Recurrent Miscarriage – Causes, Investigations and Evidence-Based Management: A Comprehensive Analysis


Recurrent miscarriage whereby pregnancy is lost before 20 weeks of gestation in three or more subsequent pregnancies affects the child bearing capacity of some 1-2 percent of couples who are trying to start a family. It is a distressing condition for the woman as well as her partner, especially when the situation occurs at a tender age. This article offers a didactic review of recurrent miscarriage and aims to include only evidenced based information supported by the RCOG guidelines.

Causes of Recurrent Miscarriage

As earlier noted, 30-50% of the cases of recurrent miscarriages can still be of unknown causes after undergoing tests. However, following studies have been established with evidence based causes.

Uterine Anomalies

The Septate uterus stands as one of the most significant causes of recurrent miscarriage involving approximately 25% of the cases. The risk depends on the type of anomaly:The risk depends on the type of anomaly:

– Septate Uterus – about 44 percent of miscarriage cases

– Arcuate Uterus – and is associated with a much lower risk.

– Uni cornuate Uterus – 46% miscarriages

– Uterine didelphys is associated with about 32% miscarriage risk.

Other structural pathologies of the uterus, such as adenomyosis, may also lead to an elevated miscarriage rate.


– 3D ultrasound scan – Ideal and most accurate method for diagnosing a condition.

– Mri scan – A non invasive imaging procedure

– Hysteroscopy – The examination wherein the uterine cavity is directly visible.


The RCOG suggests surgery as a management for septate and bicornuate uterus.Obviously, other procedures that could be useful in increasing this live birth rate include hysteroscopic metroplasty The decision to opt for surgery must always be preceded by a disclosure of all the risks and benefits of the surgery in question.

Antiphospholipid Syndrome (APS):

Antiphospholipid Syndrome (APS) is a type of autoimmune disorder.


Adverse pregnancy outcomes include:

Three or more consecutive miscarriages before 10 weeks of gestation;


One or more morphological normal fetal losses after tenth week of gestation 

Moreover, underlying conditions of lupus anticoagulant or anticardiolipin antibodies with medium or high titer received on two occasions with a time difference of at least 12 weeks between these occasions. The antibodies that are recognized include lupus anticoagulant, anticardiolipin antibodies found on different phases in patients with SLE and anti Beta 2 glycoprotein I.


Lupus anticoagulant testing as a part of APS screening

Anti beta 2-glycoprotein-I antibodies

Anti-prothrombin antibodies (repeat testing is obligatory).


Together, Aspirin 75-100 mg per day + heparin injections/LMWH during pregnancy can raise live birth rate to over 70%.


Other inherited disorders such as factor V Leiden is the cause of increased clotting.Currently, RCOG does not endorse screening and testing a woman for thrombophilia in the case of multifactorial miscarriage, that is one to two miscarriages.

 Test only with any of:


Factor V Leiden mutation       ( associated with first and second trimester

                                                    recurrent miscarriages )


Protein C                                    (has not shown a consistent association with            

                                                    recurrent miscarriages

                                                    least consistent association with miscarriages)


Protein S                                     ( associated with second trimester

                                                      recurrent miscarriages)


Prothrombin gene mutation    ( associated with recurrent miscarriages)


Antithrombin deficiency          ( rarer yet most thrombogenic mutation)

Thrombophilia panel tests


Heparin in thrombophilias and the overall process of anticoagulant treatment is not clear from the findings of the study. This means that the number and responsibilities of both the patient as well as the clinician are defined and understood by the both of them and is recommended by RCOG for implementation


Uncontrolled Diabetes

Maternal diabetes that developed before conception but before the pregnancy also affects the outcome, with Hba1c greater than 10% tripling the risk of miscarriage. Observably, there is a marked reduction in the risk with more effective glycemic control.


HbA1c, fasting plasma glucose


– Preconception HbA1c < 6.5% Where Possible

– Lifestyle management

– Drug therapy of metformin/insulin for the regulation of blood glucose.


Thyroid Dysfunction

If thyroid disease is not managed during pregnancy, the chances of miscarriage are tripled due to hypothyroidism and hyperthyroidism.


TSH, anti-TPO antibodies


– Levothyroxine used for hypothyroidism management – TSH goal <2.5 mIU/L

– Carbimazole/thyroxine for managing hyperthyroidism

– Thyroid status should be checked at least every 4-6 weeks in pregnant women.


Uterine Fibroids

Submucosal uterine fibroids, specifically those located intramurally and that distort the uterine cavity, are associated with up to three times the miscarriage risk.


Intracavitary fibroids with a diameter of more than 3 cm are most prone to be found in an ultrasound scan.


Hysteroscopic myomectomy should be used for intracavitary fibroids before becoming pregnant. This patient has to be counseled on the risks and benefits of the surgery .


Cervical Weakness (Cervical Insufficiency)

Late miscarriage, which occurs between 16-24 weeks normally, is normally caused by cervical incompetence, usually as a result of trauma or surgery to the cervical area. This study suggests that Transvaginal ultrasound measuring a cervix ≤ 25 mm in length at 20 weeks of pregnancy is useful in diagnosing.


Cervical measurement by Transvaginal ultrasound at 18-20 weeks of gestation


Cervical cerclage:<|reserved_special_token_264|>ing the cervix with a suture at around twelve weeks of pregnancy to close the cervical opening. After three mid-trimester miscarriages, there is data to back its utilization.


Luteal Phase Defects

It is used in the treatment as well as maintenance of pregnancy especially in early pregnancy or the first trimester. Luteal phase defects result in the inability of the body to manufacture enough progesterone and this greatly threatens the life of a woman with a risk of likely causing a miscarriage.


Blood test 7 days after LH surge or ovulation – Progesterone < 30 nmol/l suggests an anomaly.


The above progesterone supplements include natural micronized progesterone which is administered 400-600 mg daily via the vaginal route in the first trimester. There are questions on the effectiveness of the centers.

Genetic factor

From this it is realized that the chromosomes of the embryos are not normal; that which scientifically is called genetic factors. It also needs to be pointed out that 5-10% of all women experience a first trimester miscarriage that is caused by chromosomal abnormalities within the embryo that would not permit further development.This risk increases with the age of the mother further.


– This is because karyotyping performed on pregnancy tissue assists in identifying performance genetic disorders.

– The chances of a woman being an asymptomatic carrier of inherited genetic mutations that may affect any potential offspring should also be evaluated prior to conception.


– RCOG makes no recommendation on any particular line of management.

– PTG-A technique used in IVF means that only chromosomally normal embryos are selected.


Unexplained Recurrent Miscarriage

If there is no identifiable cause after such investigations,then the miscarriage is ‘unexplained’. It was necessary to provide empathetic counseling by giving emphasis towards supportive care.


– As outlined by the RCOG, the evaluation of recurrent miscarriages must follow a proper protocol.


Progesterone therapy in women of childbearing age is not recommended by RCOG if there are no luteal phase defects regarding empirical treatment options. Investigating off-label empiric use of progesterone/heparin seems rational after sharing that no data are available on their efficacy.

Moreover, preparing beforehand, attending proper antenatal appointments, visiting the early pregnancy unit, and patient-oriented education contribute to better results.


Investigating Recurrent Miscarriages

However, up to 45% of recurrent miscarriages have unknown causes and hence, RCOG advises a thorough evidence-based RM investigation protocol after 12 months of trying. This includes:

Blood Tests:

– Full blood count

– Thyroid function

– Health assessment with HbA1c

– Antiphospholipid antibodies

– Luteal phase progesterone

– Screening of thrombophilia where applicable inherited


– For this reason, the transvaginal 3D ultrasound of the uterine anatomy was carried out.

– TV CSL at 18-20 WGA for identifying women at risk of cervical weakness.

Other Testing:

– Parental karyotyping

– The following preconception carrier genetic screenings include


Role of IVF Treatment

For couples with unexplained secondary RM for whom fertility treatment is to be considered, RCOG advises that IVF with PGD-a should be employed in order to select embryos with chromosomal normality. IVF should be available for these patients and embryo testing if possible should be made available to them. It disposes of the risk in pregnancy loss that might be due to a bad embryo through implantation of a single normal embryo.



In conclusion, the research finds that recurrent miscarriage has many possible causes that all couples with 2+ miscarriages have to be screened for according to RCOG guidelines. Septate uterus, APS, poor glycemic control diabetes, thyroid disorders, fibroids, and weak cervical conditions contribute significantly to recurrent miscarriages. Genetic embryo factors are also contributing factors to the development of polyploid plants. An effective and systematic analysis is performed, which makes it possible to prescribe targeted interventions based on the cause in at least half of the cases. Preliminary as these approaches are, ongoing research has provided valuable guidelines to assist many such couples in achieving their goal of conceiving a pregnancy and delivering a live born infant.


Question 1

Woman has miscarriage at 18 weeks for first time , she is upset, wants to go for investigation what is correct advice for genetic testing

a-Counsel her that genetic test not required
b-Genetic testing can be done after 3 miscarriages
c-Genetic testing can be done after 2 miscarriages
d-Accept request and arrange genetic testing 

Question 2

Woman with history of 3 miscarriage has come with 6 weeks of pregnancy , previously she was tested positive for TPO antibodies
When her thyroid function test to be done

a– 5-6 weeks of pregnancy
b– 7-8 weeks of pregnancy
c– 7-9 weeks of pregnancy
d– 10-11 weeks of pregnancy  

Question 3

Woman with history of 3 miscarriages has come with 6 weeks of pregnancy , presented with bleeding , she is scare that she would miscarry again
What will be the correct advice

a– counsel her
b-400 mg micronized vaginal progesterone twice daily at the time of bleeding until 16weeks of gestation
c– 400 mg micronized vaginal progesterone twice daily at the time of bleeding until 18 weeks of gestation
d– 400 mg micronized vaginal progesterone twice daily at the time of bleeding until 34 weeks of gestation 


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