need to be adjustment to antihypertensive therapy regimes, especially if the patient is taking ACE inhibitors.
The American Society of Transplantation Consensus Opinion advises that renal function is optimal when serum creatinine <1.5 mg/dl, with <500 mg/24 h protein excretion. There should be no concurrent infections and the woman should be using nonteratogenic immunosuppressive therapy, which is stable at maintenance levels in order for conception to be attempted [33]. In practice, women should wait for one year after receiving renal transplant as the risk of rejection is highest in the first year [32,33].
Renal allograft rejection during pregnancy should be considered throughout the gestation with surveillance of serum immunosuppressive levels. Immunosuppressive drug levels may be altered due to increasing glomerular filtration as pregnancy progresses [2,33].
It is important to consider the welfare of the child before a renal transplant recipient commences any fertility treatment. This should consider the risk of prematurity and also the risk of inherited renal disease. For conditions such as Alport’s syndrome and Polycystic Kidney Disease, preimplantation genetic testing should be considered with appropriate genetic counseling.
The IVF regimen should adopt a cautious approach. The GnRH antagonist protocol can be used with a low threshold for implementing a gonadotropin agonist trigger for final oocyte maturation to reduce the risk of OHSS (Case History 2) [34]. The use of dopamine agonists to further reduce the risk of OHSS may also be considered [35].
A senior IVF clinician should be involved throughout the IVF treatment and oocyte retrieval should be performed by a clinician of appropriate expertise due to the positioning of the allografted kidney. Single embryo transfer should be advised in renal transplant recipients due to the markedly increased risks of preeclampsia, diabetes, prematurity and low birth weight babies in multiple pregnancies.
Lastly, in patients with proteinuria and/or antiphospholipid antibodies, low molecular weight heparin prophylaxis and aspirin should be considered during the IVF process to decrease the risk of thrombosis.
Key points
Challenge: Patient with renal transplant undergoing IVF.
Background:
The number of renal transplant recipients wishing to undergo IVF treatment is increasing.
Women should be encouraged to wait for 12 months after renal transplant before attempting to conceive.
Once pregnancy is achieved in renal transplant recipients, the live birth rate is approximately 75%.
Pregnancy does not have an adverse impact on graft and patient survival in patients with good graft function. In patients with significant prepregnancy renal impairment, the risk to pregnancy and graft is increased.
During IVF treatment, there are increased risks of OHSS, with oocyte retrieval and of venous thromboembolism.
Fetal risks include teratogenic effect of immunosuppressants and risk of preterm delivery, miscarriage, fetal growth restriction and stillbirth.
The risk of hypertension, preeclampsia graft rejection and venous thromboembolism is greater in renal transplant patients compared with the healthy population.
Management:
Thorough prepregnancy counseling, ensuring that patients are aware of the risks of IVF treatment specific to renal transplant recipient as well as the obstetric and fetal risks during pregnancy.
Prepregnancy consultation should be in a multidisciplinary team setting with involvement of renal physicians before embarking on IVF treatment.
Consider the welfare of the child.
Reduce risk of OHSS using the lowest effective dose of gonadotropin and the antagonist protocol.
Provide adequate thromboprophylaxis.
Ensure senior operator present for oocyte retrieval.
Consider genetic counseling for inherited renal disease as PGD may be required.
Answers to questions patients ask
1 Q1 Will getting pregnant after my kidney transplant be high risk? A1. There is an increased risk of pre‐eclampsia (six times increase) and urinary tract infections during the pregnancy and your drugs can cause increased risks to the baby. Therefore, you need a full review with a maternal medicine specialist before pregnancy to optimize your medications and to minimize risks of damage to the renal graft and of pre‐eclampsia. Some immunosuppressive drugs such as MMF should be stopped three months before getting pregnant. MMF should be changed to tacrolimus and azathioprine. Your kidney function must be optimized prepregnancy. There is a higher risk of deep venous thrombo‐embolism and problems with the growth of the baby. Reassuringly, data demonstrated a live birth rate of around 75% in women that achieved pregnancy after undergoing renal transplantation and the miscarriage and ectopic pregnancy rates are not increased.
2 Q2 Will getting pregnant alter the lifetime of my graft? A2. In women with mild kidney disease, pregnancy adds little risk to the transplanted kidney. However, for those with risk factors there is a significantly increased risk of irreversible graft damage due to pregnancy. Risk factors for graft loss include; prepregnancy hypertension, abnormal renal function and protein in the urine.Graft rejection during pregnancy can occur. Women need to have drug levels monitored throughout pregnancy to ensure adequate immunosuppressive levels. Drug levels can alter as pregnancy progresses. Recently, it has been advised that immunosuppressive drug levels should be maintained at prepregnancy levels through frequent serum monitoring to avoid graft rejection.Women are advised to wait at least one year post transplant before considering pregnancy.
3 Q3 Is it safe to have IVF if I have had a renal transplant? A3. IVF does involve stimulating the ovaries. This causes high levels of circulating estrogen and a risk of overstimulation, which stresses the kidneys and increase the risk of a venous thrombosis. These risks can be minimised by using certain IVF protocols to avoid hyperstimulation and to use blood thinning drugs to reduce thrombosis risk. The egg collection should be done by an experienced operator due to the transplanted kidney lying close to the ovaries. Only one embryo should be transferred to avoid the risks of a twin pregnancy.
References
1 1 Shah S, Verma P. Overview of pregnancy in renal transplant patients. International Journal of Nephrology 2016, Article ID 4539342.
2 2 Matuszkiewicz‐Rowinska J, Skorzewska K S. Radowicki S et al., Endometrial morphology and pituitary‐gonadal axis dysfunction in women of reproductive age undergoing chronic haemodialysis—a multicentre study. Nephrology Dialysis Transplantation. 2004; 19(8):2074–2077.
3 3 Weisinger JR, Bellorin‐Font E. Outcomes associated with hypogonadism in women with chronic kidney disease. Advances in Chronic Kidney Disease. 2004; 11(4):361–370.
4 4 Bagon JA, Vernaeve H, De M, X, Lafontaine JJ, Martens J, Van RG. Pregnancy and dialysis. Am J Kidney Dis 1998; 31(5):756–765.
5 5 Giatras I, Levy DP, Malone FD, Carlson JA, Jungers P. Pregnancy during dialysis: case report and management guidelines. Nephrology Dialysis Transplantation. 1998; 13(12):3266–3272.
6 6 Piccoli GB, Conijn A, Consiglio V, Vasario E, Attini R, Deagostini MC et al. Pregnancy in dialysis patients: is the evidence strong enough to lead us to change our counseling policy? Clin J Am Soc Nephrol 2010; 5(1):62–71.
7 7 Saha MT, Saha HHT, Niskanen LK, Salmela KT, Pasternack AI. Time course of serum prolactin and sex hormones following successful renal transplantation. Nephron 2002; 92(3):735–737.
8 8 Anantharaman P, Schmidt RJ. Sexual function in chronic kidney disease.