Early Fetal Wastage “ Miscarriage” Professor Hassan Nasrat

Definitions: A miscarriage (abortion) is defined as termination of a pregnancy before 20 weeks gestation or of a fetal weight less than 500 g. The term abortion is better reserved to cases in which termination of pregnancy “TOP” is induced.

For any single patient to fall into the 15% risk of miscarriage repeatedly on three consecutive occasions is a rare event. It is estimated that recurrent miscarriage affects about 1% of all women. Recurrent early pregnancy loss “Recurrent miscarriage”: Patients who experience recurrent miscarriage, defined as the loss of three or more consecutive pregnancies.

Causes of fetal wastage and miscarriage

Frequency of chromosomal abnormalities among miscarriages and fetal loss - In 1 st trimester: 70%. - In 2 nd trimester: 30-40% (mostly of the types observed in live born infants: trisomies 13, 18, and 21; monosomy X; and sex chromosome polysomies). - In 3 rd trimester losses (stillborn infants) 5%, a frequency that is still higher than the rate of 0.6% in live born Genetic Causes: In very small percentage (2%-3%) one of the parents may be carrier for balanced structural chromosomal rearrangement (balanced translocation or balanced chromosomal inversion), which results in abnormal gametes and embryo.

Endocrine factors: o Luteal phase deficiency (LPD): Diagnosis: the diagnostic of LPD is made if the histological secretory change in a luteal phase endometrial biopsy is lagging more than two days behind the normal expected changes following ovulation. o Polycystic ovarian syndrome “PCO”: o Thyroid Disorder: o Diabetes Mellitus:

Uterine Anatomical Factors Acquired uterine factors include:  Intrauterine Adhesions “Ashermans Syndrome”:  Uterine Leiomyomas:

O CONGENITAL UTERINE ANOMALIES: INCOMPLETE MÜLLERIAN TUBES FUSION IN UTERO EXPOSURE TO DIETHYLSTILBESTROL CERVICAL INCOMPETENCE:

Müllerian fusion tubes defects are present in about 1-3% of the general population but can reach up to 40 % among women with recurrent miscarriage and pregnancy loss. This indicates that not all cases with uterine anomalies will end in miscarriage. The discovery of uterine anomalies does not necessary means that it is the cause of miscarriage. What is more important is that surgical correction of uterine anomalies should not be undertaken except after careful consideration and evaluation of other causes of fetal loss.

o Congenital Uterine anomalies: incomplete Müllerian tubes fusion in utero exposure to diethylstilbestrol

Definition: the inability of the cervix to support pregnancy until term due to a functional or structural defect Cervical Incompetence - Causes of cervical incompetence: a)Congenital disorder b)Connective tissue disorder (e.g. Ehlers-Danlos syndrome). c)Surgical trauma of the cervix (Leep conization or amputation resulting in substantial loss of connective tissue). d)Trauma due to repeated cervical dilatation associated with previous termination of pregnancy.

Cervical Incompetence - The diagnosis of cervical incompetence: Diagnosis of established cases: The diagnosis during pregnancy based on symptoms and sings is usually a late diagnosis with poor prognosis. Identify women at risk of cervical incompetence: Either before or early in their pregnancy and plan intervention before symptoms or signs of cervical incompetence develops.

Cervical Incompetence Diagnosis of established cases: Symptoms: Patient in the second trimester (17-20 weeks). increased watery dischargee, and some lower pelvic heaviness and pressure like pain. Or symptoms suggestive of PROM not preceded by pain or contractions. Sings: effaced and dilated cervix with or without herniating membrane. Investigation: In typical cases (i.e. with signs of cervical effacement and dilatation) no further tests are required. In non-typical cases measurement of cervical length using transvaginal ultrasound is currently the gold standard for diagnosis of cervical incompetence.

Cervical Incompetence - Treatment of cervical incompetence: The treatment of cervical incompetence is "surgical cerclage" that aims to strengthen the cervical competence at the level of the internal os.

Cervical Incompetence - Treatment of cervical incompetence: The treatment of cervical incompetence is "surgical cerclage" that aims to strengthen the cervical competence at the level of the internal os.

Infection - Severe affection of fetal organogenesis during early weeks of gestation (e.g. rubella virus, parvovirus B19, cytomegalovirus (CMV). - Unfavorable implantation from endometrial infection caused by secondary ascending infection (e.g. mycoplasmas and herpesvirus). - Transplacental fetal blood born infection (as in Treponema pallidum and Toxoplasma gondii) - Intra-amniotic infection following bacterial invasion of the amniotic cavity, degradation of membranes collagen and early rupture of the membranes. - Direct effect on the ovum or the fertilization process by infected spermatozoa (Ureaplasma urealyticum).

Bacteria: -Listeria monocytogenes -Chlamydia trachomatis -Ureaplasma urealyticum -Bacterial vaginosis Viruses: -Cytomegalovirus -Herpes simplex virus -Human immunodeficiency virus Parasites: -Toxoplasma gondii -Plasmodium falciparum -Spirochetes -Treponema pallidum

Immunological factors Alloimmune reactions: is an immunological reaction against foreign tissues. The growing conceptus, which in essence is a foreign “allogenic graft”, is normally tolerated by the maternal immune system. Due to formation of “blocking antibodies”. This mechanism may fail due to significant degree of similarity between the HLA of the husband and wife Autoimmune reactions: is the body immunological reaction against its own tissues. Organ specific autoantibodies: Non- specific auto-antibodies: - antiphospholipid antibodies “aPL”.

Environmental factors ❖ Cigarette smoking and Caffeine: ❖ Alcohol: ❖ Environmental Toxins and chemicals: e.g. anesthetic gases, formaldehyde, lead, and benzene.

Thrombophilia Inherited Thrombophilia Factor V Leiden mutation Prothrombin gene mutation Protein S deficiency Protein C deficiency Antithrombin (AT) Factor V Leiden mutation

Treatment of Spontaneous Miscarriage

Approach to management of patients with recurrent miscarriage History:  Detailed descriptive history of the previous miscarriages: Early miscarriage suggests fetal factors while late ones suggest uterine factors.  History suggestive of cervical incompetence  Menstrual history Physical Examination: General Examination Pelvic examination

Approach to management of patients with recurrent miscarriage (cont.) Investigations: - Peripheral blood karyotyping of both parents: - Investigations for congenital and/or acquired uterine anomalies: -Screening tests for antiphospholipid antibodies: ( The diagnosis of APS syndrome require two positive tests at least six weeks apart for either lupus anticoagulant and/or anticardiolipin antibodies of IgG and/or IgM class in medium or high titre.) - Microbiological tests: - Hormonal studies: