Recurrent Pregnancy Loss: When Tests Are Normal, What May Be Missing

Dr. Robyn Murphy | Fertility Naturopathic Doctor

Perhaps you have been diagnosed with “idiopathic infertility or recurrent pregnancy loss”. In this case, standard testing is normal and questions to the cause of infertility are left unanswered. With up to 50% of couples with a history a recurrent loss found in this position, you are not alone. This article talks about some of the underlying causes and the next steps if you find yourself in this position.

What Is Considered Recurrent Pregnancy Loss

Recurrent pregnancy loss is generally defined as two or more pregnancy losses before twenty weeks of pregnancy. This includes biochemical pregnancies and clinical losses that have been confirmed by ultrasound. While definitions vary slightly, the emotional and physical impact is significant regardless of how early or number of losses.

What Tests Are Typically Done for Recurrent Pregnancy Loss

Standard evaluation typically includes genetic testing of parents, uterine imaging, antiphospholipid antibody testing, thyroid function testing, and basic hormonal evaluation. These tests are important to uncover known causes. However, even with thorough evaluation, approximately half of all cases are classified as unexplained. This reflects the limitations of standard fertility testing rather than the absence of a contributing factor. A normal test result does not always mean that nothing is happening beneath the surface.

Commonly Overlooked Contributors to Recurrent Pregnancy Loss

Most fertility tests provides a snapshot in time. Hormonal signaling, immune balance, metabolic health, and endometrial function are dynamic processes that shift across the menstrual cycle and over months. Subtle dysfunction may not meet diagnostic thresholds but can still interfere with implantation or early placental development. Additional factors that may be contributing, include:

• Subtle Immune Dysregulation - Early pregnancy requires a carefully balanced immune response. The immune system must tolerate the developing embryo while maintaining normal defense. In some cases, immune signaling may be overly inflammatory or poorly regulated without meeting criteria for autoimmune disease.
• Endometrial Environment and Implantation Factors - A receptive endometrial environment is essential for implantation. Inflammation, altered receptivity, luteal phase nuances, and local blood flow all influence early pregnancy success. Progesterone alone does not capture the full picture of implantation health.
• Metabolic and Insulin Signaling - Metabolic health influences early placental development. Even when glucose and hemoglobin A1C appear normal, subtle insulin resistance or metabolic stress can affect implantation and placentation.
• Coagulation and Microcirculation Factors - Classic clotting disorders are included in standard testing, but early placental development also depends on healthy microcirculation. Subtle vascular factors may not meet diagnostic criteria yet still impact pregnancy.
• Egg Quality Versus Egg Quantity - Ovarian reserve testing evaluates egg quantity, not egg quality. Normal AMH or follicle counts do not guarantee chromosomal integrity. Both age related and non age related factors can influence egg quality.

Reasonable Next Steps After Normal Testing

Identifying patterns through a comprehensive history, optimizing metabolic and inflammatory balance, and supporting reproductive physiology over time are next steps to consider. Recurrent pregnancy loss is rarely caused by a single factor. A systems-based approach focuses on pinpointing patterns and supporting the body to address underlying causes.

Other tests that may be considered:

• Metabolic markers
• Vitamin and nutrient levels
• Autoimmune and inflammatory markers
• Microbiome testing

They may be a few difference patterns that exist simultaneously. My approach is evidence informed, individualized, and focused on understanding what may be contributing beneath the surface. If you are seeking an in-depth consultation and a personalized approach to fertility care, you are welcome to book a consultation with me to explore your next steps.

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References

1. Bagkou Dimakou D, Tamblyn J, Justin C, Coomarasamy A, Richter A. Diagnosis and management of idiopathic recurrent pregnancy loss (RPL): Current immune testing and immunomodulatory treatment practice in the United Kingdom. Journal of Reproductive Immunology. 2022;153:103662.
2. Habets DHJ, Schiffer VMMM, Kraneburg LPA, et al. Preconceptional evaluation of women with recurrent pregnancy loss: the additional value of assessing vascular and metabolic status. BMC Pregnancy Childbirth. 2022;22:75.
3. American Society for Reproductive Medicine. Evaluation and treatment of recurrent pregnancy loss. Fertility and Sterility.
4. European Society of Human Reproduction and Embryology. Recurrent pregnancy loss guidelines.
5. Royal College of Obstetricians and Gynaecologists. The investigation and treatment of couples with recurrent miscarriage.