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Dr. Suvarchala Pratap (Obstetrics & Gynecology) needs a second opinion on this medical case.
THE INVESTIGATION AND TREATMENT OF COUPLES WITH RECURRENT PREGNANCY LOSS. Recurrent pregnancy loss /Recurrent reproductive loss is defined as the loss of three or more consecutive pregnancies. RISK FACTORS. 1)GENETIC FACTORS. PARENTAL CHROMOSOMAL REARRANGEMENTS. In 2-5 % of couples with RPL ,one of the partner carries a balanced chromosomal anomaly. most commonly a balanced reciprocal or robertsonian translocation.These couples are at increased risk of Miscarriage. Live birth with multiple congenital malformation. Mental disability due to unbalanced chromosomal arrangement. EMBRYONIC CHROMOSOMAL ABNORMALITIES. In couples with RPL,chromosomal abnormalities of the embryo account for 30 -60 %of further miscarriages. 2)STRUCTURAL UTERINE MALFORMATIONS. SEPTATE UTERUS. UNICORNUATE UTERUS. BICORNUATE UTERUS. Septate uterus ,unicornuate uterus ,bicornuate uterus are associated with spontaneous abortions mostly in the second trimester. CERVICAL INCOMPETANCE :diagnosis is based on history of second trimester miscarriage preceded by spontaneous rupture of membranes or painless cervical dilatation. 3)ENDOCRINE FACTORS. POORLY CONTROLLED DM. THYROID DYSFUNCTION. PCOS Well controlled diabetes and treated thyroid dysfunction do not increase the risk of abortion . Women with diabetes who have high HbA1C levels in the first trimester are associated with miscarriages and malformations. PCOS :Insulin resistance ,hyperinsulinemia and hyperandrogenaemia lead to increased risk of miscarriage in PCOS. An elevated free androgen index appears to be a prognostic factor for a subsequent miscarriage in women with recurrent miscarriage. 4)ANTI PHOSPHOLIPID ANTIBODY SYNDROME APLA is the most important treatable cause of RPL. APLA refers to association between anti phospho lipid antibodies LAC lupus anti coagulant, ACA anti cardiolipin antibodies . Anti -B2 glycoprotein -1 antibodies and adverse pregnancy outcome Three or more consecutive miscarriages <<10 weeks. One or more morphologically normal fetal losses after 10 weeks. One or more preterm births <<<34 weeks owing to placental disease. Mechanisms by which APLA causes RPL are *Inhibition of trophoblastic function and differentiation *Activation of complement pathways at maternal -fetal interface resulting in a local inflammatory response. *Thrombosis of utero placental vasculature. The effect of APLA on trophoblast function and complement activation is reversed by heparin. 5)IMMUNOLOGICAL FACTORS No clear evidence. just hypothetical. Natural killer cells are found in peripheral blood and uterine mucosa.Peripheral blood NK cells are phenotypically and morphologically different from uterine NK ceels (uNK cells ) uNK cells play a role in Trophoblast invasion. Angiogenesis. Important component of local maternal immune response to patjogens. This remains a research field and testing for peripheral blood NK cells or uNK cells SHOULD NOT BE OFFERED routinely in the investigation of RPL. Cytokines are immune molecules that control both immune and other cells.cytokine resposes are generally characterised as T -helper -1 cells (Th-1 ) produces pro inflammatory Cytokines. They are Interleukin 2 . Interferon. Tumour necrosis factor alpha (TNF ) T-helper -2 cells (Th-2 ) produces anti inflammatory cytokines .They are Interleukin 4 Interleukin 6 Interleukin 10. Normal pregnancy is the result of predominantly Th-2 cytokine response. Women with RPL have more of Th -1 cytokine response. Routine cytokine tests are NOT RECOMMENDED. 6)INFECTIONS. Any severe infection that leads to bacteremia or viraemia can cause sporadic miscarriage. The role of infection in RPL is unclear. For an infective agent to cause RPL ,it must be Capable of persistence in the genital tract and avoiding detection. Must cause insufficient symptoms to disturb the women. Toxoplasmosis .cytomegalovirus ,rubella ,herpes and Listeria infections do not fulfill these criteria and ROUTINE TORCH SCREENING SHOULD BE ABANDONED. 7)INHERITED THROMBOPHILIC DEFECTS. Inherited thrombophilias have been implicated as a possible cause of RPL 8)EPIDEMIOLOGICAL FACTORS. Advanced maternal and paternal age are risk factors for RPL. Maternal cigarette smoking and heavy alcohol consumption also increases the risk of miscarriage. INVESTIGATIONS. 1) APLA -to check for LAC and ACA.To diagnose APLA , it is mandatory that the women has TWO POSITIVE TESTS 12 weeks apart for LAC and ACA antibodies of immunoglobulin G and immunoglobulin M with titres >>>40 g/L. 2) CYTOGENETIC ANALYSIS. Cytogenetic analysis should be performed on products of conception. When testing of products of conception reports an unbalanced structural chromosomal abnormality, PARENTAL PERIPHERAL BLOOD KARYOTYPING OF BOTH PARTNERS should be performed in couples with RPL. ROUTINE KARYOTYPING OF COUPLES WITH RPL CANNOT BE JUSTIFIED. SELECTIVE PARENTAL KARYOTYPING MAY BE MORE APPROPRIATE WHEN AN UNBALANCED CHROMOSOMAL ABNORMALITY IS IDENTIFIED IN POC (PRODUCTS OF CONCEPTION ) 3) FOR UTERINE ANOMALIES. Two dimensional ultrasound and HSG are used as initial screening tests. Combined hysteroscopy and laparoscopy and three dimensional ultrasound are used for definitive diagnosis. 4)INHERITED THROMBOPHILIAS. Factor V Leiden , Factor II (prothrombin )gene mutation. Protein S deficiency. TREATMENT OPTIONS. 1) Low dose aspirin and low molecular heparin in APLA. NEITHER CORTICOSTEROIDS OR INTRAVENOUS IMMUNOGLOBULIN THERAPY IMPROVE THE LIVE BIRTH RATE IN WOMEN WITH RPL ASSOCIATED WITH APLA.THEIR USE MAY PROVOKE SIGNIFICANT MATERNAL AND FETAL MORBIDITY. 2)Abnormal parental karyotype.offer Genetic counseling. Pre implantation genetic diagnosis. 3)Transcervical hysteroscopic resection of uterine septum. THERE IS NO CONCLUSIVE EVIDENCE THAT PROPHYLACTIC CERCLAGE REDUCES THE RISK OF PREGNANCY LOSS AND PRETERM DELIVERY IN THOSE WITH CERVICAL FACTORS. In women with RPL and short cervical length <<<2.5 cms on transvaginal ultrasound ,cerclage is beneficial. Transabdominal cerclage is advocated i selected women with Previous failed transvaginal cerclage. Very short and scarred cervix. 5)THERE IS INSUFFICIENT EVIDENCE TO EVALUATE THE EFFECT OF PROGESTERONE SUPPLEMENTATION DURING PREGNANCY IN WOMEN WITH RPL. THERE IS INSUFFICIENT EVIDENCE TO EVALUATE THE EFFECT OF HUMAN CHORIONIC GONADOTROPHIN.
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