2. RECURRENT PREGNANCY
LOSS
Loss in the embryonic period: < 10 weeks: cause:
chromosomal abnormality
Loss at 18 to 20 weeks: structural cervical or uterine
problems
3. -80% of clinical abortions
occur in the first trimester
decreasing as the pregnancy
progresses
9. GENETIC FACTORS
Balanced Translocations (7,8,9)
▪ The most common inborn parental
chromosomal abnormalities contributing to
recurrent abortion
X chromosome
▪ chromosomal monosomies that typically
permits viable offspring
10. GENETIC FACTORS
▪ Neither family history nor a history of prior term
births is sufficient to rule out a potential parental
chromosomal abnormality
▪ 60% of abortuses lost before 8 weeks of gestation
have been reported to be chromosomally abnormal
11. Most causes of recurrent abortion are NOT
chromosomal abnormalities
Abortion of chromosomally normal conceptuses tend to
occur later in gestation than abortion of chromosomally
abnormal embryos. (12-13th
wk AOG)
13. ▪90 % of women had one X chromosome inactivated.Theoretically, a
gene on the X chromosome
▪overly suppressed or overly activated, that affected chromosomal
replication higher incidence of trisomy
Increased incidence of histocompatibility locus antigen (HLA)
among couples with RPL due to absence of maternal blocking
antibody against paternal antigen
15. THROMBOPHILIAS
▪ Heterogeneous group of disorders results in
increased venous or arterial thrombosis
▪ Due to alterations in placental growth and
development, particularly placental vascular
development
Most Common associated with RPL
1.Factor V Leiden mutations
2.Mutations in the promoter region of the prothrombin
gene
3.Mutations in the gene encoding methylene
tetrahydrofolate reductase (MTHFR)
16. HERITABLE THROMBOPHILIAS
▪ Associated with adverse fetal outcome due to
impaired placental development and function
secondary to venous or arterial thrombosis at the
maternal fetal interface
17. HERITABLE THROMBOPHILIAS
Disorders Isolated and recurrent pregnancy loss
Early and late spontaneous pregnancy losses
Intrauterine growth restriction (IUGR)
Intrauterine fetal demise (IUFD)
Placental abruption
Pregnancy-induced hypertension
18. HERITABLE THROMBOPHILIAS LINKED TO
RLP
1. Hyperhomocysteinemia
2. Activated protein C resistance associated with
mutations in factor V
3. Deficiencies in proteins C and S
4. Mutations in the prothrombin gene promotor
5. Mutations in prothrombin
6. Mutations in antithrombin III.
19. DE NOVO FETAL ANEUPLOIDY
▪ Results from early clinical pregnancy losses
▪ True of anembryonic pregnacy
▪ The presence or absence must be documented in all
investigations of RPL
21. ▪ The procoagulant cascade is inhibited by several physiologic
mechanisms.
▪ The balance between pro- and antithrombotic pathways determines the
state of coagulability
25. CONGENITAL
▪ linked to both isolated
spontaneous pregnancy
loss and to RPL
▪ associated with (+)
intrauterine septum and
prenatal exposure to DES
26. Surgical correction of
bicornuate and
septate uterus
Transfundal metroplasty techniques:
a.Strassman
b.Jones
c.Tompkins
Transcervical Hysteroscopic resection of
uterine septum
27. Hysteroscopic incision
▪Treatment of choice for woman with septate
uterus and had history of pregnancy loss
One study reported of successful pregnancy
outcome after cervical cerclage following
hysteroscopy
28. CONGENITAL
In Utero DES Exposure Hypoplasia
• spontaneous abortion
• incompetent cervix
• premature labor
30. ACQUIRED UTERINE DEFECT
LEIOMYOMAS
Especially if they are submucosal, maybe
associated with repetitive abortion
INTRAUTERINE ADHESIONS
Causing insufficient endometrium to support
adequate fetal growth
Major cause: CURETTAGE pregnancy related or in
early puerperium
32. ENDOCRINE ABNORMALITIES
▪ Dependent on timed endocrinologic changes of the
menstrual cycle
▪ Begin with ovulation and lasting until 7 to 9 weeks
AOG
▪ Pregnancy losses <10 weeks AOG is due to
alterations in normal progesterone production or
utilization
34. PROGESTERONE DEFICIENCY Maintained by corpus luteum
Trophoblast
Inadequate to support the implanted
blastocyst: lead to spontaneous abortion
Thyroid Disease Abnormal thyroid function
Presence of antithyroid antibodies
DM, insulin resistance and
PCOS
Diabetes without good metabolic control is
associated with an increase risk of early
pregnancy loss with a direct correlation
between the kevel of haemoglobin A
CELIAC DISEASE (SPRUE) Systemic autoimmune disease caused by an
allergy to gluten
35. MATERNAL INFECTION
▪ Infection of the reproductive tract
▪ Pathogens are mycoplasma,
ureaplasma, Chlamydia
trachomatis, and β-streptococcus
▪ Herpes simplex virus (HSV) and
Human cytomegalovirus (CMV)
can directly infect the placenta
and fetus
36. IMMUNOLOGIC PHENOMENA
CLASSIFICATION
Innate Response Body’s first line of defense against
pathogenic invasion
Rapid and are not antigen specific
Include complement activation,
phagocytosis by macrophage and lysis by
natural killer and natural killer T cells
38. CELLULAR IMMUNE
MECHANISM
▪Resident Cells
▪Immune cells populating the reproductive tract
▪ T cells, macrophage, and NK-like cells, but very few B cell
▪ Implanting fetus represents the most common model of allograft
acceptance.
▪ The ability of the maternal immune system to avoid rejection of
the implanting fetus in an uncomplicated pregnancy is a
manifestation of immune tolerance
39. AUTOIMMUNE FACTORS
• Responsible for 25 to 40% of recurrent pregnancy loss
• ANTIPHOSPHOLIPID ANTIBODY SYNDROME –(APAS)
• Increased SECOND-TRIMESTER pregnancy losses
40. ANTIPHOSPHOLIPID ANTIBODY SYNDROME
(APAS SYNDROME)
▪ 5-15 % of RPL, as well as late fetal death
▪ History of thromboembolism or pregnancy complication
with high titers of anti-cardiolipin antibody and/or lupus
anticoagulant
TREATMENT
1. Heparin (5,OOO-10,000 units BID)
2. Aspirin (81 mg)
41. Humoral immune responses and RPL focus on
organ-nonspecific autoantibodies associated with APAS.
IgG and IgM antibodies
• directed against negatively charged phospholipids,
Cardiolipin and phosphatidylserine.
Antiphospholipid antibodies cause
A. Prolongation of coagulation test
B. Thrombosis
43. ANTIPHOSPOLIPID ANTIBODY
SYNDROME
DIAGNOSIS
Clinical Pregnancy complications
• 3 or more consecutive spontaneous
pregnancy losses < 10 weeks
• one or more fetal deaths at > 10 weeks AOG
• 1 or more preterm births at < 34 weeks AOG
secondary to severe preeclampsia or
placental insufficiency
48. HISTORY
Pattern, trimester and prior pregnancy losses
History of subfertility and infertility
Menstrual history
Prior or current gynecologic or obstetric infections
Signs or symptoms of thyroid, prolactin, glucose tolerance and
hyperandrogenic disorders (including PCOS)
Personal or familial thrombotic history
Features associated with antiphospholipid syndrome (thrombosis,
false positive test for syphilis)
49. HISTORY
Other immune disorders
Medications
Environmental exposures, illicit and common drug use
Genetic relationship between reproductive partners
Family history of recurrent spontaneous abortion, obstetric
complications or any syndrome associated with embryonic or fetal
losses
Previous diagnostic test and treatments
50. PHYSICAL EXAMINATION
1. Obesity
2. Hirsutism/acanthosis
3. Thyroid examination
4. Breast examination/galactorrhea
5. Pelvic examination
a. Anatomy
b. Infection
c.Trauma
d. Estrogenization
e. Masculinization
51. LABORATORY
▪ Parental peripheral blood karyotype 2
▪ Hysterosalpingography or office hysteroscopy, followed by
hysteroscopy/laparoscopy, if indicated
▪ Thyroid-stimulating hormone level, serum prolactin level if indicated
▪ Anticardiolipin antibody level
▪ Lupus anticoagulant (activated partial thromboplastin time or Russell Viper
Venom)
▪ Complete blood count with platelets
▪ Factor V Leiden, G20210A prothrombin gene mutation, protein S activity,
homocysteine level, activated protein C resistance
▪ Protein C activity, antithrombin level if personal or family history of VTE PCOS,
polycystic ovarian syndrome; DES, diethylstilbestrol;VTE, venous
thromboembolism
53. PRECONCEPTION
EVALUATION
Closely monitored to provide psychological support and to
confirm intrauterine pregnancy and its viability
Determine serum levels of β-HCG
Serial ultrasound and a variety of hormonal and biochemical
measurements during early pregnancy
Karyotyping analysis
