This document discusses recurrent pregnancy loss (RPL), defined as 3 or more losses prior to 20 weeks. It provides background on incidence and risk factors for RPL. Etiologies of RPL include genetic, anatomic, immunologic, endocrine, inherited thrombophilias, infectious, and unexplained factors. Investigations of couples with RPL may include screening for antiphospholipid antibodies, cytogenetic analysis, karyotyping, pelvic ultrasound, and screening for inherited thrombophilias. Treatment options depend on etiology and may include aspirin and heparin for antiphospholipid syndrome, referral for genetic factors, surgery for anatomical factors, progesterone supplementation, and supportive care for unexplained RPL.

1. RECURRENT PREGNANCY LOSS
Osama M Warda MD
Professor of Obstetrics & Gynecology
Mansoura University- EGYPT

2. BACKGROUND
! Pregnancy loss is a common phenomenon
! About 12-15 % of clinically recognized
pregnancies result in miscarriage:
- Clinically recognized + unrecognized are 2-4
times higher.
- True loss rate is 30-60%
! The risk of PL increases with the number of
previous losses, but very gradually ( ≤ 30%)
! PL increases with maternal age:
Age < 30 (7-15%) Age 35-39 (17-28%)
Age 30-34 (8-21%) Age > (34-52%)
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3. INCIDENCE
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4. RECURRENT PREGNANCY LOSS
! Defined as ≥ 3 losses prior to 20 weeks
! Ectopic, molar, and biochemical pregnancies are not
included.
! RPL affects about 2% of women in reproductive age.
! Very heterogeneous disorder (no fixed pattern).
! The etiology can be reached in about ⅔ of couples
after thorough investigations.
! RPL causes fear and anxiety in couples seeking
parenthood
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5. RECURRENCE RISK
! Risk of recurrence of PL depends on:
1. Maternal age
2. Cause of pregnancy loss
3. Number of previous miscarriages
4. Number of previous term deliveries
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6. RECURRENCE RISK
Number of
prior
miscarriage
% of risk of
miscarriage in
next pregnancy
Women with ≥ 1 live
born infant
0 12%
1 24%
2 26%
3 32%
6 53%
Women with no live
born infants
≥2 40-45%
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Risk of recurrent early pregnancy loss in young women

7. ROLE OF TVS IN PREDICTING
MISCARRIAGE
! Appearance of fetal heart tone (FHT) on
TVS decreases global miscarriage risk
from 12-15% to 3-5%.
! However, in patients with past history of
RPL, the miscarriage rate after embryonic
heart activity is still 3-5 times higher
(15-25%) than those with no such history .
! The prognostic value of FHT declines with
increasing maternal age.
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8. ETIOLOGY OF RPL
1-Genetic :
- chromosomal abnormalities in embryo
(structural or numerical)
- parental chromosomal abnormalities
2- Anatomic:
- congenital uterine malformation
- leiomyoma : submucous
- intrauterine adhesions
3- Immunologic:
- Autoimmune : SLE, APLA
- Alloimmune: abnormal maternal response to
fetal or placental antigens.
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9. ETIOLOGY OF RPL (CONT.,)
4- Endocrine:
- Thyroid disease - Diabetes mellitus
- PCOS - LPD
5-Inherited thrombophilias:
Type II: over-activity of coagulation factors (most common):
- Factor V leiden mutation
- Prothrombin G20210A mutation
Type I: deficiency of natural anticoagulants:
- anti-thrombin III deficiency - Protein C deficiency
- Protein S deficiency - Factor XIII mutation
- Familial dysfibrinogenemia
6- Infectious
7- Environmental: Smoking, alcohol, heavy coffee consumption
8- Unexplained 9
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10. INVESTIGATIONS OF COUPLES WITH RPL:
(RCOG GUIDELINES)
1. Women with RPL should be looked after by a
health professional with the necessary skills &
expertise. Where available, this might be within
a RPL center. (✓)
2. All women with recurrent first-trimester and
one or more second trimester miscarriage
should be screened before pregnancy for
antiphospholipid antibodies. (D)
3. Cytogenetic analysis should be performed on
products of conception of the 3rd and subsequent
consecutive miscarriages. (D)
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11. INVESTIGATIONS OF COUPLES WITH RPL:
(RCOG GUIDELINES)
4. Parental peripheral blood karyotyping of both
partners should be performed in couples with
RPL where testing of POC reports an unbalanced
structural chromosomal abnormality. (D)
5. All women with recurrent first-trimester
miscarriage and all women with one or more
second- trimester miscarriage should have a
pelvic ultrasound to assess uterine anatomy. (✔)
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12. INVESTIGATIONS OF COUPLES WITH
RPL: (RCOG GUIDELINES)
6. Suspected uterine anomalies may require further
investigations to confirm the diagnosis, using
hysteroscopy, laparoscopy, or 3-D pelvic
ultrasound. (✔)
7. Women with second- trimester miscarriage should
be screened for inherited thrombophilias including
factor V Leiden, factor II (prothrombin) gene
mutation and protein S. (D)
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13. TREATMENT OPTIONS FOR RECURRENT
MISCARRIAGE: (RCOG GUIDELINES)
1. Women with recurrent miscarriage should be offered
referral to a specialist clinic. (✔)
Antiphospholipid syndrome:
2. Pregnant women with antiphospholipid syndrome
should be considered for treatment with low-dose aspirin
plus heparin to prevent further miscarriage. (B)
3. Neither corticosteroid nor intravenous immunoglobulin
therapy improve the live birth rate of women with
recurrent miscarriage associated with antiphospholipid
antibodies compared with other treatment modalities;
their use may provoke significant maternal and fetal
morbidity. (A)
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14. TREATMENT OPTIONS FOR RECURRENT
MISCARRIAGE: (RCOG GUIDELINES)
Genetic factors:
4. The finding of an abnormal parental karyotype
should prompt referral to a clinical geneticist. (D)
5. Pre-implantation genetic screening with IVF
treatment in women with unexplained recurrent
miscarriage does not improve live birth rates. (C)
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15. TREATMENT OPTIONS FOR RECURRENT
MISCARRIAGE: (RCOG GUIDELINES)
Anatomical factors:
6. There is insufficient evidence to assess the effect
uterine septum resection in women with recurrent
miscarriage and uterine septum to prevent further
miscarriage. (C)
7. Cervical cerclage is associated with potential
hazards related to the surgery and the risk of
simulating uterine contractions and hence should
be considered only in women who are likely to
benefit. (A)
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16. TREATMENT OPTIONS FOR RECURRENT
MISCARRIAGE: (RCOG GUIDELINES)
Anatomical factors:
8. Women with a history of 2nd trimester
miscarriage and suspected cervical weakness
who have not undergone a history-indicated
cerclage may be offered serial cervical
sonographic surveillance. (B)
9. In women with a singleton pregnancy and a
history of one 2nd trimester miscarriage
attributable to cervical factors, an ultrasound-
indicated cerclage should be offered if a cervical
length ≤ 25mm is detected by TVS before 24
weeks gestation. (B) 16
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17. TREATMENT OPTIONS FOR RECURRENT
MISCARRIAGE: (RCOG GUIDELINES)
Endocrine factors;
10. There is insufficient evidence to evaluate the
effect of progesterone supplementation in
pregnancy to prevent a miscarriage in women
with recurrent miscarriage. (B)
11. There is insufficient evidence to evaluate the
effect of HCG supplementation in pregnancy to
prevent a miscarriage in women with recurrent
miscarriage. (B)
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18. TREATMENT OPTIONS FOR RECURRENT
MISCARRIAGE: (RCOG GUIDELINES)
Endocrine factors:
9. Suppression of high LH levels among ovulatory
women with recurrent miscarriage and PCO
does not improve the live birth rate. (A)
10. There is insufficient evidence to evaluate the
effect of metformin supplementation in
pregnancy to prevent a miscarriage in women
with recurrent miscarriage. (C)
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19. TREATMENT OPTIONS FOR RECURRENT
MISCARRIAGE: (RCOG GUIDELINES)
Immunotherapy:
11. Paternal cell immunization, third-
party donor leucocytes, trophoblast
membranes & intravenous
immunoglobulin in women with
previous unexplained recurrent
miscarriage does not improve the
live birth rate. (A)
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20. TREATMENT OPTIONS FOR RECURRENT
MISCARRIAGE: (RCOG GUIDELINES)
Inherited thrombophilia:
12. There is insufficient evidence to evaluate the
effect of heparin in pregnancy to prevent a
miscarriage in women with recurrent 1st
trimester miscarriage associated with inherited
thrombophilia. (C)
13. Heparin therapy during pregnancy may
improve the live birth rate of women with 2nd
trimester miscarriage associated with inherited
thrombophilia. (A)
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21. TREATMENT OPTIONS FOR RECURRENT
MISCARRIAGE: (RCOG GUIDELINES)
Unexplained RPL:
14. Women with unexplained RPL
have an excellent prognosis for
future pregnancy outcome without
pharmacological intervention if
offered supportive care alone in
setting of a dedicated early
pregnancy assessment unit. (B)
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APPENDIX

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24. MANAGEMENT OF RPL SUMMARY
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25. THANK YOU
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