LARC at different stages of reproductive life Expert Manuela Farris, MD, PhD Consultant in Obstetrics & Gynecology Sapienza University of Rome Rome, Italy LARC = long-acting reversible contraception

Suitability of LARC LARC are valid contraceptive choice at several stages in a woman’s life:[a-f] Adolescence After an abortion After giving birth Later in life Abbreviations ACOG = American College of Obstetrics and Gynecology NICE = National Institute for Health and Care Excellence NICE website. nice.org.uk/guidance/cg30 WHO website. http://apps.who.int/iris/bitstream/10665/181468/1/9789241549158_eng.pdf. Refs American College of Obstetricians and Gynecologists Committee on Gynecologic Practice; Long-Acting Reversible Contraception Working Group. ACOG Committee Opinion no. 450: Increasing use of contraceptive implants and intrauterine devices to reduce unintended pregnancy. Obstet Gynecol. 2009 Dec;114(6):1434-8. doi: 10.1097/AOG.0b013e3181c6f965. Connolly A, Pietri G, Yu J, Humphreys S. Association between long-acting reversible contraceptive use, teenage pregnancy, and abortion rates in England. Int J Womens Health. 2014 Nov 21;6:961-74 Gemzell-Daniellson K, Kopp Kallner, H, et al. Post abortion contraception. Women’s Health. 2015;11(6):779-784. National Institute for Health and Care Excellence. Long-acting reversible contraception. Clinical Guideline. October 2005. Available at nice.org.uk/guidance/cg30. Accessed February 2016. WHO Medical eligibility for contraceptive use, 2015. http://apps.who.int/iris/bitstream/10665/181468/1/9789241549158_eng.pdf ACOG Committee on Gynecologic Practice. Obstet Gynecol. 2009;114:1434-1448. Connolly A, et al. Int J Women’s Health. 2014;6:961-974. Gemzell-Daniellson K, et al. Women’s Health. 2015;11:779-784. NICE website WHO website

LARC in Adolescents and Young Adults UK Teenage Pregnancy Strategy (1999-2010): Increased LARC Usage Associated With a 34% Reduction in Pregnancy Among Women < 18 Years 50 1400 46.6% 45 1200 40 35 1000 30.7% LARC Usage (in thousand cycles sold) 30 800 Conception Rate per 1000 Women 25 600 20 Ref Connolly A, Pietri G, Yu J, Humphreys S. Association between long-acting reversible contraceptive use, teenage pregnancy, and abortion rates in England. Int J Womens Health. 2014 Nov 21;6:961-74 Girma S, Paton D. Is education the best contraception: The case of teenage pregnancy in England? Social Sci & Med. 2015;131:1-9. Teenage Pregnancy Strategy – Beyond 2010 https://www.education.gov.uk/consultations/downloadableDocs/4287_Teenage%20pregnancy%20strategy_aw8.pdf Public Health England https://www.gov.uk/government/news/under-18-conception-rate-continues-to-fall-in-england 15 400 10 200 5 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 Connolly A, et al. Int J Women’s Health. 2014;6:961-974.

LARC in Adolescents and Young Adults (cont) Major societies recommend LARC as preferred contraception method in adolescents[a-b] Appropriate counselling is needed and women should not be forced to use LARC[c] Age and nulliparity are not a contraindication to use of LARC/IUC choices for adolescents[a] IUD, IUS, implants: no specific restrictions for use[a] DMPA (injectable): care needed due to side effects[a] not suitable Abbreviations DMPA = depot medroxyprogesterone acetate IUC = intrauterine contraception IUD = intrauterine device IUS = intrauterine system Ref Ott MA, Sucato GS; Committee on Adolescence. Contraception for adolescents. Pediatrics. 2014 Oct;134(4):e1257-81. doi: 10.1542/peds.2014-2300. American College of Obstetricians and Gynecologists Committee on Gynecologic Practice; Long-Acting Reversible Contraception Working Group. ACOG Committee Opinion no. 450: Increasing use of contraceptive implants and intrauterine devices to reduce unintended pregnancy. Obstet Gynecol. 2009 Dec;114(6):1434-8. doi: 10.1097/AOG.0b013e3181c6f965. Steyn PS, Goldstuck ND. Contraceptive needs of the adolescent. Best Pract Res Clin Obstet Gynaecol. 2014 Aug;28(6):891-901. doi: 10.1016/j.bpobgyn.2014.04.012. Epub 2014 May 9. Ott MA, et al. Pediatrics. 2014;134:e1257-1281. ACOG Committee on Gynecologic Practice. Obstet Gynecol. 2009;114:1434-1448. Steyn PS, et al. Best Pract Res Clin Obstet Gynaecol. 2014;28:891-901.

LARC After Abortion Proportion of women returning for repeat abortion within 2 years, according to contraceptive method.* Total (n=510) Repeat abortion Factor n % Hazard Ratio 95% CI Contraceptive method Oral 129 17 13.2% Reference group Injectable 67 6 9.0% 0.55 (0.21-1.45) IUD† 243 14 5.8% 0.36 (0.17-0.77) Other 71 12 16.9% 1.8 (0.83-3.92) Abbreviations CI = confidence interval LNG = levonorgestrel RCOG = Royal College of Obstetricians and Gyneaecologists Ref Sääv I, Stephansson O, Gemzell-Danielsson K. Early versus delayed insertion of intrauterine contraception after medical abortion - a randomized controlled trial. PLoS One. 2012;7(11):e48948. Sääv I, et al. Impact of long-acting reversible contraception on return for repeat abortion PLoS One. 2012;7:e48948. *Prospective cohort study[a] †Copper IUD or LNG-IUS P = .002 Offering LARC after 1st trimester abortion leads to a greater reduction repeat abortions than with other forms of contraception[a] There is no increased risk for expulsion or adverse events with immediate compared to delayed LARC insertion[b] Rose SB, Lawton BA. Am J Obstet Gynecol. 2012;206:37:e1-6; b. Sääv I, et al. PLoS One. 2012;7:e48948

LARC After Giving Birth Most combined oral contraceptives and injectables are not recommended immediately after birth IUC can be inserted < 48 hours and > 4 weeks after birth Abbreviation WHO = World Health Organization WHO Medical eligibility for contraceptive use, 2015. http://apps.who.int/iris/bitstream/10665/181468/1/9789241549158_eng.pdf. Ref World Health Organization. Medical eligibility criteria for contraceptive use. Fifth edition. 2015. Available at http://apps.who.int/iris/bitstream/10665/181468/1/9789241549158_eng.pdf. WHO Medical eligibility for contraceptive use, 2015.

LARC for Women > 40 Years of Age Frequency of intercourse Concurrent medical conditions Natural decline in fertility Contraceptive Choice Menstrual dysfunction Sexual problems FSRH Clinical Guidance. www.fsrh.org/pdfs/ContraceptionOver40July10.pdf Abbreviations FSRH = Faculty of Sexual and Reproductive Healthcare Refs Faculty of Sexual and Reproductive Healthcare Clinical Guidance. Contraception for women aged over 40 years. July 2010. http://www.fsrh.org/pdfs/ContraceptionOver40July10.pdf Desire for non-contraceptive benefits FSRH Clinical Guidance.

LARC for Women > 40 Years of Age (cont) UKMEC Age-Based Criteria for Contraceptive Use Contraceptive method CHC* POP Progestogen-only implant Injectable Copper IUD LNG-IUS Age range (years) ≥40 18-45 >45 UKMEC category† 2 1 Abbreviation CHC – combined hormonal contraception MEC = medical eligibility criteria POP = Progestogen-only pill UK = United Kingdom Ref UK Medical Eligibility Criteria for Contraceptive Use, April 2016. http://www.fsrh.org/pdfs/UKMEC2016.pdf *Combined oral contraception, transdermal patch, combined vaginal ring †Categories: 1 – no restriction; 2 – advantages outweigh the risks; 3 – risks outweigh advantages (clinical judgement needed); 4 – unacceptable health risk Adapted from UK Medical Eligibility Criteria for Contraceptive Use, April 2016.

Conclusions Women requiring contraception should be given information about and offered a choice of all methods, including LARC Women should be provided with the method of contraception that is most acceptable to them, provided it is not contraindicated Contraceptive service providers should be aware that: All currently available LARC methods are more cost effective than the combined oral contraceptive pill even at 1 year of use IUDs, IUS and implants are more cost effective than injectable contraceptives Increasing the uptake of LARC will reduce the number of unintended pregnancies

LARC for women with health conditions Expert Diana Mansour, MBBCh, FRCOG, FFSRH, DIPM Consultant in Community Gynaecology and Reproductive Healthcare; Head of Clinical Services, Sexual Health Newcastle Hospitals, Community Health Newcastle upon Tyne, United Kingdom LARC = long-acting reversible contraception

Overview Use patient cases to review contraceptive choices for women with health conditions and risks, including: Obesity T2DM CV risk factors Apply UK MEC[a-b] Abbreviations CV = cardiovascular MEC = medical eligibility criteria T2DM = type 2 diabetes mellitus http://www.fsrh.org/pdfs/UKMEC2016.pdf WHO Medical eligibility for contraceptive use, 2015. http://apps.who.int/iris/bitstream/10665/181468/1/9789241549158_eng.pdf a. UK MEC, 2016 b. WHO Medical eligibility for contraceptive use, 2015.

UK MEC: 4 Categories Category Criteria 1 There is no restriction on using the contraceptive method. 2 The advantages of using the contraceptive method outweigh the proven or theoretical risks. 3 The proven or theoretical risks of using of the contraceptive method outweigh the advantages. The provision of a method requires expert clinical judgement and/or referral to a specialist contraceptive provider, since use of the method is not usually recommended unless other more appropriate methods are not available or not acceptable. 4 There is an unacceptable risk from using the contraceptive method. Ref http://www.fsrh.org/pdfs/UKMEC2016.pdf UKMEC, 2009. www.fsrh.org Some medical conditions are associated with increased health risks when certain contraceptives are used UK MEC, 2016.

Patient Case 1 Woman aged 22, no children BMI 35; sedentary lifestyle; poor diet No relevant family history Needs contraception and is interested in the combined pill Do you prescribe the pill? Do you refer her to a specialist?

Contraception and Obesity Copper IUD IUS Implant Injectable CHC POP BMI 30-34 kg/m2 1 2 BMI ≥35 kg/m2 3 CHC is category 3 for this patient[a-b] Increased risk for VTE with CHC[c] Injectables are associated with weight gain[d] Abbreviations BMI = body mass index CHC – combined hormonal contraception IUD = intrauterine device IUS = intrauterine system POP – progestogen-only pill VTE = venous thromboembolism Refs http://www.fsrh.org/pdfs/UKMEC2016.pdf Pomp ER, le Cessie S, Rosendaal FR, Doggen CJ. Risk of venous thrombosis: obesity and its joint effect with oral 
contraceptive use and prothrombotic mutations. British Journal of Haematology. 2007;139:289-296. 
 Robinson JA, Burke AE. Obesity and hormonal contraceptive efficacy. Women’s Health (London Engl).2013;9:453-466. Beksinska ME, Smit JA, Guidozzi G. Weight Change and Hormonal Contraception: Fact and Fiction. Expert Rev of Obstet Gynecol. 2011;6(1):45-56.  UKMEC, 2016. Pomp ER, et al. Br J Haematol. 2007;139:289-296. 
 Robinson JA, Burke AE. Women’s Health (London Engl).2013;9:453-466. Beksinska ME, et al. Expert Rev of Obstet Gynecol. 2011;6:45-56. 

Contraception and Obesity (cont) LARC offer benefits for obese women LNG-IUS protects endometrium and reduces menstrual blood loss No evidence of weight gain with LARC Important to discuss lifestyle changes with obese women using LARC, in particular reducing alcohol intake LNG = levonorgestrel NICE = National Institute for Health and Care Excellence Refs NICE website. nice.org.uk/guidance/cg30 Bender NM, Segall-Gutierrez P, Najera SO, Stanczyk FZ, Montoro M, Mishell DR Jr. Effects of progestin-only long-acting contraception on metabolic markers in obese women. Contraception. 2013 Sep;88(3):418-25. National Institute for Health and Care Excellence. Long-acting reversible contraception. Clinical Guideline. October 2005. Available at nice.org.uk/guidance/cg30. Accessed February 2016. Bender NM, et al. Contraception. 2013;88:418-425. NICE website.

Patient Case 2 Woman aged 42, 3 children Needs contraception, as family complete T2DM for 5 years; mild nephropathy Abbreviation T2DM = type 2 diabetes mellitus Which contraceptive methods are most suitable?

Contraception and T2DM CHC Progestogen contraceptives Minimal effect on insulin resistance Dose dependent LNG may have more of an adverse effect Insulin sensitivity not affected by vaginal rings Estradiol pills may have minimal metabolic effects Progestogen contraceptives Minimal effects on insulin resistance No effect on glucose intolerance More insulin resistance with injectables? Refs Gourdy P. Diabetes and oral contraception. Best Pract Res Clin Endocrinol Metab. 2013 Feb;27(1):67-76. Goldstuck ND, Steyn PS. The Intrauterine Device in Women with Diabetes Mellitus Type I and II: A Systematic Review. Obstet Gynecol. 2013; 2013: 814062. http://www.fsrh.org/pdfs/UKMEC2016.pdf Gourdy P. Best Pract Res Clin Endocrinol Metab. 2013;27:67-76. Goldstuck ND, Steyn PS. Obstet Gynecol. 2013; 2013: 814062. UK MEC, 2016.

Contraception and T2DM (cont) Copper IUD IUS Implant Injectable CHC POP History of gestational diabetes 1 Nonvascular disease 2 Nephropathy, retinopathy, neuropathy 3 Other vascular disease Goldstuck ND, Steyn PS. The intrauterine device in women with diabetes mellitus type I and II: A systematic review. ISRN Obstet Gynecol. 2013;2013:814062. http://www.fsrh.org/pdfs/UKMEC2016.pdf CHC is category 3 for this patient POP, implant, copper IUD, and IUS are suitable Injectable not ideal due to possible increase in insulin resistance UK MEC, 2016.

Patient Case 3 Woman aged 38, recently had her 2nd child Controlled hypertension on medication Smoker - 20 cigarettes per day Family history of CVD Wants to start taking COC again Abbreviation T2DM = type 2 diabetes mellitus Should you prescribe COC?

Contraception and CV Risk Factors Use clinical judgement to determine the suitability of contraceptive methods, especially CHC This woman has multiple CV risk factors Blood pressure CHC Negligible effect on BP COC users have higher BP than non-users ↑BP increases risk of stroke and MI Progestogen methods have no effect on BP Abbreviation MI = myocardial infarction WHO Medical eligibility for contraceptive use, 2015. 2015. http://apps.who.int/iris/bitstream/10665/181468/1/9789241549158_eng.pdf Refs http://www.fsrh.org/pdfs/UKMEC2016.pdfWHO Medical eligibility for contraceptive use, 2015. http://apps.who.int/iris/bitstream/10665/181468/1/9789241549158_eng.pdf. UKMEC, 2016 WHO Medical eligibility for contraceptive use, 2015.

Contraception and CV Risk Factors (cont) Copper IUD IUS Implant Injectable CHC POP Controlled hypertension 1 2 3 Systolic >140 to 159 mmHg Diastolic >90 to 94 mmHg Systolic BP>/=160 or diastolic >/=95 4 CHC is category 3 for this patient POP, implant, copper IUD, and IUS are suitable Injectables lower HDL cholesterol by up to 15% and can increase endothelial resistance Clinical judgment very important Abbreviation BP = blood pressure HDL = high-density lipoprotein http://www.fsrh.org/pdfs/UKMEC2016.pdf UK MEC, 2016.

Contraception and Other Conditions HIV Interactions with ART, especially pill and implants Concerns about HIV acquisition in injectables IUS safe after STI screen Heavy menstrual bleeding/period pain CHC often used in extended regimens IUS also reduces bleeding by up to 90% Injectables also suitable Abbreviation ART = antiretroviral therapy STI = sexually transmitted infection UKMEC, 2009. www.fsrh.org Update with 2016 ref WHO Medical eligibility for contraceptive use, 2015. http://apps.who.int/iris/bitstream/10665/181468/1/9789241549158_eng.pdf UK MEC, 2016 WHO Medical eligibility for contraceptive use, 2015.

Conclusion Women with medical problems: Are often denied contraceptive choice from ignorance Rely on less effective methods Involvement of a "specialist" is key "Labelling" women with specific diseases is unhelpful Individual women need individual attention and individual choices

Overcoming patient and physiCian barriers to larc Expert Tina Peers, MBBS, DRCOG, DFSRH, FSRH Consultant in Contraception and Reproductive Healthcare Sexual Health Services Surrey, UK Abbreviation LARC = long-acting reversible contraception

LARC Has Higher Efficacy Than Other Forms of Contraception Unintended pregnancy rate within 1 year of typical use[a] Sterilization <0.5% Oral contraception 9% Subdermal implant <0.1% Hormonal patch 9% LNG-IUS 0.2% Injectable contraception 6% Ring 9% IUC 0.8% Abbreviations IUD = intrauterine devices LNG = levonorgestrel IUS = intrauterine system (IUS). IUC = intrauterine contraception Ref Trussell J. Contraceptive failure in the United States. Contraception. 2011;83(5):397–404. Winner B, Peipert JF, Zhao Q, et al. Effectiveness of Long-Acting Reversible Contraception. NEJM. 2012;366:1998-2007. Increasing effectiveness Effectiveness of LARC is independent of user age or compliance[a-b] a. Trussell J. Contraception. 2011;83:397–404. b. Winner B, et al. N Eng J Med. 2012;366:1998-2007.

Other Advantages of LARC Convenient Safe Reversible Lighter periods or amenorrhea with IUS Low risk for adverse events such as ectopic pregnancy, expulsion, and perforation eg, perforation rate with IUD and IUS c. 1 per 1000 Abbreviations NICE = National Institute for Health and Care Excellence NICE website. nice.org.uk/guidance/cg30 Gemzell-Daniellson K, Apter D, Hauck B. The effect of age, parity, and body mass index on the efficacy, safety, placement and user satisfaction associated with two low-dose levonorgestrel intrauterine contraceptive systems: subgroup analyses of data from a phase III trial. PLoS One. 2015;10(9):e0135309. Heinemann K, Reed S, Moehner S, Minh TD. Risk of uterine perforation with levonorgestrel-releasing and copper intrauterine devices in the European Active Surveillance Study on Intrauterine Devices. Contraception. 2015 Apr;91(4):274-9. National Institute for Health and Care Excellence. Long-acting reversible contraception. Clinical Guideline. October 2005. Available at nice.org.uk/guidance/cg30. Gemzell-Daniellson K, et al. PLoS One. 2015;10(9):e0135309. Heinemann K, et al. Contraception. 2015;91:274-279 NICE website.

LARC Underused by Young Women Contraception type usage among US women aged 20-24 years (2002 and 2006-2008) Ref Mosher WD, Jones J. Use of contraception in the United States: 1982-2008. Vital Health Stat 23. 2010 Aug;(29):1-44. See Mosher Table 10 Mosher WD, Jones J. Vital Health Stat 23. 2010;29:1-44.

Counselling Increases LARC Uptake Evidence from the US Contraceptive CHOICE Project Ref Peipert, J.F., Zhao, Q., Allsworth, J.E. et al, Continuation and satisfaction of reversible contraception. Obstet Gynecol. 2011;117:1105–1113. Contraception chosen by women after counselling and removal of financial barriers Peipert JF, et al. Obstet Gynecol. 2012;120:1291-1297.

Barriers and Myths Among Physicians Physician concerns Canada (n=100) France (n=150) Germany (n=150) Ireland (n=103) Netherlands (n=100) Russia (n=150) Sweden (n=100) Turkey (n=100) UK (n=150) Nulliparity 48% 57% 59% 62% 69% 34% 60% 41% PID 51% 19% 35% 36% 83% 14% 40% Insertion pain 26% 29% 18% 39% 1% 44% 24% 28% Insertion difficulty 33% 4% 25% 45% Survey of 1103 HCPs* in Europe and Canada Concerns are misplaced and not evidence based, holding HCPs back from recommending LARC LARC easy to insert and well tolerated in nulliparous women, and do not increase the risk for PID Abbreviations GP = general practitioner HCP = healthcare providers PID = pelvic inflammatory disease Refs Buhling KJ, Hauck B, Dermout S, Ardaens K, Marions L. Understanding the barriers and myths limiting the use of intrauterine contraception in nulliparous women: results of a survey of European/Canadian healthcare providers. Eur J Obstet Gynecol Reprod Biol. 2014 Dec;183:146-54. *633 obstetrician-gynecologists; 335 GPs; 135 family planning clinicians Adapted from Buhling KL, et al. Eur J Obstet Gynecol Reprod Biol. 2014;183:146-154.

Recommendations for Contraceptive Counselling Establish contraceptive needs Introduce LARC Communicate the benefits of IUC Counselling Provide reassurance and address concerns Confirm choice and schedule placement (if IUC) Help with decision making Abbreviations INTRA = intra-uterine contraception for nulliparous women: translating research into action. Refs Buhling KJ, Zite NB, Lotke P, et al Worlwide use of intrauterine contraception: a review. Contraception. 2014;89:162-173.   Buhling KJ, Hauck B, Dermout S, Ardaens K, Marions L. Understanding the barriers and myths limiting the use of intrauterine contraception in nulliparous women: results of a survey of European/Candian healthcare providers. Eur J Obstet Gyencol Reproduc Biol. 2014;183:146-154. Global INTRA group developed toolkit to support the education of HCPs about counselling 6 key recommendations Buhling KL, et al. Eur J Obstet Gynecol Reprod Biol. 2014;183:146-154; Buhling KL, et al. Contraception. 2014;89:162-173.

Establishing Contraceptive Needs and Discussing LARC Key questions "How important is it for you not to get pregnant?" "What contraception have you previously used and how did you get on?" Increase awareness and knowledge of LARC in accordance with woman’s needs Distinguish between daily contraception and "fit and forget" Show the LARC Discuss the potential benefits NICE website. nice.org.uk/guidance/cg30 Refs http://www.ghspjournal.org/content/3/3/352.full Stanback J, et al. Global Health: Sci Pract. 2015;3:352-357. WHO Tiered-Effectiveness Counseling Is Rights-Based Family Planning NICE website Stanback J, et al. Global Health: Sci Pract. 2015;3:352-357.

Addressing Concerns and Providing Guidance Reassure women regarding any concerns eg, headaches, abdominal pain, fertility returning to normal after removal Use clinical experience to support a woman’s decision Be aware that IUC is not the right contraceptive choice for every woman Discuss risks and potential side effects during counselling, eg, period-like pain on insertion Ref National Institute for Health and Care Excellence. Long-acting reversible contraception. Clinical Guideline. October 2005. Available at nice.org.uk/guidance/cg30. Accessed February 2016. http://www.ghspjournal.org/content/3/3/352.full NICE website Stanback J, et al. Global Health: Sci Pract. 2015;3:352-357.

Confirming the Choice of LARC: Key Messages IUC placement can be at any time in woman’s cycle, provided there is no risk of pregnancy STI screening can be performed at insertion Cervical screening is not a prerequisite for LARC Local requirements have to be met for informed consent Contact HCP immediately for any of the following: pain, fever, unusual discharge or severe bleeding Abbreviation STI = sexually transmitted infection NICE website Stanback J, et al. Global Health: Sci Pract. 2015;3:352-357.

Conclusions LARC is a safe, effective, and reversible method of contraception that is currently underused, especially by nulliparous women We need to increase the knowledge and confidence of HCP in using LARC, especially IUDs We also need to improve the contraceptive counselling offered to all women This will dispel the myths and misconceptions, and enable women to choose their contraceptive method with a full understanding of all the benefits of each, especially LARC

Abbreviations ACOG = American College of Obstetrics and Gynecology ART= antiretroviral therapy BMI = body mass index BP = blood pressure CHC = combined hormonal contraception CI = confidence interval CV = cardiovascular CVD = cardiovascular disease DMPA = depot medroxyprogesterone acetate FSRH = Faculty of Sexual and Reproductive Healthcare GP = general practitioner HCP = healthcare providers HDL = high-density lipoprotein INTRA = intra-uterine contraception for nulliparous women: translating research into action. IUC = intrauterine contraception IUD = intrauterine device IUS = intrauterine system LARC = long-acting reversible contraception LNG = levonorgestrel MEC = medical eligibility criteria

Abbreviations (cont) MI = myocardial infarction NICE = National Institute for Health and Care Excellence PID = pelvic inflammatory disease POP = progestogen-only pill RCOG = Royal College of Obstetricians and Gynaecologists STI = sexually transmitted infection T2DM = type 2 diabetes mellitus UK = United Kingdom VTE = venous thromboembolism WHO = World Health Organization