By Rebecca H. Allen, MD, MPH, Editor
SYNOPSIS: In this prospective cohort study of 461 women, there was no association between intrauterine device use and time to conception (hazard ratio, 1.25; 95% confidence interval, 0.99-1.58). However, past Mycoplasma genitalium infection was found to be associated with longer times to conception and lower conception rates by 12 months (68% vs. 80%, P = 0.02).
SOURCE: Peipert JF, Zhao Q, Schreiber C, et al. Intrauterine device use, sexually transmitted infections, and fertility: A prospective cohort study. Am J Obstet Gynecol 2021; Mar 10. doi: 10.1016/j.ajog.2021.03.011. [Online ahead of print].
In the past, intrauterine devices (IUDs) were falsely associated with pelvic inflammatory disease and infertility. The authors of this study sought to determine if there was an association between the types of IUDs used currently and time to conception, after controlling for sexually transmitted infections (STIs). This was a multicenter, prospective cohort study in the United States that enrolled patients discontinuing the IUD (either copper T380A or levonorgestrel 52 mg), subdermal etonogestrel implant, oral contraceptive pills, contraceptive patch or vaginal ring, depot medroxyprogesterone acetate (DMPA), or barrier method of contraception. Inclusion criteria were women who were age 18 to 35 years, English- or Spanish-speaking, desiring conception, sexually active with a male partner, and who had stopped contraception in the past 120 days. Patients were excluded if they were pregnant, sterile, had a history of infertility, or if they used DMPA in the past five months, since DMPA can be associated with a longer return to fertility. Data included reproductive and medical history, whether they had ever used an IUD in the past, and socioeconomic status. Vaginal swabs were collected for Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, and Trichomonas vaginalis. Serum was collected for evidence of past infection of C. trachomatis, M. genitalium, and T. vaginalis. Participants were followed up by phone at six, 12, 18, and 24 months after enrollment to inquire about pregnancy, menstrual cycle regularity, and frequency and timing of intercourse.
The investigators enrolled 498 women and 461 had available follow-up data for at least six months. A total of 275 women (60%) had ever used an IUD before and most of those (> 85%) stopped using their IUD recently to attempt conception. Women who had used an IUD before were more likely to be slightly older (age 28.6 years vs. 27.5 years) and had a previous pregnancy (72% vs. 46%), but there were no other significant differences between the two groups in terms of body mass index (BMI), race, marital status, socioeconomic status, and history of Chlamydia, Mycoplasma, or Trichomonas infection.
The rates of current infection were N. gonorrhoeae, 0.2%; C. trachomatis, 4.3%; T. vaginalis, 7.6%; and M. genitalium, 9.1%. The rate of women with a past infection with either C. trachomatis, T. vaginalis, or M. genitalium was 42.8%. The most frequent past infection was with M. genitalium (33%). The median time from stopping contraceptive use to conception was 6.1 months (95% confidence interval [CI], 4.9-7.3) and 76.5% of women conceived by 12 months. In a multivariable model, older age, lower socioeconomic status, nulligravidity, Black race, and positive serology for M. genitalium infection all were significantly associated with a longer time to conceive. Past M. genitalium infection was associated with lower conception rates by 12 months (68% vs. 80%, P = 0.02). Being married or having a cohabitating partner was associated with a shorter time to conceive (hazard ratio [HR], 1.59; 95% CI, 1.13-2.24). Previous use of an IUD did not meet the cutoff for significance (HR, 1.25; 95% CI, 0.99-1.58).
COMMENTARY
Since the episode of the Dalkon Shield IUD in the 1970s, providers and patients have had concerns that IUDs could be related to infertility.1 The current IUDs on the market in the United States are safe and effective. A study by Hubacher et al in 2001 showed that the copper T380A was not associated with an increased risk of tubal factor infertility; rather, past infection with C. trachomatis was the culprit.2 A recent analysis of the levonorgestrel 52-mg IUD (Liletta) showed normal conception rates after discontinuation. In this study, among 165 women who attempted to conceive, 142 (86.1%) were able to become pregnant within 12 months, with a median time to conception of 92 days. However, there have been no large, prospective cohort studies evaluating this issue. The current study adds more evidence that IUD use is not associated with longer times to conception compared to other contraceptive methods. The authors wisely evaluated the influence of STIs on time to conception and found that M. genitalium particularly was influential. Infertility rates (failure to conceive in one year) were higher than normal in this study, but the authors attributed that to the study population they enrolled, which had higher proportions of women of lower socioeconomic status and with higher rates of STIs. STIs are known to be a risk factor for tubal infertility.
The strengths of the study include a multicenter cohort followed prospectively, with 95% of conceptions dated accurately. The limitations are subject recall as to exactly when contraceptives were stopped and attempts to conceive started, and the inability to analyze duration of IUD use.
The role of M. genitalium in infertility is unclear and more research is needed. First discovered in the 1980s, M. genitalium is sexually transmitted, is known to cause non-gonococcal urethritis in men, and is associated with cervicitis and pelvic inflammatory disease (PID) in women.3 Screening for M. genitalium among asymptomatic individuals currently is not recommended in the United States. Nucleic acid amplification tests are available for testing. Nevertheless, at least in our practice, it is not a routine test that is performed in the evaluation of women with cervicitis and PID, and it is not available in our laboratory. The Centers for Disease Control and Prevention’s Sexually Transmitted Disease Treatment Guidelines from 2015 added a discussion of M. genitalium to its “Emerging Issues” section.4 Currently, testing and treatment of M. genitalium is suggested for cases in which patients fail the standard treatments for cervicitis and PID and have persistent symptoms. The best antibiotic to target M. genitalium appears to be moxifloxacin 400 mg orally for seven to 14 days. It remains to be seen whether M. genitalium will be part of routine STI testing in the future. However, at the very least, we can say that IUDs do not cause infertility.
REFERENCES
- Boonstra H, Duran V, Northington Gamble V, et al. The “boom and bust phenomenon”: The hopes, dreams, and broken promises of the contraceptive revolution. Contraception 2000;61:9-25.
- Hubacher D, Lara-Ricalde R, Taylor DJ, et al. Use of copper intrauterine devices and the risk of tubal infertility among nulligravid women. N Engl J Med 2001;345:561-567.
- Carr BR, Thomas MA, Gangestad A, et al. Conception rates in women desiring pregnancy after levonorgestrel 52 mg intrauterine system (Liletta®) discontinuation. Contraception 2021;103:26-31.
- Workowski KA, Bolan GA, Centers for Disease Control and Prevention. Sexually Transmitted Diseases Treatment Guidelines, 2015. MMWR Recomm Rep 2015;64:1-137.
