Male fertility and paternal immunosuppression after kidney transplant

Transplantmedium

A 32-year-old man with ESRD due to FSGS status post living kidney transplant from his mother 2 years ago is seen for routine follow-up. He has well-controlled hypertension, and his post-transplant course has been uneventful. His immunosuppressive regimen consists of tacrolimus and mycophenolate mofetil. Creatinine has been at his baseline level of 0.9 mg/dL (reference range, 0.7–1.3), and tacrolimus trough is usually 5–7 ng/mL (reference range, 5–10). He is recently married and is planning to have children within the year. He is concerned about infertility with his history of kidney disease and immunosuppression. Which one of the following is the MOST APPROPRIATE next step in management?

  1. A.Change tacrolimus to belatacept
  2. B.Change mycophenolate to everolimus
  3. C.No change in managementCorrect
  4. D.Change tacrolimus to sirolimus and prednisone

Explanation

No change in management is required for this patient, who has a well-functioning allograft 2 years after transplantation and a fertility rate equivalent to men in the general population. Male patients with progressive CKD have increased rates of infertility. After kidney transplant (KT), however, fertility recovers with reestablishment of normal serum testosterone levels and semen quality within months. Generally, pregnancies fathered by men with KT fare as well as pregnancies fathered by men who do not have transplants. Studies suggest that optimal pregnancy outcomes occur if men wait at least 2 years after KT and have good allograft function. Sirolimus can impact male fertility by impairing sperm development, resulting in low sperm counts and decreased testosterone levels, so there would be no reason to change to a sirolimus- or everolimus-based immunosuppressive regimen. Calcineurin inhibitors (CNI) may be used for male and female patients of reproductive age with KT. Studies in rats show that cyclosporine decreases sperm count, testosterone level, and fertility while increasing luteinizing and follicle-stimulating hormones. However, in humans, there is no evidence that CNI adversely affect male fertility or fetal development. There are no recommendations regarding CNI trough levels for men with regard to fertility and pregnancy outcomes. Mycophenolate mofetil has been associated with birth defects and pregnancy loss in women taking the medication, but such data are limited when the father is taking mycophenolate at the time of conception. A recent study found no increased risk for adverse pregnancy outcomes in which the father had exposure to mycophenolate. The European Medicines Agency and the manufacturer's medication label warn that men should use contraception and avoid sperm donation during and up to 90 days after mycophenolate treatment, but this recommendation is based on hypothetical risk rather than clinical trials or observations. Any risk for adverse pregnancy outcome would need to be weighed against an adverse patient outcome that could be precipitated by a change in immunosuppression. It is reasonable to inform prospective fathers of this hypothetical risk, but based on current information, it is not necessary to advise against conception or discontinue mycophenolate in the absence of an alternative indication. Currently, there is insufficient information available about belatacept and fertility or pregnancy outcomes to justify a change in immunosuppression in this patient with a well-functioning allograft.

Why each option

A.
There are insufficient data on belatacept and fertility or pregnancy to justify changing a stable, well-tolerated regimen in a well-functioning graft.
B.
Everolimus, like other mTOR inhibitors, can impair spermatogenesis and lower testosterone, so switching would harm rather than help his fertility.
C.
Correct. Male fertility recovers after transplant, paternal tacrolimus and mycophenolate have not shown adverse pregnancy outcomes, and his graft is stable at 2 years.
D.
Sirolimus impairs sperm development and lowers testosterone, so converting from tacrolimus would worsen male fertility and add rejection risk.

Reference: KDIGO 2009 Clinical Practice Guideline for the Care of Kidney Transplant Recipients; Midtvedt K, Transplantation 2017 (Exposure to mycophenolate and fatherhood)

This is one of 1,100 questions in the MedBoardSA nephrology bank, with timed test mode, tutor mode, and progress tracking by topic.

Practise the full bank

More Transplant questions

Browse other topics