ISSN
1916-694X

2010;
Volume 1 (Number 1): Pages 24-26

CASE
REPORT

Paternal exposure to
irbesartan coadministered with multiple antihypertensive and antidiabetic
drugs: a case report of a baby born healthy

Soon Cheol
HONGa,b, Jung Yeol HANa,c*, June Seek CHOIa,c,
Hyun Kyong AHNa,c, E. Yadira VELÁZQUEZ-ARMENTAd,
Alejandro A. NAVA-OCAMPOd,e

aThe Korean Motherisk Program, bDivision
of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Korea
University Medical Center, cDivision of Maternal Fetal Medicine,
Department of Obstetrics and Gynecology, Cheil Hospital & Women’s
Health-Care Center, Kwandong University College of Medicine, Seoul, Korea; dPharmaReasons,
Toronto, Canada; eDepartment of Pharmacology & Toxicology,
Faculty of Medicine, University of Toronto, Toronto, Canada

*Corresponding author:
[email-masked]

ABSTRACT

Objective: To report the fetal outcome of a baby with paternal exposure to
irbesartan and other antihypertensive and antidiabetic drugs. Case: The baby was conceived by in vitro fertilization with an egg
obtained from a woman with untreated diabetes and hypertension and the sperm
from a male with type-2 diabetes and hypertension. At the time of sperm
donation, he was taking irbesartan 150 mg d-1 in addition to
amlodipine, aspirin, carvedilol, glibenclamide, hydrochlorothiazide, metformin,
ramipril, and triazolam. At 38 weeks gestation, a 3,090 g female baby was
delivered by cesarean section due to placenta previa. At 40 months postnatal
age, the baby was 18 kg with normal growth and development. Conclusion: This case suggests that
paternal exposure to irbesartan as part of a combination therapy with other
antihypertensive drugs and antidiabetics, does not alter sperm cells or
increase the risk for fetal malformations.

Key
words

Angiotensin II type 1 receptor blockers;
Antihypertensive agents; Paternal exposure; Sartans

RÉSUMÉ

Objectif: Rapport du cas d’un enfant après exposition
paternelle à l’irbesartan et d’autres médicaments antihypertenseurs et à des
antidiabétiques. Rapport du cas:
L’enfant a été conçu par fertilisation in vitro à partir d’un œuf obtenu chez
une femme souffrant de diabète et d’hypertension non traités, et du sperme d’un
homme souffrant de diabète de type-2 et d’hypertension. Lors du don de sperme
l’homme prenait 150 mg/jour d’irbesartan, ainsi que de l’amlodipine, de
l’aspirine, du carvedilol, du glibenclamide, de l’hydrochlorothiazide, de la
metformine, du ramipril et du triazolam. À 38 semaines de grossesse une
fillette de 3,090 g est née par césarienne suite à un placenta praevia. À
l’âge de 40 mois l’enfant pesait 18 kg et présentait une croissance et un
développement normaux. Conclusion:
Ce cas suggère que l’exposition paternelle à l’irbesartan associée à d’autres
antihypertenseurs et à des antidiabétiques n’a aucun effet défavorable sur ses
cellules spermatiques et n’augmente pas le risque des malformations fœtales.

Mots
clés

Antagonistes
des récepteurs de l'angiotensine II; Agents antihypertenseurs;
Exposition paternelle; Sartans

RESUMEN

Objetivo: Reportar el caso de un bebé con exposición
paterna a irbesartan y otros medicamentos. Caso:
El bebé fue concebido por fertilización in vitro de un huevo proveniente de una
mujer con diabetes e hipertensión sin tratamiento farmacológico, y del esperma
de un sujeto con diabetes tipo 2 e hipertensión. Al momento de la donación del
esperma, el papá estaba tomando irbesartan 150 mg d-1 además de
amlodipina, aspirina, carvedilol, glibenclamida, hydrochlorothiazida,
metformin, ramipril, and triazolam. En la semana 38 de gestación nació una niña
de 3,090 g por cesárea debido a placenta previa. A los 40 meses de edad
postnatal, el bebé pesaba 18 kg y tenía un crecimiento y desarrollo normales. Conclusión: Este caso sugiere que la
exposición paterna a irbesartan como parte de un tratamiento combinado con
otros antihipertensivos e hipoglucemiantes, no altera los espermatozoides ni
tampoco incrementa el riesgo de malformaciones fetales.

Palabras
clave

Bloqueadores
de los receptores de angiotensina II tipo 1; Agentes antihipertensivos;
Exposición paterna; Sartanes

INTRODUCTION

A recent systematic review of the published
literature on exposure to angiotesin II receptor blockers (ARBs) in pregnancy
showed that, of the 65 cases currently available, approximately 40% had
unfavorable outcomes [1]. However, there is no information on whether paternal
exposure to ARBs may also be associated with a similar high risk of adverse
pregnancy outcome in their partner. In this context, the present case report
provides anecdotal but relevant information on the lack of adverse reproductive
outcomes when paternal exposure to irbesartan occurs.

CASE

A 31 year-old woman (gravida 2, para 0, and
therapeutic abortion 1) with untreated type-2 diabetic and untreated arterial hypertension
came to the Korean Motherisk Program with her partner to receive teratogen-risk
counseling. She had a history of secondary infertility with retrograde
ejaculations in her partner. Therefore, she conceived by in vitro fertilization
with her egg fertilized by the sperm obtained from her partner. She decided not
to take any medication for treating her metabolic disorder and hypertension
during pregnancy. Her partner was 29 years of age and had type-2 diabetes and
hypertension. Since the age of 26, he had been taking irbesartan 150 mg d-1
in addition to amlodipine besylate 5 mg d-1, aspirin 100 mg d-1,
carvedilol 25 mg d-1, glibenclamide 15 mg d-1,
hydrochlorothiazide 12.5 mg d-1, metformin 2,400 mg d-1,
ramipril 10 mg d-1, and triazolam 5 mg d-1.

The woman underwent a high-resolution
ultrasound examination at 20 weeks of pregnancy that reported a single fetus
without any evidence of major congenital malformations and normal development
(estimated fetal weight: 342 g). At 38 weeks gestation, a 3,090 g female baby
was delivered by cesarean section due to placenta previa. At 40 months
postnatal age, the baby weighed 18 kg and a detailed pediatric examination
found her healthy, with normal growth and proper development of all milestones.

DISCUSSION

Paternal exposure to irbesartan may be of
relevant concern especially when ARB exposure in pregnant women has been
related to a rate of adverse fetal outcomes in more than 40% of cases [1]. This is a case of a baby born by in vitro
fertilization with an egg obtained from a type-II diabetic woman and the sperm
of a male chronically exposed to irbesartan and other multiple medications
as part of his antihypertensive and antidiabetic treatment.

A study in insulin-dependent and
non-insulin-dependent diabetic men either with or without neuropathy found
sperm motility and semen volume to be approximately 30% and 60% less,
respectively [2]; however, sperm morphology and quality of sperm
motility remained unaffected. Of the treatment received by the male parent, angiotensin
converting enzyme lisnopril has shown to improve sperm count and motility in
both experimental animal models [3] and humans [4]. In contrast, amlodipine and aspirin may exhibit
deleterious effects on the reproductive function of males [5] [6].

In addition to the paternal morbidities and
multiple drug therapy, the mother had untreated hypertension. Fetal growth is
regulated by complex mechanism in which hormonal and vascular changes
simultaneously play a critical role [7] [8] [9] [10]. Hypertension may adversely alter the placental blood
flow subsequently negatively affecting the normal fetal growth and development.

Although anecdotal, this case suggests that
paternal exposure to irbesartan as part of combination therapy with other
antihypertensive drugs and antidiabetics, does not appear to alter sperm cells
or increases the baseline risk for fetal malformations.

AUTHORS’ PARTICIPATION

SC H, JY H, JS C, and HK A identified the
case, provided prenatal teratogen-risk counseling and medical and obstetric
follow-up. JY H, EY V-A & AA N-O conceived the idea to report the case,
drafted the manuscript, discussed the findings, and researched the literature.

ACKNOWLEDGEMENTS

None to declare.

CONFLICT OF INTERESTS/DISCLAIMERS

Y H, EY V-A & AA N-O are members of the
Editorial Board of the journal.

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