Guideline sources The following summarized guidelines for the evaluation and management of recurrent pregnancy loss (RPL) are prepared by our editorial team based on guidelines from the European Society of Human Reproduction and Embryology (ESHRE 2023; 2018), the European Association of Urology (EAU 2023), the International Federation of Gynecology and Obstetrics (FIGO 2023), the British Society for Haematology (BSH 2022; 2012), the American Urological Association (AUA/ASRM 2021), the Society of Obstetricians and Gynaecologists of Canada (SOGC 2019; 2017; 2014), the European League Against Rheumatism (EULAR 2019), the Pan-American League of Associations of Rheumatology (PANLAR 2018), the American Society for Reproductive Medicine (ASRM 2017; 2016; 2012), the American Thyroid Association (ATA 2017), the American College of Obstetricians and Gynecologists (ACOG 2014; 2012), the American College of Endocrinology (ACE/OS/AACE 2013), the American College of Medical Genetics (ACMG 2013), the American Thyroid Association (ATA/AACE 2012), the American College of Chest Physicians (ACCP 2012), and the Royal College of Obstetricians and Gynaecologists (RCOG 2011). 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 Calculator https://web.pathway.md/diseases/recl6D5toWHVLfUtL 1/12 6/24/23, 2:57 PM Recurrent pregnancy loss Pathway Classification criteria for antipho Guidelines 1. Screening and diagnosis Definition: Define RPL as 2 failed clinical pregnancies. Obtain evaluation after 2 consecutive clinical pregnancy losses. E Recognize that up to 50% of cases of RPL will not have a clearly defined etiology. E 2. Classification and risk stratification Prognosis: Base prognosis on the patient's age number and her complete pregnancy history, including the number of previous pregnancy losses, live births, and their sequence. B Consider using prognostic tools (Kolte and Westergaard) to provide an estimate of the subsequent chance of live birth in couples with RPL. C 3. Diagnostic investigations Medical history: consider eliciting medical and family history to tailor diagnostic investigations for RPL. C Diagnostic imaging, pelvic ultrasound: As per ESHRE 2023 guidelines, consider obtaining a 2D ultrasound to rule out adenomyosis in all patients with RPL. C As per ESHRE 2018 guidelines, assess uterine anatomy, preferably with transvaginal 3D ultrasound, B in all patients with RPL. B As per RCOG 2011 guidelines, obtain a pelvic ultrasound to assess uterine anatomy in patients with recurrent first-trimester miscarriages and all patients with 1 second-trimester miscarriage. B Diagnostic imaging, further investigations: As per ESHRE 2018 guidelines, consider obtaining sonohysterography to evaluate uterine morphology when a 3D ultrasound is not available or when tubal patency has to be investigated. Prefer sonohysterography over hysterosalpingography for diagnosing uterine malformations. C Show 2 more https://web.pathway.md/diseases/recl6D5toWHVLfUtL 2/12 6/24/23, 2:57 PM Recurrent pregnancy loss Pathway As per ASRM 2012 guidelines, consider obtaining sonohysterography, hysterosalpingography, and/or hysteroscopy in patients with RPL. E As per RCOG 2011 guidelines, consider obtaining further investigations (3D pelvic ultrasound, hysteroscopy, or laparoscopy) to confirm the diagnosis in patients with suspected uterine anomalies. C Thrombophilia evaluation, antiphospholipid syndrome: As per ESHRE 2018 guidelines: Obtain antiphospholipid antibodies (lupus anticoagulant and anticardiolipin antibodies IgG and IgM) after 2 pregnancy losses in patients with RPL. B Consider obtaining -2 glycoprotein 1 antibodies after 2 pregnancy losses in patents with RPL. C As per SOGC 2014 guidelines, obtain antiphospholipid antibodies in patients with recurrent miscarriage or late pregnancy loss. B As per ACCP 2012 guidelines, obtain antiphospholipid antibodies in patients with recurrent early pregnancy loss ( 3 miscarriages before 10 weeks of gestation). B As per ACOG 2012 guidelines, obtain antiphospholipid antibodies in patients with a history of one fetal loss or 3 recurrent embryonic or fetal losses. B As per ASRM 2012 guidelines, obtain lupus anticoagulant, anticardiolipin antibodies, and anti- -2 glycoprotein 1 antibodies in patients with RPL. E As per BSH 2012 guidelines, obtain antiphospholipid antibodies in patients with RPL ( 3 pregnancy losses) before 10 weeks gestation. B As per RCOG 2011 guidelines, obtain antiphospholipid antibodies before pregnancy in all patients with recurrent first-trimester miscarriages and all patients with 1 second-trimester miscarriage. B Thrombophilia evaluation, inherited causes: As per BSH 2022 guidelines, do not screen for inherited thrombophilia in patients with recurrent miscarriages. D As per ESHRE 2018 guidelines, avoid screening for inherited thrombophilia in patients with RPL unless in the context of research, or in patients with additional risk factors for thrombophilia. D As per ACMG 2013 guidelines, do not obtain MTHFR polymorphism genotyping as part of the clinical evaluation for RPL. D As per RCOG 2011 guidelines, screen for inherited thrombophilias (including factor V Leiden, prothrombin gene mutation, and protein S) in patients with second-trimester miscarriage. B Endocrinological evaluation, thyroid: As per ESHRE 2018 guidelines, obtain thyroid testing (TSH and anti-TPO antibodies) in patients with RPL. Obtain thyroxine (T4) testing in patients with abnormal TSH and anti-TPO antibody levels. B https://web.pathway.md/diseases/recl6D5toWHVLfUtL 3/12 6/24/23, 2:57 PM Recurrent pregnancy loss Pathway As per ASRM 2012 guidelines, consider obtaining testing for thyroid abnormalities in patients with RPL. E As per ATA/AACE 2012 guidelines, consider obtaining anti-TPO antibodies in the evaluation of patients with recurrent miscarriages, with or without infertility. B Endocrinological evaluation, prolactin: As per ESHRE 2018 guidelines, do not obtain prolactin testing in patients with RPL without clinical symptoms of hyperprolactinemia (oligo/amenorrhea). D As per ASRM 2012 guidelines, consider obtaining prolactin testing in patients with RPL. E Endocrinological evaluation (other): Do not obtain the following tests in the routine evaluation of patients with RPL: ovarian reserve testing D luteal phase insufficiency testing D PCOS testing D androgen level D LH level D fasting insulin and fasting glucose levels D plasma homocysteine level. D Immunological evaluation: As per ESHRE 2023 guidelines: Do not obtain HLA determination in patients with RPL in clinical practice. D Consider obtaining HLA class II determination (HLA-DRB1 15:01, HLA-DRB1 07, and HLA- DQB1 05:01/05:2) in Scandinavian patients with secondary RPL after the birth of a boy, for prognostic purposes. C As per ESHRE 2018 guidelines, consider obtaining antinuclear antibodies for explanatory purposes. C Show 3 more Parental karyotyping: As per AUA 2021 guidelines, obtain male parent karyotyping in couples with RPL. E As per ESHRE 2018 guidelines: Do not obtain routine parental karyotyping in couples with RPL. Consider obtaining this testing after an individual risk assessment. D Provide genetic counseling in all couples with abnormal fetal or parental karyotype results, and consider informing them about the possible treatment options available, including their advantages and disadvantages. B As per ASRM 2012 guidelines, consider obtaining parental peripheral karyotypic analysis in couples with RPL. E As per RCOG 2011 guidelines: https://web.pathway.md/diseases/recl6D5toWHVLfUtL 4/12 6/24/23, 2:57 PM Recurrent pregnancy loss Pathway Obtain parental peripheral blood karyotyping of both partners in couples with recurrent miscarriage where testing of products of conception reports an unbalanced structural chromosomal abnormality. B Refer couples with an abnormal parental karyotype to a clinical geneticist. B Preimplantation genetic screening: As per ESHRE 2018 guidelines, insufficient evidence to recommend preimplantation genetic testing in couples with RPL. I As per RCOG 2011 guidelines, do not obtain preimplantation genetic testing with IVF treatment in patients with unexplained recurrent miscarriages. D Products of conception genetic testing: As per ESHRE 2018 guidelines, do not obtain a routine genetic analysis of pregnancy tissue but consider obtaining it for explanatory purposes. D Use array-based comparative genomic hybridization based on a reduced maternal contamination effect for genetic analysis of the pregnancy tissue. D As per ASRM 2012 guidelines, consider obtaining a karyotypic analysis of products of conception in the setting of ongoing therapy for RPL. E As per RCOG 2011 guidelines, obtain a cytogenetic analysis of the conception products of the third and subsequent consecutive miscarriages. B Male partner evaluation: As per ESHRE 2023 guidelines: Assess the lifestyle of male partners (paternal age, smoking, alcohol consumption, exercise pattern, and body weight) in couples with RPL. B Consider obtaining sperm DNA fragmentation testing in couples with RPL. C As per AUA 2021 guidelines: Consider obtaining an evaluation of the male in couples with RPL ( 2 losses). E Obtain karyotyping E and sperm DNA fragmentation in couples with RPL. B 4. Medical management General principles: Assess patients with recurrent first-trimester and second-trimester miscarriages by a health professional with the necessary skills and expertise. B Offer patients with recurrent miscarriages referral to a specialist clinic. B Management of antiphospholipid syndrome: As per EULAR 2019 guidelines: Initiate low-dose aspirin and heparin at prophylactic dosage in pregnant patients with obstetric antiphospholipid syndrome (no prior thrombotic events), with or without SLE, and a history of 3 recurrent spontaneous miscarriages at < 10th week of gestation. B https://web.pathway.md/diseases/recl6D5toWHVLfUtL 5/12 6/24/23, 2:57 PM Recurrent pregnancy loss Pathway Consider initiating low-dose aspirin alone or in combination with heparin in patients with 2 recurrent spontaneous miscarriages at < 10th week of gestation. C As per ESHRE 2018 guidelines: Consider initiating low-dose aspirin (75-100 mg/day), starting before conception, and prophylactic dose heparin (UFH or LMWH), starting at the date of a positive pregnancy test, in patients fulfilling the laboratory criteria of antiphospholipid syndrome and having a history of 3 pregnancy losses. C Consider initiating anticoagulant therapy in patients with 2 pregnancy losses and antiphospholipid syndrome only in the context of clinical research. C As per PANLAR 2018 guidelines, initiate hydroxychloroquine plus LMWH (40 mg/day) and low- dose aspirin in pregnant patients with systemic lupus erythematous with antiphospholipid antibodies and RPL. B As per SOGC 2014 guidelines, initiate low-dose aspirin alone or combined with LMWH in pregnancy in patients with confirmed antiphospholipid syndrome. B As per ACCP 2012 guidelines, initiate antepartum prophylactic- or intermediate-dose UFH or prophylactic LMWH combined with low-dose aspirin (75-100 mg/day) in patients fulfilling the laboratory criteria for antiphospholipid syndrome and a history of 3 pregnancy losses. B As per ACOG 2012 guidelines, consider initiating prophylactic doses of heparin and low-dose aspirin during pregnancy, and continuing to 6 weeks of postpartum, in patients with antiphospholipid syndrome and a history of stillbirth or recurrent fetal loss but no prior thrombotic history. C As per ASRM 2012 guidelines, consider initiating a combination of prophylactic doses of UFH and low-dose aspirin in patients with persistent, moderate-to-high titers of circulating antiphospholipid antibodies. E As per BSH 2012 guidelines, initiate antenatal heparin therapy combined with low-dose aspirin throughout pregnancy in patients with antiphospholipid syndrome and RPL ( 3 pregnancy losses). B As per RCOG 2011 guidelines: Consider initiating low-dose aspirin and heparin to prevent further miscarriages in pregnant patients with antiphospholipid syndrome. C Do not use corticosteroids or IVIG to improve the live birth rate in patients with RPL associated with antiphospholipid antibodies. Recognize that their use may provoke significant maternal and fetal morbidity. D Management of inherited thrombophilia: As per ESHRE 2018 guidelines, avoid administering antithrombotic prophylaxis in patients with hereditary thrombophilia and a history of RPL unless in the context of research or if indicated for VTE prevention. D As per ACCP 2012 guidelines, avoid administering antithrombotic prophylaxis in patients with inherited thrombophilia and a history of pregnancy complications, including miscarriage. D https://web.pathway.md/diseases/recl6D5toWHVLfUtL 6/12 6/24/23, 2:57 PM Recurrent pregnancy loss Pathway As per RCOG 2011 guidelines: Insufficient evidence to support the use of heparin during pregnancy to prevent miscarriage in patients with first-trimester RPL associated with inherited thrombophilia. I Consider initiating heparin therapy during pregnancy to improve the live birth rate in patients with second-trimester miscarriages associated with inherited thrombophilias. B Management of thyroid dysfunction (overt hypothyroidism): initiate levothyroxine in patients with RPL with overt hypothyroidism arising before conception or during early gestation. B Management of thyroid dysfunction (subclinical hypothyroidism): Insufficient evidence to support the use of levothyroxine in patients with RPL and subclinical hypothyroidism, recognizing that treatment may reduce the risk of miscarriage but balancing the potential benefit of treatment against the risks is required. I Assess TSH level in early gestation (7-9 weeks) when patients with RPL and subclinical hypothyroidism become pregnant again, and initiate levothyroxine to treat hypothyroidism. B Management of thyroid dysfunction, thyroid autoimmunity: As per ESHRE 2023 guidelines, do not initiate levothyroxine in euthyroid patients with thyroid antibodies and RPL. D As per ESHRE 2018 guidelines: Insufficient evidence to support the use of levothyroxine in euthyroid patients with RPL and thyroid antibodies outside a clinical trial. I Assess TSH level in early gestation (7-9 weeks) when patients with RPL and thyroid autoimmunity become pregnant again, and initiate levothyroxine to treat hypothyroidism. B As per ATA 2017 guidelines: Consider initiating levothyroxine (at a starting dose of 25-50 g/day) in anti-TPO antibody- positive euthyroid pregnant patients with a prior history of pregnancy loss, given its potential benefits compared with its minimal risk. C Do not use IVIG in euthyroid patients with RPL. D Management of luteal phase insufficiency: As per FIGO 2023 guidelines, do not offer preconception progesterone supplementation (oral, vaginal, rectal, or injectable) in patients with first-trimester RPL. D Show 2 more As per ESHRE 2018 guidelines, insufficient evidence to support the use of progesterone I or hCG to improve live birth rates in patients with RPL and luteal phase insufficiency. I As per RCOG 2011 guidelines, insufficient evidence to support the use of progesterone or hCG during pregnancy to prevent miscarriage in patients with RPL. I Management of polycystic ovaries: do not offer suppression of high LH levels to improve the live birth rates in ovulatory patients with RPL and polycystic ovaries. D Management of hyperprolactinemia: consider initiating bromocriptine to increase live birth rates in patients with RPL and hyperprolactinemia. C https://web.pathway.md/diseases/recl6D5toWHVLfUtL 7/12 6/24/23, 2:57 PM Recurrent pregnancy loss Pathway Management of glucose metabolism impairment: As per ESHRE 2018 guidelines, insufficient evidence to support the use of metformin during pregnancy to prevent pregnancy loss in patients with RPL and glucose metabolism defects. I As per RCOG 2011 guidelines, insufficient evidence to support the use of metformin during pregnancy to prevent miscarriage in patients with recurrent miscarriages. I Management of cervical insufficiency: As per SOGC 2019 guidelines, perform elective cervical cerclage at 12-14 weeks of gestation in patients with a history of 3 second-trimester pregnancy losses or extreme premature deliveries if no specific cause other than potential cervical insufficiency is identified. A Show 2 more As per ESHRE 2018 guidelines: Consider performing cerclage in patients with a singleton pregnancy and a history of recurrent second-trimester pregnancy loss attributable to cervical weakness. C Obtain serial cervical ultrasound surveillance in patients with a history of second-trimester pregnancy losses and suspected cervical weakness. B As per ACOG 2014 guidelines, consider performing history-indicated cerclage in patients with a history of unexplained second-trimester delivery in the absence of labor or abruptio placentae. C As per RCOG 2011 guidelines, consider performing cervical cerclage only in patients likely to benefit, as it is associated with potential hazards related to the surgery and the risk of stimulating uterine contractions. B Show 2 more Management of uterine abnormalities (congenital anomalies): Do not perform metroplasty for bicorporeal uterus in patients with RPL and normal cervix. D Insufficient evidence to recommend metroplasty for bicorporeal uterus in patients with a double cervix. D Do not perform uterine reconstruction for hemi-uterus in patients with RPL. D Management of uterine abnormalities, uterine septum: As per ASRM 2016 guidelines, consider offering hysteroscopic septum incision to reduce subsequent miscarriage rates and improve live-birth rates in patients with RPL. C As per RCOG 2011 guidelines, insufficient evidence to recommend uterine septum resection to prevent further miscarriages in patients with RPL and uterine septum. I Management of uterine abnormalities (uterine adhesions): insufficient evidence to recommend surgical removal of intrauterine adhesions for pregnancy outcomes. Take precautions to prevent the recurrence of adhesions after hysteroscopic removal of intrauterine adhesions in patients with RPL. I Management of uterine abnormalities, uterine fibroids: As per ESHRE 2018 guidelines: https://web.pathway.md/diseases/recl6D5toWHVLfUtL 8/12 6/24/23, 2:57 PM Recurrent pregnancy loss Pathway Insufficient evidence to recommend hysteroscopic removal of submucosal fibroids or endometrial polyps in patients with RPL. I Do not perform surgical removal of intramural fibroids in patients with RPL. Insufficient evidence to recommend removing fibroids distorting the uterine cavity. D As per ASRM 2017 guidelines, insufficient evidence to recommend myomectomy (laparoscopic or open) to reduce miscarriage rates. I Management of vaginal bleeding: consider offering vaginal progesterone to improve the live birth rate in patients with 3 pregnancy losses and vaginal blood loss in a subsequent pregnancy. C Management of unexplained RPL: As per ESHRE 2023 guidelines: Consider administering repeated and high doses of IVIG very early in pregnancy to improve live birth rates in patients with 4 unexplained RPL. C Insufficient evidence to support the use of G-CSF in patients with unexplained RPL. I As per ESHRE 2018 guidelines, do not use the following therapies in patients with unexplained recurrent pregnancy: corticosteroids D lymphocyte immunization therapy D heparin or low-dose aspirin D vaginal progesterone. D Show 2 more As per RCOG 2011 guidelines: Offer supportive care alone in the setting of a dedicated early pregnancy assessment unit in patients with unexplained recurrent miscarriages, as they have an excellent prognosis for future pregnancy outcomes without pharmacological intervention. B Do not use the following therapies to improve the live birth rate in patients with unexplained RPL: paternal cell immunization third-party donor leukocytes trophoblast membranes IVIG. D Management of male partner: As per EAU 2023 guidelines, consider offering varicocelectomy in male partners of couples with RPL with raised sperm DNA fragmentation. C As per ESHRE 2023 guidelines, insufficient evidence to recommend sperm selection by physiological intracytoplasmic sperm injection in couples with RPL. I As per ESHRE 2018 guidelines, do not offer antioxidants in males to improve the chance of live birth. D https://web.pathway.md/diseases/recl6D5toWHVLfUtL 9/12 6/24/23, 2:57 PM Recurrent pregnancy loss Pathway 5. Nonpharmacologic interventions Weight loss: advise maintaining a healthy normal range BMI in patients with RPL, B as maternal obesity or significant underweight is associated with obstetric complications and can affect the chances of live birth. B Physical activity: insufficient evidence regarding the role of exercise in patients with RPL. I Advise a normal exercise pattern. I Smoking cessation: advise smoking cessation in couples with RPL, as smoking can affect the chances of live birth. B Alcohol restriction: advise limiting alcohol consumption in patients with RPL, B as excessive alcohol consumption is a possible risk factor for pregnancy loss and a proven risk factor for fetal problems, such as fetal alcohol syndrome. B Caffeine restriction: As per ESHRE 2018 guidelines, insufficient evidence to recommend caffeine intake restrictions in patients with RPL. I As per AACE 2013 guidelines, advise consuming < 300 mg of caffeine (3 cups of coffee) per day during pregnancy, as caffeine can increase the incidence of miscarriage and stillbirth when consumed in larger quantities. B Vitamin supplements: Consider offering prophylactic vitamin D supplementation during preconception counseling of patients with RPL. C Advise multivitamin supplements that are safe in pregnancy in patients with RPL asking about using multivitamin supplements. B 6. Patient education Counseling on risks: As per ESHRE 2018 guidelines, inform females sensitively that the risk of pregnancy loss is lowest in ages 20-35 years, and it rapidly increases after the age of 40 years. B Show 2 more As per SOGC 2017 guidelines, inform females that the risk of spontaneous pregnancy loss increases with age. B Psychological counseling: offer psychological counseling and support to couples with RPL. E 7. Preventative measures Thromboprophylaxis: As per SOGC 2014 guidelines, do not administer antithrombotic prophylaxis (low-dose acetylsalicylic acid and LMWH) in patients with a history of recurrent miscarriages without https://web.pathway.md/diseases/recl6D5toWHVLfUtL 10/12 6/24/23, 2:57 PM Recurrent pregnancy loss Pathway confirmed antiphospholipid syndrome. D As per ACCP 2012 guidelines, do not administer antithrombotic prophylaxis in patients with 2 miscarriages without antiphospholipid syndrome or thrombophilia. D References 1. Royal College of Obstetricians and Gynaecologists. The Investigation and Treatment of Couples with Recurrent First-trimester and Second-trimester Miscarriage. Green-top Guideline No. 17; Apr 11;. Open 2. ESHRE Guideline Group on RPL, Ruth Bender Atik, Ole Bjarne Christiansen et al. ESHRE guideline: recurrent pregnancy loss. Hum Reprod Open. 2018 Apr 6;2018 2):hoy004. Open 3. Pons-Estel BA, Bonfa E, Soriano ER et al. First Latin American clinical practice guidelines for the treatment of systemic lupus erythematosus: Latin American Group for the Study of Lupus GLADEL, Grupo Latino Americano de Estudio del Lupus)-Pan-American League of Associations of Rheumatology PANLAR . Ann Rheum Dis. 2018 Jul 25. Open 4. Practice Committee of the American Society for Reproductive Medicine. Evaluation and treatment of recurrent pregnancy loss: a committee opinion. Fertil Steril. 2012 Nov;98 5 1103 11. Open 5. Deepa J Arachchillage, Lucy Mackillop, Arvind Chandratheva et al. Guidelines for thrombophilia testing: A British Society for Haematology guideline. Br J Haematol. 2022 May 29. Open 6. ESHRE Guideline Group on RPL, Ruth Bender Atik, Ole Bjarne Christiansen et al. ESHRE guideline: recurrent pregnancy loss: an update in 2022. Hum Reprod Open. 2023 Mar 2;2023 1):hoad002. Open 7. Richard Brown, Robert Gagnon, Marie-France Delisle. No. 373 Cervical Insufficiency and Cervical Cerclage. J Obstet Gynaecol Can. 2019 Feb;41 2 233 247. Open 8. Committee on Practice Bulletins Obstetrics, American College of Obstetricians and Gynecologists. Practice Bulletin No. 132 Antiphospholipid syndrome. Obstet Gynecol. 2012 Dec;120 6 1514 21. Open 9. A. Salonia, C. Bettocchi, J. Carvalho et al. EAU Guidelines on Sexual and Reproductive Health. EAU. 2023. Open 10. Practice Committee of the American Society for Reproductive Medicine. Removal of myomas in asymptomatic patients to improve fertility and/or reduce miscarriage rate: a guideline. Fertil Steril. 2017 Sep;108 3 416 425. Open 11. Peter N Schlegel, Mark Sigman, Barbara Collura et al. Diagnosis and Treatment of Infertility in Men: AUA/ASRM Guideline Part I. J Urol. 2021 Jan;205 1 36 43. Open 12. Garber JR, Cobin RH, Gharib H et al. Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Endocr Pract. 2012 Nov-Dec;18 6 988 1028. Open 13. Keeling D, Mackie I, Moore GW et al. Guidelines on the investigation and management of antiphospholipid syndrome. Br J Haematol. 2012 Apr;157 1 47 58. Open 14. Tektonidou MG, Andreoli L, Limper M et al. EULAR recommendations for the management of antiphospholipid syndrome in adults. Ann Rheum Dis. 2019 May 15. Open https://web.pathway.md/diseases/recl6D5toWHVLfUtL 11/12 6/24/23, 2:57 PM Recurrent pregnancy loss Pathway 15. Shannon M Bates, Ian A Greer, Saskia Middeldorp et al. VTE, thrombophilia, antithrombotic therapy, and pregnancy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141 2 Suppl):e691S-e736S. Open 16. Kimberly E Liu, Allison Case. No. 346 Advanced Reproductive Age and Fertility. J Obstet Gynaecol Can. 2017 Aug;39 8 685 695. Open 17. Gonzalez-Campoy JM, St Jeor ST, Castorino K et al. Clinical practice guidelines for healthy eating for the prevention and treatment of metabolic and endocrine diseases in adults: cosponsored by the American Association of Clinical Endocrinologists/the American College of Endocrinology and the Obesity Society. Endocr Pract. 2013 Sep-Oct;19 Suppl 3 1 82. Open 18. Chan WS, Rey E, Kent NE et al. Venous thromboembolism and antithrombotic therapy in pregnancy. J Obstet Gynaecol Can. 2014 Jun;36 6 527 53. Open 19. Hickey SE, Curry CJ, Toriello HV. ACMG Practice Guideline: lack of evidence for MTHFR polymorphism testing. Genet Med. 2013 Feb;15 2 153 6. Open 20. Erik K Alexander, Elizabeth N Pearce, Gregory A Brent et al. 2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum. Thyroid. 2017 Mar;27 3 315 389. Open 21. Practice Committee of the American Society for Reproductive Medicine. Uterine septum: a guideline. Fertil Steril. 2016 Sep 1;106 3 530 40. Open 22. Hassan Shehata, Abdullatif Elfituri, Stergios K Doumouchtsis et al. FIGO Good Practice Recommendations on the use of progesterone in the management of recurrent first-trimester miscarriage. Int J Gynaecol Obstet. 2023 Apr;161 Suppl 1 3 16. Open 23. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No.142 Cerclage for the management of cervical insufficiency. Obstet Gynecol. 2014 Feb;123 2 Pt 1 372 379. Open https://web.pathway.md/diseases/recl6D5toWHVLfUtL 12/12