Recurrent miscarriage syndrome, also known as recurrent pregnancy loss, is defined as three or more consecutive losses of clinically recognized pregnancies under 20 weeks gestation. Only about 50% of causes can be determined, which may include uterine, immunologic, endocrine, genetic, thrombophilic, or environmental factors. Evaluation involves a medical and family history, physical exam, laboratory tests, and imaging of the uterus to diagnose potential causes like uterine anomalies, immunologic issues like antiphospholipid syndrome, endocrine disorders, genetic abnormalities, or thrombophilia. Management depends on the underlying cause, with treating identified issues like uterine abnormalities, controlled diabetes or thyroid conditions, anticoagulation for antiphospholipid syndrome,

1. RECURRENT
MISCARRIAGE
SYNDROME
Fahad zakwan

2. Other names
1.Recurrent fetal loss
2.Recurrent miscarriage
3.Recurrent abortions
4.Recurrent pregnancy loss
5.Habitual abortion

3. INTRODUCTION
•Emotionally traumatic, similar to stillbirth or
neonatal death
•Etiology is often unknown (in 40-50% of cases)
•Primary or secondary
•Live birth occurred at some time in secondary
•Better prognosis with secondary

4. DEFINITION
≥ 3 consecutive losses of clinically recognized
pregnancies < 20 week gestation or fetal weight
less than 500g.
Ectopic, molar, and biochemical pregnancies
not included
1-2 % of couples experience this

5. RISK FACTORS AND ETIOLOGY
• Only in 50 %, the cause can be determined
• Etiological categories:
1. Uterine
2. Immunologic
3. Endocrine
4. Genetic
5. Thrombophilic
6. Environmental

6. UTERINE FACTORS(10-15%)
CONGENITAL ANOMALIES
1. Septate uterus
2. Bicornuate uterus
3. Unicornuate
4. Didelphytic uterus
5. Cervical incompetency
ACQUIRED
1. Myoma
2. Intrauterine
adhesions
3. Cervical
incompetence

7. SEPTATE UTERUS
•Most common
•Poorest outcome
•Miscarriage > 60 %
•The longer the septum, the worse

8. LEIOMYOMA
•Submucous
•The mechanism
•Their position
•Poor endometrial receptivity
•Degeneration with increasing cytokine
production

9. •Endometrial polyps
•Intrauterine adhesions
•Curettage for pregnancy complications or
infection
•Traumatize basalis layer :Insufficient
endometrium to support fetoplacental growth

10. •Cervical insufficiency/incompetence
•Recurrent mid-trimester loss
“Generally all uterine causes of RPL
of RPL cause second trimester loss.”
trimester loss.”

11. IMMUNOLOGIC FACTORS
•Antiphospholipid syndrome (APAS)
•5 - 15 % of ♀ with RPL may have APAS
•Other immunological factors
•Not well defined

12. ENDOCRINE FACTORS
•Luteal phase defect
•Progesterone is essential for
implantation and maintenance of
pregnancy
•A defect in corpus luteum (C.L). 
impaired progesterone production

13. •Diabetes mellitus
•Poorly controlled  early (and late) loss
•No ↑ risk with well-controlled
•Mechanism
•Hyperglycemia
•Maternal vascular disease

14. •Insulin resistance
•PCOS
•Miscarriage 20 - 40% vs. baseline rate 10 -
20%
•Mechanism is unknown
•↑ LH, Testosterone, and rostenedione 
adversely affect the endometrium

15. •Thyroid disease and antibodies
•Poorly controlled hypo- or hyper - thyroidism
• Infertility & pregnancy loss
•↑ thyroid antibody, even if euthyroid.
• No strong evidence
•Hyperprolactinemia
•Rx  ↑ successful pregnancy (86 vs. 52%)
•BUT, need correct diagnosis

16. GENETIC FACTORS
•Paternal chromosomal rearrangements
•Maternal
•5 % of couples with RPL have major
chromosomal defects (vs. 0.7 %)
• Balanced translocation or an inversion
•Usually causes first trimester miscarriages.

17. THROMBOPHILIA
•Thrombosis on maternal side of
the placenta  impair placental
perfusion
•Late fetal loss, IUGR, abruption, or
PIH

18. MISCELLANEOUS
• Environmental chemicals & stress
• Anesthetic gases (nitrous oxide), formaldehyde,
pesticides, lead, mercury
• Sporadic spontaneous loss
• No evidence of associations with RPL
• Personal habits
• Obesity, smoking, alcohol, and caffeine
• Association with RPL is unclear
• May act in a dose-dependent fashion or synergistically to
↑ sporadic pregnancy loss

19. •Male factor
•Trend toward repeated miscarriages with abnormal
sperm (< 4% normal forms, sperm chromosome
aneuploidy)
• ICSI
•Paternal HLA sharing not risk factor for RPL
•Advanced paternal age may be a risk factor for
miscarriage (at more advanced age than females)
•Infection
•Listeria, Toxoplasma, CMV, and primary genital
herpes
•Cause sporadic loss, but not RPL

20. CANDIDATES FOR EVALUATION
• Evaluate and Rx ≥ 2 or 3 consecutive losses
• Most have good prognosis for a successful
pregnancy, even when no Dx or Rx
• The minimum workup:
• Complete medical, surgical, genetic, and family history
• Physical examination

21. HISTORY
GA & characteristics (anembryonic pregnancy, live
embryo) of all previous pregnancies
 RPL typically occurs at a similar GA
 Most common causes of RPL vary by trimester
○ Chromosomal & endocrine earlier than anatomic or immunological causes
Uterine instrumentation  intrauterine adhesions
Menstrual cycles regularity  endocrine dysfunction
Galactorrhea, Headache, Visual disturbances 
hyperprolactinemia

22. HISTORY
Thyroid related symptoms
Hx of congenital or karyotypic abnormalities  heritable
Was cardiac activity detected? If not  suggests
chromosomal abnormality
Does F.Hx display patterns of disease consistent with strong
genetic influence? consanguinity
Exposure to environmental toxins
Hx venous thrombosis  thrombophilia or APAS
Information from previous laboratory, pathology, and
imaging studies

23. PHYSICAL EXAMINATION
•General physical
•Signs of endocrinopathy (hirsutism,
galactorrhea, thyroid)
•Pelvic organ abnormalities (uterine
malformation, cervical laceration)

24. LABORATORY EVALUATION
•Karyotype (Parental)
•Low yield & limited prognostic value  only if the
other work-up was negative
•Karyotype (Embryonic)
•May consider after 2nd loss
•If abnormal karyotype + normal parents  “bad
luck”

25. UTERINE ASSESSMENT
• Sonohysterography (SIS)
• More accurate than HSG
• Differentiate septate & bicornuate uterus
• Hysterosalpingogram (HSG)
• Does not evaluate outer contour
• Not ideal for the cavity
• Hysteroscopy
• Gold standard for Dx + Rx intrauterine lesions
• Cannot differentiate septate from bicornuate
• Reserved for when no Dx is made

26. • Ultrasound
• Presence and location of uterine myomas
• Associated renal abnormalities
• MRI
• Differentiate septate from bicornuate
• Hysteroscopy, laparoscopy, or MRI  second-line tests when additional
information is required

27. APAS
• Dx: one lab & one clinical criteria are met
• Clinical criteria:
• Venous or arterial thrombosis
• RPL
• Laboratory criteria
• Lupus anticoagulant
• Anticardiolipin antibody (IgG and IgM)
 Medium or high titers of both
 Low to mid positive can be due to viral illness
• Repeat twice, 6-8 weeks apart

28. THROMBOPHILIA
• Contradictory literature
• Evaluate if loss > nine weeks + evidence of placental infarction or
maternal thrombosis

29. THYROID
• TSH +/- FT4 & FT3
• More important in ♀ with clinical manifestations but even in
asymptomatic
• Thyroid peroxidase antibody

30. Other tests
•Routine cervical cultures for Chlamydia, Mycoplasma &
vaginal evaluation for BV & toxoplasmosis serology
•ANA
•Screening for DM
•Immune function (HLA typing, etc.)
•Progesterone level (Single or multiple)
•Endometrial biopsy

31. MANAGEMENT
•Prognosis for successful future pregnancy depends
on:
• Number of prior loss.
• The cause
• Maternal age
• Prior successful pregnancy
•Emotional support is important and enhance success

32. PARENTAL KARYOTYPE ABNORMALITY
• Refer for genetic counseling
• Information for probability of a chromosomally normal or abnormal
conception
• May undergo prenatal genetic studies
• Amniocentesis
• CVS
IVF may be used

33. UTERINE ABNORMALITIES
• Managed hysteroscopically
• Septum, adhesions, submucosal myoma
• Cervical cerclage
• Second trimester loses

34. MANAGEMENT
• Antiphospholipid syndrome
• Aspirin & Heparin
• Suspected immunologic dysfunction
• Several immunologic Rx advocated
• None effective
• Some are harmful
• DM
• Controlled at least 6/12 prior to conception
• Thyroid
• Hyper and Hypo thyroid should be controlled
• Euthyroid with ↑ peroxidase antibody may benefit from treatment

35. • Polycystic ovary syndrome
• No agreed upon protocol
• Metformin just as effective when stopped at diagnosis of pregnancy or
12/52 gestation
• Hyperprolactinemia
• Normal levels play important role in maintaining early pregnancy (in
RPL)
• Thrombophilia ?

36. UNEXPLAINED RPL
• 50% of RPL remain unexplained

37. UNEXPLAINED RPL
• Lifestyle modification
• Eliminating use of tobacco, alcohol, and caffeine & reduction in BMI (for
obese women).
• Progesterone
• Widely used but studies on its efficacy are lacking
• Vaginally or IM
• Human menopausal gonadotropin
• Correcting LPD or creating thicker endometrium
• Clinical experience supports the efficacy
• IVF +/- PGD
• Mixed results
• Promising

38. Thank you