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A case series on the use of levonorgestrel 52 mg intrauterine system after organ transplant
CON-09100; No of Pages 3 Contraception xxx (2018) xxx–xxx
Contents lists available at ScienceDirect
Contraception journal homepage: www.elsevier.com/locate/con
Original research article
A case series on the use of levonorgestrel 52 mg intrauterine system after organ transplant Cassia R.T. Juliato ⁎, Paulo Stahlschmidt, Arlete Fernandes, Ilza Monteiro, Luis Bahamondes Family Planning Clinic, Department of Obstetrics and Gynecology, University of Campinas Medical School, 13084-971, Campinas, SP, Brazil
a r t i c l e
i n f o
Article history: Received 26 October 2017 Received in revised form 28 April 2018 Accepted 29 April 2018 Available online xxxx Keywords: Clinical performance Levonorgestrel-releasing intrauterine system Organ transplantation Contraception
a b s t r a c t Objective: To assess the clinical performance (pregnancy and occurrence of pelvic infection) of the levonorgestrel 52-mg intrauterine system (LNG IUS) in solid organ transplant recipients. Study design: We performed a retrospective chart review of all patients seen in the Family Planning Clinic at the University of Campinas Department of Obstetrics and Gynecology from 2007 to 2017 to identify women with solid organ transplantation using immunosuppression who received an LNG IUS. Our routine clinical practice for such patients is to perform initial follow-up 40–60 days after placement and then every 12 months. We analyzed women's sociodemographic characteristics, duration of use of the LNG IUS, continuation and discontinuation reasons, and complications. Results: Of the 23 women evaluated, 21 had kidney transplantation and 2 had liver transplantation. One woman received an LNG IUS prior to solid organ implantation (1.7 years, renal transplant). The 22 other women received the LNG IUS a median of 6.3 years (interquartile [IQ25–75] range 1.7–15 years). Seventeen (74%) women primarily used the LNG IUS for contraception; the other 6 desired the LNG IUS for contraception and heavy menstrual bleeding (HMB) treatment. We observed no cases of pregnancy or pelvic infection. Over the median follow-up time of 49.3 months (IQ25–75 15–80 months), 7 women used the same IUS for more than 60 months and 8 women received a second IUS. Conclusions: Due to the fact that no pregnancies or pelvic infections were observed in this case series, we concluded that the LNG IUS is an option for transplanted women for contraception and for HMB treatment. Implications: Women at reproductive age after solid organ transplantation needs contraception for long time and the LNG IUS is a safe and effective option. © 2018 Elsevier Inc. All rights reserved.
1. Introduction An estimated 40% of women worldwide are recipients of solid organ transplantation, with one third being of reproductive age and consequently at risk for unplanned pregnancy [1]. However, a survey reported that less than half of the women who had undergone transplantation received counseling on effective contraception and almost 90% of the pregnancies occurring in this group of women were unplanned [2]. Since fertility is known to return as soon as 3 weeks after transplantation, highly effective contraception options are needed for these women [3]. Long-acting reversible contraceptive (LARC) methods are highly effective and ideal for women who need long-term reliable contraception such as solid organ transplant recipients. The levonorgestrel (LNG) 52mg intrauterine system (IUS) has a contraceptive effectiveness with a typical pregnancy failure rate of 0.2/100 women-years [4,5]. Theoretically, the risk of pelvic infection may be lower in users of the LNG IUS ⁎ Corresponding author. Tel.: +55 19 3289 2856; fax: +55 19 3289 2440. E-mail address: [email protected] (C.R.T. Juliato).
than copper intrauterine device (IUD), and the 2016 U.S. Centers for Disease Control and Prevention Medical Eligibility Criteria (CDC MEC) support the use of the LNG IUS following uncomplicated transplantations. The CDC MEC advise that for complicated transplants, the risks may outweigh the benefits [6]. Data on the safety and effectiveness of the LNG IUS following transplant surgery are limited. This study reports on a case series of women with LNG IUS use before or following solid organ transplantation.
2. Material and methods We performed a retrospective chart review of all patients seen in the Family Planning Clinic at the University of Campinas Department of Obstetrics and Gynecology from 2007 to 2017 to identify women with solid organ transplantation using immunosuppression who received an LNG IUS (Mirena, Bayer Oy, Turku, Finland). The Ethical Committee approved the study protocol and authorized the data collection and analysis. Our routine clinical practice for such patients is to perform initial follow-up 40–60 days after placement and then every 12 months.
https://doi.org/10.1016/j.contraception.2018.04.017 0010-7824/© 2018 Elsevier Inc. All rights reserved.
Please cite this article as: Juliato CRT, et al, A case series on the use of levonorgestrel 52mg intrauterine system after organ transplant, Contraception (2018), https://doi.org/10.1016/j.contraception.2018.04.017
2
C.R.T. Juliato et al. / Contraception xxx (2018) xxx–xxx
Table 1 Age, body mass index and time between solid organ transplantation and initial LNG IUS placement (N=23) Variables
n (%) or Mean ± SD
Age (years) b20 20–29 30–39 ≥40 Body mass index (kg/m2) Number of pregnancies 0 1–2 3–4 ≥5 Time between organ transplantation and LNG IUS placement (years)a
34.1±8.8 1±4.4 8±34.8 7±30.4 7±30,4 25.8±4.5 10±43.4 6±26.1 4±17.4 3±13.1 6.3±4.4 1±4.4 2±8.7 2±8.7 5±21.7 8±34.8 5±21.7
0–12 months 13–24 months 25–60 months 61–120 months N121 months a
n=22, one women had placement 1.7 months before transplantation.
The women are advised to return before the scheduled period if they present any symptoms related to the use of the IUS. We deidentified the data following collection. All the participants received appropriate counseling on the contraceptive methods available at the clinic. Clinicians inserted the LNG IUS within the first 5 days of the cycle or at any day for those who were amenorrheic due to use of depotmedroxyprogesterone acetate injection. In accordance with Brazilian law, public service contraceptive methods were provided at no cost to the women as well as organ transplantation. We analyzed women's sociodemographic characteristics, duration of use of the LNG IUS, continuation and discontinuation reasons, and complications, as well as the bleeding patterns reported at the women's last visit.
3. Results We reviewed 7368 files from our clinic database and identified 23 women who received solid organ transplantation and used the LNG IUS. All the charts listed in the database were available for review. We included 23 women who chose to use the LNG IUS for contraception (n=17) or for both contraception and heavy menstrual bleeding (HMB) (n=6) following kidney or liver transplantation. Table 1 included data on age, body mass index, and time between organ transplantation and LNG IUS placement. The clinician inserted the LNG IUS after solid transplant (median 6.3 years, interquartile IQ 25–75 range 0.1-15). One woman used the IUS before transplantation (1.7 years), and 4 of the women were in the first 2 years after transplantation (Table 1). We observed no cases of pregnancy or pelvic infection. Table 2 lists details about each of the 21 kidney transplant and 2 liver transplant patients in this report. One woman had two kidney transplant procedures, and both procedures were performed before LNG IUS placement. All women were using immunosuppressive drugs at the time of LNG IUS placement; the most common drugs were prednisone, tacrolimus and mycophenolate. The median duration of LNG IUS use was 44 months (range 1–111 months, interquartile IQ25–75 range 15–80). At the time of this report, 8 women were using their second LNG IUS, with a mean duration of use of the first device of 71± 6.2 months. Of these 8 women, 7 had used the same device uninterruptedly for more than 60 months, with a maximum duration of use of 80 months. Eight women discontinued the use of the device. We removed the LNG IUS in six women: in two cases because the women wished to become pregnant, two women underwent hysterectomy (one due to HMB and uterine fibromas and one due to cervical cancer), and two women expelled the device.
4. Discussion The present study supports the safety of LNG IUS in a small cohort of organ transplant patients. This series of 23 women represents, to the best of our knowledge, the largest report of such patients. A systematic
Table 2 Indication for insertion, duration of use, infection and pregnancy outcomes in solid organ transplant recipients using the LNG IUS Case
Age at LNG IUS placement (years)
Year of transplantation
Organ
Year of insertion
Indication
Time between transplantation and LNG IUS (months)
Second LNG IUS
Follow-up (months)
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23
28 41 29 34 20 45 34 23 38 40 46 29 29 31 23 27 40 34 40 48 18 46 43
1996 1998 1999 2000 2000 2000a 2001 2001 2001 2002 2002 2005 2005 2005 2006 2007 2007 2007 2008 2008 2011 2012 2015
Kidney Kidney Kidney Kidney Kidney Kidney Kidney Kidney Kidney Kidney Kidney Kidney Kidney Kidney Kidney Liver Kidney Kidney Kidney Kidney Kidney Kidney Liver
2007 2009 2011 2007 2010 2016 2009 2009 2011 2010 2011 2008 2008 2012 2009 2008 2009 2010 2011 2013 2011 2012 2013
Contraception Contraception & HMB Contraception Contraception & HMB Contraception Contraception Contraception Contraception Contraception Contraception & HMB Contraception & HMB Contraception Contraception Contraception Contraception Contraception Contraception Contraception Contraception Contraception & HMB Contraception Contraception & HMB Contraception
141 134 147 86 128 186 101 104 111 99 110 38 39 90 31 20 23 33 39 68 1 10
2014 2015 No 2012 No No No No 2016 No No No No No 2015 2014 2015 2016 No No No No No
111 80 44 97 1 15 51 3 72 74 12 44 44 22 83 94 87 78 12 15 58 54 40
a b
b
Women with two kidney transplants. Women had LNG IUS placement 20 months before transplantation.
Please cite this article as: Juliato CRT, et al, A case series on the use of levonorgestrel 52mg intrauterine system after organ transplant, Contraception (2018), https://doi.org/10.1016/j.contraception.2018.04.017
C.R.T. Juliato et al. / Contraception xxx (2018) xxx–xxx
review that evaluated contraceptive use among women who received solid organ transplantation included five kidney recipients using IUDs. This systematic review reported inconsistent findings, including both beneficial health effects and contraceptive failure [7]. Despite the evidence regarding the need for contraception following solid organ transplantation, the World Health Organization's Medical Eligibility Criteria for Contraceptive Use [8] failed to include organ transplantation as a medical condition and provide no guidelines for the use of contraceptive methods by transplanted women. However, the U.S. Centers for Disease Control and Prevention [6] recognize that solid organ transplantation less than 2 years previously is a condition associated with an increased risk of adverse health events that may result from pregnancy, stating that long-acting, highly effective contraceptive methods might be the best choice for women under these circumstances. In this case series, more than a half of the transplanted women used condoms after IUS placement. Transplanted women should be advised that the use of condoms alone for contraception and fertility awareness contraceptive methods might not be the most appropriate choices because of their relatively higher failure rates during typical use. There is concern about the effectiveness of IUDs in organ-transplanted women due to the use of chronic immunosuppression. The theoretically decreased effectiveness was based on an old study that reported the occurrence of two pregnancies in women who had undergone organ transplantation and who were using copper IUDs, inferring that the use of immunosuppressive drugs could affect the efficacy of IUDs [9]. Therefore, there is no basis to conclude that IUDs are ineffective in transplanted women, and there is no evidence of a large number of failures in these women when compared to untransplanted women [10]. In LNG IUS users, this theoretical risk is less reasonable because, unlike the copper IUD, the contraceptive effect of the LNG IUS is achieved primarily by thickening the cervical mucus, thus interfering with sperm penetration [11]. A pilot study conducted to evaluate the uterine environment in posttransplanted and nontransplanted women before and after LNG IUS insertion showed no significant changes in the inflammatory biomarkers in either of the groups [12]. However, the women in our study were not screened for chlamydia or gonorrhea infection before IUS placement because it is not routine at the clinic. While we continue to gather more data, this case series provides additional evidence about the relative safety and efficacy of LNG IUS use in organ transplant recipients who are receiving immunosuppression. Furthermore, over one third of the women used the LNG IUS beyond the previously established effective lifetime of five years, reaching the recently suggested 7 years of use and beyond [13–16]. Acknowledgments This study received partial financial support from the Fundação de Apoio à Pesquisa do Estado de São Paulo (FAPESP) award no. 2015/ 20504-9 and from the National Research Council (CNPq) grant no. 573747/2008-3. Since 2007, the LNG IUSs used at our clinic have been
3
donated by the International Contraceptive Access Foundation, Turku, Finland, under an unrestricted grant. Conflicts of interest We declare that we have no conflicts of interest regarding this study. L.B. received an honorarium to be member of the advisory board and has been an invited speaker at scientific meetings for Bayer Healthcare Pharmaceuticals. He was also a member of the ICA Foundation Board of Trustees without remuneration. I.M. received an honorarium as a speaker at scientific meetings for Bayer Healthcare Pharmaceuticals. The remaining authors report no conflicts of interest. References [1] Organ Procurement and Transplantation Network, HRSA. Available from URL: http:// optn.transplant.hrsa.gov/, Accessed date: 12 August 2017. [2] Guazzelli CA, Torloni MR, Sanches TF, Barbieri M, Pestana JO. Contraceptive counseling and use among 197 female kidney transplant recipients. Transplantation 2008; 86(5):669–72. [3] Laifer SA, Darby MJ, Scantlebury VP, Harger JH, Caritis SN. Pregnancy and liver transplantation. Obstet Gynecol 1990;76:1083–8. [4] Bahamondes L, Bottura BF, Bahamondes MV, Gonçalves MP, Correia VM, Espejo-Arce X, et al. Estimated disability-adjusted life years averted by long-term provision of long acting contraceptive methods in a Brazilian clinic. Hum Reprod 2014;29: 2163–70. [5] Winner B, Peipert JF, Zhao Q, Buckel C, Madden T, Allsworth JE, et al. Effectiveness of long-acting reversible contraception. N Engl J Med 2012;366:1998–2007. [6] U.S. medical eligibility criteria for contraceptive use. Available at: https://www.cdc. gov/mmwr/volumes/65/rr/pdfs/rr6503.pdf, Accessed date: 12 July 2017. [7] Paulen ME, Folger SG, Curtis KM, Jamieson DJ. Contraceptive use among solid organ transplant patients: a systematic review. Contraception 2010;82:102–12. [8] World Health Organization. Medical eligibility criteria for contraceptive use. 5ª edition; 2015. [9] Zerner J, Doil KL, Drewry J, Leeber DA. Intrauterine contraceptive device failures in renal transplant patients. J Reprod Med 1981;26:99–102. [10] Estes CM, Westhoff C. Contraception for the transplant patient. Semin Perinat 2007; 31(6):372–7. [11] Moraes LG, Marchi NM, Pitoli AC, Hidalgo MM, Silveira C, Modesto W, et al. Assessment of the quality of cervical mucus among users of the levonorgestrel-releasing intrauterine system at different times of use. Eur J Contracept Reprod Health Care 2016;21:318–22. [12] Kim CR, Martinez-Maza O, Magpantay L, Magyar C, Gornbein J, Rible R, et al. Immunologic evaluation of the endometrium with a levonorgestrel intrauterine device in solid organ transplant women and healthy controls. Contraception 2016;94:534–54. [13] Rowe P, Farley T, Peregoudov A, Piaggio G, Boccard S, Landoulsi S, et al. Safety and efficacy in parous women of a 52-mg levonorgestrel-medicated intrauterine device: a 7-year randomized comparative study with the TCu380A. Contraception 2016;93: 498–506. [14] Hidalgo MM, Hidalgo-Regina C, Bahamondes MV, Monteiro I, Petta CA, Bahamondes L. Serum levonorgestrel levels and endometrial thickness during extended use of the levonorgestrel-releasing intrauterine system. Contraception 2009;80:84–9. [15] McNicholas C, Swor E, Wan L, Peipert JF. Prolonged use of the etonogestrel implant and levonorgestrel intrauterine device: 2 years beyond Food and Drug Administration-approved duration. Am J Obstet Gynecol 2017;216:586.e1–6. [16] Bahamondes L, Fernandes A, Bahamondes MV, Juliato CT, Ali M, Monteiro I. Pregnancy outcomes associated with extended use of the 52-mg 20 μg/day levonorgestrel-releasing intrauterine system beyond 60 months: a chart review of 776 women in Brazil. Contraception 2017;97:205–9.
Please cite this article as: Juliato CRT, et al, A case series on the use of levonorgestrel 52mg intrauterine system after organ transplant, Contraception (2018), https://doi.org/10.1016/j.contraception.2018.04.017
Contents lists available at ScienceDirect
Contraception journal homepage: www.elsevier.com/locate/con
Original research article
A case series on the use of levonorgestrel 52 mg intrauterine system after organ transplant Cassia R.T. Juliato ⁎, Paulo Stahlschmidt, Arlete Fernandes, Ilza Monteiro, Luis Bahamondes Family Planning Clinic, Department of Obstetrics and Gynecology, University of Campinas Medical School, 13084-971, Campinas, SP, Brazil
a r t i c l e
i n f o
Article history: Received 26 October 2017 Received in revised form 28 April 2018 Accepted 29 April 2018 Available online xxxx Keywords: Clinical performance Levonorgestrel-releasing intrauterine system Organ transplantation Contraception
a b s t r a c t Objective: To assess the clinical performance (pregnancy and occurrence of pelvic infection) of the levonorgestrel 52-mg intrauterine system (LNG IUS) in solid organ transplant recipients. Study design: We performed a retrospective chart review of all patients seen in the Family Planning Clinic at the University of Campinas Department of Obstetrics and Gynecology from 2007 to 2017 to identify women with solid organ transplantation using immunosuppression who received an LNG IUS. Our routine clinical practice for such patients is to perform initial follow-up 40–60 days after placement and then every 12 months. We analyzed women's sociodemographic characteristics, duration of use of the LNG IUS, continuation and discontinuation reasons, and complications. Results: Of the 23 women evaluated, 21 had kidney transplantation and 2 had liver transplantation. One woman received an LNG IUS prior to solid organ implantation (1.7 years, renal transplant). The 22 other women received the LNG IUS a median of 6.3 years (interquartile [IQ25–75] range 1.7–15 years). Seventeen (74%) women primarily used the LNG IUS for contraception; the other 6 desired the LNG IUS for contraception and heavy menstrual bleeding (HMB) treatment. We observed no cases of pregnancy or pelvic infection. Over the median follow-up time of 49.3 months (IQ25–75 15–80 months), 7 women used the same IUS for more than 60 months and 8 women received a second IUS. Conclusions: Due to the fact that no pregnancies or pelvic infections were observed in this case series, we concluded that the LNG IUS is an option for transplanted women for contraception and for HMB treatment. Implications: Women at reproductive age after solid organ transplantation needs contraception for long time and the LNG IUS is a safe and effective option. © 2018 Elsevier Inc. All rights reserved.
1. Introduction An estimated 40% of women worldwide are recipients of solid organ transplantation, with one third being of reproductive age and consequently at risk for unplanned pregnancy [1]. However, a survey reported that less than half of the women who had undergone transplantation received counseling on effective contraception and almost 90% of the pregnancies occurring in this group of women were unplanned [2]. Since fertility is known to return as soon as 3 weeks after transplantation, highly effective contraception options are needed for these women [3]. Long-acting reversible contraceptive (LARC) methods are highly effective and ideal for women who need long-term reliable contraception such as solid organ transplant recipients. The levonorgestrel (LNG) 52mg intrauterine system (IUS) has a contraceptive effectiveness with a typical pregnancy failure rate of 0.2/100 women-years [4,5]. Theoretically, the risk of pelvic infection may be lower in users of the LNG IUS ⁎ Corresponding author. Tel.: +55 19 3289 2856; fax: +55 19 3289 2440. E-mail address: [email protected] (C.R.T. Juliato).
than copper intrauterine device (IUD), and the 2016 U.S. Centers for Disease Control and Prevention Medical Eligibility Criteria (CDC MEC) support the use of the LNG IUS following uncomplicated transplantations. The CDC MEC advise that for complicated transplants, the risks may outweigh the benefits [6]. Data on the safety and effectiveness of the LNG IUS following transplant surgery are limited. This study reports on a case series of women with LNG IUS use before or following solid organ transplantation.
2. Material and methods We performed a retrospective chart review of all patients seen in the Family Planning Clinic at the University of Campinas Department of Obstetrics and Gynecology from 2007 to 2017 to identify women with solid organ transplantation using immunosuppression who received an LNG IUS (Mirena, Bayer Oy, Turku, Finland). The Ethical Committee approved the study protocol and authorized the data collection and analysis. Our routine clinical practice for such patients is to perform initial follow-up 40–60 days after placement and then every 12 months.
https://doi.org/10.1016/j.contraception.2018.04.017 0010-7824/© 2018 Elsevier Inc. All rights reserved.
Please cite this article as: Juliato CRT, et al, A case series on the use of levonorgestrel 52mg intrauterine system after organ transplant, Contraception (2018), https://doi.org/10.1016/j.contraception.2018.04.017
2
C.R.T. Juliato et al. / Contraception xxx (2018) xxx–xxx
Table 1 Age, body mass index and time between solid organ transplantation and initial LNG IUS placement (N=23) Variables
n (%) or Mean ± SD
Age (years) b20 20–29 30–39 ≥40 Body mass index (kg/m2) Number of pregnancies 0 1–2 3–4 ≥5 Time between organ transplantation and LNG IUS placement (years)a
34.1±8.8 1±4.4 8±34.8 7±30.4 7±30,4 25.8±4.5 10±43.4 6±26.1 4±17.4 3±13.1 6.3±4.4 1±4.4 2±8.7 2±8.7 5±21.7 8±34.8 5±21.7
0–12 months 13–24 months 25–60 months 61–120 months N121 months a
n=22, one women had placement 1.7 months before transplantation.
The women are advised to return before the scheduled period if they present any symptoms related to the use of the IUS. We deidentified the data following collection. All the participants received appropriate counseling on the contraceptive methods available at the clinic. Clinicians inserted the LNG IUS within the first 5 days of the cycle or at any day for those who were amenorrheic due to use of depotmedroxyprogesterone acetate injection. In accordance with Brazilian law, public service contraceptive methods were provided at no cost to the women as well as organ transplantation. We analyzed women's sociodemographic characteristics, duration of use of the LNG IUS, continuation and discontinuation reasons, and complications, as well as the bleeding patterns reported at the women's last visit.
3. Results We reviewed 7368 files from our clinic database and identified 23 women who received solid organ transplantation and used the LNG IUS. All the charts listed in the database were available for review. We included 23 women who chose to use the LNG IUS for contraception (n=17) or for both contraception and heavy menstrual bleeding (HMB) (n=6) following kidney or liver transplantation. Table 1 included data on age, body mass index, and time between organ transplantation and LNG IUS placement. The clinician inserted the LNG IUS after solid transplant (median 6.3 years, interquartile IQ 25–75 range 0.1-15). One woman used the IUS before transplantation (1.7 years), and 4 of the women were in the first 2 years after transplantation (Table 1). We observed no cases of pregnancy or pelvic infection. Table 2 lists details about each of the 21 kidney transplant and 2 liver transplant patients in this report. One woman had two kidney transplant procedures, and both procedures were performed before LNG IUS placement. All women were using immunosuppressive drugs at the time of LNG IUS placement; the most common drugs were prednisone, tacrolimus and mycophenolate. The median duration of LNG IUS use was 44 months (range 1–111 months, interquartile IQ25–75 range 15–80). At the time of this report, 8 women were using their second LNG IUS, with a mean duration of use of the first device of 71± 6.2 months. Of these 8 women, 7 had used the same device uninterruptedly for more than 60 months, with a maximum duration of use of 80 months. Eight women discontinued the use of the device. We removed the LNG IUS in six women: in two cases because the women wished to become pregnant, two women underwent hysterectomy (one due to HMB and uterine fibromas and one due to cervical cancer), and two women expelled the device.
4. Discussion The present study supports the safety of LNG IUS in a small cohort of organ transplant patients. This series of 23 women represents, to the best of our knowledge, the largest report of such patients. A systematic
Table 2 Indication for insertion, duration of use, infection and pregnancy outcomes in solid organ transplant recipients using the LNG IUS Case
Age at LNG IUS placement (years)
Year of transplantation
Organ
Year of insertion
Indication
Time between transplantation and LNG IUS (months)
Second LNG IUS
Follow-up (months)
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23
28 41 29 34 20 45 34 23 38 40 46 29 29 31 23 27 40 34 40 48 18 46 43
1996 1998 1999 2000 2000 2000a 2001 2001 2001 2002 2002 2005 2005 2005 2006 2007 2007 2007 2008 2008 2011 2012 2015
Kidney Kidney Kidney Kidney Kidney Kidney Kidney Kidney Kidney Kidney Kidney Kidney Kidney Kidney Kidney Liver Kidney Kidney Kidney Kidney Kidney Kidney Liver
2007 2009 2011 2007 2010 2016 2009 2009 2011 2010 2011 2008 2008 2012 2009 2008 2009 2010 2011 2013 2011 2012 2013
Contraception Contraception & HMB Contraception Contraception & HMB Contraception Contraception Contraception Contraception Contraception Contraception & HMB Contraception & HMB Contraception Contraception Contraception Contraception Contraception Contraception Contraception Contraception Contraception & HMB Contraception Contraception & HMB Contraception
141 134 147 86 128 186 101 104 111 99 110 38 39 90 31 20 23 33 39 68 1 10
2014 2015 No 2012 No No No No 2016 No No No No No 2015 2014 2015 2016 No No No No No
111 80 44 97 1 15 51 3 72 74 12 44 44 22 83 94 87 78 12 15 58 54 40
a b
b
Women with two kidney transplants. Women had LNG IUS placement 20 months before transplantation.
Please cite this article as: Juliato CRT, et al, A case series on the use of levonorgestrel 52mg intrauterine system after organ transplant, Contraception (2018), https://doi.org/10.1016/j.contraception.2018.04.017
C.R.T. Juliato et al. / Contraception xxx (2018) xxx–xxx
review that evaluated contraceptive use among women who received solid organ transplantation included five kidney recipients using IUDs. This systematic review reported inconsistent findings, including both beneficial health effects and contraceptive failure [7]. Despite the evidence regarding the need for contraception following solid organ transplantation, the World Health Organization's Medical Eligibility Criteria for Contraceptive Use [8] failed to include organ transplantation as a medical condition and provide no guidelines for the use of contraceptive methods by transplanted women. However, the U.S. Centers for Disease Control and Prevention [6] recognize that solid organ transplantation less than 2 years previously is a condition associated with an increased risk of adverse health events that may result from pregnancy, stating that long-acting, highly effective contraceptive methods might be the best choice for women under these circumstances. In this case series, more than a half of the transplanted women used condoms after IUS placement. Transplanted women should be advised that the use of condoms alone for contraception and fertility awareness contraceptive methods might not be the most appropriate choices because of their relatively higher failure rates during typical use. There is concern about the effectiveness of IUDs in organ-transplanted women due to the use of chronic immunosuppression. The theoretically decreased effectiveness was based on an old study that reported the occurrence of two pregnancies in women who had undergone organ transplantation and who were using copper IUDs, inferring that the use of immunosuppressive drugs could affect the efficacy of IUDs [9]. Therefore, there is no basis to conclude that IUDs are ineffective in transplanted women, and there is no evidence of a large number of failures in these women when compared to untransplanted women [10]. In LNG IUS users, this theoretical risk is less reasonable because, unlike the copper IUD, the contraceptive effect of the LNG IUS is achieved primarily by thickening the cervical mucus, thus interfering with sperm penetration [11]. A pilot study conducted to evaluate the uterine environment in posttransplanted and nontransplanted women before and after LNG IUS insertion showed no significant changes in the inflammatory biomarkers in either of the groups [12]. However, the women in our study were not screened for chlamydia or gonorrhea infection before IUS placement because it is not routine at the clinic. While we continue to gather more data, this case series provides additional evidence about the relative safety and efficacy of LNG IUS use in organ transplant recipients who are receiving immunosuppression. Furthermore, over one third of the women used the LNG IUS beyond the previously established effective lifetime of five years, reaching the recently suggested 7 years of use and beyond [13–16]. Acknowledgments This study received partial financial support from the Fundação de Apoio à Pesquisa do Estado de São Paulo (FAPESP) award no. 2015/ 20504-9 and from the National Research Council (CNPq) grant no. 573747/2008-3. Since 2007, the LNG IUSs used at our clinic have been
3
donated by the International Contraceptive Access Foundation, Turku, Finland, under an unrestricted grant. Conflicts of interest We declare that we have no conflicts of interest regarding this study. L.B. received an honorarium to be member of the advisory board and has been an invited speaker at scientific meetings for Bayer Healthcare Pharmaceuticals. He was also a member of the ICA Foundation Board of Trustees without remuneration. I.M. received an honorarium as a speaker at scientific meetings for Bayer Healthcare Pharmaceuticals. The remaining authors report no conflicts of interest. References [1] Organ Procurement and Transplantation Network, HRSA. Available from URL: http:// optn.transplant.hrsa.gov/, Accessed date: 12 August 2017. [2] Guazzelli CA, Torloni MR, Sanches TF, Barbieri M, Pestana JO. Contraceptive counseling and use among 197 female kidney transplant recipients. Transplantation 2008; 86(5):669–72. [3] Laifer SA, Darby MJ, Scantlebury VP, Harger JH, Caritis SN. Pregnancy and liver transplantation. Obstet Gynecol 1990;76:1083–8. [4] Bahamondes L, Bottura BF, Bahamondes MV, Gonçalves MP, Correia VM, Espejo-Arce X, et al. Estimated disability-adjusted life years averted by long-term provision of long acting contraceptive methods in a Brazilian clinic. Hum Reprod 2014;29: 2163–70. [5] Winner B, Peipert JF, Zhao Q, Buckel C, Madden T, Allsworth JE, et al. Effectiveness of long-acting reversible contraception. N Engl J Med 2012;366:1998–2007. [6] U.S. medical eligibility criteria for contraceptive use. Available at: https://www.cdc. gov/mmwr/volumes/65/rr/pdfs/rr6503.pdf, Accessed date: 12 July 2017. [7] Paulen ME, Folger SG, Curtis KM, Jamieson DJ. Contraceptive use among solid organ transplant patients: a systematic review. Contraception 2010;82:102–12. [8] World Health Organization. Medical eligibility criteria for contraceptive use. 5ª edition; 2015. [9] Zerner J, Doil KL, Drewry J, Leeber DA. Intrauterine contraceptive device failures in renal transplant patients. J Reprod Med 1981;26:99–102. [10] Estes CM, Westhoff C. Contraception for the transplant patient. Semin Perinat 2007; 31(6):372–7. [11] Moraes LG, Marchi NM, Pitoli AC, Hidalgo MM, Silveira C, Modesto W, et al. Assessment of the quality of cervical mucus among users of the levonorgestrel-releasing intrauterine system at different times of use. Eur J Contracept Reprod Health Care 2016;21:318–22. [12] Kim CR, Martinez-Maza O, Magpantay L, Magyar C, Gornbein J, Rible R, et al. Immunologic evaluation of the endometrium with a levonorgestrel intrauterine device in solid organ transplant women and healthy controls. Contraception 2016;94:534–54. [13] Rowe P, Farley T, Peregoudov A, Piaggio G, Boccard S, Landoulsi S, et al. Safety and efficacy in parous women of a 52-mg levonorgestrel-medicated intrauterine device: a 7-year randomized comparative study with the TCu380A. Contraception 2016;93: 498–506. [14] Hidalgo MM, Hidalgo-Regina C, Bahamondes MV, Monteiro I, Petta CA, Bahamondes L. Serum levonorgestrel levels and endometrial thickness during extended use of the levonorgestrel-releasing intrauterine system. Contraception 2009;80:84–9. [15] McNicholas C, Swor E, Wan L, Peipert JF. Prolonged use of the etonogestrel implant and levonorgestrel intrauterine device: 2 years beyond Food and Drug Administration-approved duration. Am J Obstet Gynecol 2017;216:586.e1–6. [16] Bahamondes L, Fernandes A, Bahamondes MV, Juliato CT, Ali M, Monteiro I. Pregnancy outcomes associated with extended use of the 52-mg 20 μg/day levonorgestrel-releasing intrauterine system beyond 60 months: a chart review of 776 women in Brazil. Contraception 2017;97:205–9.
Please cite this article as: Juliato CRT, et al, A case series on the use of levonorgestrel 52mg intrauterine system after organ transplant, Contraception (2018), https://doi.org/10.1016/j.contraception.2018.04.017