Preconception Care Part 2:  A guide to comprehensive lab testing and evaluation

Dr. Bethany Mattson, ND

Comprehensive preconception care is foundational to healthy pregnancies and future health outcomes. Thorough evaluation and appropriate management can greatly impact pregnancy in addition to long-term health of the mother and future offspring. Preconception care should include a comprehensive investigation of both partner’s foundations of health and fertility-specific outcomes. The diagnosis of infertility can often be time-sensitive, and thorough preconception testing can uncover potential fertility hurdles for both partners as well as potential pregnancy and postpartum complications. Preconception testing can be broken into the following categories: 

1. Annual well-woman care
2. Pregnancy-specific labs
3. Basic serum screening labs
4. Advanced serum testing as needed for select populations
5. Functional testing options
6. Male-specific testing

1) Annual Well-Woman Exams:

• Pap and HPV co-testing: It is important for women to be up to date on annual cervical cancer and HPV screening exams prior to pregnancy due to increased risk of cervical abnormalities in pregnancy with concurrent HPV infection. 

• Updated sexually transmitted infection (STI) panel: The presence of STIs can impact both fertility and pregnancy outcomes and should be identified and addressed prior to conception. In addition to increasing pregnancy risk, STIs can harm the fetus. Conditions to screen for before and during pregnancy include: 
  • Gonorrhea and chlamydia (GC/CT): Can lead to pelvic inflammatory disease and infertility, while also increasing the risk of neonatal conjunctivitis and pneumonia.
  • Syphilis (Treponema pallidum): Syphilis should be screened for at every initial prenatal visit due to potential of severe congenital abnormalities, miscarriage, and stillbirth. 
  • Hepatitis A, B, and C (HAV, HBV, HCB)
  • Human immunodeficiency virus (HIV) 

• Vaginitis panel: Bacterial vaginosis has been linked to increased miscarriage rates and preterm birth. Treatment of any vaginal imbalance or infection prior to pregnancy is key.   

• Genital mycoplasma testing: This test may be indicated for some patients based on risk factors and symptom history. Mycoplasma genitalium has been found to be a significant risk factor for both infertility and preterm birth. Mycoplasma hominis has also been significantly associated with infertility and premature rupture of membranes (PROM).

• Urinalysis as indicated: Indicated to rule out asymptomatic bacterial infections, or other imbalances such as proteinuria. Urinary tract infections have been linked to preterm birth and low birth weight. 

2) Pregnancy Specific Labs

Testing for immunity status prior to pregnancy is ideal to ensure the mother is immune to important conditions prior to conception, as some vaccines cannot be administered in pregnancy, or mothers may not want to receive vaccinations in pregnancy. A standard immune panel includes varicella-zoster, measles, mumps, rubella (MMR), Bordetella pertussis IgG, and Tetanus/diphtheria. The addition of ABO and Rho(D) typing can determine any risk of hemolytic disease in neonates with presence of Rh incompatibility. Rh immunoglobulin may need to be administered to Rh-negative mothers to protect future pregnancies.  

Genetic carrier screening is another important option to offer patients. This test can determine if the mother is a carrier of any autosomal recessive disorders including cystic fibrosis, spinal muscular atrophy, and hemoglobinopathies. Understanding genetic risk prior to conception can help parents make informed decisions and understand options including the use of donor egg or sperm, if needed. 

3) Basic Serum Screening Labs:

Screening labs provide a snapshot of a woman’s hormonal and metabolic health, which are critical for fertility and pregnancy. This category includes reproductive hormones, androgens, thyroid panel, cardiometabolic markers, and vitamin/nutrient levels. 

The main serum hormone tests are completed on cycle day 3 and include estradiol, follicle stimulating hormone (FSH), luteinizing hormone (LH), anti-Mullerian hormone (AMH), and prolactin. Together, these labs provide insight into suspected ovarian reserve, egg quality, androgen balance, and provide framework for natural conception success. Progesterone should be completed about 7 days after suspected ovulation has occurred to assess for luteal phase defects and need for progesterone supplementation to reduce risk of miscarriage. 

Additional labs include testosterone, sex hormone binding globulin, and DHEA to assess the full androgen picture. Conditions such as PCOS can lead to anovulation, infertility, and increased pregnancy risk, so early diagnosis and management is key. Thyroid imbalance can also affect ovulation, overall cycle balance, and increased miscarriage and fetal risk, so a full thyroid panel including thyroid antibodies is indicated.  

All metabolic markers should be a foundational aspect of preconception testing to rule out potential conditions such an insulin resistance, diabetes, hyperlipidemia, or high inflammation levels. Key tests include fasting insulin, fasting blood glucose, hemoglobin A1c, lipid panel, c-reactive protein, and homocysteine. Imbalances in these metabolic markers have been linked to increased miscarriage and rates of preterm birth. 

Vitamin and nutrient testing in the preconception period are ideal to uncover and correct any deficiencies that may impact fertility, pregnancy, and health of the fetus. Key nutrients to check include: 

4) Advanced Serum Screening Labs

The following labs are indicated for certain populations and should only be utilized when clinically indicated:

• Inhibin B: Indicated for deeper evaluation of ovarian reserve and follicular activity.
• Antiphospholipid antibodies and Lupus anticoagulant: Indicated for evaluation of recurrent pregnancy loss and risk of thrombotic events.  
• Antinuclear antibodies: Indicated for additional autoimmunity testing. 
• Epstein-Barr virus (EBV) antibody panel: Indicated for fertility evaluation as reactivation has been linked to infertility.  
• CA-125: Indicated when endometriosis is suspected.  
• 17-OH progesterone: Used to screen for congenital adrenal hyperplasia (CAH) and late-onset CAH, a disorder that can impact fertility. Testing should be performed on cycle day 3, fasting, with a collection time before 8am for accuracy. 
• Celiac testing: Undiagnosed celiac disease can cause infertility and adverse pregnancy outcomes.  
• Factor V Leiden: Active disease is strongly associated with frequent miscarriage and requires close supervision and support. However, even carrier status for Factor V can increase the risk for clotting during implantation. This prevents germination and results in early miscarriage. 

5) Functional Testing Options:

Functional tests provide deeper insights compared to serum labs and are a valuable resource to optimize preconception care. 

6) Male Partner-Specific Tests

The health status of the male partner contributes significantly to optimal fertility, pregnancy, and future health of the offspring. Although there is often little emphasis placed on the male partner, male factor infertility accounts for over 30% of all infertility cases, and a combination of male and female factors account for another 30%. The following tests are recommended for the male partner during preconception care:

1. Semen analysis:
   • Can assess for all key sperm parameters including percent of abnormal sperm present. Abnormal morphology can greatly impact fertility rates and chance of miscarriage and recurrent pregnancy loss. Optimizing sperm quality with lifestyle and supplementation can greatly improve outcomes. Other key parameters include sperm count, motility, concentration, and presence of inflammation or debris.  

• Sperm DNA fragmentation:
  • Fragmentation offers a deeper investigation into sperm quality. Sperm DNA fragmentation testing assesses the integrity of the genetic material within sperm. High levels of DNA fragmentation can impair fertilization and embryo development, which can lead to reduced fertility rates and increased risk of miscarriage. Factors such as oxidative stress levels, lifestyle choices, and environmental toxin exposure can significantly contribute to DNA fragmentation. 

• Toxin/heavy metal testing:
  • Exposure to toxins and endocrine disrupting chemicals has a known negative impact on sperm count and quality. Heavy metals easily accumulate in sperm and can cause hormonal imbalance. Common toxins that impact male fertility include lead and cadmium, pesticides, bisphenol A, and phthalates.  

• Additional male partner testing includes all the basic screening labs that females complete, with the addition of extra sensitive estradiol, STI and genital mycoplasma testing, genetic carrier screening if the female partner tests positive, and any functional testing indicated for each specific case.

• In some cases, women can have an allergic response to their partners semen. If there are no other identifiable culprits to why a couple is struggling to conceive, you may consider testing the woman for an allergic response to her partners semen. This is done through a skin test. 

Conclusion

Comprehensive testing prior to pregnancy is essential for identifying and correcting potential roadblocks to fertility and pregnancy outcomes. An integrative approach that combines conventional and functional testing in these 6 key areas is evidence-based and shown to improve health outcomes for both parents and their future children.