1. RECURRENT MISCARRIAGE GUIDELINES
MAJ DR AMINA AKBAR
MBBS, MCPS, FCPS

2. DEFINITION
A recurrent miscarriage is defined as 3 or more consecutive, spontaneous pregnancy losses, under 20 week gestation from the last menstrual period

3. Primary recurrent pregnancy loss" refers to couples that have never had a live birth
While "secondary RPL" refers to those who have had repetitive losses following a successful pregnancy

4. TERMINOLOGY
The medical term ' abortion' should be replaced with the term 'miscarriage'
Other names : Recurrent Pregnancy Loss (RPL),
Habitual Abortions ,
Habitual Miscarriages,
Recurrent Abortions ,
Recurrent Miscarriages.

5. INCIDENCE
10–15% of all clinically recognized pregnancies end in a miscarriage
Recurrent miscarriage affects 0.5-2% of all women -- Hence, only a proportion of women presenting with recurrent miscarriage will have a persistent underlying cause for their pregnancy losses

6. RISK FACTORS
Advanced maternal age adversely affects ovarian function, giving rise to a decline in the number of good quality oocytes, resulting in chromosomally abnormal conceptions that rarely develop further
Previous number of miscarriages

7. POSSIBLE CAUSES
Recurrent miscarriage is a heterogeneous condition that has many possible causes; more than one contributory factor may underlie the recurrent pregnancy losses
Each may have had a different cause

8. Recurrent Miscarriage Explained Un-explained
Genetic
factors
Infective
agents
Endocrine
Enviromental
factors
Anatomical
factors
Immune
factors
Inhereted
Thrombophilic
defect
Bacterial
Vaginosis
Body
Cervix
C I
APS
Uterine
anomalies
Paternal
karyotyping
Cytogenetic
Of miscarriage

9. GENETIC FACTORS

10. All couples with a history of recurrent miscarriage should have peripheral blood karyotyping performed. The finding of an abnormal parental karyotype should prompt referral to a clinical geneticist.
3–5% of couples with recurrent miscarriage, one of the partners carries a balanced structural chromosomal anomaly
5–10% chance of a pregnancy with an unbalanced translocation.

11. FETAL CHROMOSOMAL ABNORMALITIES
This may be due to abnormalities in the egg, sperm or both. The  most common chromosomal defects are:-
Trisomy:
Monosomy
Polyploidy

12. Chromosome Testing on Fetal (Miscarriage) Tissue
This can only be done right at the time of miscarriage.
It is an analysis of the genetic makeup of the fetus.
It can indicate genetic problems that lead to RPL.
Many miscarriages are caused by chromosomal abnormalities that are unlikely to repeat. To know if the problem is likely to recur, it is necessary to study the genetics of both parents as well.

13. Karyotyping of Parents
Chromosome analysis of blood of both parents.
It can show if there is a potential problem with one of the parents that leads to miscarriage, but often has to be done in conjunction with fetal testing to provide answers.

14. ANATOMICAL FACTORS

15. CONGENITAL ANOMALIES An abnormal or irregularly shaped uterus.
Sometimes the uterus has an extra wall down its centre, which makes it look as if it is divided into
two (bicornuate or septate uterus)
a septate uterus Where as a partial septum increases the risk to 60%-75%; a total septum carries a risk for loss of up to 90%.
Today a relatively simple surgical procedure can remove a uterine septum
or it may have only developed one half (unicornuate uterus).

16. The reported prevalence of uterine anomalies in recurrent miscarriage populations range between 1.8% and 37.6%.
The prevalence of uterine malformations appears to be higher in women with late miscarriages compared with women who suffer early miscarriages
Untreated uterine anomalies has a term delivery rate of only 66%.
Open uterine surgery is associated with postoperative infertility and carries a significant risk of uterine scar rupture during pregnancy. Therefore treatment of uterine anomalies in women with recurrant miscarriage remains controversial.

17. FIBROIDS
If fibroids are detected on the inside of the uterus (termed submucous fibroids) and distort the uterine lining, they are a significant cause of reproductive problems and should be removed. It is less clear whether fibroids in the wall of the uterus cause reproductive problems

18. All women with recurrent miscarriage should have a pelvic ultrasound to assess uterine anatomy and morphology
Two dimensional pelvic ultrasound assessment of the uterine cavity with (or without) Sonohysterography

19. HYSTEROSALPINGOGRAPHY
The routine use of hysterosalpingography as a screening test for uterine anomalies in women with recurrent miscarriage is questionable.
It is associated with patient discomfort,
carries a risk of pelvic infection and radiation exposure
and is no more sensitive than the non-invasive two dimensional pelvic ultrasound assessment of the uterine cavity with (or without) Sonohysterography when performed by skilled and experienced personnel.

20. HYSTEROSCOPY
This investigation, performed under general anaesthetic, examines the inside of the uterus with a thin
telescope (3-5 mm in diameter) . By inserting this telescope through the cervix and into the uterus,
the doctor can see the shape of the uterus and examine its lining.

21. CERVICAL WEAKNESS

22. Diagnosis of cervical incompetence is based on history of late miscarriage preceded by spontaneous rupture of memb or painless cervical dilatation. Vaginal USG is helpful in assessing early features of cervical incompetence. Cervical cerclage is associated with potential hazards associated with surgery and risk of uterine contractions.

23. ENDOCRINE FACTORS

24. Routine screening for occult diabetes and thyroid disease with oral glucose tolerance and thyroid function tests in asymptomatic women presenting with recurrent miscarriage is uninformative
Well-controlled diabetes mellitus is not a risk factor for recurrent miscarriage, nor is treated thyroid dysfunction

25. There is insufficient evidence to evaluate the effect of progesterone supplementation in pregnancy to prevent a miscarriage

26. There is insufficient evidence to evaluate the effect of human chorionic gonadotrophin (hCG) in pregnancy to prevent miscarriage.
Early pregnancy hCG supplementation failed to show any benefit in pregnancy outcome

27. IMMUNE FACTORS
One in ten women with recurrent miscarriages show evidence of auto immune factors on investigation
As much as 40 percent of unexplained infertility may be the result of immune problems. Unfortunately for couples with immunological problems, their chances of recurrent loss increase with each successive pregnancy.

28. ANTITHYROID ANTIBODIES
Routine screening for thyroid antibodies in women with recurrent miscarriage is not recommended.

29. ANTIPHOSPHOLIPID SYNDROME
To diagnose APS it is mandatory that the patient should have two positive tests at least six weeks apart for either lupus anticoagulant or anticardiolipin (aCL) antibodies of IgG and/or IgM class present in medium or high titre.
Adverse pregnancy outcomes include
Three or more consecutive miscarriages before ten weeks of gestation
One or more morphologically normal fetal deaths after the tenth week of gestation and
One or more preterm births before the 34th week of gestation due to severe pre-eclampsia, eclampsia or placental insufficiency.

30. In women with a history of recurrent miscarriage and aPL, future live birth rate is significantly improved when a combination therapy of aspirin plus heparin is prescribed.
Pregnancies associated with aPL treated with aspirin and heparin remain at high risk of complications during all three trimesters.

31. INHERITED THROMBOPHILIC DEFECTS

32. Inherited thrombophilic defects,
Including activated protein C resistance (most commonly due to factor V Leiden gene mutation), deficiencies of protein C/S and antithrombin III, hyperhomocysteinaemia and prothrombin gene mutation,
Are established causes of systemic thrombosis

33. INFECTIVE AGENTS

34. Screening for and treatment of bacterial vaginosis in early pregnancy among high risk women with a previous history of second-trimester miscarriage or spontaneous preterm labour may reduce the risk of recurrent late loss and preterm birth.

35. ENVIRONMENTAL FACTORS

36. Exposture to noxious or toxic substances are known to be associated with recurrent miscarriage ( cigarretes,alcohol and caffeine ,anaestetic gases,petrolium products )

37. UNEXPLAINED RECURRENT MISCARRIAGE
In about half the women in the research studies, no cause could be found, so no specific treatment could be given.
However, this group responded very well to a programme which removed as many stress factors as possible from their lives, resulting in an 80% success rate with the subsequent pregnancy

38. PSYCHOLOGICAL SUPPORT
The value of psychological support in improving pregnancy outcome has not been tested in the form of a randomised controlled trial. However, data from several non-randomised studies86–88 have suggested that attendance at a dedicated early pregnancy clinic has a beneficial effect, although the mechanism is unclear
All professionals should be aware of the psychological sequelae associated with miscarriage and should provide support and follow-up, as well as access to formal counselling when necessary.

39. THANK YOU