Skip to main content Accessibility help
×
Hostname: page-component-78c5997874-xbtfd Total loading time: 0 Render date: 2024-11-08T02:36:54.970Z Has data issue: false hasContentIssue false

4 - Endometrial Receptivity

from PART I - PHYSIOLOGY OF REPRODUCTION

Published online by Cambridge University Press:  04 August 2010

Botros R. M. B. Rizk
Affiliation:
University of South Alabama
Juan A. Garcia-Velasco
Affiliation:
Rey Juan Carlos University School of Medicine,
Hassan N. Sallam
Affiliation:
University of Alexandria School of Medicine
Antonis Makrigiannakis
Affiliation:
University of Crete
Get access

Summary

INTRODUCTION

Twenty-five years into the history of in vitro fertilization (IVF), endometrial receptivity remains both puzzling and challenging. The challenge comes from the fact that embryo implantation rates, however markedly improved in the later years, remain the bottleneck of assisted reproduction treatments (ART). In contrast to all the steps that take place earlier in the chain of ART measures such as notably multiple follicular stimulation, oocyte retrieval, fertilization, and cleavage rates, which have an efficacy largely more than 50 percent, embryo implantation rates continue to lag behind.

The puzzling fact about endometrial receptivity is that the simplest way of priming it is with the sole use of exogenous E2 and progesterone, as it was conceived for women whose ovaries have prematurely failed over twenty years ago. Indeed, implantations rates achieved in hormonal regimens developed for recipients of donor egg IVF remain remarkable even by today's standards, being at best equaled but to this date never surpassed, either in natural cycles or in any type of ART.

The lasting lesson that donor egg IVF has been teaching us is that E2 and progesterone suffice for triggering an optimal endometrial receptivity. This implies that other factors produced by the ovary such as notably androgens are at best unnecessary but often capable of harming. In controlled ovarian hyperstimulation (COH), as performed in ART, the ovaries are stimulated with supraphysiological levels of gonadotropins.

Type
Chapter
Information
Publisher: Cambridge University Press
Print publication year: 2008

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Garcia, E, Bouchard, P, Brux, J, Berdah, J, Frydman, R, Schaison, G, Milgrom, E, Perrot-Applanat, M. Use of immunocytochemistry of progesterone and estrogen receptors for endometrial dating. J Clin Endocrinol Metab. 1988;67:80–7.CrossRefGoogle ScholarPubMed
Bergeron, C, Ferenczy, A, Toft, , Schneider, W, Shyamala, G. Immunocytochemical study of progesterone receptors in the human endometrium during the menstrual cycle. Lab Invest. 1988;59:862–9.Google ScholarPubMed
Nestour, E, Marraoui, J, Lahlou, N, Roger, M, Ziegler, D, Bouchard, P. Role of estradiol in the rise in follicle-stimulating hormone levels during the luteal-follicular transition. J Clin Endocrinol Metab. 1993;77:439–42.Google ScholarPubMed
Navot, D, Bergh, PA, Williams, M, Garrisi, GJ, Guzman, I, Sandler, B, Fox, J, Schreiner-Engel, P, Hofmann, GE, Grunfeld, L. An insight into early reproductive processes through the in vivo model of ovum donation. J Clin Endocrinol Metab. 1991;72:408–14.CrossRefGoogle ScholarPubMed
Navot, D, Bergh, P. Preparation of the human endometrium for implantation. Ann N Y Acad Sci. 1991;622:212–9. Review. No abstract available.CrossRefGoogle ScholarPubMed
Navot, D, Anderson, TL, Droesch, K, Scott, RT, Kreiner, D, Rosenwaks, Z. Hormonal manipulation of endometrial maturation. J Clin Endocrinol Metab. 1989;68:801–7.CrossRefGoogle ScholarPubMed
Noyes, RW, Haman, JO. Accuracy of endometrial dating; correlation of endometrial dating with basal body temperature and menses. Fertil Steril. 1953;4:504–17.CrossRefGoogle ScholarPubMed
Navot, D, Anderson, TL, Droesch, K, Scott, RT, Kreiner, D, Rosenwaks, Z. Hormonal manipulation of endometrial maturation. J Clin Endocrinol Metab. 1989;68:801–7.CrossRefGoogle ScholarPubMed
Navot, D, Scott, RT, Droesch, K, Veeck, LL, Liu, HC, Rosenwaks, Z. The window of embryo transfer and the efficiency of human conception in vitro. Fertil Steril. 1991;55:114–8.CrossRefGoogle ScholarPubMed
Bergh, PA, Navot, D. The impact of embryonic development and endometrial maturity on the timing of implantation. Fertil Steril. 1992;58:537–42.CrossRefGoogle ScholarPubMed
Ziegler, D. Hormonal control of endometrial receptivity. Hum Reprod. 1995;10:4–7.CrossRefGoogle ScholarPubMed
Ziegler, D, Bouchard, P. Understanding endometrial physiology and menstrual disorders in the 1990s. Curr Opin Obstet Gynecol. 1993;5:378–88.CrossRefGoogle ScholarPubMed
Basir, GS, O WS, Ng EH, Ho, PC. Morphometric analysis of peri-implantation endometrium in patients having excessively high oestradiol concentrations after ovarian stimulation. Hum Reprod. 2001;16:435–40.CrossRefGoogle ScholarPubMed
Lessey, BA, Damjanovich, L, Coutifaris, C, Castelbaum, A, Albelda, SM, Buck, CA. Integrin adhesion molecules in the human endometrium. Correlation with the normal and abnormal menstrual cycle. J Clin Invest. 1992;90:188–95.CrossRefGoogle ScholarPubMed
Lessey, BA. The use of integrins for the assessment of uterine receptivity. Fertil Steril. 1994;61:812–4.CrossRefGoogle ScholarPubMed
Lessey, BA, Castelbaum, AJ, Sawin, SW, Buck, CA, Schinnar, R, Bilker, W, Strom, BL. Aberrant integrin expression in the endometrium of women with endometriosis. J Clin Endocrinol Metab. 1994;79:643–9.Google ScholarPubMed
Damario, MA, Lesnick, TG, Lessey, BA, Kowalik, A, Mandelin, E, Seppala, M, Rosenwaks, Z. Endometrial markers of uterine receptivity utilizing the donor oocyte model. Hum Reprod. 2001; 16:1893–9.CrossRefGoogle ScholarPubMed
Nikas, G, Drakakis, P, Loutradis, D, Mara-Skoufari, C, Koumantakis, E, Michalas, S, Psychoyos, A. Uterine pinopodes as markers of the ‘nidation window’ in cycling women receiving exogenous oestradiol and progesterone. Hum Reprod. 1995;10:1208–13.CrossRefGoogle ScholarPubMed
Nikas, G, Develioglu, OH, Toner, JP, Jones, HW Jr. Endometrial pinopodes indicate a shift in the window of receptivity in IVF cycles. Hum Reprod. 1999;14:787–92.CrossRefGoogle ScholarPubMed
Bentin-Ley, U, Sjogren, A, Nilsson, L, Hamberger, L, Larsen, JF, Horn, T. Presence of uterine pinopodes at the embryo-endometrial interface during human implantation in vitro. Hum Reprod. 1999; 14:515–20.CrossRefGoogle ScholarPubMed
Daftary, GS, Taylor, HS. Endocrine regulation of HOX genes. Endocr Rev. 2006;27:331–55.CrossRefGoogle ScholarPubMed
Taylor, HS, Arici, A, Olive, D, Igarashi, P. HOXA10 is expressed in response to sex steroids at the time of implantation in the human endometrium. J Clin Invest. 1998;101:1379–84.CrossRefGoogle ScholarPubMed
Taylor, HS. Transcriptional regulation of implantation by HOX genes. Rev Endocr Metab Disord. 2002;3:127–32.CrossRefGoogle ScholarPubMed
Daftary, GS, Taylor, HS. Hydrosalpinx fluid diminishes endometrial cell HOXA10 expression. Fertil Steril. 2002;78:577–80.CrossRefGoogle ScholarPubMed
Lutjen, PJ, Leeton, JF, Findlay, JK. Oocyte and embryo donation in IVF programmes. Clin Obstet Gynaecol. 1985;12:799–813.Google ScholarPubMed
Navot, D, Laufer, N, Kopolovic, J, Rabinowitz, R, Birkenfeld, A, Lewin, A, Granat, M, Margalioth, EJ, Schenker, JG. Artificially induced endometrial cycles and establishment of pregnancies in the absence of ovaries. N Engl J Med. 1986;314:806–11.CrossRefGoogle ScholarPubMed
Rosenwaks, Z, Veeck, LL, Liu, HC. Pregnancy following transfer of in vitro fertilized donated oocytes. Fertil Steril. 1986;45:417–20.CrossRefGoogle ScholarPubMed
Rosenwaks, Z, Garcia-Velasco, JA, Isaza, V, Caligara, C, Pellicer, A, Remohi, J, Simon, C. Factors that determine discordant outcome from shared oocytes. Fertil Steril. 2003;80:54–60.Google Scholar
Rosenwaks, Leeton J, Chan, LK, Trounson, A, Harman, J. Pregnancy established in an infertile patient after transfer of an embryo fertilized in vitro where the oocyte was donated by the sister of the recipient. J In Vitro Fert Embryo Transf. 1986;3:379–82.Google Scholar
Sauer, MV, Paulson, RJ, Lobo, RA. Simultaneous establishment of pregnancies in two ovarian failure patients using one oocyte donor. Fertil Steril. 1989;52:1072–3.CrossRefGoogle ScholarPubMed
Smitz, J, Devroey, P, Faguer, B, Bourgain, C, Camus, M, Steirteghem, AC. A prospective randomized comparison of intramuscular or intravaginal natural progesterone as a luteal phase and early pregnancy supplement. Hum Reprod. 1992;7:168–75.CrossRefGoogle ScholarPubMed
Steingold, KA, Matt, DW, Ziegler, D, Sealey, JE, Fratkin, M, Reznikov, S. Comparison of transdermal to oral estradiol administration on hormonal and hepatic parameters in women with premature ovarian failure. J Clin Endocrinol Metab. 1991;73:275–80.CrossRefGoogle ScholarPubMed
Forman, R, Fries, N, Testart, J, Belaisch-Allart, J, Hazout, A, Frydman, R. Evidence for an adverse effect of elevated serum estradiol concentrations on embryo implantation. Fertil Steril. 1988;49:118–22.CrossRefGoogle ScholarPubMed
Mahadevan, MM, Fleetham, J, Taylor, PJ. Effects of progesterone on luteinizing hormone release and estradiol/progesterone ratio in the luteal phase of women superovulated for in vitro fertilization and embryo transfer. Fertil Steril. 1988;50:935–7.CrossRefGoogle ScholarPubMed
Maclin, VM, Radwanska, E, Binor, Z, Dmowski, WP. Progesterone: estradiol ratios at implantation in ongoing pregnancies, abortions, and nonconception cycles resulting from ovulation induction. Fertil Steril. 1990;54:238–44.CrossRefGoogle ScholarPubMed
Gorkemli, H, Ak, D, Akyurek, C, Aktan, M, Duman, S. Comparison of pregnancy outcomes of progesterone or progesterone + estradiol for luteal phase support in ICSI-ET cycles. Gynecol Obstet Invest. 2004;58:140–4.CrossRefGoogle ScholarPubMed
Gelety, TJ, Buyalos, RP. The influence of supraphysiologic estradiol levels on human nidation. J Assist Reprod Genet. 1995;12: 406–12.CrossRefGoogle ScholarPubMed
Ziegler, D, Bergeron, C, Cornel, C, Medalie, DA, Massai, MR, Milgrom, E, Frydman, R, Bouchard, P. Effects of luteal estradiol on the secretory transformation of human endometrium and plasma gonadotropins. J Clin Endocrinol Metab. 1992;74:322–31.Google ScholarPubMed
Younis, JS, Ezra, Y, Sherman, Y, Simon, A, Schenker, JG, Laufer, N. The effect of estradiol depletion during the luteal phase on endometrial development. Fertil Steril. 1994;62:103–7.CrossRefGoogle ScholarPubMed
Ziegler, D, Fanchin, R, Moustier, B, Bulletti, C. The hormonal control of endometrial receptivity: estrogen (E2) and progesterone. J Reprod Immunol. 1998;39:149–66.CrossRefGoogle ScholarPubMed
Remohi, J, Gutierrez, A, Cano, F, Ruiz, A, Simon, C, Pellicer, A. Long oestradiol replacement in an oocyte donation programme. Hum Reprod. 1995;10:1387–91.CrossRefGoogle Scholar
Simon, C, Garcia Velasco, JJ, Valbuena, D, Peinado, JA, Moreno, C, Remohi, J, Pellicer, A. Increasing uterine receptivity by decreasing estradiol levels during the preimplantation period in high responders with the use of a follicle-stimulating hormone step-down regimen. Fertil Steril. 1998;70:234–9.CrossRefGoogle ScholarPubMed
Fanchin, R, Ziegler, D, Castracane, VD, Taieb, J, Olivennes, F, Frydman, R. Physiopathology of premature progesterone elevation. Fertil Steril. 1995;64:796–801.CrossRefGoogle ScholarPubMed
Fanchin, R, Righini, C, Olivennes, F, Taieb, J, Ziegler, D, Frydman, R. Premature plasma progesterone and androgen elevation are not prevented by adrenal suppression in in vitro fertilization. Fertil Steril. 1997;67:115–9.CrossRefGoogle Scholar
Fanchin, R, Ziegler, D, Taieb, J, Olivennes, F, Castracane, VD, Frydman, R. Human chorionic gonadotropin administration does not increase plasma androgen levels in patients undergoing controlled ovarian hyperstimulation. Fertil Steril. 2000;73:275–9.CrossRefGoogle Scholar
Daftary, GS, Taylor, HS. Endocrine regulation of HOX genes. Endocr Rev. 2006;27:331–55.CrossRefGoogle ScholarPubMed
Ziegler, D, Fanchin, R, Freitas, S, Bouchard, P. The hormonal control of endometrial receptivity in egg donation and IVF: from a two to a multi-player scenario. Acta Eur Fertil. 1993;24: 147–53.Google Scholar
Ziegler, D, Mattenberger, C, Schwarz, C, Ibecheole, V, Fournet, N, Bianchi-Demicheli, F. New tools for optimizing endometrial receptivity in controlled ovarian hyperstimulation: aromatase inhibitors and LH/(mini)hCG. Ann N Y Acad Sci. 2004;1034: 262–77.CrossRefGoogle ScholarPubMed
Bulletti, C, Ziegler, D, Polli, V, Diotallevi, L, Del Ferro, E, Flamigni, C. Uterine contractility during the menstrual cycle. Hum Reprod. 2000;15:81–9.CrossRefGoogle ScholarPubMed
Martinez-Gaudio, M, Yoshida, T, Bengtsson, LP. Propagated and nonpropagated myometrial contractions in normal menstrual cycles. Am J Obstet Gynecol. 1973;115:107–11.CrossRefGoogle ScholarPubMed
Bulletti, C, Rossi, S, Albonetti, A, Polli, VV, Ziegler, D, Massoneau, M, Flamigni, C. Uterine contractility in patients with endometriosis. J Am Assoc Gynecol Laparosc. 1996;34:S5.Google Scholar
Kunz, G, Leyendecker, G. Uterine peristaltic activity during the menstrual cycle: characterization, regulation, function and dysfunction. Reprod Biomed Online. 2002;4:5–9.CrossRefGoogle ScholarPubMed
Leyendecker, G, Kunz, G, Herbertz, M, Beil, D, Huppert, P, Mall, G, Kissler, S, Noe, M, Wildt, L. Uterine peristaltic activity and the development of endometriosis. Ann N Y Acad Sci. 2004;1034: 338–55.CrossRefGoogle ScholarPubMed
Lumsden, MA, Baird, DT. Intra-uterine pressure in dysmenorrhea. Acta Obstet Gynecol Scand. 1985;64:183–6.CrossRefGoogle ScholarPubMed
Fauconnier, A, Chapron, C. Endometriosis and pelvic pain: epidemiological evidence of the relationship and implications. Hum Reprod Update. 2005;11:595–606.CrossRefGoogle ScholarPubMed
Milingos, S, Protopapas, A, Kallipolitis, G, Drakakis, P, Makrigiannakis, A, Liapi, A, Milingos, D, Antsaklis, A, Michalas, S. Laparoscopic evaluation of infertile patients with chronic pelvic pain. Reprod Biomed Online. 2006;12:347–53.CrossRefGoogle ScholarPubMed
Ziegler, D, Bulletti, C, Fanchin, R, Epiney, M, Brioschi, PA. Contractility of the non-pregnant uterus: the follicular phase. Ann N Y Acad Sci. 2001;943:172–84.CrossRefGoogle Scholar
Ayoubi, JM, Fanchin, R, Kaddouz, D, Frydman, R, Ziegler, D. Uterorelaxing effects of vaginal progesterone: comparison of two methodologies for assessing uterine contraction frequency on ultrasound scans. Fertil Steril. 2001;76:736–40.CrossRefGoogle ScholarPubMed
Fanchin, R, Righini, C, Olivennes, F, Taylor, S, Ziegler, D, Frydman, R. Uterine contractions at the time of embryo transfer alter pregnancy rates after in-vitro fertilization. Hum Reprod. 1998;13:1968–74.CrossRefGoogle ScholarPubMed
Ayoubi, JM, Epiney, M, Brioschi, PA, Fanchin, R, Chardonnens, D, Ziegler, D. Comparison of changes in uterine contraction frequency after ovulation in the menstrual cycle and in in vitro fertilization cycles. Fertil Steril. 2003;79:1101–5.CrossRefGoogle ScholarPubMed
Fanchin, R, Righini, C, Ziegler, D, Olivennes, F, Ledee, N, Frydman, R. Effects of vaginal progesterone administration on uterine contractility at the time of embryo transfer. Fertil Steril. 2001;75:1136–40.CrossRefGoogle ScholarPubMed
Schoolcraft, WB, Surrey, ES, Gardner, DK. Embryo transfer: techniques and variables affecting success. Fertil Steril. 2001;76: 863–70.CrossRefGoogle ScholarPubMed
Fanchin, R, Ayoubi, JM, Righini, C, Olivennes, F, Schonauer, LM, Frydman, R. Uterine contractility decreases at the time of blastocyst transfers. Hum Reprod. 2001;16:1115–19.CrossRefGoogle ScholarPubMed
Mansour, R. Minimizing embryo expulsion after embryo transfer: a randomized controlled study. Hum Reprod. 2005 Jan; 20(1):170–4. Epub 2004 Nov 26. Erratum in: Hum Reprod. 2005;20:1118.Google ScholarPubMed
Selam, B, Arici, A. Implantation defect in endometriosis: endometrium or peritoneal fluid. J Reprod Fertil Suppl. 2000;55: 121–8.Google ScholarPubMed
Garcia-Velasco, JA, Arici, A. Is the endometrium or oocyte/ embryo affected in endometriosis?Hum Reprod. 1999;14:77–89.CrossRefGoogle ScholarPubMed
Garrido, N, Navarro, J, Garcia-Velasco, J, Remoh, J, Pellice, A, Simon, C. The endometrium versus embryonic quality in endometriosis-related infertility. Hum Reprod Update. 2002;8:95–103.CrossRefGoogle ScholarPubMed
Lessey, BA, Palomino, WA, Apparao, K, Young, SL, Lininger, RA. Estrogen receptor-alpha (ER-alpha) and defects in uterine receptivity in women. Reprod Biol Endocrinol. 2006;4:S9.CrossRefGoogle ScholarPubMed
Noble, LS, Simpson, ER, Johns, A, Bulun, SE. Aromatase expression in endometriosis. J Clin Endocrinol Metab. 1996;81:174–9.Google ScholarPubMed
Fazleabas, AT, Brudney, A, Chai, D, Langoi, D, Bulun, SE. Steroid receptor and aromatase expression in baboon endometriotic lesions. Fertil Steril. 2003;80:820–7.CrossRefGoogle ScholarPubMed
Attar, E, Bulun, SE. Aromatase and other steroidogenic genes in endometriosis: translational aspects. Hum Reprod Update. 2006; 12:49–56.CrossRefGoogle ScholarPubMed
Noble, LS, Takayama, K, Zeitoun, KM, Putman, JM, Johns, DA, Hinshelwood, MM, Agarwal, VR, Zhao, Y, Carr, BR, Bulun, SE. Prostaglandin E2 stimulates aromatase expression in endometriosis-derived stromal cells. J Clin Endocrinol Metab. 1997;82: 600–6.Google ScholarPubMed
Jakob, F, Homann, D, Seufert, J, Schneider, D, Kohrle, J. Expression and regulation of aromatase cytochrome P450 in THP 1 human myeloid leukaemia cells. Mol Cell Endocrinol. 1995;110:27–33.CrossRefGoogle ScholarPubMed
Schmidt, M, Weidler, C, Naumann, H, Anders, S, Scholmerich, J, Straub, RH. Androgen conversion in osteoarthritis and rheumatoid arthritis synoviocytes—androstenedione and testosterone inhibit estrogen formation and favor production of more potent 5alpha-reduced androgens. Arthritis Res Ther. 2005;7:R938–48.CrossRefGoogle ScholarPubMed
Schmidt, M, Naumann, H, Weidler, C, Schellenberg, M, Anders, S, Straub, RH. Inflammation and sex hormone metabolism. Ann N Y Acad Sci. 2006;1069:236–46.CrossRefGoogle ScholarPubMed
Attar, E, Bulun, SE. Aromatase inhibitors: the next generation of therapeutics for endometriosis?Fertil Steril. 2006;85:1307–18.CrossRefGoogle ScholarPubMed
Amsterdam, LL, Gentry, W, Jobanputra, S, Wolf, M, Rubin, SD, Bulun, SE. Anastrazole and oral contraceptives: a novel treatment for endometriosis. Fertil Steril. 2005;84:300–4.CrossRefGoogle ScholarPubMed
Surrey, ES, Silverberg, KM, Surrey, MW, Schoolcraft, WB. Effect of prolonged gonadotropin-releasing hormone agonist therapy on the outcome of in vitro fertilization-embryo transfer in patients with endometriosis. Fertil Steril. 2002;78:699–704.CrossRefGoogle ScholarPubMed
Diaz, I, Navarro, J, Blasco, L, Simon, C, Pellicer, A, Remohi, J. Impact of stage III-IV endometriosis on recipients of sibling oocytes: matched case-control study. Fertil Steril. 2000;74:31–4.CrossRefGoogle ScholarPubMed
Cicinelli, E, Ziegler, D, Nicoletti, R, et al. Chronic endometritis: correlation among hysteroscopic, histologic and bacteriologic findings in a prospective trial with 2190 consecutive office hysteroscopies. Fertil Steril. 2008;89 (3):677–84.CrossRefGoogle Scholar
Kiviat, NB, Wolner-Hanssen, P, Eschenbach, DA, Wasserheit, JN, Paavonen, JA, Bell, TA, et al. Endometrial histopathology in patients with culture-proved upper genital tract infection and laparoscopically diagnosed acute salpingitis. Am J Surg Pathol. 1990;14:167–75.CrossRefGoogle ScholarPubMed
Greenwood, SM, Moran, JJ. Chronic endometritis: morphologic and clinical observations. Obstet Gynecol 1981;58:176–84.Google ScholarPubMed

Save book to Kindle

To save this book to your Kindle, first ensure [email protected] is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×