RECURRENT RECURRENT MISCARRIAGEMISCARRIAGEGUIDELINESGUIDELINES

MAJ DR AMINA MAJ DR AMINA AKBARAKBARMBBS, MCPS, FCPSMBBS, MCPS, FCPS

DEFINITIONDEFINITION

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

Primary recurrent pregnancy loss" Primary recurrent pregnancy loss" refers to couples that have never had a refers to couples that have never had a live birth live birth

While While "secondary RPL""secondary RPL" refers to those refers to those who have had repetitive losses who have had repetitive losses following a successful pregnancy following a successful pregnancy

TERMINOLOGYTERMINOLOGY The medical term The medical term ' abortion' ' abortion' should be should be

replaced with the term replaced with the term 'miscarriage''miscarriage' Other names : Recurrent Pregnancy Loss (RPL), Other names : Recurrent Pregnancy Loss (RPL),

Habitual Abortions ,Habitual Abortions , Habitual Miscarriages, Habitual Miscarriages,

Recurrent Abortions ,Recurrent Abortions , Recurrent Miscarriages. Recurrent Miscarriages.

INCIDENCEINCIDENCE 1010––15%15% of all clinically recognized of all clinically recognized

pregnancies end in a miscarriage pregnancies end in a miscarriage Recurrent miscarriage affects Recurrent miscarriage affects 0.5-2%0.5-2% of all of all

women -- Hence, only a proportion of women -- Hence, only a proportion of women presenting with recurrent women presenting with recurrent miscarriage will have a persistent miscarriage will have a persistent underlying cause for their pregnancy losses underlying cause for their pregnancy losses

RISK FACTORSRISK FACTORS Advanced maternal age Advanced maternal age adversely adversely

affects ovarian function, giving rise to a affects ovarian function, giving rise to a decline in the number of good quality decline in the number of good quality oocytes, resulting in chromosomally oocytes, resulting in chromosomally abnormal conceptions that rarely abnormal conceptions that rarely develop furtherdevelop further

Previous number of miscarriages Previous number of miscarriages

POSSIBLE CAUSESPOSSIBLE CAUSES

Recurrent miscarriage is a Recurrent miscarriage is a heterogeneous condition that has heterogeneous condition that has many possible causes; many possible causes; more than one more than one contributory factor may underlie the contributory factor may underlie the recurrent pregnancy lossesrecurrent pregnancy losses

Each may have had Each may have had a different a different cause cause

Geneticfactors

Anatomicalfactors

EndocrineInfectiveagents

Immunefactors

InheretedThrombophilic

defect

Explained Un-explained

RecurrentMiscarriage

Enviromentalfactors

Body Cervix

Paternalkaryotyping

CytogeneticOf miscarriage

C I

Uterineanomalies

APS

BacterialVaginosis

GENETIC FACTORSGENETIC FACTORS

All couples with a history of recurrent All couples with a history of recurrent miscarriage should have peripheral miscarriage should have peripheral blood karyotyping performed. The blood karyotyping performed. The finding of an abnormal parental finding of an abnormal parental karyotype should prompt referral to a karyotype should prompt referral to a clinical geneticist.clinical geneticist.

33––5% of couples with recurrent miscarriage, 5% of couples with recurrent miscarriage, one of the partners carries a balanced one of the partners carries a balanced structural chromosomal anomaly structural chromosomal anomaly

55––10% chance of a pregnancy with an 10% chance of a pregnancy with an unbalanced translocation. unbalanced translocation.

FETAL CHROMOSOMAL FETAL CHROMOSOMAL ABNORMALITIESABNORMALITIES

This may be due to abnormalities in This may be due to abnormalities in the egg, sperm or both. Thethe egg, sperm or both. The   most most common chromosomal defects are:-common chromosomal defects are:- Trisomy:Trisomy: MonosomyMonosomy PolyploidyPolyploidy

Chromosome Testing on Fetal (Miscarriage) Chromosome Testing on Fetal (Miscarriage) TissueTissue

This can only be done right at the time of miscarriage.This can only be done right at the time of miscarriage. It is an analysis of the genetic makeup of the fetus. It is an analysis of the genetic makeup of the fetus. It can indicate genetic problems that lead to RPL. It can indicate genetic problems that lead to RPL. Many miscarriages are caused by chromosomal Many miscarriages are caused by chromosomal

abnormalities that are unlikely to repeat. To know if abnormalities that are unlikely to repeat. To know if the problem is likely to recur, it is necessary to study the problem is likely to recur, it is necessary to study the genetics of both parents as well.the genetics of both parents as well.

Karyotyping of ParentsKaryotyping of Parents Chromosome analysis of blood of both Chromosome analysis of blood of both

parents.parents. It can show if there is a potential problem with It can show if there is a potential problem with

one of the parents that leads to miscarriage, one of the parents that leads to miscarriage, but often has to be done in conjunction with but often has to be done in conjunction with fetal testing to provide answers.fetal testing to provide answers.

ANATOMICAL ANATOMICAL FACTORSFACTORS

CONGENITAL ANOMALIESCONGENITAL ANOMALIES An abnormal or irregularly shaped uterus.An abnormal or irregularly shaped uterus. Sometimes Sometimes the uterus has an extra wall down its centre, which

makes it look as if it is divided into it is divided into two (bicornuate or septate uterus) (bicornuate or septate uterus)

a septate uterus Where as a partial septum increases the risk to 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%. 60%-75%; a total septum carries a risk for loss of up to 90%.

Today a relatively simple surgical procedure can remove a Today a relatively simple surgical procedure can remove a uterine septum uterine septum

or it may or it may have only developed one half (unicornuate uterus)(unicornuate uterus). .

The reported prevalence of uterine anomalies The reported prevalence of uterine anomalies in recurrent miscarriage populations range in recurrent miscarriage populations range between 1.8% and 37.6%. between 1.8% and 37.6%.

The prevalence of uterine malformations The prevalence of uterine malformations appears to be higher in women with appears to be higher in women with late late miscarriages miscarriages compared with women who suffer compared with women who suffer early miscarriagesearly miscarriages

Untreated uterine anomalies Untreated uterine anomalies has a term has a term delivery rate of only 66%. delivery rate of only 66%.

Open uterine surgery Open uterine surgery is associated with is associated with postoperative infertility and carries a postoperative infertility and carries a significant risk of uterine scar rupture during significant risk of uterine scar rupture during pregnancy. Therefore treatment of uterine pregnancy. Therefore treatment of uterine anomalies in women with recurrant anomalies in women with recurrant miscarriage remains controversial.miscarriage remains controversial.

FIBROIDSFIBROIDS If fibroids are detected on the inside of the If fibroids are detected on the inside of the

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

All women with recurrent All women with recurrent miscarriage should have a miscarriage should have a pelvic ultrasound to assess pelvic ultrasound to assess uterine anatomy and uterine anatomy and

morphologymorphology

Two dimensional pelvic ultrasound Two dimensional pelvic ultrasound assessment of the uterine cavity assessment of the uterine cavity with (or without) Sonohysterographywith (or without) Sonohysterography

HYSTEROSALPINGOGRAPHYSTEROSALPINGOGRAPHYHY

The routine use of hysterosalpingography as The routine use of hysterosalpingography as a screening test for uterine anomalies in a screening test for uterine anomalies in women with recurrent miscarriage is women with recurrent miscarriage is questionablequestionable..

It is associated with patient discomfort, It is associated with patient discomfort, carries a risk of pelvic infection and radiation carries a risk of pelvic infection and radiation

exposure exposure and is no more sensitive than the non-and is no more sensitive than the non-

invasive two dimensional pelvic ultrasound invasive two dimensional pelvic ultrasound assessment of the uterine cavity with (or assessment of the uterine cavity with (or without) Sonohysterography when performed without) Sonohysterography when performed by skilled and experienced personnel. by skilled and experienced personnel.

HYSTEROSCOPYHYSTEROSCOPYThis investigation, performed under general This investigation, performed under general

anaesthetic, examines the inside of the uterus anaesthetic, examines the inside of the uterus with a thinwith a thin

telescope (3-5 mm in diameter) . By inserting this telescope (3-5 mm in diameter) . By inserting this telescope through the cervix and into the uterus,telescope through the cervix and into the uterus,

the doctor can see the shape of the uterus and the doctor can see the shape of the uterus and examine its lining.examine its lining.

CERVICAL WEAKNESSCERVICAL WEAKNESS

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

contractionscontractions..

ENDOCRINE FACTORSENDOCRINE FACTORS

Routine screening for occult Routine screening for occult diabetes and thyroid disease diabetes and thyroid disease

with oral glucose tolerance and with oral glucose tolerance and thyroid function tests in thyroid function tests in asymptomatic women asymptomatic women

presenting with recurrent presenting with recurrent miscarriage is uninformativemiscarriage is uninformative

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

There is insufficient evidence There is insufficient evidence to evaluate the effect of to evaluate the effect of

progesterone supplementation progesterone supplementation in pregnancy to prevent a in pregnancy to prevent a

miscarriagemiscarriage

There is insufficient evidence to There is insufficient evidence to evaluate the effect of human evaluate the effect of human

chorionic gonadotrophin (hCG) chorionic gonadotrophin (hCG) in pregnancy to prevent in pregnancy to prevent

miscarriagemiscarriage..

Early pregnancy hCG supplementation Early pregnancy hCG supplementation failed to show any benefit in pregnancy failed to show any benefit in pregnancy outcome outcome

IMMUNE FACTORSIMMUNE FACTORS One in ten women with recurrent miscarriages One in ten women with recurrent miscarriages show evidence of auto immune factors on show evidence of auto immune factors on investigationinvestigation

As much as As much as 40 percent 40 percent of unexplained infertility of unexplained infertility may be the result of immune problems. may be the result of immune problems. Unfortunately for couples with immunological Unfortunately for couples with immunological problems, their chances of recurrent loss problems, their chances of recurrent loss increase with each successive pregnancyincrease with each successive pregnancy..

ANTITHYROID ANTIBODIESANTITHYROID ANTIBODIES

Routine screening for thyroid Routine screening for thyroid antibodies in women with antibodies in women with recurrent miscarriage is not recurrent miscarriage is not recommendedrecommended..

ANTIPHOSPHOLIPID ANTIPHOSPHOLIPID SYNDROMESYNDROME

To diagnose APS it is mandatory that the To diagnose APS it is mandatory that the patient should have two positive tests at patient should have two positive tests at least six weeks apart for either lupus least six weeks apart for either lupus anticoagulant or anticardiolipin (aCL) anticoagulant or anticardiolipin (aCL) antibodies of IgG and/or IgM class present antibodies of IgG and/or IgM class present in medium or high titre.in medium or high titre.

Adverse pregnancy outcomes include Adverse pregnancy outcomes include Three or more consecutive miscarriages Three or more consecutive miscarriages

before ten weeks of gestationbefore ten weeks of gestation One or more morphologically normal fetal One or more morphologically normal fetal

deaths after the tenth week of gestation anddeaths after the tenth week of gestation and One or more preterm births before the 34th One or more preterm births before the 34th

week of gestation due to severe pre-eclampsia, week of gestation due to severe pre-eclampsia, eclampsia or placental insufficiency. eclampsia or placental insufficiency.

In women with a history of recurrent In women with a history of recurrent miscarriage and aPL, future live birth miscarriage and aPL, future live birth rate is significantly improved when a rate is significantly improved when a combination therapy of aspirin plus combination therapy of aspirin plus heparin is prescribed.heparin is prescribed.

Pregnancies associated with aPL treated Pregnancies associated with aPL treated with aspirin and heparin remain at high with aspirin and heparin remain at high risk of complications during all three risk of complications during all three trimesters.trimesters.

INHERITED INHERITED THROMBOPHILIC DEFECTSTHROMBOPHILIC DEFECTS

Inherited thrombophilic defects,Inherited thrombophilic defects, Including activated protein C resistance (most Including activated protein C resistance (most

commonly due to factor V Leiden gene commonly due to factor V Leiden gene mutation), deficiencies of protein C/S and mutation), deficiencies of protein C/S and antithrombin III, hyperhomocysteinaemia and antithrombin III, hyperhomocysteinaemia and prothrombin gene mutation,prothrombin gene mutation,

Are established causes of systemic thrombosis Are established causes of systemic thrombosis

INFECTIVE AGENTSINFECTIVE AGENTS

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

ENVIRONMENTAL FACTORSENVIRONMENTAL FACTORS

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

UNEXPLAINED UNEXPLAINED RECURRENT RECURRENT

MISCARRIAGEMISCARRIAGE In about half the women in the research In about half the women in the research studies, studies, no cause no cause could be found, so no

specific treatment could be given. However, this group responded very well to a However, this group responded very well to a

programme which removed as many programme which removed as many stress stress factorsfactors as possible from their lives, resulting in as possible from their lives, resulting in

an 80% success rate with the subsequent an 80% success rate with the subsequent pregnancy pregnancy

PSYCHOLOGICAL SUPPORTPSYCHOLOGICAL SUPPORT The value of psychological support in improving pregnancy The value of psychological support in improving pregnancy

outcome has not been tested in the form of a randomised outcome has not been tested in the form of a randomised controlled trial. However, data from several non-controlled trial. However, data from several non-randomised studiesrandomised studies86–88 have suggested that attendance 86–88 have suggested that attendance at a dedicated early pregnancy clinic has a beneficial at a dedicated early pregnancy clinic has a beneficial effect, although the mechanism is uncleareffect, although the mechanism is unclear

All professionals should be aware of the All professionals should be aware of the psychological sequelae associated with miscarriage psychological sequelae associated with miscarriage and should provide support and follow-up, as well and should provide support and follow-up, as well as access to formal counselling when necessary.as access to formal counselling when necessary.

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