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RECURRENT
PREGNANCY LOSS
HICHAM BABA, MED III, OBGYN

Recurrent spontaneous abortion, recurrent pregnancy loss, habitual abortion

 OUTLINE

•Definition
•Incidence
•Etiologies
•Workup
•Treatment
 THOUGHT #1

HOW MANY
FERTILIZATIONS
RESULT IN LIVE BIRTHS?
 25%

**

*Underestimated
**Between 4-20 weeks
 DEFINITION?

• Two or more failed clinical pregnancies

before 20 weeks from last LMP, documented
by ultrasonography or histopathologic
examination

OR

• Three consecutive pregnancy losses, which

are not required to be intrauterine
WHICH ONE IS IT
 INCIDENCE

• 2% of pregnant women
experience 2 consecutive
pregnancy losses

• 1% have 3 consecutive pregnancy

losses
 THOUGHT #2

TRUE OR FALSE

Women with more than 5

miscarriages have a highly
reduced chance for a
successful pregnancy
FALSE: >50%
ETIOLOGIES
 GENETICS

• 2-5% of RPL
• Spontaneous abortions are generally due to
• Aneuploidy (XO)
• Polyploidy (16>13,21)
• Reciprocal and Robertsonian translocations (50%)
 GENETICS

• Karyotyping is indicated when:

• Young maternal age at second miscarriage
• History of three or more miscarriages
• History of two or more miscarriages
in a sibling or the parents of either partner
• Family history of stillbirth
• Family history of abnormal live born
 THOUGHT #3

Most common
anatomical
cause of RPL?
SEPTATE UTERUS
 ANATOMICAL FACTORS
• Interrupt the endometrial vasculature, prompting inadequate placentation
• Impaired uterine distention and increased inflammation

• Congenital malformations

• Septate Uterus (76%)

• Mullerian anomalies
(unicornuate, didelphic, bicornuate)

• Leiomyomas
• Intramural >5cm

• any submucosal)
 ANATOMICAL FACTORS

• Intrauterine adhesions (Asherman’s)

• Incompetent Cervix (2nd)

• DES exposure

• Defective endometrial
receptivity
CONGENITAL ANOMALIES
 ENDOCRINE FACTORS

• PCOS (>20-40%)
• Premature or delayed ovulation, poor endometrial receptivity, and
disturbances in synthesis/secretion/action of prostaglandins and ovarian
growth factors/cytokines
• Insulin resistance, metformin vs clomiphene

• Diabetes mellitus (HbA1C>8%)

• Thyroid disease
• Associated with antibodies thyroid peroxidase or thyroglobulin, even in
euthyroidism; 2-3x risk of abortion
• Both hypothyroidism and hyperthyroidism

• Hyperprolactinemia
• Normal levels maintain early pregnancy
• High levels prevent ovulation and might affect implantation.

• Luteal phase defect

 LUTEAL PHASE DEFECT (LPD)

• American Society for Reproductive Medicine :

• “there is no reproducible, pathophysiologically relevant, and
clinically practical standard to diagnose luteal phase
deficiency and distinguish fertile from infertile women”-2015

• Basis: decreased progesterone production

• Luteal phase defect diagnosed by endometrial biopsy is

not predictive of infertility (25% of fertile women have
LPD)

• There is no high-quality evidence to support the use of

exogenous progesterone supplementation to prevent
early miscarriage?
 THOUGHT #4

TRUE OR FALSE?

Infections are responsible

for more than a third of RPL
 INFECTIONS

• Incidence ~2% (0.5-5%)

• Listeria, Toxoplasma, Rubella, Measles
• HSV, CMV, and Coxsackie
• Mechanisms:
• (1) direct infection of the uterus, fetus, or placenta,
(2) placental insufficiency
(3) chronic endometritis, endocervicitis,
(4) amnionitis
(5) infected intrauterine device

The most pertinent risk for RPL secondary to infection is

chronic infection in an immunocompromised patient.
 THOUGHT #5
CAUSE OF THE MISCARRIAGE?
• A 35-year-old woman, gravida 4 para 1 aborta 2, comes to the office for her first
prenatal visit. Her last menstrual period was 7 weeks ago, and she is concerned
about a recent episode of vaginal bleeding and cramping
• A home pregnancy test was positive just after the patient's missed period;
around that time, she experienced nausea that has since subsided. She has
had 1 term delivery and 2 early first-trimester losses.
• Six months ago, she had an episode of sudden right arm weakness and slurred
speech, which resolved spontaneously in approximately 2 hours.
• The patient takes prenatal vitamins and no other medications. BMI is 30. Blood
pressure is 140/80 mm Hg
• Pelvic examination shows a closed cervix; no vaginal bleeding; and a slightly
enlarged, irregularly shaped uterus.
• Ultrasound shows an empty uterus with one subserosal fibroid about 2 cm in
diameter. BhCG is 23 IU/L.

A. Balanced maternal C. Fibroid uterus F. Subclinical uterine

translocation D. Hypercoagulability infection
B. Demyelination E. Insulin resistance G. Thyroid disease
lesions
 ANTIPHOSPHOLIPID SYNDROME

• 5-15% of women with RPL

• Immunologic and thrombophilias

repeated twice at
12 weeks interval
 IMMUNOLOGICAL

• Autoimmune (APS / SLE)

• Alloimmunity
• Abnormal maternal immune response to antigens on
placental or fetal tissues.
• Normally, maintenance of pregnancy requires maternal
immunologic recognition, with formation of blocking factors
that prevent maternal rejection of fetal antigens.

• Suggested mechanisms:
• Similar to that of GVH rejection in transplant recipients
• Maternal failure to produce blocking antibodies to prevent
a cell-mediated immune attack
INHERITED THROMBOPHILIA

Hypercoagulability

-Placental thrombosis,
-Reduced uteroplacental flow
-Pregnancy loss
 OTHER CAUSES

• Environmental:

Smoking
Alcohol >2 drinks /day
Caffeine >300 mg /day

Other triggers: anesthetic gases

(NO), arsenic, aniline dyes,
benzene, ethylene oxide,
formaldehyde, pesticides, lead,
mercury, and cadmium
 OTHER CAUSES - AGE

SAB risk %

52% 52%

28%
21%
15%

before 30 age 30-34 age 35-39 age 40 age 40 +

yoa and above SAB
DIAGNOSTICS
 HISTORY

• Gestational age and characteristics of all previous

pregnancies
• Uterine instrumentation?
• Menstrual cycle description
• Congenital and karyotype abnormalities
• Family History
• History of venous and arterial thrombosis
• Previous labs, pathologies and images?
• Physical exam should look for endocrinopathies
(hirsutism, galactorrhea) and pelvic abnormalities
(malformations, lacerations)
 Etiologies Evaluation Treatment
Uterine factors: Hysteroscopy Septum removal
• Septum HSG/SHG Myomectomy
• Leiomyoma TVUS Polypectomy
• Asherman’s MRI (septate and bicornuate) Adhesiolysis
• Cx incompetence Cervical cerclage
Immunological: Lupus anticoagulant
• APS Anticardiolipin AB Aspirin (81mg)
• SLE Anti-B2 glycoprotein antibody Heparin (UFH or LMWH)

Endocrine Mid-luteal Progterone Progesterone

• PCOS TSH, LH Levothyroxine
• DM Glusose, insulin levels, Metformin
• Thyroid Prolactin, Bromocriptine
• Hyperprolactinemia
Endometrial biopsy

Genetic Karyotyping (&male) Genetic counseling

Thrombophilia Factor V Leiden Aspirin, heparin
Protein C/S resistance
Prothrombin gene mutation
MTHFR gene mutation
Homocysteine level
Others Toxins, cultures Avoidance, Antibiotics.
 PROGNOSIS

• The most effective therapy for patients with

unexplained RPL is often the most simple: antenatal
counseling and psychological support.
• Success rates of 86% when compared with success
rates of 33% in women provided with no additional
antenatal care
• Remember! Even with more than 5 consecutive
losses, there is 50% chance of a healthy live
conception happening.

• Never give up
THANK YOU – QUESTIONS?
 REFERENCES

• William’s Obstetrics
• Uptodate
• ACOG
• Recurrent Pregnancy Loss: Etiology, Diagnosis, and
Therapy
(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC27
09325/)