Most patients with inflammatory bowel disease have a young age of onset, with approximately 50% of patients being <35 years of age at first diagnosis and 25% facing their first child after diagnosis of inflammatory bowel disease. These patients with inflammatory bowel disease of childbearing age are often concerned about the impact of their disease and disease progression on their fertility, and have doubts about the safety of the drugs used to treat them. There is no doubt that the physician's advice influences the patient's attitude and choice to a great extent in the face of the patient's concerns. In addition, the physician's knowledge and control of the patient's condition and the choice of medication also play a key role in the success of the pregnancy. In order to eliminate patients' concerns and misunderstandings, clinicians should have a correct and comprehensive understanding of the issues of fertility, pregnancy and breastfeeding in patients with inflammatory bowel disease, and give scientific and reasonable advice and guidance. Here we have compiled a list of relevant questions in a question and answer format for your reference. Of course, many of the questions are controversial, and the answers provided may not be completely accurate, so it is necessary to consult your doctor for a targeted discussion of your specific condition. 1. Can a patient with inflammatory bowel disease become a parent? As a whole, the answer is yes. However, there are many basic issues that must be attended to when you are planning a pregnancy. We will discuss this in further detail below. You must understand that as long as the inflammatory bowel disease is stable. You are in remission and it is safe for you to plan a pregnancy. At this time, your fertility will not be reduced and your pregnancy will not be significantly different from that of a healthy man or woman. Of course, you must manage your disease with medications to keep it in remission as long as possible. At this time, some of the medications you are taking may have potential adverse effects that may not matter to the average patient, but may be harmful to a pregnant woman during pregnancy. Therefore, it is important that you explain to your doctor that you have a desire to become pregnant and let him/her guide your medication during pregnancy so that the safety of mother and pregnancy may be ensured. 2. Does inflammatory bowel disease affect fertility and pregnancy? Let's talk about the fertility of women with inflammatory bowel disease. Women with ulcerative colitis usually have the same fertility as healthy women. The one exception is major abdominal surgery that may affect it. Major abdominal surgery refers to partial or complete resection of the large intestine (colon), small bowel-rectal anastomosis or ileostomy. Some surveys have shown a slight decrease in overall fertility in women who have undergone such surgical procedures. Of course, there is also the subjective factor of women of childbearing age not wanting to get pregnant. These women may experience a reduction in fertility, but it is usually short-lived. Full recovery can occur within a few weeks or months. The issue of fertility in women with Crohn's disease is not known nor is it well understood. In general, when the disease is quiescent, fertility is not affected, and during the acute phase of the disease and after major surgical procedures, there will be a brief reduction in fertility. This can lead to amenorrhea, a common symptom brought on by significant weight loss due to disease activity. A slight decrease in fertility will manifest itself biologically in women of childbearing age during the active phase of the disease. To ensure a successful pregnancy, pregnancy should be delayed until the best possible time, while patients with inflammatory bowel disease and their families should avoid additional stress. After the surgical wound has fully healed and the disease has stabilized, a woman's fertility will not be greatly affected. Although studies have shown a slight decrease in fertility in patients with inflammatory bowel disease who have undergone surgical procedures. Note, however, that failure to conceive cannot always be blamed on inflammatory bowel disease. The reality is that only 90% of even healthy women can successfully conceive without protective measures. 3. What is the fertility of male patients with inflammatory bowel disease? Male fertility is usually not affected by inflammatory bowel disease. However, abscesses and fistulas in the pelvic and anal regions may affect erection and ejaculation. Similar disorders can occur in patients who have undergone major surgery, especially in the anal area, but the incidence is small. A special case needs to be noted that salazosulfapyridine causes a transient loss of male fertility. In these men who received the drug, the incidence was 80%. Why is there a transient loss of fertility? The causes are not yet unilateral and include reduced sperm count, reduced semen volume and abnormal spermatogonial cell structure and viability. However, don't worry, fertility will be restored when these drugs are stopped, or after taking only 5-aminosalicylic acid for two months. 4. How does inflammatory bowel disease affect the course of pregnancy and the health of the baby? Inflammatory bowel disease can have a negative impact on the pregnancy and the health of the baby, but it is relatively minor. In general, 85% of pregnant women with Crohn's disease or ulcerative colitis behave normally, and the incidence of babies born with congenital malformations is only 1%. This incidence is in line with the figures observed in healthy pregnant women. Therefore, the risk of such neonatal malformations is not increased after a pregnancy with inflammatory bowel disease. We would like to inform you that even in healthy women, pregnancies are not all normal. In fact, the incidence of problems of pregnancy and abnormalities affecting the health of the baby is about 15%. Inflammatory bowel disease can have a negative impact on pregnancy compared to healthy women mainly related to whether the lesion is active or not. It has been investigated that the active phase of the disease will increase the chances of having a difficult delivery. Quiescent disease or mild inflammatory activity has minimal effect on pregnancy and infants. Therefore, if possible, pregnancy should be planned during the quiescent phase of the disease or during a period of mild inflammatory activity. If the pregnancy occurs during the active phase of the disease, it is important to be aware that problems such as miscarriage, preterm delivery and obstructed labour may occur. Thus, it seems that it is most important to control the disease, and any disease that is active should be treated actively. If the disease is well controlled before pregnancy, this will ensure the safety of mother and baby. 5. Will the symptoms worsen after pregnancy? The effect of pregnancy on inflammatory bowel disease depends mainly on whether the disease is active before pregnancy. It was found that 75% of patients with quiescent disease before pregnancy will remain in quiescence during pregnancy; 51% of patients with active disease before pregnancy will remain in moderate to severe activity during pregnancy. Even with aggressive treatment, the disease will remain active during pregnancy in most cases. Therefore, we recommend that pregnancy should occur when the disease is in remission. In particular, the situation is very different for women with first onset of ulcerative colitis during pregnancy or puerperium. Once the disease has developed, it is mainly severe or violent and can be life-threatening. So although this situation is relatively rare, it should be given great attention. 6. What medical tests are needed to assess the safety of pregnancy before planning a pregnancy? There is no set practice here. This is a question you need to discuss with your doctor individually. Sometimes invasive tests such as colonoscopy and radiology may be performed if needed, but not in all cases. Discuss in detail with your doctor your medical history, current condition and laboratory tests to assess the activity of the disease and nutritional status. This should be done prior to planning a pregnancy. An appointment with a senior physician for an abdominal examination and ultrasound is recommended and the results should be well documented. These are of great value for subsequent pregnancies as well as for delivery. Individual patients with inflammatory bowel disease may require more intensive investigations, including colonoscopy and radiology. The purpose of these tests is to determine whether the disease is active or inactive and to administer regular treatment. Some results may suggest that you need to increase your intake of certain vitamins and minerals such as vitamin B12, folic acid and iron. It is recommended that pregnant women take folic acid early in pregnancy. This is because folic acid can help prevent neurological defects from occurring during fetal growth and development. Also note that taking salazosulfapyridine may reduce the absorption of folic acid in the small intestine. 7. How do you think about surgery and pregnancy? In general, previous abdominal surgery for inflammatory bowel disease has little effect on pregnancy. Pregnancy is safe even in patients with extensive colectomy and colostomy. However. There should be sufficient interval between pregnancy and surgery for recovery, and it is important to ensure that the disease is well controlled and the condition is not active after surgery. After a major surgical procedure, pregnancy is usually considered after an interval of one year. It is important to note that colostomy patients should be more careful to ensure that their general nutritional status has recovered by the time they become pregnant. If this is not the case, the incidence of preterm delivery after colectomy + colostomy increases. In some exceptional cases, certain necessary surgical procedures may be performed during pregnancy. There is no need to worry about surgery leading to preterm delivery and congenital malformations. It is the slightly larger surgical procedures that, with proper management, can lead to a safe pregnancy as usual. 8. Does pregnancy affect the natural course of inflammatory bowel disease? In most cases, pregnancy has no effect on the activity of inflammatory bowel disease and the maintenance of the recovery period. Only in isolated cases, the inflammatory bowel disease may change significantly during pregnancy, from significant improvement to significant deterioration or even exacerbation. About 15% of women who become pregnant while recovering from Crohn's disease experience an acute exacerbation of the disease. However, this rate is the same as that of other non-pregnant women. If the disease is active during the first trimester, then one third of patients will have active disease throughout pregnancy. There is also an increased likelihood of activity or exacerbation of the disease in the puerperium. In pregnant women with ulcerative colitis, pregnancy does not have an important role in influencing the period of disease activity. About 1/3 of women with ulcerative colitis who become pregnant during the recovery period of the disease have an acute attack during pregnancy, which also does not differ significantly from the changes in the course of the disease in non-pregnant female patients. Statistically, the frequency of acute exacerbations of inflammatory bowel disease conditions increases during the sixth month of pregnancy and the puerperium. Most women with active Crohn's disease who are pregnant have active disease throughout pregnancy. It is important to note that medication can accelerate remission and improvement of inflammatory bowel disease during pregnancy. Medication can also maintain the disease in a stable phase and reduce activity. Please note that although medication greatly ensures the safety of pregnancy, some patients may still experience activity. According to the survey, the worsening of inflammatory bowel disease symptoms during pregnancy may affect subsequent pregnancies. 9. Can inflammatory bowel disease develop for the first time during pregnancy? Completely. Both Crohn's disease and ulcerative colitis may have their first episode during pregnancy. However, the patient's condition is not more severe than that of a non-pregnant patient with inflammatory bowel disease. It is important to note that in the case of pregnancy, it is important to be wary of delaying clarity because of the patient's fear of endoscopy. In cases of suspected pregnancy-associated inflammatory bowel disease, colonoscopy and/or radiology should still be advocated to clarify the diagnosis. 10.Can I use drugs for inflammatory bowel disease during pregnancy? Everyone knows that medications should be avoided during pregnancy, or even before planning a pregnancy, to protect the future child from unnecessary damage. This poses a challenge to the pharmacological treatment of inflammatory bowel disease. There is a lot of concern about the safety information of medications related to inflammatory bowel disease. It is important to note that the issue of medications to be taken during a patient's pregnancy can only be determined by the advice of a physician. Medications prescribed by physicians are also individualized. If necessary, the decision needs to be made by a specialist consultation. This is the only way to achieve the highest possible safety. Therefore, the general rule for taking medication during pregnancy in inflammatory bowel disease is to choose only those medications that are absolutely necessary. Of course, it should not be forgotten: the serious threat to the health of mother and child cannot be eliminated if inflammatory bowel disease is effectively treated. Here it is necessary to repeat what we said above: even for healthy women, only 85% of pregnancies are free from complications. In a word, it is necessary to grasp the main points of treatment of inflammatory bowel disease in women during pregnancy. The principle is basically the same as in non-pregnant patients, with regular pharmacological treatment. On the other hand, it is important to pay due attention to the individual characteristics of the patient. 11.Does taking medication for inflammatory bowel disease have any effect on the baby? It is more difficult to answer this question because some drugs do not have definite research results. Therefore, the treatment of each patient with inflammatory bowel disease should be decided by a joint consultation between the obstetrician and the internal medicine specialist or gastroenterologist. Regular doses of glucocorticosteroids (e.g., prednisolone, hydrocortisone) and salazosulfapyridine or 5-ASA have not been found to be harmful to the unborn fetus. Nonetheless, the use of these drugs during the first trimester of pregnancy requires caution and rigor. Patients in remission who require maintenance treatment with 5-ASA or corticosteroids should continue to take the medication according to their condition and medical advice or reduce the dosage. This remains true even after the diagnosis of pregnancy. This is because the activity of the condition poses a greater risk to the fetus. In case of acute attack of inflammatory bowel disease during pregnancy, the medication should be adjusted in order to control the disease as soon as possible. Inadequate treatment of inflammatory bowel disease can be harmful to mother and child beyond the drug itself. Conventional treatment of inflammatory bowel disease is mainly 5-ASA or hormones. So far mainly, this conventional treatment has no adverse effects on mother and child in early pregnancy. As already mentioned, salazosulfapyridine may cause a transient decrease in fertility. Therefore, 5-ASA is more suitable for couples planning a pregnancy. There is no adequate clinical evidence regarding the safety of budesonide administration during pregnancy. At least no risk concerns for mother and child have been identified. Nevertheless, a decision must be made after appropriate discussion between the doctor and patient before budesonide is administered. Other drugs such as antibiotics or immunomodulatory agents such as azathioprine (AZA) or 6-mercaptopurine require strict indications for their use and should be decided after consultation with an experienced specialist. Immunomodulators such as cyclosporine A, methotrexate (MTX), tacrolimus, and morte-macrolimus must be discussed carefully before use. AZA is a pregnancy category D drug, and the available clinical data suggest that its use during pregnancy does not increase the risk of adverse events in pregnancy. MTX and thalidomide are class X drugs and have clear teratogenic effects. Therefore, patients treated with MTX should use contraception and discontinue the drug at least 6 months prior to planned pregnancy if pregnancy is contemplated, and 3 months prior to planned pregnancy in men due to the reversible sperm-reducing effects of MTX. The Organization of Teratology Information Specialists (OTIS) recommends discontinuation of thalidomide at least 1 month prior to planned pregnancy to reduce the incidence of birth defects. Cyclosporine is a pregnancy category C drug that crosses the placental barrier. There are no reports of teratogenicity of cyclosporine, but it has been reported to cause preterm delivery and low fetal weight. In addition, animal studies have shown adverse reactions to administration during pregnancy, particularly with methotrexate, where high doses resulted in pregnancy termination. Although some patients with inflammatory bowel disease and organ transplant recipients have not shown adverse effects with the application of tacrolimus and morte-macrolimus, the effect on pregnancy needs to be further evaluated. Therefore, there is no clear consensus on whether to terminate a pregnancy when a patient is accidentally conceived while taking cyclosporine A and tacrolimus. The biologic agents infliximab (IFX) and adalimumab (ADA) are class B drugs in pregnancy, and both can pass through the placenta in mid- to late-term pregnancy. IFX levels have been found to be detectable in newborns up to 6 months of age, and this immune tolerance may increase the risk of infection in later life and have an impact on immunizations. In the case of ADA, there is no conclusive research evidence of an effect on the fetus. Therefore, discontinuation of IFX and ADA should be considered in late pregnancy, and there is no basis for certainty that IFX is effective in combined inflammatory bowel disease pregnancies. Therefore, IFX is not recommended for use during pregnancy, and azathioprine is recommended. The duration of contraception in patients using IFX is delayed until at least three months after discontinuation. Since many mothers using IFX deliver healthy infants, there is no basis for termination of pregnancy in pregnant women using IFX. The use of antibiotics such as metronidazole or ciprofloxacin during pregnancy for inflammatory bowel disease must be strictly indicated. The long-term use of these drugs is contraindicated. The rationale is that they are less effective than standard therapy with glucocorticoids or 5-ASA for inflammatory bowel disease conditions and that they are only a backup. Standard medications are ineffective and corticosteroids should also be considered before considering antibiotics. In addition, pregnant women with inflammatory bowel disease must be careful with antidiarrheal medications (e.g., Imodium or Atropine). This is because a teratogenic risk to the fetus has been reported for the above drugs. Plantago ovata is a better choice, often useful for diarrhea. 12, oral contraceptives can cause or aggravate inflammatory bowel disease? There have been studies showing that the incidence of Crohn's disease is slightly elevated in women taking oral contraceptives, and there may be an increase in the occurrence of acute illnesses. However, some other studies do not support this. As for the relationship between oral contraceptives and ulcerative colitis, there is no evidence of an association. In general, the risk of inflammatory bowel disease or the chance of worsening symptoms with oral contraceptives is very low. There are no clear contraindications to the use of oral contraceptives for inflammatory bowel disease. In addition, some inflammatory bowel disease may interfere with drug absorption due to severe diarrhea. This is important. This is because these patients need to be made aware that the effectiveness of contraception is likely to be reduced. 13. Can the immunomodulatory drugs azathioprine or 6-mercaptopurine be taken during pregnancy? If possible, immunomodulatory drugs such as azathioprine or 6-mercaptopurine should be discontinued in the first trimester of planned pregnancy. The rationale is that, based on current knowledge, the riskiness of these drugs during pregnancy is uncertain. It is important to note that if pregnancy occurs while taking the drug, the need to terminate the pregnancy is a matter of serious consideration. There is no information that the immunosuppressive drugs mentioned above cause malformations or intrauterine death in newborns. According to recent studies in patients with inflammatory bowel disease from organ transplantation and rheumatology treatment, pregnancy may be safe in women taking azathioprine or 6-mercaptopurine, but termination of pregnancy is not contraindicated, especially in those who continue to take the drugs. If a decision is to be made to discontinue a pregnancy while a person on azathioprine is receiving treatment, this requires careful discussion between the doctor and patient to analyze the pros and cons before a decision can be made. Those involved in this decision need to have a high degree of responsibility, including the patient, the obstetrician and gynecologist, and the gastroenterologist to discuss it together. The effect of azathioprine or 6-mercaptopurine on the fetus when taken by the male partner before pregnancy is also controversial. Some foreign investigations have found an increased risk of miscarriage and congenital malformations in men taking these drugs in the first trimester of pregnancy. In view of this, it is recommended that azathioprine be discontinued by the male partner in the first trimester of planned pregnancy. The rationale is that azathioprine may cause the destruction of spermatogonial genetic material and the generation of new spermatogonial genetic material takes 90 days. 14. Is it safe to use corticosteroids in late pregnancy and during breastfeeding? It is now generally accepted that there is no relationship between the dose of corticosteroids used to treat inflammatory bowel disease and the risk of miscarriage or fetal malformation. In late pregnancy, high doses of corticosteroids may reduce adrenal corticosteroid production in the newborn, resulting in lower blood cortisone levels in the newborn after birth. Therefore, any patient taking high doses of corticosteroids in the second trimester should deliver a newborn that is closely monitored by an experienced specialist. If necessary, cortisone levels should be tested to determine if replacement therapy is needed to supplement cortisone, depending on the circumstances. Moreover, continuous follow-up by a pediatrician is sometimes required. In practice, the chances of persistent hyperalgesia in newborns are very small. Most newborns normalize adrenal function soon after interruption of cortisone therapy and secrete adequate amounts of cortisone to maintain physiological needs. There is limited experience regarding the use of budesonide during pregnancy. Theoretically, budesonide is rapidly metabolized in the mother's liver, and the amount of drug entering the circulation is small, and the amount transferred to the infant through breast milk is even smaller. Therefore, women with inflammatory bowel disease can support the use of budesonide during pregnancy and lactation. There have been no reports of any adverse reactions in infants following budesonide administration. Women with asthma who have used budesonide for longer periods of pregnancy have not seen an increased risk of fetal malformations. However, there is limited experience with the use of this drug and reasonable advice should be given to those women who are pregnant. 15. Should 5-ASA therapy be interrupted before pregnancy? Unlike aspirin, the therapeutic dose of 5-ASA does not affect clotting function and does not inhibit platelet production. Moreover, the concentration of 5-ASA absorbed into the blood is extremely low, and the possibility of affecting the fetus is extremely small. The random interruption of 5-ASA therapy can still lead to recurrence of disease in pregnant women with inflammatory bowel disease in clinical remission, which can be detrimental to pregnancy. Therefore, there is no need to interrupt 5-ASA treatment before pregnancy. 16. Is it necessary to terminate pregnancy in inflammatory bowel disease? In practice, termination of pregnancy due to inflammatory bowel disease is rarely necessary, and it can be said that it is not necessary. It should be noted that it is important that a pregnant woman's inflammatory bowel disease is treated appropriately by the doctor in charge of her. 17. Which diagnostic methods can be safely used during pregnancy? Abdominal ultrasonography and rectal ultrasonography are not harmful to the mother and child. These tests can provide important information about the activity of the disease and the course of the disease. Gastroscopy and colonoscopy are perfectly safe for women during pregnancy as long as they are well prepared and an experienced and skilled physician is the examiner. MRI is not harmful and can be performed with confidence. For radiological examinations, careful consideration should be given. They should be selected only if the condition is critical and the test must be performed. In general, radiological examinations in the second trimester are relatively safe. Of course, the detection of the disease can be understood through blood tests such as routine blood, CRP and blood sedimentation. 18.What kind of special considerations are necessary for delivery? For pregnant women with inflammatory bowel disease, vaginal delivery is preferable. In patients who have already had a colostomy, vaginal delivery is preferable because uterine contractions can cause the fistula to sag during delivery and abdominal pressure can easily rise. This is also not affected by any adhesions that may remain from previous surgery. However, many obstetricians prefer to perform a cesarean section. Cesarean delivery is beneficial for those pregnant women who have fistula formation in the rectopelvic region. Therefore, the exact choice of delivery method for patients with colostomy should be determined on a case-by-case basis, in advance, in consultation with the obstetrician. The claim that perineal incision puts the risk of rectal abscess formation at an increased risk is not certain at this time. Most obstetricians believe that, to date, there is no basis for an increased incidence of rectal abscesses after episiotomy. 19. Is a special diet during pregnancy beneficial for women with inflammatory bowel disease? In general, patients with inflammatory bowel disease do not require a special diet. However, patients should follow a recommended balanced diet to get the right amount of energy, vitamins and minerals, etc. 20. How high is the risk of children of parents with inflammatory bowel disease growing up with the same disease? Parents with inflammatory bowel disease have a lower risk of their children developing the disease. Strictly speaking, inflammatory bowel disease has not been identified as a genetic disease, but it may have some genetic susceptibility. Children have a higher incidence of the disease than other populations in some later environment. Some investigations have confirmed a significantly higher incidence of inflammatory bowel disease in certain families. When another family member has the disease, the risk of other members having the disease is difficult to predict and can only be estimated empirically. In general, the relative risk area for developing the disease is 0-36%, and the intensity is related to the proximity of the person to the person who already has the disease. If both parents have inflammatory bowel disease, there is an increased chance of the child developing the disease. Nevertheless, we do not advocate that such parents should not have children. This is because there is currently no basis for this. Modern medical technology can treat and control inflammatory bowel disease very well. Patients should not have some artificial difference in their lives from normal healthy people. 21. Can women with inflammatory bowel disease breastfeed? It is no longer a problem for breastfeeding mothers to take corticosteroids (such as prednisone) or 5-ASA. This is because although a small amount of the drug can reach the infant through the breast milk, there is no permanent damage to the infant. Hormones can be detected in breast milk, but the effect on the newborn is small. For hormone doses above 20 mg/d, breastfeeding can be done 4 h after hormone administration to reduce the concentration of the drug in the breast milk. Glucocorticoids should be reduced as soon as possible. If higher doses of glucocorticosteroids are needed, the pediatrician should be consulted. The American Academy of Pediatrics (AAP) does not recommend breastfeeding while taking AZA because of its potential to suppress the immune system of the newborn. MTX and thalidomide are strongly teratogenic and are contraindicated in breastfeeding. Because the teratogenic effects of cyclosporine are not known, breastfeeding during treatment is contraindicated. As for biologics, IFX is safe to breastfeed and even if a small amount of IFX is secreted into the milk, it is inactivated by neonatal digestive enzymes and the ADA is secreted in less than 1% of serum and has a negligible effect on the neonatal immune system and is therefore safe.