Guideline Recurrent Pregnancy Loss - PowerPoint Presentation

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Guideline

Recurrent Pregnancy Loss

Update 2022

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DEFINITION

Pregnancy loss (miscarriage);

Spontaneous demise of a pregnancy before the fetus reaches viability(until 24 GA) “Recurrent” pregnancy loss; loss of two or more pregnancies When to start investigations? Shared decision-making by the doctor and couple Recurrent “Early” Pregnancy Loss; Loss of ≥two pregnancies before 10 weeks Primary RPL; RPL without a previous ongoing pregnancy (viable pregnancy) Secondary RPL ; An episode of RPL after one or more previous pregnancies progressing beyond 24 weeks.

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DEFINITION

We recommend the use of ‘

recurrent pregnancy loss’

to describe repeated pregnancy demise. ‘Recurrent miscarriage’ ;all pregnancy losses have been confirmed as intrauterine miscarriages. The terms spontaneous abortion, chemical pregnancy and blighted ovum are ambiguous and should be avoided

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A pregnancy is confirmed by;

Either serum or urine b-

hCG

(including non- visualized (biochemical pregnancy losses and pregnancies of unknown location). Pregnancy losses (after spontaneous conception or ART treatments) Ectopic and molar pregnancies and Implantation failure should not be included in the definition.

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WHAT ARE THE KNOWN RISK FACTORS?

AGE

Female age and number of previous losses are the only known risk factors. Based on the chance of age-dependent pregnancy loss; Couples should start trying to conceive when the female partner is 31 years of age or younger to have a chance of at least 90% to realize a family with two children. If IVF is not an option, couples should start no later than age 27 years.

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WHAT ARE THE KNOWN RISK FACTORS?

AGE

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STRESS

The studies indicate that there is an association between stress and pregnancy loss, but they provide no information on whether the stress is a result of RPL, or whether stress could be a causal factor in RPL.

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Risk factors ;

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Risk factors ;

CHRONIC ENDOMETRITIS

Chronic endometritis is characterized by a plasma cell infiltrate in the endometrium associated with a range of pathogenic organisms.Antibiotics were found to reduce the endometritis with an apparent improvement in live birth rate. This concept has not been tested in randomized controlled trials. To date, there are no studies on the predictive value of vaginal or endometrial dysbiosis in RPL. Further research is needed before screening women for endometritis.

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Screening for genetic factors

GENETIC ANALYSIS OF PREGNANCY TISSUE

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Screening for genetic factors

Parental karyotyping ; in female age ≥39, ≥3 pregnancy losses and a positive family history

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THROMBOPHILIA SCREENING

HEREDITARY THROMBOPHILIA

Factor V Leiden mutation, Prothrombin mutation, Protein C, Protein S and Antithrombine deficiency. ACQUIRED THROMBOPHILIA Acquired activated protein C resistance was associated with a higher risk of RPL in the first trimester based on two studies

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THROMBOPHILIA

SCREENING

Antiphospholipid syndrome; Persistent presence of antiphospholipid antibodies Vascular thrombosis and/or pregnancy complications Three clinically antiphospholipid Ab ; Lupus anticoagulant (LA) Anticardiolipin Ab (ACA, IgG and IgM) β2 glycoprotein I Ab (aβ2GPI, IgG and IgM)

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THROMBOPHILIA SCREENING

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Screening can be considered If RF for hereditary thrombophilia are present;

family members with hereditary thrombophilia

previous VTE

THROMBOPHILIA SCREENING

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THROMBOPHILIA SCREENING

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IMMUNOLOGICAL SCREENING

HUMAN LEUKOCYTE ANTIGEN (HLA)

Investigation

of HLA genes in all women with RPL is not recommended in clinical practice but possible in a research setting. An exception could be investigation of class II HLA in women with secondary RPL after the birth of a boy in Scandinavian women

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Investigations of NK cells in RPL can be divided into ;

Flow-

cytometric analyses or tests of NK cell cytotoxicity of peripheral blood lymphocytes before or during pregnancy Studies of NK cells in pre-pregnancy endometrial biopsies.Endometrial and peripheral blood NK cell numbers fluctuate hugely in the menstrual cycle so exact timing of samples is crucial.Previous live births seem to exhibit a long term impact on NK cell frequencies in the blood and endometrium, therefore patients and controls in future studies of NK cells should have comparable parities NATURAL KILLER CELLS

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Based on a high prevalence of subclinical hypothyroidism and thyroid auto immunity in women with RPL and potential of treatment options testing for thyroid function is recommended

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Screening for Prolactin; only in women with clinical symptoms of hyperprolactinemia(oligo/amenorrhea) SCREENING FOR METABOLIC/ENDOCRINOLOGICAL ABNORMALITIES

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Treatment of RPL with metabolic or

endocrinologic

abnormalities

Evidence showed that levothyroxine treatment does not increase the chance of a live birth in women with a history of RPL and thyroid autoimmunity (normal TSH and TPO Ab+).

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SCREENING FOR METABOLIC/ENDOCRINOLOGICAL ABNORMALITIES

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PROGESTERONE

OR HCG

(FOR LUTEAL PHASE INSUFFICIENCY )

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OVARIAN RESERVE TESTING

From the association between advanced maternal age and RPL, it is suggested that diminished ovarian reserve could be a causative or prognostic factor in RPL.

Ovarian reserve can be assessed with measurements of FSH, estrogen (E2), inhibin B, and AMH, or ultrasound investigation to determine AFC and ovarian volume

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ANATOMICAL INVESTIGATIONS IN RPL?

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ANATOMICAL INVESTIGATIONS IN RPL?

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Treatment for uterine abnormalities

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Treatment for uterine abnormalities

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MALE

FACTOR

INVESTIGATIONS IN RPL?

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Treatment for unexplained RPL

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Vaginal progesterone during early pregnancy may have beneficial effect in women with unexplained

RPL with

vaginal bleeding.

There is some evidence that oral dydrogesterone initiated when fetal heart action can be confirmed may be effective, but more trials are needed. Treatment for unexplained RPL

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