Effects of clomiphene citrate on the endometrial thickness and echogenic pattern of the endometrium
Open accessAbstract
Objective To study the effects of clomiphene citrate (CC) on the endometrium by ultrasound and to reveal the echogenic difference between the control cycle and the CC cycle.Design Retrospective study of patients before and during a CC treatment.Setting Department of Obstetrics and Gynecology, Yamaguchi University School of Medicine, Ube, Yamaguchi, Japan.Patient(s) Seventy-nine infertile women who had a spontaneous ovulation and a normal luteal function.Intervention(s) Patients received 50 mg/d CC between days 5 and 9 of the menstrual cycle.Main outcome measure(s) Endometrial thickness, echogenic pattern of the endometrium, serum E2 content, and E2 and P receptor contents in the endometrium.Result(s) Endometrial thickness was significantly thinner during the CC cycle (7.6 +/- 1.4 mm, mean +/- SD, n = 79) than during the control cycle (8.5 +/- 1.7 mm, n = 79) on late proliferative days, but there was no significant difference on midsecretory days (10.8 +/- 2.2 mm during the CC cycle, n = 79; 11.2 +/- 2.2 mm during the control cycle, n = 79). The echogenic patterns, however, were different between the two cycles on midsecretory days. Moreover, the incidence in which patients showed a grade 3 endometrium on midsecretory days was significantly higher during the conceived CC cycle compared with the not-conceived CC cycle. Serum E2 levels were significantly higher, but E2 receptor contents in the endometrium were significantly lower during the CC cycle (67 +/- 46 fmol/mg, n = 13) compared with the control cycle (123 +/- 89 fmol/mg, n = 15) on late proliferative days.Conclusion(s) Clomiphene citrate affected the echogenic pattern of the endometrium, and most of the endometrium showed a grade 3 pattern on midsecretory days during the conceived CC cycle. Under the CC treatment, the comfortable endometrium for embryos might be different from the control cycle.
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Unlike CC, aromatase inhibitors do not carry an antiestrogenic effect on the endometrium.
“Unlike CC, they do not carry an antiestrogenic effect on the endometrium.”
From A new era in ovulation induction (2006) · cites this paper as [10]
The disappointing pregnancy rates with clomiphene citrate have been attributed to its peripheral antiestrogenic effects, mainly on the endometrium and the cervical mucus.
“This has been attributed to its peripheral antiestrogenic effects, mainly on the endometrium and the cervical mucus (8 -13).”
From A new era in ovulation induction (2006) · cites this paper as [10]
Prolonged endometrial estrogen receptor depletion results in significant thinning of the endometrium (endometrium thickness ≤8 mm) associated with clomiphene cycles compared with natural cycles and in clomiphene/hMG cycles compared with hMG alone.
“Prolonged endometrial estrogen receptor depletion (9 -11) results in the significant thinning of the endometrium (endometrium thickness Յ8 mm) that is associated with clomiphene cycles compared with natural cycles and in clomiphene/hMG cycles compared with hMG alone (9,10,12,13).”
From A randomized double-blind comparison of the effects of clomiphene citrate and the aromatase inhibitor letrozole on ovulatory function in normal women (2002) · cites this paper as [12]
Cites
PROTEIN MEASUREMENT WITH THE FOLIN PHENOL REAGENT
Lowry, O. H., Rosebrough, N., Farr, A. L., & Randall, R. (1951) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)52451-6 · Cited by 315,771 · see citing works
Lessey, B. A., Killam, A. P., METZGER, D. A., Haney, A. F., Greene, G. L., & McCarty, K. S. (1988) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-67-2-334 · Cited by 647 · see citing works
Clomiphene citrate: mechanism(s) and site(s) of action—a hypothesis revisited
Wallach, E. E., & Adashi, E. Y. (1984) · Fertility and Sterility · doi:10.1016/s0015-0282(16)48069-6 · Cited by 249 · see citing works
Garcia, J., Jones, G. S., & Wentz, A. C. (1977) · Fertility and Sterility · doi:10.1016/s0015-0282(16)42670-1 · Cited by 233 · see citing works
Levy, C., Röbel, P., Gautray, J. P., de Brux, J., VERMA, U., Descomps, B., & Baulieu, E. E. (1980) · American Journal of Obstetrics and Gynecology · doi:10.1016/0002-9378(80)91018-2 · Cited by 171 · see citing works
Dickey, R. P., Olar, T. T., Taylor, S. N., Curole, D. N., & Matulich, E. M. (1993) · Fertility and Sterility · doi:10.1016/s0015-0282(16)55855-5 · Cited by 171 · see citing works
Rogers, P. A. W., Milne, B. J., & Trounson, A. O. (1986) · Journal of Assisted Reproduction and Genetics · doi:10.1007/bf01139353 · Cited by 115 · see citing works
Morphometric analysis of the human endometrium in relation to peripheral hormone levels
JOHANNISSON, E., Parker, R. A., Landgren, B.-M., & Diczfalusy, E. R. (1982) · Fertility and Sterility · doi:10.1016/s0015-0282(16)46636-7 · Cited by 105 · see citing works
Ja, E., Place, J. S., Carter, G., Jones, J., Alaghband-Zadeh, J., & Me, P. (1989) · PubMed · Cited by 104 · see citing works
Induction of luteal phase defect with clomiphene citrate
Cook, C. L., Schroeder, J. A., Yussman, M. A., & Sanfilippo, J. S. (1984) · American Journal of Obstetrics and Gynecology · doi:10.1016/0002-9378(84)90244-8 · Cited by 58 · see citing works
Rogers, P. A. W., POLSON, D. W., Murphy, C. R., Hosie, M. J., Susil, B. J., & Leoni, M. A. (1991) · Fertility and Sterility · doi:10.1016/s0015-0282(16)54190-9 · Cited by 56 · see citing works
Endometrial receptivity in the light of modern assisted reproductive technologies
Wallach, E. E., Yaron, Y., Botchan, A., Amit, A., Peyser, M. R., David, M. P., & Lessing, J. B. (1994) · Fertility and Sterility · doi:10.1016/s0015-0282(16)56868-x · Cited by 44 · see citing works
Birkenfeld, A., Beier, H. M., & Schenker, J. G. (1986) · Human Reproduction · doi:10.1093/oxfordjournals.humrep.a136432 · Cited by 38 · see citing works
Lenz, S., & Lindenberg, S. (1990) · Human Reproduction · doi:10.1093/oxfordjournals.humrep.a137106 · Cited by 31 · see citing works
Estrogen and progesterone receptors of the out-of-phase endometrium in female infertile patients
Hirama, Y., & Ochiai, K. (1995) · Fertility and Sterility · doi:10.1016/s0015-0282(16)57534-7 · Cited by 23 · see citing works
Rönnberg, L., Isotalo, H., Kauppila, A., Martikainen, H. K., & Vihko, R. (1985) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1985.tb37547.x · Cited by 21 · see citing works
Check, J. H., Dietterich, C., & LURIE, D. (1995) · Obstetrics and Gynecology · doi:10.1016/0029-7844(95)00165-n · Cited by 20 · see citing works
Transvaginal ultrasonography and the assessment of luteal phase endometrium
Doherty, C. M., Silver, B., Binor, Z., Molo, M. W., & Radwańska, E. (1993) · American Journal of Obstetrics and Gynecology · doi:10.1016/0002-9378(93)90680-h · Cited by 16 · see citing works
Check, J. H., Adelson, H. G., & Davies, E. (1994) · Archives of Andrology · doi:10.3109/01485019408987770 · Cited by 11 · see citing works
Transvaginal sonography (TVS) of the endometrium: current and potential clinical applications.
Fleischer, A. C., An, G., Ss, E., & Kepple, D. M. (1990) · PubMed · Cited by 7 · see citing works
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Diagnosis and Management of Infertility: A Review
Carson, S. A., & Kallen, A. N. (2021) · JAMA · doi:10.1001/jama.2021.4788 · Cited by 1,294 · see citing works
Fisher, S. A., Reid, R. L., Van Vugt, D. A., & Casper, R. F. (2002) · Fertility and Sterility · doi:10.1016/s0015-0282(02)03241-7 · Cited by 347 · see citing works
The human endometrium as a fertility-determining factor
Strowitzki, T., Germeyer, A., Popovici, R., & von Wolff, M. (2006) · Human Reproduction Update · doi:10.1093/humupd/dml033 · Cited by 305 · see citing works
“Endometrial thickness is lower in cycles stimulated with clomiphene citrate than in natural cycles (Eden et al., 1989; Randall and Templeton, 1991; Nakamura et al., 1997), probably because of the interference of clomiphene citrate with ER kinetics in human endometrium (Birkenfeld et al., 1986).”
BackgroundKoçak, M., Çalışkan, E., ŞİMŞİR, Ç., & Haberal, A. (2002) · Fertility and Sterility · doi:10.1016/s0015-0282(01)02941-7 · Cited by 267 · see citing works
A new era in ovulation induction
Holzer, H., Casper, R., & Tulandi, T. (2006) · Fertility and Sterility · doi:10.1016/j.fertnstert.2005.05.078 · Cited by 194 · see citing works
Selective estrogen receptor modulators: an update on recent clinical findings
Shelly, W., Draper, M. W., Krishnan, V., Wong, M., & Jaffe, R. B. (2008) · Obstetrical & Gynecological Survey · doi:10.1097/ogx.0b013e31816400d7 · Cited by 193 · see citing works
“In early phase II studies, idoxifene increased endometrial thickness, measured by transvaginal ultrasound (TVU), and incidence of polyp formation, although no pathological abnormalities were identified on endometrial biopsy (82).”
BackgroundAtay, V., Çam, Ç., Muhçu, M., Cam, M., & Karateke, A. (2006) · Journal of International Medical Research · doi:10.1177/147323000603400109 · Cited by 138 · see citing works
Uterine Cancer after Use of Clomiphene Citrate to Induce Ovulation
Althuis, M. D. (2005) · American Journal of Epidemiology · doi:10.1093/aje/kwi084 · Cited by 117 · see citing works
Amer, S. A. K. S., Smith, J. A., Mahran, A., Fox, P., & Fakis, A. (2017) · Human Reproduction · doi:10.1093/humrep/dex227 · Cited by 115 · see citing works
“This discrepancy between ovulation and conception rates has been attributed to the peripheral anti-oestrogenic actions of CC on endometrial development and cervical mucus (Massai et al., 1993; Nakamura et al., 1997).”
IVF and breast cancer: a systematic review and meta-analysis
Sergentanis, T. Ν., Diamantaras, A.-A., Perlepe, C., Kanavidis, P., Skalkidou, A., & Petridou, E. T. (2013) · Human Reproduction Update · doi:10.1093/humupd/dmt034 · Cited by 110 · see citing works
Weiss, N. S., van Vliet, M. N., Limpens, J., Hompes, P. G. A., Lambalk, C. B., Mochtar, M. H., van der Veen, F., Mol, B. W., & van Wely, M. (2017) · Human Reproduction · doi:10.1093/humrep/dex035 · Cited by 100 · see citing works
“cycles (Nakamura et al., 1997; Dehbashi et al., 2003; Haritha and Rajagopalan, 2003) or than in cycles stimulated with HMG (Gonen and Casper, 1990).”
BackgroundRoy, K., Baruah, J., Singla, S., Sharma, J., Singh, N., Jain, S. K., & Goyal, M. (2012) · Journal of Human Reproductive Sciences · doi:10.4103/0974-1208.97789 · Cited by 95 · see citing works
“[2] CC has a long half-life (2 weeks), and this may have a negative effect on the cervical mucus and endometrium, leading to discrepancy between ovulation and conception rates.[3-5] There has been a search for a compound capable of inducing ovulation but devoid of the adverse antiestrogen effects of CC.”
Kolibianakis, E. M., Zikopoulos, K., Fatemi, H. M., Osmanagaoglu, K., Evenpoel, J., Steirteghem, A. V., & Devroey, P. (2004) · Reproductive BioMedicine Online · doi:10.1016/s1472-6483(10)60505-6 · Cited by 90 · see citing works
Effects of clomiphene citrate on the endometrium of regularly cycling women
Sereepapong, W., Suwajanakorn, S., Triratanachat, S., Sampatanukul, P., Pruksananonda, K., Boonkasemsanti, W., & Reinprayoon, D. (2000) · Fertility and Sterility · doi:10.1016/s0015-0282(99)00509-9 · Cited by 90 · see citing works
Ng, E. H. Y., Chan, C. C. W., Tang, O. S., Yeung, W. S. B., & Ho, P. C. (2006) · Human Reproduction · doi:10.1093/humrep/dei502 · Cited by 88 · see citing works
“1617 on the endometrium, leading to reduced endometrial thickness (Nakamura et al., 1997) and delayed endometrial maturation (Massai et al.”
BackgroundUterine effects of metformin administration in anovulatory women with polycystic ovary syndrome
Palomba, S., Russo, T., Orio, F., Falbo, A., Manguso, F., Cascella, T., Tolino, A., Carmina, E., Colao, A., & Zullo, F. (2006) · Human Reproduction · doi:10.1093/humrep/dei351 · Cited by 85 · see citing works
“The percentage of high-grade endometrial pattern detected in the current study was similar to those obtained by Triwitayakorn et al. (2002) and by Nakamura et al. (1997) in healthy women.”
ResultNg, E. H. Y., Chan, C. C. W., Tang, O. S., Yeung, W. S. B., & Ho, P. C. (2004) · Human Reproduction · doi:10.1093/humrep/deh384 · Cited by 80 · see citing works
Kamath, M. S., Maheshwari, A., Bhattacharya, S., Lor, K. Y., & Gibreel, A. (2017) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd008528.pub3 · Cited by 75 · see citing works
The luteal phase after ovarian stimulation
Kolibianakis, E. M., & Devroey, P. (2002) · Reproductive BioMedicine Online · doi:10.1016/s1472-6483(11)60214-9 · Cited by 75 · see citing works
Defining the proliferative phase endometrial defect
Bromer, J. G., Aldad, T. S., & Taylor, H. S. (2008) · Fertility and Sterility · doi:10.1016/j.fertnstert.2007.12.066 · Cited by 69 · see citing works
Haritha, S., & Rajagopalan, G. (2003) · International Journal of Gynecology & Obstetrics · doi:10.1016/s0020-7292(02)00404-6 · Cited by 67 · see citing works
Hashim, H. A., Shokeir, T. A., & Badawy, A. (2009) · Fertility and Sterility · doi:10.1016/j.fertnstert.2009.07.985 · Cited by 63 · see citing works
RetractedEffect of clomiphene citrate on endometrium thickness and echogenic patterns
Dehbashi, S., Parsanezhad, M. E., Alborzi, S., & Zarei, A. (2003) · International Journal of Gynecology & Obstetrics · doi:10.1016/s0020-7292(02)00341-7 · Cited by 63 · see citing works
Ultra‐short metformin pretreatment for clomiphene citrate‐resistant polycystic ovary syndrome
Hwu, Y., Lin, S., Huang, W. Y., Lin, M., & Lee, R. K. K. (2005) · International Journal of Gynecology & Obstetrics · doi:10.1016/j.ijgo.2005.04.004 · Cited by 60 · see citing works
Palomba, S., Russo, T., Orio, F., Falbo, A. I., Manguso, F., Sammartino, A., Tolino, A., Colao, A., Carmina, E., & Zullo, F. (2006) · Human Reproduction · doi:10.1093/humrep/del267 · Cited by 58 · see citing works
“Endometrial anti-estrogenic effects are frequently viewed as possible explanation for the relatively low pregnancy rates with clomiphene citrate (Nakamura et al., 1997).”
BackgroundTissue selective estrogen complex (TSEC): a review
Pickar, J. H., Boucher, M., & Morgenstern, D. (2018) · Menopause The Journal of The North American Menopause Society · doi:10.1097/gme.0000000000001095 · Cited by 55 · see citing works
Tsiami, A. P., Goulis, D. G., Sotiriadis, A., & Kolibianakis, E. M. (2021) · HORMONES · doi:10.1007/s42000-021-00289-z · Cited by 54 · see citing works
Shahin, A. Y., Ismail, A. M., Zahran, K. M., & Makhlouf, A. (2008) · Reproductive BioMedicine Online · doi:10.1016/s1472-6483(10)60465-8 · Cited by 54 · see citing works
“Clomiphene has negative effects on the expression of endometrial oestrogen (Nakamura et al., 1997) and progesterone receptors (Ohno and Fujimoto, 1998).”
BackgroundHu, S., Yu, Q., Wang, Y., Wang, M., Xia, W., & Zhu, C. (2018) · Archives of Gynecology and Obstetrics · doi:10.1007/s00404-018-4688-6 · Cited by 53 · see citing works
“However, clomiphene has drawbacks, such as a long half-life (2 weeks) [5] that results in long-lasting adverse effects on cervical mucus [6] and endometrial development [7], leading to discrepancies in ovulation and pregnancy rates [6, 8, 9].”
BackgroundPeeraer, K., Debrock, S., Loecker, P. D., Tomassetti, C., Laenen, A., Welkenhuysen, M., Meeuwis, L., Pelckmans, S., Mol, B. W., Spiessens, C., et al. (2015) · Human Reproduction · doi:10.1093/humrep/dev062 · Cited by 53 · see citing works
“They also received oral ethinyl estradiol (EE2) 50 mg from Day 8 until Day 12 to support endometrial growth, in order to prevent the anti-estrogenic effect of CC reducing endometrial thickness (Martinez et al., 1990; Yagel et al., 1992; Dickey et al., 1993; Gelety and Buyalos, 1993; Nakamura et al., 1997; Gerli et al.…”
MethodRisk of endometrial cancer in women treated with ovary-stimulating drugs for subfertility
Skalkidou, A., Sergentanis, T. Ν., Gialamas, S. P., Georgakis, M. K., Ψαλτοπούλου, Θ., Trivella, M., Siristatidis, C. S., Εvangelou, Ε., & Petridou, E. T. (2017) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd010931.pub2 · Cited by 52 · see citing works
Gibreel, A., Maheshwari, A., & Bhattacharya, S. (2012) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd008528.pub2 · Cited by 51 · see citing works
Jensen, A., Sharif, H., & Kjær, S. K. (2009) · American Journal of Epidemiology · doi:10.1093/aje/kwp290 · Cited by 51 · see citing works
“Lastly, clomiphene might also affect uterine cancer risk by interacting directly with estrogen receptors in the uterus (33, 34), whereas no direct effect on uterine cancer risk for gonadotropins, hCG, or GnRH analogs is known.”
BackgroundHashim, H. A., Al-Inany, H. G., Vos, M. D., & Tournaye, H. J. (2013) · Archives of Gynecology and Obstetrics · doi:10.1007/s00404-013-2808-x · Cited by 52 · see citing works
Severe maternal morbidity in women with high BMI in IVF and unassisted singleton pregnancies
Dayan, N., Fell, D. B., Guo, Y., Wang, H., Vélez, M. P., Spitzer, K. A., & Laskin, C. A. (2018) · Human Reproduction · doi:10.1093/humrep/dey224 · Cited by 50 · see citing works
“It is possible that treatment itself may predispose women to SMM, via impaired endometrial receptivity resulting from repeated cycles of ovarian stimulation (Nakamura et al., 1997).”
BackgroundKato, K., Ezoe, K., Yabuuchi, A., Fukuda, J., Kuroda, T., Ueno, S., Fujita, H., & Kobayashi, T. (2018) · Human Reproduction Open · doi:10.1093/hropen/hoy006 · Cited by 48 · see citing works
“Although CC is a safe and effective oral agent, it has been known to have antioestrogenic side effects, such as endometrial thinning (Eden et al. , 1989; Gonen and Casper, 1990; Nakamura et al. , 1997).”
Kazerooni, T., Ghaffarpasand, F., Kazerooni, Y., Kazerooni, M., & Setoodeh, S. (2009) · International Journal of Gynecology & Obstetrics · doi:10.1016/j.ijgo.2009.04.022 · Cited by 47 · see citing works
RetractedWallace, K. L., Johnson, V., Sopelak, V. M., & Hines, R. S. (2011) · Fertility and Sterility · doi:10.1016/j.fertnstert.2011.07.1092 · Cited by 45 · see citing works
“One possible explanation for the difference between ovulation and PRs could be a deleterious effect of CC on the endometrium (3).”
BackgroundEspinola, M. S. B., Laganà, A. S., Bilotta, G., Gullo, G., Aragona, C., & Unfer, V. (2021) · American Journal of Case Reports · doi:10.12659/ajcr.932722 · Cited by 44 · see citing works
Quaas, A. M., Gavrizi, S. Z., Peck, J. D., Diamond, M. P., Legro, R. S., Robinson, R. D., Casson, P. R., Christman, G. M., Zhang, H., & Hansen, K. R. (2020) · Fertility and Sterility · doi:10.1016/j.fertnstert.2020.07.030 · Cited by 44 · see citing works
Al-Inany, H. G., Azab, H., El-Khayat, W. M., Nada, A., El-Khattan, E., & Abou-Setta, A. M. (2010) · Fertility and Sterility · doi:10.1016/j.fertnstert.2010.01.069 · Cited by 42 · see citing works
“Regarding endometrial thickness, our findings match with those reported by other investigators who found thinner endometrial thickness with the use of CC when measured on late proliferative days (20).”
ResultHurst, B. S., Hickman, J. M., Matthews, M. L., Usadi, R., & Marshburn, P. B. (2008) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2008.10.031 · Cited by 41 · see citing works
Dayan, N., Lanes, A., WALKER, M. C., Spitzer, K. A., & Laskin, C. A. (2015) · Fertility and Sterility · doi:10.1016/j.fertnstert.2015.11.039 · Cited by 39 · see citing works
Mehdinejadiani, S., Amidi, F., Mehdizadeh, M., Barati, M., Pazhohan, A., Alyasin, A., Mehdinejadiani, K., & Sobhani, A. (2018) · Biology of Reproduction · doi:10.1093/biolre/ioy187 · Cited by 36 · see citing works
Warming, L., Ravn, P., & Christiansen, C. (2003) · American Journal of Obstetrics and Gynecology · doi:10.1067/mob.2003.93 · Cited by 36 · see citing works
Amita, M., Takahashi, T., Tsutsumi, S., Ohta, T., Takata, K., Henmi, N., Hara, S., Igarashi, H., Takahashi, K., & Kurachi, H. (2009) · Endocrinology · doi:10.1210/en.2009-0721 · Cited by 36 · see citing works
Seyedoshohadaei, F. (2016) · JOURNAL OF CLINICAL AND DIAGNOSTIC RESEARCH · doi:10.7860/jcdr/2016/20954.8324 · Cited by 33 · see citing works
Ovarian stimulation protocols: impact on oocyte and endometrial quality and function
Harvey, A. J., Willson, B. E., Surrey, E. S., & Gardner, D. K. (2024) · Fertility and Sterility · doi:10.1016/j.fertnstert.2024.08.340 · Cited by 32 · see citing works
Hashim, H. A., Mashaly, A. E.-M., & Badawy, A. (2010) · Archives of Gynecology and Obstetrics · doi:10.1007/s00404-010-1566-2 · Cited by 32 · see citing works
RetractedLiu, Y., Ye, X. Y., & Chan, C. (2019) · Reproductive Biology and Endocrinology · doi:10.1186/s12958-019-0455-1 · Cited by 31 · see citing works
Jwa, S. C., Seto, S., Takamura, M., Kuwahara, A., Kajihara, T., & Ishihara, O. (2020) · Fertility and Sterility · doi:10.1016/j.fertnstert.2020.06.032 · Cited by 29 · see citing works
Hendawy, S. F., Samaha, H. E., & Elkholy, M. K. A. (2011) · Clinical Medicine Insights Reproductive Health · doi:10.4137/cmrh.s6598 · Cited by 29 · see citing works
Hashim, H. A., El-lakkany, N., & Sherief, L. S. (2010) · Journal of obstetrics and gynaecology research · doi:10.1111/j.1447-0756.2010.01383.x · Cited by 29 · see citing works
Hashim, H. A. (2012) · Archives of Gynecology and Obstetrics · doi:10.1007/s00404-012-2261-2 · Cited by 28 · see citing works
Fetih, A. N., Habib, D. M., Abdelaal, I. I., Hussein, M., Fetih, G. N., & Othman, E. R. (2017) · PubMed Central · Cited by 27 · see citing works
Sinawat, S., Buppasiri, P., Lumbiganon, P., & Pattanittum, P. (2012) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd006226.pub3 · Cited by 27 · see citing works
Gaba, A., Hörath, S., Hager, M., Marculescu, R., & Ott, J. (2019) · Archives of Gynecology and Obstetrics · doi:10.1007/s00404-019-05359-7 · Cited by 26 · see citing works
Ajaj, H. S., & Hassein, M. R. (2021) · Al-Kitab Journal for Pure Sciences · doi:10.32441/kjps.04.02.p2 · Cited by 26 · see citing works
Manganiello, P. D., Stern, J. E., Stukel, T. A., Crow, H. C., Brinck‐Johnsen, T., & Weiss, J. E. (1997) · Fertility and Sterility · doi:10.1016/s0015-0282(97)00260-4 · Cited by 26 · see citing works
Inositols in the ovaries: activities and potential therapeutic applications
Laganà, A. S., Forte, G., Bizzarri, M., Kamenov, Z. A., Bianco, B. A. V., Kaya, C., Gitas, G., Alkatout, İ., Terzić, M., & Unfer, V. (2022) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1080/17425255.2022.2071259 · Cited by 25 · see citing works
Sharma, S., Rani, G., Bose, G., Saha, I., Bathwal, S., & Chakravarty, B. (2018) · Journal of Human Reproductive Sciences · doi:10.4103/jhrs.jhrs_9_17 · Cited by 25 · see citing works
“Furthermore, endometrial thinning has been observed in 15%–50% of CC users.[4,5] Introduction I insemination (IUI) is widely used as an empirical treatment for a large group of subfertile patients.”
BackgroundZeng, M., Zhou, X., & Duan, J. L. (2021) · Gynecological Endocrinology · doi:10.1080/09513590.2020.1867976 · Cited by 24 · see citing works
“However, clomiphene is a selective estrogen receptor modulator that reduces endometrial thickness [9].”
BackgroundEffect of estradiol valerate on endometrium thickness during clomiphene citrate‐stimulated ovulation
Satirapod, C., Wingprawat, S., Jultanmas, R., Rattanasiri, S., Jirawatnotai, S., & Choktanasiri, W. (2013) · Journal of obstetrics and gynaecology research · doi:10.1111/jog.12130 · Cited by 24 · see citing works
“In fact, it has been reported that the antiestrogenic activity of CC can cause thinning of endometrium.(9,10,12,13) Normally, endometrial thickness is a reflection of its ability to proliferate and of the”
BackgroundMehdinejadiani, S., Amidi, F., Mehdizadeh, M., Barati, M., Safdarian, L., Aflatoonian, R., Alyasin, A., Aghahosseini, M., Pazhohan, A., Hayat, P., et al. (2018) · Gynecological Endocrinology · doi:10.1080/09513590.2018.1446934 · Cited by 24 · see citing works
“Meanwhile, thin endometrium is known as main consequence in most of the women induced by CC [15,16] which can be due to changes in the expression of signaling molecules of Wnt pathway.”
BackgroundHashim, H. A., OMBAR, O., & Elaal, I. A. (2011) · Acta Obstetricia Et Gynecologica Scandinavica · doi:10.1111/j.1600-0412.2010.01063.x · Cited by 23 · see citing works
Samani, F. G., Farzadi, L., Nezami, N., Tarzamni, M. K., & Soleimani, F. (2008) · Archives of Gynecology and Obstetrics · doi:10.1007/s00404-008-0888-9 · Cited by 23 · see citing works
Pourali, L., Ayati, S., Tavakolizadeh, S., Soleimani, H., & Sani, F. T. (2017) · International Journal of Reproductive BioMedicine (IJRM) · doi:10.29252/ijrm.15.1.49 · Cited by 23 · see citing works
Shimoya, K., Tomiyama, T., Hashimoto, K., Moriyama, A., Kawamoto, A., Tokugawa, Y., Ohashi, K., Saji, F., & Murata, Y. (1999) · Gynecologic and Obstetric Investigation · doi:10.1159/000010116 · Cited by 23 · see citing works
A pilot study to prevent a thin endometrium in patients undergoing clomiphene citrate treatment
Takasaki, A., Tamura, H., Taketani, T., 嶋村, 勝., Morioka, H., & Sugino, N. (2013) · Journal of Ovarian Research · doi:10.1186/1757-2215-6-94 · Cited by 22 · see citing works
“cantly thinner in women taking CC than women not taking CC [3-5].”
Backgroundde Ziegler, D. (2003) · Human Reproduction · doi:10.1093/humrep/deg310 · Cited by 22 · see citing works
Sharief, M., & Nafee, N. R. (2015) · PubMed · Cited by 21 · see citing works
Palomba, S., Costanzi, F., Caserta, D., & Vitagliano, A. (2024) · Reproductive BioMedicine Online · doi:10.1016/j.rbmo.2024.104381 · Cited by 22 · see citing works
Ovarian stimulation leads to shorter stature in childhood
Savage, T., Peek, J., Robinson, E. M., Green, M. P., Miles, H. L., Mouat, F., Hofman, P. L., & Cutfield, W. (2012) · Human Reproduction · doi:10.1093/humrep/des249 · Cited by 20 · see citing works
“, 2001) and endometrial thickness (Nakamura et al., 1997), which may impact on embryonic development.”
BackgroundPoor Endometrial Proliferation After Clomiphene is Associated With Altered Estrogen Action
Bressler, L. H., Fritz, M. A., Wu, S., Yuan, L., Kafer, S., Wang, T., DeMayo, F. J., & Young, S. L. (2021) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgab381 · Cited by 18 · see citing works
Laçin, S. (2001) · Human Reproduction · doi:10.1093/humrep/16.11.2305 · Cited by 19 · see citing works
Çetinkaya, K., & Kadanalı, S. (2012) · Journal of the Turkish-German Gynecological Association · doi:10.5152/jtgga.2012.20 · Cited by 18 · see citing works
“Despite the anti-estrogenic effects of CC and its adverse effects, especially on ET and endometrial maturation, no significant difference has been found between natural cycles and those under CC regarding endometrial and subendometrial flow (11).”
BackgroundHashim, H. A., Foda, O., Ghayaty, E., & Elawa, A. (2011) · Archives of Gynecology and Obstetrics · doi:10.1007/s00404-011-1983-x · Cited by 18 · see citing works
RetractedEndometrial Evaluation Is Not Predictive for In Vitro Fertilization Treatment
Csemiczky, G., Wramsby, H., JOHANNISSON, E., & Landgren, B.-M. (1999) · Journal of Assisted Reproduction and Genetics · doi:10.1023/a:1022594729197 · Cited by 18 · see citing works
“thickening has been observed despite supraphysiological E2 levels (9,10).”
BackgroundSiristatidis, C. S., Trivella, M., Chrelias, C. G., Sioulas, V. D., Vrachnis, N., & Kassanos, D. (2012) · Archives of Gynecology and Obstetrics · doi:10.1007/s00404-012-2347-x · Cited by 17 · see citing works
Use of fertility drugs and risk of endometrial cancer in an Italian case–control study
Parazzini, F., Pelucchi, C., Talamini, R., Montella, M., & Vecchia, C. L. (2010) · European Journal of Cancer Prevention · doi:10.1097/cej.0b013e32833d9388 · Cited by 17 · see citing works
“, 2002) and have been shown to interact with uterine oestrogen receptors (Nakamura et al., 1997; Goldstein et al., 2000).”
BackgroundHarira, M. M. (2018) · Middle East Fertility Society Journal · doi:10.1016/j.mefs.2018.05.008 · Cited by 15 · see citing works
Reed, B. G., Wu, J., Nemer, L. B., Carr, B. R., & Bükülmez, O. (2018) · JBRA · doi:10.5935/1518-0557.20180070 · Cited by 15 · see citing works
“However, there are studies that have been performed on intrauterine insemination (IUI) cycles that indicate CC may have a detrimental effect on the endometrial stripe (ES) thickness and pattern (Dehbashi et al., 2003; Haritha & Rajagopalan, 2003; Nakamura et al., 1997).”
BackgroundHashim, H. A., Wafa, A. M., & Rakhawy, M. E. (2010) · Gynecological Endocrinology · doi:10.3109/09513590.2010.488771 · Cited by 15 · see citing works
RetractedSinawat, S., Buppasiri, P., Lumbiganon, P., & Pattanittum, P. (2008) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd006226.pub2 · Cited by 14 · see citing works
Triwitayakorn, A., Suwajanakorn, S., Triratanachat, S., Sampatanukul, P., Pruksananonda, K., & Sereepapong, W. (2002) · Fertility and Sterility · doi:10.1016/s0015-0282(02)03192-8 · Cited by 13 · see citing works
Amita, M., Takahashi, T., Igarashi, H., & Nagase, S. (2016) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2016.03.029 · Cited by 12 · see citing works
“However, CC treatment significantly reduces the endometrial thickness in patients compared to non-CC treatment cycles (Nakamura et al., 1997, Brome , Aldad and Taylor, 2009, Peeraer, Debrock, De Loecker et al., 2015).”
Wu, J., Keller, P. W., Kanchwala, M., Xing, C., Babayev, S. N., Carr, B. R., Bükülmez, O., & Word, R. A. (2020) · Reproductive Sciences · doi:10.1007/s43032-019-00093-6 · Cited by 12 · see citing works
Improving ovarian stimulation protocols for IVF in baboons: Lessons from humans and rhesus monkeys
Nyachieo, A., Spiessens, C., Mwenda, J. M., Debrock, S., & D’Hooghe, T. (2008) · Animal Reproduction Science · doi:10.1016/j.anireprosci.2008.08.023 · Cited by 11 · see citing works
Shui, X., Yu, C., Li, J., & Jiao, Y. (2021) · PubMed Central · Cited by 12 · see citing works
Asante, A., Coddington, C. C., Schenck, L. A., & Stewart, E. A. (2013) · Fertility and Sterility · doi:10.1016/j.fertnstert.2013.08.035 · Cited by 12 · see citing works
Atalay, E., Özakşit, M. G., Tokmak, A., & Üstün, Y. E. (2019) · Journal of Gynecology Obstetrics and Human Reproduction · doi:10.1016/j.jogoh.2019.07.002 · Cited by 10 · see citing works
Jwa, S. C., Takamura, M., Kuwahara, A., Kajihara, T., & Ishihara, O. (2021) · Scientific Reports · doi:10.1038/s41598-021-97044-6 · Cited by 10 · see citing works
Effect of clomiphene citrate on uterine hemodynamics in women with unexplained infertility
Omran, E., El-Sharkawy, M., El-Mazny, A. N., Hammam, M., Ramadan, W., Latif, D., Samir, D., & Sobh, S. M. (2018) · International Journal of Women s Health · doi:10.2147/ijwh.s155335 · Cited by 10 · see citing works
“The lower blood flow parameters in the endometrial and subendometrial regions in stimulated cycles can be due to the anti-estrogenic effect of clomiphene citrate.(20,21) In addition, some studies have suggested that the number of estrogen and progesterone receptors is lower in the endometrium of stimulated cycles when…”
Ege, S., Bademkıran, M. H., Peker, N., Tahaoğlu, A. E., Çaça, F. N., & OTCU, S. M. Ö. (2020) · Ginekologia Polska · doi:10.5603/gp.a2020.0037 · Cited by 10 · see citing works
“Letrozole and CC have different mechanisms of action; These different mechanisms of action of the two drugs may complement each other to increase ovulation rates as compared to those achieved with gonadotropin use alone [3, 8].”
BackgroundHashim, H. A., Bazeed, M. F., & Elaal, I. A. (2011) · Gynecological Endocrinology · doi:10.3109/09513590.2011.589924 · Cited by 10 · see citing works
RetractedLi, Q., Zhu, M., Deng, Z., Wang, L., Huang, Y., Ruan, L., Shao-fei, H., & Wang, L. (2020) · Journal of International Medical Research · doi:10.1177/0300060520966538 · Cited by 9 · see citing works
Is letrozole superior to clomiphene for ovarian stimulation prior to intrauterine insemination?
Khanna, S. C., Kumar, A., Joy, S. G., Tanwar, R., Sharma, S. B., & Prasad, S. (2012) · Archives of Gynecology and Obstetrics · doi:10.1007/s00404-012-2579-9 · Cited by 9 · see citing works
“However, it has disappointing results due to its peripheral antiestrogenic effects [5–8].”
BackgroundJouan, C., Emonard, V., Ruggeri, P., Debelle, L., Hincourt, N., Lorquet, S., Dechenne, V., Lloret, C. G., Dubois, M., d'HAUTERIVE, S. P., et al. (2016) · Gynecological Endocrinology · doi:10.1080/09513590.2016.1177012 · Cited by 9 · see citing works
“However, this molecule is a selective estrogen-receptor modulator that inhibits estradiol-induced cellular-proliferation in the endometrium, resulting in reduced thickness in mid-luteal phase [10].”
BackgroundUltrasound in Infertility Treatments
Klenov, V. E., & Voorhis, B. J. V. (2017) · Clinical Obstetrics & Gynecology · doi:10.1097/grf.0000000000000263 · Cited by 8 · see citing works
Alborzi, M., Zarei, A., Alborzi, S., Askary, E., & Shahbazi, F. (2018) · Journal of Advanced Pharmaceutical Technology amp Research · doi:10.4103/japtr.japtr_293_18 · Cited by 8 · see citing works
“In addition, it is well established that premature LH surge is associated with poor oocyte quality and decreased fertilization and implantation rates.[26,27]”
Background
- Authors
- Nakamura, Y., Ono, M., Yoshida, Y., Sugino, N., Ueda, K., & Kato, H.
- Affiliations
- Yamaguchi University (JP)
- Venue
- Fertility and Sterility
- Publisher
- Elsevier BV
- Published
- 1997-02
- Volume
- 67
- Issue
- 2
- Pages
- 256-260
- ISSN
- 0015-0282 (ISSN-L)
- OpenAlex
- W2000023045
- Cited by
- 161
- References
- 20
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 4 · 2023: 2 · 2022: 14 · 2021: 11 · 2020: 10 · 2019: 7 · 2018: 13 · 2017: 7 · 2016: 3 · 2015: 7 · 2014: 1 · 2013: 8 · 2012: 9
- FWCI
- 0.87
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Fertility and Sterility (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Health Sciences › Medicine › Reproductive Medicine › Reproductive Health and Technologies
- Health Sciences › Medicine › Obstetrics and Gynecology › Endometrial and Cervical Cancer Treatments
- Keywords
- clomiphene citrate, endometrial thickness, endometrial echogenicity, endometrial receptivity, serum estradiol, ovulation induction, infertility, embryo implantation
- MeSH terms
- Adult, Clomiphene, Endometrium, Female, Humans, Receptors, Estradiol, Receptors, Progesterone, Reference Values, Ultrasonography
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