STIs, IUDs and Pelvic Inflammatory Disease Jeffrey F. Peipert, MD, PhD Department of Obstetrics and GynecologyWashington University in St. Louis School of Medicine
OBJECTIVES • Briefly discuss the CHOICE Project & STI Research • Review current data regarding IUDs and infection risk • Contrast infectious risk of currently available IUDs with previously available IUDs
Many Teens Experience Pregnancy and STDs • More than 750,000 teens become pregnant each year • 82% of these pregnancies are unintended • Nine million teens and young adults acquire an STD each year • 25% of teens have an STD
Teen Pregnancy & Sexually Transmitted Diseases • Major public health problems • St. Louis: • A “unique city” to study these issues • Exceptionally high prevalence of BOTH STD & teen pregnancy
National Ranking of the City of St. Louis Among Cities with >200,000 Population • Gonorrhea: 1st in the U.S. • Chlamydia: 2nd in the U.S. • Syphilis: 5th in the U.S. Source: Centers for Disease Control and Prevention, Atlanta GA: Annual STD Surveillance Summaries
STD Epidemic in St. Louis • Dr. Peipert’ Impact……..
REVISED National Rankings! City of St. Louis (the following year) • Gonorrhea: 1st in the U.S. • Chlamydia: 1st in the U.S.
The CHOICE Project Objectives • Promote LARC (IUDs and implant) • Measure contraceptive choice, satisfaction, and continuation • Provide enough no-cost contraception to make population impact on unintended pregnancies
CHOICE Project & STI Research • Can we PROMOTE IUD use and NOT study STIs? • Concern regarding infection risk (STIs/PID) • Concern regarding INFERTILITY • Opportunity to study STI screening • Patient preferences for screening • Home versus clinic-based screening
Female participants MUCH preferred home-based STI screening over clinic-based screening • Participants choosing home-based screening were TWICE as likely to complete testing. • (RR=2.0; 95% CI 1.5, 2.8)
Key Take-Home Points: • LARC users randomized to home-based screening • More likely to self-report screening (56.3% v. 32.9%) • RR 1.7; 95% CI 1.4, 2.0 compared to clinic-based screening
History of Intrauterine Contraception 1909: German gynecologist, Ernst Grafenberg, develops ring-shaped IUD 1929: Grafenberg cited 17 cases of inflammation reported following insertion of silk IUDs; no inflammation noted following insertion of 150 silver rings
IUD History Intrauterine Contraception 1962: Population Council organizes 1st International IUD Conference— Margulies and Lippes presented designs for plastic spiral and plastic loop Early IUDs: • Margulies Spiral (1960’s–70’s)• Lippes Loop (1964–86)• Saf-T-Coil (1965–84)
History of Intrauterine Contraception 1967: “T” shaped device developed 1968: Contraceptive action of intrauterine copper reported 1971: Dalkon Shield introduced (1971–74)
HistoryIntrauterine Contraception 1974: Cu-7 enters US market 1976: Copper T 200 becomes 1st copper-T IUD 1976: Progestasert introduced as 1st hormone-releasing IUD in US (65 µg/day progesterone) (1976–2001)
IUC History 1980: Levonorgestrel IUS tested in randomized clinical trials 1984: Copper-T 380A IUD (ParaGard®) approved by FDA for US 1988: Copper-T 380A IUD available in US 2000: LNG IUS (Mirena) available in US
Market Lifeand Numberof IUDs in the US Hubacher D, Cheng D.Contraception2004;69:437–46.
History of IUDs and Infection 1929:17 cases of inflammation reported following insertion of silk IUDs (Grafenberg)— No inflammation noted following insertion of 150 silver rings¹ 1960s:Infectious risk largely ignored — <20 citations in literature before 1970² 1974:FDA convinces AH Robins, Inc. to suspend US sales of Dalkon Shield² 1976: Still no explicit warnings about IUD use in women at risk for exposure to STIs³ Malhotra N. Obstet and Gynecol, Survey, 1982 Hubacher D. Contraception, 2004 Hatcher RA. Contraceptive Technology, 1976-1977, 8th ed
IUDs and InfectionHistory 1980: AH Robins, Inc. recommended all Dalkon Shield IUDs be removed — Attributed: 18 deaths, >200,000 infections, SABs, gyn complications — AH Robins, Inc. went bankrupt • $3 billion awarded to claimants by 2000 1980’s: Other IUDs withdrawn from market— 1984: Saf-T-Coil — 1986: Lippes Loop, Cu-7, Tatum T (Copper T 200) Hubacher D. Contraception. 2004
IUDs and InfectionHistory 1985: ACOG: IUDs “not recommended for women who have not had children, or who have multiple partners, because of the risk of PID and possibly infertility” 1993: FDA required IUD product label changes — No protection against HIV or other STIs Overall Consensus:IUDs bad. Don’t use. Hubacher D. Contraception. 2004
IUDs and InfectionHistory 2000: Mirena introduced 2005: ParaGard changes its package labeling to reflect fewer restrictions on use 2009: Mirena changes its package labeling Today: IUDs again gaining in popularity and use
Contraceptive Use and Non-Use United States (2006-2008) % of Women Aged 15–44 Sterilization (male and female) None Pill Condom Absti-nence Injectable Ring NaturalFamilyPlanning IUC Other(diaphragm, patch,gel/foam, rods, EC) Method Mosher and Jones; Vital and Health Statistics 2010
The Downfall of IUDsThe Dalkon Shield • Associated with septic abortion and death • 5-fold risk of PID (compared to other IUDs)— Braided, polyfilament strings¹— Smaller Dalkon Shield for nullips²— Surface area to drag bacteria during insertion³ • Not very effective (2% failure rate/year) • Lee. Obstet Gynecol. 1983 • Hubacher. Contraception. 2004 3. Mishell. Am J Obstet Gynecol. 1966
Cervicovaginal Infection, Not IUDs, Causes PID • Risk of PID — With Lippes Loop and Cu-7 only in first 4 months after insertion¹— With 7 copper IUDs, Lippes Loop and 2 hormonal IUDs only in 1st 20 days after insertion² • Overall, PID incidence for IUD users same as for general population²— Preexisting STI at time of insertion, NOT IUD itself, incidence of PID— No risk chlamydia acquisition³ • LNG-IUS may have lower risk than Copper T380A 4 • Lee. Obstet Gynecol. 1983 • Farley. Lancet 1992 3. Grimes. Lancet. 2000 4. Pakarinen. Contraception. 2003
8 6 Rate/1000 Woman Years (baseline = 2) 4 2 0 1 2 3 4 5 6 7 8 9 10 11 12 2 3 4 5 6 7 8 Month (first year) Year Time Since Insertion PID Incidence Rate for All IUDs By Time Since Insertion Combined WHO Clinical Trial Data for All IUDs(n = 22,908 insertions) Farley et al. Lancet 1992
GC & CT Screening at IUDInsertion and PID • Retrospective cohort study • 2005 – 2009 • More than 57,000 IUD Insertions • PID within 90 days of insertion: 0.54% • No difference based on screened versus unscreened • No difference based on same-day versus prior screening Sufrin CB, et al. Obstet Gynecol, 2012,
Prophylactic Antibiotics at Insertion?Intrauterine Contraception • Risk of infection associated with IUDs relates to insertion • One woman/1,000 will develop PID in 1st 3 months (in screened population) • Meta-analysis has not shown any overall benefit of prophylactic antibiotics Grimes, Contraception 1999; Walsh, Lancet 1998
Rx of STI/PID with IUD in Place • Effective to treat STI with IUD in place— Okay to screen at time of insertion(Grimes, Lancet 2000)— RCT data (Soderberg, Contraception 1985) • Evidence that treatment of PID effective with IUD in place— Case series data (Grimes, Lancet 2000)
IUDs, STDs, PID, and Infertility Risk • What are the concerns? • Will the IUD increase the risk of PID? • Will the IUD increase the risk of tubal-factor infertility?
BACKGROUND • Early Studies: • Risk of infertility with Dalkon Shield • OR 3.3-6.8 • Risk of infertility with copper IUD • Daling: OR 1.3 (0.6-3.0) • Cramer: OR 1.6 (1.1-2.4) • More Recent Studies: • 18 month birth rate: • 76% barrier methods vs 67% copper IUD • Fertility associated with duration of IUD Use Daling, et al. NEJM 1985 Cramer, et al. NEJM 1985 Doll, et al. BJOG 2001
Safety: IUD Does Not Cause Infertility • IUD is not related to infertility • Chlamydia is related to infertility Tubal infertility by previous copper T IUD use and presence of chlamydia antibodies, nulligravid women Hubacher D, et al. NEJM. 2001.
100 80 IUC OC Diaphragm Other methods 60 Pregnancies (%) 40 20 0 12 18 24 30 36 42 0 Months After Discontinuation Fertility Rates in Parous Women After Discontinuation of Contraceptive Vessey MP, et al. Br Med J. 1983. Andersson K, et al. Contraception. 1992. Belhadj H, et al. Contraception. 1986.
Fertility After Contraceptive Termination: The FACT Study(A Preliminary Analysis)
FACT Study • Research Question: Does the IUD increase the risk of infertility? • Dispel myths &reassure providers & patients • Specifically:After controlling for current and past infections, does use of the IUD increase the risk of infertility compared to women using other methods?
SPECIFIC AIMS • Primary aim • Compare pregnancy rates between: • IUDs versus other methods • Secondary aims: • Does past infection with CT, TV, MG increase the risk of infertility? • Does IUD use exacerbate this risk?
METHODS • Inclusion Criteria: • 18-35 years of age • Discontinued IUD, pill, patch, ring, DMPA, implant or condoms to conceive • Willing and able to undergo informed consent in English • Exclusion Criteria: • No male partner • History of infertility or sterilization
METHODS • Enrollment: • Comprehensive history • Contraceptive history • STI testing (GC, CT, TV, MG) • Serologic testing (CT, TV, MG) • Prospective follow-up every 6 months: • Conception • Live birth
FACT Study: Fertility After Contraceptive Termination Recruitment as of 4/14/2014
Positive Serology and Pregnancy at 12 Months (Fertility) Yes NoYesNoYes No
Preliminary Results & Pregnancy Rates • IUD Use: • NO significant difference by EVER IUD USER status • 45% have positive serology (CT, MG, or TV) • M. Genitalium most common: 34% • Pregnancy rates: • Positive serology: 61% • Negative serology: 74% • African-American Race associated with infertility • OR = 0.75; 95% CI 0.56, 0.99
SAMPLE SIZE • Confounding Variables: • Age • Race • BMI • Smoking • Reproductive history (gravidity/parity) • Past infection • Current infection • Need 800 – 1000 participants
FACT: Future Plans • Funding secured from Teva • Augment sample size • Continue follow-up • Revise and resubmit to NIH • Additional preliminary data • Demonstrated site collaboration • Bring on additional sites • (MUSC?)
Other Considerations for IUDs and Infectious Risk • Nulliparous women • Immediate post abortion • Immediate post partum
IUDs and Nulliparous Women • No concern for future infertility • Slightly higher insertion pain— Same as for parous women without labor or SVD— Pain scores low regardless (2.7 vs 1.9) • Similar rates of continuation/satisfaction between nullips and multips • 80% and 88%, respectively Veldhuis, Eur J Gen Practice 2004; Duenas, Contraception 1996; Wildemeersch Ann NY Acad Sci 1997; Suhonen Contraception 2004
IUD Use Post-Abortion or Postpartum • Insertion post-abortion does NOT increase:— Post-abortion endometritis or PID¹˒²— Expulsion rates after 1st trimester insertion³ • Insertion immediately postpartum does NOT increase PID/endometritis • Insertion postpartum has an acceptable expulsion rate 4 5 1. WHO, Studies in Family Planning1983 4. Xu Adv Contracep 1992 2. Pakarinen, Contraception 2003 5. Chi Contraception1985 3. Moussa, Contraception 2001
1.4% 390 days 1.2% 750 days 1.0% 0.8% Discontinuation for PID 0.6% 0.4% 0.2% 0% TCu220c Lippes Copper7 PID Post-Abortion IUD Insertion1983 WHO Study WHO, Studies in Family Planning 1983
The Context for Post-Partum IUD The PP-IUD is a potential answer to issues of: More choices increases satisfaction Possibility of a long-term reversible method IUD may be an alternative to BTL Access Contact with health system during pregnancy -Convenience Immediate postpartum insertion is convenient