Cited by 1,084Reproductive System and PregnancyReproductive Biology and FertilityReproductive Health and Contraception

The DOI matches its Crossref record; 33 of the 33 references it cites were found in a registry or an index; 2 of the 23 sources its claims cite were checked for support.

Time of Implantation of the Conceptus and Loss of Pregnancy

Open access
Wilcox, Allen J., Baird, Donna Day, Weinberg, Clarice R.·1999·New England Journal of Medicine

Abstract

BACKGROUND: Implantation of the conceptus is a key step in pregnancy, but little is known about the time of implantation or the relation between the time of implantation and the outcome of pregnancy. METHODS: We collected daily urine samples for up to six months from 221 women attempting to conceive after ceasing to use contraception. Ovulation was identified on the basis of the ratio of urinary estrogen metabolites to progesterone metabolites, which changes rapidly with luteinization of the ovarian follicle. The time of implantation was defined by the appearance of chorionic gonadotropin in maternal urine. RESULTS: There were 199 conceptions, for 95 percent of which (189) we had sufficient data for analysis. Of these 189 pregnancies, 141 (75 percent) lasted at least six weeks past the last menstrual period, and the remaining 48 pregnancies (25 percent) ended in early loss. Among the pregnancies that lasted six weeks or more, the first appearance of chorionic gonadotropin occurred 6 to 12 days after ovulation; 118 women (84 percent) had implantation on day 8, 9, or 10. The risk of early pregnancy loss increased with later implantation (P<0.001). Among the 102 conceptuses that implanted by the ninth day, 13 percent ended in early loss. This proportion rose to 26 percent with implantation on day 10, to 52 percent on day 11, and to 82 percent after day 11. CONCLUSIONS: In most successful human pregnancies, the conceptus implants 8 to 10 days after ovulation. The risk of early pregnancy loss increases with later implantation.

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

In 189 naturally conceived pregnancies, implantation usually occurred 8 to 10 days after ovulation, and later implantation was strongly associated with higher risk of early pregnancy loss. The authors conclude that most successful human pregnancies implant 8 to 10 days after ovulation, while late implantation may reflect impaired embryo quality or reduced uterine receptivity.

Key findings

  • Among 189 analyzed pregnancies, 141 (75 percent) lasted at least six weeks past the last menstrual period, and 48 (25 percent) ended in early loss.
  • Among pregnancies lasting at least six weeks, first urinary chorionic gonadotropin appeared 6 to 12 days after ovulation; 118 women (84 percent) implanted on day 8, 9, or 10.
  • Risk of early loss increased with later implantation (P<0.001): 13 percent among 102 conceptuses implanting by day 9, 26 percent on day 10, 52 percent on day 11, and 82 percent after day 11.
  • Early losses had a later and broader implantation distribution (mean, 10.5 days; range, 6 to 18 days), whereas live births and clinical losses had mean implantation times of 9.1 and 9.2 days, respectively (P=0.59).

Methods

  • Prospective study of 221 women with no history of fertility problems who were attempting to conceive after stopping contraception; they collected daily first-morning urine specimens through the eighth week of clinical pregnancy or for up to six months.
  • Day of ovulation was estimated from the urinary ratio of estrone 3-glucuronide to pregnanediol 3-glucuronide, validated against the luteinizing hormone surge; implantation was defined as the first day urinary chorionic gonadotropin exceeded 0.015 ng per milliliter, with pregnancy defined as concentrations above 0.025 ng per milliliter for at least three consecutive days.
  • Distributions of implantation times were compared with contingency-table chi-square statistics, and trend in early loss with later implantation was tested by logistic regression with two-sided P values.

Limitations

  • Stated: implantation cannot be directly observed, and chorionic gonadotropin appearance may not mark the earliest implantation steps; random errors in ovulation and chorionic gonadotropin measures may spread the observed implantation distribution, so the true biologic window may be narrower.
  • Stated: fertility treatment may distort reproductive function, so findings from these naturally conceiving women may not apply to treated infertility populations.
  • Evident from the text: 10 pregnancies (5 percent) were excluded because ovulation or implantation day could not be determined due to missing data, and the sample comprised women without known fertility problems, limiting generalizability.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1056/nejm199906103402304

Cites

33 of 33 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Verification

Claims the paper makes

15 Own result · 11 Own interpretation · 9 No full text of the sources · 3 Not checked yet · 3 Own method · 1 Supported so far · 1 Couldn’t confirm · accuracy not yet measured

Verify all 2 references — free account

Show all 19 claims

  • It may state two separate claims as one. 16
  • Probably not a substantial claim. 13
  • The quote only partly states this claim. 1
24 of 24
  • The paper relies on this without support.

    The study population of 221 women attempting to conceive after ceasing contraception is representative of healthy women generally, so that findings generalize to most successful human pregnancies.

    “We studied 221 couples who had no history of fertility problems and who planned to have children.”
    “In our study, the couples had no known fertility problems, and none of the women were being treated with hormones.”
  • The paper relies on this without support.

    The 10 pregnancies excluded because of missing data did not differ systematically from the 189 analyzed pregnancies.

    “The day of ovulation or implantation could not be determined for 10 pregnancies (5 percent) because of missing data; these pregnancies were excluded from our analysis.”
2 of 2

Citations

Cites

Show all 32 references

Research works printed but not linked: 7

  1. England MA. Life before birth. 2nd ed. London: Mosby–Wolfe, 1996.
  2. Royston JP. Statistical approaches to the prediction and detection of ovulation: detecting the signal among the noise. In: Jeffcoate SL, ed. Ovulation: methods for its prediction and detection. Vol. 3 of Current topics in reproductive endocrinology. Chichester, England: John Wiley, 1983:19-32.
  3. Collins WP. Biochemical approaches to ovulation prediction and detection and the location of the fertile period in women. In: Jeffcoate SL, ed. Ovulation: methods for its prediction and detection. Vol. 3 of Current topics in reproductive endocrinology. Chichester, England: John Wiley, 1983:49-66.
  4. Norman RJ, 1987, Obstet Gynecol, 69, 590
  5. Canfield RE, 1976, Bull World Health Organ, 54, 463
  6. Psychoyos A, 1976, J Reprod Fertil Suppl, 25, 17
  7. Ringler GE, 1990, Curr Opin Obstet Gynecol, 2, 703

Cited by

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Items 601–700 of 1,084

Metadata

Authors
Wilcox, A. J., Baird, D. D., & Weinberg, C. R.
Affiliations
National Institutes of Health (US)
Venue
New England Journal of Medicine
Published
1999-06-10
Volume
340
Issue
23
Pages
1796-1799
ISSN
  • 0028-4793 (ISSN-L)
  • 1533-4406
OpenAlex
W2325674170
Cited by
1,081
References
32
Citations by year
2026: 24 · 2025: 34 · 2024: 74 · 2023: 50 · 2022: 55 · 2021: 60 · 2020: 57 · 2019: 47 · 2018: 37 · 2017: 53 · 2016: 50 · 2015: 29 · 2014: 47 · 2013: 45 · 2012: 54
FWCI
4.04
Type
journal article
Language
en
Open access
Locations
  • New England Journal of Medicine (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
  • Health Sciences › Medicine › Reproductive Medicine › Reproductive Biology and Fertility
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Health and Contraception
Keywords
conceptus implantation, implantation timing, early pregnancy loss, miscarriage, human chorionic gonadotropin, ovulation, luteinization, pregnancy outcomes
MeSH terms
Abortion, Spontaneous, Female, Humans, Embryo Implantation, Pregnancy, Risk Factors, Time Factors

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