RECURRENT PREGNANCY LOSS Osama M Warda MD

Professor of Obstetrics & Gynecology

Mansoura University- EGYPT

BACKGROUND

! Pregnancy loss is a common phenomenon ! About 12-15 % of clinically recognized

pregnancies result in miscarriage: - Clinically recognized + unrecognized are 2-4

times higher. - True loss rate is 30-60% ! The risk of PL increases with the number of

previous losses, but very gradually ( ≤ 30%) ! PL increases with maternal age:

Age < 30 (7-15%) Age 35-39 (17-28%)

Age 30-34 (8-21%) Age > (34-52%)

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INCIDENCE

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RECURRENT PREGNANCY LOSS

! Defined as ≥ 3 losses prior to 20 weeks ! Ectopic, molar, and biochemical pregnancies are not

included. ! RPL affects about 2% of women in reproductive age. ! Very heterogeneous disorder (no fixed pattern). ! The etiology can be reached in about ⅔ of couples

after thorough investigations. ! RPL causes fear and anxiety in couples seeking

parenthood

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RECURRENCE RISK

! Risk of recurrence of PL depends on:

1.  Maternal age 2.  Cause of pregnancy loss 3.  Number of previous miscarriages 4.  Number of previous term deliveries

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RECURRENCE RISK

Number of prior miscarriage

% of risk of miscarriage in next pregnancy

Women with ≥ 1 live born infant

0 12%

1 24%

2 26%

3 32%

6 53%

Women with no live born infants

≥2 40-45% 6

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Risk of recurrent early pregnancy loss in young women

ROLE OF TVS IN PREDICTING MISCARRIAGE

! Appearance of fetal heart tone (FHT) on TVS decreases global miscarriage risk from 12-15% to 3-5%.

! However, in patients with past history of RPL, the miscarriage rate after embryonic heart activity is still 3-5 times higher (15-25%) than those with no such history .

! The prognostic value of FHT declines with increasing maternal age.

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ETIOLOGY OF RPL

1-Genetic : - chromosomal abnormalities in embryo

(structural or numerical) - parental chromosomal abnormalities 2- Anatomic: - congenital uterine malformation - leiomyoma : submucous - intrauterine adhesions 3- Immunologic: -  Autoimmune : SLE, APLA -  Alloimmune: abnormal maternal response to

fetal or placental antigens. 8

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ETIOLOGY OF RPL (CONT.,) 4- Endocrine: - Thyroid disease - Diabetes mellitus - PCOS - LPD 5-Inherited thrombophilias: Type II: over-activity of coagulation factors (most common): -  Factor V leiden mutation -  Prothrombin G20210A mutation Type I: deficiency of natural anticoagulants: -  anti-thrombin III deficiency - Protein C deficiency -  Protein S deficiency - Factor XIII mutation -  Familial dysfibrinogenemia 6- Infectious 7- Environmental: Smoking, alcohol, heavy coffee consumption 8- Unexplained 9

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INVESTIGATIONS OF COUPLES WITH RPL: (RCOG GUIDELINES)

1.  Women with RPL should be looked after by a health professional with the necessary skills & expertise. Where available, this might be within a RPL center. (✓)

2.  All women with recurrent first-trimester and one or more second trimester miscarriage should be screened before pregnancy for antiphospholipid antibodies. (D)

3.  Cytogenetic analysis should be performed on products of conception of the 3rd and subsequent consecutive miscarriages. (D)

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INVESTIGATIONS OF COUPLES WITH RPL: (RCOG GUIDELINES)

4.  Parental peripheral blood karyotyping of both partners should be performed in couples with RPL where testing of POC reports an unbalanced structural chromosomal abnormality. (D)

5.  All women with recurrent first-trimester miscarriage and all women with one or more second- trimester miscarriage should have a pelvic ultrasound to assess uterine anatomy. (✔)

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INVESTIGATIONS OF COUPLES WITH RPL: (RCOG GUIDELINES)

6.  Suspected uterine anomalies may require further investigations to confirm the diagnosis, using hysteroscopy, laparoscopy, or 3-D pelvic ultrasound. (✔)

7.  Women with second- trimester miscarriage should be screened for inherited thrombophilias including factor V Leiden, factor II (prothrombin) gene mutation and protein S. (D)

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TREATMENT OPTIONS FOR RECURRENT MISCARRIAGE: (RCOG GUIDELINES)

1.  Women with recurrent miscarriage should be offered referral to a specialist clinic. (✔)

Antiphospholipid syndrome:

2.  Pregnant women with antiphospholipid syndrome should be considered for treatment with low-dose aspirin plus heparin to prevent further miscarriage. (B)

3.  Neither corticosteroid nor intravenous immunoglobulin therapy improve the live birth rate of women with recurrent miscarriage associated with antiphospholipid antibodies compared with other treatment modalities; their use may provoke significant maternal and fetal morbidity. (A)

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TREATMENT OPTIONS FOR RECURRENT MISCARRIAGE: (RCOG GUIDELINES)

Genetic factors: 4.  The finding of an abnormal parental karyotype

should prompt referral to a clinical geneticist. (D)

5.  Pre-implantation genetic screening with IVF treatment in women with unexplained recurrent miscarriage does not improve live birth rates. (C)

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TREATMENT OPTIONS FOR RECURRENT MISCARRIAGE: (RCOG GUIDELINES)

Anatomical factors: 6.  There is insufficient evidence to assess the effect

uterine septum resection in women with recurrent miscarriage and uterine septum to prevent further miscarriage. (C)

7.  Cervical cerclage is associated with potential hazards related to the surgery and the risk of simulating uterine contractions and hence should be considered only in women who are likely to benefit. (A)

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TREATMENT OPTIONS FOR RECURRENT MISCARRIAGE: (RCOG GUIDELINES)

Anatomical factors: 8.  Women with a history of 2nd trimester

miscarriage and suspected cervical weakness who have not undergone a history-indicated cerclage may be offered serial cervical sonographic surveillance. (B)

9.  In women with a singleton pregnancy and a history of one 2nd trimester miscarriage attributable to cervical factors, an ultrasound-indicated cerclage should be offered if a cervical length ≤ 25mm is detected by TVS before 24 weeks gestation. (B) 16

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TREATMENT OPTIONS FOR RECURRENT MISCARRIAGE: (RCOG GUIDELINES)

Endocrine factors; 10. There is insufficient evidence to evaluate the

effect of progesterone supplementation in pregnancy to prevent a miscarriage in women with recurrent miscarriage. (B)

11. There is insufficient evidence to evaluate the effect of HCG supplementation in pregnancy to prevent a miscarriage in women with recurrent miscarriage. (B)

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TREATMENT OPTIONS FOR RECURRENT MISCARRIAGE: (RCOG GUIDELINES)

Endocrine factors: 9.  Suppression of high LH levels among ovulatory

women with recurrent miscarriage and PCO does not improve the live birth rate. (A)

10. There is insufficient evidence to evaluate the effect of metformin supplementation in pregnancy to prevent a miscarriage in women with recurrent miscarriage. (C)

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TREATMENT OPTIONS FOR RECURRENT MISCARRIAGE: (RCOG GUIDELINES)

Immunotherapy:

11. Paternal cell immunization, third-party donor leucocytes, trophoblast membranes & intravenous immunoglobulin in women with previous unexplained recurrent miscarriage does not improve the live birth rate. (A)

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TREATMENT OPTIONS FOR RECURRENT MISCARRIAGE: (RCOG GUIDELINES)

Inherited thrombophilia: 12. There is insufficient evidence to evaluate the

effect of heparin in pregnancy to prevent a miscarriage in women with recurrent 1st trimester miscarriage associated with inherited thrombophilia. (C)

13. Heparin therapy during pregnancy may improve the live birth rate of women with 2nd trimester miscarriage associated with inherited thrombophilia. (A)

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TREATMENT OPTIONS FOR RECURRENT MISCARRIAGE: (RCOG GUIDELINES)

Unexplained RPL:

14. Women with unexplained RPL have an excellent prognosis for future pregnancy outcome without pharmacological intervention if offered supportive care alone in setting of a dedicated early pregnancy assessment unit. (B)

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MANAGEMENT OF RPL SUMMARY

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THANK YOU

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