FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 340:1796-1799 June 10, 1999 Number 23 Next

	Full Text PDF Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

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 6 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.

Source Information

From the Epidemiology Branch (A.J.W., D.D.B.) and the Biostatistics Branch (C.R.W.), National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, N.C.

Address reprint requests to Dr. Wilcox at the Epidemiology Branch, MD A3-05, NIEHS, Research Triangle Park, NC 27709.

Full Text of this Article

This article has been cited by other articles:

• Sarno, J., Schatz, F., Huang, S. J., Lockwood, C., Taylor, H. S. (2009). Thrombin and interleukin-1{beta} decrease HOX gene expression in human first trimester decidual cells: implications for pregnancy loss. Mol Hum Reprod 15: 451-457 [Abstract] [Full Text]  
• Allegra, A., Marino, A., Coffaro, F., Lama, A., Rizza, G., Scaglione, P., Sammartano, F., Santoro, A., Volpes, A. (2009). Is there a uniform basal endometrial gene expression profile during the implantation window in women who became pregnant in a subsequent ICSI cycle?. Hum Reprod 0: dep222v1-dep222 [Abstract] [Full Text]  
• Boomsma, C.M., Kavelaars, A., Eijkemans, M.J.C., Lentjes, E.G., Fauser, B.C.J.M., Heijnen, C.J., Macklon, N.S. (2009). Endometrial secretion analysis identifies a cytokine profile predictive of pregnancy in IVF. Hum Reprod 24: 1427-1435 [Abstract] [Full Text]  
• Van Vaerenbergh, I., Van Lommel, L., Ghislain, V., In't Veld, P., Schuit, F., Fatemi, H. M., Devroey, P., Bourgain, C. (2009). In GnRH antagonist/rec-FSH stimulated cycles, advanced endometrial maturation on the day of oocyte retrieval correlates with altered gene expression. Hum Reprod 24: 1085-1091 [Abstract] [Full Text]  
• Schreiner-Karoussou, A. (2009). A PRELIMINARY STUDY OF ISSUES AND PRACTICES CONCERNING PREGNANCY AND IONISING RADIATION. Radiat Prot Dosimetry 0: ncp047v1-ncp047 [Abstract] [Full Text]  
• Haouzi, D., Mahmoud, K., Fourar, M., Bendhaou, K., Dechaud, H., De Vos, J., Reme, T., Dewailly, D., Hamamah, S. (2009). Identification of new biomarkers of human endometrial receptivity in the natural cycle. Hum Reprod 24: 198-205 [Abstract] [Full Text]  
• Peralta, C. G., Han, V. K., Horrocks, J., Croy, B. A., van den Heuvel, M. J. (2008). CD56bright cells increase expression of {alpha}4 integrin at ovulation in fertile cycles. J. Leukoc. Biol. 84: 1065-1074 [Abstract] [Full Text]  
• Usadi, R. S., Groll, J. M., Lessey, B. A., Lininger, R. A., Zaino, R. J., Fritz, M. A., Young, S. L. (2008). Endometrial Development and Function in Experimentally Induced Luteal Phase Deficiency. J. Clin. Endocrinol. Metab. 93: 4058-4064 [Abstract] [Full Text]  
• Franchi, A., Zaret, J., Zhang, X., Bocca, S., Oehninger, S. (2008). Expression of immunomodulatory genes, their protein products and specific ligands/receptors during the window of implantation in the human endometrium. Mol Hum Reprod 14: 413-421 [Abstract] [Full Text]  
• Guffanti, E., Kittur, N., Brodt, Z. N., Polotsky, A. J., Kuokkanen, S. M., Heller, D. S., Young, S. L., Santoro, N., Meier, U. T. (2008). Nuclear pore complex proteins mark the implantation window in human endometrium. J. Cell Sci. 121: 2037-2045 [Abstract] [Full Text]  
• Nepomnaschy, P.A., Weinberg, C.R., Wilcox, A.J., Baird, D.D. (2008). Urinary hCG patterns during the week following implantation. Hum Reprod 23: 271-277 [Abstract] [Full Text]  
• Horne, F. M., Blithe, D. L. (2007). Progesterone receptor modulators and the endometrium: changes and consequences. Hum Reprod Update 13: 567-580 [Abstract] [Full Text]  
• Feroze-Zaidi, F., Fusi, L., Takano, M., Higham, J., Salker, M. S., Goto, T., Edassery, S., Klingel, K., Boini, K. M., Palmada, M., Kamps, R., Groothuis, P. G., Lam, E. W.-F., Smith, S. K., Lang, F., Sharkey, A. M., Brosens, J. J. (2007). Role and Regulation of the Serum- and Glucocorticoid-Regulated Kinase 1 in Fertile and Infertile Human Endometrium. Endocrinology 148: 5020-5029 [Abstract] [Full Text]  
• Baldwin, D. S, Reines, E. H., Guiton, C., Weiller, E. (2007). Escitalopram Therapy for Major Depression and Anxiety Disorders. The Annals of Pharmacotherapy 41: 1583-1592 [Abstract] [Full Text]  
• Chakrabarty, A., Tranguch, S., Daikoku, T., Jensen, K., Furneaux, H., Dey, S. K. (2007). MicroRNA regulation of cyclooxygenase-2 during embryo implantation. Proc. Natl. Acad. Sci. USA 104: 15144-15149 [Abstract] [Full Text]  
• Diedrich, K., Fauser, B.C.J.M., Devroey, P., Griesinger, G., on behalf of the Evian Annual Reproduction (EVAR), (2007). The role of the endometrium and embryo in human implantation. Hum Reprod Update 13: 365-377 [Abstract] [Full Text]  
• Song, H., Han, K., Lim, H. (2007). Progesterone supplementation extends uterine receptivity for blastocyst implantation in mice. Reproduction 133: 487-493 [Abstract] [Full Text]  
• Sherwin, J. R. A., Sharkey, A. M., Cameo, P., Mavrogianis, P. M., Catalano, R. D., Edassery, S., Fazleabas, A. T. (2007). Identification of Novel Genes Regulated by Chorionic Gonadotropin in Baboon Endometrium during the Window of Implantation. Endocrinology 148: 618-626 [Abstract] [Full Text]  
• Achache, H., Revel, A. (2006). Endometrial receptivity markers, the journey to successful embryo implantation. Hum Reprod Update 12: 731-746 [Abstract] [Full Text]  
• Campbell, E.A., O'Hara, L., Catalano, R.D., Sharkey, A.M., Freeman, T.C., Johnson, M. H. (2006). Temporal expression profiling of the uterine luminal epithelium of the pseudo-pregnant mouse suggests receptivity to the fertilized egg is associated with complex transcriptional changes. Hum Reprod 21: 2495-2513 [Abstract] [Full Text]  
• Kelley, R. L., Kind, K. L., Lane, M., Robker, R. L., Thompson, J. G., Edwards, L. J. (2006). Recombinant human follicle-stimulating hormone alters maternal ovarian hormone concentrations and the uterus and perturbs fetal development in mice. Am. J. Physiol. Endocrinol. Metab. 291: E761-E770 [Abstract] [Full Text]  
• Strowitzki, T., Germeyer, A., Popovici, R., von Wolff, M. (2006). The human endometrium as a fertility-determining factor. Hum Reprod Update 12: 617-630 [Abstract] [Full Text]  
• Wang, H., Dey, S. K., Maccarrone, M. (2006). Jekyll and Hyde: Two Faces of Cannabinoid Signaling in Male and Female Fertility. Endocr. Rev. 27: 427-448 [Abstract] [Full Text]  
• Nepomnaschy, P. A., Welch, K. B., McConnell, D. S., Low, B. S., Strassmann, B. I., England, B. G. (2006). Cortisol levels and very early pregnancy loss in humans. Proc. Natl. Acad. Sci. USA 103: 3938-3942 [Abstract] [Full Text]  
• Makker, A, Bansode, F W, Srivastava, V M L, Singh, M M (2006). Antioxidant defense system during endometrial receptivity in the guinea pig: effect of ormeloxifene, a selective estrogen receptor modulator. J Endocrinol 188: 121-134 [Abstract] [Full Text]  
• Simon, C., Oberye, J., Bellver, J., Vidal, C., Bosch, E., Horcajadas, J.A., Murphy, C., Adams, S., Riesewijk, A., Mannaerts, B., Pellicer, A. (2005). Similar endometrial development in oocyte donors treated with either high- or standard-dose GnRH antagonist compared to treatment with a GnRH agonist or in natural cycles. Hum Reprod 20: 3318-3327 [Abstract] [Full Text]  
• Nguyen, R. H N, Wilcox, A. J (2005). Terms in reproductive and perinatal epidemiology: I. Reproductive terms. J. Epidemiol. Community Health 59: 916-919 [Abstract] [Full Text]  
• Mirkin, S., Arslan, M., Churikov, D., Corica, A., Diaz, J.I., Williams, S., Bocca, S., Oehninger, S. (2005). In search of candidate genes critically expressed in the human endometrium during the window of implantation. Hum Reprod 20: 2104-2117 [Abstract] [Full Text]  
• Lovely, L. P., Fazleabas, A. T., Fritz, M. A., McAdams, D. G., Lessey, B. A. (2005). Prevention of Endometrial Apoptosis: Randomized Prospective Comparison of Human Chorionic Gonadotropin Versus Progesterone Treatment in the Luteal Phase. J. Clin. Endocrinol. Metab. 90: 2351-2356 [Abstract] [Full Text]  
• McChesney, R., Wilcox, A. J., O'Connor, J. F., Weinberg, C. R., Baird, D. D., Schlatterer, J. P., McConnaughey, D.R., Birken, S., Canfield, R. E. (2005). Intact HCG, free HCG {beta} subunit and HCG {beta} core fragment: longitudinal patterns in urine during early pregnancy. Hum Reprod 20: 928-935 [Abstract] [Full Text]  
• Lee, K. Y, DeMayo, F. J (2004). Animal models of implantation. Reproduction 128: 679-695 [Abstract] [Full Text]  
• Mirkin, S., Nikas, G., Hsiu, J.-G., Diaz, J., Oehninger, S. (2004). Gene Expression Profiles and Structural/Functional Features of the Peri-Implantation Endometrium in Natural and Gonadotropin-Stimulated Cycles. J. Clin. Endocrinol. Metab. 89: 5742-5752 [Abstract] [Full Text]  
• Tong, S., Rombauts, L., Mulder, A., Marjono, B., Onwude, J. L., Wallace, E. M. (2004). Increased Day 15-17 Serum Pro-{alpha}C Inhibin Levels Specific to Successful Pregnancy. J. Clin. Endocrinol. Metab. 89: 4464-4468 [Abstract] [Full Text]  
• Hatakeyama, S., Ohyama, C., Minagawa, S., Inoue, T., Kakinuma, H., Kyan, A., Arai, Y., Suga, T., Nakayama, J., Kato, T., Habuchi, T., Fukuda, M. N. (2004). Functional Correlation of Trophinin Expression with the Malignancy of Testicular Germ Cell Tumor. Cancer Res. 64: 4257-4262 [Abstract] [Full Text]  
• Wang, H., Ma, W.-g., Tejada, L., Zhang, H., Morrow, J. D., Das, S. K., Dey, S. K. (2004). Rescue of Female Infertility from the Loss of Cyclooxygenase-2 by Compensatory Up-regulation of Cyclooxygenase-1 Is a Function of Genetic Makeup. J. Biol. Chem. 279: 10649-10658 [Abstract] [Full Text]  
• Rodriguez, C. I., Cheng, J.-G., Liu, L., Stewart, C. L. (2004). Cochlin, a Secreted von Willebrand Factor Type A Domain-Containing Factor, Is Regulated by Leukemia Inhibitory Factor in the Uterus at the Time of Embryo Implantation. Endocrinology 145: 1410-1418 [Abstract] [Full Text]  
• Bartsch, O., Bartlick, B., Ivell, R. (2004). Phosphodiesterase 4 Inhibition Synergizes with Relaxin Signaling to Promote Decidualization of Human Endometrial Stromal Cells. J. Clin. Endocrinol. Metab. 89: 324-334 [Abstract] [Full Text]  
• Los, F. J., Van Opstal, D., van den Berg, C. (2004). The development of cytogenetically normal, abnormal and mosaic embryos: a theoretical model. Hum Reprod Update 10: 79-94 [Abstract] [Full Text]  
• Almagor, M., Hazav, A., Yaffe, H. (2004). The levels of C-reactive protein in women treated by IVF. Hum Reprod 19: 104-106 [Abstract] [Full Text]  
• Nakayama, J., Aoki, D., Suga, T., Akama, T. O., Ishizone, S., Yamaguchi, H., Imakawa, K., Nadano, D., Fazleabas, A. T., Katsuyama, T., Nozawa, S., Fukuda, M. N. (2003). Implantation-Dependent Expression of Trophinin by Maternal Fallopian Tube Epithelia during Tubal Pregnancies: Possible Role of Human Chorionic Gonadotrophin on Ectopic Pregnancy. Am. J. Pathol. 163: 2211-2219 [Abstract] [Full Text]  
• Harville, E.W., Wilcox, A.J., Baird, D.D., Weinberg, C.R. (2003). Vaginal bleeding in very early pregnancy. Hum Reprod 18: 1944-1947 [Abstract] [Full Text]  
• Catalano, R.D., Yanaihara, A., Evans, A.L., Rocha, D., Prentice, A., Saidi, S., Print, C.G., Charnock-Jones, D.S., Sharkey, A.M., Smith, S.K. (2003). The effect of RU486 on the gene expression profile in an endometrial explant model. Mol Hum Reprod 9: 465-473 [Abstract] [Full Text]  
• Sun, Y., Che, Y., Gao, E., Olsen, J., Zhou, W. (2003). Induced abortion and risk of subsequent miscarriage. Int J Epidemiol 32: 449-454 [Abstract] [Full Text]  
• Keen, C. L., Clegg, M. S., Hanna, L. A., Lanoue, L., Rogers, J. M., Daston, G. P., Oteiza, P., Uriu-Adams, J. Y. (2003). The Plausibility of Micronutrient Deficiencies Being a Significant Contributing Factor to the Occurrence of Pregnancy Complications. J. Nutr. 133: 1597S-1605 [Abstract] [Full Text]  
• Creus, M., Ordi, J., Fabregues, F., Casamitjana, R., Carmona, F., Cardesa, A., Vanrell, J. A., Balasch, J. (2003). The effect of different hormone therapies on integrin expression and pinopode formation in the human endometrium: a controlled study. Hum Reprod 18: 683-693 [Abstract] [Full Text]  
• Strotmeyer, E. S., Steenkiste, A. R., Foley, T. P. Jr, Berga, S. L., Dorman, J. S. (2003). Menstrual Cycle Differences Between Women With Type 1 Diabetes and Women Without Diabetes. Diabetes Care 26: 1016-1021 [Abstract] [Full Text]  
• Song, H., Lim, H., Paria, B. C., Matsumoto, H., Swift, L. L., Morrow, J., Bonventre, J. V., Dey, S. K. (2003). Cytosolic phospholipase A2{alpha} is crucial for 'on-time' embryo implantation that directs subsequent development. Development 129: 2879-2889 [Abstract] [Full Text]  
• Ma, W.-g., Song, H., Das, S. K., Paria, B. C., Dey, S. K. (2003). Estrogen is a critical determinant that specifies the duration of the window of uterine receptivity for implantation. Proc. Natl. Acad. Sci. USA 100: 2963-2968 [Abstract] [Full Text]  
• Baird, D. D., Weinberg, C. R., McConnaughey, D. R., Wilcox, A. J. (2003). Rescue of the Corpus Luteum in Human Pregnancy. Biol. Reprod. 68: 448-456 [Abstract] [Full Text]  
• Carson, D. D., Lagow, E., Thathiah, A., Al-Shami, R., Farach-Carson, M. C., Vernon, M., Yuan, L., Fritz, M. A., Lessey, B. (2002). Changes in gene expression during the early to mid-luteal (receptive phase) transition in human endometrium detected by high-density microarray screening. Mol Hum Reprod 8: 871-879 [Abstract] [Full Text]  
• Sherwin, J. R. A., Smith, S. K., Wilson, A., Sharkey, A. M. (2002). Soluble gp130 is Up-Regulated in the Implantation Window and Shows Altered Secretion in Patients with Primary Unexplained Infertility. J. Clin. Endocrinol. Metab. 87: 3953-3960 [Abstract] [Full Text]  
• Paria, B. C., Reese, J., Das, S. K., Dey, S. K. (2002). Deciphering the Cross-Talk of Implantation: Advances and Challenges. Science 296: 2185-2188 [Abstract] [Full Text]  
• Norwitz, E. R., Schust, D. J., Fisher, S. J. (2001). Implantation and the Survival of Early Pregnancy. NEJM 345: 1400-1408 [Full Text]  
• Wilcox, A. J., Baird, D. D., Dunson, D., McChesney, R., Weinberg, C. R. (2001). Natural Limits of Pregnancy Testing in Relation to the Expected Menstrual Period. JAMA 286: 1759-1761 [Abstract] [Full Text]  
• Manson, J. M., McFarland, B., Weiss, S. (2001). Use of an Automated Database to Evaluate Markers for Early Detection of Pregnancy. Am J Epidemiol 154: 180-187 [Abstract] [Full Text]  
• Behre, H.M., Kuhlage, J., Ga{beta}ner, C., Sonntag, B., Schem, C., Schneider, H.P.G., Nieschlag, E. (2000). Prediction of ovulation by urinary hormone measurements with the home use ClearPlan(R) Fertility Monitor: comparison with transvaginal ultrasound scans and serum hormone measurements. Hum Reprod 15: 2478-2482 [Abstract] [Full Text]  
• Rosene-Montella, K., Keely, E., Laifer, S. A., Lee, R. V. (2000). Evaluation and Management of Infertility in Women: The Internists' Role. ANN INTERN MED 132: 973-981 [Abstract] [Full Text]  
• (1999). Embryos Destined to Abort Implant Later Than Healthy Embryos. JWatch Women's Health 1999: 13-13 [Full Text]