Recurrent Abortion

Mullerian fusion defects REF: William’s 22′ ed chapter 9

Abnormal Mullerian duct formation or fusion defects may develop spontaneously or may follow in utero exposure to diethylstilbestrol is the commonest cause of uterine factors leading to recurrent spontaneous abortions.

Laparoscopic myomectomy is  best treatment for  such  young infertile patients, but  it  requires subserosal pedunculated fibroids and surgical expertise.

Hysterectomy is advisable in patients who had completed their family.

Myolysis is myoma coagulation with laparoscopic lasers. (Nd- YAG) or bipolar needle & used in perimenopausal patients.

UAE is newer intervention for fibroid management in surgically unfit high risk patients, but it causes decreased fertility & carries risk of placental insufficiency and uterus rupture in subsequent pregnancy.

Lupus anticoagulant [Dutta 6^th/e p 169, 343, 636, Fernando Aries 2nd/e p 61]

• They have asked about antiphospholipid antibody syndrome.
• Antiphospholipid antibodies account for 3% to 5% of patients with repetitive pregnancy losses.
• The frequency of fetal death and recurrent abortion in untreated patients with antiphospholipid antibodies is greater than 90%.
• There are several antiphospholipid antibodies. The most relevant to obstetricians are:

– The lupus anticoagulant (LAC),

– The anticardiolipin antibody and

– The antibody that cause false positive syphilis test (BFP-ST).

• The name lupus anticoagulant was derived from the fact that this antibody was found first in patients with systemic lupus erythematosus and acted as an anticoagulant by prolonging the partial thromboplastin time (PTT).
• This name was a poor choice because soon it was found that lupus anticoagulant was present in many patients who did not have lupus and that in majority of patients the antibody was responsible for episodes of thrombosis, rather than anticoagulation.
• In the laboratory, LAC is not measured directly.

– It is assessed by its effect on PTT and the kaolin clotting time.

– Typically patients with lupus anticoagulant have a prolonged PTT and a normal PT.

– Unfortunately, a normal PTT does not exclude the possibility of LAC, and if the clinical suspicion is strong

and the PIT is normal a kaolin clotting time or a dilute Russel viper venom time should be performed.

– It has also been found that some patients with LAC and recurrent abortions have elevated values of serum

1gM.

Other antiphospholipid antibodies

The anticardiolipin antibody is the antiphospholipid antibody, most commonly found in patients with repetitive early pregnancy losses.

Anlicardiolipin antibody is found in 90% of patients with L.A.C. but the majority of patients with positive anticardiolipin antibody do not have L.A.C.

– Anticardiolipin antibody is measured in the laboratory by the ELISA test.

BFP-ST

– It is the less common antiphospholipid antibody.

– Both BFP-ST and Anticardiolipin antibody, measure the antibody against cardiolipin but they are not the same.

Clinical features of antiphospholipid antibodies.

• The presence of any or several of the three antiphospholipid antibodies is associated with

–  Recurrent early pregnancy losses.

– Episodes of venous and arterial thrombosis

– Severe preeclampsia

– Chorea gravidarum

– Pilo ischemic strokes, transient ischemic episodes, migraine headaches.

– Postpartum complications such as pulmonary infiltrates, fever, and cardiac symptoms.

Abortions in antiphospholipid antibody syndrome

– Typically these patients give a history of a live fetus documented by ultrasound or by Doppler before demise or abortion occurs.

The majority of the pregnancy losses occur between 14 and 18 weeks.

Fetal death is these patients is caused by extensive thrombosis of the placental vessels and the placenta is usually smaller than expected for the gestational age.

Ans. is d i.e. All are correct

Characteristics of autosomal recessive disorders

Autosomal recessive inheritance is the single largest category of Mendelian disorders.

They have following features :

• The trait does not usually affect the parents but siblings may show the disease (Option “c” is correct).
• Siblings have one chance in four of being affected (i.e. recurrence risk is 25% for each birth).
• Cor,Inguineoo. ,;c1r.rojc^: may :./c:                 tjaue• ₍option a is correct).
• The expression of the defect tends to be more uniform than in autosomal dominant disorders.
• Complete nPnotranre ^is rnnimon (Option “b is correct).
• Onset is frequently early in life.

In the question the lady has recurrent abortions and H/o autosomal recessive disorder in the family, therefore all features of autosomal recessive disorders .1pply to her

Ans. is a i.e. Chromosomal abnormalities

Historically. recurrent pregnancy loss or “habitual abortion” was defined as 3 or more consecutive s^pontaneous miscarriages.

Today, recurrent pregnancy is usually defined as 3 or more pregnancy losses (not necessarily cnnc,ecr_itive).

Most obstetricians also consider clinical investigation and treatment should be considered in couples with ,„,ntaneo— miscarriages, especially when any of the following are present :

• Embryonic heart activity observed before any earlier pregnancy loss.
• Normal karyotype of products on conception from an earlier loss.
• Female partner age over 35 years.
• Infertility.

cause r^f recurrent abortions

1st trimester • Genetic factor / defective germplasm.

• Most common type of chromosomal abnormality is balanced translocation.

2nd trimester • Cervical incompetence

Ans. is a and c i.e. TORCH infection; and Herpes infection

Remember all causes of abortions given earlier in the chapter for spontaenous abortions hold good for recurrent abortions also except for infections be it — TORCH infections or any other infection.

According to Williams Gynae lie, p 149

Few infections are firmly associated with early pregnancy loss. Moreover, if any of those infections are associ­ated with miscarriage, they are even less likely to cause recurrent miscarriage because maternal antibodies usually develop with primary infection.

Leon Speroff says :

“Overall, data , L9arding the possibility that cervicovaginal infections might be a cause of early preg­nancy loss are relatively scarce. Despite periodic reports that have implicated specific infectious agents as risk factors for miscarriages, there remains no compelling evidence that bacterial or viral infections are a cause of recurrent pregnancy loss.”

It further says on Gage 1091

“Routine serological tests, cervical cultures and endometrial biopsy to detect genital infections in women with recurrent pregnancy loss can not be justified. Evaluation should be limited to women with clinical cervicitis, chronic or recurrent bacterial vaginosis or other symptoms of pelvic infection.”

Ans. is a i.e TORCH infection

As discussed in previous question TORCH infection do not lead to recurrent abortion.

SLE is an established cause for recurrent abortion

SLE is associated with antiphospholipid syndrome (anti-cardiolipin antibodies) and is known to cause recurrent abortions.

RH incompatibility is a known cause for spontaneous abortion and may lead to recurrent abortions if it remains unrecognized.

Syphillis also does not lead to recurrent abortions but if you have to choose between TORCH infection and syphillis go for TORCH infection.

Ans. is a i.e. Lupus anticoagulant

Lupus anticoagulant (LAC)

—   It was named so because it was first found in patients with SLE & prolonged partial thrombo­plastin time

—   But the name is a misomer as though it increases PTT (i.e., similar to anticoagulant) but functions as a procoagulant & causes thrombosis

Anticardiolipin antibody

–      It is most commonly seen in patients with repetitive early pregnancy loss

BFP – ST

i.e. antibody which causes biologically false positive syphilis test

— Less common antiphospho­lipid antibody

–    Both anticardio lipin & BFP­ST antibodies measure the antibody against cardiotipin but they are not same.

Diagnosis For diagnosis of antiphospholipid antibody syndrome there should be two positive tests 6 weeks apart for lupus anticoagulant or anticardiolipin antibody.

M^qr^pclerrient 7 Treatment as proposed by ACOG is a combination of low dose aspirin (81 mg) daily and low molecular weight heparin (LMWH) in prophylactic doses (e.g. dalteparin 5000 units S/C twice daily), started as soon as pregnancy is confirmed. Aspirin can be initiated preconceptionaly and is usually discontinued at 36 weeks. LMWH is continued up to term and for 5 days postpartum.

Women with previous history of thrombosis will usually already be on maintenance therapy with warfarin. In such cases as soon as pregnancy is confirmed, warfarin is changed to LMWH and aspirin.

Although this treatment improves overall pregnancy success, these women remain at high risk for preterm labor, PROM. IUGR. preeclampsia and placental abruption.

In question 10 Patient is presenting with recurrent abortions with isolated increase in APTT which leaves no doubt that lupus anticoagulant is the cause.

Ans. is a i.e. Karyotyping

Ans. is c i.e. Testing for TORCH infections.

• Chromosomal abnormality is the commonest cause for  fire,t trimpstpr
• In 3-5% of couples with recurrent miscarriage, one of the partners will have a chromosomal anomaly.
• is a balanced translocation of the chromosomes, more likely in the mother. In such cases, the genetic information is intact and so there is no problem for the parents. But this can lead to an unbalanced translocation in the conceptus, causing an early miscarriage.

Hence karyotyping of the both partners is recommended in recurrent miscarriage. Prenatal diagnosis is usually advised in the next pregnancy.

As discussed earlier infections be it HIV / TORCH are not a cause of recurrent abortion and SLE i.e. Lupus anticoagulant causes abortion in 14-18 weeks and not in 1st trimester: Therefor Ans of Q 13 is karyotyping.

Because TORCH infections are not a cause of recurrent abortionf‑

TORCH profile should not be included in the set of investigations done to find out the cause of recurrent abortion (Ans. 14).

Investigative measures useful in the evaluation of recurrent early pregnancy loss :

• Parental peripheral blood karyotyping with banding technique.
• Assessment of the intrauterine cavity with either office i’_.oloiusGOp or hysterosalpingography.
• 1;:, serum prolactin levels if indicated.
• Anticardiolipin antibody                                                                 (aPTT or Russell Viper venom testing).
• Complete blood counts with platelet count.
• Thrombophilia testing :

–    Factor V leiden, prothrombin p^onr    PrrifPirt

–      Serum homocvsteine level.

–      In the presence of a family or personal history of venous thromboembolism. protein C and antithrom­bin activity.

The American college of obstetricians and Gynaecology recognizes only 2 types of tests as having clear value in the investigation of recurrent miscarriages :

1. Parental cytogenetic analysis
2. Lupus anticoagulant and anticardiolipin antibodies assay.

SLE is associated with antiphospholipid syndrome (anti cardiolipin antibodies) and is known to cause recurrent abortions.

Recurrent miscarriage is defined as a sequence of three or more consecutive spontaneous abortion before 20 weeks.

Investigations:

1) Blood glucose (fasting and post prandial), VDRL, thyroid function test, ABO and Rh grouping (husband and wife), toxoplasma antibodies IgG&IgM

2) Autoimmune screening – lupus anticoagulant and anticardiolipin antibodies

3) Serum LH on D2/D3 of the cycle

4) Ultrasonography – to detect congenital malformations of uterus, polycystic ovaries and uterine fibroid

5) Hysterosalpingography in the secretory phase

6) Laryngoscopy

7) Karyotyping (husband and wife)

8) Endocervical swab to detect chlamydia, mycoplasma, and bacterial vaginosis

Mullerian duct anomaly is an important cause of recurrent miscarriage in early and midtrimester. Septate or arcuate uterus is the most common uterine anomaly associated with mullerian fusion defects and it is the most common defect associated with repeated pregnancy loss.

• Chromosomal abnormalities: karyotypic evaluation of both parents
• Genital tract anatomical abnormalities : three-dimensional sonography, hysteroscopy
• Autoimmune Factors like SLE: antiphospholipid antibodies
• Alloimmune Factors 
• Inherited Thrombophilias
• Endocrinological factors like progesterone deficiency, PCOS, diabetes mellitus, hypothyroidism 

Answer is B (Aspirin + Low molecular weight Heparin):

The recommended treatment for women with recurrent pregnancy loss associated with antiphospholipid syndrome includes combined Aspirin and Heparin therapy.

‘In pregnant SLE patients with Antiphospholipid antibodies and prior fetal loss, treatment with heparin (standard or low –molecular- weight) plus low dose aspirin has been shown in prospective controlled trials to increase significantly the proportion of live births’. – Harrison’s 17th/2082

‘Combined aspirin and heparin therapy has proven effectiveness and is the preferred treatment for women with recurrent pregnancy loss associated with antiphospholipid syndrome’ – Speroff 7th/1084

Antiphospholipid syndrome in pregnancy

• The risk of pregnancy loss in women with APS and prior pregnancy loss may exceed 60%
• History of recurrent fetal loss in a pregnant woman with Antiphospholipid antibodies is an indication of treatment during pregnancy as these are identifiable and treatable immunologic disorders
• Treatment options include Antiplatelet agents such as Aspirin, Anticoagulants such as Heparin / LMWH, and corticosteroids

Aspirin along with Heparin / LMWH is the recommended treatment of choice.

Corticosteroids should be avoided ifpossible. If required to control maternal SLE, these should be used at the lowest effective doses for the shortest time required.