Contraception xx (2016) xxx xxx

Case report

Use of the levonorgestrel 52-mg intrauterine system in adolescent and

young adult solid organ transplant recipients: a case series
PS Huguelet a,, C Sheehan b , RF Spitzer b , S Scott a
a
Department of Obstetrics and Gynecology and Pediatrics, University of Colorado Hospital and Children's Hospital Colorado, Aurora, Colorado
b
Department of Obstetrics and Gynecology, University of Toronto and The Hospital for Sick Children, Toronto, Ontario, Canada
Received 15 September 2016; revised 29 November 2016; accepted 30 November 2016

Abstract

This case series reports on the safety and efficacy of the levonorgestrel 52-mg intrauterine system in adolescent and young adult solid
organ transplant recipients. All patients used the device for contraception, with no documented cases of disseminated pelvic infection or
unplanned pregnancy.
2016 Elsevier Inc. All rights reserved.

Keywords: Adolescent; Levonorgestrel-releasing intrauterine system; Solid organ transplant; Intrauterine device

1. Introduction first line for adolescents and young adults, based on

Women of reproductive age who have received solid
organ transplants are at risk for unplanned pregnancy.
Fertility may return as quickly as 1 month after transplan-
tation [1]. Pregnancy, although not absolutely contraindi-
cated, carries greater risk than the general population,
including increased risk for Cesarean delivery, gestational
diabetes, preeclampsia and preterm delivery [2,3].
Following organ transplantation, approximately one half
of women who receive a liver [4] or kidney [5,6] transplant
resume regular menstruation. In addition, sexual dysfunction
and loss of libido often resolve [4,7]. As quality of life
improves, sexual activity may resume posttransplant,
necessitating effective and safe contraception for both
adolescent and adult transplant recipients. It therefore
becomes critical that physicians have contraceptive options
that are safe and effective, with high adherence rates.
In December 2009, the American College of Obstetricians
and Gynecologists released a committee opinion recommend-
ing the use of long-acting reversible contraceptive methods as
Conflicts of interest: none.
Corresponding author. Tel.: +1-303-724-2038; fax: +1-303-724-2056.
E-mail addresses: patricia.huguelet@ucdenver.edu (P.S. Huguelet),
Carolyn.sheehan@sickkids.ca (C. Sheehan), rspitzer@mtsinai.on.ca
(R.F. Spitzer), Stephen.scott@ucdenver.edu (S. Scott).
http://dx.doi.org/10.1016/j.contraception.2016.11.008
0010-7824/ 2016 Elsevier Inc. All rights reserved.
effectiveness, satisfaction and continuation rates [8]. This
position has been further supported by the American Academy
of Pediatrics and the Society of Obstetricians and Gynecol-
ogists of Canada [9,10]. Despite these endorsements, the
Center for Disease Control (CDC) remains one of the only
organizations to specifically address the safety of the
intrauterine device (IUD) in solid organ transplant recipients.
The 2016 CDC Medical Eligibility Criteria support the use of
the levonorgestrel 52-mg intrauterine system (LNG 52-mg
IUS) in uncomplicated transplant patients [11]. However, the
American Society of Transplantation (AST) consensus
statement from 2005 conflicts with this recommendation.
Specifically, the AST recommends against the use of the
intrauterine contraceptive device (IUD), stating that immuno-
suppressive agents decrease the effectiveness of IUDs and
immunocompromised subjects using such devices have an
increased risk of infection [12]. Outdated guidelines such as
the 2005 AST consensus statement have the potential to
decrease provider recommendation and patient acceptance of
this method of contraception.
To date, there are no published series on adolescents and
young adults with solid organ transplants and the LNG
52-mg IUS. We present a case series of six adolescent and
young adult transplant recipients from two institutions.
Institutional review board approval was obtained prior to
collecting our data.
2 P.S. Huguelet et al. / Contraception xx (2016) xxxxxx

2. Cases routine testing for Neisseria gonorrhea and Chlaymdia

We performed a retrospective chart review to identify
female solid organ transplant recipients, ages 922 who
received an LNG 52-mg IUS at one of two locations: The
Adolescent Medicine and Gynecology Clinics at Children's
Hospital Colorado or the Pediatric and Adolescent Gyne-
cology Clinic at The Hospital for Sick Children in Toronto,
Canada. Age limits for care at the institutions are 24 and 18,
respectively. We searched charts from January 2004, when
electronic records became available, through December
2015. We identified all patients with international classifi-
cation of diseases, 9th edition (ICD-9) codes for both solid
organ transplantation and concurrent use of levonorgestrel
medication, which revealed 12 patient charts. We then
performed direct chart review and found that 6 of the 12
patients used the LNG 52-mg IUS. From the six identified
charts, we extracted age, year of transplantation, type of
organ transplanted, current and past immunosuppressant use,
indication for LNG 52-mg IUS insertion, duration of use,
discontinuation, and complications, including pelvic infec-
tion. A description of selected data for each patient appears
in Table 1. The main outcome measure was discontinuation
of the LNG 52-mg IUS due to pelvic infection.
2.1. Case 1
A 17-year-old female with a history of liver transplant at
the age of 9 due to liver failure from biliary atresia presented
for a contraception consultation. She denied sexual activity,
and the LNG 52-mg IUS was inserted without screening for
genital tract infection. She was followed for 8 months with
gynecology without developing any complications and was
then lost to follow-up when she transferred care to an adult
facility.
2.2. Case 2
A 17-year-old female presented for contraception
counseling, reporting a history of small bowel transplant at
the age of 3 for gastroschisis complicated by gut volvulus.
She decided to proceed with the LNG 52-mg IUS, and
trachomatis cervicitis were negative at insertion. During her
annual exams over the next 2 years, repeat sexual transmitted
infection (STI) testing was negative. After 32 months of use,
she underwent removal of the LNG 52-mg IUS for persistent
irregular spotting.
2.3. Case 3
An 18-year-old female with a history of renal transplant at
the age of 17 due to chronic renal failure from polycystic
kidney disease presented requesting contraception. She
reported using condoms intermittently and desired a more
effective method of birth control. Routine testing for N.
gonorrhea and C. trachomatis cervicitis were negative, and
the LNG 52-mg IUS was inserted without complication. She
then presented to the emergency department 3 months later,
complaining of increasing vaginal discharge. The patient did
not show evidence of pelvic inflammatory disease, but final
testing was positive for endocervical C. trachomatis. The
patient was treated with outpatient oral antibiotics and the
LNG 52-mg IUS remained in situ. She then represented to
clinic 3 months later, after a change in sexual partners, and
all STI testing was negative. The patient underwent
uncomplicated removal of the LNG 52-mg IUS after 21
months of use because of her concerns about future fertility.
She subsequently conceived an unplanned pregnancy 2
months after removal, resulting in spontaneous abortion at 5
weeks gestation. She continued to decline contraception at
follow-up visits.
2.4. Case 4
A 17-year-old female with a history of cardiac transplant
at 9-months-old secondary to pulmonary atresia with an
intact ventricular septum presented for contraception con-
sultation and opted for an LNG 52-mg IUS. The patient had
previously tested negative for N. gonorrhea and C.
trachomatis 1 month prior and elected to proceed with IUS
placement on the day of consultation. She continued care for
1 month without any IUS-related complications after which
she transferred care to an adult facility.

Table 1
Indication for insertion, duration of use, infection and pregnancy outcomes and immunosuppressants used in solid organ transplant recipients using the LNG
52-mg IUS
Case Age at insertion Year of Organ Indication Year of Duration of follow-up PID Pregnancy Immunosuppressants
transplant insertion (months) prescribed
1 17 1998 Liver Contraception 2006 8 No No Mycophenolate, Tacrolimus
2 17 1997 Small bowel Contraception 2010 32 No No Prednisone, Tacrolimus
3 18 2011 Renal Contraception 2012 21 No No Azathioprine, Mycophenolate,
Prednisone, Sirolimus
4 17 1996 Cardiac Contraception 2013 1 No No Mycophenolate, Tacrolimus
5 17 1994 Cardiac Contraception 2014 12 No No Cyclosporine, Mycophenolate,
Sirolimus
6 21 2008 Renal Contraception 2014 22 No No Azathioprine, Prednisone,
Tacrolimus
PID, pelvic inflammatory disease.
 P.S. Huguelet et al. / Contraception xx (2016) xxxxxx
2.5. Case 5
A 17-year-old female with a past medical history
significant for cardiac transplant for hypoplastic left heart
syndrome at 12 months of age underwent LNG 52-mg IUS
insertion at an outside clinic for contraception. The patient
had been using depo medroxyprogesterone acetate for the
previous 9 months and continued to experience irregular
bleeding. During the patient's routine follow-up exam in
cardiology 1 month postinsertion, she reported regular
sexual activity and denied any problems with the IUS. She
then consulted adolescent gynecology 9 months later given
increasing pain with the LNG 52-mg IUS. The contraceptive
device was noted to be located within the cervix. Routine
testing for N. gonorrhea and C. trachomatis cervicitis were
negative, and the LNG 52-mg IUS was removed and
reinserted. One year later, the patient suffered an acute
myocardial infarction and died. Final autopsy demonstrated
severe transplant coronary artery disease, with 95% blockage
of right coronary artery and 80% blockage of left coronary
artery. There was no evidence of cellular or humoral-mediated
graft rejection.
2.6. Case 6
A 21-year-old female with a history of renal transplant at
the age of 16 due to end-stage renal disease from focal
segmental glomerulosclerosis presented to discuss contra-
ception. Routine testing for N. gonorrhea and C. trachomatis
cervicitis were negative, and the patient underwent uncom-
plicated LNG 52-mg IUS insertion the same day. At routine
follow-up visits, she continued to deny any problems.
3. Comment
The AST issued a consensus statement in 2005
recommending against the use of the IUD, stating that
immunosuppressive agents decrease the effectiveness of
IUDs and immunocompromised subjects using such devices
have increased risk of infection [12]. However, these
recommendations regarding contraceptive failure are based
on a single case series describing two cases of contraceptive
failure with a copper-containing IUD, resulting in unplanned
pregnancy [13]. These two cases involved adolescents and
represent some of the only adolescent case reports in the
literature. The authors postulated that the failure was due to
the immunosuppressive effect on macrophage activity.
However, the mechanism of the LNG 52-mg IUS differs
from the copper IUD. The LNG 52-mg IUS prevents
conception by thickening cervical mucus and decreasing
endometrial receptivity to implantation [14]. Therefore, the
mechanism of failure that provided the basis for the
consensus statement against IUD use in transplant recipients
may not apply to the LNG 52-mg IUS.
The AST consensus conference also cited a theoretical
increased risk of pelvic infection as a reason to recommend
3
against use of the LNG 52-mg IUS in solid organ transplants.
There is currently no evidence for this recommendation.
Multiple case series in the adult literature have demonstrated
safety in both the immunocompromised and immunocompetent
patient [15,16]. Adding to this body of evidence, recent research
into the genital tract immune cell population of women with
IUDs demonstrated decreased expression of the human
immunodeficiency virus (HIV) coreceptor on T cells, suggest-
ing that susceptibility to HIV infection is not increased with IUD
use [17]. In addition, Turok et al. [18] demonstrated that genital
tract infections are infrequent in the first 2 years of LNG 52-mg
IUS use and are not temporally related to IUS placement.
Although the AST has more recently updated its website to
reflect the positive recommendation of IUD use among solid
organ transplant patients, the existing 2005 consensus statement
may continue to deter use of the LNG 52-mg IUS in this
population [19].
The CDC's most recent recommendation [11] for the
insertion of IUS in solid organ transplant recipients is based
on a systematic literature review of four case reports identifying
five patients [20]. Only two patients were under the age of 22,
and only one patient (43 years old) had a confirmed LNG-IUS.
Our case series identified six adolescents and young adults who
had undergone solid organ transplant and were also using the
LNG 52-mg IUS system (Table 1). All transplant recipients
were using the IUD for contraception, with no patients
noting concurrent use for management of heavy or irregular
menstrual bleeding.
Although we only have data for more than a year in four cases,
there were no unintended pregnancies among the six individuals
using the LNG 52-mg IUS. There were no cases of pelvic
inflammatory disease during LNG 52-mg IUS use. Case two in
particular had a documented localized cervicitis but did not
progress to pelvic inflammatory disease or systemic infection,
despite exposure to a total of four different immunosuppressants.
The current series has several limitations, most notably, the
small number of total cases. Furthermore, different organs were
transplanted, and multiple immunosuppressants were used to
treat our subjects, limiting the interpretation of our results. Since
our patients did not have complicated transplants, defined as
graft failure, rejection, or cardiac allograft vasculopathy, we
cannot extrapolate our data to women who have complicated
transplants. Finally, it is unknown whether these adolescents
were at risk for sexual infection or pregnancy during the entire
study period.
Despite the small number of subjects, our study
constitutes the largest case series published in the adolescent
and young adult transplant population, demonstrating the
safety of the LNG 52-mg IUS in six solid organ transplant
recipients. Based on published CDC recommendations and
further supported by our findings, we encourage healthcare
providers to feel comfortable using IUDs in this population.
We also encourage providers to report their outcomes to
further strengthen the amount of information in the literature,
thereby ensuring reliable and effective contraception for
these high-risk patients.
4 P.S. Huguelet et al. / Contraception xx (2016) xxxxxx
Funding
This research did not receive any specific grant from
funding agencies in the public, commercial or not-for-profit
sectors.
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