Clin J Am Soc Nephrol 3: S117-S125, 2008
© 2008 American Society of Nephrology
doi: 10.2215/CJN.02980707
Pregnancy after Kidney Transplantation
Dianne B. McKay*, and
Michelle A. Josephson
* Department of Immunology, The Scripps Research Institute, La Jolla, California; and Section of Nephrology, Department of Medicine, University of Chicago, Chicago, Illinois
Correspondence: Dr. Dianne B. McKay, Department of Immunology, IMM-1, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037. Phone: 858-784-9716; Fax: 858-784-8069; E-mail: dmckay{at}scripps.edu
 |
Abstract
|
|---|
Reproductive success is a common, expected outcome for male and female recipients of solid-organ transplants. Men can father children, and women can become pregnant and carry the fetus to delivery. There are, however, important maternal and fetal complications that need to be considered to provide optimal care to the mother and her infant. Although pregnancy is common after the transplantation of all solid organs, guidelines for optimal counseling and clinical management are limited. This review discusses information to help the physician counsel the kidney transplant recipient about risks of pregnancy for the mother and the fetus and provides information to help guide treatment of the pregnant transplant recipient.
|
Prevalence of Pregnancy in Transplant Recipients
|
|---|
End-stage organ disease disrupts normal gonadal function; consequently, pregnancies in patients with end-stage disease are still relatively uncommon (1). Fertility is improved within months after the successful replacement of an infirmed organ (2); therefore, it is not surprising that increasing numbers of pregnancies are reported in patients with transplanted kidneys, liver, heart, lungs, and small bowel and even in those with multiple organ transplants. The numbers of pregnancies that have actually occurred in maternal or paternal transplant recipients have not been quantified. In an attempt to estimate numbers of pregnancies that have occurred in transplant recipients, Davison and Baylis (3) tabulated all pregnancies reported within the worldwide literature up to the year 2001. Reports of 14,000 pregnancies were acquired through review of case, center, and registry reports. Certainly this number is an underestimation, because reporting of all pregnancies in transplant recipients is no longer widespread practice.
Several pregnancy registries exist and have published information on maternal, paternal, and infant outcomes. Three of these registries have reported the largest numbers to date and include in United States the National Transplantation Registry (NTPR), a voluntary registry initiated in 1991 that relies on transplant center or patient self-reporting (4); the United Kingdom Registry, which has collected information on the majority of transplantation units in the United Kingdom from 1997 to 2002 (5,6), and the European Dialysis and Transplant Association Registry, which collected information on outcomes from European countries (7). The NTPR registry has reported approximately 1500 outcomes in female and 1000 outcomes in male transplant recipients (4), the European Dialysis and Transplant Association has reported approximately 400 pregnancies in renal transplant recipients, and the UK Registry has reported data on outcomes of approximately 200 transplant recipients. Although these registries provide essential information, a comparison of the total number of pregnancies tabulated in the three registries with the total number of patients reported in the literature by the year 2001 shows that the three registries have captured only a minority of the pregnancies in transplant recipients. Because many more have occurred than have been reported, the registries have captured information on far fewer pregnancies than can be estimated by tabulations of reported pregnancies. Unfortunately, registry data are limited by small patient numbers and by unavoidable reporting bias. It is important to realize these limitations because the registry data provide the primary source of data that guide patient treatment. The limited published information is a wake-up call to the need for enhanced registry reporting as well as large-scale prospective studies that allow the design of evidence-based care of the pregnant transplant recipient, information that is essential to providing accurate advice for preconception counseling.
|
Fertility, Contraception, and Optimal Timing of Pregnancy
|
|---|
Male and female patients with end-stage kidney disease commonly experience sexual dysfunction and infertility as a result of endocrine aberrations, vasomotor dysfunction, prescribed medications, and psychological factors (8,9). Sexual function in both men and women improves after transplantation (8,10–12), although one report suggested that one quarter of patients remained sexually dysfunctional 3 yr after transplantation (12). Female infertility results from altered hypothalamic function and is associated with high follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin levels (8). The hormone aberrations are usually reversed after transplantation, resulting in normal ovulatory cycles and regular menstruation (8,13,14). Many women with chronic kidney disease (CKD) experience premature menopause, on an average of 4.5 yr earlier than in the general population (15); therefore, chronological age and risk for early menopause should be considered in the optimal timing of pregnancy after transplantation.
Male infertility during ESRD is associated with low testosterone; high FSH, LH, and prolactin levels; and high estrogen levels, resulting in impotence as well as spermatogenic abnormalities (8,16). The testis is marked by several signs of histologic injury, including germinal aplasia and seminiferous tubule destruction, the extent of which determines the reversibility after transplantation (8,16). Transplantation restores the balance in the hypothalamic-pituitary axis and consequently is associated with improvements in sperm motility but not in sperm counts or morphology (17). The true incidence and prevalence of infertility are difficult to determine, and it is unknown whether immunosuppressive medications have an independent effect on fertility of the recipient, although calcineurin inhibitors (CNI) and azathioprine do not seem to alter male fertility after transplantation (18). There have been several reports of male infertility associated with sirolimus, marked by low free testosterone and significantly elevated levels of LH and FSH (19). Sirolimus seems to cause a block in testosterone synthesis at either the receptor or the postreceptor level, where the cascade of transformation of cholesterol into testosterone might be inhibited (18).
One potential way to gauge prevalence of infertility in the posttransplantation population is to tabulate usage of assisted reproduction by transplant recipients. Indeed, several cases of female renal transplant patients who have undergone successful in vitro fertilization treatments have been reported (20–23). As a word of caution, these treatments might result in pregnancies that are more complicated than natural pregnancies, particularly because of the risk for multiple births (24,25). Although there are no reports yet tabulating the incidence or prevalence of assisted reproduction usage by transplant recipients, this might be a useful exercise that could help yield information about infertility in transplant recipients. The predominance of reports on pregnancies after transplantation suggest restoration of fertility to an extent that at least should inspire the practicing transplant physician to advise the patient with a new transplant to use effective contraception.
Optimal contraception is important to initiate before transplantation in women of childbearing age. Contraception should be used before transplantation, because there have been several reports of women who were pregnant in the peritransplantation period (26–29). The peritransplantation period is not the optimal time for pregnancy because this is a time of highest use of potentially fetotoxic or teratogenic medications and a time when optimization of immunosuppression is essential. The best contraception has historically been considered to be barrier methods, but because of potential for contraception failure, the American Society of Transplantation Consensus Conference report recommended that transplant recipients be advised that barrier methods and intrauterine devices are not optimal forms of contraception (30). Intrauterine devices are not optimal because they require an intact immune system for efficacy (31). Progestin-only oral contraceptives as well as estrogen/progestin are probably acceptable for use in this patient population as long as hypertension is well controlled (32–34). The best contraceptive agent to use after transplantation depends on considerations, made between the patient and her physician, of the desirability of pregnancy and considerations of the risks and benefits of each contraceptive method (30).
The optimal timing of pregnancy depends somewhat on individual circumstances of the transplant recipient. Historically, the recommendation was to wait 2 yr after successful transplantation (33). This recommendation has been replaced by the American Society of Transplantation Consensus Opinion that as long as graft function is optimal, defined as a serum creatinine <1.5 mg/dl, with <500 mg/24 h protein excretion, and no concurrent fetotoxic infections or use of teratogenic or fetotoxic medications, and immunosuppressive dosing is stable at maintenance levels, the patient can safely proceed with the pregnancy (30). Given the increasing age of the transplant population, these recommendations might even be liberalized to waiting 6 mo after transplantation in specific situations (30,35). There have been no specific recommendations for male transplant recipients with regard to posttransplantation intervals and fathering a child.
A common concern during the peritransplantation period is the optimal choice of immunosuppressive agents for women who wish to become pregnant. The transplant physician is often confronted with a dilemma: To continue mycophenolate or rapamycin in a stable pregnant transplant recipient and risk fetal abnormalities or to switch the immunosuppressive regimen (e.g., to azathioprine). Fetal risks associated with immunosuppressive medications are discussed in the Risks of Pregnancy to the Fetus section, but it should be mentioned that current recommendations are to avoid mycophenolate mofetil (MMF) and rapamycin for 6 wk before pregnancy (30,35,36). A switch of immunosuppressive agents is particularly concerning in the stable patient prescribed a steroid-free, two-immunosuppressive drug regimen. Unfortunately, there are few data on which to base firm recommendations at this time.
|
Risks of Pregnancy to the Mother
|
|---|
Outcomes of pregnancy for the maternal transplant recipient must focus on the affect of the pregnancy on maternal graft function and on whether the pregnancy induces graft-independent comorbidities. Preexisting kidney disease is an independent risk factor for preeclampsia, prematurity, low birth weight, and neonatal death (37,38). In the transplant setting, the impact of kidney disease on these outcomes is influenced by the degree of renal dysfunction, preexisting hypertension, and the extent of proteinuria (38). A general guide for pre- and posttransplantation medical management of pregnancy is provided in Table 1.
An important concern for the potential mother is the effect of the pregnancy on long-term allograft function. Several studies have compared serum creatinine as an index of graft function before and after pregnancy (5,39–43). Observations from pregnant patients with CKD have shown that mild kidney disease (creatinine <1.3 mg/dl) does not seem to risk worsening of kidney function (38,44). Patients with moderate kidney disease (defined as serum creatinine of 1.3 to 1.9 mg/dl) or severe kidney disease (creatinine >1.9 mg/dl) often experience a decline in kidney function that can proceed to ESRD (38). Generally, the observations in patients with CKD support those in kidney transplant recipients, in who a serum creatinine 
1.3 mg/dl, independent of immunosuppressive drug use, confers little risk for short-term graft loss. Davison et al. (45) reported that a serum creatinine >1.5 mg/dl and proteinuria >500 mg/24 h significantly increase the risk for irreversible graft loss as a result of the pregnancy, consistent with expert consensus opinion (30).
Another significant risk to consider for the mother is graft rejection. As a result of changes in blood volume, maintenance of immunosuppressive medication dosing can be difficult, and vigilance of serum immunosuppressive levels is recommended (36,46,47). Data from the NTPR suggested that higher dosages of immunosuppressive medications are required to maintain graft function (48). By contrast, others have not modified immunosuppressive dosing and found no resulting graft dysfunction (49); however, the lack of negative consequences should not be interpreted to mean that it is without risk. The recommendation by the American Society of Transplantation Consensus Conference is that to avoid graft rejection, immunosuppressive dosing should be maintained at prepregnancy levels through frequent monitoring of serum drug levels (36,30,47,50). Pregnancy induces hyperfiltration in transplanted kidneys, as it does in normal kidneys during pregnancy (51); therefore, detection of rejection can be very difficult when monitoring for changes in serum creatinine. If rejection is suspected, then the kidney can be safely biopsied under ultrasound guidance (52). If rejection occurs, then it can be treated with corticosteroids (52,53). There are very few data on which to base recommendations for treatment of rejection with other agents, such as OKT3 or anti-thymocyte globulin (47).
Another maternal concern is hypertension during pregnancy, as a result of either preexisting chronic hypertension or the development of hypertension during gestation. Data from registry reports suggest a high prevalence of hypertension in pregnant renal transplant patients (up to 73% in the NTPR) (6,54,55). During normal pregnancy, BP is lowest in the first trimester but slowly returns to prepregnancy levels in late gestation. The transplant recipient often experiences a similar but blunted pattern of BP variation (52). Therapeutic targets for mild to moderate hypertension in the CKD population are not known, although recommendations have been made for treatment at BP levels 
150/90 mmHg (56). Treatment recommendations in the gravid renal transplant recipient have been more aggressive, with advice now to achieve a normotensive state (30,52). The optimal choice of antihypertensive therapy depends on the severity of hypertension. For mild hypertension, methyldopa was recommended by several consensus studies, because it is well tolerated and does not alter uteroplacental or fetal hemodynamics (57). Other antihypertensive agents that are considered acceptable include labetolol, nifedipine, and thiazide diuretics (57). For urgent BP control, hydralazine, labetolol, and nifedipine have been considered the drugs of choice (57). Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are contraindicated in pregnancy because of adverse fetal effects, and atenolol should be avoided because of concerns about fetal growth (56,57).
Maternal renal transplant patients with hypertension are at increased risk for development of superimposed preeclampsia, with an incidence of 15 to 25% compared with 5% of normotensive pregnancies (56). Preeclampsia is a syndrome characterized by the development of hypertension in association with new-onset proteinuria during the second half of pregnancy. The incidence of preeclampsia is up to 32% in kidney/pancreas recipients in the NTPR registry data (4); higher rates were reported in recent center reports (58,59). Preeclampsia causes severe maternal and fetal complications, such as renal failure, HELLP syndrome (hemolysis, elevated liver enzymes, and thrombocytopenia), seizures, liver failure, stroke, or death for the mother. For the fetus, preeclampsia can result in being small for gestational age, preterm delivery, hypoxic neurologic injury, or death (60). Diagnosis of preeclampsia is difficult in the gravid renal transplant recipient because BP commonly rises late in pregnancy and many patients have preexisting proteinuria (61). In addition, associated features of hyperuricemia and edema are often coexistent in renal transplant patients (62). It is interesting that histologic and molecular information show that preeclampsia is a disorder of placental hypoxia and endothelial dysfunction, although many mechanisms are yet unknown (60,63). Whether markers of preeclampsia such as angiogenic or antiangiogenc proteins will provide specific markers for preeclampsia is unknown but could provide a very important area for future study.
Other comorbidities to be considered in the maternal transplant recipient include gestational diabetes, anemia, and infections such as urinary tract infections (58,59,64–66). Because allograft recipients have increased risk for gestational diabetes, they should be screened every trimester with a 50-g oral glucose load (52). Urinary tract infections occur in up to 42% of pregnant renal transplant patients (64), although pyelonephritis is rare (52).
The maternal transplant recipient is placed at increased risk for infection as a result of the use of immunosuppressive medications; therefore, maternal–fetal transmission of infectious agents needs to be considered as a potential risk not only to the mother but also to the fetus. Cytomegalovirus infection is particularly serious because it is associated with hearing/vision loss and mental retardation and can be transmitted from the mother to the fetus through a transplacental route, as well as during delivery or breastfeeding (52,67). Unfortunately, the presence of maternal immunity does not absolutely protect the fetus, although it does reduce the likelihood of transmission (68,69). Antiviral medication prophylaxis has not generally been recommended during pregnancy (70). Other infections that may pose additional risks in the immunosuppressed mother include toxoplasmosis, primary herpes simplex infection, primary varicella infection, HIV infection, and infection with either hepatitis B or C virus (71,72). Prenatal screening can detect each of these infections, although in many cases the mother presents before prenatal screening when maternal prophylaxis can no longer be considered.
It is interesting that most infants are delivered by cesarean section (6), although the presence of the transplanted kidney in the false pelvis does not in itself indicate the need for cesarean delivery (52,73). Expert consensus opinion has been that unless there is an obstetric reason to indicate cesarean delivery, vaginal delivery is preferred (30).
|
Risks of Pregnancy to the Fetus
|
|---|
Determining risks of pregnancy from the fetus’s perspective requires consideration of length of gestation, maternal health, transmission of infections, and risks associated with in utero immunosuppressive exposure on organogenesis and maturation. Published registry reports, as well as case and center reports, consistently point to a high risk for preterm delivery (<37 wk) and low birth weight (<2500 g). The rates of preterm delivery have been reported to be approximately 50% in the US and European and UK registries (47) and even higher (64%) in recent center reports (65). Most deliveries occur early because of maternal and/or fetal compromise, rather than spontaneous preterm labor (52). Transplant recipients are at high risk for premature rupture of membranes, which also contributes to the increased risk for preterm labor, as does pyelonephritis and acute allograft rejection (52).
The mean gestational age at delivery in kidney transplant recipients is 34 wk (52), and approximately 50% of infants are delivered with low birth weight (47). Approximately 22% of the infants in the UK registry had very low birth weight (<1500 g) (6). Sibanda et al. (6) reported that when adjusted for gestational age, there was no significant association between birth weight and any other factor, except perhaps drug-treated hypertension, suggesting that fetal growth was not compromised. Because of likelihood of preterm delivery, recommendations are to give steroids late in pregnancy (between 28 and 34 wk) to promote lung maturity, if there is any sign of fetal compromise (52,74). This recommendation is applicable to the fetus with intrauterine growth restriction (IUGR), because there is a high rate of associated perinatal mortality (52). The definition for IUGR includes being 10th percentile of weight for gestational age, suggesting a pathologic alteration in the placenta. The incidence of IUGR is as high as 30 to 50% in kidney transplant patients, believed to be secondary to the existing hypertension and kidney disease and the propensity of these women to develop preeclampsia (52,61,75). Serial sonographic assessments of fetal growth are recommended in pregnant transplant recipients to help assess for evidence of fetal growth compromise (52).
The consequences of low and very low birth weight for the fetus are substantial and include varied neurologic, endocrine, cardiac, and renal abnormalities (76–83). Prospective evaluations of childhood development have not been conducted in infants who were born to transplant recipients. Data from the NTPR are limited but suggest that developmental delays have been seen in up to 26% of children after the age of 5 yr (84). The significance of this finding, though, is not known, because prospective neurocognitive testing has not routinely been performed on children who were born to maternal transplant recipients.
A major concern for the fetus is the potential effects of in utero exposure to medications during organogenesis and development. In the transplant setting, there is no choice but to expose the fetus to immunosuppressive agents, because all immunosuppressive medications pass through the maternal–fetal circulation to varying degrees (47). There is much still to be learned about the pharmacokinetics and pharmacodynamics of medications that routinely are given to maternal transplant recipients, making assertions about medication exposures difficult. There is no reliable information that can be derived from the Food and Drug Administration labeling because of limited clinical data on which to determine the safety of many medications during pregnancy (57). None of the medications is labeled A; in other words, there are no prospective, randomized trials indicating safety (Table 2). Further complicating the situation is that there are unknown alterations in drug bioavailability, drug elimination, and activity and distribution of drug transporters within the placenta and fetus during pregnancy (85). All immunosuppressive medications have been detected to varying degrees in either the placental or the fetal circulation. The placenta metabolizes prednisone; therefore, only low levels have been detected in the fetal circulation. Azathioprine is a prodrug that is rapidly metabolized to 6-mercaptopurine. This moiety does pass into the fetus; however, a relative fetal lack of the enzyme inosine pyrophosphorylase prevents it from being transformed into its active form thioinosinic acid (86). CNI readily cross the placenta and enter the fetal circulation. In fact, in one study, it was found that cyclosporine in fetal blood was able to inhibit T cell function to the same degree as that found in maternal serum (87). Much less is known about the maternal–fetal transport of MMF and sirolimus.
Immunosuppressive medication exposure may continue after birth if the mother opts to breastfeed. Most physicians advise against breastfeeding (30), although this has not persuaded all new mothers with kidney transplants. The American Academy of Pediatrics supports breastfeeding for mothers who are taking prednisone and advises against it for those who are taking cyclosporine (88). There are no specific American Academy of Pediatrics recommendations for mothers who are taking azathioprine or tacrolimus (88). Prednisone and azathioprine are detected in breast milk (in small amounts) (89), but there are no human data for MMF or sirolimus. Studies are needed on pharmacokinetics and transfer of immunosuppressive medications to breast milk. Until these studies are available, expert consensus is that breastfeeding need not be seen as absolutely contraindicated (30).
The impact of immunosuppressive exposure on the developing fetus is often measured by the presence of major structural malformations at birth. Data from the NTPR registry as well as many case and center reports suggest that the incidence of major malformations is not much higher than that in the general population. A concern, though, has been raised for in utero exposure to MMF, which may be associated with severe structural malformations in case reports and in NTPR registry data (90–92). Information regarding sirolimus is still too limited to make recommendations. It should be mentioned that it is often difficult to discern which agent is responsible for birth defects because patients are often taking more than one immunosuppressive agent.
It is not known whether infants who are born to maternal transplant recipients have an increased risk for more subtle defects. Subtle defects that may not be apparent at birth are difficult to measure and require greater evaluations than can be obtained by observational studies. CNI have been known for many years to target a critical phase in T cell development within the fetal thymus. By blocking normal T cell development, CNI have been shown to block the normal process by which self-reactive T cells are eliminated during thymic development, leading to autoimmunity in animal models (93–95). Whether exposure to CNI increases the likelihood of autoimmunity in offspring of transplant recipients is not yet known, although one case report suggested that there might be an association (96). Concerns have also been raised about neurocognitive deficits. It is has been known for some time that calcineurin and FKBP12 (FK506-binding protein) are enriched in the fetal brain and stimulation with FK506 causes functional changes in the fetal brain (97,98). There are may other factors, though, that might also contribute to alterations in fetal neurologic development in the gravid transplant recipient (99–102). Whether subtle defects are induced during pregnancies of maternal transplant recipients is not known; therefore, this is an area that requires more study, optimally by prospective analysis of children who are born to transplant recipients. While these and other appropriate studies are designed, it is critically important that all pregnancies be reported to existing transplantation registries so that information continues to accumulate on the outcomes of maternal and paternal transplant recipients and their offspring.
|
Risks of Pregnancy to Female Kidney Donors
|
|---|
The issue of kidney donation and subsequent pregnancy has been mostly ignored, but it has been part of the transplant pregnancy story from the very beginning. The first woman with a kidney transplant to deliver a child received her kidney from an identical twin (103). Not only did this individual go on to become pregnant after the transplant operation, but so did her sister (103). Several small self-reporting surveys of women who became pregnant after donation indicated little cause for concern (104,105). A recent abstract presented at the 2006 meeting of the American Society of Nephrology brought out the possibility that donation may increase the risk for preeclampsia in postdonation pregnancies (106). Further data, though, are needed before any firm conclusions are drawn. This potentially important observation finding serves as a call for additional investigation in this area, particularly when living donation is increasing and woman constitute nearly 60% of live donors (107).
|
Conclusions
|
|---|
There are many questions to be answered about the safety of pregnancy in the transplant setting. Transplant recipients and their donors have been conceiving for more than 50 yr, yet only limited, retrospective data are available about the short- and long-term outcomes for the mother and her infant. Concerns linger for both the mother and the fetus as a result of a paucity of data on which to base treatment recommendations and on which to offer advice to prospective parents.
|
Disclosures
|
|---|
None.
|
References
|
|---|
- Reddy SS, Holley JL: Management of the pregnant chronic dialysis patient.
Adv Chronic Kidney Dis14
:146
–155,2007[CrossRef][Medline]
- Davison JM: Dialysis, transplantation, and pregnancy.
Am J Kidney Dis17
:127
–132,1991[Medline]
- Davison JM, Baylis C: Renal disease. In:
Medical Disorders in Medical Practice, 4th Ed., edited by De Swiet M, Malden, Blackwell Publishing, pp198
–266,2002
- Armenti VT, Radomski JS, Moritz MJ, Gaughan WJ, Hecker WP, Lavelanet A, McGrory CH, Coscia LA: Report from the National Transplantation Pregnancy Registry (NTPR): Outcomes of pregnancy after transplantation.
Clin Transpl103
–119,2005
- Sibanda N, Briggs JD, Davison JM, Johnson RJ, Rudge CJ: Outcomes of pregnancy after renal transplantation: A report of UK Transplant Pregnancy Registry.
Hypertens Pregnancy23[Suppl 1]
:136
,2004
- Sibanda N, Briggs JD, Davison JM, Johnson RJ, Rudge CJ: Pregnancy after organ transplantation: A report from the UK Transplant pregnancy registry.
Transplantation83
:1301
–1307,2007[CrossRef][Medline]
- Rizzoni G, Ehrich JH, Broyer M, Brunner FP, Brynger H, Fassbinder W, Geerlings W, Selwood NH, Tufveson G, Wing AJ: Successful pregnancies in women on renal replacement therapy: Report from the EDTA registry.
Nephrol Dial Transplant7
:279
–287,1992[Abstract/Free Full Text]
- Anantharaman P, Schmidt RJ: Sexual function in chronic kidney disease.
Adv Chronic Kidney Dis14
:119
–125,2007[CrossRef][Medline]
- Palmer BF: Sexual dysfunction in uremia.
J Am Soc Nephrol10
:1381
–1388,1999[Free Full Text]
- Raiz L, Davies EA, Ferguson RM: Sexual functioning following renal transplantation.
Health Soc Work28
:264
–272,2003[Medline]
- Ghahramani N, Behzadi A, Gholami S, Salahi H, Rais-Jalali GA, Malek-Hosseini SA, Ahmad E, Behzadi S, Jan-Ghorban P: Postrenal transplant improvement of sexual function.
Transplant Proc31
:3144
,1999[CrossRef][Medline]
- Schover LR, Novick AC, Steinmuller DR, Goormastic M: Sexuality, fertility, and renal transplantation: a survey of survivors.
J Sex Marital Ther16
:3
–13,1990[Medline]
- Saha MT, Saha HH, Niskanen LK, Salmela KT, Pasternack AI: Time course of serum prolactin and sex hormones following successful renal transplantation.
Nephron92
:735
–737,2002[CrossRef][Medline]
- Lim VS, Henriquez C, Sievertsen G, Frohman LA: Ovarian function in chronic renal failure: Evidence suggesting hypothalamic anovulation.
Ann Intern Med93
:21
–27,1980[Medline]
- Holley JL, Schmidt RJ, Bender FH, Dumler F, Schiff M: Gynecologic and reproductive issues in women on dialysis.
Am J Kidney Dis29
:685
–690,1997[Medline]
- Zeyneloglu HB, Oktem M, Durak T: Male infertility after renal transplantation: Achievement of pregnancy after intracytoplasmic sperm injection.
Transplant Proc37
:3081
–3084,2005[CrossRef][Medline]
- Akbari F, Alavi M, Esteghamati A, Mehrsai A, Djaladat H, Zohrevand R, Pourmand G: Effect of renal transplantation on sperm quality and sex hormone levels.
BJU Int92
:281
–283,2003[CrossRef][Medline]
- Tondolo V, Citterio F, Panocchia N, Nanni G, Favi E, Brescia A, Castagneto M: Gonadal function and immunosuppressive therapy after renal transplantation.
Transplant Proc37
:1915
–1917,2005[CrossRef][Medline]
- Kaczmarek I, Groetzner J, Adamidis I, Landwehr P, Mueller M, Vogeser M, Gerstorfer M, Uberfuhr P, Meiser B, Reichart B: Sirolimus impairs gonadal function in heart transplant recipients.
Am J Transplant4
:1084
–1088,2004[CrossRef][Medline]
- Tamaki M, Ami M, Kimata N, Tsutsui T, Watanabe Y, Saito T, Muto J, Kumagai N, Shimizu A, Saito K, Takahashi K: Successful singleton pregnancy outcome resulting from in vitro fertilization after renal transplantation.
Transplantation75
:1082
–1083,2003[Medline]
- Khalaf Y, Elkington N, Anderson H, Taylor A, Braude P: Ovarian hyperstimulation syndrome and its effect on renal function in a renal transplant patient undergoing IVF treatment: Case report.
Hum Reprod15
:1275
–1277,2000[Abstract/Free Full Text]
- Furman B, Wiznitzer A, Hackmon R, Gohar J, Mazor M: Multiple pregnancies in women after renal transplantation: Case report that rises a management dilemma.
Eur J Obstet Gynecol Reprod Biol84
:107
–110,1999[CrossRef][Medline]
- Lockwood GM, Ledger WL, Barlow DH: Successful pregnancy outcome in a renal transplant patient following in-vitro fertilization.
Hum Reprod10
:1528
–1530,1995[Abstract/Free Full Text]
- Wang JX, Norman RJ, Kristiansson P: The effect of various infertility treatments on the risk of preterm birth.
Hum Reprod17
:945
–949,2002[Abstract/Free Full Text]
- Jackson RA, Gibson KA, Wu YW, Croughan MS: Perinatal outcomes in singletons following in vitro fertilization: A meta-analysis.
Obstet Gynecol103
:551
–563,2004[Medline]
- Hold PM, Wong CF, Dhanda RK, Walkinshaw SA, Bakran A: Successful renal transplantation during pregnancy.
Am J Transplant5
:2315
–2317,2005[CrossRef][Medline]
- Miller BW, Howard TK, Goss JA, Mostello DJ, Holcomb WL Jr, Brennan DC: Renal transplantation one week after conception.
Transplantation60
:1353
–1354,1995[Medline]
- Pergola PE, Kancharla A, Riley DJ: Kidney transplantation during the first trimester of pregnancy: Immunosuppression with mycophenolate mofetil, tacrolimus, and prednisone.
Transplantation71
:994
–997,2000
- Kenny LC, Baker PN, Venning M, Parrott N: Successful renal transplant during the first trimester of pregnancy.
Transpl Int20
:390
–391,2007[CrossRef][Medline]
- McKay D, Josephson M: Reproduction and transplantation: Report on the AST consensus conference on reproductive issues and transplantation.
Am J Transplant5
:1
–8,2005[CrossRef][Medline]
- Zerner J, Doil KL, Drewry J, Leeber DA: Intrauterine contraceptive device failures in renal transplant patients.
J Reprod Med26
:99
–102,1981[Medline]
- Lessan-Pezeshki M, Ghazizadeh S, Khatami MR, Mahdavi M, Razeghi E, Seifi S, Ahmadi F, Mazia S: Fertility and contraceptive issues after kidney transplantation in women.
Transplant Proc36
:1405
–1406,2004[CrossRef][Medline]
- Davison JM, Bailey DJ: Pregnancy following renal transplantation.
J Obstet Gynaecol Res29
:227
–233,2003[CrossRef][Medline]
- Mastrobattista JM, Katz AR: Pregnancy after organ transplant.
Obstet Gynecol Clin North Am31
:415
–428,2004[CrossRef][Medline]
- Josephson MA, McKay DB: Considerations in the medical management of pregnancy in transplant recipients.
Adv Chronic Kidney Dis14
:156
–167,2007[CrossRef][Medline]
- EBPG expert group in renal transplantation: European best practice guidelines for renal transplantation. Section IV: Long-term management of the transplant recipient. IV. 10. Pregnancy in renal transplant recipients.
Nephrol Dial Transplant17]Suppl 4]
:50
–55,2002
- Fischer MJ, Lehnerz SD, Hebert JR, Parikh CR: Kidney disease is an independent risk factor for adverse fetal and maternal outcomes in pregnancy.
Am J Kidney Dis43
:415
–423,2004[CrossRef][Medline]
- Fischer MJ: Chronic kidney disease and pregnancy: Maternal and fetal outcomes.
Adv Chronic Kidney Dis14
:132
–145,2007[CrossRef][Medline]
- Sturgiss SN, Davison JM: Effect of pregnancy on long-term function of renal allografts.
Am J Kidney Dis19
:167
–172,1992[Medline]
- First MR, Combs CA, Weislttel P, Miodovnik M: Lack of effect of pregnancy on renal allograft survival or function.
Transplantation59
:472
–478,1995[Medline]
- Rahamimov R, Ben-Haroush A, Wittenberg C, Mor E, Lustig S, Gafter U, Hod M, Bar J: Pregnancy in renal transplant recipients: Long-term effect on patient and graft survival. A single-center experience.
Transplantation81
:660
–664,2006[CrossRef][Medline]
- Salmela KT, Kyllonen LE, Holmber C, Gronhagen-Riska C: Impaired renal function after pregnancy in renal transplant recipients.
Transplantation56
:1372
–1375,1993[Medline]
- Ghanem ME, El-Baghdadi LA, Badawy AM, Bakr MA, Sobhe MA, Ghoneim MA: Pregnancy outcome after renal allograft transplantation: 15 years experience.
Eur J Obstet Gynecol Reprod Biol121
:178
–181,2005[CrossRef][Medline]
- Katz AI, Davison JM, Hayslett JP, Singson E, Lindheimer MD: Pregnancy in women with kidney disease.
Kidney Int18
:192
–206,1980[CrossRef][Medline]
- Davison JM, Lind T, Uldall PR: Planned pregnancy in a renal transplant recipient.
Br J Obstet Gynaecol83
:518
–527,1976[Medline]
- Thomas AG, Burrows L, Knight R, Panico M, Lapinski R, Lockwood CJ: The effect of pregnancy on cyclosporine levels in renal allograft patients.
Obstet Gynecol90
:916
–919,1997[CrossRef][Medline]
- McKay DB, Josephson MA: Pregnancy in recipients of solid organs: Effects on mother and child.
N Engl J Med354
:1281
–1293,2006[Free Full Text]
- Armenti VT, Ahlswede KM, Ahlswede BA, Cater JR, Jarrell BE, Mortiz MJ, Burke JF Jr: Variables affecting birthweight and graft survival in 197 pregnancies in cyclosporine-treated female kidney transplant recipients.
Transplantation59
:476
–479,1995[Medline]
- Jain AB, Shapiro R, Scantlebury VP, Potdar S, Jordan ML, Flohr J, Marcos A, Fung JJ: Pregnancy after kidney and kidney-pancreas transplantation under tacrolimus: A single center’s experience.
Transplantation77
:897
–902,2004[CrossRef][Medline]
- Armenti V, Moritz M, Davison JM: Drug safety issues in pregnancy following transplantation and immunosuppression: Effects and outcomes.
Drug Saf19
:219
–232,1998[CrossRef][Medline]
- Davison JM: Changes in renal function in early pregnancy in women with one kidney.
Yale J Biol Med51
:347
–349,1978[Medline]
- del Mar Colon M, Hibbard JU: Obstetric considerations in the management of pregnancy in kidney transplant recipients.
Adv Chronic Kidney Dis14
:168
–177,2007[CrossRef][Medline]
- Hou S: Pregnancy in chronic renal insufficiency and end stage renal disease.
Am J Kidney Dis33
:235
–252,1999[Medline]
- Armenti VT, Moritz MJ, Davison JM: Pregnancy in female pediatric solid organ transplant recipients.
Pediatr Clin North Am50
:1543
–1560, xi,2003[CrossRef][Medline]
- Armenti VT, Moritz MJ, Cardonick EH, Davison JM: Immunosuppression in pregnancy: Choices for infant and maternal health.
Drugs62
:2361
–2375,2002[CrossRef][Medline]
- Podymow T, August P: Hypertension in pregnancy.
Adv Chronic Kidney Dis14
:178
–190,2007[CrossRef][Medline]
- Umans JG: Medications during pregnancy: Antihypertensives and immunosuppressives.
Adv Chronic Kidney Dis14
:191
–198,2007[CrossRef][Medline]
- Yassaee F, Moshiri F: Pregnancy outcome in kidney transplant patients.
Urol J (Tehran)4
:14
–17,2007
- Gutierrez MJ, Acebedo-Ribo M, Garcia-Donaire JA, Manzanera MJ, Molina A, Gonzalez E, Nungaray N, Andres A, Morales JM: Pregnancy in renal transplant recipients.
Transplant Proc37
:3721
–3722,2005[CrossRef][Medline]
- Baumwell S, Karumanchi SA: Pre-eclampsia: Clinical manifestations and molecular mechanisms.
Nephron Clin Pract106
:c72
–c81,2007[CrossRef][Medline]
- Stratta P, Canavese C, Giacchino F, Mesiano P, Quaglia M, Rossetti M: Pregnancy in kidney transplantation: Satisfactory outcomes and harsh realities.
J Nephrol16
:792
–806,2003[Medline]
- Morales J, Hernandez Poblete G, Andres A, Prieto C, Hernandez E, Rodicio J: Uric acid handling, pregnancy and cyclosporin in renal transplant women.
Nephron56
:97
–98,1990[Medline]
- Mutter WP, Karumanchi SA: Molecular mechanisms of preeclampsia.
Microvasc Res75
:1
–8,2008[CrossRef][Medline]
- Oliveira LG, Sass N, Sato JL, Ozaki KS, Medina Pestana JO: Pregnancy after renal transplantation: A five-yr single-center experience.
Clin Transplant21
:301
–304,2007[CrossRef][Medline]
- Cruz Lemini MC, Ibarguengoitia Ochoa F, Villanueva Gonzalez MA: Perinatal outcome following renal transplantation.
Int J Gynaecol Obstet96
:76
–79,2007[CrossRef][Medline]
- Ghanem ME, El-Baghdadi LA, Badawy AM, Bakr MA, Sobhe MA, Ghoneim MA: Pregnancy outcome after renal allograft transplantation: 15 years experience.
Reprod Biol121
:178
–181,2005
- Ross DS, Dollard SC, Victor M, Sumartojo E, Cannon MJ: The epidemiology and prevention of congenital cytomegalovirus infection and disease: Activities of the Centers for Disease Control and Prevention Workgroup.
J Womens Health (Larchmt)15
:224
–229,2006[CrossRef][Medline]
- Ornoy A, Diav-Citrin O: Fetal effects of primary and secondary cytomegalovirus infection in pregnancy.
Reprod Toxicol21
:399
–409,2006[CrossRef][Medline]
- Mendelson E, Aboudy Y, Smetana Z, Tepperberg M, Grossman Z: Laboratory assessment and diagnosis of congenital viral infections: Rubella, cytomegalovirus (CMV), varicella-zoster virus (VZV), herpes simplex virus (HSV), parvovirus B19 and human immunodeficiency virus (HIV).
Reprod Toxicol21
:350
–382,2006[CrossRef][Medline]
- Michaels MG: Treatment of congenital cytomegalovirus: Where are we now?
Expert Rev Anti Infect Ther5
:441
–448,2007[CrossRef][Medline]
- Gardella C, Brown ZA: Managing varicella zoster infection in pregnancy.
Cleve Clin J Med74
:290
–296,2007[Abstract/Free Full Text]
- Shiono Y, Mun HS, He N, Nakazaki Y, Fang H, Furuya M, Aosai F, Yano A: Maternal-fetal transmission of Toxoplasma gondii in interferon-gamma deficient pregnant mice.
Parasitol Int56
:141
–148,2007[CrossRef][Medline]
- Davison JM: Renal transplantation and pregnancy.
Am J Kidney Dis9
:374
–380,1987[Medline]
- Effect of corticosteroids for fetal maturation on perinatal outcomes. NIH Consensus Development Panel on the Effect of Corticosteroids for Fetal Maturation on Perinatal Outcomes.
JAMA273
:413
–418,1995[Abstract/Free Full Text]
- Davison JM, Lindheimer MD: Renal disorders. In:
Maternal-Fetal Medicine: Principles and Practice, 5th Ed., edited by Creasv RK, Resnik R, Iams J, Philadelphia, Saunders, pp901
–924,2004
- Phillips DI: Programming of the stress response: A fundamental mechanism underlying the long-term effects of the fetal environment?
J Intern Med261
:453
–460,2007[CrossRef][Medline]
- Neubauer AP, Voss W, Kattner E: Outcome of extremely low birth weight survivors at school age: The influence of perinatal parameters on neurodevelopment.
Eur J Pediatr167
:87
–95,2008[CrossRef][Medline]
- Phillips DI: External influences on the fetus and their long-term consequences.
Lupus15
:794
–800,2006[Abstract/Free Full Text]
- Saenger P, Czernichow P, Hughes I, Reiter EO: Small for gestational age: Short stature and beyond.
Endocr Rev28
:219
–251,2007[Abstract/Free Full Text]
- Schreuder M, Delemarre-van de Waal H, van Wijk A: Consequences of intrauterine growth restriction for the kidney.
Kidney Blood Press Res29
:108
–125,2006[CrossRef][Medline]
- Gluckman PD, Hanson MA: The consequences of being born small: An adaptive perspective.
Horm Res65[Suppl 3]
:5
–14,2006
- Reyes L, Manalich R: Long-term consequences of low birth weight.
Kidney Int SupplS107
–S111,2005
- Taylor HG, Minich N, Bangert B, Filipek PA, Hack M: Long-term neuropsychological outcomes of very low birth weight: Associations with early risks for periventricular brain insults.
J Int Neuropsychol Soc10
:987
–1004,2004[CrossRef][Medline]
- Stanley CW, Gottlieb R, Zager R, Eisenberg J, Richmond R, Moritz MJ, Armenti VT: Developmental well-being in offspring of women receiving cyclosporine post-renal transplant.
Transplant Proc31
:241
–242,1999[CrossRef][Medline]
- Ceckova-Novotna M, Pavek P, Staud F: P-glycoprotein in the placenta: Expression, localization, regulation and function.
Reprod Toxicol22
:400
–410,2006[CrossRef][Medline]
- Saarikoski S, Seppla M: Immunosuppression during pregnancy: Transmission of azathioprine and its metabolites from the mother to the fetus.
Am J Obstet Gynecol115
:1100
–1106,1973[Medline]
- Flechner SM, Katz AR, Rogers AJ, Van Buren C, Kahan BD: The presence of cyclosporine in body tissues and fluids during pregnancy.
Am J Kidney Dis5
:60
–63,1985[Medline]
- American Academy of Pediatrics Committee on Drugs: The transfer of drugs and other chemicals into human milk.
Pediatrics93
:137
–150,1994[Abstract/Free Full Text]
- Coulam CB, Moyer TP, Jiang NS, Zincke H: Breast-feeding after renal transplantation.
Transplant Proc14
:605
–609,1982[Medline]
- Pergola PE, Kancharla A, Riley DJ: Kidney transplantation during the first trimester of pregnancy: immunosuppression with mycophenolate mofetil, tacrolimus, and prednisone.
Transplantation71
:994
–997,2000
- LeRay C, Coulomb A, Elefant E, Frydman R, Audibert F: Mycophenolate mofetil in pregnancy after renal transplantation: A case of major fetal malformations.
Obstet Gynecol103
:1091
–1094,2004[Medline]
- Sifontis NM, Coscia LA, Constantinescu S, Lavelanet AF, Moritz MJ, Armenti VT: Pregnancy outcomes in solid organ transplant recipients with exposure to mycophenolate mofetil or sirolimus.
Transplantation82
:1698
–1702,2006[CrossRef][Medline]
- Hollander GA, Bierer B, Burakoff SJ: Molecular and biological actions of cyclosporin A and FK506 on T cell development and function.
Transfus Sci15
:207
–220,1994[CrossRef][Medline]
- Jenkins MK, Schwartz RH: Effects of cyclosporin A on T cell development and clonal deletion.
Science241
:1655
–1658,1988[Abstract/Free Full Text]
- Sakaguchi S, Sakaguchi N: Organ-specific autoimmune disease induced in mice by elimination of T cell subsets. V: Neonatal administration of cyclosporin A causes autoimmune disease.
J Immunol142
:471
–479,1989[Abstract]
- Scott JR, Branch DW, Holman J: Autoimmune and pregnancy complications in the daughter of a kidney transplant patient.
Transplantation73
:815
–816,2002[CrossRef][Medline]
- Victor RG, Thomas GD, Marban E, O’Rourke B: Presynaptic modulation of cortical synaptic activity by calcineurin.
Proc Natl Acad Sci U S A92
:6269
–6273,1995[Abstract/Free Full Text]
- Avramut M, Zeevi A, Achim CL: The immunosuppressant drug FK506 is a potent trophic agent for human fetal neurons.
Brain Res Dev Brain Res132
:151
–157,2001[CrossRef][Medline]
- Hayes K, Symington G, Mackay IR: Maternal immunosuppression and cytomegalovirus infection of the fetus.
Aust N Z J Med9
:430
–433,1979[Medline]
- Murthy V, Kennea NL: Antenatal infection/inflammation and fetal tissue injury.
Best Pract Res Clin Obstet Gynaecol21
:479
–489,2007[CrossRef][Medline]
- Talge NM, Neal C, Glover V: Antenatal maternal stress and long-term effects on child neurodevelopment: How and why?
J Child Psychol Psychiatry48
:245
–261,2007[CrossRef][Medline]
- Lozoff B, Georgieff MK: Iron deficiency and brain development.
Semin Pediatr Neurol13
:158
–165,2006[CrossRef][Medline]
- Murray JE, Reid DE, Harrison JH, Merrill JP: Successful pregnancies after human renal transplantation.
N Engl J Med269
:341
–343,1963[Medline]
- Wrenshall LE, McHugh L, Felton P, Dunn DL, Matas AJ: Pregnancy after donor nephrectomy.
Transplantation62
:1934
–1936,1996[CrossRef][Medline]
- Buszta C, Steinmuller DR, Novick AC, Schreiber MJ, Cunningham R, Popowniak KL, Streem SB, Steinhilber D, Braun WE: Pregnancy after donor nephrectomy.
Transplantation40
:651
–654,1985[Medline]
- Reisaeter A, Roslien J, Henriksen T, Irgens LM, Hartmann A: A national survey of pregnancies and outcome in live kidney donors [Abstract].
J Am Soc Nephrol17
:68A
,2006
- 2004 Annual Report of the United States Organ Procurement and Transplantation Network and the Scientific Registry of Transplant Recipients: Transplant Data 1994–2003. Department of Health and Human Services, H.R.A.S.A., Health Care Systems Bureau, Division of Transplantation, Rockville, United Network for Organ Sharing, Richmond, VA, University Renal Research and Education Association, Ann Arbor MI,2004
This article has been cited by other articles:
|
|
|
|
 
C. K. Cheung and S. Bhandari
The effect of spontaneous twin pregnancy on renal transplant function and haemodynamics
NDT Plus,
September 23, 2009;
(2009)
sfp137v1.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Bargman
How did cyclophosphamide become the drug of choice for lupus nephritis?
Nephrol. Dial. Transplant.,
February 1, 2009;
24(2):
381 - 384.
[Full Text]
[PDF]
|
|
|
Top
Abstract
Prevalence of Pregnancy in...
