Lisa Hofler, MD, MPH, MBA

Turok DK, Gero A, Simmons RG, et al. Levonorgestrel vs copper intrauterine devices for emergency contraception. N Engl J Med. 2021;384:335-344.

EXPERT COMMENTARY

Emergency contraception refers to therapies used to prevent pregnancy after inadequately protected intercourse.¹ Evidence-based forms of EC available in the United States include oral LNG, oral ulipristal acetate, and the copper IUD. The copper IUD provides not only EC but also highly effective contraception after placement.² The LNG-IUD has a favorable side effect profile compared with the copper IUD and is theorized to act as EC through direct interference with sperm and oviduct transport.³ Recently, Turok and colleagues conducted a noninferiority trial designed to investigate the EC effectiveness of the LNG-IUD compared with the copper IUD.³

Details of the study

Turok and colleagues recruited participants aged 18 to 35 who requested EC from 6 family planning clinics in Utah from 2016 to 2019. Participants who reported unprotected intercourse within the past 120 hours and who desired an IUD to prevent pregnancy for at least 1 year were randomly assigned to receive either the LNG-IUD or the copper IUD. Individuals were excluded from the trial if they had contraindications to IUD placement, were breastfeeding, had abnormal uterine bleeding, had irregular menses, were currently using highly effective contraception, or had recent EC use. Researchers determined pregnancy status at 1 month through a pregnancy test or clinical records review.

Results. Of 711 participants randomly assigned, 317 who received the LNG-IUD and 321 who received the copper IUD provided 1-month outcome data. Pregnancy 1 month after IUD placement occurred in 1 participant (0.3%) in the LNG-IUD group and in no participants in the copper IUD group (0%). The between-group difference of 0.3 percentage points was within the margin of noninferiority and was not significant.

Study strengths and limitations

This large, multicenter randomized controlled trial contributes novel information about the effectiveness and noninferiority of the LNG-IUD as EC. Unlike prior studies of oral EC, which commonly limited participants to 1 episode of unprotected intercourse, this trial enrolled women at potentially higher risk of pregnancy with multiple episodes of intercourse and found fewer pregnancies than expected. Randomization ensured equivalence between groups, with the exception of the reason for needing EC.

Study limitations include a higher than expected rate of loss to follow-up, requiring clinical records and survey data to confirm pregnancy status. After randomization, clinicians were unable to place IUDs in more than 5% of participants in both groups; noninferiority was demonstrated nonetheless. This study did not include participants receiving oral EC, so direct comparison of effectiveness is not possible. Pregnancy rates among IUD users in this study were favorable to rates reported in previous studies of oral EC.⁴

When choosing an IUD for contraception, more women select the LNG-IUD for its favorable side effect profile and reduction in menstrual bleeding. In this randomized IUD study, only 7% of eligible participants enrolled, potentially introducing selection bias. The majority who declined enrollment did not want an IUD. Previous studies that allowed participants to choose their IUD had higher enrollment rates. ● 

Turok DK, Gero A, Simmons RG, et al. Levonorgestrel vs copper intrauterine devices for emergency contraception. N Engl J Med. 2021;384:335-344.

EXPERT COMMENTARY

Emergency contraception refers to therapies used to prevent pregnancy after inadequately protected intercourse.¹ Evidence-based forms of EC available in the United States include oral LNG, oral ulipristal acetate, and the copper IUD. The copper IUD provides not only EC but also highly effective contraception after placement.² The LNG-IUD has a favorable side effect profile compared with the copper IUD and is theorized to act as EC through direct interference with sperm and oviduct transport.³ Recently, Turok and colleagues conducted a noninferiority trial designed to investigate the EC effectiveness of the LNG-IUD compared with the copper IUD.³

Details of the study

Turok and colleagues recruited participants aged 18 to 35 who requested EC from 6 family planning clinics in Utah from 2016 to 2019. Participants who reported unprotected intercourse within the past 120 hours and who desired an IUD to prevent pregnancy for at least 1 year were randomly assigned to receive either the LNG-IUD or the copper IUD. Individuals were excluded from the trial if they had contraindications to IUD placement, were breastfeeding, had abnormal uterine bleeding, had irregular menses, were currently using highly effective contraception, or had recent EC use. Researchers determined pregnancy status at 1 month through a pregnancy test or clinical records review.

Results. Of 711 participants randomly assigned, 317 who received the LNG-IUD and 321 who received the copper IUD provided 1-month outcome data. Pregnancy 1 month after IUD placement occurred in 1 participant (0.3%) in the LNG-IUD group and in no participants in the copper IUD group (0%). The between-group difference of 0.3 percentage points was within the margin of noninferiority and was not significant.

Study strengths and limitations

This large, multicenter randomized controlled trial contributes novel information about the effectiveness and noninferiority of the LNG-IUD as EC. Unlike prior studies of oral EC, which commonly limited participants to 1 episode of unprotected intercourse, this trial enrolled women at potentially higher risk of pregnancy with multiple episodes of intercourse and found fewer pregnancies than expected. Randomization ensured equivalence between groups, with the exception of the reason for needing EC.

Study limitations include a higher than expected rate of loss to follow-up, requiring clinical records and survey data to confirm pregnancy status. After randomization, clinicians were unable to place IUDs in more than 5% of participants in both groups; noninferiority was demonstrated nonetheless. This study did not include participants receiving oral EC, so direct comparison of effectiveness is not possible. Pregnancy rates among IUD users in this study were favorable to rates reported in previous studies of oral EC.⁴

When choosing an IUD for contraception, more women select the LNG-IUD for its favorable side effect profile and reduction in menstrual bleeding. In this randomized IUD study, only 7% of eligible participants enrolled, potentially introducing selection bias. The majority who declined enrollment did not want an IUD. Previous studies that allowed participants to choose their IUD had higher enrollment rates. ● 

Turok DK, Gero A, Simmons RG, et al. Levonorgestrel vs copper intrauterine devices for emergency contraception. N Engl J Med. 2021;384:335-344.

EXPERT COMMENTARY

Emergency contraception refers to therapies used to prevent pregnancy after inadequately protected intercourse.¹ Evidence-based forms of EC available in the United States include oral LNG, oral ulipristal acetate, and the copper IUD. The copper IUD provides not only EC but also highly effective contraception after placement.² The LNG-IUD has a favorable side effect profile compared with the copper IUD and is theorized to act as EC through direct interference with sperm and oviduct transport.³ Recently, Turok and colleagues conducted a noninferiority trial designed to investigate the EC effectiveness of the LNG-IUD compared with the copper IUD.³

Details of the study

Turok and colleagues recruited participants aged 18 to 35 who requested EC from 6 family planning clinics in Utah from 2016 to 2019. Participants who reported unprotected intercourse within the past 120 hours and who desired an IUD to prevent pregnancy for at least 1 year were randomly assigned to receive either the LNG-IUD or the copper IUD. Individuals were excluded from the trial if they had contraindications to IUD placement, were breastfeeding, had abnormal uterine bleeding, had irregular menses, were currently using highly effective contraception, or had recent EC use. Researchers determined pregnancy status at 1 month through a pregnancy test or clinical records review.

Results. Of 711 participants randomly assigned, 317 who received the LNG-IUD and 321 who received the copper IUD provided 1-month outcome data. Pregnancy 1 month after IUD placement occurred in 1 participant (0.3%) in the LNG-IUD group and in no participants in the copper IUD group (0%). The between-group difference of 0.3 percentage points was within the margin of noninferiority and was not significant.

Study strengths and limitations

This large, multicenter randomized controlled trial contributes novel information about the effectiveness and noninferiority of the LNG-IUD as EC. Unlike prior studies of oral EC, which commonly limited participants to 1 episode of unprotected intercourse, this trial enrolled women at potentially higher risk of pregnancy with multiple episodes of intercourse and found fewer pregnancies than expected. Randomization ensured equivalence between groups, with the exception of the reason for needing EC.

Study limitations include a higher than expected rate of loss to follow-up, requiring clinical records and survey data to confirm pregnancy status. After randomization, clinicians were unable to place IUDs in more than 5% of participants in both groups; noninferiority was demonstrated nonetheless. This study did not include participants receiving oral EC, so direct comparison of effectiveness is not possible. Pregnancy rates among IUD users in this study were favorable to rates reported in previous studies of oral EC.⁴

When choosing an IUD for contraception, more women select the LNG-IUD for its favorable side effect profile and reduction in menstrual bleeding. In this randomized IUD study, only 7% of eligible participants enrolled, potentially introducing selection bias. The majority who declined enrollment did not want an IUD. Previous studies that allowed participants to choose their IUD had higher enrollment rates. ● 

Yland JJ, Bresnick KA, Hatch EE, et al. Pregravid contraceptive use and fecundability: prospective cohort study. BMJ. 2020;371:m3966.

EXPERT COMMENTARY

Most US women aged 15 to 49 currently use contraception, with long-acting reversible contraception (LARC)—IUDs and the contraceptive implant—increasing in popularity over the last decade.¹ Oral contraceptive pills, male condoms, and LARC are the most common reversible methods used.¹ While the efficacy and safety of contraception have been established, few studies have examined the effect of recent contraceptive use on fertility.

Fecundability is the probability of pregnancy during a single menstrual cycle for a couple engaging in regular intercourse and not using contraception.² Small studies have found short-term reductions in fecundability after discontinuing combined oral contraceptives and larger reductions after stopping injectable contraceptives, with no long-term differences among methods.^3,4

Data are limited regarding the effects of other forms of contraception on fecundability, particularly LARC methods. A recent study was designed to evaluate the association between the last contraceptive method used and subsequent fecundability.²

Details of the study

Yland and colleagues pooled data from 3 prospective cohort studies of 17,954 women planning pregnancies in Denmark, Canada, and the United States. Participants reported the contraceptive method used most recently before trying to conceive. They completed questionnaires every 2 months for 12 months or until they reported a pregnancy. Women were excluded if they tried to conceive for more than 6 menstrual cycles at study entry.

The authors calculated the fecundability ratio—the average probability of conception per cycle for a specific contraceptive method compared with a reference method—using proportional probability models adjusted for potential confounders. They also calculated pregnancy attempt time using participant-reported menstrual cycle length and date of last menstrual period during follow-up questionnaires.

Continue to: Injectable contraceptives associated with longest delayed fertility return...

After adjusting for personal factors, medical history, lifestyle characteristics, and indicators of underlying fertility, the authors found that injectable contraceptive use was associated with decreased fecundability compared with barrier method use (fecundability ratio [FR], 0.65; 95% confidence interval [CI], 0.47–0.89). Hormonal IUD use was associated with slight increases in fecundability compared with barrier method use (FR, 1.14; 95% CI, 1.07–1.22) and copper IUD use (FR, 1.18; 95% CI, 1.05–1.33). All other contraceptive methods were not significantly different from barrier methods.

LARC method use was associated with the shortest delay in return of normal fertility (2 cycles), followed by oral and ring contraceptives (3 cycles) and patch (4 cycles). Women using injectable contraceptives experienced the longest delay (5–8 menstrual cycles). Lifetime duration of contraceptive use did not impact fecundability in the North American cohort.

Study strengths and limitations

This large, prospective study contributes useful information about fecundability after stopping contraceptive methods. It confirms earlier studies’ findings that showed decreased fecundability after stopping injectable contraceptives. Study participants’ most recent method used was similar to overall US method distribution.¹

Study limitations include online recruitment of self-selecting participants, which introduces selection bias. The study population was overwhelmingly white (92%) and highly educated (70% with college degrees), quite different from the US population. These findings may therefore have limited generalizability. Additionally, injectable contraceptive users had higher body mass index and were more likely to smoke and have diabetes, infertility, or irregular menstrual cycles. IUD users were more likely to be parous and have a history of unplanned pregnancy, indicating possible higher baseline fertility. Even after adjusting, possible unmeasured factors could impact study results. ●

Yland JJ, Bresnick KA, Hatch EE, et al. Pregravid contraceptive use and fecundability: prospective cohort study. BMJ. 2020;371:m3966.

EXPERT COMMENTARY

Most US women aged 15 to 49 currently use contraception, with long-acting reversible contraception (LARC)—IUDs and the contraceptive implant—increasing in popularity over the last decade.¹ Oral contraceptive pills, male condoms, and LARC are the most common reversible methods used.¹ While the efficacy and safety of contraception have been established, few studies have examined the effect of recent contraceptive use on fertility.

Fecundability is the probability of pregnancy during a single menstrual cycle for a couple engaging in regular intercourse and not using contraception.² Small studies have found short-term reductions in fecundability after discontinuing combined oral contraceptives and larger reductions after stopping injectable contraceptives, with no long-term differences among methods.^3,4

Data are limited regarding the effects of other forms of contraception on fecundability, particularly LARC methods. A recent study was designed to evaluate the association between the last contraceptive method used and subsequent fecundability.²

Details of the study

Yland and colleagues pooled data from 3 prospective cohort studies of 17,954 women planning pregnancies in Denmark, Canada, and the United States. Participants reported the contraceptive method used most recently before trying to conceive. They completed questionnaires every 2 months for 12 months or until they reported a pregnancy. Women were excluded if they tried to conceive for more than 6 menstrual cycles at study entry.

The authors calculated the fecundability ratio—the average probability of conception per cycle for a specific contraceptive method compared with a reference method—using proportional probability models adjusted for potential confounders. They also calculated pregnancy attempt time using participant-reported menstrual cycle length and date of last menstrual period during follow-up questionnaires.

Continue to: Injectable contraceptives associated with longest delayed fertility return...

After adjusting for personal factors, medical history, lifestyle characteristics, and indicators of underlying fertility, the authors found that injectable contraceptive use was associated with decreased fecundability compared with barrier method use (fecundability ratio [FR], 0.65; 95% confidence interval [CI], 0.47–0.89). Hormonal IUD use was associated with slight increases in fecundability compared with barrier method use (FR, 1.14; 95% CI, 1.07–1.22) and copper IUD use (FR, 1.18; 95% CI, 1.05–1.33). All other contraceptive methods were not significantly different from barrier methods.

LARC method use was associated with the shortest delay in return of normal fertility (2 cycles), followed by oral and ring contraceptives (3 cycles) and patch (4 cycles). Women using injectable contraceptives experienced the longest delay (5–8 menstrual cycles). Lifetime duration of contraceptive use did not impact fecundability in the North American cohort.

Study strengths and limitations

This large, prospective study contributes useful information about fecundability after stopping contraceptive methods. It confirms earlier studies’ findings that showed decreased fecundability after stopping injectable contraceptives. Study participants’ most recent method used was similar to overall US method distribution.¹

Study limitations include online recruitment of self-selecting participants, which introduces selection bias. The study population was overwhelmingly white (92%) and highly educated (70% with college degrees), quite different from the US population. These findings may therefore have limited generalizability. Additionally, injectable contraceptive users had higher body mass index and were more likely to smoke and have diabetes, infertility, or irregular menstrual cycles. IUD users were more likely to be parous and have a history of unplanned pregnancy, indicating possible higher baseline fertility. Even after adjusting, possible unmeasured factors could impact study results. ●

Yland JJ, Bresnick KA, Hatch EE, et al. Pregravid contraceptive use and fecundability: prospective cohort study. BMJ. 2020;371:m3966.

EXPERT COMMENTARY

Most US women aged 15 to 49 currently use contraception, with long-acting reversible contraception (LARC)—IUDs and the contraceptive implant—increasing in popularity over the last decade.¹ Oral contraceptive pills, male condoms, and LARC are the most common reversible methods used.¹ While the efficacy and safety of contraception have been established, few studies have examined the effect of recent contraceptive use on fertility.

Fecundability is the probability of pregnancy during a single menstrual cycle for a couple engaging in regular intercourse and not using contraception.² Small studies have found short-term reductions in fecundability after discontinuing combined oral contraceptives and larger reductions after stopping injectable contraceptives, with no long-term differences among methods.^3,4

Data are limited regarding the effects of other forms of contraception on fecundability, particularly LARC methods. A recent study was designed to evaluate the association between the last contraceptive method used and subsequent fecundability.²

Details of the study

Yland and colleagues pooled data from 3 prospective cohort studies of 17,954 women planning pregnancies in Denmark, Canada, and the United States. Participants reported the contraceptive method used most recently before trying to conceive. They completed questionnaires every 2 months for 12 months or until they reported a pregnancy. Women were excluded if they tried to conceive for more than 6 menstrual cycles at study entry.

The authors calculated the fecundability ratio—the average probability of conception per cycle for a specific contraceptive method compared with a reference method—using proportional probability models adjusted for potential confounders. They also calculated pregnancy attempt time using participant-reported menstrual cycle length and date of last menstrual period during follow-up questionnaires.

Continue to: Injectable contraceptives associated with longest delayed fertility return...

After adjusting for personal factors, medical history, lifestyle characteristics, and indicators of underlying fertility, the authors found that injectable contraceptive use was associated with decreased fecundability compared with barrier method use (fecundability ratio [FR], 0.65; 95% confidence interval [CI], 0.47–0.89). Hormonal IUD use was associated with slight increases in fecundability compared with barrier method use (FR, 1.14; 95% CI, 1.07–1.22) and copper IUD use (FR, 1.18; 95% CI, 1.05–1.33). All other contraceptive methods were not significantly different from barrier methods.

LARC method use was associated with the shortest delay in return of normal fertility (2 cycles), followed by oral and ring contraceptives (3 cycles) and patch (4 cycles). Women using injectable contraceptives experienced the longest delay (5–8 menstrual cycles). Lifetime duration of contraceptive use did not impact fecundability in the North American cohort.

Study strengths and limitations

This large, prospective study contributes useful information about fecundability after stopping contraceptive methods. It confirms earlier studies’ findings that showed decreased fecundability after stopping injectable contraceptives. Study participants’ most recent method used was similar to overall US method distribution.¹

Study limitations include online recruitment of self-selecting participants, which introduces selection bias. The study population was overwhelmingly white (92%) and highly educated (70% with college degrees), quite different from the US population. These findings may therefore have limited generalizability. Additionally, injectable contraceptive users had higher body mass index and were more likely to smoke and have diabetes, infertility, or irregular menstrual cycles. IUD users were more likely to be parous and have a history of unplanned pregnancy, indicating possible higher baseline fertility. Even after adjusting, possible unmeasured factors could impact study results. ●