1. Mycoplasa genitalium in pregnancy
Craig R. Cohen, MD, MPH
Professor, Department of Obstetrics, Gynecology & Reproductive Sciences

2. Epidemiology of M. genitalium
Men associations:
non-GC urethritis (+++)
Women associations (less data):
Associated with cervicitis (++)
PID/endometritis (+)
Tubal factor infertility (serology) (+/-)

3. Prevalence of M. genitalium
20.5% in women in the US (multisite, N=1139)
Risk factors: <21 years and Black race
8.4% in pregnant women in MA (N=100)
<1% in other studies of pregnant women
AC Sena, et al, CID 2018; Averbach SH, et al., IJGO, 2013;

4. Prevalence of Mycoplasmas and Ureoplasma in pregnancy
□, M. hominis; ▪, M. genitalium; ▵, U. parvum; ▴, U. urealyticum; ○, C. trachomatis MG
Kataoka S, et al. J Clin Micro, 2006

5. Incidence of M. genitalium
Kaplan-Meier survival curve for incident M. genitalium infection in a cohort of female sex workers in Nairobi, Kenya
CR Cohen, et al. Sexually Transmitted Diseases 2007

6. Persistence of M. genitalium in women
Duration of M. genitalium in months in a cohort of female sex workers in Nairobi, Kenya. Cervical specimen collected every 2 months
CR Cohen, et al. Sexually Transmitted Diseases 2007

7. Association of M. genitalium and HIV Infection
Overall, individuals infected with M. genitalium were twice as likely to be HIV-seropositive (summary OR = 2.01, 95% CI = 1.44–2.79; Table 2, Fig. 2a). However, there was strong evidence of between-study heterogeneity (P < 0.001) and the summary OR should be interpreted with caution.
Fig. 2 . Odds ratio of HIV infection associated with Mycoplasma genitalium infection in 19 studies. The area of the black square reflects the weight of each trial. Weights are from adjusted (where available and indicated by [a]) or unadjusted effect estimates. The diamonds represent the combined odds ratio and 95% confidence interval using the random-effects model for (a) all studies, (b) sub-Saharan Africa studies, and (c) studies with healthy control populations.
S Napierala Mavedzenge, AIDS. 23(5): , March 13, 2009
© 2009 Lippincott Williams & Wilkins, Inc. Published by Lippincott Williams & Wilkins, Inc. 2

8. Identification of M. genitalium in Women
Upper genital tract
1/123 (<1%) Fallopian tubes in women with acute salpingitis
9/123 (7%) endometrium and/or cervix
Amniotic cavity
0/232 at time of C/S
0/344 asymptomiatic women mid-trimester
Blanchard A, CID, 1993; Rowlands S, AMJOG, 2017; Cohen CR, Sex Trans Dis, 2005

9. M. genitalium Diagnostics
No FDA approved assays
Aptima TMA for M. genitalium
Highly sensitive and specific
Under evaluation for FDA approval

10. Treatment of M. genitalium
Doxycycline
Resistant and contraindicated in pregnancy
Azithromycin
Resistance increasing
US FDA pregnancy category B
Moxifloxacin/Clarithromycin—used for azithromycin resistant cases
US FDA pregnancy category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks
Lefamulin (BC-3781)
Pleuromutilin class of antimicrobials, which has been used for decades in the veterinary industry for infections in pigs
Phase 2 clinical trials—limited safety data in pregnancy

11. Mycoplasmas and Risk of Adverse Outcomes
Condition
M. hominis
Ureaplasma spp.
M. genitalium BV
++++/+
+++/−
+/−
Ectopic Pregnancy
++/+
++/?
Low Birth Weight
++/−
+++/+ ?
PTB
+++/++
Maternal Fever
Neonate Conjunctivitis
−/−
Neonate Resp. Disease
+/?
D Taylor-Robinson, BJOG 2010

12. Association of M. genitalium on Preterm Birth
Although the nearly 2-fold increased risk of preterm delivery in meta-analysis (OR = 1.9; 95% CI = 1.25–2.85) (Figure 1) is lower than the 5–6-fold increase associated with syphilis and gonorrhea [61], it is higher than the 40%–80% increase associated with T. vaginalis and BV [62, 63] and may warrant intervention. However, the relatively low prevalence of M. genitalium in the populations studied to date argues against universal screening of pregnant women. Whether a targeted strategy testing women at high risk of M. genitalium could prevent preterm birth requires prospective clinical trials.
From: Mycoplasma genitalium Infection and Female Reproductive Tract Disease: A Meta-analysis
Clin Infect Dis. 2015;61(3): doi: /cid/civ312
Clin Infect Dis | © The Author Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please

13. Infectious Etiology of Preterm Birth
BV (complicated) (aOR: 2.7; 95% CI: 1.7–4.5)
Leptotrichia/Sneathia (aOR: 9.1; 95% CI: 1.9)
BVAB3: (aOR 0.55; 95% CI: 0.39–0.78)
Treatment studies with mixed results
Trichomonas (OR: 1.3; 95% CI: 1.1–1.4)
Treatment associated with increased risk of PTB
Chlamydia (OR: 2.2; 95% CI: )
Treatment (<20 weeks) associated with decreased risk of PTB
Gonorrhea (aOR: 2.50; 95% CI: 1.39–4.50)
No treatment studies
Put the Mg in context with other infectious etiologies of PTB. Intrauterine infection by known microbes is thought to cause 25% of all PTBs.
Hugh C.G.Nadeau, et al. Seminars Fetal Neonatal Med, 2016

14. Challenges with reducing impact of M. genitalium in women
Diagnosis
Treatment
Reduce Sequelae

15. Possible Research Questions
Does M. genitalium infect the placenta, chorion and/or amnion and cause inflammation?
Does treatment in pregnancy reduce sequelae—and if so in what trimester(s)
What’s the number of Mg cases to diagnose to reduce one case of an adverse pregnancy event?
What antibiotic choice to treat azithromycin resistant cases?
Role for partner treatment to reduce recurrence?

16. Thank You