Organ Transplantation and Pregnancy

1. Organ Trasplantation & Pregnancy
Salah Roshdy Ahmed
Professor of Obstetrics & Gynecology
Sohag University 2017

2. Introduction
• Organ transplantation is a life-saving
procedure for those with end stage
disease.
• Since the first documented pregnancy in
a transplant recipient occurred in 1958,
successful pregnancies have been
reported in female recipients of kidney,
liver, pancrease kidney, heart, and lung
transplants.

3. Introduction
• Advances in surgical techniques and
immunosuppressive therapy have helped to
increase the numbers of women who undergo
allogeneic organ transplantation each year.
• Many times, a transplanted organ normalizes a
woman’s hormonal imbalance and restores
fertility, thus offering the prospect of pregnancy
and providing many women with end-stage
organ disease a chance to conceive and bear
children.

4. Types of organ transplants
• Kidney
• Liver
• Kidney/pancreas
• Heart
• Lung
• Liver/kidney
• Heart/lung

5. Kidney transplant recipients
• Most patients with advanced renal failure
have impaired reproductive function, mainly
related to dysfunction in the hypothalamo-
pituitary-gonadal axis.
• Sexuality and fertility are usually restored in
these women 1-12 months after renal
transplantation.

6. Kidney transplant recipients
• Reports show that pregnancy is common after
kidney transplantation and occurs in 5-12% of
women who undergo kidney transplantation
and are of childbearing age
• The first reported successful pregnancy in a
kidney transplant recipient occurred in
1958.Since then, thousands of pregnancies in
kidney transplant recipients have been reported
worldwide, with a success rate of 60-80%.

7. Kidney transplant recipients
• Despite the large number of reported
pregnancies in this patient group, the high
rate of complications indicates that such
pregnancies should still be considered high-
risk and need to be monitored closely by a
medical team that consists of a transplant
nephrologist surgeon, obstetrician, urologist,
and pediatrician.

8. Maternal complication
• Infection,
• Ectopic pregnancy,
• Gestational diabetes, and increased
likelihood of cesarean delivery.
• In addition, hypertension
and preeclampsia are common; these
conditions affect 27-38% of patients.

9. Fetal complication
• Prematurity 50%
• IUGR 20%
• Low birth weight, immune deficiency,
• Perinatal infections, especially with hepatitis
B virus (HBV) and cytomegalovirus (CMV).
• The incidence of congenital anomalies is
similar to that in the general population,
though few data exist with regard to the
effect of the newer drugs.

10. Other factors that favor a good
outcome of pregnancy
• Serum creatinine level less than 1.5 mg/dL
• No recent episodes of acute rejection
• Blood pressure within the reference range
• Proteinuria level less than 500 mg/d
• Maintenance level of immunosuppression
• Normal appearance of allograft
ultrasonography

11. Liver transplant recipients
• Advanced liver disease causes menstrual
dysfunction and infertility in women of
reproductive age; more than half of such
patients experience amenorrhea.
• It is observed that successful OLT helps restore
the menstrual function and childbearing
potential in 97% of cases.
• Studies have shown that menstrual function is
restored in more than 85% of these patients at a
median of 1 month after liver transplantation.

12. Liver transplant recipients
• The first successful pregnancy in a liver
transplant recipient was reported in 1978.
Since then, the reported number of such
pregnancies has grown dramatically.
• Improved transplantation techniques, better
immunosuppressive agents, and intensive
monitoring after the operation have helped
many of these patients restore hormonal
balance and even have children.

13. Pregnancy outcomes among liver
transplant recipients
• Although reports show a good success rate of
pregnancy in liver transplant recipients, these
pregnancies carry high risk to the patient,
fetus, and allograft .
• It needs to be closely monitored in
specialized centers by an integrated team
that includes a transplant hepatologist, a
transplant surgeon, an obstetrician , and a
perinatologist or neonatologist.

14. Maternal complication
• Pregnancy-induced hypertension
• Intrauterine infections
• Anemia
• Preeclampsia
• Cholestasis
• Pyelonephritis

15. Obstetric complication
• Congenital CMV infection (highest in
pregnancies occurring < 6 months after
transplantation)
• Perinatal infection with HBV (≤80%) or HCV
(7%)

16. Fetal complication:
• Prematurity (40% )
• Intrauterine growth restriction ( 20%),
• Prenatal infections
• Birth defects
• Immune suppression

17. Pancreas and kidney/pancreas transplant
recipients
• Patients with diabetes mellitus type I may
qualify for allogeneic pancreas transplantation.
• However, concomitant renal failure is a
common problem in patients with brittle
diabetes that makes them candidates for
combined kidney/pancreas transplantation.
• Successful pancreas transplantation results in an
insulin-independent normoglycemic state in
recipients with diabetes who are insulin-
dependent.

18. Pancreas and kidney/pancreas
transplant recipients
• 4,014 female patients received pancreas
transplants and 8,717 female patients received
kidney/pancreas transplants in the United States
from 1988 through 2016. As of 2004
kidney/pancreas recipients had been reported
to conceive; some of them had multiple
pregnancies, raising the number of pregnancies .
• 57% of the infants were delivered by cesarean
delivery.

19. Lung and heart/lung transplant
recipients
• The first successful heart transplantation was
performed in 1967; the first combined heart-
lung transplant was performed in 1981.
• The first reported successful lung
transplantation was performed in 1983.
• Even though 16,000 heart, lung,
and heart/lung transplantations have been
performed, pregnancy is still rare among
thoracic organ transplant recipients.

20. Heart transplant recipients
• Studies of pregnancy in recipients of heart
transplants have reported that 69% of such
pregnancies resulted in live births, although 32%
of newborns were premature and had low birth
weight.
• The most common reported maternal
complications were hypertension ( 46% ), acute
allograft rejection (21%), infection (11%),
preeclampsia (10%), and gestational diabetes
(4%).

21. Lung transplant recipients
• The worldwide experience with pregnancy
after lung transplantation is limited, but,
when compared to other recipients of solid
organs, female recipients of lung transplants
are at high risk for acute allograft rejection,
low birth weight in the infant, and
complications of pregnancy.

22. Intestine transplant recipients
• To date, eight pregnancies with 100%
successful live births have been reported
worldwide in intestinal/multivisceral
transplant recipients.
• Important factors to be considered in these
cases are the absorptive function of the
transplanted bowel and higher need for
immunosuppressants.

23. Preconceptional Counseling Issues
• Contraception
• Optimal timing for pregnancy
• Continuation of immunosuppressant
medication
• Folic acid and calcium supplementations .
• Performing rubella and varicella vacciniation.
• Screening and treating anemia and
infections.

24. Vaccination
• An immunization history of the nonpregnant
transplant patient is essential.
• Laboratory evaluations for CMV, rubella,
varicella, HSV, HIV and hepatitis panel should be
performed before pregnancy.
• Vaccination of an immunosuppressed patient
using live virus vaccines could result in systemic
sepsis and death.
• Therefore rubella and varicella vaccines should
be administered to women of childbearing age
before organ transplantation

25. Vaccination
• The patient should be vaccinated for
hepatitis B virus, Streptococcus pneumoniae,
tetanus, and influenza.
• The patient should be vaccinated before
transplantation, if possible.
• If that timing is not feasible, the patient
should be vaccinated before pregnancy.

26. Optimal timing of pregnancy
• Although gonadal dysfunction usually resolves
by 6 months after successful transplantation,
patients are generally advised to wait 2 years
after transplantation to become pregnant.
• This time is based on the timeframe to establish
stable graft function on maintenance
immunosuppression.
• It is also expected that transplant recipients will
have completed postoperative treatment of
opportunistic infections by this time.

27. Optimal timing of pregnancy
• For liver transplant recipients, acute
cytomegalovirus (CMV) infection usually
occurs within 6 months after transplantation,
coinciding with the period of maximal
immunosuppression after transplantation.
• It is therefore recommended that a liver
transplant recipient should delay conception
at least 6 months after transplantation.

28. Contraception
• There are limited data on appropriate
contraception following transplantation,
including barrier methods, the intrauterine
device, and oral contraceptives .
• IUCD and subdermal implants have been
shown to have great efficacy as well as low
systemic drug absorption.

29. Contraception
• Oral contraceptives are effective, but are
generally recommended in normotensive
women and are to be avoided in hepatic
allograft patients because of the possible
negative hepatic effects of these
medications.
• Also oral contraceptives can potentially affect
certain medications.

30. Factors that are associated with
favorable pregnancy outcomes
• Good general health for about 2 years after
transplantation
• No graft rejection in the last year
• Adequate and stable graft function
• No acute infections that might affect the
fetus

31. Factors that are associated with
favorable pregnancy outcomes
• Maintenance immunosuppression at stable
doses
• Patient compliance with treatment and
follow-up
• Normal blood pressure or blood pressure
that is well controlled with one medication
• Normal allograft US results

32. Comorbid factors that may worsen
pregnancy outcomes
• Etiology of the original disease that necessitated
transplantation
• Chronic allograft dysfunction
• Renal insufficiency
• Cardiopulmonary diseases
• Hypertension
• Diabetes mellitus
• Obesity
• Maternal infection with hepatitis B (HBV) or C
(HCV) or cytomegalovirus (CMV)

33. GRAFT REJECTION AND DYSFUNCTION
• It is suggested that pregnancy is an
immunosuppressed state but evidence shows
pregnant women do not have diminished
systemic immunity.
• Inappropriate reduction in
immunosuppression during pregnancy will
lead to rejection of the transplanted organ.

34. GRAFT REJECTION AND DYSFUNCTION
• Studies have shown that pregnancy
does not appear to cause excessive or
irreversible problems in the graft, if the
function of the transplanted organ is
stable prior to pregnancy.

35. Management of Pregnant Transplant
Recipients
• Patient self-monitoring of daily blood pressure
• Aggressive management of hypertension: The
drug of choice is methyldopa ; second-line
agents include clonidine and calcium channel
alpha blockers
• Contraindicated drugs include angiotensin-
converting enzyme inhibitors (ACEIs) and
angiotensin receptor blockers (ARBs) .
• Close monitoring of graft function; if rejection is
suspected, consider biopsy .
• In cases of acute rejection, steroids are the
preferred drugs.

36. Obstetric management of pregnant
transplant recipients
• The pregnancy of a transplant recipient should
be managed by an obstetrician experienced in
high-risk pregnancies, in collaboration with a
transplant physician and perinatologist or
neonatologist.
• Frequent evaluations, preferably every 2 weeks.
• Vaginal delivery (preferred): Usually delayed
until labor onset unless maternal/fetal
indications for induction exist .

37. Obstetric management of pregnant
transplant recipients
• Cesarean delivery is only indicated for obstetric
reasons (in such cases, avoid injury to the
allograft by knowing its exact location) .
• Antibiotic prophylaxis for all surgical
procedures .
• The dose of steroids should be increased at the
onset of labor to overcome the stress of labor
and prevent postpartum transplant rejection.

38. Obstetric management of pregnant
transplant recipients
• No specific anaesthetic agents for general or
regional anaesthetics are contraindicated.
• Patients who undergo lung or heart-lung
transplants have a decreased threshold for
developing pulmonary edema secondary to
disruption of lymphatic vessels.
• Pelvic osteodystrophy was described in
patients with prolonged exposure to
corticosteroids. This may necessitate
cesarean delivery.

39. Immunosuppression in pregnant
transplant recipients
• Corticosteroids: For induction, acute
rejection, and maintenance
immunosuppression.
• Cyclosporine (cyclosporin A): To prolong the
survival of liver transplants .
• Azathioprine: Mainly for maintenance
immunosuppression

40. Immunosuppression in pregnant
transplant recipients
• Mycophenolate mofetil: For maintenance
immunosuppression and for treating chronic
rejection .
• Tacrolimus: For immunosuppression .
• Sirolimus: For immunosuppression .
• Anti-CD3 (OKT3): (Rare) To treat acute
rejection in pregnant transplant recipients.

41. Drug FD
A
Maternal
effects
Fetal
effects
Breast
feeding
A-Corticosteroids B Cushing’s
disease, bone
disease (eg,
osteoporosis,
avascular
necrosis),
cataracts,
glucose
intolerance,
infections,
hyperlipidemia,
peptic ulcer,
diabetes, and
psychiatric
disturbances
IUGR
.Low
birth
weight .
PL.PRO
M
May
increase
risk for
cleft lip
Safe

42. Drug FD
A
Maternal
effects
Fetal
effects
Breast
feeding
B-Calcineurin inhibitors
1. Cyclosporin A (CyA)
C nephrotoxicity,
hypertension,
hypertrichosis,
tremor and
hyperlipidemia
IUGR
and
prematur
e birth
Avoid
2. Tacrolimus C Nephrotoxicit
y,
hypertension,
diabetes
mellitus
Transient
perinatal
hyperkale
mia,
higher
incidence
of
diabetes
Avoid

43. Drugs
Category*
Maternal
Effects
Fetal Effects
Breastfeedi
ng
C-Purine
metabolism
inhibitors 1.
Azathioprine
(AZA)
D
Leukopenia,
thrombocyt
openia,
hepatitis,
cholestasis,
alopecia
IUGR,
increased
risk for
congenital
malformatio
ns, neonatal
immunosup
pression,
leukopenia,
and/or
pancytopeni
a
Avoid

44. Drugs
Category*
Maternal
Effects
Fetal Effects
Breastfeedi
ng
2.
Mycophenola
te Mofetil
(MMF)
D
Thrombocyt
openia and
increased
risk of
developmen
t developing
lymphomas
and other
malignancie
s,
Caused fetal
resorptions
and
malformatio
ns in
pregnant
rats and
rabbits
Data
insufficient
to conclude
that the use
of this agent
during
pregnancy
is safe
Safety
unknown

45. Drugs
Category*
Maternal
Effects
Fetal Effects
Breastfeedi
ng
D-Sirolimus C
Thromboc
ytopenia,
leucopenia
,
hyperkale
mia,
hypomagn
esemia,
hyperlipide
mia,
hypertrigly
ceridemia,
Human
data are
limited
Safety
unknown

46. Drugs
Category*
Maternal
Effects
Fetal Effects
Breastfeedi
ng
E.OKT3
(Orthoclone)
C
Wheezing,
difficulty in
breathing,
chest pain,
fever, chills,
nausea,
vomiting,
diarrhea,
tremor,
headache,
rapid heart
rate, muscle
stiffness,
high or low
blood
pressure
Effect on
fetus not
known; can
cross
placenta
Avoid

47. • A = Safe in pregnancy
B = Usually safe but benefits must outweigh the
risks
C = Safety for use during pregnancy has not been
established
D = Unsafe in pregnancy
X = Contraindicated

48. Immunosuppression in pregnant
transplant recipients
• The safety of these immunosuppressive agents
for use in pregnancy has not been established,
except for azathioprine and mycophenolate
mofetil—both are unsafe in pregnancy.
• Babies exposed to biologic drugs in utero
should therefore avoid live vaccines (Bacillus
Calmette–Guerin (tuberculosis), rotavirus, live
attenuated influenza, oral polio, typhoid,
yellow fever, varicella, and measles, mumps
and rubella) during the first 6 months of life.

49. Medical and Legal Pitfalls
Failure to do any of the following is problematic:
• Inform the patient that ovulatory cycles may
begin within 1-2 months after transplantation,
so pregnancy can occur after that time
• Advise the patient that adequate contraceptive
measures should be taken to prevent unwanted
pregnancy
• Inform the patient about the optimal timing of
pregnancy

50. Medical and Legal Pitfalls
• Inform the patient that pregnancy in a
transplant recipient is considered a high-risk
pregnancy; patients should be made aware of
the potential risks before conception
• Send the patient for genetic counseling if the
transplant was performed to treat an inheritable
disease
• Inform the patient about the potential fetal risks
of immunosuppressive agents
• Inform the patient that breastfeeding must be
avoided if the patient is taking certain
immunosuppressive therapies