What lab tests and management are recommended for a woman with a history of Polycystic Ovary Syndrome (PCOS) and a previous miscarriage, who now has a regular menstrual cycle, and is trying to conceive?

Laboratory Recommendations for Preconception Evaluation in PCOS with Prior Miscarriage

Order a comprehensive preconception laboratory panel including TSH, prolactin, total testosterone (via LC-MS/MS), 75-gram oral glucose tolerance test, and fasting lipid profile—these tests are essential regardless of regular menstrual cycles, as 30% of women with PCOS have normal testosterone levels and metabolic screening is mandatory before attempting conception. 1, 2

Essential First-Line Laboratory Tests

Hormonal Assessment

• Measure thyroid-stimulating hormone (TSH) to exclude thyroid disease as a contributor to the prior miscarriage and to optimize thyroid function before conception 1, 3
• Measure prolactin using morning resting serum levels (not post-stress), with levels >20 μg/L considered abnormal—hyperprolactinemia can contribute to both infertility and miscarriage 1, 3
• Measure total testosterone using liquid chromatography-tandem mass spectrometry (LC-MS/MS) as the preferred method, which shows 92% specificity compared to 78% for direct immunoassays—remember that 30% of women with confirmed PCOS have normal testosterone levels 1
• Measure free testosterone or calculate Free Androgen Index (FAI) if LC-MS/MS is available, as free testosterone demonstrates superior sensitivity (89%) compared to total testosterone (74%) 1

Critical Metabolic Screening (Mandatory Before Conception)

• Perform a 75-gram oral glucose tolerance test at preconception or within the first 20 weeks if not done preconceptionally, as women with PCOS have 31-35% risk of impaired glucose tolerance and 7.5-10% risk of type 2 diabetes 2, 4
• Obtain fasting lipid profile including total cholesterol, LDL, HDL, and triglycerides, as insulin resistance in PCOS creates an atherogenic lipid profile that increases cardiovascular risk during pregnancy 1, 2
• Measure fasting glucose and insulin levels with calculation of glucose/insulin ratio, where a ratio >4 suggests reduced insulin sensitivity 3, 1

Additional Hormonal Tests to Consider

• Measure LH and FSH between cycle days 3-6 (average of three samples taken 20 minutes apart) to assess the hormonal profile, though an LH/FSH ratio >2 is only abnormal in 35-44% of PCOS cases and should not be used as a standalone diagnostic marker 3, 1
• Measure mid-luteal progesterone (approximately day 21 of a 28-day cycle) to confirm ovulation, with levels <6 nmol/L indicating anovulation—this is particularly important given the history of miscarriage, as anovulatory cycles may indicate luteal phase defects 3, 1

Secondary Laboratory Tests Based on Clinical Suspicion

• Measure androstenedione only if testosterone levels are normal but clinical hyperandrogenism persists, with levels >10.0 nmol/L warranting evaluation for adrenal/ovarian tumor 3, 1
• Measure DHEAS if there are features suggesting adrenal androgen excess (severe hirsutism, rapid onset of symptoms), with age-adjusted thresholds used to rule out non-classical congenital adrenal hyperplasia 3, 1
• Measure 17-hydroxyprogesterone if DHEAS is markedly elevated to exclude congenital adrenal hyperplasia 5

Physical Assessment Parameters

• Calculate body mass index (BMI), with BMI >25 considered obese in the context of PCOS—even 5% weight loss improves ovulation and pregnancy rates 3, 6
• Measure waist-hip ratio (WHR), with WHR >0.9 indicating truncal obesity that exacerbates metabolic, reproductive, and psychological features of PCOS 3, 5
• Examine for acanthosis nigricans, which indicates underlying insulin resistance and increased metabolic risk 5

Critical Pitfalls to Avoid

• Do not skip metabolic screening even with regular cycles—the regular menstrual pattern does not exclude metabolic dysfunction, and women with PCOS have significantly elevated risks of gestational diabetes, pregnancy-induced hypertension, and pre-eclampsia 2, 4
• Do not rely solely on LH/FSH ratio for diagnosis—it is abnormal in only 35-44% of PCOS cases and has poor diagnostic utility 1
• Do not use ultrasound as a primary diagnostic tool if the patient already has clinical hyperandrogenism and irregular cycles (though she now has regular cycles, the PCOS diagnosis is established), as ultrasound adds little diagnostic value when two Rotterdam criteria are already met 1
• Confirm any prolactin elevation with 2-3 samples at 20-60 minute intervals via indwelling cannula to exclude stress-related spurious elevation before pursuing further pituitary imaging 5

Preconception Management Considerations

• Initiate lifestyle modification targeting 5-10% weight loss with a 500-750 kcal/day energy deficit and at least 250 minutes/week of moderate-intensity exercise before attempting conception 6, 5
• Consider metformin in addition to lifestyle modification for weight management and improving cardiometabolic risk factors, particularly if overweight or obese—metformin appears safe in pregnancy and may reduce miscarriage rates 6, 2
• Screen and treat hypertension and optimize glucose control prior to attempting conception to reduce risks of pre-eclampsia, placental abruption, and gestational diabetes 4
• Repeat the 75-gram oral glucose tolerance test at 24-28 weeks of pregnancy if conception occurs, as rates of progression to gestational diabetes are high 2