Long-acting reversible contraception immediately after medical abortion: systematic review with meta-analyses.

Long-acting reversible contraceptives (LARCs) are safe, effective and convenient post-abortal methods. However, there is concern that some LARCs may reduce the effectiveness of abortifacient drugs or result in other adverse outcomes. We undertook two systematic reviews to examine the early administration of LARCs in women undergoing medical abortion with mifepristone and misoprostol. (i) For women who are having a medical abortion and who plan to use a progestogen-only contraceptive implant or injectable, does administration of the contraception at the same time as mifepristone influence the efficacy of the abortion? (Implant/injectable review). (ii) For women who have had a medical abortion, how soon after expulsion of the products of conception is it safe to insert an intrauterine contraceptive device/system? (LNG-IUS/Cu-IUD review). On 19 November 2018, we searched Embase Classic, Embase; Ovid MEDLINE(R) including Daily and Epub Ahead-of-Print, In-Process and Other Non-Indexed Citations; the Cochrane Library; Cinahl Plus; and Web of Science Core Collection. Eligible studies were randomised controlled trials (RCTs), in English from 1985 (Implant/injectable review) or 2007 (LNG-IUS/Cu-IUD review) onwards, conducted in women undergoing medical abortion with mifepristone and misoprostol and studying either (i) simultaneous administration of mifepristone and a progestogen-only contraceptive implant or injectable compared to administration >24 h after mifepristone, or (ii) immediate insertion of intrauterine contraception after expulsion of the products of conception compared to early insertion (≤7 days) or to delayed insertion (>7 days) or early compared to delayed insertion. One author assessed the risk of bias in the studies using the Cochrane Collaboration checklist for RCTs. All the outcomes were analysed as risk ratios and meta-analysed in Review Manager 5.3 using the Mantel-Haenszel statistical method and a fixed-effect model. The overall quality of the evidence was assessed using GRADE. Two RCTs (n = 1027) showed lower 'subsequent unintended pregnancy' rates and higher 'patient satisfaction' rates, and no other differences, after simultaneous administration of mifepristone and the implant compared to delayed administration. One RCT (n = 461) showed higher 'patient satisfaction' rates after simultaneous administration than after delayed administration of mifepristone and the injectable, but no other differences between these interventions. Three RCTs (n = 536) found no differences other than higher copper IUC uptake after early compared to delayed insertion at ≤9 weeks of gestation and higher rates of IUC expulsion, continuation and uptake after immediate compared to delayed insertion at 9+1-12+0 weeks of gestation and higher IUC continuation rates after immediate compared to delayed insertion at 12+1-20+0 weeks of gestation. The quality of this evidence ranged from very low to high and was mainly compromised by low event rates, high attrition and no blinding. The contraceptive implant or injectable should be offered on the day of taking mifepristone. Intrauterine methods of contraception should be offered as soon as possible after expulsion of the pregnancy.

Schmidt-Hansen M ，Hawkins JE ，Lord J ，Williams K ，Lohr PA ，Hasler E ，Cameron S ... -  《-》

Immediate versus delayed insertion of an etonogestrel releasing implant at medical abortion-a randomized controlled equivalence trial.

Does a progestin releasing subdermal contraceptive implant affect the efficacy of medical abortion if inserted at the same visit as the progesterone receptor modulator, mifepristone, at medical abortion? A etonogestrel releasing subdermal implant inserted on the day of mifepristone did not impair the efficacy of the medical abortion compared with routine insertion at 2-4 weeks after the abortion. The etonogestrel releasing subdermal implant is one of the most effective long acting reversible contraceptive methods. The effect of timing of placement on the efficacy of mifepristone and impact on prevention of subsequent unintended pregnancy is not known. This multicentre, randomized controlled, equivalence trial with recruitment between 13 October 2013 and 17 October 2015 included a total of 551 women with pregnancies below 64 days gestation opting for the etonogestrel releasing subdermal implant as postabortion contraception. Women were randomized to either insertion at 1 hour after mifepristone intake (immediate) or at follow-up 2-4 weeks later (delayed insertion). An equivalence design was used due to advantages for women such as fewer visits to the clinic with immediate insertion. The primary outcome was the percentage of women with complete abortion not requiring surgical intervention within 1 month. Secondary outcomes included insertion rates, pregnancy and repeat abortion rates during 6 months follow-up. Analysis was per protocol and by intention to treat. Women aged 18 years and older who had requested medical termination of a pregnancy up to 63 days of gestation and opted for an etonogestrel releasing contraceptive implant were recruited in outpatient family planning clinics in six hospitals in Sweden and Scotland. Efficacy of medical abortion was 259/275 (94.2%) in the immediate insertion group and 239/249 (96%) in the routine insertion group with a risk difference of 1.8% (95% CI -0.4 to 4.1%), which was within the ±5% margin of equivalence. The insertion rate was 275/277 (98.9%) in the immediate group compared to 187/261 (71.6%) women in the routine group (P < 0.001). At 6 months of follow-up significantly fewer women in the immediate group had become pregnant again (2/277, 0.8%) compared to the routine group (10/261, 3.8%) P = 0.018. For the main outcome loss to follow-up data was minimized through access to patient records. Efforts were made to reduce loss to follow-up also for secondary outcomes. The results of the sensitivity analysis did not differ from the intention to treat or per protocol analysis. Guidelines on postabortion contraception should be amended to include insertion of the etonogestrel releasing implant at the time of mifepristone intake for medical abortion up to and including a gestation of 63 days. This study was funded by the Swedish Research Council (2012-2844), Stockholm City County and Karolinska Institutet (ALF). The contraceptive implants were provided by Merck and supplied by MSD Sweden. HKK and KGD have received honorariums for giving lectures for MSD/Merck and have participated in the national (HKK and KGD) and international (KGD) medical advisory boards for MSD/Merck. The other authors have nothing to declare. ClinicalTrials number NCT01920022. 06 August 2013. 13 October 2013.

Hognert H ，Kopp Kallner H ，Cameron S ，Nyrelli C ，Jawad I ，Heller R ，Aronsson A ，Lindh I ，Benson L ，Gemzell-Danielsson K ... -  《-》

Canadian Contraception Consensus (Part 3 of 4): Chapter 7--Intrauterine Contraception.

To provide guidelines for health care providers on the use of contraceptive methods to prevent pregnancy and on the promotion of healthy sexuality. Overall efficacy of cited contraceptive methods, assessing reduction in pregnancy rate, safety, ease of use, and side effects; the effect of cited contraceptive methods on sexual health and general well-being; and the relative cost and availability of cited contraceptive methods in Canada. Published literature was retrieved through searches of Medline and The Cochrane Database from January 1994 to January 2015 using appropriate controlled vocabulary (e.g., contraception, sexuality, sexual health) and key words (e.g., contraception, family planning, hormonal contraception, emergency contraception). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies published in English from January 1994 to January 2015. Searches were updated on a regular basis in incorporated in the guideline to June 2015. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. The quality of the evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table 1). CHAPTER 7: INTRAUTERINE CONTRACEPTION: 1. Intrauterine contraceptives are as effective as permanent contraception methods. (II-2) 2. The use of levonorgestrel-releasing intrauterine system (LNG-IUS) 52 mg by patients taking tamoxifen is not associated with recurrence of breast cancer. (I) 3. Intrauterine contraceptives have a number of noncontraceptive benefits. The levonorgestrel-releasing intrauterine system (LNG-IUS) 52 mg significantly decreases menstrual blood loss (I) and dysmenorrhea. (II-2) Both the copper intrauterine device and the LNG-IUS significantly decrease the risk of endometrial cancer. (II-2) 4. The risk of uterine perforation decreases with inserter experience but is higher in postpartum and breastfeeding women. (II-2) 5. The risk of pelvic inflammatory disease (PID) is increased slightly in the first month after intrauterine contraceptive (IUC) insertion, but the absolute risk is low. Exposure to sexually transmitted infections and not the IUC itself is responsible for PID occurring after the first month of use. (II-2) 6. Nulliparity is not associated with an increased risk of intrauterine contraceptive expulsion. (II-2) 7. Ectopic pregnancy with an intrauterine contraceptive (IUC) is rare, but when a pregnancy occurs with an IUC in situ, it is an ectopic pregnancy in 15% to 50% of the cases. (II-2) 8. In women who conceive with an intrauterine contraceptive (IUC) in place, early IUC removal improves outcomes but does not entirely eliminate risks. (II-2) 9. Intrauterine contraceptives do not increase the risk of infertility. (II-2) 10. Immediate insertion of an intrauterine contraceptive (10 minutes postplacental to 48 hours) postpartum or post-Caesarean section is associated with a higher continuation rate compared with insertion at 6 weeks postpartum. (I) 11. Immediate insertion of an intrauterine contraceptive (IUC; 10 minutes postplacental to 48 hours) postpartum or post-Caesarean section is associated with a higher risk of expulsion. (I) The benefit of inserting an IUC immediately postpartum or post-Caesarean section outweighs the disadvantages of increased risk of perforation and expulsion. (II-C) 12. Insertion of an intrauterine contraceptive in breastfeeding women is associated with a higher risk of uterine perforation in the first postpartum year. (II-2) 13. Immediate insertion of an intrauterine contraceptive (IUC) post-abortion significantly reduces the risk of repeat abortion (II-2) and increases IUC continuation rates at 6 months. (I) 14. Antibiotic prophylaxis for intrauterine contraceptive insertion does not significantly reduce postinsertion pelvic infection. (I) RECOMMENDATIONS: 1. Health care professionals should be careful not to restrict access to intrauterine contraceptives (IUC) owing to theoretical or unproven risks. (III-A) Health care professionals should offer IUCs as a first-line method of contraception to both nulliparous and multiparous women. (II-2A) 2. In women seeking intrauterine contraception (IUC) and presenting with heavy menstrual bleeding and/or dysmenorrhea, health care professionals should consider the use of the levonorgestrel intrauterine system 52 mg over other IUCs. (I-A) 3. Patients with breast cancer taking tamoxifen may consider a levonorgestrel-releasing intrauterine system 52 mg after consultation with their oncologist. (I-A) 4. Women requesting a levonorgestrel-releasing intrauterine system or a copper-intrauterine device should be counseled regarding changes in bleeding patterns, sexually transmitted infection risk, and duration of use. (III-A) 5. A health care professional should be reasonably certain that the woman is not pregnant prior to inserting an intrauterine contraceptive at any time during the menstrual cycle. (III-A) 6. Health care providers should consider inserting an intrauterine contraceptive immediately after an induced abortion rather than waiting for an interval insertion. (I-B) 7. In women who conceive with an intrauterine contraceptive (IUC) in place, the diagnosis of ectopic pregnancy should be excluded as arly as possible. (II-2A) Once an ectopic pregnancy has been excluded, the IUC should be removed without an invasive procedure. The IUC may be removed at the time of a surgical termination. (II-2B) 8. In the case of pelvic inflammatory disease, it is not necessary to remove the intrauterine contraceptive unless there is no clinical improvement after 48 to 72 hours of appropriate antibiotic treatment. (II-2B) 9. Routine antibiotic prophylaxis for intrauterine contraceptive (IUC) insertion is not indicated. (I-B) Health care providers should perform sexually transmitted infection (STI) testing in women at high risk of STI at the time of IUC insertion. If the test is positive for chlamydia and/or gonorrhea, the woman should be appropriately treated postinsertion and the IUC can remain in situ. (II-2B) 10. Unscheduled bleeding in intrauterine contraception users, when persistent or associated with pelvic pain, should be investigated to rule out infection, pregnancy, gynecological pathology, expulsion or malposition. (III-A)

Black A ，Guilbert E ，Costescu D ，Dunn S ，Fisher W ，Kives S ，Mirosh M ，Norman W ，Pymar H ，Reid R ，Roy G ，Varto H ，Waddington A ，Wagner MS ，Whelan AM ，Mansouri S ... -  《-》

Simultaneous compared to interval administration of mifepristone and misoprostol for medical abortion up to 10(+0) weeks' gestation: a systematic review with meta-analyses.

Medical abortion with mifepristone and misoprostol usually involves an interval of 36-48 hours between administering these drugs; however, it is possible that the clinical efficacy at early gestations may be maintained when the drugs are taken simultaneously. The objective of this systematic review was to determine the safety and effectiveness of simultaneous compared with interval administration of mifepristone and misoprostol for abortion up to 10+0 weeks' gestation. We searched Embase Classic, Embase; Ovid MEDLINE(R) including Daily, and Epub Ahead-of-Print, In-Process & Other Non-Indexed Citations; and Cochrane Library on 11 December 2019. We included randomised controlled trials (RCTs), published in English from 1985, comparing simultaneous to interval administration of mifepristone and misoprostol for early abortion. Risk of bias was assessed using the Cochrane Collaboration checklist for RCTs. Meta-analysis of risk ratios (RRs) using the Mantel-Haenszel method were performed. The quality of the evidence was assessed using GRADE. Meta-analyses of three RCTs (n=1280) showed no differences in 'ongoing pregnancy' (RR 1.78, 95% CI 0.38 to 8.36), 'haemorrhage requiring transfusion or ≥500 mL blood loss' (RR 0.11, 95% CI 0.01 to 2.03) and 'incomplete abortion with the need for surgical intervention' (RR 1.30, 95% CI 0.76 to 2.25) between the interventions. Individual study results showed no difference in patient satisfaction, or 'need for repeat misoprostol', although 'time to onset of bleeding or cramping' was longer after simultaneous than interval administration. The quality of evidence was very low to moderate. The published data support the use of simultaneous mifepristone and misoprostol for medical abortion up to 9+0 weeks in women who prefer this method of administration.

Schmidt-Hansen M ，Lord J ，Hasler E ，Cameron S ... -  《-》

Follow-up strategies to confirm the success of medical abortion of pregnancies up to 10 weeks' gestation: a systematic review with meta-analyses.

To compare the effectiveness, safety, and acceptability of in-clinic and remote/self-assessment, as well as different remote/self-assessments, for confirming the success of medical abortion at ≤10+0 weeks' gestation. Ovid Embase Classic and Embase; Ovid MEDLINE(R) and Epub Ahead-of-Print, In-Process & Other Non-Indexed Citations and Daily; and the Cochrane Library. We also consulted experts in this field for any ongoing or missed trials. Randomized controlled trials published in English from 2000 onward, comparing in-clinic assessment with ultrasound to remote or self-assessment or comparing different remote or self-assessment strategies to confirm the success of medical abortion of pregnancies up to and including 10+0 weeks gestation, reporting any of the following outcomes: "missed ongoing pregnancy," "correct implementation of the follow-up strategy," patient satisfaction/preference, "adherence to follow-up strategy," "unscheduled visits/telephone calls to the abortion service," and surgical intervention. One author assessed the risk of bias in the studies using the Cochrane Collaboration checklist for randomized controlled trials. All outcomes were analyzed as risk ratios and meta-analysed in Review Manager 5.3 using the Mantel-Haenszel statistical method and a fixed effect model. The overall quality of the evidence was assessed using GRADE. Four randomized controlled trials (n = 5761) compared in-clinic to remote self-assessment and found no clinically significant differences apart from higher preference rates for remote follow-up, especially in the remote follow-up groups. The quality of this evidence was compromised by attrition, no blinding, inconsistency, indirectness, and low event rates. Two randomized controlled trials (n = 1125) compared different remote assessment strategies (using urine pregnancy tests) and also found no clinically significant differences apart from a clinically significantly lower rate of unscheduled visits to the abortion service in the remote follow-up group using a multilevel urine pregnancy test compared to remote follow-up using a high-sensitivity urine pregnancy test. The quality of this evidence was compromised by small event rates, lack of blinding, indirectness and high attrition rates. The published data support offering women who have had a medical abortion up to and including 10+0 weeks' gestation the choice of self-assessment, remote assessment, or clinic follow-up.

Schmidt-Hansen M ，Cameron S ，Lohr PA ，Hasler E ... -  《-》