we try to review cause specific treatment of RPL

1. Treatment of RPL
Myths of RPL
Ahmad Saber (MD)
Consultant of Female Reproductive medicine
Obstetrics and Gynecology Department
Benha University

2. (‫أ‬‫رب‬‫يت‬ ‫ن‬‫أ‬ ً‫ا‬‫ر‬‫عا‬ ‫ابجلهل‬ ‫وكفى‬ ،‫ههل‬‫أ‬ ‫من‬ ‫ليس‬ ‫من‬ ‫يدعيه‬ ‫ن‬‫أ‬ ً‫ا‬‫ف‬‫رش‬ ‫ابلعمل‬ ‫كفى‬‫فيه‬ ‫هو‬ ‫من‬ ‫منه‬)
‫طالب‬ ‫ىب‬‫أ‬ ‫بن‬ ‫عىل‬ ‫الامام‬

4. Causes
Thrombophilia :
Acquired , inherited
Genetic factors
(Parental chromosomal rearrangements)
Anatomical factors
Congenital uterine malformations
Acquired lesions ( myoma –IU adhesions)
Cervical weakness
Endocrinal causes:
Anti-thyroid antibodies
Polycystic ovary syndrome (PCOS)
IR
Diabettes
Immune factors ( auto , allo )
Infective agents

5. Thrombophilia
• Inherited ( Genes mutations )
TTT :
 Heparin
• Acquired ( Antiphospholipid antibody Syndrome )
TTT:
 LDA
 Heparin
 Corticosteroids
 Cytotoxic drugs

6. Common pathologies associated
• Recurrent miscarriage !!!!!!!!
• Late pregnancy loss (IUFD)
• Fetal growth restriction (FGR)
• Placental abruption (PA)
• Pre-eclampsia (PE)

7. Pregnant women with antiphospholipid syndrome should be treated
with low-dose aspirin plus heparin to prevent further
miscarriage. B Green Top 2011

8. Early : LMWH may improve the implantation rate. Qublean et al;2008
Hazards: Ectopic ??!!
Start

9. Unfractionated
heparin
LMWH
antithrombin (AT) thrombin (Th, factor IIa
Target is to inactivate activated factor xa

10. • potentiates the action of AT III
• Heparin-AT III-complex neutralizes the
actions of: Factors II, IX, X, XI, XII and XIII
Binds to AT III

11. Heparin-induced thrombocytopenia :
Risk of developing a new thrombus (heparin-induced
thrombocytopenia and thrombosis)
Rebound hyperlipidemia on discontinuation
Heparin induced osteoprosis
Common S.E:

12. Enoxaparin
Deltaparin
Nadroparin
Reviparin
Tinzaparin
LMWH types ?

13. LMWH Vs Unfractionated Heparin
less heparin-induced thrombocytopenia
Once daily administration ↓↓↓↓heparin-induced osteoporosis.

14. LMWH dosage in case of thrombopilia
due to APS

15. The American College of Chest Physicians guidelines for the
management of obstetric APS merely early RPL [Bates et al; 2008]:
These guidelines are supported by 3 meta- analyses
• Empson et al; 2005Cochrane Database Syst Rev
• Mak et al; 2010
• Ziakas et al; 2010
without previous thrombosis:
LDA + UFH (5,000–7,000 IU sc every
12 h) or LMWH in usual prophylactic
doses (i.e., enoxaparin 40 mg sc every
24 h).
with previous thrombosis:
LDA + therapeutic UFH or LMWH in
usual therapeutic doses (i.e.,
enoxaparin 1 mg/kg sc every 12 h).

16. Heparin monitoring
activated Partial Thromboplastin Time (aPTT)
Lab. Tip in monitoring:
prolonged aPTT should be investigated prior to initiating therapy.
For example, if the reason is a lupus anticoagulant
Routine monitoring of LMW heparin is not generally required.

17. Remember

18. Thrombo-(prophylaxis not therapy)
i.e : low-dose heparin
Route: subcutaneous tissue only (not muscle tissue).
Dosage: 5000 units every 8-12 hours.
Dose adjustment: aPTT or anti-Xa activity.
Injection sites should be rotated (usually left and right portions of the
abdomen, above iliac crest).

19. COMPARISON OF TINZAPARIN WITH ENOXAPARIN IN
UNEXPLAINED RECURRENT MISCARRIAGE
Tinzaparin is efficacious as enoxaparin, and can be considered as an
alternative to enoxaparin.

20. Based on saftey of LMWH thromboprophylaxis in women with
recurrent miscarriage without thrombophilia. (unexplained RPL)
Greer et al; 2005 , Nelson et al; 2011
Emperic heparin

21. • Intralipids >>>>>>>> aNK suppressors
• Immunoglobulins (IVIG) very expensive , many risks
• Dexamethazone/Prednisone >>>>>>>>>> CTL suppressors
Twice dailty till 10th week gestation
Other immunotherapies
Neither steroids nor IVIG improve the live birth rate of women with
RPL associated with aPL compared with other treatment modalities;
their use may provoke significant maternal and fetal morbidity. [A]
Green top 2011

23. Content
Intralipid 10%:
1000ml contain (purified soybean oil 100g, purified egg phospholipids
12g, glycerol anhydrous 22g, water for injection.
It is composed of 10% soybean oil, 1.2 % egg yolk phospholipids, 2.25 % gylcerine
and water.
Dosage:
2g of fat/kg body weight/day (20ml, 10ml and 6.7ml/kg of intralipid 10%,
20% and 30% respectively)
Infusion rate:
The drip rate is about 2 to 3 ml/min for intralipid 10%.
It should be started at half the infusion rate during the first 30mins under
supervision.
Protocol:
Repeated again with a positive pregnancy test and administer every month
until the 20th week

24. propofol is widely used, and in volume doses that are higher than
those suggested for the treatment of RIF.
many IVF programs, perform egg retrieval by
general anaesthesia, applying propofol as a short
acting hypnotic agent. Propofol solution contains
the same components of intralipid emulsion (10 %
soybean oil, and 1.2 % purified egg phospholipid,
with 2.25 % glycerol), supplemented with 1 %
propofol.
5/27/2017

25. Endocrinal causes

26. Major endocrinal causes of recurrent spontaneous abortions
• PCO
• Hyperandrogenism
• DM
• IR
• Hyperprolactinemia
• LPD
• Thyroid disorders
( Hypothyroidism –Hyperthroidism-Thyroid autoabs)
• Low serum hCG

27. Corpus luteum insufficiency
LPD

28. “No diagnostic test for luteal phase insufficiency has been proven in
a clinical setting.”
“No treatment for luteal phase insufficiency has been shown to
improve outcomes in natural unstimulated cycles.”
ASRM 2012
Good follicle = good corpus luteum
The new term of Fulliculo-Luteal Insufficiency
Progesterone secretion pulsatile blood may be drawn at a pulse
peak or nadir. These may vary ten-fold. Abraham et al; 1974

29. Progesterone supplementation
There is insufficient evidence to evaluate the effect of progesterone
supplementation in pregnancy to prevent a miscarriage in women
with recurrent miscarriage. B Green-top Guideline 2011

30. Meta-analysis of 4 trials involving 225 women with a history of RPL
reported that progestogen treatment is associated with a statistically
significant decrease in the miscarriage rate compared to placebo
or no treatment (OR 0.39; 95% CI 0.21 to 0.72).
Cochrane 2013
However, the quality of the methodology was considered to be poor.

31. Which Progesterone ?
Micronised
IM
Dyderogesterone

32. Prontogest
cyclogest
Uterocare
Uterogestan
Micronized progesterone

33. PROMISE Study on (826) ----- 400mg
Double-Blinded RCT in 39 hospital in UK
Arri et al; 2015
Disappointing results
- Progesterone supplementation in the first trimester of
pregnancy do NOTimprove outcomes in women with a
history of unexplained RPL
Positives
- Progesterone was safe
- did noteven Delayedthe miscarriage
‫المثبت‬‫أسطورة‬‫على‬ ‫القضاء‬-

34. Dydrogesterone
Reduction of miscarriage rate with the use of dydrogesterone in RPL.
European Progestin Club Guidelines for prevention and treatment of threatened or recurrent
(habitual) miscarriage with progestogens.
Dydrogesterone was associated with a more significant increase in the live birth rate
than the other progestogens . Cochrane 2013

35. IM (OHPC)
OHPC was a category D progestin (FDA 2008). !!!!!!!!!
There is speculation that the castor oil in the OHPC formulation may
not be beneficial for pregnancy
The FDA expressed concern about miscarriage at the 2006
advisory committee meeting; the committee voted totally that further
study was needed to evaluate the potential association of OHPC with
increased risk of second trimester miscarriage and stillbirth.

36. PCOs

37.  Obesity
 hyperinsulinemia
 IR
 Hyperandrogenemia
 Hyperhomocysteinemia
 high levels of plasminogen activator inhibitor-1 factor
 poor endometrial receptivity
 elevated levels of luteinizing hormone (LH).
Associated pathophysiology with PCOS

38. Metformine
Metformine
Metformine
Metformine
Metformine
Metformine

39. Tonically elevated insulin
inappropriate cell growth stimuli
abnormal folliculogenesis
and
angiogenesis
Metformin

40. Dangerous
But rare..
Lactic acidosis
1:33000
Myalgia Fatigue
Abdominal
distress
Respiratory
depression
S.E

41. 500 500 500
500
500
500
1st week 2nd week 3rd week
Incremental dose protocol

42. Long term ( up to one year )
BMI ˃30
patient with glucose intolerance
Acanthosis nigricans
Hirsutism
Short term (up to 3 months )
BMI about 25-30
Duration of treatment :

43. Hyperprolactinemia
Irregular cycle
Poor ovarian reserve !!!
laboratory rather than clinical diagnosis

44. PRL
One of stress hormone
Short half life 20 minutes
secreted in pulsatile fashion
PRL is the only pitutary hormone whose principal control is
inhibitory.
While estrogen is the most important stimulatory factor of PRL
secretion .
Discovered in non-human animals around
1930 by Oscar Riddle
confirmed in humans in 1970 by Henry
Friesen prolactin is a peptide hormone,
encoded by the PRL gene.

45. Normal fasting prolactin level is 30 ng/ml
Prolactin level above 20 ng/ml should be treated in RPL

46. Moderate HPRL 50 -100 ng/mL ( amenorrhea or oligomenorrhea).
Severe HPRL: 100 ng/mL ( amenorrhea, hot flashes ?? , and vaginal
dryness ??) . Necessitates sella evaluation ???!!!
Mild HPRL : 20 to 50 ng/mL may cause only insufficient P4
secretion Polymenorrhea and LPD .
Degrees

47. most premenopausal women who have hyperprolactinemia do not have
galactorrhea. On the other hand, many women who have galactorrhea
have normal serum prolactin concentrations .
Breast examination ??!!
Galactorrhea

48. Treatment of hyperPRL should be cause specific
Drugs
Hypothyroidism
Tumors
Idiopathic ???!!!!!

49. More D2 sensitivity ½ life 65 hs
½ life 3hs
Bromotemia

50. Cabergoline is the 1st line treatment in HyperPRL:
starting dose : 0.25 mg up to 0.5 mg two times a week.
Follow up :
PRL has to be controlled after 3 weeks of treatment
then; Do PRL level weekly
when PRL plasma levels are stabilized below 10 ng/ ml, cabergoline
dosage can be reduced to the minimum (i.e., 0.25 mg twice weekly).
In cases of hyperPRL rather than hypothroidism :
therapeutic effect of cabergoline in treatment of hyperprolactinemia
will typically persist for at least 4 weeks after cessation of treatment.

51. When :
TSH is normal,
+
fT3 levels are low (below 2.2 pg/ml).
It is called “low T3 syndrome” a defensive adaptation due to the lack
of energy
TTT:
- Do not give L-Thyroxine
- Only reduction of the physical activity (Genazzani et al; 1998).
Role of fT3 assay in RPL ???!!

52. High TSH requires the measurement of free T4 to confirm the diagnosis
of subclinical hypothyroidism.
Role of T4 assay in RPL ???!!

53. 8 weeks to change the dose of L – thyroxine and assessment of TSH.
Keep TSH below 2.5mU/mL

54. Infections
BV
CE

55. Diagnosis and post-treatment surveillance modalities
Culture: Hysteroscopy
CE

56. • Positive in 75% of histologically confirmed CE
• Common Bacteria :
E Coloi, streptococcus agalactiae: 77%
Mycoplasma/ Ureaplasma :25%
Chlamydia : 13%
(cicinelli et al; 2014)
• Often a causal organism can not be identified
• CE have no correlation with ;
Bacterial colonization of the EM or
Clinical presentation of PID
Korrn et al; 1995; Andrews et al; 2005
Culture:

57. Hysteroscopy is reliable in diagnosing Chronic endometritis
and it can assess clinical effectiveness of antibiotic therapy
(Among 211 patients with CE diagnosed by hysteroscopy,
200 cases were confirmed histologically) (Guo et al; 2013).

58. Micropolps is considered a reliable diagnostic sign for CE . (Ettore et al; 2005).

59. (B) At histology
++ inflammatory cells (lymphocytes, plasma cells or eosinophilic granulocytes)
Hysteroscopic guided biopsy

60. Prehysteroscopic diagnosis
No pathognomonic features !!!
While may be suspected by indirect features :
• Tender probing
• women with CE show altered endometrial patterns in both the periovulatory and
midluteal phases. (Pinto et al., 2015).
• ECF
• Folliculo-endometrial asynchorony (increased endometrial thickness
asynchronous with follicular growth)
• Intracavitary synechiae ( 3D SIS )

61. Clinical relation between RPL and CE??
Untreated CE may contribute to poor pregnancy outcomes .
McQueen et al 2015

62. Role of US
delayed differentiation of the endometrium in mid secretory phase
out – of – phase morphology (Mishera et al; 2008).
2nd look hysteroscopy :
The normalization of the hysteroscopic endometrial pattern seems to
be associated with a significant improvement in the reproductive
outcome. Cicinelli et al; 2014
Post treatment Surveillance

63. Degree of echogenicity

65. no agreement has been reached on endometrial thickness. Although
most clinicians empirically prefer endometria >7 mm, available
evidence does not support any specific thickness, as pregnancies with
similar success have been described from 5 mm to more than 15 mm
(Cai et al., 2011; Remohn et al., 1997).
Endometrial thickness ??!!

66. Regimen:
• Ofloxacin: 400mg daily for 2w OR
• Doxycycline : 100 mg twice daily for 2 W
Histological Cure: 70-95%
Treatment of Chronic endometritis
Persistent CE :
• Ciprofloxacin : 500 mg and
• Metonidazole : 500 mg twice daily for 2 weeks

67. Bacterial vaginosis treatment
Recommended Regimens
Metronidazole 500 mg orally twice a day for 7 days
OR
Metronidazole gel 0.75%, one full applicator (5 g) intravaginally, once a day for 5
days
OR
Clindamycin cream 2%, one full applicator (5 g) intravaginally at bedtime for 7
days
Alternative Regimens
Tinidazole 2 g orally once daily for 2 days
OR
Tinidazole 1 g orally once daily for 5 days
OR
Clindamycin 300 mg orally twice daily for 7 days
OR
Clindamycin ovules 100 mg intravaginally once at bedtime for 3 days

68. Monthly oral metronidazole 2g administered with fluconazole 150 mg
has also been evaluated as suppressive therapy; this regimen reduced the incidence
of BV and promoted colonization with normal vaginal flora
suppressive therapy

69. Anatomical causes of RPL

70. Mullerian duct anomalies
Endometrial polyps
IU Synechiae
Myomas

71. Hysteroscopic metroplasty

72. 3rd
Hysteroscopic treatment
2nd
rule out other potential causes such as genetic, metabolic,
and endocrine causes
1st
accurate imaging in order to determine the exact anomaly.

73. Effectiveness of metroplasty in management of RPL

74. Hysteroscopic metroplasty has been suggested to have a positive effect
on pregnancy outcomes. (Kowalik et al Cochrane review 2011)
While :
elective hysteroscopic removal of the septum in asymptomatic patients
before the first pregnancy is not supported. (Parsanezhad et al; 2006)

75. Tips and Tricks in treatment

79. Common morphological forms of the uterus in 3D ultrasonography
Normal Arcuate uterus !!!!!!

80. CONUTA (CONgenitalUTerine Anomalies) Working Group Human Reproduction
2013

81. Septate uterus by ESHRE–ESGE includes three morphological classes by ASRM; Top row,
norm (internal indentation ,1 cm); middle row, arcuate; and bottom row, septate uterus

82. Quiz ??
Two different cases of RPL

83. Normal uterus by ASRM with the same length of internal fundal indentation in coronal view
(top row); may be recognized paradoxically by ESHRE-ESGE as a septate (case on left) or
normal uterus (case on right) depending on the thickness of the uterine wall in the sagittal
view (bottom row).

84. We recommend ASRM classification in
management of RPL

85. Hysteroscopic metroplasty

86. Preoperative
Prophylactic Antibiotic:
no prospective randomized studies have been performed to
demonstrate their efficacy.
GnRH analogues ( to have thin endometrium ) (Colacurci et al; 1998).

87. •Semi rigid instruments (5 or 7 French Guage)
Unipolar electrode (thicker septum )
Scissor (small septum )
•Resectoscope blade with cutting current of 30 to 40 W/sec
low current to minimize thermal damage to endometrium
Surgical division BY :

89. Control laparoscopy
diaphanoscopy

90. Abdominal ultrasound-guided metroplasty by
hysteroscopy seems to reduce the rates of re-intervention
Vigoureux et al 2016
Role of US for aiding optimal correction

91. Minimizes endometrial trauma especially near the ostia /
subsequent risk of Ashermans
When the ostia are seen, stop cutting.
The fundus is kept convex and we should avoid making it concave
in the middle.
Remember

92. Post division ??
Immediately post procedure
•IUCD insertion , catheters and inflated balloons (2 to
3 months) unnecessary because division of the uterine septum does not lead
to formation of adhesions.
•Antibiotics –1 to 2 weeks ???!!
•Hormone therapy –3 cycles ??!!
not entirely supported by the evidence base!
AssafIntJ ObstetGynecol1990; Verceliniet al J ReprodMed 1989; Dabirashrafi et al J AAGL 1996

93. Should the Cervical Portion of the Septum Be Spared in
Patients with a Complete Septate Uterus?
Avoid secondary cervical incompetence.
Resection of the cervical portion was reported to make the procedure
safer, easier, and less complicated than preservation
of the cervical septum. (Parsanezhad et al; 2006)

94. Clinical tip :
if septate uterus is associated with mixed history
hysteroscopic metroplasty is of little value .
Challenge
Septum(RPL) ⇒⇒Ashermans $ (Infertility)

95. Myoma
• When should myomectomy be performed ?
• What is the role of Non surgical treatments ?

96. 1st step to manage Myoma is to do
SIS (FIGO classification) submucous
or
MRI (Endomyometrial junction) intramural

101. Intramural Myoma is associated with an increased risk of
spontaneous miscarriage [Ezzati et al; 2009].
Size ????
Before you do myomectomy complete evaluation evaluation has been
completed”. ASRM 2012
The location and size of the myomas are the two parameters that
influence the success of a future pregnancy. Kolankaya et al; 2006
BUT

102. Non surgical treatments :
• Drugs
• Embolization
• MRI US ablation
Has no role till now in mangment of myomas affecting
reproductive outcomes

103. Endometrial polyp

104. Although the association between endometrial polyps and pregnancy
loss has not been proven, polyps are more common in patients with
recurrent spontaneous abortion. Valli et al; 2001
Surgical excision is usually recommended, Devi et al; 2006

105. Hysteroscopic polypectomy can be performed by excision with
forceps or gentle curettage.
While resectoscope had a 0% recurrence rate and that
grasping forceps had a 15% recurrence rate. Preutthipan et al; 2005
If endometrial polyp less than 1.5 cm try 1st synthetic progestagens

106. Cervical insufficiency
recurrent 2nd trimester pregnancy losses
cervical length <25 mm
and/or
cervical changes on physical examination before 24 wks of gestation
The diagnosis cannot be made or excluded outside of pregnancy
by any test.

107. Evidence based approach to cerculage the cervix

108. Patient with Interventions
≥2 consecutive prior 2
nd
trimester losses
Or
•≥3 early (<34 weeks) preterm births
Transvaginal cerclage at 12 to 14 weeks
+
17-α –OH progesterone caproate 250 mg IM
weekly from 16 to 36 weeks
One prior 2
nd
trimester loss
Or
One or two preterm births <37 weeks
17-α-OH progesterone caproate 250 mg IM
weekly from 16 to 36 weeks
+
Serial measurement of cervical length beginning at
14 to 16 weeks and ending at 24 weeks
If cervical length <25 mm before 24 weeks, place
transvaginal cerclage
Options in next pregnancy if history-indicated cerclage was not
successful (ie, preterm birth <33 weeks)
Transabdominal cerclage
17-alpha-hydroxyprogesterone caproate 250 mg IM weekly from 16 to 36 weeks

109. Funnel length should not be measured or recorded as it is not an independent predictor of
preterm labor risk when the closed length of the cervical canal is considered

110. Evaluation of cervical length in a patient with a curved cervix. If the widest distance (A, red
arrow) between the yellow lines is greater than 5 mm, use the sum of B and C as the best
measurement of cervical length. If less than or equal to 5 mm, use D as the best measurement
of cervical length

116. Evidence - based progesterone use

117. • Natural progesterone metabolite
Minimal to No androgenic activity.
• Route : Only IM.
• Doses : 25 mg every five days - 1000 mg weekly
Recommended dose: 250 mg dose. (Cidulot Depot)
• Start: as early as 16 weeks of gestation.
• Contraindications:
Hormone-sensitive cancer, liver disease, or uncontrolled
hypertension Preeclampsia !!!!!!.
17-alpha-hydroxyprogesterone (17P) FDA approved march 2011 for
prevention of PTL and mid Trimesteric abortion
Safe drug by numerous
epidemiologic studies (Schardein
1980 -Resseguie et al; 1985- Raman et al;
1995-Northen et al; 2007) and clinical
trials ( Meis et al; 2003 -Fonseca et al;
2003 - O'Brien et al; 2007)

118. Risk of hypospadias in male offspring exposed to exogenous
progestins; even if confirmed, this risk is limited to exposure prior to
11 weeks of gestation and thus is not relevant to women with
prior preterm delivery, as they will receive the drug after 16
weeks of gestation [Silver et al; 1996 – Carmichael et al; 2005 ].
Treatment-genotype interactions, which could
result in either a beneficial or harmful treatment response [Manuck et
al; 2011 ].

119. Biological half-life Non-pregnant: 7.8 days
Singlet: 16 days
Twins: 10 days

120. Hydrosalpinx
5/27/2017

121. Chromosomal causes of RPL
IVF as an alternative treatment of RPL

123. According to probability theory, at least 50% of embryos created by a
parent with a balanced translocation and 67% of embryos created by
a parent with a Robertsonian translocation will be abnormal
At least one euploid embryo was identified in 61% of initiated IVF
cycles, and in 79% of cycles in which PGS was performed.

124. Extraordinary genetic diversity of the
human embryos at implantation
That put another question about the
value of PGS before embryo transfer
??!!!
Is it a help or a hype

125. FISH Vs CGH
Comparative genomic hybridization (CGH) is a
genetic test that identifies all chromosomes
within the embryo , not as FISH which detect
defects in some individualized chromosomes
،‫السبت‬02،‫رمضان‬1438

126. PGS is notan indicative marker for embryo quality, but a definite genetic
diagnostic test to excludedevelopmentally incompetent embryos from the
cohort, those that are at risk to generate miscarriage or implantation failures

127. trophectoderm biopsy (Scott et al., 2013) and vitrification do
not compromise the reproductive competence of blastocysts
(Schoolcraft et al., 2011).
Morphological criteria, even coupled with morphokinetic analysis, are
very poor predictors of embryo chromosomal
architecture and viability (Capalbo et al., 2014; Rienzi et al., 2015).
So
Poor-quality blastocysts have significant euploidy rate and considerable
delivery potential (Capalbo et al., 2014); poor embryo quality should
not be used as a reason to cancel the genetic-testing procedure when
PGS has been indicated before starting the IVF cycle.

128. TTT :
just Genetic counseling
Financial cost as well as implantation and live birth rates per
cycle following in vitro fertilisation/ preimplantation genetic
diagnosis.
They should be informed that they have a higher (50–70%)
chance of a healthy live birth in future untreated pregnancies
following natural conception Franssen et al; 2006 than is
currently achieved after preimplantation genetic diagnosis/in vitro
fertilisation (approximately 30%). Lalioti 2008

129. Indicated only in :
women of advanced reproductive age with RPL:
• There is no evidence that IVF with PGS improves
overall live birth rates compared with expectant
management, because a significant number of IVF cycles
either do not undergo PGS or fail to identify euploid
embryos.
However, when euploid embryos are identified in women
older than age 35, the live birth rate is improved.

130. Observational studies have shown that increased consumption of folic
acid in the periconceptional period may reduce this risk. George et al;
2002 – Gaskins et al; 2014

131. Psycological aspect of RPL

132. A review of all published large RCTs and metaanalyses
undertaken by the ESHRE Special Interest Group for Early
Pregnancy (SIGEP) protocol for the investigation and medical
management of recurrent miscarriage concluded that the only
interventions that do not require more randomized controlled
trials are tender loving care and health advice.
Jauniaux et al; ESHRE 2006

133. Interpregnancy spacing
superfertility is a cause of RPL

134. Male as a cause of RPL

135. Sperm DNA fragmentation test
Sperm as a cause of RIF ?
DNA fragmentation

136. ،‫السبت‬02،‫رمضان‬1438
Two tests encountered with cases of RIF !!
Sperm Chromatin Structure Assay (SCSA):
Sperm chromatin dispersion test (SCD)
DNA fragmentation index >27%: RIF (Larson et al.,2000; Larson-Cook
et al., 2003)

137. • Avoidance of toxicities such as smoking, hot tubs/saunas, etc.
• Antioxidant vitamin supplements may reduce sperm DNA damage
(we have published reports of this benefit).
• Encourage the patient to eat food rich in antioxidants (fruit, veg,
dried tomatoes etc)
• Treatment of infection may reduce sperm DNA damage.
• Varicolectomy may reduce sperm damage. TESE (testicular
extraction of sperm) has been proposed as being beneficial (we
recommend it in some cases).
• Decreased abstinence days to only one day !!! Isabel et al; 2013.
Treatments for elevated sperm DNA fragmentation include:
Cause specific treatment :

139. To conclude, the findings of this systematic review demonstrate a
significant relationship between levels of DNA damage in sperm and
spontaneous pregnancy loss
Tests for DNA damage and selection of undamaged sperm should be
considered as part of the diagnostic and treatment pathways for those
suffering from recurrent pregnancy loss

140. Does we have an overlap between
RPL and infertility ??!!!
To consider in treatment

142. Take home message
If the treatment of RPL is not cause specific treatment consider
abortion rate in the current pregnancy to be near 100%
If your patient respond to EL FANKOSH; you or your patient or
both of you are so lucky .