Hormonal tests for miscarriage: what and when to take

Pregnancy loss includes single and repeated spontaneous losses. Hormonal imbalances can be both direct and indirect causes of loss, but their contribution varies depending on the type of imbalance and the woman's age. Current guidelines recommend targeted hormonal assessment within the context of a comprehensive examination, rather than routine "broad" testing for all women. [1]

Direct evidence linking certain hormonal parameters to miscarriage risk is limited: it often involves a combination of clinical presentation and laboratory data. Therefore, the diagnostic strategy is focused on identifying conditions for which treatment options are available or for which an impact on pregnancy prognosis has been demonstrated. [2]

A key principle is that testing should be clinically justified. For example, thyroid function testing is recommended for most women with recurrent pregnancy losses, as the abnormalities identified are treatable. In contrast, a number of other hormonal tests are not recommended in the absence of relevant symptoms. [3]

When evaluating results, it is important to use population-specific reference ranges and take into account the phase of the menstrual cycle. Incorrect interpretation of a single value without context can lead to unnecessary interventions. [4]

Thyroid Function: What to Test and How to Interpret It

The thyroid gland affects fertility and pregnancy. Recommended initial testing includes thyroid-stimulating hormone (TSH) measurement and, if abnormal or to clarify risk, thyroid peroxidase antibody testing. These tests are warranted because both overt and subclinical hypothyroidism are associated with an increased risk of pregnancy loss, and levothyroxine therapy improves outcome in overt cases. [5]

Thyroid-stimulating hormone levels vary by age, population, and pregnancy status. For women of reproductive age and those planning a pregnancy, local and international recommendations for upper thyroid-stimulating hormone levels should be followed. In cases of confirmed overt hypothyroidism, treatment with levothyroxine is mandatory. [6]

Thyroid peroxidase antibodies can be a marker of increased risk even with normal thyroid-stimulating hormone. The presence of a positive antibody titer alone does not always require treatment, but some guidelines suggest considering treatment for subclinical hypothyroidism in those with positive antibodies and a high risk of loss. The decision should be individualized. [7]

Rule of thumb: The standard thyroid function screening test for women with recurrent losses is a thyroid-stimulating hormone (TSH) test. Additional antibody testing is recommended if TSH is abnormal or if there is clinical evidence of autoimmune thyroiditis. [8]

Table 1. Recommended thyroid tests and interpretation

Test	Target	Clinical interpretation
Thyroid stimulating hormone (TSH)	Thyroid function screening	Initial assessment; rely on local references. [9]
Free thyroxine (FT4)	Confirmation of abnormal TSH	Necessary for low or high TSH. [10]
Thyroid peroxidase antibodies (TPO-Ab)	Search for autoimmune component	A positive titer increases the risk of losses; evaluate in the context of TSH. [11]

Prolactin: When to Measure and What the Results Mean

Elevated prolactin leads to anovulation and can be a cause of infertility and irregular menstruation. However, in women with recurrent pregnancy losses, asymptomatic hyperprolactinemia is rare, and the association between prolactinemia and recurrent pregnancy losses is insufficiently proven. Therefore, prolactin measurement is recommended for clinical signs of hyperprolactinemia: amenorrhea, galactorrhea, and severe oligomenorrhea. [12]

Occasional slightly elevated prolactin levels may be a result of stress or improperly prepared blood sampling. If an elevated level is detected, a repeat test is recommended, ensuring proper preparation and ruling out medication-related causes. If a pathological increase is confirmed, a search for a prolactinoma and treatment, usually with medication, are necessary. [13]

Low prolactin levels are not yet considered a definitive cause of miscarriage. There are some hypotheses in the literature about the role of low normal levels, but the evidence base is weak. Therefore, low prolactin without clinical symptoms is not an indication for specific treatment to reduce the risk of pregnancy loss. [14]

A clinically important rule: check prolactin in the presence of corresponding symptoms and only if pathology is confirmed, conduct further diagnostics and treatment aimed at restoring ovulation and normalizing the menstrual cycle. [15]

Table 2. Approach to prolactin in case of miscarriage

Scenario	Recommended action	Comment
Symptoms of hyperprolactinemia	Measure prolactin, repeat if necessary, MRI if concentration is high	Look for prolactinoma. [16]
Mild elevation without symptoms	Re-test with proper preparation	Consider stress and medications. [17]
Normal or low prolactin without symptoms	No further action is required.	There is no evidence of benefit of treatment for preventing losses.[18]

Progesterone and luteal phase assessment: limitations of testing

Progesterone is necessary for maintaining early pregnancy after ovulation. However, evidence that measuring progesterone levels at a single point in the cycle reliably predicts the risk of recurrent pregnancy loss is limited. "Luteal phase" testing, in the form of a single progesterone measurement, is not recommended for determining the cause of recurrent pregnancy loss. [19]

If there is a clinical suspicion of luteal phase insufficiency, some guidelines indicate that dynamic parameters and clinical assessment are more informative. Endometrial biopsy as a method for diagnosing luteal phase insufficiency is rarely used and only for specific indications. [20]

Progesterone supplementation is used in certain situations, such as in the case of threatened miscarriage with confirmed fetal heartbeat or during assisted reproductive technologies. However, for the prevention of recurrent early pregnancy loss, the evidence for the effectiveness of progesterone supplementation is mixed and depends on the specific clinical situation. [21]

The takeaway message: Do not routinely test progesterone in an attempt to explain recurrent pregnancy loss. The decision to provide progesterone support should be based on the clinical picture and evidence for the individual case. [22]

Table 3. The role of progesterone in miscarriage

Question	Recommendation	Note
Routine progesterone testing	Not recommended	Single values are of little information. [23]
Progesterone support for threatened miscarriage	Consider according to indications	There is evidence in individual situations. [24]
Endometrial biopsy for luteal phase assessment	Apply selectively	Not routine for RPL. [25]

Polycystic ovary syndrome and metabolic testing

Polycystic ovary syndrome is associated with infertility and some early pregnancy complications, but there is no direct and definitive link to recurrent pregnancy loss. Research and guidelines do not recommend routine insulin resistance testing in all women with recurrent pregnancy loss. Evaluation is indicated if polycystic ovary syndrome is suspected based on clinical features. [26]

Routine testing of glucose levels and lipid profile may be warranted in women with excess body weight or clinical features of metabolic syndrome. Correction of excess body weight and improvement of the metabolic profile are associated with an increased likelihood of successful pregnancy. [27]

Fasting insulin and the HOMA-IR index are not recommended as part of routine testing for recurrent pregnancy losses, as their predictive value for subsequent pregnancies has not been proven. Assessment should be targeted and based on symptoms and risk factors. [28]

Therefore, screening for polycystic ovary syndrome and insulin resistance is performed in appropriate clinical settings, rather than routinely in all patients with recurrent pregnancy losses. Emphasis is placed on lifestyle modification and weight management, if necessary. [29]

Table 4. Metabolic tests: when testing is warranted

Indicator	When to explore	What to do if the result is abnormal
Glucose level and glycated hemoglobin	If you are overweight or have risk factors for diabetes	Dietary and medicinal corrections as indicated. [30]
Fasting insulin, HOMA-IR	Only if there is clinical suspicion of insulin resistance	Consider in PCOS with metabolic disorders. [31]
Lipid profile	For cardiovascular risk factors	Lifestyle correction and treatment as indicated. [32]

Ovarian Reserve and Androgens: What's Important to Know

Studies have linked decreased ovarian reserve to increased rates of spontaneous miscarriage, but the idea that routine ovarian reserve testing in all women with recurrent miscarriages is necessary is unproven. Therefore, testing for anti-Müllerian hormone and follicle-stimulating hormone is advisable in cases of clinical suspicion: age above the threshold, previous signs of low reserve, or when planning assisted reproductive technologies. [33]

Androgen profile and testosterone levels are not recommended for routine screening in cases of recurrent pregnancy loss in the absence of clinical evidence of hyperandrogenism. Similarly, luteinizing hormone measurement outside the context of cycle irregularities generally does not provide clinically relevant information. [34]

Assessing ovarian reserve helps in planning a strategy for further reproductive care and in informing the couple about the reproductive prognosis. This information is important when deciding on the indications for in vitro fertilization and the need to accelerate pregnancy attempts. [35]

Conclusion: Ovarian reserve testing is appropriate in the assessment of fertility and in the presence of risk factors, but is not necessary as a routine part of the workup of all women with recurrent pregnancy losses.[36]

Table 5. Ovarian reserve and androgens in RPL

Test	Indications	Significance for clinical practice
Anti-Müllerian hormone	Age, suspected low reserve, ART planning	Evaluation of prognosis and treatment planning. [37]
Follicle-stimulating hormone	At an early stage of the cycle, if there is a suspicion of a decrease in reserve	Used in conjunction with other markers. [38]
Androgens	Only in the clinic of hyperandrogenism	Not routine for RPL. [39]

Practical examination algorithm and key recommendations

Current recommendations converge on the following algorithm for recurrent losses: collect a detailed medical history and perform targeted first-level investigations; among hormonal tests, thyroid function screening is mandatory; other hormonal tests are performed when clinically indicated. This approach reduces unnecessary investigations and focuses resources on important and treatable conditions. [40]

Routine testing of parameters for which there is no evidence that correction improves prognosis is not recommended. These include standard prolactin testing in the absence of symptoms, luteal phase tests with single measurements, and androgen and insulin resistance testing without clinical justification. [41]

If positive findings are detected, the management algorithm should take into account proven therapeutic options. For example, in cases of overt hypothyroidism, replacement therapy should be administered; in cases of prolactinoma, appropriate specialized treatment should be administered; and in cases of decreased ovarian reserve, reproductive medicine strategies should be discussed. [42]

It is important to ensure a multidisciplinary approach: hormonal testing should be integrated with genetic, anatomical, and immunological examinations as indicated. Individualized management increases the chances of a successful outcome in subsequent pregnancies. [43]

Table 6. Final diagnostic algorithm (schematic)

Stage	Action	Note
1	Detailed history and basic examination	A benchmark for further testing. [44]
2	Thyroid function screening (TSH)	Most women with RPL.[45]
3	Targeted hormonal tests in the clinic	Prolactin for symptoms, reserve tests if indicated. [46]
4	Integration with other studies	Genetics, anatomy, autoimmunity as indicated. [47]

Conclusion and practical summary

Hormonal assessment in cases of miscarriage should be targeted and clinically justified. Thyroid function screening is a mandatory component of most protocols. Other hormonal tests are performed as indicated. This approach is cost-effective and clinically justified. [48]

Routine, broad hormonal test panels without clinical context do not add prognostic value and may lead to unnecessary anxiety and interventions. Positive findings should be addressed with proven therapeutic strategies and a multidisciplinary team. [49]