We describe the epidemiologic characteristics of conception, including subclinical early pregnancy loss, in a population of healthy women volunteers who had heterogeneous fertility experiences, and we describe the conception experience of women within this group who had evidence of impaired fertility.
Study Design
This was a prospective observational study of a cohort of women employed in two semiconductor manufacturing facilities. A total of 148 volunteers completed interviews and daily diaries and collected daily urine specimens for an average of 7 months. Conception, including subclinical losses and clinical pregnancies, was determined with a highly sensitive and specific assay for urinary human chorionic gonadotropin, and ovulation was determined with assays of urinary ovarian steroid hormones.
Results
There were 679 menstrual cycles at risk for pregnancy contributed by 124 (84%) of the 148 women. Women with evidence of subfertility before or during the study period had a rate of early pregnancy loss of 70% compared with 21% in women without fertility problems (relative risk 2.6, 95% confidence interval 1.8 to 3.8). The risk of pregnancy loss associated with subfertility increased with age and remained the same in women treated with clomiphene citrate.
Conclusions
These results suggest that subfertile women have increased subclinical pregnancy losses regardless of fertility treatment and that the association between reduced fertility and advancing age may be related, in part, to early subclinical pregnancy loss.
subclinical early pregnancy loss subfertility urinary hCG, infertility subclinical miscarriage prospective cohort study, early pregnancy loss age subfertile women, urinary human chorionic gonadotropin subclinical pregnancy detection, clomiphene citrate treatment early pregnancy loss rate, impaired fertility early embryo loss epidemiology, subclinical miscarriage rate subfertile vs fertile women, prospective urine collection ovulation pregnancy loss detection, advancing age subfertility subclinical pregnancy loss association, chemical pregnancy loss infertility risk factor
PMID 7755065 7755065 DOI 10.1016/0002-9378(95)90489-1 10.1016/0002-9378(95)90489-1 Hakim et al. 1995, Hakim 1995
Cite this article
Hakim, R. U., Gray, R. H., & Zacur, H. A. (1995). Infertility and early pregnancy loss. American journal of obstetrics and gynecology, 172(5), 1510-1517. https://doi.org/10.1016/0002-9378(95)90489-1
Hakim RU, Gray RH, Zacur HA. Infertility and early pregnancy loss. Am J Obstet Gynecol. 1995;172(5):1510-1517. doi:10.1016/0002-9378(95)90489-1
Hakim, Raiyan Ul, et al. "Infertility and early pregnancy loss." American journal of obstetrics and gynecology, vol. 172, no. 5, 1995, pp. 1510-1517.
Tamblyn JA et al., 2022·Fertility and sterility·
Open Access
To investigate whether a significant association between vitamin D status and the risk of miscarriage or recurrent miscarriage (RM) exists. Systematic review and meta-analysis. Not applicable. PATIENT(S): Women with miscarriage and RM. INTERVENTION(S): We searched the Ovid MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature, and Cochrane Central Register of Controlled Trials from database inception to May 2021. Randomized and observational studies investigating the association between maternal vitamin D status and miscarriage and/or vitamin D treatment and miscarriage were included. MAIN OUTCOME MEASURE(S): The primary outcome was miscarriage or RM, with vitamin D status used as the predictor of risk. Whether vitamin D treatment reduces the risk of miscarriage and RM was also assessed. RESULT(S): Of 902 studies identified, 10 (n = 7,663 women) were included: 4 randomized controlled trials (n = 666 women) and 6 observational studies (n = 6,997 women). Women diagnosed with vitamin D deficiency (<50 nmol/L) had an increased risk of miscarriage compared with women who were vitamin D replete (>75 nmol/L) (odds ratio, 1.94; 95% confidence interval, 1.25-3.02; 4 studies; n = 3,674; I2 = 18%). Combined analysis, including women who were vitamin D insufficient (50-75 nmol/L) and deficient (<50 nmol/L) compared with women who were replete (>75 nmol/L), found an association with miscarriage (odds ratio, 1.60; 95% confidence interval, 1.11-2.30; 6 studies; n = 6,338; I2 = 35%). Although 4 randomized controlled trials assessed the effect of vitamin D treatment on miscarriage, study heterogeneity, data quality, and reporting bias precluded direct comparison and meta-analysis. The overall study quality was "low" or "very low" using the Grading of Recommendations, Assessment, Development and Evaluations approach. CONCLUSION(S): Vitamin D deficiency and insufficiency are associated with miscarriage. Whether preconception treatment of vitamin D deficiency protects against pregnancy loss in women at risk of miscarriage remains unknown. CRD42021259899.
To estimate the burden of miscarriage in the Norwegian population and to evaluate the associations with maternal age and pregnancy history. Prospective register based study. Medical Birth Register of Norway, the Norwegian Patient Register, and the induced abortion register. All Norwegian women that were pregnant between 2009-13. Risk of miscarriage according to the woman's age and pregnancy history estimated by logistic regression. There were 421,201 pregnancies during the study period. The risk of miscarriage was lowest in women aged 25-29 (10%), and rose rapidly after age 30, reaching 53% in women aged 45 and over. There was a strong recurrence risk of miscarriage, with age adjusted odds ratios of 1.54 (95% CI 1.48 to 1.60) after one miscarriage, 2.21 (2.03 to 2.41) after two, and 3.97 (3.29 to 4.78) after three consecutive miscarriages. The risk of miscarriage was modestly increased if the previous birth ended in a preterm delivery (aOR 1.22, 95% CI 1.12 to 1.29), stillbirth (1.30, 1.11 to 1.53), caesarean section (1.16, 1.12 to 1.21), or if the woman had gestational diabetes in the previous pregnancy (1.19, 1.05 to 1.36). The risk of miscarriage was slightly higher in women who themselves had been small for gestational age (1.08, 1.04 to 1.13). The risk of miscarriage varies greatly with maternal age, shows a strong pattern of recurrence, and is also increased after some adverse pregnancy outcomes. Miscarriage and other pregnancy complications might share underlying causes, which could be biological conditions or unmeasured common risk factors.
Fourteen women experiencing early pregnancy failure have been studied during the time of conception and at frequent intervals until spontaneous abortion occurred. Serial measurements of serum estradiol, progesterone, 17 alpha-hydroxyprogesterone, prolactin, human placental lactogen (hPL), and human chorionic gonadotropin (hCG) were determined; regular sonar scanning allowed the time of fetal death to be determined to within 7 days in six patients and a diagnosis of blighted ovum to be made in the remainder. In all patients serum progesterone and estradiol concentrations were within the normal range up to 7 weeks but appeared to decrease from about 8 weeks' gestation whether or not a living fetus was present. The placenta continued to produce hCG and hPL but, despite the continuing presence of hCG, the levels of 17 alpha-hydroxyprogesterone declined to concentrations below those associated with normal pregnancy. These data suggest that the placenta may require a particular stimulus to take over production of progesterone and estradiol.
Guidelines by Clinical Area · Fertility and Infertility Guidelines
Practice Committee of the American Society for Reproductive Medicine, 2026·Fertility and Sterility
Current strategies for the assessment and treatment of recurrent pregnancy loss are discussed. This replaces the previous document, titled, "Evaluation and treatment of recurrent pregnancy loss: a committee opinion," last published in 2012.