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    Problems of the Mother

    Hormone disorder

    Some women may miscarry due to low progesterone levels. Progesterone is a hormone produced following ovulation and is necessary in pregnancy, as it enables embryo implantation. When progesterone levels are low, it is difficult for the embryo to implant in the endometrium.
    Women with short menstrual cycles are more prone to such problems, especially if the interval between ovulation and menstruation is shorter than 12 days.
    Diagnosis in those cases is verified via a blood test (low progesterone levels one week after ovulation) and an endometrial biopsy. In that case, progesterone is administered to the patient for the last 2 weeks of her menstrual cycle.
    However, recent findings suggest that sometimes, progesterone levels are actually low because ovulation – pregnancy does not progress normally, which indicates the existence of a problem.

    Polycystic Ovary Syndrom (PCOS)

    No one knows exactly why women with PCOS miscarry more often. According to the predominant theory, in those patients, ovaries produce large amounts of luteinizing hormone (LH) and androgens. Usually, the same women also have insulin resistance.
    High LH, androgen and insulin levels impair oocyte quality, which will not be appropriate at ovulation. If one such oocyte is fertilised, there is a possibility that the embryo will not be healthy, thus will be rejected by the woman’s body after 6-8 weeks (miscarriage).
    In patients with PCOS, it is important to regulate the hormone disorder (LH, androgens, insulin), so that the oocyte is healthy at fertilisation and yields a healthy embryo.
    There are three ways to achieve this, depending on the severity of each case:
    • Weight loss and exercise
    • Medical treatment
    • Laparoscopic ovarian diathermy

    Uterine conditions

    Miscarriages due to uterine conditions are caused by the following reasons:
    • Congenital uterine anomalies, with which a woman is born, but which do not cause any problem until she gets pregnant. The most common anomalies are: diaphragm (dividing the uterine cavity), unicornate uterus (only one half of the uterus developed), bicornuate uterus (uterus consisting of two cavities due to its irregular development). It is difficult for a uterus with such anomalies to sustain a pregnancy, which leads more often to miscarriages. However, this doesn’t mean that some women with such anomalies do not have full-term and problem - free pregnancies. Moreover, it is important to stress that all the aforementioned anomalies constitute as well infertility causes (i.e. pregnancy is not achieved).
    Fibroids: benign tumours of smooth muscle tissue inside the uterus. Most fibroids do not hinder pregnancy, however if a fibroid is very close to the endometrium, it may impede embryo implantation.
    • Adhesions, consisting of fibrous tissue following a uterine trauma. Adhesions inhibit embryo implantation. They are usually formed after ablations and are detected with hysteroscopy or hysterosalpingogram. They can be removed with hysteroscopic surgery.
    • Cervical incompetency (weak, lax cervix): Under the pressure of the growing embryo, insufficient cervix opens, putting the embryo at risk. This may happen either due to a congenital anomaly or because the cervix has been injured in a previous pregnancy or miscarriage. In those cases, cervical cerclage is applied and is removed two weeks before or during labour. Cervical cerclage is a simple operation and is usually carried out after the 12th week of pregnancy, as long as the ultrasonogram shows that the embryo is healthy. At “gennima”, we examine the cervix and proceed with cerclage only if there are indications of insufficiency. Although cervical cerclage is a simple operation, it may have complications, such as infection or hemorrhage, and must not be carried out with no substantial reason. These anatomic problems are diagnosed via hysteroscopy or hysterosalpingogram.

    For that matter, please read a recent article below:
    ‘Reproductive performance of women with mullerian anomalies’ Current Opinion in Obstetrics and Gynecology: June 2007 - Volume 19 - Issue 3 - p 229-237
    http://journals.lww.com/co obgyn/Abstract/2007/06000/Reproductive_performance_of_women_with_mullerian.5.aspx

    Thrombophilias

    When a patient tends to generate clots, we say that he/ she has “thrombophilia”. Thrombophilia may put the patient’s life at risk if a clot blocks blood flow. Thrombophilia may be hereditary or caused by external factors, such as surgeries, obesity, pregnancy, the use of contraceptive pills, the antiphospholipid syndrome or a long period of immobility.
    The doctor suspects the existence of thrombophilia if the patient has clotted blood vessels at a young age or if there is a strong relevant family history, such as stroke, pulmonary embolism or thrombosis. However, some patients with thrombophilia are asymptomatic; sometimes though, they are symptomatic, but remain undiagnosed, because the clotting tendancy is not strong.
    Hereditary thrombophilia entails the existence of mutations in the genes that control the patient’s blood clotting. These genes are antithrombin III, protein S, or protein C. Mutations in these genes influence blood clotting and bring on a tendency to generate clots.
    Recent studies indicate that hereditary thrombophilia and recurrent miscarriage may be related. Genetic factors examined in that case are the mutation of factor V Leiden as well as the mutation G20210A of prothrombin (factors that regulate blood clotting). These two mutations are the most common causes of hereditary thrombophilia and can be easily detected with a blood test. Both of these mutations, as well as other ones, have been associated with recurrent miscarriage. Recent studies show that these thrombophilia indicators may be detected in patients with a history of recurrent miscarriage. Namely, based on a study, 19% of the patients with a history of miscarriage (15 out of 80) had the factor V Leiden mutation (compared to 4% of women with no history of miscarriage). Also high among women prone to miscrriage are the percentages and other indicators of thrombophilia (prothrombin mutation, energised vitamin C resistance and antithrombin deficiency). Although many researchers have stated such results, there is no doubt that this scientific field must be further investigated.
    Mutations in other genes that control blood clotting are related to recurrent miscarriage. These are factor V Leiden, prothrombin factor II, fibrinogen, factor XIII. In fact, it seems that the more mutations a patient has, the more probable it is for her to miscarry at early stages of pregnancy. Within the framework of a study, 8% of the women with a history of recurrent miscarriage had a combination of thrombophilia factors, compared to 1% of the women with no history of miscarriages.

    Besides tests for antiphospholipid antibodies, lupus erythematosus and anticardiolipin antibodies, patients with recurrent miscarriage must also be tested for the following indicators of thrombophilia:
        • Anti-Phosphatidyl Serine
        • PAI-1
    ​    • Antithrombin ΙII
        • Prothrombin II
        • Protein C activity
        • Protein S activity
        • Factor V Leiden
        • Homocysteine
        • MTHFR
        • GPIα

    If the results of even one of the above tests are not normal, this may imply an increased risk of clot formation in the placenta circulation and a possibility of pulmonary embolism of the embryo. Treatments proposed in case of thrombophilia usually include heparin or low- molecular - weight heparin and aspirin. In this way, blood circulation theoretically improves, better quality oocytes are produced and a pregnancy with the desired outcome is more probable. In all patients following a similar protocol, blood clotting must be constantly monitored.
    ​To conclude, since it has been proved that hereditary thrombophilias have significant impact on recurrent miscarriage, patients who face this problem must also be examined for blood clotting disorders, even without having any clinical symptoms. Once thrombophilia is detected, the appropriate treatment and monitoring of the patient begins.

    Important clinical notes:
        • Some of the aforementioned thrombophilias are very common.
        • Treatments proposed and applied today haven’t proved helful to all patients aiming to achieve a normal pregnancy: they are only effective in some cases.
        • Recent clinical research concerning the administration of different treatments (aspirin alone or aspirin plus heparin) to patients with unexplained recurrent miscarriage has shown that such treatments do not offer any help.

    Please read below:
    ‘Aspirin plus Heparin or Aspirin Alone in Women with Recurrent Miscarriage’ New England Journal of Medicine 2010 362:1586
    http://search.nejm.org/search?w=miscarriages%2C+aspirin%2C+heparin

        • For that reason, at “gennima”, we evaluate severe problems of thrombophilia, which must be further investigated. • It is imperative to be tested for thombophilias in case of 1-2 miscarriages after the detection of cardiac function in the embryo.

    Diseases

    The diseases of the mother that can cause recurrent miscarriage are the following:
        • Thyroiditis, especially hypothyroidism, when not medically controlled,
        • Severe heart, liver or kidney disease,
        • Lupus erythomatosus, an autoimmune disease that makes the system produce antibodies against its own tissues,
        • Undiagnosed or unregulated diabetes,
        • Endometriosis. As for the urinary system infections (e.g. mycoplasma), there is no evidence that they cause miscarriages.

    Lifestyle

    If women are systematically exposed to toxic gases or chemical substances (such as organic solvents, insecticides, fertilisers, heavy metals, e.g due to professional reasons), this may harm the embryo – which is particularly sensitive - and lead to miscarriage.
    Women who smoke, are alcoholic or drug addicts also have increased chances of miscarrying. Immunological problems.
    The main function of the immune system is to protect the organism from infections. It “rejects”, i.e. repels, invaders (viruses, bacteria) perceived as “foreing bodies”.
    In some cases, the immune system does not function properly, which leads to various health problems. Concerning reproduction, it is clear today that many miscarriages at early stages of pregnancy are caused by the irregular activity of the woman’s immune system.
    Scientific research has shown that, in a normal pregnancy, the woman’s immune system functions under “special conditions”, in order to protect the embryo and let it grow. If this mechanism doesn’t work, the embryo may fail to implant, a miscarriage may be caused or complications for the mother or the embryo may occur during pregnancy. Today, there still is no cure, however, various treatments (immunotherapy) are proposed by research centres abroad (mainly in the U.S.), aiming at restoring the “proper” function of the mother’s immune system, so as to increase possibilities of miscarrying.

    Gennima | Gynaecology & Reproduction Center

    346 Kifisias Avenue, 15233 Chalandri - Athens, Hellas
    +30 210 68 16 100
    +30 210 68 30 321 (fax)
    info[at]gennima[.]eu

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