Kohl Schwartz, A. S., Wölfler, M. M., Mitter, V., Rauchfuss, M., Haeberlin, F., Eberhard, M., von Orelli, S., Imthurn, B., Imesch, P., Fink, D., & Leeners, B. (2017). Endometriosis, especially mild disease: a risk factor for miscarriages. Fertility and sterility, 108(5), 806-814.e2. https://doi.org/10.1016/j.fertnstert.2017.08.025
Kohl Schwartz AS, Wölfler MM, Mitter V, Rauchfuss M, Haeberlin F, Eberhard M, et al. Endometriosis, especially mild disease: a risk factor for miscarriages. Fertil Steril. 2017;108(5):806-814.e2. doi:10.1016/j.fertnstert.2017.08.025
Kohl Schwartz, A. S., et al. "Endometriosis, especially mild disease: a risk factor for miscarriages." Fertility and sterility, vol. 108, no. 5, 2017, pp. 806-814.e2.
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Endometriosis linked to more miscarriages, especially mild disease
Women with surgically confirmed endometriosis had more miscarriages than matched women without it, in a cross-sectional study of 143 women in each group who had been pregnant. Miscarriage ended about 36 of 100 pregnancies with endometriosis and 22 of 100 without. The gap held in women with trouble conceiving and grew in mild disease.
Key Findings
Miscarriage rates were 35.8% (95% CI 29.6%–42.0%), 86 of 240 pregnancies, in women with endometriosis and 22.0% (16.7%–27.0%), 59 of 268 pregnancies, in control women.
After adjustment for age, BMI, smoking and subfertility, the incidence rate ratio for miscarriage was 1.97 (95% CI 1.41–2.75) in women with endometriosis versus control women.
Among subfertile women, miscarriage rates were 50.0% (40.7%–59.4%) with endometriosis and 25.8% (8.5%–41.2%) in controls. Among fertile women, they were 24.5% (16.3%–31.6%) and 21.5% (15.9%–26.8%).
Stage I and II disease carried a miscarriage rate of 42.1% (32.6%–51.4%), stage III and IV 30.8% (22.6%–38.7%), and control women 22.0% (16.7%–27.0%).
Three or more miscarriages occurred in 7 of 143 women with endometriosis (4.9%) and 4 of 143 control women (2.8%), P = .874.
Interpretation
Researchers compared women who had been pregnant, with and without endometriosis, using questionnaires and surgery records. The study looks back at past pregnancies in these women, so it can show an association between endometriosis and miscarriage. The authors say a retrospective study cannot definitively prove their hypothesis. Women came from hospitals and private practices in Switzerland, Germany and Austria. Undiagnosed endometriosis in some control women could lead to an overestimate of the difference, the authors write. In this sample, women with endometriosis had fewer births: 152 children against 204 among control women. The authors adjusted for subfertility, meaning trouble conceiving.
RRM Context
Restorative reproductive medicine looks for a cause when a pregnancy ends in miscarriage. The study reports an association of surgically confirmed endometriosis with miscarriage, stronger in mild disease. A Canadian registry study the authors cite found an odds ratio of 1.89 (95% CI 1.23–2.93) in 784 women with endometriosis and 30,284 controls. Its endometriosis diagnoses were of limited quality. The authors discuss inflammation and progesterone resistance as possible mechanisms.
Our editorial summary of this paper, not the article's abstract.
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.
Patients
Previously pregnant women (n = 268) within reproductive age in matched pairs.
Interventions
Retrospective analysis of surgical reports and self-administered questionnaires.
Main Outcome Measures
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).
Results
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%]).
Conclusions
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.
Zhu TY et al., 2021·Journal of medical Internet research·Free full text on PubMed Central
As a daily point measurement, basal body temperature (BBT) might not be able to capture the temperature shift in the menstrual cycle because a single temperature measurement is present on the sliding scale of the circadian rhythm. Wrist skin temperature measured continuously during sleep has the potential to overcome this limitation. This study compares the diagnostic accuracy of these two temperatures for detecting ovulation and to investigate the correlation and agreement between these two temperatures in describing thermal changes in menstrual cycles. This prospective study included 193 cycles (170 ovulatory and 23 anovulatory) collected from 57 healthy women. Participants wore a wearable device (Ava Fertility Tracker bracelet 2.0) that continuously measured the wrist skin temperature during sleep. Daily BBT was measured orally and immediately upon waking up using a computerized fertility tracker with a digital thermometer (Lady-Comp). An at-home luteinizing hormone test was used as the reference standard for ovulation. The diagnostic accuracy of using at least one temperature shift detected by the two temperatures in detecting ovulation was evaluated. For ovulatory cycles, repeated measures correlation was used to examine the correlation between the two temperatures, and mixed effect models were used to determine the agreement between the two temperature curves at different menstrual phases. Wrist skin temperature was more sensitive than BBT (sensitivity 0.62 vs 0.23; P<.001) and had a higher true-positive rate (54.9% vs 20.2%) for detecting ovulation; however, it also had a higher false-positive rate (8.8% vs 3.6%), resulting in lower specificity (0.26 vs 0.70; P=.002). The probability that ovulation occurred when at least one temperature shift was detected was 86.2% for wrist skin temperature and 84.8% for BBT. Both temperatures had low negative predictive values (8.8% for wrist skin temperature and 10.9% for BBT). Significant positive correlation between the two temperatures was only found in the follicular phase (rmcorr correlation coefficient=0.294; P=.001). Both temperatures increased during the postovulatory phase with a greater increase in the wrist skin temperature (range of increase: 0.50 °C vs 0.20 °C). During the menstrual phase, the wrist skin temperature exhibited a greater and more rapid decrease (from 36.13 °C to 35.80 °C) than BBT (from 36.31 °C to 36.27 °C). During the preovulatory phase, there were minimal changes in both temperatures and small variations in the estimated daily difference between the two temperatures, indicating an agreement between the two curves. For women interested in maximizing the chances of pregnancy, wrist skin temperature continuously measured during sleep is more sensitive than BBT for detecting ovulation. The difference in the diagnostic accuracy of these methods was likely attributed to the greater temperature increase in the postovulatory phase and greater temperature decrease during the menstrual phase for the wrist skin temperatures.
Duffy JMN et al., 2020·Human Reproduction·Free full text on PubMed Central
Can a core outcome set to standardize outcome selection, collection and reporting across future infertility research be developed? A minimum data set, known as a core outcome set, has been developed for randomized controlled trials (RCTs) and systematic reviews evaluating potential treatments for infertility. Complex issues, including a failure to consider the perspectives of people with fertility problems when selecting outcomes, variations in outcome definitions and the selective reporting of outcomes on the basis of statistical analysis, make the results of infertility research difficult to interpret. STUDY DESIGN, SIZE, A three-round Delphi survey (372 participants from 41 countries) and consensus development workshop (30 participants from 27 countries). MAIN The core outcome set consists of: viable intrauterine pregnancy confirmed by ultrasound (accounting for singleton, twin and higher multiple pregnancy); pregnancy loss (accounting for ectopic pregnancy, miscarriage, stillbirth and termination of pregnancy); live birth; gestational age at delivery; birthweight; neonatal mortality; and major congenital anomaly. Time to pregnancy leading to live birth should be reported when applicable. Embedding the core outcome set within RCTs and systematic reviews should ensure the comprehensive selection, collection and reporting of core outcomes. Research funding bodies, the SPIRIT statement, and over 80 specialty journals, including Cochrane Gynaecology and Fertility Group, Fertility and Sterility and Human Reproduction, have committed to implementing this core outcome set.
Goodale BM et al., 2019·J Med Internet Res·Free full text on PubMed Central
Previous research examining physiological changes across the menstrual cycle has considered biological responses to shifting hormones in isolation. Clinical studies, for example, have shown that women's nightly basal body temperature increases from 0.28 to 0.56 ˚C following postovulation progesterone production. Women's resting pulse rate, respiratory rate, and heart rate variability (HRV) are similarly elevated in the luteal phase, whereas skin perfusion decreases significantly following the fertile window's closing. Past research probed only 1 or 2 of these physiological features in a given study, requiring participants to come to a laboratory or hospital clinic multiple times throughout their cycle. Although initially designed for recreational purposes, wearable technology could enable more ambulatory studies of physiological changes across the menstrual cycle. Early research suggests that wearables can detect phase-based shifts in pulse rate and wrist skin temperature (WST). To date, previous work has studied these features separately, with the ability of wearables to accurately pinpoint the fertile window using multiple physiological parameters simultaneously yet unknown. In this study, we probed what phase-based differences a wearable bracelet could detect in users' WST, heart rate, HRV, respiratory rate, and skin perfusion. Drawing on insight from artificial intelligence and machine learning, we then sought to develop an algorithm that could identify the fertile window in real time. We conducted a prospective longitudinal study, recruiting 237 conception-seeking Swiss women. Participants wore the Ava bracelet (Ava AG) nightly while sleeping for up to a year or until they became pregnant. In addition to syncing the device to the corresponding smartphone app daily, women also completed an electronic diary about their activities in the past 24 hours. Finally, women took a urinary luteinizing hormone test at several points in a given cycle to determine the close of the fertile window. We assessed phase-based changes in physiological parameters using cross-classified mixed-effects models with random intercepts and random slopes. We then trained a machine learning algorithm to recognize the fertile window. We have demonstrated that wearable technology can detect significant, concurrent phase-based shifts in WST, heart rate, and respiratory rate (all P<.001). HRV and skin perfusion similarly varied across the menstrual cycle (all P<.05), although these effects only trended toward significance following a Bonferroni correction to maintain a family-wise alpha level. Our findings were robust to daily, individual, and cycle-level covariates. Furthermore, we developed a machine learning algorithm that can detect the fertile window with 90% accuracy (95% CI 0.89 to 0.92). Our contributions highlight the impact of artificial intelligence and machine learning's integration into health care. By monitoring numerous physiological parameters simultaneously, wearable technology uniquely improves upon retrospective methods for fertility awareness and enables the first real-time predictive model of ovulation.
Shilaih M et al., 2017·Biosci Rep·Free full text on PubMed Central
Core and peripheral body temperatures are affected by changes in reproductive hormones during the menstrual cycle. Women worldwide use the basal body temperature (BBT) method to aid and prevent conception. However, prior research suggests that taking one's daily temperature can prove inconvenient and subject to environmental factors. We investigate whether a more automatic, non-invasive temperature measurement system can detect changes in temperature across the menstrual cycle. We examined how wrist skin temperature (WST), measured with wearable sensors, correlates with urinary tests of ovulation and may serve as a new method of fertility tracking. One hundred and thirty-six eumenorrheic, non-pregnant women participated in an observational study. Participants wore WST biosensors during sleep and reported their daily activities. An at-home luteinizing hormone (LH) test was used to confirm ovulation. WST was recorded across 437 cycles (mean cycles/participant = 3.21, S.D. = 2.25). We tested the relationship between the fertile window and WST temperature shifts, using the BBT three-over-six rule. A sustained 3-day temperature shift was observed in 357/437 cycles (82%), with the lowest cycle temperature occurring in the fertile window 41% of the time. Most temporal shifts (307/357, 86%) occurred on ovulation day (OV) or later. The average early-luteal phase temperature was 0.33°C higher than in the fertile window. Menstrual cycle changes in WST were impervious to lifestyle factors, like having sex, alcohol, or eating prior to bed, that, in prior work, have been shown to obfuscate BBT readings. Although currently costlier than BBT, the present study suggests that WST could be a promising, convenient parameter for future multiparameter fertility awareness methods.
Related research
Fertility and Outcomes · Conception After Excision
Minebois H et al., 2017·Gynécologie Obstétrique Fertilité & Sénologie
In spontaneous pregnancies, endometriosis appears to be a risk factor of miscarriage. The aim of this study is to evaluate the association between endometriosis and miscarriage in spontaneous pregnancy. We searched the Cochrane Library, Medline of eligible studies from inception to December 2016, without any restriction. We selected studies that compared endometriosis-affected pregnant women to disease-free pregnant women. To ensure the quality of the methodology, the PRISMA criteria have been met at all stages of the development of this meta-analysis. The primary adverse pregnancy outcomes studied was miscarriage. Three reviewers independently extracted the studies' characteristics and outcome data. Of 225 identified abstracts, 4 primary studies met our inclusion criteria by comparing spontaneous pregnant patients with endometriosis to disease-free women. Miscarriage rate was higher in the endometriosis group (OR 1.77 [CI 95% 1.13-2.78]). In spontaneous pregnancies, endometriosis appears to be a risk factor of miscarriages (almost 80% increased risk). Further prospective studies are needed to confirm these results in order to establish the exact impact of endometriosis on spontaneous pregnancy course.
Fertility and Outcomes · Conception After Excision
Were spontaneous miscarriages more frequent in women with histologically proven endometriosis when compared with endometriosis-free controls? Endometriosis-affected women display a significantly higher rate of previous spontaneous miscarriages than endometriosis-free controls. The association between endometriosis and miscarriages has long been debated without reaching a consensus. STUDY DESIGN, SIZE, We conducted a retrospective cohort study comparing exposed women (endometriosis) and control (without endometriosis) regarding the incidence of miscarriages. All study participants underwent surgery for benign gynaecological conditions in a tertiary-care university hospital between January 2004 and March 2013. After thorough surgical examination of the abdominopelvic cavity, 870 women with histologically proven endometriosis were allocated to the endometriosis group and 981 unaffected women to the control group. Only previously pregnant women were finally included for the study analysis: 284 women in the endometriosis group and 466 in the control group. PARTICIPANTS/MATERIALS, SETTING, Data were collected preoperatively using a structured questionnaire. Among women with at least one pregnancy before the surgery, the type and number of the different previous first trimester pregnancies outcomes were studied. Previous history of miscarriage was studied according to the existence of previous infertility history and the disease severity (revised American Fertility Society and surgical classification). MAIN Four hundred and seventy-eight pregnancies in endometriosis-affected women and 964 pregnancies in controls were analysed. The previous miscarriage rate was significantly higher in women with endometriosis compared with the controls (139/478 [29] versus 187/964 [19%], respectively; ITALIC! P < 0.001). After a subgroup analysis, the miscarriage rates of women with endometriosis and the controls were, respectively: 20 versus 12% ( ITALIC! P = 0.003) among women without a previous history of infertility and 53 versus 30% ( ITALIC! P < 0.001) for women with a previous history of infertility. After using a random-effects Poisson regression and adjusting for confounding factors, we found a significantly increased incidence rate ratio (IRR) for miscarriages in women with endometriosis (adjusted 1.70, 95% confidence interval: 1.34-2.16). LIMITATIONS, There is a possible selection bias due to the specificity of the study design which included only surgical patients. In the control group, certain of the surgical gynaecological conditions, such as fibroids, ovarian cysts or tubal pathologies, might be associated with higher spontaneous miscarriage rates. In the endometriosis group, asymptomatic women were less likely to be referred for surgery and might therefore be underrepresented. This study opens the doors to future, more mechanistic studies to establish the exact link between endometriosis and spontaneous miscarriage rates. No external funding was used for this study. The authors have no conflicts of interest to declare.
Fertility and Outcomes · Conception After Excision
Pregnancy outcomes were evaluated retrospectively in 350 women to investigate the relationship between endometriosis and spontaneous abortions. The frequency of spontaneous abortions in women with endometriosis was significantly higher than in both a fertile nonendometriosis group and an infertile group with tubal disease. There was no correlation between the severity of the endometriosis and the frequency of spontaneous abortions. After treatment, the frequency of spontaneous abortions was significantly decreased in both the endometriosis and the tubal disease group, but these values were not significantly different from each other. We conclude that high spontaneous abortion rates are a characteristic of other subgroups of women with secondary infertility and not just in women with endometriosis, and that the majority of spontaneous abortions associated with endometriosis are not caused by the condition.
Fertility and Outcomes · Conception After Excision
Hsu JZ et al., 2025·Eur J Obstet Gynecol Reprod Biol
Endometriosis is a chronic gynaecological condition affecting reproductive-aged women. It has been associated with infertility and potential risks for adverse pregnancy outcomes, although population-level evidence remains limited. This retrospective cohort study, including 147,950 pregnant women aged 20-45 years, used nationwide population-based data to compare the outcomes between women with (n = 11,400) and without (n = 136,550) endometriosis between 2000 and 2021. Baseline characteristics, comorbidities and pregnancy outcomes were compared between the groups. Multivariable regression analyses were performed to calculate adjusted relative risks (aRR) and 95 % confidence intervals (CI) for various pregnancy outcomes, and subgroup analyses were conducted by maternal age and infertility status. Among 147,950 pregnancies, women with endometriosis [mean ± standard deviation (SD) age 32.38 ± 4.51 years] had higher socio-economic status, more comorbidities, and more surgical history compared with women without endometriosis (mean ± SD age 30.06 ± 4.96 years). Women with endometriosis had increased risk of miscarriage (aRR 1.13, 95 % CI 1.03-1.24), preterm birth (aRR 1.31, 95 % CI 1.26-1.37), premature rupture of membranes (aRR 1.11, 95 % CI 1.06-1.16), placenta previa (aRR 1.63, 95 % CI 1.45-1.84), urinary tract infection (aRR 1.44, 95 % CI 1.31-1.59), and caesarean section (aRR 1.13, 95 % CI 1.11-1.16). Subgroup analysis revealed that risk of miscarriage was only higher in women aged 35-45 years and women without infertility. Risks of preterm birth, placenta previa and caesarean section were elevated across all subgroups, suggesting that endometriosis contributes independently to adverse pregnancy outcomes. Endometriosis is an independent risk factor for several pregnancy complications, supporting the need for tailored prenatal care and closer monitoring of affected women to improve maternal outcomes.
Endometriosis › Fertility and Outcomes › Conception After Excision · Pregnancy › Early Pregnancy › Miscarriage · Infertility › Recurrent Pregnancy Loss › Anatomic Causes
Martina Rauchfuss, Markus Eberhard, Patrick Imesch, Daniel Fink, Brigitte Leeners, Felix Haeberlin, Bruno Imthurn, Stephanie von Orelli, Monika Martina Wölfler
M Rauchfuss, M Eberhard, Pat Imesch, P Imesch, Dan Fink, Danny Fink, D Fink, B Leeners, F Haeberlin, B Imthurn, S Orelli, M Wölfler
PMID 29079275 29079275 DOI 10.1016/j.fertnstert.2017.08.025 10.1016/j.fertnstert.2017.08.025 Kohl Schwartz et al. 2017, Kohl Schwartz 2017
Cite this article
Kohl Schwartz, A. S., Wölfler, M. M., Mitter, V., Rauchfuss, M., Haeberlin, F., Eberhard, M., von Orelli, S., Imthurn, B., Imesch, P., Fink, D., & Leeners, B. (2017). Endometriosis, especially mild disease: a risk factor for miscarriages. Fertility and sterility, 108(5), 806-814.e2. https://doi.org/10.1016/j.fertnstert.2017.08.025
Kohl Schwartz AS, Wölfler MM, Mitter V, Rauchfuss M, Haeberlin F, Eberhard M, et al. Endometriosis, especially mild disease: a risk factor for miscarriages. Fertil Steril. 2017;108(5):806-814.e2. doi:10.1016/j.fertnstert.2017.08.025
Kohl Schwartz, A. S., et al. "Endometriosis, especially mild disease: a risk factor for miscarriages." Fertility and sterility, vol. 108, no. 5, 2017, pp. 806-814.e2.
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