Contraceptive efficacy of emergency contraception with levonorgestrel given before or after ovulation

Background

We aimed to evaluate whether emergency contraception with levonorgestrel (LNG-EC) administered after ovulation is equally effective to LNG-EC administered before ovulation.

Study design

We studied a cohort of women attending a family planning clinic for EC. From interview, we recorded menstrual history, time of intercourse and of intake of LNG-EC. On the day of intake of LNG-EC and during 5 days' follow-up, blood samples were taken for examination of luteinizing hormone, estradiol and progesterone concentrations, and vaginal ultrasound examinations were done for size of the leading follicle and/or corpus luteum. Thereafter women were not contacted until next menses or pregnancy occurred.

Results

Of 388 women attending for LNG-EC, 122 women had intercourse on fertile cycle days according to ultrasound and endocrine findings. At the time of LNG-EC intake, 87 women were in Days −5 to −1 and 35 women were in Day 0 (day of ovulation) or beyond. With the use of the probability of clinical pregnancy reported by Wilcox et al. [N Engl J Med 333 (1995) 1517-1521], expected numbers of pregnancies among the 87 and 35 women were 13 and 7, respectively, while 0 and 6 pregnancies, respectively, occurred.

Conclusion

We conclude that LNG-EC prevents pregnancy only when taken before fertilization of the ovum has occurred.     

Contraceptive efficacy of emergency contraception with levonorgestrel given before or after ovulation

Background

The contraceptive efficacy of emergency contraceptive pills containing levonorgestrel (LNG-EC) has been estimated in most previous studies by judging the day of ovulation from presumptive menstrual cycle data, thus providing poorly reliable estimates.

Methods

In the present study, the efficacy of LNG-EC was determined in 393 cycles by dating ovulation on the basis of reliable hormonal and ovarian parameters validated by a database constructed in a separate study. In addition, the efficacy was determined separately for cycles in which LNG-EC was given before or after ovulation.

Results

For the 148 women who had sexual intercourse during the fertile days, the overall accumulated probability of pregnancy was 24.7, while altogether 8 pregnancies were observed. Thus, the overall contraceptive efficacy of LNG-EC was 68%. Among the 103 women who took LNG-EC before ovulation (days −5 to −1), 16 pregnancies were expected and no pregnancy occurred (p<.0001). Among the 45 women who took LNG-EC on the day of ovulation (day 0) or thereafter, 8 pregnancies occurred and 8.7 were expected (p=1.00). These findings are incompatible with the inhibition of implantation by LNG-EC in women. The same cases were also analyzed using the presumptive menstrual cycle data, and important discrepancies were detected between the two methods.

Conclusion

The efficacy of LNG-EC has been overestimated in studies using presumptive menstrual cycle data. Our results confirm previous similar studies and demonstrate that LNG-EC does not prevent embryo implantation and therefore cannot be labeled as abortifacient.     

Effect of single administration of levonorgestrel on the menstrual cycle

BACKGROUND: Levonorgestrel (LNG) 1.5 mg administered within 72 h of unprotected coitus is an established method of emergency contraception. Currently, there is some, although incomplete, knowledge about the mechanism of action. METHODS: We administered 1.5 mg LNG peri-ovulatory to determine the effects on serum gonadotrophins, estradiol and progesterone levels. Fourteen women were studied in a pretreatment and treatment cycle; eight women (Group A) took LNG 3 days before the expected day of ovulation, while 6 (Group B) took LNG a day before the expected day of ovulation. RESULTS: The women in Group A had a significant delay in their LH peak and onset of the next menses compared with their pretreatment cycles (26.4 vs. 39.1 days, p<.05). Those in Group B had no significant changes in the endocrine parameters but there was a significant shortening of the mean cycle length in comparison with their pretreatment cycles (25.1 vs. 20.2 days). CONCLUSION: Levonorgestrel 1.5 mg acts as an emergency contraception by delaying the LH surge and interfering with ovulation. It may also disrupt corpus luteum formation causing premature luteinization of unruptured follicles.     

紧急避孕效果评价的可信性研究

目的:探索以月经周期和末次月经推算受孕期与生化诊断间出现差异的原因,进而评价紧急避孕效果判断的可信性。方法:对100例要求紧急避孕服务的妇女末次月经日期、月经周期和未保护性生活时间的确信程度进行回忆问卷调查,同时以B超作为月经周期、排卵监测手段进行对比性研究。结果:51例(52.04%)妇女确信知道末次月经的日期;9例(9.18%)妇女不能准确回忆无保护性生活时间;58.16%的妇女在该研究周期中有过1次以上的性生活;32例(32.65%)妇女B超证实与她们的周期不符合;2例妊娠,其中1例根据wilcox方法评估其妊娠危险概率为0%。结论:对于一部分妇女依赖于对末次月经、性生活时间的回忆和排卵日的推算来评价紧急避孕效果的方法显然是不准确的,应采用更合理的评价方法。     

Effectiveness of the Yuzpe regimen of emergency contraception by cycle day of intercourse: implications for mechanism of action

OBJECTIVE: The purpose of this study was to provide evidence about the mechanism of action of the Yuzpe method of emergency contraception by examining effectiveness by cycle day of intercourse relative to ovulation. METHODS: Through a literature search, we identified eight studies that present the number of women treated and outcome of treatment by cycle day of unprotected intercourse relative to expected day of ovulation. Using five sets of external estimates of conception probabilities by cycle day of intercourse among women not using contraception, we assessed and compared the effectiveness of the Yuzpe regimen by whether intercourse occurred on or before the second day before ovulation or afterward, and whether intercourse occurred on or before the first day before ovulation or afterward. RESULTS: In 36 of the 45 pairs of estimates of effectiveness, based on eight separate studies and the eight studies combined and five different sets of conception probabilities by cycle day, effectiveness was higher-and in most cases substantially higher-when intercourse occurred on or before the second day before ovulation (day -2) than when it occurred later. When data were stratified by whether intercourse occurred on or before the day before ovulation (day -1), effectiveness was greater when intercourse occurred early in 43 of 45 pairs. CONCLUSIONS: These results suggest that one hypothesized mechanism of action of the Yuzpe method, inhibiting implantation of a fertilized egg, is unlikely to be the primary mechanism of action.     

Embryo transfer in the dromedary camel (Camelus dromedarius) using non-ovulated and ovulated, asynchronous progesterone-treated recipients

The aim of the present study was to investigate the use of exogenous progesterone and equine chorionic gonadotrophin (eCG) in non-ovulated and ovulated, asynchronous dromedary camel recipients being prepared for an embryo transfer programme. The uteri of 12 mated donor camels were flushed non-surgically 7 days after ovulation and 42 embryos were recovered. In Experiment 1, 16 embryos were transferred non-surgically to recipients on Day 3 or 4 after ovulation (ov+3 and ov+4, respectively). Each recipient received a daily dose of 75 mg, i.m., progesterone-in-oil from 2 days before embryo transfer until 6 days after ovulation. Thereafter, the progesterone dose was reduced to 50 mg on Day 7 and finally to 25 mg day(-1) on Days 8 and 9. Nine of 16 recipients (56%; ov+3, n=4; ov+4, n=5) became pregnant compared with none of eight non-progesterone treated controls, into which embryos were transferred on Day 4 after ovulation. In Experiment 2, 18 non-ovulated recipients received 75 mg, i.m., progesterone-in-oil daily from 3 days before until 12 days after non-surgical transfer of a Day 7 blastocyst, at which time pregnancy was diagnosed by ultrasonography. All pregnant recipients continued to receive 75 mg progesterone-in-oil daily for a further 6 days, when each camel received 2000 IU, i.m., eCG. Progesterone treatment was then reduced to 50 mg day(-1) and, when a follicle(s) ≥1.3 cm in diameter were present in the ovaries, each animal received 20 μg buserelin to induce ovulation. Once the corpora lutea had developed, progesterone treatment was reduced to 25 mg day(-1) for a final 3 days. Fourteen of 18 recipients (78%) became pregnant and seven of these (50%) remained pregnant after eCG treatment. Of the seven pregnancies that were lost, two were lost before eCG treatment, two did not respond to eCG treatment and three responded to eCG treatment and ovulated, but lost their pregnancies 6-8 days after the last progesterone injection.     

Hormonal evaluation and midcycle detection of intrauterine glycodelin in women treated with levonorgestrel as in emergency contraception

Background

The study was conducted to assess the effects of levonorgestrel (LNG) on hormonal behavior and on the secretory pattern of intrauterine glycodelin at the midcycle of ovulatory women.

Study Design

Thirty healthy sterilized women with normal ovarian function were studied during one control untreated cycle and one LNG-treated cycle. In the treated cycle, each woman received two doses of 0.75 mg of LNG 12 h apart during the preovulatory phase approximately 2 days before the LH surge. Daily follicle development recordings were performed until follicle rupture was observed, and serum glycodelin, LH, estradiol, estrone and progesterone were measured as well. In addition, glycodelin concentrations were assayed in uterine flushing obtained on Days LH+1 and LH+12.

Results

LNG did not modify follicle rupture in 20 of 30 women. In spite of ovulatory progesterone and the occurrence of follicle rupture in these women, luteal phase length was significantly decreased, as well as the serum concentrations of LH, estradiol and estrone in the periovulatory phase. Glycodelin in serum and uterine flushings was significantly elevated in the periovulatory phase when compared to control cycles.

Conclusions

LNG taken at the dose used in emergency contraception before the LH surge increased prematurely serum and intrauterine concentrations of glycodelin at the time of ovulation. Since there are well established glycodelin inhibitory effects upon fertilization, these results may represent an additional action of LNG in situations where the intervention did not interfere with ovulation.     

Ulipristal acetate: a new emergency contraceptive that is safe and more effective than levonorgestrel

Ulipristal acetate (UPA), a selective progesterone receptor modulator, when taken as a single 30-mg dose, is safe and effective for emergency contraception up to 5 days (120 h) following unprotected intercourse. This indication has been approved in Europe since May 2009 and was approved by the US FDA in August 2010. The older progesterone-only emergency contraceptive, levonorgestrel (LNG), is approved only up to 72 h after unprotected intercourse. UPA is effective in delaying or inhibiting ovulation, even if taken 24 to 48 h prior to expected ovulation, a time when LNG is no longer effective. A recent meta-analysis of two randomized clinical trials showed UPA to have a pregnancy risk 42% lower than LNG up to 72 h, and 65% lower in the first 24 h following unprotected intercourse. In a randomized trial enrolling women up to 5 days after unprotected intercourse, significantly more pregnancies were prevented with UPA than with LNG when taken beyond 72 h.     

使用母体乐375 SL IUD与左炔诺孕酮紧急避孕的临床研究

目的:评价母体乐375 SL IUD用于紧急避孕的安全性、有效性和可接受性。方法:以100例无保护性生活后120小时内放置MLCu375 SLIUD者为IUD组,术前行尿妊娠试验检查,排除已有妊娠;另110例无保护性生活后72小时内口服LNG 0.75mg,12小时后再服0.75mg者为LNG组,服药前行尿妊娠试验排除已有妊娠。结果:IUD组经产妇高于LNG组(P<0.05),紧急避孕距性生活的时间及其它一般情况两组无差别;IUD组避孕有效率为100％,LNG组为91.40％,两组的实际妊娠数均明显低于预期妊娠数(P<0.05);IUD组在排卵日及其后置器者19.14有点滴出血,但无盆腔炎及大出血的发生。LNG组18％有恶心等副作用但不需处理,其中有36.36％妇女有月经延迟现象,无需特殊处理。讨论:本文提示含铜IUD用于紧急避孕安全有效,最好在性生活5日内放置,且可以长期避孕。对于未产妇和有生殖器炎症放置IUD禁忌者可建议口服LNG等紧急避孕药物。     

Postcoital treatment with levonorgestrel does not disrupt postfertilization events in the rat

Levonorgestrel (LNG), a progestin widely used for regular hormonal contraception, is also used for emergency contraception (EC) to prevent pregnancy after unprotected intercourse. However, its mode of action in EC is only partially understood. One unresolved question is whether or not EC prevents pregnancy by interfering with postfertilization events. Here, we report the effects of acute treatment with LNG upon ovulation, fertilization and implantation in the rat. LNG inhibited ovulation totally or partially, depending on the timing of treatment and/or total dose administered, whereas it had no effect on fertilization or implantation when it was administered shortly before or after mating, or before implantation. It is concluded that acute postcoital administration of LNG at doses several-fold higher than those used for EC in women, which are able to inhibit ovulation, had no postfertilization effect that impairs fertility in the rat.     

Can we identify women at risk of pregnancy despite using emergency contraception? Data from randomized trials of ulipristal acetate and levonorgestrel

Background

Emergency contraception (EC) does not always work. Clinicians should be aware of potential risk factors for EC failure.

Study Design

Data from a meta-analysis of two randomized controlled trials comparing the efficacy of ulipristal acetate (UPA) with levonorgestrel were analyzed to identify factors associated with EC failure.

Results

The risk of pregnancy was more than threefold greater for obese women compared with women with normal body mass index (odds ratio (OR), 3.60; 95% confidence interval (CI), 1.96–6.53; p<.0001), whichever EC was taken. However, for obese women, the risk was greater for those taking levonorgestrel (OR, 4.41; 95% CI, 2.05–9.44, p=.0002) than for UPA users (OR, 2.62; 95% CI, 0.89–7.00; ns). For both ECs, pregnancy risk was related to the cycle day of intercourse. Women who had intercourse the day before estimated day of ovulation had a fourfold increased risk of pregnancy (OR, 4.42; 95% CI, 2.33–8.20; p<.0001) compared with women having sex outside the fertile window. For both methods, women who had unprotected intercourse after using EC were more likely to get pregnant than those who did not (OR, 4.64; 95% CI, 2.22–8.96; p=.0002).

Conclusions

Women who have intercourse around ovulation should ideally be offered a copper intrauterine device. Women with body mass index >25 kg/m² should be offered an intrauterine device or UPA. All women should be advised to start effective contraception immediately after EC.     

Investigation of factors affecting pregnancy rate after embryo transfer in the dromedary camel

The uteri of 36 adult dromedary camels were flushed non-surgically three times each with 90-120 mL of embryo flushing medium 7 days after ovulation. A total of 242 embryos were recovered, of which 139 were transferred non-surgically to recipient camels that were either at different levels of synchrony with respect to the Day 7 donor (+1 to -3 days; n = 58), or were at Day 6 after ovulation, but received one of the following treatments: (i) none (controls, n = 15); (ii) 150 mg progesterone-in-oil injected intramuscularly once daily during Days 5-20 after ovulation inclusive (n = 16); (iii) 500 mg flunixin meglumine given intravenously 15 min before transfer of the embryo (n = 6); (iv) 20 microg of the gonadotrophin-releasing hormone (GnRH) analogue buserelin given on Day 5 after ovulation (n = 12); or (v) the embryo was cooled to 4 degrees C and held at this temperature in an insulated container for 24 h before being transferred (n = 32). Jugular vein blood samples, taken daily from all the recipient camels during Days 0-20 after ovulation, were assayed for progesterone concentration and closely timed serial samples taken from the camels receiving flunixin meglumine or GnRH were assayed for 13,14-dihydro-15-keto prostaglandin F2alpha (PGFM) or oestradiol concentrations. The pregnancy rate increased to a maximum of 67% when ovulation in the recipient was negatively synchronized to have occurred 1 day behind that in the donor, and it fell dramatically when the level of asynchrony between recipient and donor increased to +1 (9%) or -3 (10%) days. It was not improved by daily injections of progesterone (44%), flunixin meglumine given before transfer (16%), or GnRH given on Day 5 (33%). Of the 32 embryos that were cooled to 4 degrees C before being transferred to Day 6 recipients, 20 resulted in pregnancies (63%) to give a success rate similar to that attained with the control fresh embryos (67%). Serum progesterone concentrations in the recipients increased to a mean +/- SEM of 2.6 +/- 0.8 ng mL(-1) by Day 8 after ovulation and, in those that were pregnant, levels remained elevated at 3-5 ng mL(-1) for the remainder of the sampling period; in non-pregnant recipients the concentrations declined to <1 ng mL(-1) by Day 11. Plasma PGFM concentrations in the flunixin meglumine-treated camels remained low (40-90 pg mL(-1)) compared with those in the untreated control camels, in which peak values of around 180 pg mL(-1) were reached within 10 min after transfer after which a steady decline occurred until resting concentrations of 90-100 pg mL(-1) were reached by 110 min after transfer. Treatment with GnRH on Day 5 after ovulation produced a transitory increase in serum oestradiol-17beta concentrations for 24 h. However, from Day 8, oestradiol concentrations in both the GnRH-treated and the untreated camels increased steadily to reach 2.5-3.5 pg mL(-1) by Day 12.     

The ovulation method of family planning

The ovulation method of family planning relies on self-recognition of physiological changes occuring around time of ovulation rather than a calendar to enable a couple to avoid sexual intercourse during the fertile period. The most practical signs are elevated basal body temperature, changes in the amount and physicochemical properties of cervical mucus, and ovulation pain. The basal body temperature rises about .3 degrees C following ovulation. The problem with this method is that it is retrospective. The mucus symptoms, as described by Billings and associates in Melbourne, Australia, are: 1) a variable number of days with no vaginal discharge following menstrual bleeding; 2) onset of mucus symptoms characterized by increasing quantities of 'cloudy' or 'sticky' secretion; 3) a clear, slippery lubricative mucus having the characteristics of raw white of egg (spinnbarkeit), which is an immediate forwarning of ovulation; 4) a variable period of thick, opaque, diminished volume discharge followed by dry days. The clear 'peak symptom' mucus lasts 1-2 days; in a study of 22 women followed for 27 cycles this symptom occurred .9 days +3 or -2 days before ovulation. The problem is that 2 of the 22 cycles reported in detail had ovulation 3 days after the peak symptom and 1 had ovulation 4 days after. Intercourse on the 4th day, therefore, would have had a significant risk of pregnancy. Weissman and associates collected data on 282 women on the Pacific island of Tonga who used the mucus symptoms alone to control conception. In the 2503 cycles there were 53 unplanned pregnancies, 25.4 per 100 woman-years using the Pearl formula. 50 resulted from the couples 'taking a chance,' 2 misunderstood the method, 28 abandoned the method because they wanted more children, and 1 woman became pregnant even though she thought she understood the method. Field trials with groups who are more motivated than those in the Tongan trial are needed.     

Estimating the efficacy of emergency contraception--how reliable are the data?

Ninety-four women attending a family planning clinic for emergency contraception (EC) were asked how certain they were of the date of their last menstrual period (LMP), of the timing of intercourse, and how many times in the cycle they had had sex. Urinary pregnanediol concentrations were analyzed in 64 women to assess whether they had ovulated before they used EC. Forty-five women were certain of the date of the LMP, the rest were not. Only four women could not accurately recall the timing of intercourse, and 60% had had intercourse more than once in the cycle. Twenty-one women had urinary pregnanediol concentrations that were inconsistent with their cycle day. Calculations of the efficacy of EC depend on knowing the timing of intercourse in relation to the estimated day of ovulation. The results of this study suggest that these calculations are likely to be inaccurate for a significant minority of women.     

The effects of peri-ovulatory administration of levonorgestrel on the menstrual cycle

Levonorgestrel (LNG) 0.75 mg administered 12 h apart within 72 h of unprotected coitus, is an established method of emergency contraception (EC). The mechanism of action of LNG used in this manner is unknown. We administered LNG 0.75 mg twice immediately before ovulation, to test the hypothesis that LNG acts as an emergency contraceptive by abolishing the pre-ovulatory lutenizing hormone (LH) surge and thereby delaying ovulation. Twelve women took LNG on or before the day of the first significant rise in urinary LH in 12 cycles. In four women, the LH peak and the onset of next menses were significantly delayed (delay of 16.8 days (SD +/- 8.7) from the day of mean LH peak in placebo cycles). One woman did not ovulate at all, despite a normal LH peak and cycle length. In the remaining eight women, LNG did not affect ovulation or the cycle length, but the length of the luteal phase and the total luteal phase LH concentrations were significantly reduced. We suggest that LNG acts as an emergency contraceptive by other mechanisms as well as delaying the LH surge and interfering with ovulation.     

Embryo transfer in the dromedary camel (Camelus dromedarius) using asynchronous, meclofenamic acid-treated recipients

A total of 40 (Day 7) embryos were recovered from the uteri of 10 superovulated camels. Recipient camels (n = 30) were prepared by injection with 20 (1/4)g of the gonadotrophin-releasing hormone analogue buserelin (i.v.) to induce ovulation and then treatment with 1 g meclofenamic acid (a prostaglandin synthetase inhibitor), orally, once on Day 7 and twice daily on Days 8 and 9 after ovulation and thereafter at a dose of 1 g day(-1) until 8 days after embryo transfer. Embryos were transferred into recipients on Day 8 (n = 10), Day 10 (n = 10) or Day 12 (n = 10) after ovulation and another 10 embryos were transferred into untreated recipients on Day 8 after ovulation as controls. In addition, serum samples from all recipient camels were recovered daily throughout the period of meclofenamic acid administration and for a further 7 days after treatment had ceased and were assayed for progesterone concentrations. Results showed that whereas only one of 10 of the control group of recipients (10%) was diagnosed pregnant, a total of eight of 10 Day 8 (80%), six of 10 Day 10 (60%) and seven of 10 Day 12 (70%) recipients were diagnosed pregnant by ultrasonography 12 days after the embryo had been transferred. Subsequently, however, four pregnancies were lost when the conceptus was aged between 22 and 60 days, but this is not considered above the early fetal mortality rate expected in camels after natural mating or after transferring camel embryos to untreated recipients. Serum progesterone concentrations remained elevated, above 2 ng mL(-1), throughout the period of meclofenamic acid administration in all recipient camels; thereafter, concentrations remained above 2 ng mL(-1) in pregnant animals, whereas in non-pregnant camels concentrations had declined to baseline values (<1 ng mL(-1)) within 3 days of the end of the treatment period. In conclusion, treatment of recipient camels with meclofenamic acid reduced the need for tightly timed synchrony between donor and recipient because pregnancies were established in recipients that had ovulated as much as 5 days ahead of the donor.     

米非司酮用于排卵期房事后避孕的子宫内膜形态学观察

为了解米非司酮用于排卵期房事后避孕引起的子宫内膜形态学改变,选择21名健康育龄妇女做为受试者,于排卵后72小时内口服300mg米非司酮。排卵后7～8天取内膜做常规光镜下观察。结果发现所有内膜改变都与原周期时相不同步。说明排卵后服用米非司酮使内膜所发生的形态学改变足以防止胚胎种植,故可作为一月一次排卵期房事后有效的避孕药物。     

左旋18-甲基炔诺酮用于紧急避孕的效果与不良反应评价

目的和方法:对100例月经规律,未避孕或避孕措施失败性交后72小时内的妇女,口服左旋18-甲基炔诺酮(LNG),观察避孕效果与不良反应,并以50例妇女应用紧急避孕的经典方法Yuzpe法作对照。结果:LNG组2例妊娠,Yuzpe组1例妊娠,按Wilcox方法推算,避孕有效率分别为83％和82％,但LNG组的不良反应明显降低,P<0.001,优于经典的Yuzpe法。结论:推广使用LNG法将有利于减少非意愿妊娠,保障妇女身心健康。     

Estimating the effectiveness of emergency contraceptive pills

OBJECTIVE: We use new estimates of conception probabilities by cycle day of intercourse, where cycle day is measured with day 1 being the first day of bleeding in a cycle, to propose a new approach for estimating the effectiveness of emergency contraceptive pills (ECPs). We use this new approach to examine the absolute effectiveness and the cost-effectiveness of ECPs and whether ECPs are more effective the sooner after unprotected intercourse they are initiated. METHODS: Using the new set of conception probabilities, we employ data from two recent clinical trials of ECPs, one from the Population Council and the other from the World Health Organization (WHO), to examine the effectiveness of the combined ECP regimen. RESULTS: The expected pregnancy rate among typical users was 6.2% in the Population Council trial and 7.4% in the WHO trial based on conception probabilities by cycle day relative to the day of ovulation. Based on conception probabilities by cycle day relative to the first day of bleeding, the expected pregnancy rates dropped to 5.4% and 5.2%, respectively. The two trials yield conflicting evidence regarding whether effectiveness declines with treatment delay. CONCLUSIONS: Our results suggest that the absolute levels of effectiveness for the Yuzpe regimen of emergency contraception and the cost-effectiveness of this regimen have probably been overstated when based on conception probabilities by cycle day relative to day of ovulation.     

A single-arm study to evaluate the efficacy,safety and acceptability of pericoital oral contraception with levonorgestrel

Background

An oral dose of 0.75 mg levonorgestrel (LNG) taken shortly after sex was marketed as a routine, nonemergency contraceptive method until the 1990s. Because a hormonal method used only at the time of intercourse may be desirable for women who have infrequent sex, we conducted a study to reevaluate the potential of pericoital LNG as a primary means of contraception.

Methods

We enrolled women aged 18–45 years in Brazil and the USA who expected to have sex 1–4 days per month for 6.5 months. Participants were instructed to take one tablet 0.75 mg LNG within 24 h before or after sex, with no more than one dose in any 24-h period. The primary efficacy measure was the Pearl Index among women aged 18–35 years.

Results

The study was stopped after 72 of the planned 300 participants were enrolled due to slow recruitment and related feasibility considerations. In the primary analysis, three pregnancies occurred during 13.4 woman-years of follow-up, resulting in a Pearl Index of 22.4 (95% confidence interval, 4.6–65.4). No serious adverse events were reported, and vaginal bleeding patterns were generally acceptable.

Conclusions

Our estimated Pearl Index was noticeably higher than expected from previous research of LNG for pericoital contraception. Although the regimen was safe and generally acceptable, the study was challenged by slow enrollment and curtailed person-years of follow-up, resulting in poor precision for the estimated treatment effect. Future research may inform whether our results are symptomatic of the regimen, study design or characteristics of the populations from which we recruited.

Implications

Our study failed to confirm prior data suggesting that 0.75 mg LNG for pericoital contraception could be more effective than typical use of barrier methods among women having infrequent sex. Characterizing populations most likely to adhere to, and benefit from, pericoital regimens is essential to future research on these methods.