WRITE UPS - RECURRENT PREGNANCY LOSS - Recent trends in the management of recurrent pregnancy wastage


Recurrent miscarriage is traditionally defined as three or more consecutive losses of pregnancy. This distressing problem affects approximately 1% of all women. By contrast, sporadic miscarriage affects 25% of all women who conceive a pregnancy. As such, sporadic pregnancy loss is the commonest complication of pregnancy and it is important to recognize that the causes of sporadic and recurrent miscarriage are diverse.


Chromosomal abnormalities of the embryo are the most common cause of sporadic miscarriage. In women with a history of recurrent miscarriage, chromosomal abnormalities of the embryo occur much less frequently3. There is a tendency for successive abortuses to be karyotypically normal or karyotypically abnormal 4,5 suggesting that some couples are at a risk of recurrent aneuploidy. However, the risk of a subsequent miscarriage is higher when the index loss has a normal karyotype 5.

Structural anomaly is seen in 3% of cytogenetically abnormal conceptuses. The commonest type of structural chromosomal anomaly is Robertsonian translocation. Structural chromosomal anomalies are higher in couples with history of RSA as well as past history of birth of anomalous or stillborn infants. Recurrent aneuploidy & Recurrent Pregnancy Loss:

Chromosomal anomalies of the embryo are the most common cause of early pregnancy loss. Couples in whom one or other partner carries a chromosomal rearrangement are at risk of RPL with loss of conceptus with an abnormal karyotype. An increased number of chromosome breaks and eccentric fragments and pericentric inversions are seen in recurrent abortion group.


Congenital anomalies of the uterus have been cited repeatedly as an important cause of recurrent miscarriage, both in the midtrimester and in early pregnancy. In order to cause early pregnancy loss, the embryo supposedly implants in an avascular part of the endometrium, such as a uterine septum, leading to arrested development and early pregnancy failure.

The prevalence of uterine anomalies in women with recurrent miscarriage has been reported to be in the region of 10% 6,10.

The optimal treatment for uterine anomalies is still a matter of debate. Open surgical correction of congenital anomalies has been reported to give successful subsequent pregnancy outcome. However the value of treatment of these conditions in recurrent pregnancy loss is unclear. Majority of studies of RPL on uterine anomalies are without control, comparing miscarriage rates before and after treatment in the same woman can give flawed interpretation of results..

CERVICAL INCOMPETENCE: Cervical Incompetence is one acquired cause of recurrent pregnancy loss that is well-described 14. Incidence of cervical incompetence was put upto 0.5 % to 1% of all pregnancies 18. Cervical incompetence as a cause of mid-trimester miscarriage has been well described. Cervical cerclage is not associated with significant difference in the fetal survival rate between the cerclage and control groups. In addition, cerclage is associated with increased obstetrics intervention and an increased incidence of puerperal pyrexia.

Several avenues have been explored in an effort to arrive at successful treatment of cervical incompetence. By far the most effort has been expended on surgical approaches to cervical incompetence, and this is at present, the mainstay of treatment.


Many infections of the genital tract have been reported to be associated with sporadic pregnancy loss. Bacterial vaginosis, a polymicrobial anaerobic infection, has been implicated in the etiology of preterm labour 26-28, but its role in recurrent pregnancy loss is doubtful. Maternal infection with Toxoplasma gondii, cytomegalovirus, rubella and herpes [TORCH] can cause sporadic pregnancy loss but evidence that these organisms are associated with recurrent miscarriage is lacking.


Hyper secretion of luteinizing hormone: Miscarriage rate was significantly higher in patients with high LH levels than in those with normal LH levels. In contrast to the normal population, who have a reported prevalence of PCO of 22% 36, the prevalence of PCO in women with a history of recurrent early pregnancy loss was found to be 82% 37 and in infertile women attending for in vitro fertilization (IVF) the prevalence of PCO is as high as 50% 38.


Autoimmune disease: The association between raised circulating Antiphospholipid antibodies (APAs) and recurrent pregnancy failure is now well established. Recurrent spontaneous missed abortions, IUGR, recurrent stillbirths, accidental hemorrhage and thromboembolism are some diverse conditions that have this as its etiological factor. The primary Antiphospholipid syndrome recurrent pregnancy loss, arterial and venous thrombosis or thrombocytopenia in the absence of over autoimmune disease, is now well documented. Diagnosis is also helped by asking a history of allied complications of APA like RSA of missed type, recurrent stillbirths 46, recurrent IUGR, etc. The standard classification used for classifying APA cases is: Negative ® < 10 GPL units , Low positive ®10-20 GPL units , Mod. Positive ®20-100 GPL units, Strong positive ®> 100 GPL units. TREATMENT: Nearly 18 different protocols have been tried over the period of years for the treatment of APA syndrome. But the main stay is Heparin, Low dose Aspirin and corticosteroids. We use the following protocol 51: In interval period:
® For low and moderate positive, Aspirin in a dose of 1.2 mg/kg./day for three months – Allow a conception – Restart aspirin in the same dose upto 36 weeks.
® For High positive, Prednisolone in a dose of 10 mgms. /day for 3 months in the interval period; Allow conception- start aspirin from 12 weeks upto 36 weeks
In Pregnancy: For these cases we give only the post-conception protocol of aspirin specified above.

However, we now use aspirin and heparin combination in refractory subjects and in subjects who test positive for both ACA and LAC. Heparin is used in prophylactic doses in the interval period of 1000 i.u. and later as soon as pregnancy is diagnosed we give 5000 i.u of heparin daily till 36 weeks of pregnancy. This combination of aspirin and heparin gives the best results.

Alloimmune causes: It has been suggested that a necessary prerequisite for successful pregnancy involves maternal recognition of the embryo, leading to a protective immune response. Further a failure to mount the appropriate maternal immune response will lead to recurrent pregnancy loss. Based on this hypothesis, immunization treatment for recurrent early miscarriage was developed the female partner is immunized with paternal third-party or fetal material in order to potentiate the maternal immune response. The most common method of treatment utilized is paternal leukocyte immunization. That an increased degree of human leukocyte antigen sharing between the parents could be responsible for the lack of maternal immune recognition is now strongly disputed52, 53 and most workers have now abandoned human leukocyte antigen typing for couples suffering from recurrent miscarriage. Only one randomized controlled trial of immune therapy has shown benefit following treatment 54. More recent randomized trials have failed to confirm this finding 55,56, 57 - a striking feature being the success rate in the control group of these studies. This treatment must therefore be considered of no proven benefit.


The management of recurrent miscarriage can be confusing and frustrating for both the women and her doctor, frequently hindered by the bias of the investigating clinician and the uncontrolled reports found in the literature. Using systematic approach to screening, it is possible to identify a probable cause for the repeated pregnancy losses in over 50% of couples attending a specialized recurrent miscarriage clinic. The importance of randomized controlled trials of new treatments for women with recurrent miscarriage in the future cannot be overstated.



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