RECURRENT PREGNANCY LOSS / RECURRENT ABORTION I

RECURRENT MISCARRIAGE/HABITUAL ABORTION  

Tabassum Parveiz M D

 

 

Definition:

RPL is defined as 3 or more consecutive spontaneous abortions before 20 wks of gestation or a fetal weight less than 500 gms

♦      2 Types - Primary Aborters Women without a previous livebom infant

Secondary Aborters Women with atleast one prior livebom infant

Incidence: 0 5 - 1% of all pregnancies

Recurrence Risk:

The reproductive H/o patient is \ ery important as relative risk of abortion increases with no of previous pregnancy failures

No of Prior losses % Risk of loss in next pregnancy Atleast one live born infant

0                                                                                        12%

1                                                                                        24 %

2                                                                                        26 %

3                                                                                        32 %

4                                                                                        26 %

No live born infant

2                                                                        or more  40 - 45 %

Etiology: In 50 % cases a Probable cause is identified

1.    Genetic factors: (5%)

A)   Chromosomal abnormalities of conceptus

♦     Are a common cause of early sporadic abortion [single losses] but not a major cause of RPL

♦     Responsible for 50-60% of 1^st TM abortion

♦      Most common are aneuploidics, which are present m 80% of blighted ova and 5-10% abortion in which fetus are present

♦     Are detected by examination of POC

♦      Occur due to errors of maternal or paternal meiosis I or II, super fecundation of an egg by 2 sperms of form a chromosome division in absence of cytoplasmic division with advancing maternal age or due to fertilization of ageing ova or sperm

i) Autosomal trisomies (40 - 5 0%)

□     Includes 13, 16* 18, 21 and 22 u) Monosomy X - (20-25%)

□     Have a karyotype 45 X

□     If pregnancy is not aborted identified at birth as individual with Turner’s syndrom,

in) Polyploidy - Triploidy (16%)

-       Mostly seen in IVF conceptuses

-       Triploid fetus may result in formation of V mole

B) Parental chromosomal abnormalities (3-5%)

-       Is higher m couples who have not experienced a live birth

-       The structural re-arrangements could be de- no\ a Occurring during gametogenesis or could be inherited from one of the parents who is a carrier for these abnormalities

Includes:

♦      Translocations - 2/3^rd reciprocal balanced translocation

-        l/3^rd Robertsonian translocation

-       Translocation carriars are phenotypically normal

♦      Others -

-        Inversions

-        Mosaicism

II     Anatomic abnormalities of uterus (10-15%)

-       Usually responsible for 2^nd Tm abortion

-        May be congenital or acquired

A)    Congenital -

a)    Mullerian duct abnormalities -

1                                                                       Umcomuate uterus 2 Bicomuate uterus

3                                                                       Septate uterus        4 Didelphic uterus

b)    DES exposure in utero -

Can cause multiple uterme anomalies most common hypoplasia contributing to 1^st and 2^nd Tm spontenous abortion, incompetent cervix and prematiure labour

c)    Uterme artery anomalies -

B)   Acquired -

1      Cervical incompetence -

-       May be congenital (rare) or acquired (iatrogenic)

-       Usually late 2^nd Tm abortion

-        Caused by - cervical trauma

-       Following D&C, Vaginal operative delivery through an undilated cervix, amputation of cervix, cone biopsy

2      Intrauterine adhesions (synechiae) -

-       Result from intrauterine infection combined with surgical trauma like - postabortal or postpartum curettage for retained POC

-       Tubercular endometritis

3       Submucus fibroids -

Less common causes includes

4      Endometriosis

5      Retroverted uterus

III   Endocrine abnormalities (10 —15%) —

a)    Luteal phase deficiency

In adequate endometrial maturation due to insufficient progesteron - early pregnancv loss

♦     There is much controversy about LPD as a cause of RPL

♦      Decreased progesteron level is the effect rather than cause of abortion

b)    Polycystic ovarian syndrome - (PCOS)

♦      In RPL, 82% pt Shows a evidence of PCOS

♦      Hypersecretion of LH, may lead to

1      Direct inhibition of oocyte maturation inhibitor (omi) leading to production of physiologically aged oocyte

2      Altered synthesis of prostaglandins

3      Increased androgen systhesis by theca cells

4      Production of abnormal glycoform of LH causing abnormal signal transduction and anovulation

c)     Thyroid deficiency -

♦     Unlikely cause of RPL

d)    Diabetes -

Poorly control diabetes with elevated blood sugar and glycosylated Hb in first Tm

e)     Androgen and Prolectin disorders - can lead to corpus leuteum dysfunction

IV.                                  Infections                - (5%)

♦      More likely to cause sporadic loss

♦       Uterine or disseminated List includes -

Syphilis, Rubella, Herpes, Cytomegalovirus, Listeria, Toxoplasmosis, Ureaplasma, Brucella, Mycoplasma, E coli Tubercular bacilli

V.    Immunological factors - (20 - 40%)

a)    Abnormal cellular immuno response- (Embryo/ trophoblast toxic factors/cytokines)

Trophoblast antigens----------- + —a macrophages

and lymphocytes —a abnormal cellular response

by TH1 cells             a release of cytokins, IFN - g

and TNF -a inhibit in-vitro development of embryo

b)    Abnormal humoral immune response.

1.    Autoimmune factors

Include antiphosphohpid antibody syndrome

(APAS), SLE

♦     Antibodies are formed against negatively charged phospholipids In my recent case study of 5 0 pts of recurrent abortions in 2001 - 2002 the autoimmune factor of antiphosphohpid antibody formed against negatively charged phospholipid has been demonstrated m 4 patients Its occurrence would be surely demonstrated in more pts of recurrent abortions If all such patients are thoroughly screened for these autoimmune factors

Mainly 2 types - LA & ACA

MOA - Increased thromoboxane and

decreased prostacyclme synthesis, reduced

anti thrombin III synthesis and protine C

deficency

♦     APA can inhibit m vitro syncytial trophoblast formation

2.     Alio - immune factors -

♦      Active immune modulation of maternal system protects the embryo from rejection

♦      Circulating factors proposed as being immuno suppresive include blocking antibodies, early pregnancy factor IL-2, local suppressor cells & certain cytokines

VI.    Miscellaneous factors - (10%)

l) Environmental toxins - heavy metal toxicity, prolonged exposure to organic solvents u) Drugs - Antiprogestogens, Antineoplastic agents, inhalation anaesthetics, Nicotine and ethanol in) Ionizing radiation

ιν) Medical illnesses - Cardiac renal, Hematological, Wilson’s disease, Crohn’s disease

v)    Coitus

vi)   Exercise

vu) Incompatible ABO group matings

VII.    Idiopathic - (40 -50%)

Management —

History to be elicited m between the pregnancies - From the female partner -

Age, Menstrual history, duration of marriage contraception use, no of previous pregnancies and their outcome, gestational age at outcome Type of abortions associated with pam, post-abortal curretage, histopath confirmation of POC, karyotype of abortions Past Medical History:

 

1      Diabetes Mellitus

2      Thyroid

3      TB

4      Chronic renal disease

5      TORCH infection

Past surgical history: On genital tract Family History:

1      Chromosomal disorders

2      Congenital anomalies

3      Diabetes mellitus History of subtance abuse:

From the husband -

Age, H/o previous successful proven fertility, occupation, medical illness, testicular trauma, family H/o

-    Chronic disease

♦      Oligo/Polyspermia

♦      Substance abuse

♦      H/o consanguinity Historj during Pregnancy:

LMP. precious cycles, use of oral contraceptive, use of ovulation inducing agents Bleeding/pain/pelvic pressure On examination:

♦      Mental status

♦      General examination

♦      Vital signs

♦      Stigma of endocrmal / systemic disease

♦      Systemic examination P/S ♦ Cervix / vaginal infection

♦      Condition of ext OS

P/V ♦ Uterus ♦ size, shape, mobility, tenderness

♦      any anomalies

♦      adenexa

♦      cervical mcompitence/tears

Investigations:

1.     Genetic:

♦      Parental peripheral blood karyotyping with banding techniques

♦      Karyotyping of abortus/amniotic fluid/amnion/ placenta

2.     Antiphospholipid antibody svndrome-

♦      Plateletcount, B T C T

♦     To detect LA

-        Activated partial thromboplstm time (APTT)

-        Kaolin clotting time (KCT)

-        Dilute Russel viper λ enom time * (d RVVT)

-       Tissue thromboplastin inhibition time (TTIT)

To detect ACA

-       A standerdised ELISA is used for both IgG & IgM classes of ACA

3.     Luteal Phase Defect

♦      Fndometrial biopsy - Ideally 10 days after LH surge In out of phase biopsies - Scram androgen & prolactin

profile

♦ Serum progestron assay - Sum of three values obtained

3   days apart between 4 & 11 days before the next expected menses Value < 15ngm /ml is significant

4.     Hypothyrodism-

♦      TFT including T3, T4 & TSH

♦      Detection of antithyroid antibody

5.     Diabetes -

♦      Blood sugar profile

♦      Glycosylated Hb estimation

6.     PCOS-

♦      Estimation of LH, FSH LH

♦      USG - Most sensitive

♦      Laparoscopy

7.     Infections -

♦      Complete hemogram

♦      TORCH titre

♦      ELISA

♦      Cervical swab culture

8.     Uterine Anomalies-

♦      Clinical examination

♦      HSG

♦      Laproscopy

9.     Cervical incompitence-

♦      Interconceptional period -

-       Eaxy passage of No 8 Hegar’s dilator

-        Premenstrual hystro - cervicography

♦      During pregnancy-

-        P/V examination

-        On USG cervical length < 2 5 cm

-                Diamter of mt os > 23 mm 10 Endometnosis-

♦      USG                             ♦ Laproscopy

Treatment

1.     Genetic

♦     No specific therapy

♦      Genetic counselling

♦      Donor sperm/Donor eggs

♦      Gene treapy

♦      The couple may opt Or adoption

2.    Anatomic abnormalities—

♦      Uterine septum - Transcervical lysis

♦      Broad uterine septum - Modified Jone's mctroplasty

♦     Tompkin’s mctroplasty

♦      Bicornuate & didelphic uterus - Strassman’s metroplasty

♦      Intrauterine adhesions - hystroscopic resection

♦      Submucous fibroids - myomectomy

♦      Cervical mcompitence - interval tracheloraphj

♦      during pregnancy - Macdonald’s stitch

♦      Shirodkar’s stitch

♦      Endometriosis -