Introduction
On March 10, 1958, the first woman to undergo kidney transplantation from her twin sister, she was able to bring a healthy baby without receiving Immunosuppression. This led to the important point that kidney transplantation could restore fertility, and normal kidney function alone is enough to tolerate pregnancy, and the proximity of the uterus to the kidneys cannot cause mechanical problems. The challenge for women undergoing transplantation with a pregnancy intention is that women are exposed to opportunistic infections, which have devastating effects on the fetus, because of their inability to avoid taking immunosuppressive drugs. On the other hand, these drugs may have the ability to be teratogens for the fetus. Obviously, women undergoing dialysis are significantly diminished in their ability to become pregnant, and it has been proven that kidney transplant significantly increases the chance of this ability. This can be generalized even in women with luteinizing hormone (LH) and follicular stimulatory hormones (FSH) in near menopause level, and after transplantation, hormonal levels have been activated and pregnancy has been re-established. However, in women aged 18 to 49 years with ESRD (End-Stage Renal Disease), childbirth is about 10 times lower than that of normal people, with an average of 1-7% in hemodialysis patients. In any case, the ability to get pregnant after kidney transplants is not a general rule. In a study conducted by Peterzaque et a. in 2006 on these women, it was observed that 68% of 63 women undergoing kidney transplants had a normal menstrual cycle, and ovulation (which can be verified by using elevated serum progesterone levels and observations of ultrasound scan) in 60% of women with normal menstrual cycle. However, it has not been determined that infertility in transplant recipients is more than the general population. Although it has been observed that Sirolimus, reduces the number of sperms and fertility in men, the effect of these drugs is still a question of increasing fertility in women. The issue of pregnancy and childbirth in a transplanted woman should be emphasized prior to transplantation and during counseling that immunosuppressive drugs should be continued during pregnancy, although these drugs should be modified before pregnancy. The reason for taking medications during pregnancy is that taking medications has less risk for fetus compared to reduction of kidney functions, and from medications, only mycophenolate has teratogenic effects. Another important issue that women should be aware of is that pregnancy should be postponed at least one to two years after the transplant.However, in many studies, it has been shown that a long delay in pregnancy following a transplant can reduce the chance of a pregnancy [1]. Therefore, the present study was conducted to investigate the immunologic factors in kidney transplantation and pregnancy.
In this study, more than 40 articles about immunologic factors involved in kidney transplantation, as well as pregnancy and kidney transplantation were investigated. With regard to renal transplantation studies, several factors are involved in this complication. Relevant sources and line guides on kidney transplantation and pregnancy were reviewed and presented in the light of the experiences of the researcher.
NTPR (National Transplantation Pregnancy Registry) is the largest research organization of pregnancy outcomes in women of the kidney recipient until this time. Within 20 years, the organization has collected 922 women who have undergone kidney transplants and 1490 pregnancies have occurred for them. In the study of these women, interesting results have been observed [2] (Table 1).

Table 1) Results of NTPR research on pregnancy outcomes in renal receptor women

 

In addition, NTPR has mentioned in its research that pregnancy in these individuals has a higher rate of defect in fetal development and intrauterine growth restriction. Also, 52% of pregnancies has ended before 37 weeks.
Kidney transplantation line referrals and guidelines for women have listed items that should be considered in connection with pregnancy after transplantation (Table 2).

Table 2) Guidelines for pregnancy after transplantation

 

Treatment and considerations for pregnant women under transplantation
1) Reduction of transplanted renal function: Reduction of transplanted renal function during pregnancy is common, and is found to be between 10-18%, which is either permanent or after a period of pregnancy [3]. These women have different causes for reducing renal function, which is rarely due to the growth of the uterus during pregnancy and the pressure on the kidneys, may reduce the function of the kidney transplant. On the other hand, because of the need for changes in cyclosporine A or other immunosuppressive drugs, there is a possibility of kidney damage. It has been shown in numerous studies that the risk of renal transplant failure is likely to increase in the future if maternal creatinine is greater than 0.5 mg / dL and proteinuria is greater than 500 mg / day [4]. One of the most important causes of creatinine increase after transplantation is acute rejection of the transplant, but it is known that acute rejection of the transplant one year after transplantation is rare. In any case, if we suspect acute rejection, the biopsy of the kidney must be done to prove it. Other causes of creatinine increase include preeclampsia in these individuals, that its differentiation them from other causes of increased creatinine disturbances. However, problems with this pathway can be somewhat overcome by measuring the antiangiogenic factors.
These women, if they have blood pressure, are at risk of developing preeclampsia with an incidence of 15-25%. While if these people do not have blood pressure, this risk is 5% [5]. Preeclampsia is a syndrome that presents itself with hypertension and a new onset and proteinuria attack during the second half of pregnancy. This syndrome causes severe maternal and fetal complications, such as renal failure, HELLP syndrome (hemolysis, elevated liver enzymes, and thrombocytopenia), epilepsy, hepatic failure, stroke, and maternal death. In the fetus of preeclampsia, it causes lack of growth, preterm delivery, and neurological damage resulting from hypoxia and death.
2) Blood pressure: Increased blood pressure in pregnant women is common. The information indicates that during normal pregnancy, during the first period, the blood pressure is at its lowest level and goes back to pre-pregnancy levels at a late stage of pregnancy. Many of the antihypertensive drugs are safe during pregnancy, and the treatment usually starts at a pressure above 140/90 mmHg. Choosing the best blood pressure medication in pregnant women depends on the severity of blood pressure. In mild hypertension, methyldopa is used. Other accepted drugs for use are lebutala, nifedipine and thiazides, but ACEI (angiotensin converting enzyme inhibitors) and angiotensin receptor blockers and atenolol should not be used.
3) Anemia: Anemia is common in renal transplant women, even in those with mild chronic kidney disease, hematocrit rarely exceeds 30-40%. On the other hand, immunosuppressive drugs may reduce bone marrow activity and contribute to anemia. In a normal pregnancy, women need about 700-1000 mg of iron and need more after 30 weeks of gestation. Erythropoietin does not appear to be teratogenic in these women, but in all renal patients, the risk of increased stroke with high doses of erythropoietin should be taken into account. For this reason, it is logical that other factors that cause anemia be corrected when hemoglobin is less than 10 mg / dL, and erythropoietin is used in these women.
4) Immunosuppressive drugs:
A. Prednisolone: ​​As pregnancy progresses, the level of prednisolone passes through cord, so that at the end of pregnancy, the ratio of maternal prednisolone to cord is about 8 to 1 to 10 to 1. Prednisolone increases the risk of hypertension and gestational diabetes mellitus. If the dose of prednisone is greater than 20 mg per day, the risk of opportunistic infections increases.
B. Azathioprine: This drug is in Group D in pregnant women. Studies by numerous researchers have showed that the percentage of congenital adaptation of the neonates with the consumption of this drug does not statistically change much with congenital defects in mothers who do not consume it [6].
C. Cyclosporine A: This drug is necessary to prevent rejection of implant, and it has been proven that the drug well transferred via placenta but it has been shown that with taking or not taking of this drug, the found defects are almost identical. The dosage of the drug should be adjusted in terms of the amount of drug left in the blood, and this should be done every month. The remained dose for this drug is about 200-300 ng / ml during the first 2 months of pregnancy and is then reduced to about 100-200 ng / ml.
D. Tacrolimus: The placenta seems to be a strong barrier for tacrolimus, so that the levels of tacrolimus in placenta 56 is 2 times higher than cord blood and is 4 times higher than the mother's blood, and 36% of the infants  whose mother consume tacrolimus during pregnancy, had transient hyperkalemia and mild renal impairment [7]. The remained tolerable dose for this drug is 10-15 mg / L for the first 2 months of pregnancy, and then this dose is reduced to 5-10 mg / L.
E. Mycophenolate mofetil: This drug is contractile during pregnancy because it causes significant imbalance in the fetus, including small ears, cleft palate, auditory canal atresia, small mouth, eye coloboma, small fingers and hypoplastic nails. Therefore, this medication should be discontinued at least 6 weeks before pregnancy.
F. Antibodies: There is little information on the use of monoclonal and polyclonal antibodies during pregnancy, and one year pregnancy postpone after renal transplantation can reduce the risk of acute rejection of the transplant and hence the likelihood of antibodies being used. All types of immunoglobulins are more likely to cross the placenta with gestational age. Particularly, during the last month of pregnancy, women who have had an acute rejection of the transplant and who have received antibodies are advised to avoid at least one year for pregnancy after receiving antibodies.
5) Infections caused by renal transplantation:
A. Cytomegalovirus (CMV): Pregnant women undergoing renal transplantation are at risk for opportunistic infections. The most common of these infections is CMV. If the CMV infection is in the mother's early pregnancy, the chance of transmission to the fetus is about 30-40%, and if the mother's CMV infection is recurrent, the chance of transplantation becomes 1%, and the more the mother reaches to the end of pregnancy, the greater is the chance of a disease transmission. However, if the disease is transmitted at the beginning of pregnancy, it will be more intense in the fetus [8]. If the mother is seriously ill, she should take antiviral medicine. These drugs are safe during pregnancy. Diagnosis of intrauterine CMV infection is performed using the amniotic fluid polymerase chain reaction for CMV. Fetal infection with CMV may lead to microcephaly, intracerebral calcification and growth impairment.
B-Herpes Simplex Virus (HSV): The transmission of this disease is usually from the mother to the fetus during birth through the uterus. Therefore, the chances of transmitting disease from mother to fetus decrease with cesarean section.
C-Toxoplasmosis: Primary toxoplasma infection in pregnant women include 25-65% of children's toxoplasmosis infections. The closer to the end of pregnancy, the greater is the chance of neonatal involvement, but the severity of the disease is reduced. To diagnose the disease in the fetus, an amniotic fluid PCR for toxoplasmosis and the magnitude of fetal brain ventricles using ultrasound can be used in weeks 20-24. Even if the mother is not heavily ill, she should be treated with cure. Even if the anti-Toxoplasmosis antibody titer of pregnant women increases with immunosuppressive drugs, the mother should be treated again and pregnant mothers undergoing renal transplantation should be evaluated for toxoplasmosis in each period.
D. Urinary tract infections (UTI): This infection is the most common non-opportunistic infection in pregnant women undergoing renal transplantation. Some studies have cited it in pregnant mothers as high as 40% [9]. These mothers may even have pyelonephritis with a negative urine culture and should be checked for urine a month. The reason is that the urethra is enlarged and pressured by the womb. Therefore, the likelihood of acute pyelonephritis increases in the mother receiving the anti-immunological drug.
6) Lactation: It is generally recommended that women who are under any transplant avoid lactation. NTPR has reported lactation without any side effect in the fetus in 2011[2]. At present, no side effect has yet been seen in infants by lactation, but caution is required to refrain from lactation until information is complete.
7) Pregnancy status in women whose husband is undergoing renal transplantation: Several studies have shown that pregnancies in women whose husbands are undergoing renal transplantation are similar to those of the general population and do not have a significant change [10].
Conclusion
There are still many uncertainties about renal transplantation and its complications during pregnancy, and it is not well known how much it can have short-term or long-term effects on mother and fetus. Therefore, the necessity of more extensive research in this field and the comprehensive examination of its effects seems necessary.

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Contribution of authors
Contribution of the authors: Nader Rabat Moradi (First author), all the sections of this article has been carried out by him [100%).
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