure to tobacco smoke. nitrous oxide (anesthetic agent) and other chemicals. Recent evidence suggests that fragmentation of sperm DNA might contribute to miscarriage risk. In the presence of either personal or family history of clotting disorders, evaluation for mutations in Factor V (Leiden), Factor II (Prothrombin) and fasting homocysteine. In rare cases cervical infection with Myocoplasma and Ureoplasma appear to be associated with miscarriages. Bacterial vaginosis (BV) may be associated with premature rupture of membranes and untoward pregnancy outcomes.
Patients at risk for miscarriage come to us from Sacramento, San Francisco, the Bay Area, Berkeley, Oakland and nearby communities.