Risk of unintended pregnancy based on intended compared to actual contraceptive use

Accepted Manuscript Risk of Unintended Pregnancy Based on Intended Compared to Actual Contraceptive Use Matthew F. Reeves, MD, MPH, Qiuhong Zhao, MS, Gina M. Secura, PhD, MPH, Jeffrey F. Peipert, MD, PhD PII:

S0002-9378(16)00174-5

DOI:

10.1016/j.ajog.2016.01.162

Reference:

YMOB 10892

To appear in:

American Journal of Obstetrics and Gynecology

Received Date: 7 January 2016 Accepted Date: 15 January 2016

Please cite this article as: Reeves MF, Zhao Q, Secura GM, Peipert JF, Risk of Unintended Pregnancy Based on Intended Compared to Actual Contraceptive Use, American Journal of Obstetrics and Gynecology (2016), doi: 10.1016/j.ajog.2016.01.162. 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

Risk of Unintended Pregnancy Based on Intended Compared to Actual Contraceptive Use Matthew F. REEVES, MD, MPH1,2, Qiuhong ZHAO, MS3, Gina M. SECURA, PhD, MPH3, Jeffrey F. PEIPERT, MD, PhD 3 National Abortion Federation, 1660 L Street NW, Washington, DC 20036, USA

2

Department of Population, Family, and Reproductive Health, Johns Hopkins Bloomberg

RI PT

1

School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205, USA

Division of Clinical Research, Department of Obstetrics & Gynecology, Washington

SC

3

M AN U

University School of Medicine, 4533 Clayton Avenue, St. Louis, MO 63110, USA Conflict of Interest: M.F.R. serves as a consultant to ContraMed, LLC. J.F.P. receives research support from Bayer and Teva. The other authors report no conflicts of interest. Funding source: An anonymous foundation funded this work. The funder had no role in the

TE D

collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the article for publication. Trial registration: ClinicalTrials.gov NCT01986439

EP

Paper presentation: A preliminary analysis was present as an abstract at the North American Forum on Family Planning, organized by the Society of Family Planning, in Miami, FL,

AC C

October 12-13, 2014.

Study Location: St. Louis, MO, USA Correspondence: Matthew Reeves, 1660 L Street NW, Suite 450, Washington, DC 20036 USA [email protected]; tel 202-667-5881

Word count, abstract: 292 Word count, main text: 2,217

ACCEPTED MANUSCRIPT

Brief Title: Risk of Pregnancy by Initial Contraception Choice Condensation: Within the CHOICE project, women initially choosing injectable contraception had pregnancy rates similar to oral contraception and significantly worse than intrauterine or

AC C

EP

TE D

M AN U

SC

RI PT

implantable contraception.

2

ACCEPTED MANUSCRIPT

ABSTRACT

2

Background: After initiating a new contraceptive method, the provider has little control of how

3

or whether that method is used.

4

Objective: We sought to compare unintended pregnancy rates by the initial contraceptive method

5

after counseling to traditional contraceptive effectiveness in the same study population.

6

Study Design: The Contraceptive CHOICE Project provided reversible contraception to 9,252

7

women at no cost during 2-3 years of follow-up. We performed two analyses of contraceptive

8

efficacy in this prospective cohort: (1) Intent-to-use (ITU), grouping participants based on their

9

chosen method at enrollment and (2) As-used, categorizing participant time according to the

M AN U

SC

RI PT

1

method used. In ITU analysis, switching of methods and method continuation were not

11

considered, as we wanted to assess outcomes based on the method chosen at baseline. We used

12

Cox proportional hazards models to compare rates of unintended pregnancy.

13

Results: During 20,017 woman-years, we identified 615 unintended pregnancies. In ITU

14

analysis, pregnancy rates were 5.3, 5.5, 2.0, 1.7, and 1.9 per 100 woman-years for women

15

initiating oral, injectable, implantable, copper and hormonal intrauterine contraception at

16

baseline, respectively. The adjusted hazard ratio (HRadj) for injectable compared to hormonal

17

intrauterine contraception was 2.4 (95% confidence interval 1.8, 3.3). Delaying initiation of

18

intrauterine or implantable contraception increased unintended pregnancies by 60% (HRadj 1.6,

19

95%CI: 1.2, 2.0). In as-used analysis, pregnancy rates were 6.7, 1.6, 0.2, 0.6 and 0.2 per 100

20

woman-years for women using oral, injectable, implantable, copper and hormonal intrauterine

21

contraception, respectively.

AC C

EP

TE D

10

3

ACCEPTED MANUSCRIPT

Conclusions: Although highly effective in the as-used analysis, women initially choosing

23

injectable contraception had pregnancy rates similar to oral contraception and significantly worse

24

than intrauterine or implantable contraception. Despite switching and discontinuation, women

25

choosing an intrauterine or implantable contraception at baseline were much less likely to have

26

an unintended pregnancy compared to women selecting other methods.

27

Keywords: contraception, continuation, unintended pregnancy, injectable contraception

SC

RI PT

22

AC C

EP

TE D

M AN U

28

4

ACCEPTED MANUSCRIPT

INTRODUCTION

30

In clinical practice, a medical professional can only directly influence the contraceptive method

31

that an individual patient initiates at that particular visit. Many patients subsequently stop using

32

the initial contraceptive method without consulting a medical professional or change to a less

33

effective method.1, 2 By examining unintended pregnancy rates by the method chosen initially,

34

we are able to examine the combined effects of the effectiveness and continuation of that

35

method. More practically, with an analysis of intended use, we can examine the results after a

36

patient leaves the medical professional’s office with a new contraceptive method.

37

We are particularly interested in how injectable methods would perform in this analysis.

38

Consensus has not been reached as to whether injectable contraception should be considered a

39

long-acting reversible contraceptive (LARC) method. With perfect use, injectable contraceptives

40

have contraceptive efficacy similar to intrauterine and implantable contraception,3 but in typical

41

use, injectable contraception is more similar to oral contraception.4, 5 Likewise, the continuation

42

rate of injectable methods is more similar to oral contraception than intrauterine or implantable

43

contraception.6 Internationally, LARC is defined as intrauterine and implantable contraception.7

44

However, the National Institute for Health and Clinical Excellence includes injectable

45

contraceptive methods, such as depot medroxyprogesterone acetate (DMPA), as LARC.8

46

The Contraceptive CHOICE Project (CHOICE) was a longitudinal cohort study of 9,256 women

47

who were provided with no-cost, reversible contraception for two to three years.9, 10 A prior

48

analysis of contraceptive method use among CHOICE participants found that intrauterine

49

contraception (IUC) and implantable contraception were 20 times more effective in preventing

AC C

EP

TE D

M AN U

SC

RI PT

29

5

ACCEPTED MANUSCRIPT

pregnancy during typical use than the contraceptive pill, patch, or ring.11 Women who were

51

using depot-medroxyprogesterone acetate were observed to have an unintended pregnancy rate

52

that was similar to women using LARC methods. However, in that analysis women were only

53

considered DMPA users if they received a DMPA injection in the past three months. Thus, the

54

pregnancy risk for DMPA is closer to perfect use, and not comparable to the other methods

55

reported.

56

To examine real-world use of all methods used in the CHOICE Project and to better quantify

57

pregnancy risk of the contraceptive method a woman begins, this analysis estimates the risk of

58

unintended pregnancy based on the initial method choice of each participant. For the intent-to-

59

use analysis, we grouped women by the method they chose and initiated regardless of subsequent

60

switching or discontinuation. We then compared the results of the intent-to-use analysis to an

61

updated analysis of the previously reported pregnancy rates based on traditional as-treated

62

(termed “as-used” in this analysis) contraceptive effectiveness.11

63

METHODS

64

The CHOICE Project had two main objectives: 1) to promote the use of the most effective

65

methods of reversible contraception (IUCs and implant); and 2) to assess the population impact

66

of providing no-cost contraception to approximately 10,000 women in the St. Louis region.

67

Participants were provided reversible contraception of their choice at no cost, and were allowed

68

to switch methods during their two to three years of follow-up. A prior publication provides a

69

full description of the methods of the CHOICE Project.10

AC C

EP

TE D

M AN U

SC

RI PT

50

6

ACCEPTED MANUSCRIPT

Inclusion criteria for CHOICE were: 1) female age 14-45 years; 2) residence in the St. Louis

71

region; 3) ability to speak English or Spanish; 4) interest in reversible contraception; 5) sexually

72

active with a male partner in the past six months or anticipate sexual activity in the next six

73

months; 6) no desire for pregnancy in the next year; and 7) interest in starting a new reversible

74

contraceptive method. In the baseline interview, study staff collected comprehensive information

75

on demographic characteristics and reproductive history.

76

Participants were followed with telephone interviews at three and six months and every six

77

months thereafter. At each survey, we asked participants about contraceptive use, missed

78

menses, and possible pregnancy. Specifically, we asked participants what contraceptive

79

method(s) they used, if they had stopped using each method, and their start and stop dates. Any

80

participant who thought she might be pregnant was asked to return for urine pregnancy testing.

81

We estimated the conception date from the date of the last menstrual period or by

82

ultrasonography. We censored participants who were lost to follow-up at the time of their last

83

completed interview. If a participant discontinued a method to conceive, we censored her when

84

she stopped the method.

85

For the intent-to-use (ITU) analysis, we sought to compare rates of unintended pregnancy by the

86

contraceptive method chosen at baseline. To assess the practice of providing specific

87

contraceptive methods at baseline, regardless of duration of use or change of method, we did not

88

consider change of contraceptive method or method continuation in the ITU analysis. This

89

analysis can be considered analogous to an intent-to-treat analysis for a randomized trial.

90

However, in this case, each woman was able to choose which “treatment” to use. We grouped

91

participants by baseline chosen method: intrauterine, implantable, injectable, oral, vaginal, or

AC C

EP

TE D

M AN U

SC

RI PT

70

7

ACCEPTED MANUSCRIPT

transdermal. Women who delayed initiation of intrauterine, implantable, or injectable

93

contraception until after the day of counseling or for more than 30 days for oral, transdermal, or

94

transvaginal contraception were considered to have a “delayed” start and analyzed separately.

95

For the as-used contraceptive efficacy analysis, we categorized periods of contraceptive method

96

use by each woman throughout study participation. Information about method start and stop

97

dates was collected from three sources: scheduled telephone interviews; pharmacy data obtained

98

from the partner pharmacy where participants obtained pills, patch, or ring; and the participant

99

contraceptive-method log that documented when the participant initiated or discontinued use of a

100

method or switched to another method (i.e., insertion or removal of an IUC or implant; receipt of

101

an initial pill supply, patch, or ring; and DMPA injection). A participant was considered to have

102

used DMPA for the 16-week interval after a record of an injection, based on the World Health

103

Organization recommendation.12 In the case of expulsion of an IUC, if the participant knew the

104

device had fallen out and she became pregnant, the unintended pregnancy was attributed to “no

105

method” (unless an alternative method was used). However, if the participant was unaware that

106

the device had fallen out, the pregnancy was attributed to IUC failure.

107

Contraceptive-method failure was defined as conception that occurred during a period when the

108

contraceptive method was used. If the participant reported she had stopped using the method, we

109

categorized use as “no method” and the pregnancy was not considered a contraceptive-method

110

failure. We excluded conception that occurred after a participant stopped using a method owing

111

to a desire to conceive (intended pregnancy).

112

We used the chi-square test to compare baseline demographic characteristics. We used Kaplan-

113

Meier survival curves to estimate the cumulative incidence rate at year one, two, and three. We

AC C

EP

TE D

M AN U

SC

RI PT

92

8

ACCEPTED MANUSCRIPT

used Cox proportional hazards models to control for confounders in the final adjusted model.

115

Confounding effect was defined as a greater than 10% change in associations between

116

contraceptive method and risk of unintended pregnancy with or without the potential

117

confounding variable in the model. We used the levonorgestrel IUC as the referent group since

118

this was the largest group of women in the CHOICE Project. The Washington University in St.

119

Louis School of Medicine Human Research Protection Office approved the CHOICE protocol

120

before participant recruitment began and all study participants provided written informed consent

121

(ClinicalTrials.gov Identifier: NCT01986439). In this analysis LARC methods are defined as

122

intrauterine and implantable contraception.

123

RESULTS

124

During 20,017 woman-years of follow-up, we identified 615 unintended pregnancies for a rate of

125

3.1 per 100 women-years. Sixty-five percent of women were between ages 20 and 29; 50% were

126

black; and 35% had less than or equal to a high school education; 37% of participants were

127

receiving public assistance; 47% were nulliparous; 63% had a previous unintended pregnancy;

128

and over 40% had a previous sexually transmitted infection (Table 1).

129

In Table 2, we provide the unintended pregnancy rates for the intent-to-use and as-used analyses

130

by contraceptive method. Women initiating LARC methods (IUCs or implants) had a pregnancy

131

risk of 1.9 per 100 women-years, compared to 0.3 per 100 women-years in the as-used analysis.

132

Women who began non-LARC methods (DMPA, pills, patch, ring) had a pregnancy rate of 5.3

133

per 100 women-years. Notably, the pregnancy rate among women initiating DMPA was 5.5 per

134

100 women-years. The hazard ratios for all methods are shown in Table 3 for ITU and as-used

135

analyses. Time to unintended pregnancy is shown in Figure 1. Among the women who did not

AC C

EP

TE D

M AN U

SC

RI PT

114

9

ACCEPTED MANUSCRIPT

receive their chosen intrauterine or implantable contraceptive method on the day of counseling,

137

the risk of unintended pregnancy was increased by 60% (HR 1.6, 95% CI: 1.2-2.0) in both

138

unadjusted and adjusted analyses, compared to women who initiated the hormonal IUC on the

139

day of counseling. Of women who delayed the initiation of a LARC method, 1628 (74%)

140

initiated intrauterine contraception within 16 weeks of enrollment and 420 (82%) initiated

141

implantable contraception within 16 weeks of enrollment.

142

COMMENT

143

We found that intrauterine and implantable contraceptives were significantly more effective in

144

both intent-to-use and as-used analyses. We believe our findings from the intent-to-use analysis

145

provide practical information to healthcare providers counseling individual patients. These data

146

present the risk of pregnancy for a woman as she leaves the office with a given method. If

147

anything, these data underestimate the differences outside of a research project. Women in the

148

CHOICE Project had access to no-cost contraception of their choosing throughout the study.

149

Thus, a woman discontinuing oral contraception had ready access to an IUC if she desired. The

150

effect of this is apparent from the fact that in these data, women choosing oral contraceptives in

151

the ITU analysis had a lower pregnancy rate than the women who used oral contraceptives in the

152

as-used analysis. In contrast, past research has found that many women stopping oral

153

contraceptives choose a less effective method.1, 13 The survival curves for non-LARC methods

154

are very distinct when we compared the intent-to-use analysis to the as-used analysis. The

155

difference in the non-LARC survival curves reflects the variability in continuation rates and

156

changes to more or less effective contraceptive methods.

AC C

EP

TE D

M AN U

SC

RI PT

136

10

ACCEPTED MANUSCRIPT

An important difference was observed between the two analyses for DMPA. In the as-used

158

analysis, DMPA use was assumed to have stopped at 16 weeks after each injection, making the

159

as-used results essentially perfect use for DMPA, though still significantly less effective than the

160

hormonal IUC. In contrast, women initiating DMPA in the intent-to-use analysis had a

161

pregnancy rate similar to those initiating oral contraceptives. Although in the first year after

162

initiation of DMPA, woman had a relatively lower pregnancy rate, the rate rose with time to be

163

the second highest among the methods studied (Figure 1 and Table 2). This finding is in contrast

164

to the as-used analysis where no pregnancies occurred after the first year. We suspect that this

165

divergence between the ITU and as-used analyses reflected self-sorting of women into those who

166

like DMPA and were able to return for injection and those who did not like it and/or could not

167

return. Although the ITU analysis includes those women who continued DMPA to three years,

168

the pregnancy rate remains constant after the first year, likely due to substantial self-selection

169

and discontinuation of DMPA by 12 months, with just 189 woman-years in year two and 116

170

woman-years in year three.

171

In comparison to the traditional as-used effectiveness analysis,11 the differences between

172

contraceptive method effectiveness are less pronounced in the ITU analysis. For example, in the

173

as-used analysis, hormonal IUC use was found to be roughly 22-31 times more effective than

174

oral contraceptives, the contraceptive patch, or ring. In the intent-to-use analysis, IUC initiation

175

was found to be just three to four times more effective than oral contraceptives. The reduced risk

176

ratio can be attributed to switching from IUCs to less effective methods, or from switching from

177

oral contraceptives to IUCs or an implant. Furthermore, for most individual methods, the

178

absolute risk of pregnancy is much higher in the ITU analysis than the as-used analysis. For

179

example, women who initiated injectable contraceptives had a pregnancy rate of 5.5 per 100

AC C

EP

TE D

M AN U

SC

RI PT

157

11

ACCEPTED MANUSCRIPT

women-years in the ITU analysis compared to 1.6 per 100 women-years in the as-used analysis.

181

The much lower apparent effectiveness shown in the ITU analysis is likewise attributable to

182

women switching from injectable contraceptives to less effective methods or from high

183

discontinuation rates with DMPA. We plan to examine switching patterns in future analyses of

184

the CHOICE data.

185

Generalizability of these data may be limited by the setting in which they were collected.

186

Although LARC uptake was high and may reflect an ideal setting, it does not reflect the reality in

187

many clinical settings. Increasing LARC uptake may require additional provider training, tier-

188

based contraceptive counseling, and ensuring that methods are available for insertion on the day

189

of counseling.

190

It is important to note that women who did not initiate intrauterine, implantable or injectable

191

contraception on the day of counseling were 60% more likely to have an unintended pregnancy.

192

Providing contraception on the same day as counseling is feasible and increases uptake of these

193

methods,14 and, as can be seen in Figure 1, part A, has an immediate effect in reducing

194

unintended pregnancy.

195

The risk of pregnancy after initiation of LARC methods is substantially lower than all other

196

methods. These findings should encourage more healthcare providers to initiate IUCs and

197

implants at the time of contraceptive counseling when patients choose these methods. Injectable

198

contraception is no more effective in practice than oral contraceptives.

AC C

EP

TE D

M AN U

SC

RI PT

180

199

12

ACCEPTED MANUSCRIPT

ACKNOWLEDGEMENT

201

(None)

AC C

EP

TE D

M AN U

SC

RI PT

200

13

ACCEPTED MANUSCRIPT

202

REFERENCES

203

1.

205

of frequency and reasons. Am J Obstet Gynecol. Sep 1998;179(3 Pt 1):577-582. 2.

Vaughan B, Trussell J, Kost K, Singh S, Jones R. Discontinuation and resumption of

RI PT

204

Rosenberg MJ, Waugh MS. Oral contraceptive discontinuation: a prospective evaluation

206

contraceptive use: results from the 2002 National Survey of Family Growth.

207

Contraception. 2008;78(4):271-283. 3.

Kaunitz AM, Darney PD, Ross D, Wolter KD, Speroff L. Subcutaneous DMPA vs.

SC

208

intramuscular DMPA: a 2-year randomized study of contraceptive efficacy and bone

210

mineral density. Contraception.80(1):7-17. 4.

212 213

404. 5.

214 215

Kost K, Singh S, Vaughan B, Trussell J, Bankole A. Estimates of contraceptive failure from the 2002 National Survey of Family Growth. Contraception. 2008;77(1):10-21.

6.

216 217

Trussell J. Contraceptive failure in the United States. Contraception. 2011;83(5):397-

Diedrich JT, Zhao Q, Madden T, Secura GM, Peipert JF. Three-year continuation of

TE D

211

M AN U

209

reversible contraception. Am J Obstet Gynecol. Nov 2015;213(5):662 e661-668. 7.

Department of Reproductive Health and Research. From Evidence to Policy: Expanding Access to Family Planning: Strategies to increase use of long-acting and permanent

219

contraception. Geneva: World Health Organization; 2012. 8.

221 222

August 21, 2015.

9.

223 224

Long-Acting Reversible Contraception (Update). guidance.nice.org.uk/cg30. Accessed

AC C

220

EP

218

Peipert JF, Madden T, Allsworth JE, Secura GM. Preventing Unintended Pregnancies by

Providing No-Cost Contraception. Obstet Gynecol 2012;120(6):1291-1297.

10.

Secura GM, Allsworth JE, Madden T, Mullersman JL, Peipert JF. The Contraceptive

225

CHOICE Project: reducing barriers to long-acting reversible contraception. Am J Obstet

226

Gynecol. 2010;203(2):115.e111-115.e117.

14

ACCEPTED MANUSCRIPT

227

11.

228 229

Winner B, Peipert JF, Zhao Q, et al. Effectiveness of Long-Acting Reversible Contraception. N Engl J Med. 2012;366(21):1998-2007.

12.

World Health Organization Department of Reproductive Health and Research, Johns Hopkins Bloomberg School of Public Health Center for Communication Programs.

231

Family Planning: A Global Handbook for Providers (2011 Update). Baltimore and

232

Geneva: CCP and WHO; 2011.

233

13.

RI PT

230

Stuart JE, Secura GM, Zhao Q, Pittman ME, Peipert JF. Factors Associated With 12Month Discontinuation Among Contraceptive Pill, Patch, and Ring Users. Obstet

235

Gynecol. 2013;121(2, PART 1):330-336. 14.

Goodman S, Hendlish SK, Benedict C, Reeves MF, Pera-Floyd M, Foster-Rosales A.

M AN U

236

SC

234

237

Increasing intrauterine contraception use by reducing barriers to post-abortal and interval

238

insertion. Contraception.78(2):136-142.

AC C

EP

TE D

239

15

ACCEPTED MANUSCRIPT

Table 1. Baseline characteristics of participants, by initial contraceptive method.

History of STI

3,745 (40.5)

Implant N (%) 1,056

(14.7) (37.3) (27.6) (17.4) (2.9)

232 914 698 544 74

(9.4) (37.1) (28.4) (22.1) (3.0)

45 (6.3) 199 (27.9) 222 (31.1) 214 (30.0) 33 (4.6)

335 393 200 115 13

(31.7) (37.2) (18.9) (10.9) (1.2)

1,115 753 568 311

(40.6) (27.4) (20.7) (11.3)

938 650 527 347

(38.1) (26.4) (21.4) (14.1)

287 (40.3) 152 (21.3) 146 (20.5) 128 (18.0)

537 263 149 107

877 802 509 551

(31.9) (29.2) (18.5) (20.1)

749 625 471 614

(30.4) (25.4) (19.1) (24.9)

233 (32.7) 165 (23.1) 132 (18.5) 182 (25.5)

421 304 156 175

1,199 (48.7) 1,092 (44.4) 171 (6.9)

269 (37.7) 381 (53.4) 63 (8.8)

Patch N (%) 166

Ring N (%) 642

p

<0.01

172 (19.9) 372 (43.0) 217 (25.1) 90 (10.4) 14 (1.6)

28 (16.9) 69 (41.6) 48 (28.9) 20 (12.0) 1 (0.6)

69 (10.7) 322 (50.2) 161 (25.1) 89 (13.9) 1 (0.2)

(50.9) (24.9) (14.1) (10.1)

288 (47.9) 139 (23.1) 96 (16.0) 78 (13.0)

642 (74.2) 136 (15.7) 61 (7.1) 26 (3.0)

94 (56.6) 44 (26.5) 17 (10.2) 11 (6.6)

449 (69.9) 123 (19.2) 47 (7.3) 23 (3.6)

(39.9) (28.8) (14.8) (16.6)

207 (34.4) 173 (28.8) 104 (17.3) 115 (19.1)

496 (57.3) 208 (24.0) 92 (10.6) 66 (7.6)

65 (39.2) 54 (32.5) 19 (11.4) 28 (16.9)

350 (54.5) 161 (25.1) 68 (10.6) 63 (9.8)

M AN U

TE D

1,388 (50.5) 1,150 (41.9) 209 (7.6)

Oral N (%) 865

118 (19.6) 240 (39.9) 132 (22.0) 94 (15.6) 17 (2.8)

SC

405 1,026 758 477 81

Injectable N (%) 601

RI PT

Hormonal IUC Copper IUC N (%) N (%) 2,462 713

EP

Total Age (years) 1,404 (15.2) Less than 20 3,535 (38.2) 20-24 2,436 (26.3) 25-29 1,643 (17.8) 30-39 234 (2.5) 40 or more Parity 4,350 (47.0) 0 2,260 (24.4) 1 1,611 (17.4) 2 1,031 (11.1) 3 or more Unintended pregnancies 3,398 (36.7) 0 2,492 (26.9) 1 1,551 (16.8) 2 1,794 (19.4) 3 or more Race 4,669 (50.5) Black 3,867 (41.8) White 715 (7.7) Others Education High school or 3,205 (34.7) less 3,901 (42.2) Some college College or 2,143 (23.2) more Receiving public 3,440 (37.2) assistance

Delayed N (%) 2,747

<0.01

<0.01

<0.01 651 (61.6) 301 (28.5) 104 (9.8)

448 (74.5) 123 (20.5) 30 (5.0)

370 (42.8) 424 (49.0) 71 (8.2)

99 (59.6) 55 (33.1) 12 (7.2)

245 (38.2) 341 (53.1) 55 (8.6) <0.01

1,023 (37.2)

764 (31.0)

186 (26.1)

546 (51.8)

283 (47.2)

227 (26.2)

52 (31.3)

124 (19.3)

1,155 (42.0)

1,075 (43.7)

297 (41.7)

376 (35.6)

256 (42.7)

384 (44.4)

77 (46.4)

281 (43.8)

569 (20.7)

622 (25.3)

230 (32.3)

133 (12.6)

61 (10.2)

254 (29.4)

37 (22.3)

237 (36.9)

1,230 (44.8)

930 (37.8)

242 (34.0)

443 (42.0)

248 (41.3)

176 (20.3)

55 (33.3)

116 (18.1)

<0.01

1,211 (44.1)

990 (40.2)

281 (39.4)

416 (39.4)

277 (46.1)

253 (29.3)

72 (43.4)

245 (38.2)

<0.01

AC C

Total N (%) 9,252

16

ACCEPTED MANUSCRIPT

Abbreviations: Did not initiate chosen contraceptive method on day of enrollment for intrauterine, implantable and injectable methods, or more than 30 days for oral, patch and ring Levonorgestrel 52 mg intrauterine contraceptive

Copper IUC

Copper T380A intrauterine contraceptive

Implant

Etonogestrel 68 mg subdermal implant

Injectable

Depot medroxyprogesterone acetate 150 mg

Oral

Oral contraceptive

Patch

Transdermal contraceptive

Ring

Vaginal ring contraceptive

M AN U

SC

Hormonal IUC

RI PT

Delayed

AC C

EP

TE D

Note: Totals for some contraceptive methods do not add to 100% for unintended pregnancy and race due to missing values.

17

ACCEPTED MANUSCRIPT

Table 2. Incidence of Unintended Pregnancy by Contraceptive Method. Women who delayed initiation of their chosen method are excluded from the intent-to-use results in all rows except “overall.”

Baseline Method

Unintended Women Woman- Pregnancies (n) years (n) Rate*

As-used Cumulative Incidence** Year Year Year 1 2 3

RI PT

Intent-to-use

Unintended Woman- Pregnancies years (n) Rate*

Cumulative Incidence** Year Year Year 1 2 3

9,252

20,017

615

3.1

2.7

5.9

9.1

20,318

380

1.9

2.4

3.3

4.2

LARC

4,231

9,246

176

1.9

1.5

3.6

5.9

13,877

40

0.3

0.3

0.6

0.8

non-LARC

2,274

4,921

260

5.3

4.3

9.9

15.1

6,441

340

5.3

5.5

8.3

11.2

Hormonal IUC

2,462

5,472

106

1.9

1.8

3.8

5.8

8,534

19

0.2

0.2

0.4

0.7

713

1,563

26

1.7

1.2

3.1

5.1

2,269

14

0.6

0.6

1.3

1.7

1,056

2,210

44

2.0

1.1

3.6

7.0

3,074

7

0.2

0.3

0.5

0.5

Injectable

601

1,237

68

5.5

2.4

8.9

17.9

1,709

27

1.6

1.9

1.9

1.9

Oral

865

1,838

97

5.3

4.5

10.5

14.4

2,687

180

6.7

6.8

10.9

14.0

Patch

166

360

28

Ring

642

1,487

67

Abbreviations:

M AN U

7.8

6.9

16.0

20.5

389

28

7.2

7.7

10.4

16.0

4.5

5.0

8.4

12.7

1,657

105

6.3

6.9

9.7

13.4

AC C

*pregnancies per 100 woman-years **pregnancies per 100 women

TE D

Implant

EP

Copper IUC

SC

Overall

LARC

Hormonal IUC, copper IUC, implant

non-LARC

Injectable, oral, patch, ring

Hormonal IUC

Levonorgestrel 52 mg intrauterine contraceptive

Copper IUC

Copper T380A intrauterine contraceptive 18

ACCEPTED MANUSCRIPT

Etonogestrel 68 mg subdermal implant

Injectable

Depot medroxyprogesterone acetate 150 mg

Oral

Oral contraceptive

Patch

Transdermal contraceptive

Ring

Vaginal ring contraceptive

AC C

EP

TE D

M AN U

SC

RI PT

Implant

19

ACCEPTED MANUSCRIPT

Table 3. Hazard Ratios for Unintended Pregnancy by Contraceptive Method. Women who delayed initiation of their chosen method are excluded from the intent-to-use analysis.

Adjusted*

Contraceptive Method

Hazard Ratio (95% CI)

Hazard Ratio (95% CI)

Hormonal IUC Copper IUC

1.0 0.9

ref (0.6, 1.3 )

1.0 1.0

ref (0.6, 1.5 )

Implant Injectable Oral

1.0 2.8 2.7

(0.7, 1.5 ) (2.1, 3.9 ) (2.1, 3.6 )

0.8 2.4 3.6

(0.6, 1.2 ) (1.8, 3.3 ) (2.7, 4.7 )

Patch

4.0

(2.6, 6.1 )

4.1

Ring

2.3

(1.7, 3.1 )

3.3

As-used

Unadjusted ref

Copper IUC Implant Injectable

2.8 1.0 5.5

(1.4, 5.6 ) (0.4, 2.4 ) (3.0, 10.0 )

Oral Patch Ring

24.6 25.1 24.2

(15.1, 40.0 ) (13.8, 45.6 ) (14.7, 40.0 )

SC

Hazard Ratio [95% CI] 1.0

ref

3.1 0.8 4.5

(1.5, 6.2 ) (0.4, 2.0 ) (2.5, 8.2 )

AC C

EP

1.0

(2.4, 4.5 )

Adjusted*

Hazard Ratio [95% CI]

Hormonal IUC

(2.7, 6.2 )

TE D

Contraceptive Method

RI PT

Unadjusted

M AN U

Intent-to-use

28.0 22.8 31.3

(17.3, 45.4 ) (12.7, 41.0 ) (19.1, 51.3 )

*Adjusted for age, prior unintended pregnancies, race, education, and public assistance Abbreviations: Hormonal IUC

Levonorgestrel 52 mg intrauterine contraceptive

Copper IUC

Copper T380A Intrauterine Contraceptive 20

ACCEPTED MANUSCRIPT

Etonogestrel 68 mg subdermal implant

Injectable

Depot medroxyprogesterone acetate 150 mg

Oral

Oral contraceptive

Patch

Transdermal contraceptive

Ring

Vaginal ring contraceptive

AC C

EP

TE D

M AN U

SC

RI PT

Implant

21

ACCEPTED MANUSCRIPT

Figure 1. Kaplan-Meier graph of time to pregnancy. The y-axis shows the probability of remaining without an unintended pregnancy.

RI PT

Part A. Time to pregnancy by initial chosen contraceptive method (Intent-to-use). Delayed LARC includes all women who did not initiate intrauterine or implantable contraception on the day of counseling.

AC C

EP

TE D

M AN U

SC

Part B. Time to pregnancy by contraceptive method used (as-used).

22

AC C

EP

TE

D

M AN U

SC

RI PT

Part A. Time to pregnancy by initial chosen contraceptive method (Intent-to-use). Delayed LARC includes all women who did not initiate intrauterine or implantable contraception on the day of counseling.

AC C

EP

TE

D

RI PT

M AN U

SC

Part B. Time to pregnancy by contraceptive method used (as-used).