Maternal antidepressant use associated with increased risk of miscarriage

Major depression, antidepressant use, and male and female fertility : Cohort study

2018 Study Abstract

Objective
To determine if maternal major depression (MD), antidepressant use, or paternal MD are associated with pregnancy outcomes after non-IVF fertility treatments.

Design
Cohort study, DOI: https://doi.org/10.1016/j.fertnstert.2018.01.029, May 2018.

Setting
Clinics.

Patient(s)
Participants in two randomized trials: PPCOS II (clomiphene citrate versus letrozole for polycystic ovary syndrome), and AMIGOS (gonadotropins versus clomiphene citrate versus letrozole for unexplained infertility).

Intervention(s)
Female and male partners completed the Patient Health Questionnaire (PHQ-9). Female medication use was collected. PHQ-9 score ≥10 was used to define currently active MD.

Main Outcome Measure(s)
Primary outcome: live birth. Secondary outcomes: pregnancy, first-trimester miscarriage. Poisson regression models were used to determine relative risks after adjusting for age, race, income, months trying to conceive, smoking, and study (PPCOS II versus AMIGOS).

Result(s)
Data for 1,650 women and 1,608 men were included. Among women not using an antidepressant, the presence of currently active MD was not associated with poorer fertility outcomes (live birth, miscarriage), but rather was associated with a slightly increased likelihood of pregnancy. Maternal antidepressant use (n = 90) was associated with increased risk of miscarriage, and male partners with currently active MD were less likely to achieve conception.

Conclusion(s)
Currently active MD in the female partner does not negatively affect non-IVF treatment outcomes; however, currently active MD in the male partner may lower the likelihood of pregnancy. Maternal antidepressant use is associated with first-trimester pregnancy loss, which may depend upon the type of antidepressant.

Ambient air pollution and the risk of pregnancy loss

A prospective cohort study, January 2018

2018 Study Abstract

Objective
To estimate the association of pregnancy loss with common air pollutant exposure. Ambient air pollution exposure has been linked to adverse pregnancy outcomes, but few studies have investigated its relationship with pregnancy loss.

Design
Prospective cohort study.

Setting
Not applicable.

Patient(s)
A total of 343 singleton pregnancies in a multisite prospective cohort study with detailed protocols for ovulation and pregnancy testing.

Intervention(s)
None.

Main Outcome Measure(s)
Timing of incident pregnancy loss (from ovulation).

Result(s)
The incidence of pregnancy loss was 28% (n = 98). Pollutant levels at women’s residences were estimated using modified Community Multiscale Air Quality models and averaged during the past 2 weeks (acute) and the whole pregnancy (chronic). Adjusted Cox proportional hazards models showed that an interquartile range increase in average whole pregnancy ozone (hazard ratio [HR] 1.12, 95% confidence interval [CI] 1.07–1.17) and particulate matter <2.5 μm (HR 1.13, 95% CI 1.03–1.24) concentrations were associated with faster time to pregnancy loss. Sulfate compounds also appeared to increase risk (HR 1.58, 95% CI 1.07–2.34). Last 2 weeks of exposures were not associated with loss.

Conclusion(s)
In a prospective cohort of couples trying to conceive, we found evidence that exposure to air pollution throughout pregnancy was associated with loss, but delineating specific periods of heightened vulnerability await larger preconception cohort studies with daily measured air quality.

One particular flu vaccine linked with early miscarriages

Association of spontaneous abortion with receipt of inactivated influenza vaccine containing H1N1pdm09 in 2010–11 and 2011–12

A study, funded by the Centers for Disease Control and Prevention, found that women who had received an influenza vaccine containing the 2009 pandemic strain pH1N1 and who were also vaccinated in the next flu season had a statistically significant, 7.7-fold higher odds of spontaneous abortion within 28 days of the second vaccination. Image credit @rich_hurley.

2017 Study Abstract

Introduction
Inactivated influenza vaccine is recommended in any stage of pregnancy, but evidence of safety in early pregnancy is limited, including for vaccines containing A/H1N1pdm2009 (pH1N1) antigen. We sought to determine if receipt of vaccine containing pH1N1 was associated with spontaneous abortion (SAB).

Methods
We conducted a case-control study over two influenza seasons (2010–11, 2011–12) in the Vaccine Safety Datalink. Cases had SAB and controls had live births or stillbirths and were matched on site, date of last menstrual period, and age. Of 919 potential cases identified using diagnosis codes, 485 were eligible and confirmed by medical record review. Exposure was defined as vaccination with inactivated influenza vaccine before the SAB date; the primary exposure window was the 1–28 days before the SAB.

Results
The overall adjusted odds ratio (aOR) was 2.0 (95% CI, 1.1–3.6) for vaccine receipt in the 28-day exposure window; there was no association in other exposure windows. In season-specific analyses, the aOR in the 1–28 days was 3.7 (95% CI 1.4–9.4) in 2010–11 and 1.4 (95% CI 0.6–3.3) in 2011–12. The association was modified by influenza vaccination in the prior season (post hoc analysis). Among women who received pH1N1-containing vaccine in the previous influenza season, the aOR in the 1–28 days was 7.7 (95% CI 2.2–27.3); the aOR was 1.3 (95% CI 0.7–2.7) among women not vaccinated in the previous season. This effect modification was observed in each season.

Conclusion
SAB was associated with influenza vaccination in the preceding 28 days. The association was significant only among women vaccinated in the previous influenza season with pH1N1-containing vaccine. This study does not and cannot establish a causal relationship between repeated influenza vaccination and SAB, but further research is warranted.

Petites-filles DES : malformations utérines, fertilité, reproduction

Professeur Michel Tournaire, Réseau DES France, Forum d’Infertilité 2017

Vidéos en français: Distilbène DES : 60 vidéos à visionner sur YouTube.

Le troisième génération de victimes du médicament Distilbène® arrive aujourd’hui en âge de procréer.

Qu’en est-il au niveau de leur fertilité et risques supplémentaires en cas de grossesse ?

Le Professeur Michel Tournaire, membre du Conseil Scientifique de Réseau DES France, présente de nouveaux résultats de l’étude Distilbène 3 générations :

  • petites filles DES : malformations utérines.
  • petites filles DES : fertilité et reproduction.

Enregistrement provenant de la 4ème Journée Nationale de l’Infertilité, un forum d’information et d’aide aux personnes infertiles organisé cet automne 2017, Paris 12.

Le Distilbène DES, en savoir plus

Ambient air pollution and the risk of pregnancy loss

Air pollution exposure in early pregnancy linked to miscarriage

Exposure to common air pollutants, such as ozone and fine particles, may increase the risk of early pregnancy loss, according to a new study.

2017 Study Abstract

Objective
To estimate the association of pregnancy loss with common air pollutant exposure. Ambient air pollution exposure has been linked to adverse pregnancy outcomes, but few studies have investigated its relationship with pregnancy loss.

Design
Prospective cohort study.

Setting
Not applicable.

Patient(s)
A total of 343 singleton pregnancies in a multisite prospective cohort study with detailed protocols for ovulation and pregnancy testing.

Intervention(s)
None.

Main Outcome Measure(s)
Timing of incident pregnancy loss (from ovulation).

Result(s)
The incidence of pregnancy loss was 28% (n = 98). Pollutant levels at women’s residences were estimated using modified Community Multiscale Air Quality models and averaged during the past 2 weeks (acute) and the whole pregnancy (chronic). Adjusted Cox proportional hazards models showed that an interquartile range increase in average whole pregnancy ozone (hazard ratio [HR] 1.12, 95% confidence interval [CI] 1.07–1.17) and particulate matter <2.5 μm (HR 1.13, 95% CI 1.03–1.24) concentrations were associated with faster time to pregnancy loss. Sulfate compounds also appeared to increase risk (HR 1.58, 95% CI 1.07–2.34). Last 2 weeks of exposures were not associated with loss.

Conclusion(s)
In a prospective cohort of couples trying to conceive, we found evidence that exposure to air pollution throughout pregnancy was associated with loss, but delineating specific periods of heightened vulnerability await larger preconception cohort studies with daily measured air quality.

More Information

  • Ambient air pollution and the risk of pregnancy loss: a prospective cohort study, Fertility and Sterility, dx.doi.org/10.1016/j.fertnstert.2017.09.037, November 16, 2017.
  • Air pollution exposure in early pregnancy linked to miscarriage, NIH study suggests, National Institutes of Health, news-releases, November 16, 2017.
  • Pregnancy loss featured image credit Heather Kittredge

Endometriosis, especially mild disease : a risk factor for miscarriages

Prenatal exposure to estrogenic substances (such as DES) and environmental toxins (such as bisphenols) may increase the incidence of endometriosis in female offspring

2017 Study Abstract

Objective
To investigate the prevalence of miscarriage in women with endometriosis (WwE) compared with disease-free control women (CW).

Design
Cross-sectional analysis nested in a retrospective observational study (n = 940).

Setting
Hospitals and associated private practices.

Patient(s)
Previously pregnant women (n = 268) within reproductive age in matched pairs.

Intervention(s)
Retrospective analysis of surgical reports and self-administered questionnaires.

Main Outcome Measure(s)
Rate of miscarriage, subanalysis for fertility status (≤12 vs. >12 months’ time to conception), endometriosis stages (revised American Society of Reproductive Medicine classification [rASRM] I/II vs. III/IV) and phenotypic localizations (superficial peritoneal, ovarian, and deep infiltrating endometriosis).

Result(s)
The miscarriage rate was higher in WwE (35.8% [95% confidence interval 29.6%–42.0%]) compared with CW (22.0% [16.7%–27.0%]); adjusted incidence risk ratio of 1.97 (95% CI 1.41–2.75). This remained significant in subfertile WwE (50.0% [40.7%–59.4%]) vs. CW (25.8% [8.5%–41.2%]) but not in fertile WwE (24.5% [16.3%–31.6%]) vs. CW (21.5% [15.9%–26.8%]). The miscarriage rate was higher in women with milder forms (rASRM I/II 42.1% [32.6%–51.4%] vs. rASRM III/IV 30.8% [22.6%–38.7%], compared with 22.0% [16.7%–27.0%] in CW), and in women with superficial peritoneal endometriosis (42.0% [32.0%–53.9%]) compared with ovarian endometriosis (28.6% [17.7%–38.7%]) and deep infiltrating endometriosis (33.9% [21.2%–46.0%]) compared with CW (22.0% [16.7%–27.0%]).

Conclusion(s)
Mild endometriosis, as in superficial lesions, is related to a great extent of inflammatory disorder, possibly leading to defective folliculogenesis, fertilization, and/or implantation, presenting as increased risk of miscarriage.

Genetic Associations with Gestational Duration and Spontaneous Preterm Birth

Massachusetts Medical Society, NEJM, 2017

Abstract

BACKGROUND
Despite evidence that genetic factors contribute to the duration of gestation and the risk of preterm birth, robust associations with genetic variants have not been identified. We used large data sets that included the gestational duration to determine possible genetic associations.

METHODS
We performed a genomewide association study in a discovery set of samples obtained from 43,568 women of European ancestry using gestational duration as a continuous trait and term or preterm (<37 weeks) birth as a dichotomous outcome. We used samples from three Nordic data sets (involving a total of 8643 women) to test for replication of genomic loci that had significant genomewide association (P<5.0×10−8) or an association with suggestive significance (P<1.0×10−6) in the discovery set.

RESULTS
In the discovery and replication data sets, four loci (EBF1, EEFSEC, AGTR2, and WNT4) were significantly associated with gestational duration. Functional analysis showed that an implicated variant in WNT4 alters the binding of the estrogen receptor. The association between variants in ADCY5 and RAP2C and gestational duration had suggestive significance in the discovery set and significant evidence of association in the replication sets; these variants also showed genomewide significance in a joint analysis. Common variants in EBF1, EEFSEC, and AGTR2 showed association with preterm birth with genomewide significance. An analysis of mother–infant dyads suggested that these variants act at the level of the maternal genome.

CONCLUSIONS
In this genomewide association study, we found that variants at the EBF1, EEFSEC, AGTR2, WNT4, ADCY5, and RAP2C loci were associated with gestational duration and variants at the EBF1, EEFSEC, and AGTR2 loci with preterm birth. Previously established roles of these genes in uterine development, maternal nutrition, and vascular control support their mechanistic involvement. (Funded by the March of Dimes and others.)

Could taking Vitamin B3 prevent miscarriages and birth defects ?

Claims that niacin prevents miscarriages in humans grossly exaggerated

The “blockbuster breakthrough to prevent birth defects and miscarriages” releaseHistoric Discovery Promises to Prevent Miscarriages and Birth Defects Globally – describes a “double discovery” made by researchers at the Victor Chang Cardiac Research Institute in Australia that, theoretically, will greatly reduce the number of birth defects and miscarriages worldwide.

The premise rests on the discovery that genetic mutations causing a deficiency in one type of molecule (Nicotinamide adenine dinucleotide, or NAD) can lead to birth defects in humans. The researchers then tested the impact of vitamin B3 (or niacin) supplements on mouse models engineered to have the same mutations who were deficient in NAD. They found that the mice who had higher levels of niacin were less likely to have offspring with birth defects.

The news release hid the fact that the vitamin supplements (referring only to “preclinical models”) were tested in mice, and not humans. But most worrying was the use of extremely sensationalist language prevalent throughout the release. The language was so overblown that it could give false hope to women without properly describing the limits of the research.

continue reading Claims that niacin prevents miscarriages in humans grossly exaggerated, healthnewsreview, August 14, 2017.

  • NAD Deficiency, Congenital Malformations, and Niacin Supplementation, N Engl J Med 2017; 377:544-552, DOI: 10.1056/NEJMoa1616361, August 10, 2017.
  • Vitamin profile of 563 gravidas during trimesters of pregnancy, Journal of the American College of Nutrition, NCBI PubMed PMID: 11838885, 2002 Feb.
  • Featured image credit @HealthNewsRevu.

Endocrine disrupting chemicals and endometriosis

Endocrine disruptors and reproductive disorders

Abstract

Endometriosis is an estrogen dependent gynecologic disease with lasting implications for many women’s fertility, somatic health, and overall quality of life.

Growing evidence suggests that endocrine disrupting chemicals (EDCs) may be etiologically involved in the development and severity of disease.

We weigh the available human evidence focusing on EDCs and endometriosis, restricting to research that has individually quantified chemical concentrations for women, included a comparison group of unaffected women, and used multivariable analytic techniques.

Endocrine disrupting chemicals and endometriosis, Fertility and Sterility, Volume 106, Issue 4, Pages Pages 959–966, September 15, 2016.

laparoscopic surgery for endometriosis: fuschia_foot.

Evidence supporting an environmental etiology for endometriosis includes metals/trace elements, dioxins, and other persistent organic pollutants, as well as nonpersistent chemicals, such as benzophenones and phthalates.

To address the equivocal findings for various EDCs, future research directions for filling data gaps include

  1. use of integrated clinical and population sampling frameworks allowing for incorporation of new diagnostic modalities;
  2. the collection of various biologic media, including target tissues for quantifying exposures;
  3. study designs that offer various comparison groups to assess potentially shared etiologies with other gynecologic disorders;
  4. and novel laboratory and statistical approaches that fully explore all measured EDCs for the assessment of mixtures and low dose effects and the use of directed acyclic graphs, and supporting causal analysis for empirically delineating relationships between EDCs and endometriosis.

Environmental exposure to endocrine-disrupting chemicals and miscarriage

The role of environmental toxins in reproduction

Abstract

Establishment of early pregnancy is the result of complex biochemical interactions between the decidua and blastocyst.

Any alteration in this chemical dialogue has the potential to result in adverse pregnancy outcomes including miscarriage.

Sporadic miscarriage is the most common complication of pregnancy and can be caused by multiple factors.

While the most common cause of miscarriage is genetic abnormalities in the fetus, other contributing factors certainly can play a role in early loss.

Environmental exposure to endocrine-disrupting chemicals and miscarriage, Fertility and Sterility, Volume 106, Issue 4, Pages Pages 941–947, September 15, 2016.

Miscarriage Tattoo: stacylynn.

One such factor is environmental exposure, in particular to endocrine-disrupting chemicals, which has the potential to interfere with endogenous hormone action.

These effects can be deleterious, especially in early pregnancy when the hormonal milieu surrounding implantation is in delicate balance.

The purpose of this paper is to review the current evidence on the role of environmental toxins in reproduction.