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Threatened Abortion
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National Vice President FOGSI - 2017 Founder President Prayagraj Chapter of ISOPARB 2021-23 ICOG Governing Council Member 2021-23 President AOGS (Allahabad) 2013 – 2016 Honorary Secretary AOGS 2011 – 2012; Treasurer AOGS 2008 – 2010 Organizing Chairperson, National FOGSI Conference –BOH – The Triology Delhi 2017 Organizing Secretary, National FOGSI Conference-SAVMA-2016, Allahabad Faculty at various National and International Conferences and webinars. National Awards - FOGSI Smriti Mylan Award “Save the Girl Child” AICOG 2013, FOGSI - Dr D.K Tank Reproductive Healthcare Promotion Trophy AICOG 2015. Felicitations - Safe Motherhood Committee at AICOG 2014 & Public Awareness Committee and Family Welfare Committee at AICOG 2016, Oncology & Midlife management committee at AICOG 2018, Public Awareness, Adolescent and Breast Committee at AICOG 2019, Endometriosis Committee at AICOG 2020 She has authored many articles and chapters in various books and journals. Dr. Ranjana Khanna (MS, DGO, FICOG) Senior Consultant & Director Ranjana Hospital, Prayagraj
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Abortion A pregnancy loss before 20 weeks of gestational age The types of spontaneous abortion include Threatened, Inevitable, Incomplete, Complete, Septic, Missed Abortion Mouri MI, Hall H, Rupp TJ. Threatened Abortion. [Updated 2021 May 19]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430747/
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Threatened Abortion vaginal bleeding before 20 weeks gestational age in the setting of a positive urine and/or blood pregnancy test with a closed cervical os, without passage of products of conception and without evidence of a fetal or embryonic demise Does not meet diagnostic criteria for spontaneous abortion “Threatened abortion as pregnancy-related bloody vaginal discharge or frank bleeding during the first half of pregnancy without cervical dilatation” -WHO Mouri MI, Hall H, Rupp TJ. Threatened Abortion. [Updated 2021 May 19]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430747/
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First Trimester Abortion
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Present during early pregnancy with lower abdominal pain, and/or vaginal bleeding Nearly 25% of have some degree of vaginal bleeding during the first 2 trimesters about 50 % of these progress to an actual abortion Bleeding in a threatened abortion is mild to moderate Abdominal pain may present as Intermittent Cramps, Suprapubic Pain, Pelvic Pressure, or Lower Back Pain Threatened Abortion Mouri MI. Threatened Abortion. [Updated 2021 May 19]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430747/
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Threatened abortion: Risk factors Can occur in any pregnancy regardless of maternal age, race, comorbidities, lifestyle, Previous history of 1st trimester bleeding, increases subsequent risk Risk factors for any type of miscarriage include Advanced Maternal , Paternal Age, Prior history of Pregnancy Loss, TORCH infections, Uncontrolled hyperglycemia, obesity, uncontrolled Thyroid disease Significant stressors, use of teratogenic medications, Presence of a subchorionic hemorrhage
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Etiology Exact etiology is not always known Chromosomal Abnormalities Maternal and paternal factors play a more significant role in euploid abortions Increasing paternal age -increased chromosomal abnormalities Chronic illnesses – diabetes, thyroid disease, extremes of weight, use of tobacco, alcohol, or illicit drugs Traumatic events/intimate partner violence Maternal health Factors: Structural abnormalities of the uterus and Exposure to teratogens or Infections during early pregnancy Mouri MI, Hall H, Rupp TJ. Threatened Abortion. [Updated 2021 May 19]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430747/
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Causes Of Miscarriage Arab H. The Role Of Progestogens In Threatened And Idiopathic Recurrent Miscarriage. Int J Womens Health. 2019;11:589-596 https://doi.org/10.2147/IJWH.S224159 Continued…..
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Pathophysiology < 20 weeks gestation presents with vaginal bleeding Cervical os is closed on a physical exam Abdominal cramping, pelvic pain, pelvic pressure, and/or back pain First- vaginal bleeding usually begins followed by cramping abdominal pain hours to days later Bleeding is the most predictive risk factor for pregnancy loss Risk of spontaneous abortion is less ( in a patient with threatened abortion) if fetal cardiac activity is present Mouri MI, Hall H, Rupp TJ. Threatened Abortion. [Updated 2021 May 19]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430747/
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Histopathology Histopathological examination strongly recommended for products of conception For repeat pregnancy loss, karyotyping should be given as an option for products of conception to rule in or rule out chromosomal abnormalities Help patients determine best options if they desire future pregnancies Mouri MI, Hall H, Rupp TJ. Threatened Abortion. [Updated 2021 May 19]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430747/
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History and Physical Examination Pelvic exam to determine the type of abortion Amount and site of bleeding Whether the cervix is dilated, and whether fetal tissue has passed In a threatened abortion, vaginal exam may reveal a closed cervical os with no tissue Usually no cervical motion tenderness Pelvic exam will reveal uterine and bilateral adnexal tenderness (rarely) In a threatened abortion There is no passage of tissue and cervical os is, by definition, closed These observations differentiate condition from an inevitable or incomplete abortion Mouri MI, Hall H, Rupp TJ. Threatened Abortion. [Updated 2021 May 19]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430747/
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Hendriks E. First Trimester Bleeding: Evaluation and Management. Am Fam Physician. 2019 Feb 1;99(3):166-174..
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Continued…….. Women with a threatened abortion usually have stable vital signs If hypovolemia is present, one should suspect bleeding or sepsis Abdomen in most cases is non-tender and soft If it is confirmed that there is no viable fetus, a discussion concerning expectant management or induction of abortion should occur with the patient Mouri MI, Hall H, Rupp TJ. Threatened Abortion. [Updated 2021 May 19]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430747/
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Evaluation: USG Transvaginal Ultrasound used to locate the pregnancy and determine if the fetus is viable also help rule out ectopic pregnancy to evaluate for retained products of conception Yolk sac is typically seen at 36 days Heartbeat is seen on USG at approx. 45 days after the last menstruation Fetal cardiac activity suggests a better prognosis than those without FHR less than 120 bpm suggests impending fetal death (only 6 % survival) Mouri MI. Threatened Abortion. [Updated 2021 May 19]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430747/ Nickels L.C., De Portu G. (2016) Ultrasonography for Threatened, Incomplete, or Compete Abortion. In: Ganti L. (eds) Atlas of Emergency Medicine Procedures. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-2507-0_113
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USG Findings Hendriks E. First Trimester Bleeding: Evaluation and Management. Am Fam Physician. 2019 Feb 1;99(3):166-174..
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Factors predicting an increased risk of miscarriage Qureshi NS. Treatment options for threatened miscarriage. Maturitas. 2009 Dec;65 Suppl 1:S35-41.
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β-hCG level 1500 to 2000 lU/mL is associated with a gestational sac on ultrasound β-hCG doubles in 48 hours in 85% of intrauterine pregnancies β-hCG is usually detectable - first 9 to 11 days following ovulation and reaches 200 IU/mL at the expected time of menses Rh factor will also determine if Rhogam should be administered to prevent hemolytic disease of the newborn in this pregnancy/subsequent pregnancies Hemoglobin/hematocrit levels help monitor the degree of blood loss Urinalysis can also be obtained UTI been associated with signs and symptoms of threatened abortion Mouri MI, Hall H, Rupp TJ. Threatened Abortion. [Updated 2021 May 19]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430747/
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Bed rest Avoid stress/Intercourse Progesterone-300-400mg/day, Dydrogesterone (20-60mg/day) Folate Immunoglobulin Rh(D) hCG Injection ? Treatment / Management Mouri MI, Hall H, Rupp TJ. Threatened Abortion. [Updated 2021 May 19]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430747/
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Progestogens Currently Available For The Treatment Of Threatened abortion
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Treatment / Management Immunoglobulin Rh(D) Alloimmunization prevention by administration of Rh(D) immunoglobulin should be considered for who have vaginal bleeding in the setting of pregnancy who is Rh-ve 50 mcg dose of immunoglobulin is effective at alloimmunization prevention up to and through the 12th week of gestation, However, it is considered acceptable to give the standard 300 mcg dose due to availability or provider preference Mouri MI, Hall H, Rupp TJ. Threatened Abortion. [Updated 2021 May 19]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430747/
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Threatened abortion: Expectant Management Managed expectantly without any medical or surgical interventions Patients should be given strict return precautions concerning excessive vaginal bleeding, abdominal pain, or fever/patients educated on importance of follow-up Analgesia can be provided to help relieve discomfort from cramping NSAIDs should be avoided (as pregnancy may continue to progress to viability) Follow-up is recommended with serial transvaginal ultrasounds until a viable intrauterine pregnancy is confirmed or until progression to an inevitable, incomplete, or complete abortion occurs Mouri MI, Hall H, Rupp TJ. Threatened Abortion. [Updated 2021 May 19]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430747/
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β-hCG testing recommended for a pregnancy of unknown origin to continue to monitor for the viability, especially in setting where intrauterine pregnancy with cardiac activity has not been confirmed by ultrasound possible that the pregnancy has not reached the gestational age by which cardiac activity would be expected on ultrasound or it is possible that the pregnancy will not be viable The patient counseled about the possibility of spontaneous abortion, as well as the possibility of pregnancy to continue towards viability Mouri MI, Hall H, Rupp TJ. Threatened Abortion. [Updated 2021 May 19]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430747/
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Bedrest and other activity restrictions not been found to be efficacious in the prevention of a threatened abortion progressing to spontaneous abortion and have been shown to increase the risk of other complications including deep vein thrombosis and/or pulmonary embolism and therefore should not be recommended Advise patients to avoid strenuous activities and to maintain pelvic rest at least until the cessation of vaginal bleeding. Recommend patients start prenatal vitamins with folic acid supplementation Mouri MI, Hall H, Rupp TJ. Threatened Abortion. [Updated 2021 May 19]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430747/
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Role of Dydrogesterone in Threatened Abortion
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Cytokines and Pregnancy ‘‘Natural pregnancy-induced immunomodulation’’ Downregulation of Th1 responses Upregulation of Th2 responses Raghupathy R. Current Medicine Research and Practice. 2016 Nov 1;6(6):233-9. Patki A. Gynecol Endocrinol. 2007 Oct;23 Suppl 1:68-72.
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Patki A. Gynecol Endocrinol. 2007 Oct;23 Suppl 1:68-72. Immunological reactions during successful pregnancy
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Progesterone-Induced Blocking Factor (PIBF) Trophoblast tissue (special characteristics): induces an immunomodulation process- actively protect itself from maternal immune system PIBF, a protein that can block natural killer (NK) cell-mediated lysis of certain tumor cells, has been identified in pregnant women PIBF is thought to have an anti-abortive effect that may be related to a shift from Th1 to Th2 cytokines Asher Bashiri. Recurrent Pregnancy Loss, Evidence-Based Evaluation, Diagnosis and Treatment. DOI10.1007/978-3-319-27452-2
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Pro-inflammatory cytokines (Th1) - cytotoxic and tissue-damaging capabilities Women with recurrent spontaneous miscarriage (RSM) have a greater bias towards a Th1-type or pro-inflammatory cytokine profile as compared to women with healthy pregnancy women with threatened miscarriage produce elevated levels of Th1 cytokines Women with healthy pregnancy have decreased Th1 cytokines and increased Th2 cytokines Thus, there is an increased pro-inflammatory cytokine bias in unexplained recurrent miscarriage Cytokines and Pregnancy Loss Raghupathy, R. (2016). Immunomodulation with progestogens as a therapeutic approach in pregnancy complications. Current Medicine Research and Practice, 6(6), 233–239.
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Immunological reactions in recurrent/spontaneous abortion Patki A. Gynecol Endocrinol. 2007 Oct;23 Suppl 1:68-72.
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Pregnancy Loss: mechanisms of cytokine action Increased activity of NK cells in blood/uterus linked to miscarriage NK cells, like activated Th1 cells, could release cytokines deleterious to trophoblast Th1 cytokines also convert NK cells into lymphokine-activated killer (LAK) cells Systemic levels of LAK-like cells correlate with high miscarriage rates Th1-dominated response detrimental to early placental differentiation & embryonic development Inflammatory Th1 cytokines- TNF-α and IFN-γ causes apoptosis of trophoblast cells and thus directly damage “conceptus” also inhibits secretion of GM-CSF from uterine epithelium Cytokines activate coagulation mechanisms leads to vasculitis affecting blood supply to the implanted embryo, a process that they have termed ‘‘cytokine-triggered vascular auto-amputation’’ Raghupathy R. Current Medicine Research and Practice. 2016 Nov 1;6(6):233-9.
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The relationship of cytokines, progesterone, other immune factors and cells with miscarriage Raghupathy R. Current Medicine Research and Practice. 2016 Nov 1;6(6):233-9. NK cells- Natural Killer
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The impact of cytokines, progesterone, PIBF, and other factors and cells on the success of pregnancy Raghupathy R. Current Medicine Research and Practice. 2016 Nov 1;6(6):233-9. Studies have shown that there is a Th1 tendency (shift) in RPL In women with a history of unexplained RPL, the Th1/Th2 cytokines ratio was higher in the RPL group whereas there was a clear Th2 shift during first trimester in the successful pregnancy group
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Dydrogesterone
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Dydrogesterone Dydrogesterone is retroprogesterone, stereoisomer of progesterone, with additional double bond between carbons 6 and 7 These small differences in chemical structure account for the Increased bioavailability (~5.6 times higher) for oral intake High selectivity for progesterone receptors 20 times higher potency Pickar JH. Progesterone. Climacteric. 2018;21(4):305. Endocr Rev. 2013;34(2):171-208. Maturitas. 2008;61(1–2):171–180.
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Receptor Selectivity Dydrogesterone is selective for progesterone receptors, avoiding other receptor related side effects Schindler AE. Maturitas. 2009;65 Suppl 1:S3-S11. 2. Kuhl H. Climacteric. 2005;8(Suppl 1):3–6. 3. Rizner TL et al. Steriods. 2011;76(6):607–615.
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Affinity to Progesterone Receptors Progesterone molecule is almost “flat” while dydrogesterone is bent With its cis-orientation High specific affinity for progesterone receptors: ~1.5 times better affinity than progesterone Dihydrodydrogesterone, the main metabolite of dydrogesterone, also has progestogenic activity2 No affinity for androgen, mineralocorticoid, glucocorticoid, and estrogenic receptors Schindler AE. Maturitas. 2009;65 Suppl 1:S3-S11. Schindler AE. Maturitas. 2008;61(1–2):171–180.
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Dydrogesterone Vs. Micronized Progesterone
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Bioavailability Dydrogesterone Vs. Micronized Progesterone
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Tolerability Unlike micronized progestogens, Dydrogesterone is not chemically related to testosterone Its low affinity for the androgen receptor explains why it has no unwanted androgenic even at high doses & after prolonged treatment no virilisation (acne, voice changes, hirsutism) of the adult female no virilising effects on the genital tract of the female foetus no effect on the fertility of the offspring Dydrogesterone is not converted into oestrogen, and has no adverse oestrogenic effects on fertility or sexual development Schindler AE. Maturitas. 2009;65 Suppl 1:S3-S11. Aydar CK, Greenblatt RB. Int J Fertil 1964;9:585-595.
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Favorable Pharmacokinetic Profile Good oral bioavailability 5.6 times higher oral bioavailability than progesterone requires a 10-20 times lower oral dose, providing clear clinical benefits Hepatic first class metabolism Dydrogesterone puts less burden on liver as it requires a 10-20 times lower dose No risk of cholestasis in pregnancy Has quick onset of action Rapidly absorbed, reaching maximal levels between 30 min to 2.5 hours after administration Has long and stable half life (mean terminal half life is 5-7 hours) Griesinger G, et al. Reprod Biomed Online. 2019;38(2):249-259
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Small Change can make a difference Light technology bends progesterone into a curved retro-steroid structure- Dydrogesterone Enhanced Progestogenic effect- Improved bioavailability improved specificity and affinity to progesterone receptor Its conformation is induced by exposing progesterone to ultraviolet light, a reaction first described in the 1950s by Reerink et al Gruber CJ, Huber JC. The role of dydrogesterone in recurrent (habitual) abortion. J Steroid Biochem Mol Biol. 2005 Dec;97(5):426-30.
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Pharmacological actions of Dydrogesterone DSC-decidual stromal cells; EVT-extravillous trophoblasts; Gal-galectin; tDC- tolerogenic dendritic cell; Teff-effector T cell; Th-T helper cell; Treg- regulatory T cell. Reproductive BioMedicine Online 2019 38249-259DOI: (10.1016/j.rbmo.2018.11.017)
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The potential immunomodulatory effects of Dydrogesterone Multiple immunomodulatory effects, including Expanding the number of local Treg cells, Arresting dendritic cells in a tolerogenic state Increase the expression of the immunosuppressive molecule Galectin-1, which promotes the generation of tolerogenic dendritic cells Progesterone may also epigenetically silence chemokine genes, thereby preventing homing of effector T cells to the decidua Reproductive BioMedicine Online 2019 38249-259DOI: (10.1016/j.rbmo.2018.11.017)
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Dydrogesterone: Immunomodulatory effects Dydrogesterone retains “immunomodulatory effect” of progesterone Dydrogesterone plays a role in establishing the appropriate local immunological environment for the developing fetus Raghupathy R. Current Medicine Research and Practice. 2016 Nov 1;6(6):233-9.
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Patki A. Gynecol Endocrinol. 2007 Oct;23 Suppl 1:68-72. Raghupathy R. Current Medicine Research and Practice. 2016 Nov 1;6(6):233-9.
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47 Dydrogesterone: Indications Role in safe motherhood Recurrent Pregnancy Loss (Habitual abortion) Infertility due to luteal dysfunction- Luteal support as part of ART Threatened preterm birth Menstrual Disorders Dysmenorrhea Secondary amenorrhea Dysfunctional uterine bleeding and irregular cycles Endometriosis Hormonal replacement therapy Premenstrual syndrome
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Dosage in Threatened Abortion Threatened abortion : Initial dose of upto 40 mg Dydrogesterone may be given followed by 20 or 30 mg per day until symptoms remit
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Dydrogesterone in Recurrent Pregnancy Loss: FOGSI Position statement 2015 Dydrogesterone derived from a plant source. i.e. Diosgenin ( Dioscorea villosa ) Dydrogesterone known to have immunomodulatory properties such as decreasing pro-inflammatory increasing anti-inflammatory cytokines in early pregnancy Based on the available clinical data, progesterone support (dydrogesterone) is beneficial in women presenting with a clinical diagnosis of threatened miscarriage with relative risk reduction in the miscarriage rate of 47% with the use of progesterone (risk ratio (RR) 0.53) The argument for use of progesterone (vaginal micronized progesterone & dydrogesterone) is that there is no evidence of harm and there is some evidence of benefit https://www.fogsi.org/wp-content/uploads/2017/07/Progesterone-position-paper-Oct-2015.pdf
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FOGSI Position statement 2015 The doses of progesterone that are generally used in clinical practice as per current evidence are as follows: Threatened Miscarriage : Micronized Progesterone : 400mg /day vaginal till bleeding stops Dydrogesterone : 40 mg loading dose followed by 20-30 mg daily till 7 days after bleeding stops https://www.fogsi.org/wp-content/uploads/2017/07/Progesterone-position-paper-Oct-2015.pdf
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Recommendations The Position Statement on the Use of Progestogens by (FOGSI) indicates beneficial evidence for the use of dydrogesterone The more recent European Progestin Club Guidelines (EPC) Consensus-based recommendation suggests that a reduction in miscarriage is observed with the use of dydrogesterone for women presenting with a clinical diagnosis of threatened and recurrent miscarriage Guideline of the European Society of Human Reproduction and Embryology Oct recommends Dydrogesterone, where infertility due to luteal insufficiency is suspected As per The Royal Australian and New Zealand College of Obstetricians and Gynecologists Consensus-based recommendation, for women presenting with clinical diagnosis of threatened miscarriage evidence suggests reduction in the rate of spontaneous miscarriage with the use of progestogens
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> 55 Years of Clinical experience > 113 million women 20 million fetuses have been exposed to dydrogesterone since 1960 Griesinger G. Reprod Biomed Online. 2019;38(2):249-259. Safety: Summary In view of this extensive use, a substantial fetal risk of dydrogesterone can be ruled out Overall, new-born safety data, including the incidence of congenital, familiar and genetic disorders, were comparable between the oral dydrogesterone and micronized vaginal progesterone groups in the Lotus I study
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Meta-analysis comparing the efficacy and safety of progestogens in threatened abortion Progesterone is widely used to prevent threatened miscarriage. A total of 59 RCTs with 10, 424 participants were included. Oral dydrogesterone (DYD) had the lowest risk of miscarriage (SUCRA 100.0%), followed by vaginal progesterone (SUCRA 67.9%). Oral micronized progesterone had the highest risk of miscarriage (SUCRA 15.7%). Oral DYD (dydrogesterone) is effective in the treatment of threatened miscarriage. The results of the present study can help patients make informed decisions about treatment options for threatened miscarriage Zhao H. A pairwise and network meta-analysis comparing the efficacy and safety of progestogens in threatened abortion. Int J Gynaecol Obstet. 2021 Apr 17. doi: 10.1002/ijgo.13707. Epub ahead of print. PMID: 33864694.
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Progestogen for treating threatened Miscarriage 7 trials (involving 696 participants) in this update of the review Treatment of miscarriage with progestogens compared to placebo or no treatment probably reduces the risk of miscarriage Treatment with oral progestogen (Dydrogesterone) compared to no treatment also probably reduces the miscarriage rate. However treatment with vaginal progesterone compared to placebo, probably has little or no effect in reducing the miscarriage rate Cochrane Review suggest that progestogens are probably effective in the treatment of threatened miscarriage but may have little or no effect in the rate of preterm birth Wahabi HA. Cochrane Database Syst Rev. 2018 Aug 6;8(8):CD005943.
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A systematic review of dydrogesterone for the treatment of threatened miscarriage 5 randomized trials were identified, including 660 women who fulfilled the criteria for metaanalysis The number of subsequent miscarriages or continuing pregnancies per randomized woman was compared in women receiving dydrogesterone compared to standard bed rest or placebo intervention There was a 13% (44/335) miscarriage rate after dydrogesterone administration compared to 24% in control women The adverse and side effects were summarized in all 21 reports, and seemed to be minimal the results of this systematic review show a significant reduction of 47% in the odds for miscarriage when dydrogesterone is compared to standard care indicating a real treatment effect Carp H. A systematic review of dydrogesterone for the treatment of threatened miscarriage. Gynecol Endocrinol. 2012;28(12):983-990. doi:10.3109/09513590.2012.702875
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The influence of oral dydrogesterone and vaginal progesterone on threatened abortion: A systematic review and meta-analysis 9 randomized trials that included 913 pregnant women (including 322 treated with oral dydrogesterone, 213 treated with vaginal progesterone, and 378 control subjects) who met the selection criteria incidence of miscarriage was significantly lower in the total progesterone group vs. control group (13.0% vs 21.7%) Moreover, the incidence of miscarriage was significantly lower in the oral dydrogesterone group than in the control group (11.7% vs 22.6%) and was lower in the vaginal progesterone group than in the control group, although this difference was nonsignificant (15.4% vs 20.3%) Conclusion: Progesterone therapy, especially oral dydrogesterone, can effectively prevent miscarriage in pregnant women experiencing threatened abortion Lee HJ. The Influence of Oral Dydrogesterone and Vaginal Progesterone on Threatened Abortion: A Systematic Review and Meta-Analysis. Biomed Res Int. 2017;2017:3616875.
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Threatened Abortion Prognosis Complication Patient education
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Prognosis About 20% of women experience vaginal bleeding before 20 weeks of pregnancy About 50% of those progress to a pregnancy loss Increased risk of adverse outcomes later in pregnancy if there was vaginal bleeding during the first trimester of that pregnancy e.g., Placenta previa Placental abruption Necessitation for manual removal of the placenta after delivery, Cesarean delivery PPRM Preterm birth Low-birthweight infant Fetal or neonatal death Mouri MI, Hall H, Rupp TJ. Threatened Abortion. [Updated 2021 May 19]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430747/
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Adverse Prognostic factors A large empty gestational sac Discrepancy : gestational age and crown to rump length Fetal bradycardia or absence of fetal heart activity Advanced maternal age History of recurrent pregnancy loss Maternal serum Progesterone < 25 ng/ml or low maternal serum hCG Mouri MI, Hall H, Rupp TJ. Threatened Abortion. [Updated 2021 May 19]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430747/
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Complications Pregnancy loss (progression to inevitable, incomplete, complete, missed abortion) Heavy bleeding Retained products of conception Endometritis Septic abortion Complications later in pregnancy
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Consultations Patients with recurrent pregnancy loss or recurrent bleeding during pregnancy should be offered evaluation by a reproductive endocrinology and infertility specialist and/or by a maternal-fetal medicine specialist If a patient is determined to have a coagulopathy, a hematology consult should be considered Mouri MI, Hall H, Rupp TJ. Threatened Abortion. [Updated 2021 May 19]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430747/
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Deterrence and Patient Education Provided as both verbal and written explanations and instructions Explained to the patient that it is possible her pregnancy will continue and it is also possible that she will undergo a miscarriage Patient needs to understand that majority of miscarriages are not preventable She is not at fault for the loss of the pregnancy if a loss does occur Providers should explain to the patient that mild to moderate bleeding and cramping can be expected, but uncontrolled pain or heavy bleeding should be evaluated by an obstetric care provider or in the emergency department. Patients can be instructed to take acetaminophen as directed for pain relief Patients should avoid ibuprofen for pain control Patients who undergo threatened abortion should be evaluated for mood disorders including depression and anxiety. if a threatened abortion proceeds to pregnancy loss, the patient should be allowed to grieve as appropriate for each individual (counselling)
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Summary Most patients with a threatened abortion observed from home with close follow-up Repeat ultrasounds and beta-hCG levels will help to determine progression to a viable pregnancy or to an inevitable, complete, incomplete, or missed abortion Patients with increased vaginal bleeding require evaluation for hemorrhagic anemia and may be candidates for a blood transfusion or pregnancy evacuation Mouri MI, Hall H, Rupp TJ. Threatened Abortion. [Updated 2021 May 19]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430747/
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Thank You !