RECURRENT MISCARRIAGE GUIDELINES MAJ DR AMINA AKBAR MBBS

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

DEFINITION tiage or more consecutive, spontaneous pregnancy losses, under 20 week gestation from the last menstrual period

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

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

INCIDENCE l 10– 15% of all clinically recognized pregnancies end in a miscarriage l Recurrent miscarriage affects 0. 5 -2% of all women -- Hence, only a proportion of women presenting with recurrent miscarriage will have a persistent underlying pregnancy losses cause for their

RISK FACTORS l 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 l Previous number of miscarriages

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

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

GENETIC FACTORS

l 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. l 3– 5% of couples with recurrent miscarriage, one of the partners carries a balanced structural chromosomal anomaly l 5– 10% chance of a pregnancy with an unbalanced translocation.

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

l Chromosome Testing on Fetal (Miscarriage) Tissue l l This can only be done right at the time of miscarriage. It is an analysis of the genetic makeup of the fetus. l It can indicate genetic problems that lead to RPL. l 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.

l Karyotyping of Parents l Chromosome analysis of blood of both parents. l 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.

ANATOMICAL FACTORS

CONGENITAL ANOMALIES l An abnormal or irregularly shaped uterus. l 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

l l 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.

FIBROIDS l 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

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

HYSTEROSALPINGOGRAPHY l The routine use of hysterosalpingography as a screening test for uterine anomalies in women with recurrent miscarriage is questionable. l It is associated with patient discomfort, l carries a risk of pelvic infection and radiation exposure l 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.

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

CERVICAL WEAKNESS

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.

ENDOCRINE FACTORS

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 l Well-controlled diabetes mellitus is not a risk factor for recurrent miscarriage, nor is treated thyroid dysfunction

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

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

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.

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

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 (a. CL) antibodies of Ig. G and/or Ig. M class present in medium or high titre. l Adverse pregnancy outcomes include l Three or more consecutive miscarriages before ten weeks of gestation l One or more morphologically normal fetal deaths after the tenth week of gestation and l One or more preterm births before the 34 th week of gestation due to severe pre-eclampsia, eclampsia or placental insufficiency.

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

INHERITED THROMBOPHILIC DEFECTS

l l 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, l Are established causes of systemic thrombosis

INFECTIVE AGENTS

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

ENVIRONMENTAL FACTORS

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

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

PSYCHOLOGICAL SUPPORT l 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 studies 86– 88 have suggested that attendance at a dedicated early pregnancy clinic has a beneficial effect, although the mechanism is unclear l 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.

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