- What is infertility?
- Causes of infertility
- Testing for infertility
- Treatment of infertility
- Infertility treatment and miscarriage
- Conclusion
- Frequently Asked Questions about Infertility
What is infertility?
In the Japan Society of Obstetrics and Gynecology, recurrent miscarriage is defined as follows.
If there is a history of two or more miscarriages (before 22 weeks of pregnancy) or stillbirths (after 22 weeks of pregnancy), it is diagnosed as recurrent miscarriage. Ectopic pregnancy, molar pregnancy (hydatidiform mole), and biochemical pregnancies are not included in the count of miscarriages.
Japan Society of Obstetrics and Gynecology – “Please tell me about recurrent miscarriage“
Experiencing repeated miscarriages or stillbirths can lead to feelings of anxiety, fearing that “if I get pregnant again, will I miscarry again?” This can mentally strain individuals and cause them to endure difficult emotions. Additionally, since the cause is often unknown, many pregnant women blame themselves.
Causes of infertility
The main causes of recurrent miscarriage include antiphospholipid syndrome, congenital uterine abnormalities, chromosomal abnormalities in either parent or the fetus, and endocrine disorders.
Risk factors for infertility
According to a 2019 survey, the main risk factors for recurrent miscarriage were antiphospholipid antibody positivity (8.7%), uterine abnormalities (7.9%), thyroid dysfunction (9.5%), and chromosomal abnormalities in either parent (3.7%). Other risk factors include deficiency of the 12th factor (factor XII) and protein S deficiency.
The most frequent causes were spontaneous miscarriage (fetal chromosomal abnormalities) and unknown risk factors, categorized as “unknown causes,” accounting for as much as 65.2% of all cases. Despite the high frequency of fetal chromosomal abnormalities as a cause of recurrent miscarriage, they were often labeled as “unknown causes” due to the lack of testing.
引用:厚生労働省 – 医学的見地からみた不育症治療の現状や問題点について
Antiphospholipid antibody syndrome
Antiphospholipid antibodies, also known as “antiphospholipid antibodies,” are autoimmune antibodies that appear in the mother’s bloodstream. They increase the tendency of blood to clot, leading to conditions such as thrombosis and an increased risk of miscarriage.
Uterine abnormalities
Anomalies in the shape of the uterus are mostly congenital (present at birth). Uterine abnormalities that can cause miscarriage include uterine malformations such as bicornuate uterus, septate uterus, unicornuate uterus, and didelphys uterus, as well as uterine conditions like submucosal fibroids or acquired abnormalities. Particularly, septate uterus is known to have a high miscarriage rate.
Chromosomal abnormalities in either parent
If either parent has a chromosomal abnormality called “balanced translocation,” the frequency of miscarriage increases. Balanced translocation refers to a situation where a segment of one chromosome swaps places with a segment of another chromosome. While there is no gain or loss of genetic material, individuals with balanced translocation do not experience issues themselves. However, during the formation of eggs or sperm, disruptions in genes can occur, leading to miscarriage.
Chromosomal abnormalities in the fetus
Abnormalities in the number of chromosomes in the fetus, such as trisomy where there is one extra chromosome instead of the usual two, can lead to miscarriage. The most common cause of recurrent miscarriage is chromosomal abnormalities in the fetus.
Endocrine disorders
Pregnant women with conditions such as hypothyroidism, diabetes, and other illnesses are believed to be more prone to miscarriage.
Testing for infertility
Starting from April 2022, the “products of conception (POC) chromosomal testing,” which examines fetal chromosomal abnormalities, became covered by insurance. However, it’s important to note that not all facilities offer insurance coverage for this test; only facilities meeting specific requirements are eligible for insurance reimbursement. The cost of the test is estimated to be approximately 20,000 to 50,000 yen when combined with other tests.
If there’s a concern about recurrent miscarriage, it’s recommended to undergo screening tests for the following risk factors to investigate the cause of miscarriage:
Testing according to risk factors
Antiphospholipid antibody test
In blood tests, various factors such as anticardiolipin antibodies and lupus anticoagulant are examined.
Uterine morphology test
There are procedures such as hysterosalpingography, ultrasound (echo) examination, hysteroscopy, and MRI examination.
Chromosomal testing for either parent
In blood tests, it’s possible to examine for chromosomal abnormalities. It’s also advisable to receive genetic counseling from a specialist along with the testing.
Miscarriage chorionic villus testing (POC testing)
Tissue from the chorion, a part of the early placenta, is collected from the miscarried fetus to examine for chromosomal abnormalities. If the abnormalities are found on the baby’s side, the miscarriage can be diagnosed as accidental, increasing the likelihood of a successful next pregnancy and childbirth.
Endocrine testing
Thyroid hormone levels, diabetes, and other factors are examined through blood tests.
Treatment of infertility
The treatment for recurrent miscarriage varies depending on the underlying cause. It’s important to undergo testing first to determine the cause of recurrent miscarriage.
Treatment according to risk factors
Antiphospholipid antibody syndrome
If the result is positive, another test is conducted with an interval of at least 12 weeks. The basic treatment involves the administration of low-dose aspirin and calcium heparin, with thorough monitoring throughout the pregnancy.
Uterine abnormalities
Septate uterus is the most common uterine anomaly associated with recurrent miscarriage, and it’s said to have a high miscarriage rate. If miscarriages persist, surgical intervention may be necessary. Surgery can improve the chances of maintaining a pregnancy.
Bicornuate uterus, the second most common anomaly, is less likely to cause miscarriage. However, it can lead to complications such as preterm birth or fetal growth restriction, and in such cases, surgery may be considered.
Chromosomal abnormalities in either parent
While direct treatment may not be possible, undergoing genetic counseling is crucial. Ultimately, the chance of having a child is not significantly lower compared to couples with normal chromosomes.
About 80% of early miscarriages are due to random chromosomal abnormalities in the fetus. However, in cases of recurrent miscarriage, there’s a higher likelihood of one partner having structural chromosomal abnormalities such as balanced translocation.
Balanced translocation occurs in about 5% of couples with recurrent miscarriage. However, with this chromosomal abnormality, there’s a good chance of successful childbirth, with research showing that ultimately 60-80% of couples can achieve successful pregnancies.
Chromosomal abnormalities in the fetus
Currently, medical technology does not allow for the treatment of chromosomal abnormalities in the fetus. However, it is possible to detect chromosomal abnormalities in the fetus beforehand through various prenatal screening tests.
NIPT(Non-Invasive Prenatal Testing) is a test that examines chromosomal abnormalities such as Trisomy 21 (Down syndrome), Trisomy 18 (Edwards syndrome), and Trisomy 13 (Patau syndrome) in the fetus from blood samples taken from the mother. Compared to traditional prenatal testing through blood, it is considered to have extremely high accuracy in terms of sensitivity and specificity.
NIPT, which can be conducted through blood sampling from the mother’s arm, is considered a safe test without the risk of miscarriage. Furthermore, since it can be performed immediately after pregnancy confirmation through ultrasound examination, it enables early assessment of the baby’s condition.
Endocrine abnormalities
After receiving treatment from a specialist in internal medicine, treatment is administered for conditions such as hyperthyroidism or hypothyroidism until normal function is restored. For diabetes, it’s important to achieve adequate blood sugar control before planning the next pregnancy. Treatment and regular monitoring continue during pregnancy and afterward.
![不育症のリスク因子](/nipt/wp-content/uploads/2022/12/recurrent-pregnancy-loss02-1.jpg)
Costs associated with infertility treatment
Since 2021, the testing and treatment costs for recurrent miscarriage have become eligible for insurance coverage, with patients responsible for 30% of the expenses. Consequently, many local governments have discontinued subsidies for recurrent miscarriage. However, some regions may still provide subsidies, so it’s advisable to inquire with your local municipality for more information.
Can treatment be covered by insurance?
Many common tests and treatments for recurrent miscarriage are covered by insurance, but there are some newer treatments or tests that may not be covered. The cost of treatment varies depending on the cause of recurrent miscarriage, so it’s important to verify with your healthcare provider.
Are there any subsidies?
Since 2021, treatment for recurrent miscarriage has become eligible for insurance coverage, and subsidy programs provided by local governments may vary, with some discontinuing or partially subsidizing them. It’s advisable to contact your local authorities to inquire about the details of subsidy programs in your area.
Number of miscarriages and success rate of subsequent pregnancies
If there is a history of two or more miscarriages (before 22 weeks of pregnancy) or stillbirths (after 22 weeks of pregnancy), the condition is diagnosed as recurrent miscarriage. However, ectopic pregnancy (tubal pregnancy), molar pregnancy (hydatidiform mole), and biochemical pregnancy (chemical miscarriage) are not included in the count of miscarriages.
Even if a woman has already given birth and has a first child, if she experiences two or more miscarriages or stillbirths afterward, she is considered to have recurrent miscarriage. It is estimated that there are approximately 30,000 people with recurrent miscarriage in Japan, which is not uncommon.
Even after being diagnosed with recurrent miscarriage, it is said that over 70% of women can still achieve successful pregnancies.
Approximately half of recurrent miscarriages are due to what is called “random miscarriage,” repeatedly experiencing pregnancies with fetal chromosomal abnormalities by chance. This type of miscarriage occurs more frequently as the mother’s age increases. Even if no abnormalities are found in recurrent miscarriage testing, it is possible to have a successful pregnancy in the next conception.
Infertility treatment and miscarriage
“Infertility” refers to the inability of healthy men and women who are not using contraception during sexual intercourse to conceive within one year. Infertility and recurrent miscarriage are categorized based on the presence or absence of pregnancy.
In cases where multiple healthy embryos are transferred during infertility treatment but fail to implant, or in cases of two or more miscarriages or stillbirths, or when multiple embryo transfers fail to result in pregnancy, infertility may coexist with recurrent miscarriage. Reports suggest that around 20-30% of couples with infertility also experience recurrent miscarriage.
Conclusion
Since recurrent miscarriage treatment can be prolonged, it’s important to explore coping strategies during difficult times. Recurrent miscarriage can be emotionally challenging, but gaining knowledge about it can sometimes provide relief and reassurance. Try to educate yourself with accurate information and seek support when needed.
【References】
- Ministry of Health, Labour and Welfare – Efforts on Recurrent Miscarriage
- Japan Society of Obstetrics and Gynecology – “Please Tell Me About Recurrent Miscarriage“
- Japan Society of Obstetrics and Gynecology – 5. Uterine Disorders
- Japan Society of Obstetrics and Gynecology – 2. Chromosomal Abnormalities
- Ministry of Health, Labour and Welfare – Current Status and Issues of Recurrent Miscarriage Treatment from a Medical Perspective
- Advanced Medical Care.net – Investigating the Causes of Recurrent Miscarriage and Connecting to Patient Care: “Chromosomal Testing Using Miscarriage Samples”
- Effects of Thrombophilia and Antithrombotic Therapy on Embryonic Chromosomal Aberration Rates in Patients with Recurrent Pregnancy Loss
- Nozomi Ouchi,Toshiyuki Takeshita,2022 Volume 89 Issue 1 Pages 40-46
Q&A
Some frequently asked questions about infertility are summarised below. Please refer to.
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QHow often do miscarriages occur?The age of the pregnant woman also matters, with about 10-20% of pregnancies being reported as miscarriages.
This rate increases when the woman is over 35 years old. Biochemical pregnancies (chemical miscarriages) occur at a higher rate (30-40%), but are not counted in the miscarriage statistics. Miscarriages before 12 weeks of pregnancy, in the early stages, account for about 90% of all miscarriages, while the frequency decreases for late miscarriages before 22 weeks of pregnancy. -
QIf a woman has given birth after fertility treatment, will she need fertility treatment for the next pregnancy?The causes of infertility vary depending on the individual. It may be necessary to undergo infertility treatment for the next pregnancy, so we recommend consulting a obstetrician/gynecologist before the next pregnancy.
Article Editorial Supervisor
![Dr Hiroshi Oka](/nipt/wp-content/uploads/2020/01/doctor_oka.jpg)
Dr Hiroshi Oka
NIPT specialist clinic, MD
Graduated from Keio University, School of Medicine