Is there a preterm placental microbiome?

Results of a UK study show that while intrauterine infection may contribute to preterm birth (PTB), a reproducible “preterm placental microbiome” does not exist. The findings, published in Applied and Environmental Microbiology, are from DNA analysis of placental samples from both PTB and term deliveries.

For the case-control study, the researchers used 16S targeted amplicon sequencing to evaluate differences in placental microbiota in term and PTB deliveries in a large UK pregnancy cohort. DNA was extracted from 400 placental samples from 256 singleton pregnancies and analyzed for bacterial DNA. The samples were from spontaneous preterm births (sPTB), PTB, and term deliveries and most (89%) were from parenchyma, but for a few pregnancies, matching villous tissue also was available.

The authors hypothesized that a distinct microbial profile would be seen in samples from sPTB versus those from term deliveries. What they found was widespread contamination across all placental samples, which implicated both delivery method and reagent contamination. In sequenced reads, 136 contaminating operational taxonomic units (OTUs) from 44 genera were found. Thirty-two of the genera (73%) had previously been reported as reagent contaminants.

After contaminant reads and low-abundance samples were removed from the dataset, the researchers found that Lactobacillus crispatus was the most abundant OTU in the remaining samples, found in 59.4% of them. Eight of the top 20 OTUs in the filtered dataset mapped to the Lactobacillus genus. In placental tissue from vaginal deliveries, Lactobacillus and Bacteroides were the most common genera seen, whereas Streptococcus and Corynebacterium were most abundant in placental tissue from cesarean deliveries.

Six genera were significantly more abundant (P < 0.01) in placental tissue from sPTB versus PTB (Ureaplasma, Prevotella, Salnicoccus, Mycoplasma, Capnocytophaga, Anaerococcus) and 7 genera were more abundant in sPTB versus term samples (Tepidomonas, Salnicoccus, Capnocytophaga, Mycoplasma, Anaerococcus, Truepera, Coprobacillus). After adjustment for delivery method, recruiting hospital, maternal ethnicity, body mass index, smoking and tissue type, 4 genera were significantly more abundant in the tissue from sPTB versus PTB (P < 0.01) (Mycoplasma, Ureaplasma, Mogibacterium, Salnicoccus). A similar difference was found for abundance of 8 genera in sPTB versus term delivery (Anaerococcus, Capnocytophaga, Coprabacillus, Erwinia, Mycoplasma, Salnicoccus, Turicibacter, Tepidimonas).

The authors acknowledged that their study was limited, in that the placental samples were not originally collected for use in microbial analysis. They said theirs is one of the largest cohorts of 16S sequenced placental tissue from SPTB in the literature. Their findings, they believe, “suggest that there may be a low-level non-pathogenic placental microbiome present in many, if not all, placentas. However, differentiating this from organisms picked up at delivery, or during experimental handling is an on-going challenge.” 

Does male depression impact likelihood of pregnancy?

Depression in the male partner of couples being treated for infertility was linked to lower pregnancy chances, according to results of a study published in Fertility and Sterility. The study also found that depression in the female partner did not influence the rate of live birth, but a class of antidepressants known as non-selective serotonin reuptake inhibitors (non-SSRIs) was associated with early pregnancy loss. SSRIs, another class of antidepressants, were not linked to pregnancy loss.

The study included data from two previous studies (Pregnancy in PCOS II [PPCOSII] and Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation [AMIGOS]) funded by National Institute of Child Health and Human Development’s Reproductive Medicine Network. PPCOSII (n=750 couples) compared the effectiveness of two ovulation-inducing drugs for establishment of pregnancy and live birth in women with polycystic ovary syndrome (PCOS). The AMIGOS study (n=900 couples) compared the effectiveness of three ovulation-inducing drugs at achieving pregnancy and live birth in couples struggling with unexplained fertility.

From these studies, the researchers analyzed data for 1650 women and 1608 men. Both of these studies used the Patient Health Questionnaire (PHQ-9) which screened for depression in both men and women, but only women were asked whether they were taking any antidepressants. Depression was classified as PHQ-9 scores of 5, 10, 15, and 20 representing, mild, moderate, moderately severe, and severe, respectively. In this study, PHQ-9 scores of ≥ 10 were classified as active major depression. The primary outcome was live birth and secondary outcomes of interest included pregnancy and first-trimester pregnancy loss, defined as cessation of pregnancy up to 13 weeks’ gestation.

When the researchers stratified the data by study and thus diagnosis, (PCOSII or AMIGOS, i.e., PCOS vs. unexplained fertility) there was a highly significant difference in the prevalence of currently active major depression among female subjects (11.02% vs. 1.63%, respectively, P < .001). The researchers found that, among women not using an antidepressant, presence of active major depression was not associated with poorer fertility outcomes, but was instead associated with a slightly increased likelihood of pregnancy (RR 1.38, 95% CI 1.07-1.78). In addition, in women without currently active major depression, antidepressant use was associated with a slightly increased likelihood of first-trimester loss (RR 1.87, 95% CI 1.18-2.99). Women who used non-SSRIs (n=6) exclusively had an increased risk of first-trimester loss (RR 3.45, 95% CI 1.99-5.98) compared with antidepressant nonuse. Women who used only SSRIs did not have a statistically significant live birth or pregnancy rate or increased first trimester loss.  

In male participants, those with currently active major depression (n=34) were less likely to have a partner achieve conception (RR 0.44, 95% CI 0.20-0.98). Between the two included studies, the pregnancy rates for men with active major depression differed (10.5% vs. 20% in AMIGOS and PPCOSII, respectively). In addition, sensitivity analysis showed that the worse the male depression, the worse the fertility treatment outcome.

The authors note a few strengths and limitations to their study. This was a secondary analysis of two randomized controlled trials that included different populations of subjects. However, they believe that these results potentially make them more generalizable. There was also limited information available on nonpharmacologic treatments for depression being used by the participants–by both males and females. The recognized strengths of the study were the use of two multicenter studies, large sample sizes, prospective collection of outcomes after assessment of major depression at baseline, and availability of data for both partners. The researchers suggest further studies to confirm their results, especially in regard to the findings on non-SSRI antidepressants.