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Recurrent miscarriage

Recurrent miscarriage, also known as recurrent pregnancy loss (RPL), is defined as two or more failed clinical pregnancies prior to 20 weeks of gestation, confirmed by ultrasound or histopathologic examination; definitions vary, with some guidelines requiring three or more losses.^[1]^[2] This condition affects approximately 1% to 3% of couples attempting to conceive, with risk increasing after age 35 due to declining egg quality and chromosomal abnormalities.^[2]^[3] Although single miscarriages occur in 10% to 20% of recognized pregnancies, recurrent cases warrant thorough evaluation.^[1] The etiology is multifactorial, with identifiable causes in about 50% of cases and the rest unexplained.^[2] Evaluation involves personalized testing per guidelines from ACOG (reviewed 2024) and ESHRE (updated 2022), including history, imaging, and select labs, avoiding unproven tests like routine immunological screening.^[1]^[3] Management targets identified causes, with supportive care; most couples achieve live birth rates over 60% in subsequent pregnancies.^[2]^[3]

Definition and Terminology

Diagnostic criteria

Recurrent pregnancy loss (RPL), also known as recurrent miscarriage, is clinically defined as the loss of two or more pregnancies before 24 weeks of gestation, according to the European Society of Human Reproduction and Embryology (ESHRE) guideline update of 2022.^[3] This threshold represents a shift from earlier criteria that often required three or more losses, based on accumulating evidence as of the 2022 guideline demonstrating similar prognostic implications and improved research facilitation with the lower threshold.^[3] The American Society for Reproductive Medicine (ASRM) defines RPL as two or more failed clinical pregnancies before 20 weeks of gestation, excluding biochemical losses and aligning on the threshold of two but differing in gestational age limit and loss types included.^[4]^[5] RPL affects approximately 1-5% of couples attempting to conceive.^[6] Pregnancy losses qualifying for the RPL diagnosis are categorized as early or late. Early RPL refers to losses occurring before 10 weeks of gestation, while late RPL involves losses from 10 weeks up to 24 weeks.^[3] These losses can be further classified by confirmation criteria: biochemical losses are identified by elevated serum or urine β-hCG levels or a positive pregnancy test without subsequent clinical evidence; clinical losses involve symptoms such as bleeding or cramping alongside ultrasonographic confirmation of an intrauterine pregnancy; and morphological losses include visualization of embryonic or fetal structures, potentially with heartbeat detection.^[3] Non-consecutive losses are included in the diagnostic count, as no evidence indicates that consecutiveness alters the risk profile or prognosis.^[3] The diagnosis also encompasses secondary RPL, defined as two or more losses following a prior viable pregnancy beyond 24 weeks or a live birth.^[3] Certain pregnancy outcomes are explicitly excluded from the RPL criteria to maintain diagnostic specificity: ectopic pregnancies, molar pregnancies, and induced abortions do not count toward the threshold.^[3] This framework ensures a standardized approach to identifying couples warranting further investigation for underlying causes, such as uterine abnormalities that may contribute to qualifying losses.^[3]

Terminology variations

The terminology surrounding recurrent miscarriage has evolved to promote clarity, reduce stigma, and align with clinical evidence, with "recurrent pregnancy loss (RPL)" increasingly preferred over "recurrent miscarriage" in contemporary medical literature and guidelines.^[7] The European Society of Human Reproduction and Embryology (ESHRE) in its 2022 guideline explicitly adopts "recurrent pregnancy loss" to encompass the condition defined as two or more pregnancy losses before 24 weeks' gestation, excluding ectopic and molar pregnancies, emphasizing a neutral and precise descriptor for affected individuals.^[3] This shift reflects broader efforts to standardize language that supports patient-centered communication without implying fault.^[8] Historically, the condition was termed "habitual abortion," a phrase originating in mid-20th-century medical texts to denote repeated pregnancy losses, often requiring three or more events for diagnosis.^[9] This terminology has largely been abandoned due to its stigmatizing connotations, as "abortion" evokes moral or ethical judgments rather than a medical event, and patients and clinicians alike favor "miscarriage" or "pregnancy loss" for its less judgmental tone.^[10] By the late 20th century, professional bodies began transitioning away from such language to mitigate emotional distress for those experiencing losses.^[11] Specific variations include "recurrent early pregnancy loss (REPL)," which refers to two or more losses occurring before 10 weeks' gestational age, including non-consecutive events and sometimes biochemical pregnancies detected only by hormone levels without ultrasound confirmation.^[12] This term is particularly useful in assisted reproductive technology contexts to distinguish early losses from later ones. International differences persist in usage and thresholds; for instance, in the United States, the American Society for Reproductive Medicine (ASRM) defines RPL as two or more clinical pregnancy losses before 20 weeks (documented by ultrasound or histopathology), while in the United Kingdom, the Royal College of Obstetricians and Gynaecologists traditionally requires three consecutive miscarriages before investigation.^[4]^[13] These distinctions aid in diagnostic criteria, typically involving two or more losses, but biochemical events are often excluded from RPL counts unless recurrent and clinically significant.^[14]

Epidemiology

Prevalence and incidence

Recurrent pregnancy loss (RPL), defined as two or more consecutive miscarriages before 20 weeks of gestation, affects approximately 1-5% of couples attempting conception worldwide.^[3] This range aligns with estimates from major reproductive health organizations, where the prevalence is about 1-2% for three or more losses and up to 5% when including two losses.^[4] The figure may vary based on whether biochemical pregnancies are included, with rates reaching 2-3% in such cases.^[3] The risk of subsequent miscarriage increases with the number of prior losses, providing key incidence data for RPL. After two consecutive miscarriages, the probability of another loss rises to about 25%, compared to 15-20% after a single miscarriage.^[15] Following three or more losses, this risk further escalates to 30-40%.^[15] Differences exist between early RPL (before 10 weeks) and late RPL (10-24 weeks), with early losses more commonly linked to chromosomal anomalies (up to 45% in sporadic cases, 39% in subsequent RPL) and late losses associated with factors like uterine malformations or thrombophilias.^[3] RPL appears more frequent in assisted reproductive technology (ART) cycles, often due to higher maternal age and embryo aneuploidy. Underreporting is common, particularly for early biochemical losses that may go unrecognized without sensitive testing. Prevalence rates have remained stable over recent decades, though improved diagnostics have led to greater recognition of cases. Recent studies suggest that prior COVID-19 infection may increase the risk of early pregnancy loss by 2-3 times in affected pregnancies.^[16]

Demographic patterns

Recurrent miscarriage risk escalates with advancing maternal age, particularly after 35 years, due to diminished oocyte quality, reduced ovarian reserve, and elevated embryonic chromosomal abnormalities. Studies demonstrate a nearly linear increase in incidence after age 30, culminating in risks approaching 54% for women aged 45 and older.^[17] Advanced paternal age exceeding 40 years further contributes, with affected men exhibiting 69% higher odds of miscarriage compared to those aged 20-29 (odds ratio 1.69, 95% CI 1.18-2.43).^[18] Parity significantly shapes the epidemiology of recurrent miscarriage, with prevalence varying between nulliparous and multiparous women. Overall rates stand at 1-2% among couples attempting conception, but primary recurrent pregnancy loss—occurring in nulliparous women without prior live births—accounts for roughly 15-20% of cases, while secondary recurrent pregnancy loss in multiparous women predominates at 80-85%. Secondary cases are linked to lower risks of certain complications relative to primary cases.^[19]^[20]^[21] Geographic and ethnic disparities highlight elevated rates in regions with prevalent consanguineous marriages, such as the Middle East, where consanguinity affects 20-50% of unions and correlates with higher recurrent miscarriage incidence (P < 0.001 in Iranian cohorts).^[22]^[23] This pattern stems partly from increased homozygosity for genetic variants, though not all studies confirm a direct causal link. In contrast, high-resource settings exhibit lower effective incidence through superior prenatal screening and management.^[22]^[23] Socioeconomic factors exacerbate disparities, as low-income groups face heightened risks from restricted prenatal care access and elevated stress or environmental exposures. Enhanced healthcare availability in higher socioeconomic contexts mitigates incidence by facilitating timely diagnostics and interventions.^[24]^[25]

Causes

Genetic factors

Genetic factors play a significant role in recurrent pregnancy loss (RPL), encompassing both inherited parental chromosomal rearrangements and de novo embryonic abnormalities that disrupt normal development. These genetic contributions account for a substantial portion of RPL cases, with embryonic aneuploidy being the predominant mechanism, often arising from errors in meiosis or early mitosis. Parental genetic variants, including balanced translocations, further elevate the risk by producing unbalanced gametes that lead to nonviable embryos.^[2] Parental chromosomal abnormalities, particularly balanced translocations, are identified in approximately 2-5% of couples experiencing RPL, compared to less than 1% in the general population. These include Robertsonian translocations, where two acrocentric chromosomes fuse at their centromeres, and reciprocal translocations involving segments exchanged between non-homologous chromosomes; carriers are phenotypically normal but produce gametes with unbalanced chromosomal content, resulting in frequent miscarriages. For instance, a 2025 study of over 4,000 couples with RPL detected structural chromosomal anomalies in 3.3% of cases, predominantly translocations. Such abnormalities follow mendelian inheritance patterns, with each pregnancy having a 50% chance of being balanced, unbalanced, or normal depending on segregation during meiosis.^[26]^[27]^[4] Embryonic aneuploidy, characterized by an abnormal number of chromosomes, underlies 50-70% of RPL cases, far exceeding rates in sporadic miscarriages due to recurrent production of chromosomally unstable embryos. Common trisomies involve chromosomes 13, 16, 21, and 22, which often lead to arrest in the first trimester; monosomy X (Turner syndrome) is also frequent. These de novo errors typically occur during maternal meiosis, influenced by advanced maternal age, and result in embryonic lethality, explaining the high miscarriage rate in affected couples. Cytogenetic analysis of miscarriage products confirms aneuploidy in over 50% of RPL specimens, highlighting its central etiologic role.^[28]^[29]^[2] Single gene disorders contribute to RPL through inherited variants affecting hemostasis and placentation, with thrombophilias such as the factor V Leiden mutation (a G1691A polymorphism in the F5 gene) increasing risk via hypercoagulability that impairs trophoblast invasion. Heterozygous carriers face a 2-7-fold elevated odds of RPL, particularly in certain populations like Iranians, following autosomal dominant inheritance with incomplete penetrance. Other monogenic causes include variants in genes related to antiphospholipid syndrome pathways, such as those in the complement system or coagulation factors, which promote thrombosis and inflammation at the maternal-fetal interface. These disorders are less common than aneuploidy but identifiable through targeted sequencing, with inheritance patterns varying from autosomal recessive (e.g., certain protein C deficiencies) to dominant.^[30]^[31]^[32] Preimplantation genetic testing (PGT) for aneuploidy, performed on embryos during IVF, improves outcomes in RPL by selecting euploid embryos for transfer, reducing miscarriage rates by up to 58% and boosting live birth rates per transfer by over twofold in unexplained cases. A 2024 meta-analysis reported clinical pregnancy rates of 73% and live birth rates of 62% with PGT versus 61% and 41% without, particularly benefiting women over 35 with prior losses. However, cumulative live birth rates may not differ significantly across cycles due to the limited number of transferable embryos.^[33]^[29]^[34] Despite comprehensive karyotyping of parents and products of conception, 10-15% of RPL cases remain unexplained by 2025 data, often attributed to undetected submicroscopic variants or complex polygenic interactions rather than overt chromosomal issues. Genetic counseling is recommended for affected couples to discuss recurrence risks based on identified inheritance patterns.^[4]

Uterine abnormalities

Uterine abnormalities encompass both congenital and acquired structural defects that can contribute to recurrent pregnancy loss (RPL) by disrupting normal embryonic implantation and development. These anomalies affect approximately 13.3% of women with RPL, compared to 5.5% in the general population.^[3] Congenital uterine malformations, arising from developmental errors in the Müllerian ducts, are particularly implicated, with the septate uterus being the most common type associated with RPL, occurring in 15-20% of cases involving uterine factors.^[3]^[35] Other congenital anomalies include the unicornuate uterus, which features a single functional uterine horn and is linked to reduced uterine capacity, further elevating miscarriage risk.^[2] Acquired uterine abnormalities, which develop later in life, include submucosal fibroids, endometrial polyps, and intrauterine adhesions, the latter often resulting from Asherman syndrome following uterine curettage procedures such as dilation and curettage after miscarriage or abortion.^[2]^[36] Submucosal fibroids distort the endometrial cavity, while polyps and adhesions impair the endometrial surface integrity. These acquired defects are identified in about 12.9% of women with RPL.^[3] The pathophysiology of these abnormalities centers on impaired implantation and inadequate vascular supply to the developing placenta. In congenital cases like the septate uterus, the fibrous or muscular septum reduces intrauterine space and disrupts blood flow, leading to early pregnancy failure.^[2] Similarly, the unicornuate uterus limits expansion and vascular support during gestation.^[2] For acquired anomalies, submucosal fibroids and polyps alter the endometrial environment, hindering embryo attachment, while adhesions in Asherman syndrome cause deficient endometrial vascularization and reduced receptivity, resulting in miscarriage.^[36]^[37] The 2022 European Society of Human Reproduction and Embryology (ESHRE) guidelines recommend assessing uterine anatomy in all women with RPL using transvaginal three-dimensional ultrasound as the initial imaging modality for detection, with hysteroscopy advised for confirming and evaluating specific defects like septate uteri or adhesions.^[3] Hysteroscopic resection of the septate uterus is not recommended by the 2022 ESHRE guidelines due to insufficient evidence of benefit in live birth rates from high-quality studies, such as the TRUST trial (RR 2.3, 95% CI 0.86-5.9). However, the 2024 American Society for Reproductive Medicine (ASRM) guideline moderately recommends offering hysteroscopic septum incision to patients with a septate uterus and recurrent miscarriage in a shared decision-making model, based on moderate evidence showing reduced miscarriage risk (pooled OR 0.45, 95% CI 0.22-0.90).^[3]^[38]

Endocrine disorders

Endocrine disorders contribute to recurrent pregnancy loss (RPL) through disruptions in hormonal balance that affect implantation, placentation, and early embryonic development. These imbalances often involve the thyroid, glucose metabolism, and ovarian steroidogenesis, with evidence indicating that targeted screening can identify at-risk individuals, though routine testing for all parameters is not universally recommended. Laboratory investigations, such as thyroid-stimulating hormone (TSH) assays and glucose tolerance tests, form the basis for evaluating these conditions in women with RPL history.^[3] Thyroid dysfunction, particularly subclinical hypothyroidism defined by TSH levels exceeding 2.5 mIU/L, is prevalent in 2.4% to 27% of reproductive-age women and up to 19% of those with RPL, with conflicting evidence on its direct impact on miscarriage risk. However, elevated TSH in this range has been associated with increased odds of pregnancy loss (OR 1.86, 95% CI 1.18–2.94), potentially doubling the baseline risk in some cohorts through impaired endometrial receptivity and embryonic development. Autoimmune thyroiditis, marked by thyroid peroxidase antibodies (TPOAb), affects 8% to 14% of fertile women and up to 31% of RPL cases, exacerbating miscarriage risk via inflammatory mechanisms that compromise placentation. The European Society of Human Reproduction and Embryology (ESHRE) 2022 guidelines strongly recommend screening for TSH and TPOAb in RPL evaluation, though levothyroxine treatment for euthyroid autoimmune cases does not improve live birth rates.^[3]^[39]^[40] Uncontrolled diabetes mellitus, characterized by hyperglycemia with HbA1c levels above 6.5%, significantly elevates RPL risk by impairing trophoblast invasion and placentation, leading to structural placental abnormalities and increased apoptosis in placental cells. In women with pregestational diabetes, poor glycemic control correlates with higher rates of early pregnancy loss due to oxidative stress and vascular dysfunction at the maternal-fetal interface. The American Society for Reproductive Medicine (ASRM) 2012 committee opinion emphasizes screening via HbA1c in RPL patients with suspected metabolic issues, as well-controlled diabetes does not confer additional risk.^[4]^[41]^[42] Luteal phase defect, arising from corpus luteum insufficiency and resulting in low progesterone levels during the luteal phase, has been implicated in 23% to 60% of RPL cases historically, though contemporary evidence describes an inconsistent association with pregnancy loss. This condition manifests as inadequate endometrial preparation for implantation, with progesterone deficiency potentially contributing to early miscarriage in a subset of patients; estimates suggest involvement in up to 35% of unexplained RPL through shortened luteal phases or suboptimal progesterone output. ESHRE guidelines advise against routine testing or progesterone supplementation for luteal phase defect in RPL due to low-quality evidence, prioritizing clinical history over invasive diagnostics like endometrial biopsy.^[43]^[44]^[3] Polycystic ovary syndrome (PCOS), driven by insulin resistance, is linked to RPL through hyperinsulinemia and hyperandrogenism that disrupt ovarian function and endometrial receptivity, with studies indicating a higher miscarriage odds (OR 1.49, 95% CI 1.20–1.85) in affected women. Approximately 15% of RPL cases may involve PCOS-related metabolic pathways, as insulin resistance prevalence reaches 24% in RPL cohorts versus 8% in controls (OR 3.6), exacerbating ovulatory irregularities and early loss. The 2023 International Evidence-based Guideline for PCOS highlights insulin resistance as a key mediator but notes insufficient RPL-specific data for routine screening; ASRM concurs that PCOS evaluation should be history-based rather than universal.^[45]^[46]^[47] Routine prolactin testing is not recommended in RPL evaluation, as hyperprolactinemia shows only tenuous links to pregnancy loss and lacks consistent prognostic value without symptoms like oligo- or amenorrhea. Elevated prolactin may indirectly contribute via ovulatory dysfunction, but ESHRE and ASRM guidelines deem it unnecessary in asymptomatic cases, reserving assessment for those with galactorrhea or irregular cycles.^[3]^[4]

Coagulation disorders

Coagulation disorders contribute to recurrent pregnancy loss (RPL) primarily through thrombophilic conditions that disrupt normal hemostasis, leading to vascular complications in the placenta. Inherited thrombophilias, such as Factor V Leiden and the prothrombin G20210A mutation, are associated with an increased risk of RPL, with a combined prevalence of approximately 5-10% among affected women. These mutations impair the regulation of the clotting cascade, promoting a hypercoagulable state that can adversely affect placental development. Although not all carriers experience pregnancy loss, the odds ratio for RPL is elevated, at 2.02 (95% CI 1.60-2.55) for Factor V Leiden and 1.81 (95% CI 1.26-2.60) for prothrombin G20210A, particularly in cases involving fetal loss after 10 weeks of gestation.^[3]^[48]^[49] Acquired thrombophilias, notably antiphospholipid syndrome (APS), represent a more directly treatable cause, occurring in about 15% of women with RPL. APS is characterized by the presence of antiphospholipid antibodies, including lupus anticoagulant and anticardiolipin antibodies (IgG/IgM), which trigger a prothrombotic state and are confirmed through persistent positivity after 12 weeks. The underlying pathophysiology involves microthrombosis within placental vessels, resulting in infarction, reduced blood flow, and subsequent fetal demise, often in the second trimester. This mechanism is distinct from broader immune dysregulation, focusing instead on aberrant activation of the coagulation system.^[50]^[4]^[51] According to the 2022 European Society of Human Reproduction and Embryology (ESHRE) guidelines, routine testing for inherited thrombophilias is not recommended due to limited clinical utility and weak causal evidence, but screening for APS—via lupus anticoagulant and anticardiolipin antibodies—is advised after two pregnancy losses. Protein C and protein S deficiencies, while rare (prevalence <1% in the general population), are significant when present, as they markedly increase the risk of late fetal loss through similar thrombotic pathways, warranting consideration in women with additional risk factors like family history of venous thromboembolism. These deficiencies highlight the need for targeted evaluation in select cases, though their overall contribution to RPL remains infrequent compared to more common thrombophilias.^[3]^[52]

Immunological factors

Immunological factors contribute to recurrent miscarriage through disruptions in maternal-fetal immune tolerance, where the maternal immune system inappropriately targets fetal antigens, leading to inflammation, impaired placentation, and pregnancy loss. This pathophysiology primarily involves alloimmune and autoimmune mechanisms that prevent the establishment of a balanced immune environment at the maternal-fetal interface.^[53] In alloimmune responses, the mother's immune system may fail to adequately suppress recognition of paternal antigens expressed by the fetus, resulting in heightened natural killer (NK) cell activity and cytokine dysregulation. Elevated peripheral and uterine NK cell levels or cytotoxicity have been associated with unexplained recurrent pregnancy loss (RPL), observed in approximately 20-30% of such cases, potentially disrupting trophoblast invasion and vascular remodeling essential for implantation. Additionally, a shift toward Th1-dominant responses promotes pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ), while suppressing anti-inflammatory Th2 cytokines like interleukin-10 (IL-10) and IL-4, exacerbating immune rejection.^[53]^[54]^[55] Autoimmune mechanisms further compound these issues, with non-thrombotic immune dysregulation linked to RPL in about 20% of cases. For instance, elevated NK cell activity or pro-inflammatory cytokine profiles, including increased Th17-related IL-17, are frequently noted in unexplained RPL, contributing to chronic inflammation at the decidua. Celiac disease exemplifies this link, as undiagnosed cases carry up to a nine-fold increased risk of recurrent miscarriage due to autoimmune-mediated nutrient malabsorption and placental insufficiency, with serological screening recommended in evaluation.^[55]^[53]^[56] Current guidelines reflect ongoing controversies in managing these factors; the 2025 American Society for Reproductive Immunology (ASRI) recommendations advise against routine intravenous immunoglobulin (IVIG) therapy due to inconsistent evidence from randomized trials, emphasizing its use only in specialized, evidence-based contexts. Similarly, natural killer cell testing is deemed controversial and not routinely endorsed, given the lack of standardized assays and proven clinical utility for predicting or preventing RPL.^[57]^[58]

Infectious causes

Infections can contribute to recurrent pregnancy loss (RPL) by directly damaging fetal tissues, inducing inflammatory responses in the endometrium or placenta, or disrupting maternal-fetal immune tolerance, leading to miscarriage through mechanisms such as ascending genital tract infections or systemic effects.^[3] Bacterial infections, particularly those causing chronic endometritis, are implicated in RPL, where persistent low-grade inflammation in the endometrium impairs implantation and placental development. Common pathogens include Ureaplasma urealyticum and Mycoplasma hominis, which colonize the genital tract and have been detected in 10-20% of women with RPL based on cervical swab cultures or PCR testing.^[59]^[60] For instance, one case-control study found U. urealyticum positivity in 16.5% of women experiencing spontaneous abortion compared to 7.3% in controls, suggesting a potential role in recurrent cases.^[59] Chronic endometritis itself, often bacterial in origin, affects 7-58% of women with RPL, diagnosed via endometrial biopsy showing plasma cell infiltration.^[3] Viral infections may also play a role in RPL through reactivation or primary infection during pregnancy, causing fetal viremia or placental insufficiency. Cytomegalovirus (CMV) and herpes simplex virus (HSV) reactivation have been linked to increased miscarriage risk, while parvovirus B19 can lead to non-immune hydrops fetalis and loss, particularly in early gestation.^[61] A study evaluating women with recurrent spontaneous abortions found frequent associations with parvovirus B19 (detected in endometrial samples) and HSV-2 seropositivity, with odds ratios indicating elevated risk compared to fertile controls.^[61] Similarly, CMV IgM positivity has been observed more often in RPL cohorts, though causality remains debated due to the virus's ubiquity.^[62] Parasitic infections like toxoplasmosis, caused by Toxoplasma gondii, are relevant in endemic regions where seroprevalence exceeds 50%, increasing miscarriage risk via protozoal invasion of the placenta and fetus. In areas with high exposure from contaminated water or undercooked meat, acute maternal infection during pregnancy elevates the odds of loss by 1.5-2 times, with serologic studies showing higher IgG/IgM rates in women with habitual abortion.^[63]^[64] The 2022 European Society of Human Reproduction and Embryology (ESHRE) guideline advises against routine screening for infectious causes in RPL unless clinical history (e.g., symptoms of pelvic infection or exposure risks) suggests involvement, due to insufficient evidence linking most pathogens to recurrent loss. Laboratory tests, such as endometrial biopsy for chronic endometritis or serology/PCR for viruses and parasites, may be considered in targeted cases. Antibiotic treatment for confirmed bacterial chronic endometritis, using regimens like doxycycline or broad-spectrum combinations, has been associated with improved live birth rates in RPL, rising from approximately 40% to over 70% in treated cohorts compared to untreated.^[3]^[65]

Lifestyle and environmental factors

Cigarette smoking is a modifiable risk factor for recurrent pregnancy loss (RPL), with smokers exhibiting approximately twice the odds of RPL compared to non-smokers (odds ratio [OR] 2.1, 95% confidence interval [CI] 1.1–4.1).^[66] This association is attributed to oxidative stress induced by tobacco smoke, which disrupts placental function and increases cellular damage in reproductive tissues.^[67] Similarly, heavy alcohol consumption elevates the risk of RPL; intake of five or more drinks per week (equivalent to approximately 10 units) has been linked to higher miscarriage rates, with dose-dependent effects observed in early pregnancy.^[68] Obesity, defined as a body mass index (BMI) greater than 30 kg/m², is associated with a 25–37% increased risk of RPL, independent of other factors.^[69] This elevated risk stems from chronic low-grade inflammation in adipose tissue, which promotes pro-inflammatory cytokine production and impairs endometrial receptivity and placental development.^[70] Weight loss interventions targeting obesity have shown potential to mitigate this risk in women with RPL. Exposure to environmental toxins also contributes to RPL. Bisphenol A (BPA), a common endocrine disruptor found in plastics, is associated with higher rates of unexplained recurrent miscarriage through mechanisms involving hormonal disruption and increased aneuploidy in oocytes.^[71] Pesticides, such as organophosphates, have been linked to RPL by inducing oxidative stress and apoptosis in placental cells, with occupational or residential exposure elevating odds.^[72] Caffeine intake exceeding 300 mg per day (roughly three cups of coffee) is associated with a modestly increased risk of repeated miscarriage (OR 2.7, 95% CI 1.1–6.2 in non-smokers), though evidence suggests this effect is minor compared to other factors.^[73] Folic acid deficiency has been implicated in RPL, with low serum folate levels correlating to a 50% higher risk of early pregnancy loss; recent analyses indicate that up to 10% of women with RPL may have suboptimal folate status, underscoring the importance of preconception supplementation.^[74] Psychological stress acts primarily as a confounder in RPL rather than a direct cause, potentially exacerbating other risk factors through indirect pathways like altered sleep or diet but without independent causation.^[75]

Investigation

Clinical history and examination

The clinical history for recurrent miscarriage begins with a detailed assessment of the patient's pregnancy outcomes, including the total number of previous losses, live births, and their sequence, whether consecutive or interspersed with successful pregnancies.^[3] This evaluation should specify the gestational age at each loss and the interval between pregnancies to identify patterns that may inform prognosis, as the chance of a live birth decreases with increasing numbers of miscarriages—for instance, approximately 72% after three losses compared to 50% after six or more.^[3] Symptoms associated with each miscarriage, such as vaginal bleeding, abdominal pain, or cramping, are documented to contextualize the events and rule out acute complications during prior episodes.^[1] The obstetric history encompasses details of all prior pregnancies, including modes of delivery and any complications, while the broader medical history probes for conditions like diabetes, thyroid disorders, or polycystic ovary syndrome that could contribute to losses.^[3]^[1] Family history is a critical component, focusing on patterns of recurrent miscarriage, genetic disorders, or hereditary thrombophilias among first-degree relatives, which may suggest inherited etiologies.^[3] Lifestyle factors for both partners are routinely explored, including smoking, alcohol consumption, diet, occupational exposures, and patterns of physical activity, as these modifiable elements—such as obesity or tobacco use—adversely affect live birth rates.^[3] Maternal age is noted as a key prognostic indicator, with advancing age correlating to diminished fertility and higher miscarriage risk.^[3] Partner involvement is emphasized throughout the evaluation process, with the male partner's history including age, similar lifestyle risks, and, if indicated, semen analysis to assess sperm quality or DNA fragmentation in selected cases.^[3] The physical examination prioritizes anthropometric measures, such as body mass index (BMI), to identify obesity or underweight status, both of which are associated with increased miscarriage risk through mechanisms like insulin resistance.^[3] Thyroid palpation is performed to detect goiter or nodules suggestive of dysfunction, guiding subsequent screening.^[3] A comprehensive pelvic examination evaluates for uterine abnormalities, such as fibroids or structural anomalies, which may be suspected based on historical symptoms of pain or irregular bleeding.^[1] General systemic assessment, including signs of endocrine or autoimmune disorders, completes the initial evaluation to direct further investigations without interpreting diagnostic tests.^[1]

Laboratory investigations

Laboratory investigations play a crucial role in evaluating recurrent miscarriage by identifying underlying genetic, hematologic, endocrine, and infectious causes that may be amenable to intervention. These tests are typically initiated after a thorough clinical history and physical examination, which guide the selection of appropriate assessments to avoid unnecessary testing. According to guidelines from the European Society of Human Reproduction and Embryology (ESHRE), evaluation can proceed following two consecutive clinical pregnancy losses, focusing on targeted laboratory panels rather than broad screening.^[76] Parental karyotyping, involving chromosomal analysis of both partners' peripheral blood, is recommended to detect balanced structural abnormalities such as reciprocal or Robertsonian translocations, which occur in approximately 2-5% of couples experiencing recurrent pregnancy loss. These rearrangements can lead to unbalanced gametes and subsequent embryonic aneuploidy, explaining the miscarriages. If an abnormality is identified, genetic counseling is advised to discuss reproductive options, including preimplantation genetic testing. The yield of this test underscores its value in a subset of cases, though it is not universally abnormal.^[76] Testing for antiphospholipid syndrome (APS) is a cornerstone of laboratory evaluation, particularly after two or more pregnancy losses. The panel includes assays for lupus anticoagulant, anticardiolipin antibodies (IgG and IgM), and anti-β2-glycoprotein I antibodies (IgG and IgM), which should be repeated at least 12 weeks apart to confirm persistence and avoid false positives from transient elevations. Positive results diagnose APS, a condition linked to thrombotic events in the placental vasculature, and warrant consideration of antithrombotic therapy in subsequent pregnancies. This testing is prioritized due to its established association with recurrent loss and proven treatment benefits.^[76] Endocrine screening focuses on treatable disorders that may contribute to miscarriage risk. Thyroid function and autoimmunity are assessed via serum thyroid-stimulating hormone (TSH) levels and thyroid peroxidase (TPO) antibodies, with subclinical hypothyroidism (TSH >2.5 mIU/L with normal free T4), for which levothyroxine treatment may be considered to potentially reduce miscarriage risk (conditional recommendation), particularly if TPO antibodies are present. Glycemic control is evaluated using hemoglobin A1c (HbA1c) to detect prediabetes or diabetes, which should be optimized preconceptionally. Prolactin levels are measured only if indicated by symptoms such as galactorrhea or irregular menses, as routine screening is not recommended without clinical suspicion. These tests address endocrine imbalances that affect implantation and early placentation.^[76] Beyond APS, routine thrombophilia screening for inherited conditions such as factor V Leiden or prothrombin G20210A mutations is not advised by ASRM guidelines, as evidence does not support improved outcomes with anticoagulation in asymptomatic carriers. This recommendation, reaffirmed in recent reviews, avoids over-testing given the low attributable risk in recurrent miscarriage without personal thrombosis history.^[12] For infectious etiologies, endometrial biopsy is considered only if chronic endometritis is suspected based on persistent symptoms or recurrent infections, using immunohistochemical staining for CD138-positive plasma cells to confirm the diagnosis. Routine biopsy is not recommended, as the prevalence of chronic endometritis in unexplained recurrent loss is low and treatment benefits remain unproven in large trials.^[12]

Imaging studies

Imaging studies play a crucial role in the investigation of recurrent pregnancy loss (RPL) by identifying structural uterine abnormalities, such as congenital Müllerian anomalies, fibroids, polyps, and adhesions, which may contribute to pregnancy failure.^[3] These assessments are recommended for all women with RPL to evaluate uterine anatomy, with non-invasive options prioritized to guide further management.^[3] Transvaginal ultrasound, particularly three-dimensional (3D) imaging, serves as the first-line modality for assessing uterine structure due to its high sensitivity and specificity in detecting fibroids, endometrial polyps, and Müllerian anomalies like septate or bicornuate uteri.^[3] It effectively differentiates between uterine septum and bicorporeal uterus, which is essential for accurate diagnosis, and is preferred over other techniques for its accessibility and non-invasive nature.^[3] Two-dimensional (2D) transvaginal ultrasound is also conditionally recommended to rule out adenomyosis in RPL patients, though it has lower sensitivity for intrauterine adhesions.^[3] Hysteroscopy remains the gold standard for direct visualization and confirmation of intrauterine pathologies, including polyps, fibroids, and synechiae, with studies reporting a yield of 15-27% for detecting uterine anomalies in women with RPL.^[3]^[77] Although routine diagnostic hysteroscopy is not universally recommended due to limited evidence of benefit in all cases, it is valuable when initial ultrasound findings suggest abnormalities or for therapeutic intervention in confirmed lesions.^[3] Hysterosalpingography (HSG) provides an outline of the uterine cavity and fallopian tubes through contrast radiography, offering moderate sensitivity for pronounced malformations but lower accuracy in distinguishing anomaly types compared to 3D ultrasound or sonohysterography.^[3] It is often used complementarily when tubal patency assessment is needed alongside cavity evaluation.^[3] For complex cases, magnetic resonance imaging (MRI) is conditionally advised by the 2022 European Society of Human Reproduction and Embryology (ESHRE) guidelines when 3D ultrasound is unavailable or inconclusive, as it provides detailed soft-tissue imaging of uterine anomalies without radiation exposure.^[3] Laparoscopy, typically combined with hysteroscopy, is reserved for suspected endometriosis or to confirm congenital malformations like rudimentary horns, serving as the definitive diagnostic tool in select invasive scenarios.^[3] These imaging approaches collectively detect uterine abnormalities in approximately 13% of RPL cases, higher than the general population rate of 5.5%.^[78]

Management

Supportive care

Supportive care for recurrent pregnancy loss (RPL) emphasizes general, non-targeted strategies to optimize health and provide reassurance during preconception and subsequent pregnancies. Preconception counseling is a key component, where individuals are advised to initiate folic acid supplementation at a dose of 400 micrograms daily to reduce the risk of neural tube defects, a recommendation applicable to all women of reproductive age planning pregnancy, including those with a history of RPL.^[79] This supplementation should begin at least one month prior to conception and continue through the first trimester.^[80] Lifestyle modifications form another cornerstone of preconception care, with evidence indicating that smoking cessation, limiting alcohol intake to less than 1 unit per day, reducing caffeine to under 200 mg daily, and achieving a healthy body weight (BMI 18.5–24.9 kg/m²) can positively influence pregnancy outcomes in couples affected by RPL.^[3] Obesity and underweight status have been associated with increased RPL risk, underscoring the importance of weight management through balanced diet and moderate exercise prior to conception.^[81] These adjustments not only mitigate modifiable risk factors but also enhance overall fertility potential.^[82] A multidisciplinary approach is recommended, involving referral to specialized RPL clinics that integrate expertise from reproductive endocrinologists, geneticists, hematologists, and psychologists to deliver coordinated care.^[83] These clinics provide comprehensive evaluation, ongoing support, and tailored monitoring without focusing on unproven interventions. In subsequent pregnancies, early ultrasound monitoring—typically starting at 6–7 weeks gestation and repeated as needed—helps confirm viability and detect issues promptly, offering reassurance and enabling timely intervention if required.^[4] General measures such as adequate hydration and rest are advised during early pregnancy to support maternal well-being, particularly if symptoms like spotting occur, though bed rest is not routinely recommended absent complications.^[1] Psychological support can be integrated into this care framework to address the emotional toll of RPL, with brief counseling sessions helping to alleviate anxiety.^[84]

Cause-specific interventions

Once a specific cause of recurrent pregnancy loss (RPL) has been identified through investigation, targeted interventions can be implemented to address the underlying etiology and improve subsequent pregnancy outcomes.^[85] For genetic causes, such as parental balanced chromosomal rearrangements (e.g., translocations), in vitro fertilization (IVF) combined with preimplantation genetic testing for structural rearrangements (PGT-SR) is offered to carriers to select euploid embryos for transfer, thereby reducing the risk of miscarriage due to unbalanced gametes. The European Society of Human Reproduction and Embryology (ESHRE) 2022 guidelines conditionally recommend discussing PGT-SR with affected couples, noting a cumulative live birth rate of 67.5% across cycles, though it is not routinely advised due to limited high-quality evidence on overall benefit compared to natural conception attempts.^[85] In a cohort of 300 couples with balanced rearrangements undergoing PGT-SR, the cumulative live birth rate reached 55.8%, with complex translocations and advanced maternal age identified as factors lowering success.^[86] Uterine anomalies, particularly a septate uterus, are addressed through hysteroscopic metroplasty to resect the septum and potentially enhance implantation and reduce loss rates. Although the ESHRE 2022 guidelines do not recommend this procedure due to insufficient evidence of benefit (relative risk for live birth 2.3, 95% CI 0.86-5.9), multiple meta-analyses indicate improved reproductive outcomes post-resection in women with RPL. A systematic review reported live birth rates increasing to 50.2% after hysteroscopic metroplasty, with a corresponding reduction in spontaneous abortion rates from 38.6% to lower levels in treated groups.^[85]^[87] The American Society for Reproductive Medicine (ASRM) 2024 guideline supports metroplasty for symptomatic septate uteri, citing live birth rates of 34.1% at 12 months post-procedure in RPL patients.^[38] Endocrine disorders require correction of hormonal imbalances to mitigate RPL risk. Overt hypothyroidism is treated with levothyroxine to normalize thyroid function, as untreated cases are associated with higher miscarriage rates; ESHRE guidelines strongly recommend this intervention, with one study showing miscarriage rates dropping from 20.6% to 4.7% post-treatment.^[85] For subclinical hypothyroidism, evidence is conflicting, but a 2024 meta-analysis found levothyroxine reduced pregnancy loss risk by 31% (risk ratio 0.69, 95% CI 0.52-0.92) in affected women.^[88] In polycystic ovary syndrome (PCOS)-related RPL, metformin is used to improve insulin sensitivity and ovulation, with a 2025 meta-analysis demonstrating a 40% reduction in first-trimester miscarriage risk when administered preconceptionally and continued into early pregnancy.^[89] ESHRE guidelines note insufficient evidence for routine metformin use but suggest it for PCOS management in RPL contexts.^[85] Coagulation disorders, notably antiphospholipid syndrome (APS), are managed with a combination of low-molecular-weight heparin (LMWH) and low-dose aspirin to prevent thrombotic events in the uteroplacental circulation. ESHRE 2022 guidelines conditionally recommend preconceptional aspirin (75-100 mg/day) plus prophylactic LMWH from pregnancy confirmation in women with APS and three or more losses, reporting live birth rates of 85.7% versus 67.5% without treatment (an absolute improvement of 18.2%).^[85] A 2021 meta-analysis confirmed this approach improves live birth rates by 20-30% in APS-associated RPL, though aspirin alone shows no benefit.^[90] Infectious causes like chronic endometritis are treated with targeted antibiotics following endometrial biopsy confirmation, as untreated infection may impair implantation and increase loss risk. Although ESHRE 2022 guidelines highlight a lack of randomized controlled trials and do not routinely recommend screening, observational studies demonstrate improved outcomes post-treatment; a 2020 cohort reported live birth rates rising from 42% to 75% after 14-day antibiotic regimens in RPL patients with endometritis.^[85]^[91] A 2023 meta-analysis further supported this, showing a 25% increase in live birth rates and reduced abortion rates after eradication.^[92] The ESHRE 2022 guidelines specify that progesterone supplementation is not routinely recommended for RPL unless there are three or more prior losses accompanied by vaginal bleeding in the current pregnancy, where vaginal progesterone may conditionally improve live birth rates (relative risk 1.28).^[85]

Approaches for unexplained cases

Approximately 40-50% of cases of recurrent pregnancy loss (RPL) remain unexplained after comprehensive evaluation.^[93] For these idiopathic cases, expectant management—close monitoring without specific interventions—is the primary approach, with subsequent pregnancies achieving live birth rates of 60-70% in the absence of identifiable risk factors.^[4] Empiric therapies are sometimes considered for unexplained RPL, though evidence is limited and recommendations are cautious. The European Society of Human Reproduction and Embryology (ESHRE) provides a conditional recommendation for vaginal progesterone supplementation (typically 400 mg daily) in women with three or more prior miscarriages, based on moderate-quality evidence suggesting a potential improvement in live birth rates, though it does not benefit those with fewer losses.^[7] This intervention is initiated from the time of positive pregnancy test until 12-16 weeks of gestation and is thought to support endometrial receptivity and uterine quiescence.^[94] Low-dose aspirin (81 mg daily) combined with low-molecular-weight heparin (e.g., enoxaparin 40 mg subcutaneously daily) has been used empirically in unexplained RPL outside of antiphospholipid syndrome (APS), but recent meta-analyses, including a 2024 Cochrane review, demonstrate no significant benefit in live birth rates and highlight potential risks such as bleeding complications.^[95] Guidelines therefore advise against routine use in non-APS cases due to lack of efficacy.^[94] Intravenous immunoglobulin (IVIG) and corticosteroids, such as prednisone, are not recommended for unexplained RPL owing to insufficient evidence of efficacy and associated risks including infection, thromboembolism, gestational hypertension, and preterm birth.^[96] A 2023 randomized trial found prednisone (20 mg daily) did not improve live birth rates compared to placebo and increased adverse outcomes.^[96] Similarly, multiple systematic reviews conclude IVIG provides no reproducible benefit over placebo in idiopathic cases.^[97]

Prognosis

Live birth outcomes

Women with a history of two prior miscarriages have a live birth rate of approximately 70% in their subsequent pregnancy, while those with three prior losses experience rates of 50-60%.^[98]^[99] These figures reflect baseline prognosis without targeted interventions and vary based on factors such as maternal age.^[4] Live birth outcomes differ significantly by underlying cause. For anatomical abnormalities, such as a septate uterus, surgical correction yields live birth rates of around 80-83% in subsequent pregnancies.^[4]^[100] In contrast, untreated genetic causes, including parental balanced chromosomal translocations, are associated with lower rates of 30-50% per pregnancy due to recurrent aneuploidy.^[101] Recent registry-based studies from 2025 indicate that cumulative live birth rates exceed 90% after four pregnancy attempts in women with recurrent miscarriage, highlighting the value of persistence.^[102] Assisted reproductive technologies, particularly when combined with preimplantation genetic testing for aneuploidy, can boost cumulative live birth rates to approximately 70% in affected couples.^[103]

Influencing factors

Several factors influence the prognosis of recurrent miscarriage, with the number of prior pregnancy losses being one of the most significant. Each additional miscarriage increases the risk of subsequent loss. For instance, the odds of a live birth decrease by about 32% per additional loss (OR 0.68, 95% CI 0.51-0.92). After three losses, the live birth rate is substantially lower, roughly halving compared to fewer losses, dropping from around 72% after three losses to 50% or less after six or more.^[104]^[3] Maternal age also plays a critical role in modifying outcomes, as advancing age is associated with higher rates of chromosomal abnormalities leading to miscarriage. Women under 30 years have live birth success rates of 70-80% (specifically 81.3% within five years), while those over 40 experience rates below 40% (41.7%). This age-related decline is independent of other factors and underscores the importance of timely evaluation.^[3] A history of prior live birth may exert a protective effect on prognosis, with women experiencing secondary recurrent miscarriage (after at least one live birth) showing similar or slightly improved live birth rates compared to primary cases. This benefit likely reflects underlying fertility and health factors. Similarly, elevated maternal BMI greater than 30 kg/m² reduces live birth chances by approximately 20%, with an associated increased miscarriage risk (OR 1.73, 95% CI 1.06-2.83).^[3]^[19] According to the 2022 ESHRE guidelines, paternal factors such as age and lifestyle have only a minor influence on prognosis, with no strong evidence linking sperm parameters or DNA fragmentation to recurrent outcomes beyond general fertility assessments.^[3]

Emotional consequences

Recurrent miscarriage often triggers intense emotional responses, including profound grief, anxiety, and depression among affected individuals and couples. Women, in particular, frequently report feelings of loss and emptiness, with grief manifesting as sadness, guilt, and anger toward the body or circumstances. Research indicates that 30-50% of women may develop PTSD-like symptoms, such as intrusive memories, hypervigilance, and emotional numbness, following recurrent losses, with prevalence rates reaching up to 39% in some cohorts.^[105]^[106] These reactions are compounded for couples, where men may experience similar but often less intense grief, leading to mismatched coping styles that exacerbate emotional distress.^[107] Long-term psychological effects include an elevated risk of chronic anxiety, with odds ratios of approximately 1.5-2 compared to women without pregnancy loss history, persisting into subsequent pregnancies and daily life. Depression rates can remain high, affecting 20-55% of women over time, contributing to ongoing emotional burden. Relationship strain is prevalent in 20-40% of couples, often involving communication breakdowns, reduced intimacy, and feelings of isolation between partners, as differing grief expressions heighten tensions.^[108]^[106]^[107] Recent 2025 studies highlight that emotional impacts of recurrent pregnancy loss include heightened distress, such as intensified fears of further loss and amplified grief. Cultural stigma surrounding miscarriage further worsens isolation, as societal silence and taboos discourage open discussion, leading to disenfranchised grief and heightened loneliness for affected individuals.^[109]^[110] These factors underscore the need for emotional consequences to be addressed alongside medical evaluations in RPL care.

Support strategies

Support strategies for addressing psychological distress following recurrent miscarriage encompass a range of therapeutic, medical, and community-based interventions tailored to individual needs. Given the high prevalence of emotional consequences such as anxiety and depression in affected individuals, these strategies aim to mitigate long-term mental health impacts through evidence-based care. The 2022 European Society of Human Reproduction and Embryology (ESHRE) guideline emphasizes considering the emotional burden of recurrent pregnancy loss (RPL) and providing supportive care in specialist settings, including access to multidisciplinary teams with expertise in psychological support.^[7] Counseling plays a central role, with cognitive behavioral therapy (CBT) demonstrating effectiveness in reducing symptoms of anxiety and depression among women with RPL. A preliminary open-label study involving 14 women found that individual CBT, averaging 8.9 sessions, significantly lowered state anxiety scores from 49.0 to 38.0 on the State-Trait Anxiety Inventory (P=0.016) and depression scores from 13.6 to 5.2 on the Beck Depression Inventory-II (P=0.001).^[111] Peer support groups specifically for RPL offer a vital community outlet, allowing individuals to share experiences and coping mechanisms in a non-judgmental environment. Organizations like RESOLVE: The National Infertility Association provide virtual and in-person support groups focused on pregnancy loss, incorporating elements such as expressive arts and trauma processing to foster emotional recovery.^[112] Medical interventions, including antidepressants, are recommended for cases involving clinical depression, particularly when symptoms persist despite counseling. The American College of Obstetricians and Gynecologists (ACOG) highlights that antidepressant medication can help manage severe stress and anxiety post-pregnancy loss, with careful consideration of risks during subsequent pregnancies.^[113] Multidisciplinary clinics integrate psychological care with medical evaluation, offering holistic management that includes routine assessment of distress and coordinated referrals. The ESHRE guideline advocates for such clinics to ensure compassionate, couple-centered support, including clear communication and tailored emotional resources.^[7] Online resources further enhance accessibility to support, with platforms like Tommy's providing dedicated communities for miscarriage and recurrent loss. Tommy's operates moderated Facebook groups and informational hubs that connect users with peers and expert advice on coping with grief and anxiety.^[114] These digital tools, alongside professional interventions, align with guideline recommendations for proactive emotional care, such as those in the 2022 ESHRE update, which stress the importance of information provision and listening skills in RPL management.^[7]

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Preconception and first-trimester metformin on pregnancy outcomes ...
Jun 3, 2025 · This meta-analysis specifically examined how the timing of metformin treatment affects pregnancy outcomes in women with PCOS. Our findings ...
[90]
Meta-analysis on aspirin combined with low-molecular-weight ... - NIH
Aspirin combined with LMWH for APS may improve live birth rate, and detection of d-dimer levels in APS pregnant women may predict pregnancy complications.
[91]
Impact of antibiotic treatment for chronic endometritis on ... - PubMed
Dec 8, 2020 · Conclusion: In our patients examined for RPL, the live birth rate was improved after treatment of chronic endometritis with 14-day antibiotic ...
[92]
The effect of chronic endometritis and treatment on patients with ...
Jun 30, 2023 · Effective antibiotic treatment for chronic endometritis may improve the clinical pregnancy rate and live birth rate with unexplained recurrent ...
[93]
Recurrent Pregnancy Loss Etiology, Risk Factors, Diagnosis, and ...
The original ESHRE guideline defines RPL as the spontaneous loss of two or more pregnancies from the time of conception until 24 weeks of gestation [4,5]. This ...<|separator|>
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Guideline on the management of recurrent pregnancy loss - ESHRE
Guideline on the management of recurrent pregnancy loss. Issued: 1 February 2023. RPL The updated guideline is now available. The guideline development ...Missing: diagnostic | Show results with:diagnostic
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a systematic review and meta-analysis - PMC - PubMed Central - NIH
Jun 19, 2024 · Aspirin and/or heparin for women with unexplained recurrent miscarriage with or without inherited thrombophilia. Cochrane Database Syst. Rev ...
[96]
Prednisone vs Placebo and Live Birth in Patients With Recurrent ...
May 2, 2023 · Data suggested that the use of prednisone may increase the risk of preterm delivery and biochemical pregnancy loss. Our results challenge the ...
[97]
Intravenous immunoglobulin treatment in women with four or more ...
Jun 28, 2022 · High dose of IVIG in very early pregnancy improved pregnancy outcome in women with ≥4 RPLs of unexplained aetiology. This new treatment will ...
[98]
Recurrent Early Pregnancy Loss: Overview, Etiology, Genetic Causes
Oct 6, 2025 · Early pregnancy loss is defined as the termination of pregnancy before 20 weeks' gestation or with a fetal weight of below 500 g.
[99]
Does surgery improve live birth rates in patients with ... - PubMed
Jul 24, 2014 · The infertility rates were similar in both groups, while the cumulative live birth rate (76.1%) tended to be higher than without surgery (60.0%) ...
[100]
Parental karyotype and subsequent live births in recurrent miscarriage
Most series 19, 20 investigating recurrent miscarriage claim that the untreated subsequent live birth rate is 60% with a 40% abortion rate. In addition ...
[101]
Comparative analysis of cumulative live birth rates in patients ... - NIH
Jul 3, 2025 · Recurrent pregnancy loss (RPL) affects 1–2% of women worldwide and poses diagnostic and therapeutic challenges due to its multifactorial causes.
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(PDF) Preimplantation Genetic Testing for Aneuploidy Improves ...
Oct 7, 2025 · Results Among women with recurrent pregnancy loss, preimplantation genetic testing for aneuploidy increased the cumulative live birth rate to 70 ...
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[PDF] Annex 10: Evidence tables - ESHRE
RM care preferably should be provided by only one doctor per couple. A treatment strategy should be designed with the couple for a subsequent pregnancy.
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Pregnancy loss leads to post-traumatic stress in one in three women
Feb 9, 2021 · Research shows post-traumatic stress disorder (PTSD) can develop in a third of women after miscarriage or an ectopic pregnancy.Missing: grief | Show results with:grief
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https://evidence.nihr.ac.uk/alert/pregnancy-loss-post-traumatic-stress/
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The Posttraumatic Impact of Recurrent Pregnancy Loss in Both ... - NIH
Jan 11, 2023 · Further, this grief can evolve into psychological disorders, such as depression, anxiety and progress to a posttraumatic stress disorder (PTSD) ...
[107]
Anxiety and PTSD Symptoms Common and Persistent After ...
Early pregnancy loss is common, affecting up to 25% of pregnancies. Studies looking at the emotional consequences of miscarriage have shown that...Missing: impact | Show results with:impact
[108]
Recurrent pregnancy loss, psychological distress and wellbeing ...
Nov 3, 2025 · Comparative studies have suggested that women who report RPL experience significantly greater psychological distress and poorer quality of life ...
[109]
Global prevalence of post-miscarriage anxiety, depression, and stress
Sep 26, 2025 · The impact of pregnancy loss is typically more profound for the mother than the father, often linked to anxiety, depression, and stress.<|control11|><|separator|>
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Cognitive behavior therapy for psychological distress in patients with ...
Jul 19, 2013 · The current preliminary open study confirmed that individual CBT was potentially useful for women with RM and depression and/or anxiety.
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Pregnancy Loss | RESOLVE: The National Infertility Association
This 8-week group will meet virtually via Zoom. It will incorporate journal writing, expressive arts, and EMDR to process the trauma of losing your baby.
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Finding Emotional Support After Pregnancy Loss - ACOG
So she saw a therapist and took antidepressant medication to cope with her stress and anxiety. She gave birth to a healthy baby, and she and the baby are both ...Should I See A Therapist... · My Partner Doesn't Seem As... · Will Getting Pregnant Again...<|control11|><|separator|>
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Online communities for baby loss | Tommy's
Tommy's Facebook support groups. Tommy's runs a general support group on Facebook for those who have suffered miscarriage, ectopic or molar pregnancy, ...Missing: Resolve | Show results with:Resolve<|control11|><|separator|>