This document discusses recurrent pregnancy loss. It defines recurrent miscarriage as three or more consecutive spontaneous abortions before 20 weeks of gestation. Evaluation and treatment should focus on common and treatable causes like uterine anomalies, endocrine abnormalities, autoimmune disorders, thrombophilia, and genetic factors. Management may include surgical correction of septate uterus, treatment of thyroid disorders, anticoagulation for antiphospholipid syndrome, and assisted reproductive technology for translocations. Unexplained recurrent loss can be managed with lifestyle changes, progesterone, low-dose aspirin, and close monitoring during subsequent pregnancies.

1. Recurrent Pregnancy Loss
Dr. Rokeya Begum
Honarary Advisor and prof
USTC
and
Director
Surgiscope Fertility Centre
Chittagong, Bangladesh

2. The loss of pregnancy at any
stage - devastating experience,
both patient and physician.

3. Recurrent miscarriage is defined as the
occurrence of three or more consecutive
spontaneous abortion before 20wks of
gestation.
Ectopic, molar and biochemical
pregnancies not included.

4. Clinical entity requiring diagnostic
and therapeutic intervention rests
on knowledge and evaluation of
risk for subsequent fetal loss.
The probability of finding a
treatable etiology for the disorder.

5. 1. When fetal heart activity had been identified
prior to the pregnancy loss.
2. When the women is older than 35 years of age.
3. When the couple has had difficulty to
conceiving.
Early evaluation may be indicated-

6. MIND DOES NOT KNOW EYE
CAN NOT SEE

7. Primary : Never had previous viable infant.
Secondary : Woman with previous H/O delivery beyond
20wks and then suffered subsequent losses.
Tertiary : Refers to those who have multiple miscarriage
interspersed with normal pregnancies.
Types of Recurrent miscarriage-

8. - 50% of all conception fail (most unrecognized)
-The ESHRE guidelines emphasis the need to have at least a
positive  human chorionic gonadotropin(hCG) level to confirm
pregnancy.
- Lost before implantation.
-13-15% of recognized pregnanciesare lost
-90% of these before 12-14 weeks.
-10-20% of pregnant woman have sporadic spontaneous abortion.
-2% have two consecutive spontaneous abortion.
0.4-1% have 3 consecutive spontaneous abortion.
Incidence……..

9. 1. Only in 50% the cause can be determined.
2. Uterine / Anatomical cause 10-15%.
3. Genetic 2-5%
4. Autoimmune-20%
5. Infection/Endometritis-0.5-5%
6. Endocrine-17-20%
Etiology…..

11. Investigate commoner and
treatable cause first.
Do not order a blind screen.
How to investigate……

12. No cause is found but this
finding has a prognostic
value for future
pregnancy.

13. Reassurance eliminates not only the
stress in conceiving but allows to
enjoy those first days of fear about
pregnancy.

14. . Age of parents
. Maternal age
. Advanced age declines both the
number and quality of oocytes.

15. < 35 – 10-15%
35-39 – 25%
40-44 – 50%
> 45yrs – 90%
Age

16. Advanced paternal
age is also a risk.
Paternal age

17. Advanced parental age……
Maternal age –
increased risk of chromosomal
abnormality (Trisomy 13, 18, 21,
47 xxy, 47xxx).
Paternal age-
Increased risk of autosomal
dominate, x lined recessive
disorder.

18. 1. Recurrent spontaneous Ab.
2. Chemical pregnancy loss.
3. Early pregnancy loss
-before 8wks
-after 8wks
4. Second trimester abortions.
5. Still births
Reproductive history………

19. Gestational age at abortion guides
us the cause of abortion-
4-7 weeks – genetic cause 60-70%
8-10 weeks – APLA/TB
10 weeks or mid trimester –
Anatomical causes

20. RPL typically occurs at a similar
gestational age in consecutive
pregnancies.

21. Obesity
Over weight BMI > 22.5
Obese BMI > 27.5
Even obese BMI > 32.5
Morbid obese BMI > 37.5
Life style………..
Patients of BMI > 27.5 kg/m2
are likely to take longer to conceive.

22. So it is good to lose
weight by structured
weight loss program.

23. Environmental factor……..
1. Smoking
2.Alcohol
3.Caffeine
4.Use of NSAIDs

24. 1.Congenital malformation
- Septum
- Partial
- Complete
- Unicornuate
- Bicornuate
2. Intra uterine adhesion.
3. Intra uterine lesion
- fibriod
- polyp
4. Cervical weakness.
Uterine structural abnormality………..

25. Abnormal implantation
-  vascularity (septum)
-  inflammation (fibroid, polyp)
-  Sensitivity to steroid hormones.

26. There is also an
association between
mullerian anomaly with
second trimester loss.
Septet uterus-
higher rate of pregnancy
loss and correction can
lead to reduced rate of
miscarriage.

27. The correction of other
anomelies is not associated with
any improvement in miscarriage
rates.
ESHRE guidelines recognize
that the septate uterus is linked
to first trimester loss.

28. Evidence for treatment and
subsequent reduction in incidence
of miscarriage is weak.
Recommend
Surgical treatment of septa be a
attempted in the context of a
clinical trial.

29. 1. Subserosal
2. Intramural
3. Submucosal
Subserosal – No impact on pregnancy.
Submucosal – Any size removed.
Increase pregnancy outcome.
Leiomyoma……

30. - evidence for removal is uncertain.
- >5cm remove.
Intramural fibroid………….

31. ESHRE guidelines-
role of fibroid is controversial but
surgical management can be
considered on case by case.

32. Uterine
adhesion/Synechiae/Tuberculosis

33. ESHRE guideline point out that there is
weak evidence for resection of uterine
synechiae in reducing miscarriage rate.
Surgery itself can promote more
adhesions formation so precautions must
be taken in the preoperative setting to
minimize their formation.

34. Endometrial polyp –
more common.

35. Cervical incompetence mid trimester
miscarriage.
Preceded by SROM or painless cervical.

36. 1. USG – two dimensional/three dimensional
- myoma, polyp
2. Sonohysterography (SIS)
* More accurate than HSG
* Differentiate septate and biaornuate uterus.
Uterine factor assessment-

37. 3. MRI – Differentiate septate from
bicornuate uterus.
4. Hysteroscopy – Gold standard for diagnosis
and treatment of intrauterine lesion.
Reserved for when no diagnosis is made.

39. Treatment
Yes May be No
Submucosal
fibroid
Hysteroscopic
removal
Septum
Polyps
synechiae
Other
mullerian
anomality
Intramural-
Laporoscopy/
Laparotomy
- - - -

40. 1. H/O second trimester miscarriage and
suspected cervical weakness who have not
undergone history-indicated cerclage.
Cervical incompetence-
May offer serial cervical
sonographic survillance.

41. 2. In women with a singleton pregnancy
and a history of one second trimester
miscarriage attributable to cervical factors,
an ultrasound indicated cerclage should be
offered.

42. Cerclage is associated with potential
hazards related to-
- surgery
- stimulate uterine contraction.

43. Only be considered in
women who are likely to
benefit.

44. Route
Trans vaginal
Trans Abdominal
failed transvaginal cerclage
very short and scarred cervix

45. Immunologic factors
Foetus is not genetically identical to its
mother.
Autoimmune directed
to self tissues/cells
1. SLE
2.Antiphospholipid antibody

46. SLE
Risk loss is 20% mostly second
and third trimester of
pregnancy associated with
antiphospholipid antibodies.

47. Antiphospholipid antibody-
5-15% of women with RPL may have APA
this induce microthrombi at placental site
altered vascularty affects developing embyo
induces abortion.

48. Antiphopholipid syndrome-
Diagnosis requires at least one of each either
clinical or lab criteria.
Clinical-
1. Thrombolic events- arterial, venous smell
vessels.
2. Pregnancy loss
• ≥ 3 losses at < 10weeks gestation
• Fetal death after 10weeks
• Premature birth at <34 weeks associated with
severe PET or placental insufficiency

49. Lab
1. LAC
2. ACA
3. 2 glycoprotein antibodies
Lab test must be observed on at
least two separate occasions
6 weeks apart

50. Treatment…..
* LDA – commencing prior to pregnancy until 34 weeks
of gestation.
* LMWH once daily
[less chance of oesterpenia and thrombo cytopenia]
This treatment combination significantly reduces the
miscarriage by > 50%

51. Normally pregnancy is tolerated by the maternal immune
system through formation of blocking antibodies.
Couple that share similar type of HLA-there is
inadequate formation of blocking antibodies in maternal
environment.
Alloimmune mechanism…..
Diagnosis
HLA crossmataling between
husband’s lymphocytes and
wife’s serum.
- Not recommended routine
-costly.

52. Treatment--
1. Paternal leukocyte immunisation
2. IVIg (IV immunoglobin)
3. Intralipid
- NK all 
- TH 1 cytokine activity 

53. Endocrine causes……
- Thyroid diseases
- Poor controlled hypo and hyper thyroid.
- Subclinical hypothyroidism TSH > 4mIU/L
- Thyroid autoimmunity Co-exists with SCH

54. Thyroid screening by
* TSH
* Anti TPO antibody
* Anti TG antibody

55. Thyroid hormone replacement therapy
along with careful monitor prior to
pregnancy and early pregnancy periods is
associated with improved outcome.

56. • Diabetes poorly controlled
- Blood glucose
- HbAIC-
• High risk for pregnancy loss
- Diabetes screening
- Glucose tolerance test
- HbAIC

57. Well controlled – Not increases risk.
Diabetic patients should be euglycaemic
before attempting a pregnancy.

58. • Polycystic ovarian syndrome.
PCOS – the risk of recurrent
miscarriage is attributed to-
Insulin resistance Hyper insulinaemia
Hyper androgenism.

59. Diagnosis
1. USG picture
2. Reverse FSH/LH ratio
3. Free testosterone

60. There is insufficient evidence
to advocate the use of
progesterone or metformin
in women with recurrent
miscarriage.

61. Hyper prolactinaemia-
There is some evidence to suggest that
normalising hyper protectinaemia with a
dopamine agonist can improve live births in
RPL.
The agent with most evidence is bromocriptine.

62. Luteal phase defect-
Progesterone is essential for implantation
and maintenance of pregnancy.
Luteal phase support with progesterone.
All guidelines recommend against using
progesterone in RPL but it is noted that
progesterone supplementation causes no
harm.

63. Thrombophilia
It has hypothesised that thrombophilic disorders
causes thrombosis of uteroplacental vasculature
due to an increased haemostatic response-causes
miscarriage , IUGR, PET.

64. Inharited thrombophilia is a genetic condition in
which there is an increased risk of venous thrombosis.
1. Factor V leiden mutation.
2. Prothrombin gene mutation.
3. Protein S deficiency.
4. Protein C deficiency.
5.Anti thrombin III deficiency
Among them 50-60% are due to FVL
mutation and PGM.

65. Evaluation
When pregnancy loss more than 9 weeks
and evidence of placental infraction or
maternal thrombosis.
Anti thrombotic therapy aspirin with or
without LMWH.

66. 1. Repetitive first trimester losses.
2. An embryonic pregnancies.
3. History of malformation or
mental retardation.
4. Advanced maternal age.
Genetic factors-

67. Chromosomal rearrangements
3-5% of couple with recurrent miscarriage
one of the partners carries a balanced
structural chromosomal.
only 5-10% chance of a pregnancy with an
unbalanced translocation.
Even it present may not be the cause.

68. Karyotype( Parental)
• 1. Low yield and limited prognostic value- only if
other work up negative.
• 2 Karyotype of blood cells misses abnormalities of
meiosis which can be found in sperm cells.

69. Karyotype of POC is recommended for couples
with two or more miscarriages.
Disadvantage of fetal Karyotype
1. Difficulty of obtaining of tissue
2.Incorrect preparation
3.Maternal contamination
4.Failed test
Karyotyping of parents

70. • Karyotype abnormality( Parent)
1. PGD-ART
2.Spontaneous conception
ANC screening-
NIPT.CVS,Aminiocentasis
3.Gamate donation

71. • A recent study comparing –natural conception and
PGD-ART in patient with a balanced
translocation failed to demonstrated improved live
birth rates.
• In presence of a balanced translocation couples
still have a 70% live birth rate in a subsequent
pregnancy.
• Only 1% of offspring from couples with balanced
translocations have unbalanced translocation.

73. •Infection
No infections agent has been
proven to cause RPL
Syphilis- Untreated in subsequent
pregnancy cause RPL
TB-implantation failure
Early embryonic rejection

74. 1. Life style
- Smoking
- Alcohol
- Exercise
- BMI
2. Sperm DNA fragmentation index
Male factor

75. • Treatment of high sperm DNA fragmentation
1. Anti oxidants
2. Annexin-V
3. Intracytoplasmic morphologically
selected sperm( IMSI)
4. Surgically retrieval of sperm-
Seminiferous tubules than epididymis.

76. Recurrent miscarriage
1.Psychological effects .
2.Association with later disease

77. Association with later disease
1. Coronary artery disease
2. Increase risk of ovarian cancer
3. Pre eclampsia in later pregnancy.
4. Increase morbidity and mortality

78. Management should be
guided to
underlying cause

79. Treated by
Sensitive
Sympathetic
Appropriate emotional support

80. Recurrent pregnancy loss managed
Dedicated clinic
Focus to find out cause

82. Management of unexplained
Preconception
1.Folic acid
2.Correct nutritional deficiencies
3. Prophylactic Doxycycline
4. Luteal support

83. Postconception
1. Prophylactic aspirin
2.Prophylactic cervical cerclage
3.Test for APLA
4.Steriod for pulmonary maturity
5.Monitor closely near term

84. • Supportive treatment
Tender love and care
1. Psychological support
2. Weekly follow up
3. Rest as much as possible
4. Avoid heavy work
5.Coitus prohibited

85. •Fate
1. A woman who has an suffered a single sporadic
miscarriage has an 80% chance .
2. A woman with three consecutive miscarriage a 40-
60% chance of her next pregnancy being
successful.