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,
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
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
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.
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
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
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
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 ?
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