From Iusmicm

Contents 1 Early Pregnancy Loss 1.1 Objectives 1.2 Scenario #1 1.3 Abortions: Definitions 1.4 Epidemiology of Early Pregnancy Loss 1.5 Etiology of Early Pregnancy Loss 1.5.1 Etiology: Genetics 1.5.2 Etiology: Environmental and Occupational 1.5.3 Etiology: Medications 1.5.4 Etiology: Endocrine 1.5.5 Etiology: Anatomy (uterine malformations) 1.5.6 Etiology: Infectious agents 1.5.7 Etiology: Immune 1.6 Abortions: Dx, Px, Tx 1.6.1 Threatened abortion 1.6.2 Inevitable abortion and Incomplete abortion 1.6.3 Complete abortion 1.6.4 Missed abortion 1.6.5 Septic abortion 1.6.6 Overview 1.7 Scenario #1 Continued 1.8 Scenario #2 1.9 Ectopic Pregnancy: Definitions 1.10 Ectopic pregnancies 1.10.1 Ectopic pregnancy: General 1.10.2 Ectopic pregnancy: Incidence 1.10.3 Ectopic pregnancy: Mortality 1.10.4 Ectopic pregnancy: Risk Factors 1.10.5 Ectopic pregnancy: Diagnosis 1.10.5.1 Diagnosis: Clinical Presentation 1.10.6 =Diagnosis: Serum beta-HCG 1.10.6.1 Diagnosis: Transvaginal Ultrasound 1.10.6.2 Diagnosis: Progesterone 1.10.6.3 Diagnosis: Others 1.10.7 Ectopic Pregnancy: Treatment 1.10.8 Ectopic Pregnancy: Take Home Points 1.11 Grief Following Miscarriage 1.11.1 Unique Aspects of Grief 1.11.2 Uncertainty and Ambiguity 1.11.3 Implications for Clinical Care 1.11.4 Grief Counseling

Early Pregnancy Loss

Objectives

• By the end of the lecture, the student will have a basic understanding of:
  • The different types of abortions
  • The management of the different types of abortions
  • Ectopic pregnancy
  • The management of ectopic pregnancy
  • Grief related to early pregnancy loss and its implications for clinical care

Scenario #1

• 25yo G2P1001
• LMP (last menstrual period) of 8 wks ago
• Presents to your ER complaining of vaginal bleeding. Pt reports the bleeding began earlier today and has been very brisk, with moderate cramping.

• PMH / PSHx are non-contributory.
• PObHx is significant for one prior NSVD.
• VS (vitals): Tc 97.6, P 78, R 20, BP 120/78
• PEx:
  • Scant vaginal bleeding.
  • Cervix long & closed.
  • Uterus normal in size and non-tender.
  • No adnexal masses appreciated.
• Labs:
  • (+) UPT

• The most likely diagnosis for the patient’s problem is:
  • A) Complete Ab
  • B) Septic Ab
  • C) Threatened Ab
  • D) Incomplete Ab

Abortions: Definitions

• Abortion: termination of pregnancy before 20 weeks gestation or deliver of a fetus with a weight of less than 500 g.
• Threatened Abortion: any uterine bleeding from a gestation of less than 20 weeks without any cervical dilation or effacement.
• Inevitable Abortion: uterine bleeding from a gestation of less than 20 weeks accompanied by cervical dilation but without expulsion of any placental or fetal tissue through the cervix.
• Incomplete Abortion: passage of some but not all fetal or placental tissue through the cervix before 20 weeks gestation.
• Complete Abortion: spontaneous expulsion of all fetal and placental tissue from the uterine cavity before 20 weeks gestation.
• Missed Abortion: fetal death before 20 weeks gestation without expulsion of any fetal or maternal tissue for at least 8 weeks thereafter.
• Septic abortion: any type of abortion that is accompanied by uterine infection.
• Recurrent Spontaneous Abortion: loss of (two) three or more (consecutive) pregnancies before 20 weeks gestation.
• Therapeutic, elective, or induced abortion: intentional expulsion or extraction of fetal and placental tissue.

Epidemiology of Early Pregnancy Loss

• 15-25% of recognized pregnancies in the 4-20 week range undergo spontaneous abortions.
  • This number is actually around 40% when on considers unrecognized pregnancies.
• 80% of spontaneous abortions occur in the first 12 weeks of gestation.
• 50% of spontaneous abortions are credited to chromosomal abnormalities.
• Spontaneous abortions increase with age:
  • < 20 yo: 12% of recognized pregnancies
  • > 40 yo: 26% of recognized pregnancies
  • > 40 yo: 75% of all pregnancies (recognized and unrecognized)
• Once an embryo has become detectable by ultrasonography, fetal loss rate is 5%.

Etiology of Early Pregnancy Loss

• Genetics
• Environmental exposures
• Endocrine
• Anatomic
• Infectious
• Immunologic
• Idiopathic

Etiology: Genetics

• 50% of early spontaneous abortions are associated with fetal chromosomal abnormalities
• Autosomal trisomies are the most common abnormality.
  • Most are due to nondisjuction or translocation
  • Most common trisomies are: 13, 16, 18, 21, and 22
• Polyploides are more common than monosomies.
  • Recall that Turner syndrome is monosomal X

• A common cause of consecutive spontaneous early pregnancy losses is abnormal karyotype in the parents.
  • Parental abnormal karyotype are usually balanced chromosomal rearrangements or translocation.
  • The patients usually have not had an previously live births (RPL).

• The later in gestation the spontaneous abortion occurs, the less likely it is due to chromosomal defects:
  • 90% of anembryonic POCs are due to chromosomal defects
  • 50% of abortuses at 8-11 weeks are due to chromosomal defects
  • 30% of abortuses at 16-19 weeks are due to chromosomal defects
  • 3% of stillbirths are due to chromosomal defects
• POC = products of conception

• For abortuses from 6-18 weeks of gestation:
  • 46% have a trisomy
  • 32% have normal karyotype
  • 12% have a polyploidy
  • 7% have a monosomy
  • 3% have a rearrangement
• Trisomy > normal > polyploidy > monosomy > rearrangement

Etiology: Environmental and Occupational

• Smoking increases the risk of early fetal loss.
  • The risk increases in proportion with the number of cigarettes smoked.
• Alcohol increass the risk of early fetal loss.
• Heavy coffee consumption increases the risk of early fetal loss.
• Anesthetic gases, mercury, PBCs, radiation, pesticides, lead, and tetrachloroethylene (a dry cleaning agent) all increase the risk of early spontaneous abortion.

Etiology: Medications

• Accutane (isotretinoin) is known to cause an increased incidence of spontaneous abortion.

Etiology: Endocrine

• Hypothyroidism
  • Monitor TSH levels during pregnancy
  • Treat low TSH levels with levothyroxine

• Hyperprolactinemia
  • Monitor PRL, galactorrhea
  • Treat high PRL with dopamine agonist
  • Recall that PRL (from the anterior pit) is inhibited by dopamine release (from the hypothalamus)

• Hypoprogesteronemia
  • Results in an inadequate luteal phase to support the pregnancy
  • Treat with supplemental progesterone in early pregnancy

• Type 1 Diabetes
  • An issue when poorly controlled
  • Associated with spontaneous abortions and malformations

Etiology: Anatomy (uterine malformations)

• Uterine abnormalities can lead to spontaneous early abortions
• 12-15% of women with spontaneous abortions have uterine malformations.
• Diagnosis of uterine malformations can be made by:
  • Hysterosalpingogram (HSG)
  • Ultrasound
  • MRI
  • Laparoscopy

• Leiomyomata: can result in submucosal fibroids or polyps.
• Septate uterus:
  • Most common anatomical cause of spontaneous early abortsions.
  • Treatment is surgical repair.
  • With surgical treatment, prognosis is good in many cases.
• Intrauterine adhesions (Asherman's syndrome)
• DES exposure:
  • Results in a T-shaped uterus
  • Only historically relevant as there is very little DES exposure
• Incompetent cervix:
  • The incompetent cervix spontaneously dilates the internal os which results in membrane rupture and expulsion of the fetus

Etiology: Infectious agents

• Infectious agents have been implicated in spontaneous early abortions but never substantiated.
• Suspect agents include: C. trachomatis, L. monocytogens, Syphilis, HIV, group B streptococci.
• There is no hard evidence that bacterial or viral infections cause recurrent abortions.

**+ / - ureaplasma urealyticum, mycoplasma hominis

Etiology: Immune

• Antiphospholipid antibodies:
  • Directed against platelets and vascular endothelium
  • Cause thrombosis
  • Cause recurrent spontaneous abortions
• Antiphospholipid antibodies include: lupus anticoagulant, anticardiolipin Ab, and Beta2-glycoprotein Ab
• 10-16% of women with recurrent abortions have had antiphospholipid antibodies.
• Treatment for antiphospholipid antibodies is low dose aspirin, low dose heparin as soon as pregnancy is diagnosed.

• Thrombophilias:
  • Factor V leiden
  • Prothrombin gene mutation

• Chronic illness
  • Heart disease, HTN, renal disease, vascular disease, uncontrolled DM, lupus, obesity, anorexia

Abortions: Dx, Px, Tx

Threatened abortion

• Recall that threatened abortions are those with bleeding before week 20 but without any cervical effacement or dilation.
• Dx: serial HCG and ultrasound can gauge prognosis
  • Ultrasonographic detection of a heart yields a 95% chance of pregnancy continuing as viable.
• 50% of threatened abortions proceed to spontaneous abortions
• Tx:

**Expectant management (?),

• • Pelvic rest (put nothing in the vagina),
  • Reassurance

Inevitable abortion and Incomplete abortion

• Recall that inevitable abortions are those with uterine bleeding before 20 weeks gestation and cervical dilation without expulsion of any fetal or membrane material.
• Recall that incomplete abortions are those in which part but not all of the fetus and membranes are expelled through the cervix.

• Inevitable and incomplete abortions are usually accompanied with profuse bleeding.
• Inevitable and incomplete abortions usually occur in weeks 6-12.

• Tx:
  • Expectant management
  • Methergine:
    • a smooth muscle agonist (induces contractions to help expel fetus and membranes)
    • a blood vessel constrictor (to reduce bleeding on uterine surface)

**Dilation and curettage

• • Anti-D immunoglobulin for RH- mothers

Complete abortion

• Recall that a complete abortion is uterine bleeding within 20 weeks gestation and complete expulsion of fetus and membranes.
• Tx:
  • Need not be hospitalized, can be treated as outpatient
  • Methergine (depending on symptoms)
  • Anti-D immunoglobulin for RH- mothers

Missed abortion

• Recall that a missed abortion is death of the fetus before 20 gestation weeks without expulsion of any material for 8 weeks post-fetal-fatality.
• Tx:
  • Surgery (suction dilation and curettage, manual vacuum aspiration)

**Misoprostol:

Septic abortion

• Infections are seen with 1-2% of all spontaneous abortions.
• Septic abortions are potentially fatal for the mother.
• Septic abortions are of poor prognosis when infectious agent produces endotoxin which can lead to shock.
• Septic abortions may be due to introduction of infectious agents via non-sterile material upon an attempted unsafe abortion.
• Tx:
  • IV Broad spectrum antibiotics
  • Curettage

Overview

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Abortion Type	Cervix State	Bleeding	Pain	Product of Conception (POC)	Fetal Heart Activity (FH)	Treatment
Threatened	Closed
No	No
Expectant management (ExpMang)
Inevitable	Open
Yes	No	-	ExpMang, Medicine (Med), Surgery (Sx)
Incomplete	Open
Yes	Yes	-	ExpMang, Med, Sx
Complete	Closed
Yes / No	Yes	-	None (Rhogam?)
Missed	Closed	-	No	No	-	Med, Sx

• Medicines: misoprostol, methergine
• Surgery: D&C (dilation and curettage), MVA (manual vacuum aspiration)

Scenario #1 Continued

• 25yo G2P1001
• LMP (last menstrual period) of 8 wks ago
• Presents to your ER complaining of vaginal bleeding. Pt reports the bleeding began earlier today and has been very brisk, with moderate cramping.

• PMH / PSHx are non-contributory.
• PObHx is significant for one prior NSVD.
• VS (vitals): Tc 97.6, P 78, R 20, BP 120/78
• PEx:
  • Scant vaginal bleeding.
  • Cervix long & closed.
  • Uterus normal in size and non-tender.
  • No adnexal masses appreciated.
• Labs:
  • (+) UPT

• The most likely diagnosis for the patient’s problem is:
  • A) Complete Ab
  • B) Septic Ab

**C) Threatened Ab

• • D) Incomplete Ab

• The next best step(s) in this patient’s management would include:
  • A) obtaining a blood type & antibody screen (always)
  • B) obtaining a pelvic ultrasound (probably)
  • C) performing a D&C (no)
  • D) sending the patient home (maybe)
• Threatened abortions: do an ultrasound for fetal heart; 95% continue if fetal heart found; 50% spontaneously abort

Scenario #2

• 25yo G2P1001
• LMP of 8 wks ago
• Presents to your ER complaining of vaginal bleeding. Pt reports that spotting and right lower quadrant abdominal pain began earlier today.

• PMH / PSHx are non-contributory.
• PObHx is significant for one prior NSVD.
• VS: Tc 97.6, P 78, R 20, BP 120/78
• PEx:
  • Scant vaginal bleeding.
  • Cervix long & closed.
  • Uterus normal in size and non-tender.
  • (R) adnexal fullness appreciated.
• Labs:
  • (+) UPT

• In addition to obtaining a CBC, the next step in this patient’s management would include which of the following?

**A) Obtaining a beta-HCG (definitely)

• • B) Obtaining a pelvic ultrasound (possibly)
  • C) Obtaining a blood type and antibody screen (definitely)
  • D) Sending the patient home (no)

• Labs:
  • BHCG: 4000 IU

• What would you like to do now?

**A)Obtain a TVUS (transvaginal ultrasound)

• • B)Obtain a pelvic CT Scan
  • C)Send the Patient home
  • D)Perform a D&C

• TVUS Shows

**?

Ectopic Pregnancy: Definitions

• Ectopic Pregnancy: a pregnancy in which the blastocyst implants in any location other than the endometrium lining the uterine cavity.
• Heterotopic Pregnancy: a pregnancy that has both intrauterine and extrauterine implantations.
  • Very uncommon in vivo (1/30k)
  • Common with ART (assistant reproductive therapy, 1/100).
• Tubal Pregnancy: a pregnancy occur in a portion of the oviduct (ampulla, fimbria, or isthmus).
  • The fallopian tube is the most common site of ectopic pregnancy.
• Ruptured Ectopic Pregnancy: an ectopic pregnancy that erodes through the tissue in which it implanted (perhaps fallopian tube) and is producing hemorrhage from exposed blood vessels.
• Hemoperitoneum: blood in the peritoneal cavity.

Ectopic pregnancies

Ectopic pregnancy: General

• 98% of ectopic pregnancies implant in the fallopian tube.
• 80% implant in the ampulla of the fallopian tube.
• Tubal pregnancies can resolve in one of three ways:
  • Spontaneous resolution
  • Tubal abortion
  • Tubal rupture

Ectopic pregnancy: Incidence

• The incidence of ectopic pregnancies has increased since the 1970s for several reasons:
  • Earlier, more accurate detection.
  • ART
  • Reconstructive tubal surgeries
  • Rise in Chlamydia trachomonas

Ectopic pregnancy: Mortality

• Ectopic pregnancy mortality:
  • Fatality droped 90% from 1970 to 1987.
  • Ectopic pregnancy is the most common cause of maternal death in the first half of pregnancy.
  • Ectopic pregnancy is the second most common cause of maternal death over the whole span of pregnancy.

Ectopic pregnancy: Risk Factors

• Risk factors include:
  • Prior pelvic inflammatory disease
  • Chlamydia infection
  • Salpingitis
  • Prior tubal sx

***1/3 of tubal failures are do to a previous ectopic pregnancy

• • Prior ectopic pregnancy
  • Use of ART
    • ART is associated with an increase incidence of hetertopic (a pregnancy that has both intrauterine and extrauterine implantations)
  • Pregnancy with IUD in situ
  • Cigarette smoking
  • DES exposure
  • Increase age

Ectopic pregnancy: Diagnosis

• Clinical presentation
• Serum beta-HCG levels (elevated)
• TVUS (transvagina

Diagnosis: Clinical Presentation

• The clinical story of ectopic pregnancy can vary widely from mild spotting to full shock.
• There is a classic triad in ectopic pregnancy:
  • Delayed menses
  • Irregular vaginal bleeding
  • Abdominal pain
• Other possible S&S:
  • Adnexal tenderness
  • Adnexal mass
  • Uterine enlargement

• The differential for these S&S should include:
  • Ectopic pregnancy
  • Normal pregnancy
  • Ruptured ovarian cyst
  • Bleeding ovarian cyst
  • Spontaneous abortion
  • Salpingitis
  • Appendicitis
  • Adnexal torsion
  • Endometriosis

=Diagnosis: Serum beta-HCG

• Serum beta-HCG normally doubles every 2 days until it reaches a titer of about 100k.
• Serum bHCG peaks at 50k-100k IU / L at 8-10 weeks.

• Serum beta-HCG can be used to asses pregnancy viability:
  • A normal bHCG rise (double every 2 days) suggests a normal IUP (intra-uterine pregnancy).
  • A normal bHCG level (1000-1500 IU / L) suggests a normal IUP (intra-uterine pregnancy).
  • Confirm bHCG levels with an TVUS:
    • If IUP not seen, normal bHCG levels are likely from an ectopic pregnancy.

• Serum beta-HCG can be used to asses treatment results:
  • Declining bHCG levels indicate adequate medical / surgical treatment of an ectopic pregnancy.

Diagnosis: Transvaginal Ultrasound

• Transvaginal ultrasound (TVUS) is useful for:
  • Documenting intrauterine sac
  • Visualizing adnexal masses
  • Detecting adnexal cardiac activity
• Cardiac activity in an ectopic pregnancy is usually a contraindication for medical management.

Diagnosis: Progesterone

• Progesterone is actually not that helpful in diagnosis of an ectopic pregnancy.
• Progesterone levels in IUP (intra-uterine pregnancies) are generally > 25 ng / ml (98% of the time).
• Progesterone levels < 5 ng / ml represent nonviable pregnancies.

Diagnosis: Others

• Uterine curettage can be used as a diagnostic and treatment if the pregnancies is not desired.
• Culdocentesis is rarely used today.
  • Culdocentesis is the extraction of fluid from the retrouterine pouch by trans-vaginal needle aspiration.
• Laparoscopy

Ectopic Pregnancy: Treatment

• When bHCG is < 1000 ng / ml, the location of the pregnancy is unclear so proper treatment includes expectant management.
• When bHCG is persistently falling, the pregnancy is unlikely to complete so proper treatment includes expectant management.

• Methotrexate:
  • A folic acid antagonist
  • Interferes with DNA synthesis

**Effective against thromboblastic tissue.

• • Check bHCG at day 4 and day 7; a 15% decline in bHCG by day 7 merits treatment with methotrexate.
  • Contraindications are many:
    • Breastfeeding
    • Immunodeficiency
    • Liver disease
    • Renal disease
    • Peptic ulcer disease
    • Gestation sac > 3.5 cm
    • Embryonic cardiac motion

***Hemoperitoneum or hemodynamic instability (unable to f/u)

• Surgery:
  • Diagnostic laparoscopy: salpingectomy versus salpinostomy
    • Salpinectomy is the removal of the fallopian tube.
    • Salpinostomy = salpingotomy is the creation of an opening in the fallopian tube.
  • Surgeries have a good prognosis:
    • 90% are successful
    • 84% result in tubal patency
    • 70% allow for an IUP
    • 12% result in ectopic pregnancies

Ectopic Pregnancy: Take Home Points

• Classic triad (missed period, abnormal bleeding, abdominal pain); not always present

**UPT in all women with abdominal pain or vaginal spotting

• Diagnosis of ectopic pregnancy relies on clinical presentation, bHCG levels, and TVUS
• Treatment of ectopic pregnancy is
  • surgery with laproscopic salpingectomy / salpingostomy
  • medicine with methotrexate
• Successful pregnancy is possible post ectopic pregnancy.
• Recurrence risk is 15-33%
• Don't forget to give Rhogam if Rh-!

Grief Following Miscarriage

• 80% with grief reactions
• 12% depressive symptoms
• Intensity significantly diminished by 6mo
• Subsequent pregnancy shortens duration

• Moderators of grief
  • Childlessness
  • Prior loss
  • Maternal age
  • Desired / Intendedness

Unique Aspects of Grief

• “Loss of possibility”
• Uncertainty
• Isolation / sequestration / silence
  • “Traditionally it’s an untalked about thing, isn’t it, miscarriage? You go back to work and tell them you've had the ‘flu’ or something”

Uncertainty and Ambiguity

• Making sense of the loss
• An incomplete or failed attempt to conceive
• A baby that was lost.
• "I don’t feel as though I’ve lost a few cells that might have become a child, I feel as though I’ve lost a baby."
• Part of their family was lost.
• The loss of possibilities.
  • “You can say: ‘well there was never anything to actually lose’, but there was 12 weeks of expectations to lose”

Implications for Clinical Care

• Women’s experience of three early miscarriage management options:
• Intervention
• Finality
• Pain and bleeding
• Experience of caring
• The “baby”

• Selecting a method of management:
  • No one best treatment
  • Avoid medicalizing or minimizing loss
  • In addition to technique and cost considerations, discuss setting, privacy, pain and bleeding, finality.

Grief Counseling

• Grief likely to improve by 6 months
• Articulate meaning of the loss
• Concretize / Memorialize
• Reassure patients that this is a significant event
• Establish formal follow-up