The Effect of Immediate Postpartum Compared to Delayed Postpartum and Interval Etonogestrel Contraceptive Implant Insertion on Removal Rates for Bleeding Luu Doan Ireland MD, MPH, Vinita Goyal MD, MPH, Christina A. Raker ScD, Anne Murray MD, Rebecca H. Allen MD, MPH PII: DOI: Reference:
S0010-7824(14)00291-1 doi: 10.1016/j.contraception.2014.05.010 CON 8345
To appear in:
Contraception
Received date: Revised date: Accepted date:
18 December 2013 8 May 2014 21 May 2014
Please cite this article as: Ireland Luu Doan, Goyal Vinita, Raker Christina A., Murray Anne, Allen Rebecca H., The Effect of Immediate Postpartum Compared to Delayed Postpartum and Interval Etonogestrel Contraceptive Implant Insertion on Removal Rates for Bleeding, Contraception (2014), doi: 10.1016/j.contraception.2014.05.010
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT TITLE PAGE 1. The Effect of Immediate Postpartum Compared to Delayed Postpartum and
T
Interval Etonogestrel Contraceptive Implant Insertion on Removal Rates for
RI P
Bleeding 2. Authors:
SC
a. Luu Doan Ireland MD, MPH (David Geffen School of Medicine at the
NU
University of California, Los Angeles)
b. Vinita Goyal MD, MPH (The Warren Alpert Medical School of Brown
MA
University and Women and Infants Hospital) c. Christina A. Raker ScD (The Warren Alpert Medical School of Brown
ED
University and Women and Infants Hospital)
PT
d. Anne Murray MD (The Warren Alpert Medical School of Brown
CE
University and Women and Infants Hospital) e. Rebecca H. Allen MD, MPH (The Warren Alpert Medical School of
AC
Brown University and Women and Infants Hospital) 3. We gratefully acknowledge the financial support provided by the Department of Obstetrics and Gynecology of the Warren Alpert Medical School of Brown University and Women and Infants Hospital 4. No conflicts of interest 5. Clinical trial registration number is not applicable 6. Abstract: 247 words 7. Text: 2006 words
ACCEPTED MANUSCRIPT 8. Keywords: Postpartum contraception; Etonogestrel; Implant; Implanon; Nexplanon; Continuation; Vaginal bleeding
T
9. A short running title: Timing of Etonogestrel Implant Insertion and Effect on
RI P
Removal for Bleeding
AC
CE
PT
ED
MA
NU
SC
10. Corresponding author: Luu Doan Ireland [email protected]
ACCEPTED MANUSCRIPT ABSTRACT
T
Objective: To determine whether the discontinuation rate of the etonogestrel
RI P
contraceptive implant due to irregular vaginal bleeding among women with immediate postpartum insertion is increased compared to delayed postpartum and
NU
SC
interval placement.
Study Design: This retrospective cohort study compared women who underwent
MA
immediate postpartum etonogestrel contraceptive implant insertion (within 96 hours of delivery) to delayed postpartum (6 to 12 weeks postpartum) and interval
ED
insertion between January 2008 and December 2010. Charts were reviewed for
PT
date and reason for removal. A chi-squared test was used to compare
CE
discontinuation due to bleeding between cohorts. Baseline characteristics predictive
AC
of implant removal were evaluated by simple logistic regression.
Results: There were 259 women in the immediate postpartum group, 49 in the delayed postpartum group and 106 in the interval group. Average age at insertion was 22.6 (± 5.5) years. Overall, 19.3% of women in the immediate postpartum group requested removal due to irregular bleeding compared to 18.4% in the delayed postpartum group (OR 1.06, 95% CI 0.48 – 2.33) and 20.8% in the interval group (OR 0.91, 95% CI 0.52 – 1.60). There was no difference between groups in premature removal rates for any side effect. There were no sociodemographic or clinical characteristics predictive of removal in any group.
ACCEPTED MANUSCRIPT
Conclusion: One-fifth of etonogestrel contraceptive implant users requested
T
premature removal due to irregular bleeding. Immediate postpartum implant
RI P
insertion does not lead to increased removal rates and may help reduce unintended pregnancy. Mechanisms to help women manage irregular bleeding due to the
NU
SC
implant are needed.
IMPLICATIONS
MA
Immediate postpartum insertion of the etonogestrel contraceptive implant does not lead to increased removal rates due to vaginal bleeding compared to
ED
delayed postpartum or interval insertion. Immediate postpartum implant insertion
PT
may increase uptake of long-acting reversible contraception and help reduce short
CE
inter-pregnancy intervals and unintended pregnancy.
AC
INTRODUCTION
The immediate postpartum period offers an ideal time for women to initiate contraception due to patient access and convenience. Delaying initiation of contraceptionto the standard 6 week postpartum visit places many women at risk for unintended pregnancy. By 6 weeks postpartum, up to 40% of women will have had unprotected intercourse(1) and nearly 50% will have ovulated (2). Furthermore, not all women seek postpartum medical care, resulting in a large proportion with unmet contraceptive need (3).
ACCEPTED MANUSCRIPT The etonogestrel contraceptive implant is highly effective at preventing pregnancy with failure rates of less than 2 per 1000 insertions (4). The method is
T
ideal for women desiring long-acting reversible contraception (LARC) and can be
RI P
initiated safely at any time in the post-partum period (5). Among women with breastfeeding intent, immediate (between 1 to 3 days postpartum) versus delayed
SC
(4 to 8 weeks postpartum) etonogestrel implant insertion results in comparable
NU
breastfeeding outcomes (13). Approximately one-third of users, however, will undergo premature implant removal prior to the 3-year period of efficacy (6). The
MA
main reason for premature discontinuation is irregular vaginal bleeding (7), with one-third to one-half of women citing this as a their primary reason for removal (5,
ED
8).
PT
Little is known about differences in bleeding patterns between postpartum
CE
or interval placement of the etonogestrel contraceptive implant and its potential effect on continuation. In a study of breastfeeding mothers comparing immediate
AC
postpartum insertion of the etonogestrel implant to delayed administration of depot medroxyprogesterone acetate (DMPA) at 6 weeks postpartum, there was no difference in bleeding days for up to 12 weeks postpartum (12). Another study randomized 250 non-breastfeeding women to immediate versus delayed postpartum insertion of the levonorgestrel contraceptive implant and found more bleeding days in the first 6 weeks postpartum in the immediate insertion group but continuation rates were not reported (1). Finally, a small retrospectivestudy on predictors of premature discontinuation of etonogestrel contraceptive implant
ACCEPTED MANUSCRIPT among U.S. women did not find thatpostpartum or breastfeeding status were associated with removal (14).
T
In this study, we investigated the discontinuation rates due to irregular
RI P
bleeding among women who had the etonogestrel contraceptive implant inserted within 96 hours of delivery compared to women who had the device placed outside
SC
the immediate postpartum period. Based on the previous research with
NU
levonorgestrel implant (1) and anecdotal experience, we hypothesized that women who have immediate postpartum etonogestrel contraceptive implant insertion
MA
would have higher rates of premature removal for bleeding complaints.
ED
MATERIALS AND METHODS
PT
We conducted a retrospective cohort study comparing discontinuation rates
CE
due to vaginal bleeding in women who had the etonogestrel contraceptive implant inserted within 96 hours of delivery at Women and Infants Hospital compared to
AC
women who had placement outside the immediate postpartum period. Women undergoing immediate postpartum insertion were included if they received prenatal care at the Women’s Primary Care Center (WPCC), a large hospital-based obstetrics and gynecology clinic, or the Providence Community Health Centers (PCHC), both located in Rhode Island and providing care to underserved women in the Providence area. Both of these practices deliver at Women and Infants Hospital, the primary obstetrical hospital in Rhode Island with 8,500 deliveries in 2012, accounting for 80% of all births in the state. The comparison group included women undergoing implant insertion at the WPCC outside of the immediate
ACCEPTED MANUSCRIPT postpartum period. The comparison group was further subdivided into women who underwent delayed postpartum insertion from 6 to 12 weeks postpartum and
T
women who underwent interval insertion at a gynecologic visit (either more than
RI P
12 weeks postpartum or unrelated to a pregnancy event). It was clinic policy at the time of the study to schedule postpartum visits no earlier than 6 weeks postpartum.
SC
Pharmacy records were reviewed from January 2008 to December 2010 to identify
NU
subjects for the study and insertion timing was verified during chart review. Women were excluded if they received an implant between 96 hours to 6 weeks postpartum
MA
or less than 6 weeks postabortion. Pharmacy records and medical charts were reviewed to confirm placement date in relation to any pregnancy event.
ED
Sociodemographic and clinical variables were collected during the chart review as
PT
well as data on clinic visits related to implant side effects, removal of the implant,
CE
date of removal, reasons for removal, complications of removal, and post-implant removal contraceptive choice. This study was approved by the Institutional Review
Centers.
AC
Boards at both Women and Infants Hospital and the Providence Community Health
The primary outcome in this study was the difference in discontinuation rates of the etonogestrel contraceptive implants due to irregular vaginal bleeding among women who received the implant during the immediate postpartum period compared to women who underwent delayed postpartum or interval insertion. Based on review of pharmacy records, we estimated 304 subjects in the immediate postpartum group and 188 subjects in the comparison group. This gave us the ability to detect a minimum 10% difference in discontinuation rates due to irregular
ACCEPTED MANUSCRIPT bleeding between the two cohorts with 80% power. This sample size calculation assumed an 11% discontinuation rate in the interval group due to bleeding based on
T
prior studies (6).
RI P
The statistical software package SAS version 9.2 (SAS Institute, Cary, NC) was used for all data analyses. Categorical variables were compared by Chi-square or
SC
Fisher’s exact test. Continuous variables were compared between groups by T-test
NU
or Wilcoxon rank-sum test. Two-tailed p-values of less than 0.05 were considered statistically significant. Discontinuation rates between cohorts and by baseline
MA
characteristics were evaluated by simple logistic regression with a threshold of p
S0010-7824(14)00291-1 doi: 10.1016/j.contraception.2014.05.010 CON 8345
To appear in:
Contraception
Received date: Revised date: Accepted date:
18 December 2013 8 May 2014 21 May 2014
Please cite this article as: Ireland Luu Doan, Goyal Vinita, Raker Christina A., Murray Anne, Allen Rebecca H., The Effect of Immediate Postpartum Compared to Delayed Postpartum and Interval Etonogestrel Contraceptive Implant Insertion on Removal Rates for Bleeding, Contraception (2014), doi: 10.1016/j.contraception.2014.05.010
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT TITLE PAGE 1. The Effect of Immediate Postpartum Compared to Delayed Postpartum and
T
Interval Etonogestrel Contraceptive Implant Insertion on Removal Rates for
RI P
Bleeding 2. Authors:
SC
a. Luu Doan Ireland MD, MPH (David Geffen School of Medicine at the
NU
University of California, Los Angeles)
b. Vinita Goyal MD, MPH (The Warren Alpert Medical School of Brown
MA
University and Women and Infants Hospital) c. Christina A. Raker ScD (The Warren Alpert Medical School of Brown
ED
University and Women and Infants Hospital)
PT
d. Anne Murray MD (The Warren Alpert Medical School of Brown
CE
University and Women and Infants Hospital) e. Rebecca H. Allen MD, MPH (The Warren Alpert Medical School of
AC
Brown University and Women and Infants Hospital) 3. We gratefully acknowledge the financial support provided by the Department of Obstetrics and Gynecology of the Warren Alpert Medical School of Brown University and Women and Infants Hospital 4. No conflicts of interest 5. Clinical trial registration number is not applicable 6. Abstract: 247 words 7. Text: 2006 words
ACCEPTED MANUSCRIPT 8. Keywords: Postpartum contraception; Etonogestrel; Implant; Implanon; Nexplanon; Continuation; Vaginal bleeding
T
9. A short running title: Timing of Etonogestrel Implant Insertion and Effect on
RI P
Removal for Bleeding
AC
CE
PT
ED
MA
NU
SC
10. Corresponding author: Luu Doan Ireland [email protected]
ACCEPTED MANUSCRIPT ABSTRACT
T
Objective: To determine whether the discontinuation rate of the etonogestrel
RI P
contraceptive implant due to irregular vaginal bleeding among women with immediate postpartum insertion is increased compared to delayed postpartum and
NU
SC
interval placement.
Study Design: This retrospective cohort study compared women who underwent
MA
immediate postpartum etonogestrel contraceptive implant insertion (within 96 hours of delivery) to delayed postpartum (6 to 12 weeks postpartum) and interval
ED
insertion between January 2008 and December 2010. Charts were reviewed for
PT
date and reason for removal. A chi-squared test was used to compare
CE
discontinuation due to bleeding between cohorts. Baseline characteristics predictive
AC
of implant removal were evaluated by simple logistic regression.
Results: There were 259 women in the immediate postpartum group, 49 in the delayed postpartum group and 106 in the interval group. Average age at insertion was 22.6 (± 5.5) years. Overall, 19.3% of women in the immediate postpartum group requested removal due to irregular bleeding compared to 18.4% in the delayed postpartum group (OR 1.06, 95% CI 0.48 – 2.33) and 20.8% in the interval group (OR 0.91, 95% CI 0.52 – 1.60). There was no difference between groups in premature removal rates for any side effect. There were no sociodemographic or clinical characteristics predictive of removal in any group.
ACCEPTED MANUSCRIPT
Conclusion: One-fifth of etonogestrel contraceptive implant users requested
T
premature removal due to irregular bleeding. Immediate postpartum implant
RI P
insertion does not lead to increased removal rates and may help reduce unintended pregnancy. Mechanisms to help women manage irregular bleeding due to the
NU
SC
implant are needed.
IMPLICATIONS
MA
Immediate postpartum insertion of the etonogestrel contraceptive implant does not lead to increased removal rates due to vaginal bleeding compared to
ED
delayed postpartum or interval insertion. Immediate postpartum implant insertion
PT
may increase uptake of long-acting reversible contraception and help reduce short
CE
inter-pregnancy intervals and unintended pregnancy.
AC
INTRODUCTION
The immediate postpartum period offers an ideal time for women to initiate contraception due to patient access and convenience. Delaying initiation of contraceptionto the standard 6 week postpartum visit places many women at risk for unintended pregnancy. By 6 weeks postpartum, up to 40% of women will have had unprotected intercourse(1) and nearly 50% will have ovulated (2). Furthermore, not all women seek postpartum medical care, resulting in a large proportion with unmet contraceptive need (3).
ACCEPTED MANUSCRIPT The etonogestrel contraceptive implant is highly effective at preventing pregnancy with failure rates of less than 2 per 1000 insertions (4). The method is
T
ideal for women desiring long-acting reversible contraception (LARC) and can be
RI P
initiated safely at any time in the post-partum period (5). Among women with breastfeeding intent, immediate (between 1 to 3 days postpartum) versus delayed
SC
(4 to 8 weeks postpartum) etonogestrel implant insertion results in comparable
NU
breastfeeding outcomes (13). Approximately one-third of users, however, will undergo premature implant removal prior to the 3-year period of efficacy (6). The
MA
main reason for premature discontinuation is irregular vaginal bleeding (7), with one-third to one-half of women citing this as a their primary reason for removal (5,
ED
8).
PT
Little is known about differences in bleeding patterns between postpartum
CE
or interval placement of the etonogestrel contraceptive implant and its potential effect on continuation. In a study of breastfeeding mothers comparing immediate
AC
postpartum insertion of the etonogestrel implant to delayed administration of depot medroxyprogesterone acetate (DMPA) at 6 weeks postpartum, there was no difference in bleeding days for up to 12 weeks postpartum (12). Another study randomized 250 non-breastfeeding women to immediate versus delayed postpartum insertion of the levonorgestrel contraceptive implant and found more bleeding days in the first 6 weeks postpartum in the immediate insertion group but continuation rates were not reported (1). Finally, a small retrospectivestudy on predictors of premature discontinuation of etonogestrel contraceptive implant
ACCEPTED MANUSCRIPT among U.S. women did not find thatpostpartum or breastfeeding status were associated with removal (14).
T
In this study, we investigated the discontinuation rates due to irregular
RI P
bleeding among women who had the etonogestrel contraceptive implant inserted within 96 hours of delivery compared to women who had the device placed outside
SC
the immediate postpartum period. Based on the previous research with
NU
levonorgestrel implant (1) and anecdotal experience, we hypothesized that women who have immediate postpartum etonogestrel contraceptive implant insertion
MA
would have higher rates of premature removal for bleeding complaints.
ED
MATERIALS AND METHODS
PT
We conducted a retrospective cohort study comparing discontinuation rates
CE
due to vaginal bleeding in women who had the etonogestrel contraceptive implant inserted within 96 hours of delivery at Women and Infants Hospital compared to
AC
women who had placement outside the immediate postpartum period. Women undergoing immediate postpartum insertion were included if they received prenatal care at the Women’s Primary Care Center (WPCC), a large hospital-based obstetrics and gynecology clinic, or the Providence Community Health Centers (PCHC), both located in Rhode Island and providing care to underserved women in the Providence area. Both of these practices deliver at Women and Infants Hospital, the primary obstetrical hospital in Rhode Island with 8,500 deliveries in 2012, accounting for 80% of all births in the state. The comparison group included women undergoing implant insertion at the WPCC outside of the immediate
ACCEPTED MANUSCRIPT postpartum period. The comparison group was further subdivided into women who underwent delayed postpartum insertion from 6 to 12 weeks postpartum and
T
women who underwent interval insertion at a gynecologic visit (either more than
RI P
12 weeks postpartum or unrelated to a pregnancy event). It was clinic policy at the time of the study to schedule postpartum visits no earlier than 6 weeks postpartum.
SC
Pharmacy records were reviewed from January 2008 to December 2010 to identify
NU
subjects for the study and insertion timing was verified during chart review. Women were excluded if they received an implant between 96 hours to 6 weeks postpartum
MA
or less than 6 weeks postabortion. Pharmacy records and medical charts were reviewed to confirm placement date in relation to any pregnancy event.
ED
Sociodemographic and clinical variables were collected during the chart review as
PT
well as data on clinic visits related to implant side effects, removal of the implant,
CE
date of removal, reasons for removal, complications of removal, and post-implant removal contraceptive choice. This study was approved by the Institutional Review
Centers.
AC
Boards at both Women and Infants Hospital and the Providence Community Health
The primary outcome in this study was the difference in discontinuation rates of the etonogestrel contraceptive implants due to irregular vaginal bleeding among women who received the implant during the immediate postpartum period compared to women who underwent delayed postpartum or interval insertion. Based on review of pharmacy records, we estimated 304 subjects in the immediate postpartum group and 188 subjects in the comparison group. This gave us the ability to detect a minimum 10% difference in discontinuation rates due to irregular
ACCEPTED MANUSCRIPT bleeding between the two cohorts with 80% power. This sample size calculation assumed an 11% discontinuation rate in the interval group due to bleeding based on
T
prior studies (6).
RI P
The statistical software package SAS version 9.2 (SAS Institute, Cary, NC) was used for all data analyses. Categorical variables were compared by Chi-square or
SC
Fisher’s exact test. Continuous variables were compared between groups by T-test
NU
or Wilcoxon rank-sum test. Two-tailed p-values of less than 0.05 were considered statistically significant. Discontinuation rates between cohorts and by baseline
MA
characteristics were evaluated by simple logistic regression with a threshold of p
