Infertility affects nearly 10% to 15% of couples of reproductive age worldwide. Identification of reversible contributing factors represents a critical step in optimizing fertility outcomes. Among endocrine disorders, thyroid dysfunction is of particular clinical importance because of its high prevalence, relative ease of diagnosis, and potential for therapeutic modification. Thyroid hormones play an essential role in reproductive physiology, with effects on ovarian function, endometrial receptivity, implantation, and early fetal development.

While overt hypothyroidism is a well-established cause of menstrual irregularities, anovulation, and adverse pregnancy outcomes, the impact of subclinical hypothyroidism (SCH), defined as elevated thyroid-stimulating hormone (TSH) levels with normal free thyroxine (FT4), remains a subject of ongoing debate. SCH is relatively common among women seeking fertility care, including those undergoing assisted reproductive technology (ART); however, evidence regarding its effects on ovarian reserve, miscarriage, and live birth rates (LBRs) remains inconsistent [1-3].

Similarly, thyroid autoimmunity (TAI), characterized by the presence of anti-thyroid peroxidase antibody (TPOAb) or anti-thyroglobulin antibody (TgAb), has been associated with increased risks of miscarriage, implantation failure, and ovarian insufficiency. These associations may be mediated through immune-related endometrial dysfunction or alterations in thyroid-binding globulin during ovarian stimulation [4]. However, the causal nature of these relationships and the potential benefits of levothyroxine (LT4) treatment in euthyroid women with TAI remain a matter of debate [5].

This uncertainty is reflected in divergent recommendations across major international guidelines. The European Thyroid Association (ETA), in its 2021 guideline on thyroid disorders before and during ART, generally supports proactive screening and treatment, particularly in women undergoing ART [6]. In contrast, the American Society for Reproductive Medicine (ASRM) 2024 guideline focusing on SCH in infertile women [7] and the European Society of Human Reproduction and Embryology (ESHRE) 2023 recommendations addressing thyroid factors in recurrent implantation failure (RIF) [8] adopt a more conservative and individualized approach, citing limited evidence from randomized controlled trials.

Hence, inconsistencies persist in clinical practice, particularly with respect to TSH thresholds for initiating treatment and the role of LT4 in euthyroid women with TAI. These differences contribute to heterogeneous management strategies across regions and institutions. In light of this variability, a critical synthesis of existing international guidelines is needed to assist clinicians in evidence-based decision-making for the management of SCH and TAI in infertile women. Accordingly, this review aims to summarize current international recommendations, delineate areas of consensus and controversy, and provide a practical framework to support clinical management decisions, with the ultimate goal of improving ART outcomes.

A systematic literature review was conducted to identify clinical guidelines addressing thyroid disorders in infertility and ART. PubMed, Embase, and relevant professional society websites were searched using keywords including ‘thyroid disorders,’ ‘subclinical hypothyroidism,’ ‘thyroid autoimmunity,’ ‘infertility,’ ‘assisted reproductive technology,’ and ‘guidelines,’ covering the period from January 2020 to August 2025. Inclusion criteria comprised English-language or bilingual guidelines issued by major professional societies that addressed screening, diagnosis, or treatment of thyroid disorders in infertile women. Exclusion criteria included non-guideline documents or publications focusing exclusively on overt hypothyroidism. Four primary guidelines were selected for comparative analysis: Korean Thyroid Association (KTA) 2023, ASRM 2024, ETA 2021, and ESHRE 2023. Data extraction focused on definitions, screening recommendations, TSH thresholds, treatment strategies, and ART-specific guidance. Similarities and differences among guidelines were systematically tabulated. Reported recommendations were interpreted qualitatively, with contextual support from relevant studies [9].

The four guidelines share several overarching principles but diverge in specific recommendations. Table 1 summarizes the key comparative elements. Overall, all guidelines define SCH as elevated TSH with normal FT4 levels and recommend LT4 treatment for overt hypothyroidism or clinically significant hypothyroidism to optimize reproductive outcomes. However, notable variations exist in TSH cutoff values used to diagnose SCH, approaches to routine versus targeted thyroid screening, and management strategies for subtle abnormalities or euthyroid TAI. These differences reflect variation in the underlying evidence base, as well as contrasting clinical philosophies, with ASRM adopting a selective, outcome-oriented approach emphasizing proven reproductive benefit, whereas ETA favors a more comprehensive and preventive strategy that supports intervention even in milder clinical scenarios.

Regarding the definition of SCH, all guidelines converge on a core description of elevated TSH with normal FT4, while recognizing TAI as a distinct entity that often involves thyroid antibodies in the absence of overt dysfunction. Commonalities include acknowledgment that TAI may exist independently of TSH elevation and may still be clinically relevant in infertility. Differences arise primarily in TSH cutoff thresholds. KTA and ETA generally define SCH using a TSH level >4.0 mIU/L, with a lower threshold of >2.5 mIU/L applied in pregnancy or pre-ART settings. ASRM (2024) considers an upper limit of normal TSH of 4.12 mIU/L, while acknowledging that subtler elevations between 2.5 and 4.0 mIU/L have been examined in relation to miscarriage and adverse pregnancy outcomes; however, it explicitly states that evidence remains insufficient to support intervention in this range. ESHRE does not primarily define SCH but considers thyroid dysfunction relevant to RIF when TSH exceeds 4.0 mIU/L. ASRM guidelines emphasize that recommendations should be based on clear evidence of benefit, noting that low cost or minimal harm of an intervention alone does not justify screening or treatment in the absence of demonstrated efficacy.

Screening recommendations show general agreement on focusing evaluation in high-risk populations. However, KTA and ETA advocate broader or routine screening for TSH and TAI among subfertile women, particularly those with polycystic ovary syndrome, diminished ovarian reserve (DOR), or plans for ART. In contrast, ASRM does not recommend routine screening for TAI in asymptomatic women with infertility or pregnancy, but supports targeted screening in women with a history of recurrent pregnancy loss (strength of evidence C; strength of recommendation: weak) or other established risk factors. ESHRE further restricts screening to women with RIF, reflecting its narrower clinical focus and outcome-driven framework.

With respect to TSH thresholds for initiating treatment, all guidelines recommend LT4 therapy for overt hypothyroidism in infertility or ART settings with the goal of achieving euthyroidism. KTA and ETA recommend LT4 treatment for women with TSH >4.0 mIU/L and suggest individualized decision-making for women with TSH levels between 2.5 and 4.0 mIU/L who are TAI-positive. In contrast, ASRM does not recommend LT4 treatment for pregnant women or women desiring pregnancy who are diagnosed with SCH, citing evidence that treatment has not been shown to reduce pregnancy loss or improve clinical pregnancy or live birth outcomes (strength of evidence B; strength of recommendation: moderate). ESHRE recommends evaluation of thyroid function in RIF cases with TSH >4.0 mIU/L but does not specify a definitive LT4 treatment threshold.

Management of euthyroid TAI is approached cautiously across all guidelines, with none strongly endorsing routine LT4 treatment in the absence of elevated TSH due to inconsistent evidence from randomized controlled trials. Although all societies adopt a generally conservative stance, ETA and KTA are comparatively more proactive in ART contexts, considering low-dose LT4 in women with TSH >2.5 mIU/L to mitigate ovarian stimulation-related TSH increases. In contrast, ASRM and ESHRE conclude that available evidence is insufficient to support routine treatment of euthyroid TAI.

For ART-specific recommendations, ETA emphasizes optimization of TSH levels before ART initiation and continued monitoring during ovarian stimulation, citing potential adverse effects of SCH or TAI on outcomes such as embryo quality or LBR. ETA uniquely suggests consideration of intracytoplasmic sperm injection (ICSI) in women with TAI. In contrast, ASRM does not recommend screening or treatment for asymptomatic SCH in women with infertility or pregnancy. ESHRE adopts a probabilistic definition of RIF (>60% cumulative implantation failure) as a trigger for thyroid evaluation. KTA highlights the association between thyroid dysfunction and pregnancy-related complications. Overall differences include ETA’s emphasis on proactive ART-specific interventions and ESHRE’s indirect thyroid assessment through the RIF framework.

Across guidelines, recommendations are grounded in available evidence, frequently citing randomized controlled trials and meta-analyses. Higher grades of recommendation (A/B) are more commonly assigned in KTA and ETA guidelines, whereas ASRM and ESHRE more frequently apply low-to-moderate evidence ratings, reflecting concerns related to study heterogeneity, limited power, and inconsistent outcomes. The ASRM 2024 update incorporates more recent evidence suggesting a limited impact of mild SCH on reproductive outcomes, a position that may influence future realignment of international recommendations.

The international guidelines reviewed, including ETA 2021, KTA 2023, ESHRE 2023, and ASRM 2024, demonstrate both areas of consensus and meaningful divergence in their approaches to diagnosing and managing SCH in infertile women [6-8,10]. Although all guidelines acknowledge the potential impact of thyroid dysfunction on fertility and pregnancy outcomes, they differ with respect to diagnostic thresholds, treatment recommendations, and ART–specific considerations. Variable cutoff values have been used to define the upper limit of normal TSH, and the absence of well-designed prospective studies has contributed to inconsistent and sometimes contradictory conclusions [11-14]. Nevertheless, adverse fertility outcomes appear more consistently evident at TSH levels exceeding 4.0 mIU/L [13], and all four guidelines ultimately converge around this threshold.

Other international societies, including ATA 2017, similarly define SCH as a TSH level above the assay- or pregnancy-specific reference range, or greater than 4.0 mIU/L when such ranges are unavailable, in the presence of normal FT4. In infertility and ART contexts, ATA acknowledges the potential clinical relevance of SCH but emphasizes the ongoing uncertainty regarding the benefit of LT4 treatment [2].

Evidence linking elevated TSH levels to reduced fertilization rates, impaired embryo quality, and lower LBR remains limited and inconsistent [15,16]. Five retrospective studies, including four low-quality and one intermediate-quality study, have evaluated SCH in infertile women. One retrospective analysis comparing 244 infertile women with 155 fertile controls reported a significantly higher prevalence of SCH in the infertile group (13.9% vs. 3.9%, p<0.002) [17]. In an intermediate-quality randomized controlled trial (RCT) involving 64 infertile women with SCH undergoing in vitro fertilization (IVF), LT4 treatment was associated with a significantly higher LBR (53.1% vs. 25.0%, p=0.04) and a lower miscarriage rate (0% vs. 33%, p=0.02); however, statistical significance was lost in overall analyses due to small sample size [18]. Although these findings suggest a possible benefit of treatment, ASRM concludes that current evidence is insufficient to justify universal screening or treatment of SCH in infertile populations. The negative impact of thyroid dysfunction before ART on LBR appears most pronounced at TSH levels above 3.5–4.0 mIU/L [19]. Consistently, a meta-analysis restricted to women with TSH >4.0 mIU/L demonstrated that LT4 treatment improved LBR to levels comparable with those observed in euthyroid women [16]. Data on TAI further complicate the interpretation of thyroid-related reproductive risk. For example, among women with primary ovarian insufficiency, Hashimoto’s thyroiditis has been reported to be significantly more prevalent than in the general female population [20]. Large cross-sectional studies have also demonstrated higher TPOAb positivity rates in women with DOR [21], as well as associations between TSH levels exceeding 3.0 mIU/L and lower anti-Müllerian hormone (AMH) concentrations [22-26]. A systematic review encompassing 38 studies linked thyroid antibody positivity to increased risks of unexplained subfertility, miscarriage, recurrent miscarriage, preterm birth, and postpartum thyroiditis [27]. However, substantial heterogeneity in SCH definitions, study populations, and methodological design limits the strength of causal inference.

Systematic reviews and meta-analyses of RCTs evaluating LT4 treatment in women with SCH and/or TAI undergoing IVF have reported reductions in miscarriage risk [28], although these findings were largely driven by a single trial [29]. Other studies have failed to demonstrate a consistent effect of TAI on ART outcomes [30-32]. Accordingly, while select evidence supports LT4 treatment in specific clinical scenarios, a universal benefit across all infertile women with SCH or TAI has not been established.

Screening strategies therefore vary substantially across guidelines. ETA 2021 recommends systematic screening for TSH and TPOAb in all subfertile women, with optional antibody testing depending on local practice patterns. ATA 2017 similarly supports systematic thyroid testing in women undergoing ART. In contrast, ASRM 2024 and ESHRE 2023 advocate selective screening approaches, emphasizing evaluation of populations in whom test results are likely to alter clinical management. KTA 2023 aligns more closely with obstetric guidelines, supporting routine thyroid testing during pregnancy and targeted preconception assessment in women with high-risk features. Reflecting a conservative stance, the American College of Obstetricians and Gynecologists 2020 guideline does not endorse universal thyroid screening.

Several cohort studies evaluating different TSH thresholds, such as 2.5 versus 4.5 mIU/L, have not demonstrated significant differences in pregnancy rates, miscarriage rates, or LBR [16,18,19,29]. These findings reinforce ongoing uncertainty regarding the clinical relevance of lower TSH cutoffs. Overall, the balance between preventive intervention and evidence-based restraint remains central to guideline development. KTA supports broader LT4 utilization, ETA and ESHRE emphasize antibody status and TSH thresholds, and ASRM 2024 favors targeted intervention. This variation highlights persistent uncertainty and underscores the need for adequately powered RCTs to determine whether treatment of all infertile women with SCH improves reproductive outcomes.

An increased prevalence of TAI, particularly TPOAb positivity, has been consistently observed in women with recurrent pregnancy loss and subfertility, often in association with reduced AMH levels [27,33,34]. Although thyroid dysfunction may adversely affect ovarian reserve, fertilization potential, and early embryo development, reported ART outcomes remain inconsistent [35,36]. Some studies have demonstrated associations between higher TSH levels (>3.9 mIU/L) and fertilization failure [37], and meta-analyses suggest LT4 benefit when TSH exceeds 4.0 mIU/L [16]. However, ICSI may mitigate the negative effects of thyroid antibodies, as comparable fertilization and miscarriage rates have been reported between TAI-positive and TAI-negative women [38]. Management of euthyroid women with TAI therefore remains controversial. None of the reviewed organizations currently recommend routine LT4 treatment in this population, as large observational studies [39] and the Thyroid AntiBodies and LEvoThyroxine (TABLET) trial [40] failed to demonstrate benefit. ETA uniquely suggests consideration of ICSI in TAI-positive women and emphasizes close monitoring during ovarian stimulation, during which increased thyroid hormone demand may unmask SCH [41]. For pre-ART optimization, ETA recommends LT4 treatment when TSH exceeds 2.5 mIU/L, whereas ASRM cites insufficient evidence to support this approach [42,43].

Emerging evidence suggests population-specific nuances in thyroid thresholds. A Korean study reported poorer IVF outcomes at TSH levels ≥3.4 mIU/L, independent of TAI status [9], indicating that optimal cutoff values may vary across ethnic groups and healthcare settings. These findings may inform future refinements of KTA recommendations. Discrepancies in TSH thresholds, antibody management, and ART optimization strategies collectively underscore the need for large, multinational RCTs.

Clinically, current guidelines favor personalized care, including screening for TSH and TAI during infertility evaluations, treating SCH when established thresholds are exceeded, and counseling women with TAI regarding potential reproductive risks. Future guideline updates should address outcomes of ICSI in TAI, long-term neonatal follow-up, and ethnic variation in diagnostic thresholds. Integration of probabilistic models, such as those proposed in ESHRE’s RIF framework, with thyroid biomarkers may further refine precision medicine approaches in infertility.

In conclusion, international guidelines converge on thyroid screening and SCH treatment in infertility but diverge with respect to thresholds and TAI management. Recognizing these differences is essential for developing standards tailored to individual countries, healthcare systems, or institutional practices.