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Recurrent pregnancy loss

Recurrent pregnancy loss can be physically and emotionally tough for couples.

Recurrent pregnancy loss is historically defined as 3 consecutive pregnancy losses prior to 20 weeks from the last menstrual period. Based on the incidence of sporadic pregnancy loss, the incidence of recurrent pregnancy loss should be approximately 1 in 300 pregnancies. However, epidemiologic studies have revealed that 1% to 2% of women experience recurrent pregnancy loss. The best available data suggests that the risk of miscarriage in subsequent pregnancies is 30% after 2 losses, compared with 33% after 3 losses among patients without a history of a live birth.3 This strongly suggests a role for evaluation after just 2 losses in patients with no prior live births. An earlier evaluation may be further indicated if fetal cardiac activity was identified prior to a loss, the woman is older than 35 years, or the couple has had difficulty in conceiving.

Factors of recurrent pregnancy loss

Genetic (5%)

Endocrine(17%)

Anatomic (13%)

Autoimmune(50%)

Infections( 0,5-5%)

In 50% of women with recurrent pregnancy loss , the cause of the preceding miscarriages is unknown .

Genetic factors

Spontaneous pregnancy loss is a surprisingly common occurrence, with approximately 15% of all clinically recognized pregnancies resulting in pregnancy failure.

Approximately 2% to 4% of RPL is associated with a parental balanced structural chromosome rearrangement, most commonly balanced reciprocal or Robertsonian translocations. Additional structural abnormalities associated with RPL include chromosomal inversions, insertions, and mosaicism. Appropriate evaluation of RPL should include parental karyotyping. Genetic counseling is indicated in all cases of RPL associated with parental chromosomal abnormalities. Depending on the particular diagnosis, directed therapy may include in vitro fertilization with preimplantation genetic diagnosis.

Anatomic factors

Anatomic abnormalities account for 10% to 15% of cases of RPL. These include congenital uterine anomalies, intrauterine adhesions, and uterine fibroids or polyps. Although more readily associated with second trimester losses or preterm labor, congenital uterine anomalies also play a part in RPL. The uterine septum is the congenital uterine anomaly most closely linked to RPL, with as much as a 76% risk of spontaneous pregnancy loss among affected patients.4 Other Müllerian anomalies, including unicornuate, didelphic, and bicornuate uteri have been associated with smaller increases in the risk for RPL.4,5 The role of the arcuate uterus in causing RPL is

unclear. The presence of intrauterine adhesions, sometimes associated with Asherman syndrome, may significantly impact placentation and result in early pregnancy loss. Intramural fibroids larger than 5 cm, as well as submucosal fibroids of any size, can cause RPL.6 Although congenital anomalies caused by prenatal exposure to diethylstilbestrol are clearly linked to RPL, this is becoming less clinically relevant as most affected patients move beyond their reproductive years.

Diagnostic evaluation for uterine anatomic anomalies should include office hysteroscopy or hysterosalpingography (HSG). Hysteroscopic resection of intrauterine adhesions and intrauterine septa are indicated if these abnormalities are identified. Patients undergoing successful hysteroscopic septum resection seem to enjoy near normal pregnancy outcomes, with term delivery rates of approximately 75% and live birth rates approximating 85%.7 .

A unicornuate uterus accounts for 2.4 to 13% of all Müllerian anomalies. A unicornuate uterus with a non-communicating rudimentary horn may be associated with gynecological and obstetric complications such as infertility, endometriosis, hematometra, urinary tract anomalies, abortions, and preterm deliveries. It has a poor reproductive outcome and pregnancy management is still unclear.

The incidence of bicornuate uterus has historically been the most frequent, although, as stated before, uterine septi and arcuate uteri appear to be the most common. Surgical reconstruction for the bicornuate uterus can be considered for patients with recurrent miscarriages and no other obvious etiologies although data on improved pregnancy maintenance are limited. In general, live birth rates improve in a selected population from 2%-21% to 60%-86%. if surgical correction of a bicornuate uterus for pregnancy maintenance is elected, a Strassman metroplasty is performed.[20] This technique involves a transverse fundal incision into the separated uterine cavity and subsequent reconstruction in a layered closure of a vertical incision similar to the closure of a classic incision during a cesarean section. No data exist advocating surgical correction for infertility indications, and this is not recommended. Uterus didelphys (sometimes also uterus didelphis) represents a uterine malformation where the uterus is present as a paired organ when the embryogenetic fusion of the Müllerian ducts fails to occur. As a result there is a double uterus with two separate cervices, and often a double vagina as well. Each uterus has a single horn linked to the ipsilateral fallopian tube that faces its ovary. Patients with a double uterus may need special attention during pregnancy as premature birth and malpresentation are common. Cesarean section was performed in 82% of patients

Asherman's Syndrome

Asherman's Syndrome, or intrauterine adhesions/scarring or synechiae, is an acquired uterine condition, characterized by the formation of adhesions (scar tissue) inside the uterus and/or the cervix. Asherman's syndrome occurs when trauma to the endometrial lining triggers the normal wound-healing process, which causes the damaged areas to fuse together. Most commonly, intrauterine adhesions occur after a dilation and curettage (D&C) that was performed because of a missed or incomplete miscarriage, retained placenta with or without hemorrhage after a delivery, or elective abortion. Pregnancy-related D&Cs have been shown to account for 90% of Asherman's Syndrome cases. Sometimes adhesions also occur following other pelvic surgeries such as Cesarean section, surgery to remove fibroids or polyps, or in the developing world, as a result of infections such as genital tuberculosis(3) and schistosomiasis

Asherman's Syndrome must be treated by a very experienced surgeon via hysteroscopy (sometimes assisted by laparoscopy. Those few surgeons experienced enough in treating severe Asherman's Syndrome recommend the avoidance of energy sources inside the uterus (this means removing scars with scissors rather than with energy-generating instruments such as resectoscopes or lasers, although not all surgeons agree with this). Adhesions have a tendency to reform, especially in more severe cases. There are different methods to prevent re-scarring after surgery for Asherman´s Syndrome. Many surgeons prescribe estrogen supplementation to stimulate uterine healing and place a splint or balloon to prevent apposition of the walls during the immediate post-operative healing phase. Other surgeons recommend weekly in-office hysteroscopy after the main surgery to cut away any newly formed adhesions. As of yet, studies have not confirmed the method of treatment that is most likely to have a successful outcome, which would be one where the uterus/cervix remains scar-free and fertility is restored.In cases of mild and moderate adhesions rate of future pregnancy is 60-80 %.

Cervical insufficiency (cervical incompetence) is defined as the inability of the uterine cervix to retain a pregnancy in the second trimester, in the absence of uterine contractions.

Risk factors

* diagnosis of cervical incompetence in a previous pregnancy,

* previous preterm premature rupture of membranes, * history of conization (cervical biopsy), * diethylstilbestrol exposure, which can cause anatomical defects, and

* uterine anomalies.

Repeated procedures (such as mechanical dilation, especially during late pregnancy) appear to create a risk.[6] Additionally, any significant trauma to the cervix can weaken the tissues involved.

Diagnosis of cervical incompetence can be challenging and is based on a history of painless cervical dilation usually after the first trimester without contractions or labor and in the absence of other clear pathology. Other diagnostic tests that have been suggested which have not been validated include hysterosalpingography and radiographic imaging of balloon traction on the cervix, assessment of the patulous cervix with Hegar or Pratt dilators, the use of a balloon elastance test, and use of graduated cervical dilators to calculate a cervical resistance index.[1]

According to a 2014 practice bulletin from the ACOG concerning the management of cervical insuffiisciency, cervical cerclage, in which a stitch is placed at the cervicovaginal junction, may benefit women with a history of cervical insufficiency or painless cervical dilatation in the second trimester on physical examination.Benefit of procedure 80-90%.

Endocrine factors( 17%)

Luteal phase defect

Diabetis mellitus

Thyroid disfunction

Hyperandrogenia

Hyperprolactinemia

Infections( 5%)

Infection is considered a rare cause of recurrent miscarriage. Most patients with a history of recurrent miscarriage do not benefit from an extensive infection workup. Infections more often lead to complications in the third trimester of pregnancy- IUGR,premature rupture of membranes,premature delivery

Immunologic causes

Several diseases are caused by apparent confusion within the body's normal mechanisms that respond to disease. Normally, the human body makes antibodies against infection or any foreign tissue (as in rejection of organ transplants). In some disease states, the body becomes confused and apparently makes antibodies against its own normal tissue. Some of these disease states are associated with recurrent pregnancy loss.

Tests for antiphospholipid antibodies (APLAs), signaling the presence of the autoimmune disease antiphospholipid antibody syndrome (APS), have reportedly been positive in 10-20% of women with early pregnancy losses..

Diagnosis

Diagnosis of APS requires the presence of at least 1 of the clinical criteria and at least 1 of the laboratory criteria. The clinical criteria include the following:

* Vascular thrombosis

* 3 or more consecutive unexplained miscarriages

* At least 1 unexplained death of a morphologically normal fetus at or after 10 weeks' gestation

* At least 1 premature birth of a morphologically normal neonate at or before 34 weeks' gestation, associated with severe preeclampsia or severe placental insufficiency

The laboratory criteria include the following:

* aCL: Immunoglobulin G (IgG) and/or immunoglobulin M (IgM) isotype is present in medium or high titer on 2 or more occasions, 6 or more weeks apart

* Prolonged phospholipid-dependent coagulation on screening tests

* Inability to correct the prolonged screening test with normal platelet-poor plasma

* Successful correction of the prolonged screening test with excess phospholipids

* Exclusion of other coagulopathies as clinically indicated and heparin

Management

Treatment options for APS include the following:

* Subcutaneous heparin

* Low-dose aspirin

* Prednisone

* Immunoglobulins

* Combinations of these therapies

Not only antiphospholipid antibodies,but other autoantibodies are associated with recurrent pregnancy loss,and RPL may be the first manifestation of autoimmune conditions.

The association between thrombophilia and recurrent pregnancy loss (RPL) has become an undisputed fact. Thorombophilia creates a hypercoaguable state which leads to arterial and/or venous thrombosis at the site of implantation or in the placental blood vessels. Anticoagulants are an effective treatment against RPL in women with acquired thrombophilia due to antiphospholipid syndrome. The results of the use of anticoagulants for treating RPL in women with inherited thrombophilia (IT) are encouraging, but recently four major multicentre studies have shown that fetal outcomes (determined by live birth rates) may not be as favourable as previously suggested. Although the reported side-effects for anticoagulants are rare and usually reversible, the current recommendation is not to use anticoagulants in women with RPL and IT, or for those with unexplained losses Thrombophilia is a common cause of RPL and may be seen in 40–50% of cases.6,7 Pregnancy is a hypercoaguable state and if the pregnancy is affected by thrombophilia, the hypercoaguable state becomes worse and may impair blood flow through the maternal veins, leading to deep vein thrombosis, and clots in the placental blood vessels, leading to fetal growth restriction and/or fetal demise.8,9 Due to this fact, anticoagulants have become very popular for treating RPL.

Thrombophilia is a term which describes the increased tendency of excessive blood clotting. It is a normal phenomenon during pregnancy, where there is an increase in most clotting factors

Currently, many clinicians treat RPL—either associated with all types of thrombophilia or unexplained—with low-molecular-weight heparin (LMWH) combined with low-dose aspirin (LDA). This treatment became popular in the late 1990s, after Sanson et al. reported that thrombophilia is associated with the high risk of fetal loss in early and late pregnancy

The following studies, all of them prospective case-control studies, did not find an association between IT and adverse pregnancy outcomes.

There are a few studies that show that treating women who suffer from IT and RPL with anticoagulants is beneficial; however, these studies have many limitations.

Because of the results of the previously summarised investigations, the majority of clinicians worldwide have started prescribing heparin and/or aspirin for pregnant women with RPL, either with or without thrombophilia. However, because of the limitations of these studies, many researchers have conducted controlled, randomised, double-blind, multicentre studies to find out whether the current practice of prescribing anticoagulants to women with RPL with or without thrombophilia is justified.

However, LMWH for women with RPL which is not associated with APS it is not recommended. In women with RPL and APS, LMWH can be used as early as six weeks’ gestation until 34–36 weeks’ gestation.

 

This article outlines all common causes of recurrent miscariage,and describes in details causes, which can be treated by endoscopic methods.

In every case diagnostic and treatment methods must be selected individually for each patient.

Diagnostic methods

Physical examination

Laborator testing

Cariotype of couple

Hysterosalpingography,hysteriscopy and laparoscopy if indicated

Endometrial byopsy

Hormonal scrining

Scrining for AFS

Hemstasiogramm

Blood count

Rules for pregnant women with recurrent pregnancy loss

Lie down and listento relaxing music for 0,5-1 hour

Stop working after the 9th week of pregnancy

Repeated ultarsound screening for fetal heart detection

In clinical cases of miscarriage bed rest for 1 week is recomended

Avoid sexual contacts up to 13th week of pregnancy, or up to2 weeks after first miscarriage

Do not travel during pregnancy

Do not go to the sport club, do not play tennis

Do not go to parties, weddings, or funerals

Do not put flowers at home

Use folic acid up to 15th week of pregnancy

Do not have hot shower and do not bathe in healing springs

Avoid contact with chemical products,do not use sprays

Do not sweep the floors and vacuume

Do not go to the cinema in the evening

Avoid places with many people