When I first see a patient in consultation for recurrent early pregnancy loss, I usually spend at least an hour with them. The first part of the appointment is spent in obtaining a detailed history – medical, social, and family. Since many different factors may be contributing to their difficulty carrying a baby, I ask them to be as accurate and honest as they can be in answering my questions. The following will give you some idea (by no means complete!) on the direction of my queries (and if you plan to see someone for a history of recurrent pregnancy loss, it is a good idea to be prepared to answer them!):
Were you born with any congenital problems? How old were you when you started having periods? Are they regular now? How many days in a cycle? How many days do you bleed? Bleeding between periods? Symptoms related to menstruation? Past/present gynecological problems and surgery (D&Cs, cervical procedures,…)? Past and current medical problems? Recent changes in weight, skin, appetite, hair, bowel habits, etc…? Medications? Over-the-counter therapies? Smoking, caffeine, alcohol, and substance abuse history? Work environment and exposures? Living situation? Family history (patient and partner!) with attention to thyroid disorders, diabetes, clotting problems, difficulty carrying pregnancies, repetitive miscarriages, chromosomal or genetic conditions, autoimmune diseases, mental retardation, birth defects…?
I spend a lot of time gathering details about their pregnancy losses: How long did it take to conceive? Have you been evaluated for ‘infertility’? What sort of evaluation did you have? Were any of your pregnancies conceived by infertility treatment and what kind? How far did you carry each pregnancy? What sort of pregnancy ‘symptoms’ did you have? How many weeks size were the babies when you were told they were lost? Was a baby ever seen? Was a heart beat ever seen? Did you have a D&C? Did you have the ‘products of conception’ analyzed by pathology or for chromosomal abnormalities? Were any abnormalities of the babies seen before or after they were lost?
Once this information has been gathered, a comprehensive physical exam is also warranted. Items of special attention include: height, weight, blood pressure, body type, thyroid gland, skin, hair and fat distribution, breast exam (to look for galactorrhea - milk production), and a very thorough gynecological evaluation to assess any gross evidence of congenital or acquired uterine, cervical, or vaginal abnormalities. It is only after all the above is done that I sit down with a pad of paper, discuss the various factors that may be associated with recurrent pregnancy loss, identify specific areas of concern based on the patient’s own history and physical findings, and outline a possible diagnostic evaluation. In reference to the individual posts I have written on these factors, among the diagnostic options to be considered are:
• Hormonal tests: Basic testing includes - thyroid stimulating hormone (TSH); mid-luteal phase (menstrual cycle day 21) progesterone; prolactin; fasting blood sugar (usually coupled with a ‘complete metabolic profile’ study) and if this is abnormal, a full glucose tolerance test. If there is a history of irregular menstrual and/or physical findings of excessive androgenization (male hormone) production, consider: early proliferative phase (menstrual cycle day 3) follicle stimulating hormone (FSH) and estradiol, and luteinizing hormone (LH) (cycle day 9 or 10); androgen levels, including free and total testosterone, dehydroepiandrosterone sulfate (DHEA-S), and 17-hydroxyprogesterone (17-OH-P). For these latter studies, I will often send the woman to a specialist in reproductive endocrinology and infertility (REI) for evaluation and, if necessary, management through conception.
• Chromosome studies: Offered to both partners (start with the woman if resources are limited).
• Uterine abnormalities: Sonohysterogram (uterine ultrasound done with fluid distention of the uterus), best coupled with hysteroscopy (looking inside the uterus with a small scope). If any abnormality is suggested, a diagnostic laparoscopy (to further evaluate the uterus and pelvis) and, perhaps, an intravenous pyelogram (IVP) since ‘Mullerian’ defects are often associated with urinary tract abnormalities as well.
• Immunologic and hematological tests: complete blood count (CBC); blood type and antibody screen; antinuclear antibodies (ANA); lupus anticoagulant, antiphospholipid antibodies (usually start with screen for anticardiolipin antibodies); Factor V Leiden; prothrombin mutation; methylenetetrahydrofolate reductase (MTHFR) mutations; antithrombin III; protein C; protein S; homocysteine levels. Further testing depends on the results of these initial studies. On rare occasions, or if consanguinity is suggested or the patient fails initial attempts at ‘therapy’, consider maternal and paternal HLA testing.
• Known medical conditions: If the patient has known diabetes, hypertension, autoimmune condition, seizure disorder requiring ongoing medical therapy, or some other chronic medical condition, further evaluation appropriate to that condition is also conducted.
In my next final posts on the subject of recurrent early pregnancy loss, I will outline general recommendations for ‘empiric’ treatment, as well as specific options for therapy, based on results of the diagnostic studies above, to help a couple achieve a successful pregnancy…